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nanoparticles in dental tissue regeneration
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Biomimetics using nanotechnology/ nanoparticles in dental tissue regeneration
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Shengbin Huang1,2, Tingting Wu1,2 and Haiyang Yu1,2 1
State Key Laboratory of Oral Diseases, Chengdu, P.R. China 2West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
20.1 INTRODUCTION Tissue engineering is a multidisciplinary field by nature, bringing together biology, engineering, and clinical sciences with the goal of generating new tissues and organs [1]. This field builds on the interface between material science and biocompatibility, and integrates cells, natural or synthetic scaffolds, and specific signals to create new tissues. Nowadays, regenerative dentistry is viewed synonymous to tissue engineering in dentistry. Continuous research is going on in this field at both preclinical and clinical levels; remarkable and promising results are also being obtained. However, the high demand for aesthetics of dental tissue structures and the complex atmosphere poses special challenges in this area [2]. Nanotechnology is described as science and techniques which control and manipulate matter at a nanometric level. It has progressed tremendously in the last few decades. Nanomaterials are materials with basic structural units, grains, particles, fibers, or other constituent components smaller than 100 nm in at least one dimension [3] and have great potential in disease prevention, diagnosis, and treatment. To date, advances in this field have led to significant progress in tissue repair and regeneration. With the help of nanotechnology it is possible to interact with cell components, to manipulate cell proliferation and differentiation, and in the production and organization of extracellular matrices. New nanomaterials are leading to a range of emerging dental treatments that utilize more biomimetic materials that closely duplicate natural tooth structure. The uses of nanostructures that will work in harmony with the body’s own regenerative processes are moving into dental clinical practice. In this chapter, we will focus on the recent progress of the applications of nanotechnology in dental tissue regeneration, the contributions of these new technologies in the development of innovative biomimetic materials, and their potential clinical applications.
Nanobiomaterials in Clinical Dentistry. DOI: https://doi.org/10.1016/B978-0-12-815886-9.00020-6 © 2019 Elsevier Inc. All rights reserved.
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20.2 NANOTECHNOLOGY FOR CRANIOFACIAL BONE AND CARTILAGE TISSUE ENGINEERING Craniofacial bone defects secondary to trauma, infection, cancer, and congenital disorders represent a major health problem. Current strategies aimed at replacing bony defects include the utilization of autografts, allografts, and synthetic biomaterials. Despite the fact that these substitutes restore stability and function to a reasonable degree, however they still have limitations. Tissue engineering is considered as an optimal approach for various tissue repairs including craniofacial defect repairs [4]. Biomaterials, acting as scaffolds for tissue engineering, play an essential role in the process of tissue regeneration. Moreover, incorporation of nanotechnology into scaffold design and manufacture will further enhance the quality and function of regenerated tissues. Due to the biomimetic features and excellent physiochemical properties, nanomaterials have been shown to improve adhesion, proliferation, and differentiation of cells, which would finally guide tissue regeneration (Fig. 20.1) [5]. Within the craniofacial tissue engineering field, the major types of materials used are natural and synthetic polymers, ceramics, composite materials, and electrospun nanofibers. Synthetic and natural polymers are excellent candidates for bone/cartilage tissue engineering applications due to their biodegradability and ease of fabrication. Numerous studies have shown successful bone formation with nanofibrous synthetic and natural polymer scaffolds such as electrospun polycaprolactone [6], poly(lactic-co-glycolic acid) [7], polyvinyl alcohol/type I collagen blend [8], and many others [9]. Nanofibrous scaffolds would be an advantageous microenvironment for bone tissue formation by mimicking the type I collagen fibers that are a major component of bone and provide a cellular platform for bone formation [10]. Nanophase ceramics are popular as bone substitutes, coatings, and filler materials due to their dimensional similarity to bone/cartilage tissue and unique surface properties, including surface topography, surface chemistry, surface wettability, and surface energy. Numerous in vitro studies have revealed that nanohydroxyapatite (HA) significantly enhances osteoblast adhesion and function [11 13]. In vivo studies have also demonstrated that nanostructured HA can improve cell attachment and mineralization, suggesting that nanosized HA may be a better candidate for clinical use in terms of bioactivity [14 19]. In general, nanostructured ceramics offer much improved performances compared to their larger particle-sized counterparts due to their huge surface-to-volume ratio and unusual chemical synergistic effects. Nanosized HA is expected to have a better bioactivity than coarser crystals [12,20,21]. Similar tendencies have been reported for other nanoceramics including alumina, zinc oxide, and titania. Osteoblast adhesion increased by 146% and 200% on nanophase zinc oxide (23 nm) and titania (32 nm) compared to microphase zinc oxide (4.9 μm) and titania (4.1 μm), respectively [22,23].
FIGURE 20.1 The biomimetic advantages of nanomaterials. (A) The nanostructured hierarchal self-assembly of bone. (B) Nanophase titanium (top, the atomic force microscopy image) and nanocrystalline HA/HRN hydrogel scaffold (bottom, the SEM image). (C) Schematic illustration of the mechanism by which nanomaterials may be superior to conventional materials for bone regeneration. The bioactive surfaces of nanomaterials mimic those of natural bones to promote greater amounts of protein adsorption and efficiently stimulate more new bone formation than conventional materials. HA, Hydroxyapatite; SEM, Scanning Electron Microscope. Adapted from L.J. Zhang, T.J. Webster, Nanotechnology and nanomaterials: promises for improved tissue regeneration, Nano Today 4 (2009) 66 80, with permission from Elsevier.
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Commercial formulations (nanobone) have also been developed and extensively used in the clinic. nanOss bone void filler from Angstrom Medica Inc. is considered as the first nanotechnological medical device, and received clearance by the US Food and Drug Administration in 2005. Its major composition is calcium orthophosphate nanoparticles, which mimics the nanostructure, composition, and performance of human bone. nanOss is remodeled over time into human bone with applications in sports medicine, trauma, spine, and general orthopedics [24]. Ostim (Osartis GmbH & Co. KG, Obernburg, Germany) is another popular commercial formulation. It is a ready-to-use injectable paste that received Conformite Europeans approval in 2002. Ostim is a suspension of synthetic nano-HA in water, prepared by a wet chemical reaction [25]. Ostim can be used to treat metaphyseal fracture and cysts, alveolar ridge augmentation, osteotomies, etc. [24,26 36]. Although inorganic and organic substances show potential to promote bone regeneration, they have inferior mechanical properties. Bone is composed of both collagen (mainly type I) and mineralized substances (mainly HA), therefore, a biomimetic scaffold should contain both inorganic and organic components. Kim et al. demonstrated that a rapid screening tool for potential biomimetic analogs of collagen mineralization and the nanoscopic protocol could accelerate the application of collagen-HA in bone regeneration [37]. Recently, another study showed that chondroitin sulfate combined with nano-HA exhibited the potential to mimic native bone extracellular matrix (ECM) to promote bone regeneration [38]. These findings show that tissue engineering based on nanotechnology could become a breakthrough approach to reconstructing bone deformities in a more effective and less traumatic way. As it relates to craniofacial reconstruction, the design of polymer scaffolds with defined mechanical and degradative properties has opened a new avenue to cartilage reconstruction. Cartilage destruction is associated with trauma and with degenerative articular cartilage destruction at the temporomandibular joint. The limited capacity of cartilaginous tissue to regenerate and the lack of inductive molecules have focused interest among researchers and manufacturers in developing engineered cartilage. Cartilage itself is avascular and has relatively limited ability for intrinsic repair. A pilot clinical study showed that a newly developed biomimetic osteochondral scaffold with nucleating collagen fibrils along with HA nanoparticles could be used to repair femoral condyle defects of knee joints. Magnetic resonance imaging demonstrated good short-term stability of the scaffold. Histologic analysis showed the formation of subchondral bone without the presence of biomaterials. This result is encouraging and should be a cue for temporomandibular joint (TMJ) defect repair [39]. Gene therapy approaches based on nanotechnology are promising for growth factor signaling mediated cartilage regeneration. As shown by Erisken et al. [40], osteochondral tissue regeneration could be induced with nanofibrous scaffolds fabricated with two different layers that were respectively conjugated with insulin (for chondrogenic differentiation) or with A-glycerophosphate (for osteogenic differentiation). After
20.3 Nanotechnology for Periodontal Regeneration
being seeded on this mimetic scaffold, adipose-derived stem cells could be induced to chondrogenic cells at an insulin-rich location and to osteogenic cells at an A-glycerophosphate-released region. This approach may also be applied for regenerating complex craniofacial tissues such as the TMJ [40].
20.3 NANOTECHNOLOGY FOR PERIODONTAL REGENERATION Periodontal disease leads to destruction of the periodontium: alveolar bone, cementum, the periodontal ligament, and gingiva. Effective treatment for periodontal tissue regeneration plays an important role in the normal function of the craniofacial and systemic system. However, various conventional therapies [open flap debridement, guided tissue regeneration (GTR), and bone replacement grafts, provide either alone or in combination] for periodontal tissue regeneration have shown limited and variable clinical outcomes (Fig. 20.2) [41]. To accelerate clinical translation, there is an ongoing need to develop therapeutics based on endogenous regenerative technology (ERT), which can stimulate latent self-repair mechanisms in patients and harness the host’s innate capacity for regeneration. ERT in periodontics applies the patient’s own regenerative “tool,” that is, patient-derived growth factors and fibrin scaffolds, sometimes in association with commercialized products (e.g., Emdogain and Bio-OSS), to create a material niche in an injured site where the progenitor/stem cells from neighboring tissues can be recruited for in situ periodontal regeneration. The selection and design of materials influence the therapeutic potential and the number and invasiveness of the associated clinical procedures [41]. This has shifted the focus from the attempt to recreate tissue replacement/constructs ex vivo to the development of biofunctionalized biomaterials that incorporate and release regulatory signals in a precise and near-physiological fashion to achieve in situ regeneration. Therefore, certain artificially designed scaffold features, such as porosity, pore size, and interpore connectivity are necessary for optimal tissue engineering applications (accelerated/expedited tissue regeneration), no matter which biomaterial scaffold is proposed [42]. In this regard, a biomimetic scaffold mimicking certain features such as nanoscale topography and biological cues of natural ECM is advantageous for facilitating cell recruitment, seeding, adhesion, proliferation, differentiation, and neotissue genesis [41]. Thus, as mentioned above, biomimetic features and excellent physiochemical properties of nanomaterials play a key role in stimulating cell growth and guiding tissue regeneration. Nanotechnology is expected to play an important role in the design and application of biofunctionalized biomaterials in the periodontal tissue repair process. For example, alginate/nBGC (synthesis of nanobioactive glass ceramic particles) composite scaffolds were successfully fabricated using lyophilization technique and characterized. The scaffolds were found to have characteristic materialistic and biological properties essential to
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FIGURE 20.2 Schematic diagrams of several techniques commonly used in periodontal surgery. (A) OFD procedure involves the periodontal surgeon lifting the gum away from the tooth and surrounding bone, providing increased access for scaling and root planning. However, periodontal defects, if left empty after OFD, fill with the first cells to reach the area, that is, epithelial cells (1) and fibroblasts (2), after cell proliferation, which generates a core of fibroepithelial tissues that attach to the root surface, hence bone (3) and periodontal ligament (3) regeneration are encumbered. (B) GTR is a surgical procedure that utilizes a barrier membrane which is placed under the gum and over the remaining bone to prevent epithelial down-growth (1) and fibroblast trans-growth (2) into the wound space, thereby maintaining a space for true periodontal tissue regeneration (3 and 4). (C) The use of bone grafts is a surgical procedure that replaces missing bone with materials from the patient’s own body (autogenous bone) or an artificial, synthetic, or natural substitute. Bone growth may be stimulated by the grafts and new bone fills the defect which may provide support for the tooth. OFD, Open flap debridement; GTR, guided tissue regeneration. Adapted from F.M. Chen, J. Zhang, M. Zhang, Y. An, F. Chen, Z.F. Wu, A review on endogenous regenerative technology in periodontal regenerative medicine, Biomaterials 31 (2010) 7892 7927, with permission from Elsevier.
20.4 Nanotechnology for Tooth Regeneration
facilitate periodontal regeneration [43]. The composite scaffolds had a pore size of about 100 300 μm, controlled porosity and swelling ability, limited degradation and enhanced biomineralization, due to the presence of nBGC in the alginate scaffold. Incorporation of nBGC did not alter the viability of MG-63 and hPDLF cells and also helped to attain good protein adsorption, cell attachment, and cell proliferation onto the scaffolds. The hPDLF cells also showed distinct osteoblastlike behavior with enhanced alkaline phosphatase activity. All these results suggested that alginate/nBGC composite scaffold serves as an appropriate bioactive matrix for periodontal tissue regeneration, thus indicating signs of another successive outbreak in the field of periodontal tissue engineering. In another study, Fang Yang and colleagues developed an electrospun nanoapatite/PCL (polycaprolactone) composite membrane for GTR/GBR (guided bone regeneration) application, the results showed that the electrospun membrane incorporating nanoapatite is strong, enhances bioactivity, and supports osteoblast-like cell proliferation and differentiation. The membrane system can be used as a prototype for the further development of an optimal membrane for clinical use [44].
20.4 NANOTECHNOLOGY FOR TOOTH REGENERATION Tooth regeneration has long been the dental profession’s aspiration, however, the combination of tissue bioengineering along with the development of genetically designed trigger nanoparticles, which are biomimetic with mineralized tissues, has begun to bear fruit in the manufacturing of in vitro teeth. Jeremy J. Mao, the pioneer researcher in dental regeneration, suggested that the regeneration of teeth can be divided into several specific areas as follows [45]: 1. 2. 3. 4. 5. 6. 7. 8.
Regeneration or de novo formation of an entire, anatomically correct tooth; Regeneration of the root; Regeneration of dental pulp; Regeneration of dentin that may either act as reparative dentin to seal off an exposed pulp chamber or as a replacement of current synthetic materials; Regeneration of cementum as a part of periodontium regeneration or for loss of cementum and/or dentin resulting from orthodontic tooth movement; Regeneration of periodontium including cementum, periodontal ligament, and alveolar bone; Regeneration or synthesis of enamel-like structures that may be used as biological substitute for enamel; Remineralization of enamel and dentin.
For tooth regeneration, biomaterials have served primarily as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. It is indispensable for the regeneration of tooth root, tooth crown, dental pulp, or an
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entire tooth. Nanomaterials, which can mimic the surface properties of natural tissues, have been highlighted as promising candidates for improving traditional dental tissue engineering materials. The various forms of tooth tissue engineering related to nanotechnology and nanomaterials are described in the following sections.
20.4.1 NANOMATERIALS IN BIOMIMETIC ENAMEL REGENERATION Enamel is the hardest material formed by vertebrates and is the most highly mineralized skeletal tissue present in the body. Mature enamel is composed of 95% 97% carbonated HA by weight with less than 1% organic material. Mature dental enamel has a complex form, providing a striking example of a highly mineralized structure exquisitely adapted to absorb essential mechanical and abrasive stresses throughout the lifetime of the organism (Fig. 20.3) [46]. However, enamel cannot heal itself by a cellular repair as enamel is both acellular and avascular. It loses mineral substances due to caries, trauma, and erosion. Restorations of damaged tooth tissues with artificial materials represent the traditional therapeutic solutions. Although many sophisticated materials are now available for restoration, their use is not yet completely satisfactory. A combination of tissue bioengineering with the development of genetically designed trigger nanoparticles which are biomimetic with mineralized tissues, has begun to bear
FIGURE 20.3 The organization of dental enamel. Scanning electron micrograph of the surface of an acid-etched ground section of mature mouse incisal dental enamel. Ordered arrays of enamel prisms are each constructed of parallel bundles of carbonated hydroxyapatite enamel crystallites. Reproduced from A.G. Fincham, J. Moradian-Oldak, J.P. Simmer, The structural biology of the developing dental enamel matrix, J. Struct. Biol. 126 (1999) 270 299, with permission from Elsevier.
20.4 Nanotechnology for Tooth Regeneration
fruit in the manufacturing of in vitro teeth tissue, even whole teeth. For example, the amelogenin gene has been manipulated to adhere to HA nanoparticles. When these are directly shot to pluripotential cells encapsulated in nanohydrogels they begin to work on the formation of the enamel tissue [47]. Previous attempts to engineer enamel focused mainly on chemical synthesis. Chen and collaborators synthesized and modified the HA nanorod surface with monolayers of surfactants to create specific surface characteristics that allowed the nanorods to selfassemble into an enamel prism-like structure at the water air interface. The size of the synthetic HA nanorods can be controlled, and synthesized nanorods were similar in size to both human and rat enamel crystals [48]. In their other studies, prism-like structures, consisting of fluorapatite crystals similar to the dimensions of those seen in human enamel have been synthesized using hydrothermal method [49]. This method is a widely adopted nanotechnology to create nanorods, nanowires, and whiskers and has already been shown to be an effective way to create different kinds of nanomaterials [50 52]. However, the majority of these synthesis methods were developed use high temperature, high pressure, and extremely acidic pH, or in the presence of a concentrated solution of surfactants. It is generally accepted that the biomimetic synthesis of enamellike apatite structures under physiological conditions is an alternative restorative pathway. Recently, Lili et al. reported that a bio-inspired cooperative effect of an amino acid (glutamic acid, Glu) and nanoapatite particles can result in the regeneration of enamel-like structure under physiological conditions. Importantly, the mechanical characteristics of the repaired enamel are well maintained by using this feasible enamel remodel [53]. These successful approaches of enamel regeneration imply a potential of material-inspired strategy of nanoassembling in biomedical applications and open the possibility that in the future dental practice might drastically change, allowing the manufacturing of teeth in the dental practice office.
20.4.2 NANOMATERIAL IN ENAMEL AND DENTINE REMINERALIZATION The prevention of tooth decay and the treatment of lesions and cavities are ongoing challenges in dentistry. In recent years, biomimetic approaches have been used to develop nanomaterials for the remineralization of early enamel lesions [54]. Nowadays, nano-HA is widely studied as a biomimetic material for the reconstruction of tooth enamel suffering from mineral loss and as an effective anticaries agent because of its unique potential for remineralization [55 62]. Our previous studies demonstrated that nano-HA has the potential to remineralize initial enamel caries lesions under dynamic pH cycling conditions. In addition, a concentration of 10% nano-HA may be optimal for remineralization of early enamel caries in vitro [63]. In further research, however we found that nano-HA helped mineral deposition predominantly in the outer layer of the lesion and only
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had a limited capacity to reduce lesion depth. Nevertheless, the remineralization effect of nano-HA increased significantly when the pH was less than 7.0 [64]. Further, our research showed that there was a significant synergistic effect of combined galla chinensis (GCE) and nano-HA treatment on promoting the remineralization of initial enamel lesion [65]. When GCE was added with nano-HA, a significantly higher volume percent mineral was present in the body of the lesion, it would not completely inhibit the deposition of nano-HA on the out layer of lesion in the remineralization process, so full remineralization on the initial enamel lesion was obtained. The scanning electron microscope (SEM) images showed that the crystals of the surface layer in the GCE 1 nano-HA group were arranged regularly and a densely uniform structure was formed (Fig. 20.4E), whereas, irregularly arranged crystals were present in the nano-HA group (Fig. 20.4C). Accumulated evidence has demonstrated that the average size of the calcium phosphate crystals plays an essential role in the formation of hard tissues and has a significant influence on its intrinsic properties, including solubility and biocompatibility [66,67]. An in vitro study demonstrated that evenly sized nanoapatite particles (20 nm-sized HA and building blocks of biological apatite of dental enamel) could simultaneously repair and prevent initial erosive lesions in enamel compared with conventional HA crystals that are hundreds of nanometers in length [61]. Our in vitro study also demonstrated that nano-HA provides better remineralization than micro-HA. Generally, these studies suggest that analogues of nanobuilding blocks of biominerals should be highlighted in the entire subject of biomineralization. In summary, the remineralization effect of nano-HA on caries lesions is clear, but the mechanism of action is still open to debate. A number of researchers have proposed that nano-HA promotes remineralization through excellent deposition onto etched enamel [61] or by depositing apatite nanoparticles in the defects on demineralized enamel. Other researchers, however, have suggested that nano-HA acts to deliver a calcium source to the mouth, which can increase oral calcium levels, and has the potential to limit acid challenges by reducing enamel demineralization while promoting enamel remineralization [55 57]. Based on these theories combined with our current results, we propose that the mechanism of remineralization is that HA acts as a calcium phosphate reservoir, helping to maintain a state of supersaturation with respect to enamel minerals, thereby depressing enamel demineralization and enhancing remineralization; this is in accordance with the classic paradigm of “top-down” ion-mediated crystalline growth to account for the intricate biomineralization strategies identified in nature [68]. Nano-HA, on the other hand, shows promising remineralization efficacy on enamel lesions in view of its unique characteristics, including excellent deposition properties, which are in good agreement with the “bottom-up” concept of particle-mediated nanoprecursor assembly and mesocrystalline transformation in the biomineralization process [69].
FIGURE 20.4 SEM images of the enamel surfaces in different groups (60,000 3 ). Many micropores and honeycomb structures were apparently on enamel surface in DDW group (B), however, after application of nano-HA, acicular crystals had sedimented on the lesion surface and the cavities and microspores significantly decreased, meanwhile, the surface of the demineralized enamel appeared to be covered by crystal, arranged in a thick and homogeneous apatite layer (C). Some fingerlike crystals disorderly distributed on the surface of enamel after treated with GCE, a honeycomb structure still remained in some regions on the surface of the lesion (D). In GCE 1 nano-HA group, the surface morphology was similar to that in the nano-HA group, however, the crystals were arranged regularly and a dense layer was also obtained after addition of GCE (E). Different-sized globules were formed on the lesion surface in the NaF group (A). HA, Hydroxyapatite.
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Other biomimetic approaches for remineralization of initial submicrometer enamel erosions and lesions are based on nanosized casein phosphopeptide amorphous calcium phosphate (CPP ACP). The CPP ACP prevents demineralization and promotes remineralization of initial enamel lesions in laboratory, animal, and human experiments and in randomized, controlled clinical trials [70 78]. The CPP ACP literature has been reviewed by several authors [79 81] with the most recent being a systematic meta-analysis concluding that there is sufficient clinical evidence demonstrating enamel remineralization and caries prevention by regular use of products containing CPP ACP [82]. The CPPs stabilize calcium and phosphate ions through the formation of amorphous nanocomplexes, which would be expected to enter the porosities of an enamel subsurface lesion and diffuse down concentration gradients into the body of the subsurface lesion. Once present in the enamel subsurface lesion, the CPP ACP would release the weakly bound calcium and phosphate ions which then deposit into crystal voids [82]. Further, the CPP ACP nanocomplexes have also been demonstrated to bind onto the tooth surface and into supragingival plaque to significantly increase the level of bioavailable calcium and phosphate ion [83]. In all of the remineralization technologies currently available commercially, the CPP ACP and CPP ACFP (amorphous calcium fluoride phosphate) technology has the most evidence to support its use. Except for the nano-HA and CPP ACP, other nanosize calcium phosphates have also been considered as remineralization agents due to their unique properties. For nanodimensional dicalcium phosphate anhydrous (DCPA), decreasing of DCPA particle dimensions was found to increase the Ca21 and PO32 4 ions release from DCPA-based biocomposites. Nano-DCPA-based biocomposites, possessing both high strength and good release of Ca21 and PO32 4 ions, may therefore, provide the needed and unique combination of stress-bearing and caries-inhibiting capabilities suitable for dental applications [84]. A positive influence of adding nanodimensional β-TCP (tricalcium phosphate) against acid demineralization and promoted remineralization of enamel surface was also detected [85]. In another in vitro study, nanosized amorphous calcium carbonate particles applied twice a day for 20 days promoted remineralization of artificial white-spot enamel lesions [86]. Dentine remineralization is clinically significant for the prevention and treatment of dentine caries, root caries, and dentine hypersensitivity. Dentine remineralization is, however, more difficult than enamel remineralization due to the abundant presence of organic matrix in dentine. An accepted notion is that dentine remineralization occurs neither by the spontaneous precipitation nor by the nucleation of mineral on the organic matrix (mainly type I collagen) but by the growth of residual inorganic crystals in the lesions [87]. Reconstitution and remineralization of dentine using nanosized bioactive glass particles and betatricalcium phosphate was also tested in vitro, however, the mechanical properties
20.4 Nanotechnology for Tooth Regeneration
of original dentine could not be reproduced [88,89]. Fortunately, the biomimetic remineralization scheme provides a proof-of-concept for the adoption of nanotechnology as an alternative strategy to remineralization of dentine. Metastable ACP nanoprecursors were generated when polyacrylic acid was included in the phosphate-containing fluid. The nanoprecursors were attracted to the acid-demineralized collagen matrix and transformed into polyelectrolytestabilized apatite nanocrystals that assembled along the microfibrils (intrabrillar remineralization) and surface of the collagen fibrils (interfibrillar remineralization) to achieve dentine remineralization [90]. The results revealed that guided tissue remineralization based on nanotechnology is potentially useful in the remineralization of acid-etched dentine that is incompletely infiltrated by dentine adhesives, and partially demineralized caries-affected dentine.
20.4.3 NANOMATERIAL IN DENTIN PULP COMPLEX REGENERATION Restorative dentistry is looking for techniques and materials to regenerate the dentin pulp complex in a biological manner. This showed the great potential in the treatment of our most common oral health problem and cavities. There is evidence suggesting that odontoblasts (cells that produce dentin), dental pulp stem cells (DPSC), and stem cells from human exfoliated deciduous teeth (SHED) are able to produce pulp/dentin-like tissues when seeded on specific condition or scaffolds [91 94]. In the process, advanced biomimetic scaffolding materials are versatile enough to provide a suitable 3D network to accommodate these cells and guide their growth, organization, and differentiation. One important step toward regenerative endodontics was achieved when SHED mixed with nanofiber peptide scaffold and injected into full-length root canals were able to generate a dental pulp. Fig. 20.5 shows the presence of a pulp tissue fulfilling the hollow passageway of the root canal, with proliferative activity and blood network maturity comparable to those observed in a young human dental pulp [95]. Another in vitro study showed that peptide-amphiphile molecules provide a nanostructured, cell-responsive matrix that is specifically conducive to dental stem cells. The SHED and DPSC seeded in phosphate (PA) hydrogels show differences in morphology, proliferation, and differentiation behavior. SHED appears to be a suitable tool for soft tissue regeneration, such as dental pulp, whereas DPSC might be useful for engineering mineralized tissues like dentin [96]. Further development and successful application of these strategies to regenerate dentin and dental pulp could one day revolutionize the treatment of our most common oral health problem and cavities.
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FIGURE 20.5 Dental pulp tissue engineered for 35 days inside root canal using SHED cells (A) and natural dental pulp from premolar (B). It is possible to observe the formation of a healthy tissue without inflammatory signs and a densification of odontoblast-like cell along dentin walls in the SHED originated tissue similar to the control. The engineered tissue occupies the whole apical portion (C) and immunohistochemistry with PCNA and factor VIII shows a proliferative tissue with a well-established and mature blood network (D and E). PCNA, proliferating cell nuclear activity; SHED, Stem cells from human exfoliated deciduous teeth. Reproduced from V. Rosa, A. Della Bona, B.N. Cavalcanti, J.E. No¨r, Tissue engineering: from research to dental clinics, Dent. Mater. 28 (2012) 341 348, with permission from Elsevier.
References
20.5 CONCLUSIONS Despite the challenges in dental tissue regeneration that lie ahead, significant evidence exists to support the premise that recent advances in nanotechnology, acting as biomimetic tools, show great potential to overcome the challenges and promise for improved dental tissue regeneration. Nanomaterials tailored for engineering dental tissues are continually being introduced and yield numerous clinical dental benefits. These include improved treatments for periodontal defects, enhanced maxillary and mandibular bone regeneration, perhaps more biological methods to repair teeth after carious damage and possibly even regrowing lost teeth. In the near future, advances in bioengineering research will lead to wide application of regenerative dentistry into general dental practice to produce wonderful treatments and dramatically improve patients’ quality of life.
REFERENCES [1] R. Langer, J.P. Vacanti, Tissue engineering, Science 260 (1993) 920 926. [2] S. Yildirim, S.Y. Fu, K. Kim, H. Zhou, C.H. Lee, A. Li, et al., Tooth regeneration: a revolution in stomatology and evolution in regenerative medicine, Int. J. Oral Sci. 3 (2011) 107 116. [3] R.W. Siegel, G.E. Fougere, Mechanical properties of nanophase metals, Nanostruct. Mater. 6 (1995) 205. [4] S.M. Warren, K.D. Fong, C.M. Chen, E.G. Loboa, C.M. Cowan, H.P. Lorenz, et al., Tools and techniques for craniofacial tissue engineering, Tissue Eng. 9 (2003) 187 200. [5] L.J. Zhang, T.J. Webster, Nanotechnology and nanomaterials: promises for improved tissue regeneration, Nano Today 4 (2009) 66 80. [6] H. Yoshimoto, Y. Shin, H. Terai, J. Vacanti, A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering, Biomaterials 24 (2003) 2077 2082. [7] M. Jose, V. Thomas, Y. Xu, S. Bellis, E. Nyairo, D. Dean, Aligned bioactive multicomponent nanofibrous nanocomposite scaffolds for bone tissue engineering, Macromol. Biosci. 10 (2010) 433 444. [8] A. Asran, S. Henning, G. Michler, Polyvinyl alcohol-collagen-hydroxyapatite biocomposite nanofibrous scaffold: mimicking the key features of natural bone at the nanoscale level, Polymer 51 (2010) 868 876. [9] J. Venugopal, M. Prabhakaran, Y. Zhang, S. Low, A.T. Choon, S. Ramakrishna, Biomimetic hydroxyapatite-containing composite nanofibrous substrates for bone tissue engineering, Philos. Trans. A Math. Phys. Eng. Sci. 368 (2010) 2065 2081. [10] M.J. Gupte, P.X. Ma, Nanofibrous scaffolds for dental and craniofacial applications, J. Dent. Res. 91 (2012) 227 234. [11] T.J. Webster, C. Ergun, R.H. Doremus, R.W. Siegel, R. Bizios, Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics, J. Biomed. Mater. Res. 51 (2000) 475 483.
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[12] T.J. Webster, C. Ergun, R.H. Doremus, R.W. Siegel, R. Bizios, Enhanced osteoclastlike cell functions on nanophase ceramics, Biomaterials 22 (2001) 1327 1333. [13] S.P. Nukavarapu, S.G. Kumbar, J.L. Brown, N.R. Krogman, A.L. Weikel, M.D. Hindenlang, et al., Polyphosphazene/nano-hydroxyapatite composite microsphere scaffolds for bone tissue engineering, Biomacromolecules 9 (2008) 1818 1825. [14] M. Sato, M.A. Sambito, A. Aslani, N.M. Kalkhoran, E.B. Slamovich, T.J. Webster, Increased osteoblast functions on undoped and yttrium-doped nanocrystalline hydroxyapatite coatings on titanium, Biomaterials 27 (2006) 2358 2369. [15] E.S. Thian, J. Huang, S.M. Best, Z.H. Barber, R.A. Brooks, N. Rushton, et al., The response of osteoblasts to nanocrystalline silicon-substituted hydroxyapatite thin films, Biomaterials 27 (2006) 2692 2698. [16] K.U. Lewandrowski, S.P. Bondre, D.L. Wise, D.J. Trantolo, Enhanced bioactivity of a poly(propylene fumarate) bone graft substitute by augmentation with nanohydroxyapatite, Biomed. Mater. Eng. 13 (2003) 115 124. [17] E.S. Thian, Z. Ahmad, J. Huang, M.J. Edirisinghe, S.N. Jayasinghe, D.C. Ireland, et al., Bioactivity of nanoapatite produced by electrohydrodynamic atomization, J. Bionanosci. 1 (2007) 60 63. [18] S. Pezzatini, R. Solito, L. Morbidelli, S. Lamponi, E. Boanini, A. Bigi, et al., The effect of hydroxyapatite nanocrystals on microvascular endothelial cell viability and functions, J. Biomed. Mater. Res. A 76A (2006) 656 663. [19] S. Pezzatini, L. Morbidelli, R. Solito, E. Paccagnini, E. Boanini, A. Bigi, et al., Nanostructured HA crystals up-regulate FGF-2 expression and activity in microvascular endothelium promoting angiogenesis, Bone 41 (2007) 523 534. [20] S.I. Stupp, G.W. Ciegler, Organoapatites: materials for artificial bone. I. Synthesis and microstructure, J. Biomed. Mater. Res. 26 (1992) 169 183. [21] J. Huang, S.M. Best, W. Bonfield, R.A. Brooks, N. Rushton, S.N. Jayasinghe, et al., In vitro assessment of the biological response to nanosized hydroxyapatite, J. Mater. Sci. Mater. Med. 15 (2004) 441 445. [22] G. Colon, B.C. Ward, T.J. Webster, Increased osteoblast and decreased Staphylococcus epidermidis functions on nanophase ZnO and TiO2, J. Biomed. Mater. Res. A 78 (2006) 595 604. [23] T.J. Webster, E.L. Hellenmeyer, R.L. Price, Increased osteoblast functions on theta 1 delta nanofiber alumina, Biomaterials 26 (2005) 953 960. [24] W. Paul, C.P. Sharma, Nanoceramic matrices: biomedical applications, Am. J. Biochem. Biotechnol. 2 (2006) 41 48. [25] F.X. Huber, N. McArthur, J. Hillmeier, H.J. Kock, M. Baier, M. Diwo, et al., Void filling of tibia compression fracture zones using a novel resorbable nanocrystalline hydroxyapatite paste in combination with a hydroxyapatite ceramic core: first clinical results, Arch. Orthop. Trauma Surg. 126 (2006) 533 540. [26] R. Smeets, G. Jelitte, M. Heiland, A. Kasaj, M. Grosjean, D. Riediger, et al., Hydroxylapatit-Knochenersatzmaterial (Ostim®) bei der Sinusbodenelevation, Schweiz Monatsschr. Zahnmed. 118 (2008) 203 208. [27] K.L. Gerlach, D. Niehues, Die Behandlung der Kieferzysten mit einem neuartigen nanopartikula¨ren Hydroxylapatit, Mund Kiefer GesichtsChir. 11 (2007) 131 137. [28] F. Schwarz, K. Bieling, T. Latz, E. Nuesry, J. Becker, Healing of intrabony periimplantitis defects following application of a nanocrystalline hydroxyapatite (Ostimt) or a bovine-derived xenograft (Bio-Osst) in combination with a collagen membrane (Bio-Gidet). A case series, J. Clin. Periodontol. 33 (2006) 491 499. Materials 2 (2009) 2037.
References
[29] F.P. Strietzel, P.A. Reichart, H.L. Graf, Lateral alveolar ridge augmentation using a synthetic nano-crystalline hydroxyapatite bone substitution material (Ostim®). Preliminary clinical and histological results, Clin. Oral Implants Res. 18 (2007) 743 751. [30] C. Spies, S. Schnu¨rer, T. Gotterbarm, S. Breusch, Tierexperimentelle Untersuchung des Knochenersatzstoffs Ostimt im kno¨chernen Lager des Go¨ttinger Miniaturschweins, Z. Orthop. Unfall. 146 (2008) 64 69. [31] M. Thorwarth, S. Schultze-Mosgau, P. Kessler, J. Wiltfang, K.A. Schlegel, Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite, J. Oral Maxillofac. Surg. 63 (2005) 1626 1633. [32] J. Brandt, S. Henning, G. Michler, M. Schulz, A. Bernstein, Nanocrystalline hydroxyapatite for bone repair, Key Eng. Mater. 361 363 (2008) 35 38. [33] F.X. Huber, J. Hillmeier, L. Herzog, N. McArthur, H.J. Kock, P.J. Meeder, Open reduction and palmar plate-osteosynthesis in combination with a nanocrystalline hydroxyapatite spacer in the treatment of comminuted fractures of the distal radius, J. Hand Surg. (Brit). 31B (2006) 298 303. [34] F.X. Huber, J. Hillmeier, N. McArthur, H.J. Kock, P.J. Meeder, The use of nanocrystalline hydroxyapatite for the reconstruction of calcaneal fractures: preliminary results, J. Foot Ankle Surg. 45 (2006) 322 328. [35] M.W. Laschke, K. Witt, T. Pohlemann, M.D. Menger, Injectable nanocrystalline hydroxyapatite paste for bone substitution: in vivo analysis of biocompatibility and vascularization, J. Biomed. Mater. Res. B Appl. Biomater. 82B (2007) 494 505. [36] C.K.G. Spies, S. Schnu¨rer, T. Gotterbarm, S. Breusch, The efficacy of Biobont and Ostimt within metaphyseal defects using the Go¨ttinger Minipig, Arch. Orthop. Trauma Surg. 129 (2009) 979 988. [37] Y.K. Kim, L.S. Gu, T.E. Bryan, J.R. Kim, L. Chen, Y. Liu, et al., Mineralisation of reconstituted collagen using polyvinylphosphonic acid/polyacrylic acid templating matrix protein analogues in the presence of calcium, phosphate and hydroxyl ions, Biomaterials 31 (2010) 6618 6627. [38] Y. Zhang, V.J. Reddy, S.Y. Wong, X. Li, B. Su, S. Ramakrishna, et al., Enhanced biomineralization in osteoblasts on a novel electrospun biocomposite nanofibrous substrate of hydroxyapatite/collagen/chitosan, Tissue Eng. Part A 16 (2010) 1949 1960. [39] E. Kon, M. Delcogliano, G. Filardo, D. Pressato, M. Busacca, B. Grigolo, et al., A novel nanocomposite multilayered biomaterial for treatment of osteochondral lesions: technique note and an early stability pilot clinical trial, Injury 41 (2010) 693 701. [40] C. Erisken, D.M. Kalyon, H. Wang, C. Ornek-Ballanco, J. Xu, Osteochondral tissue formation through adipose-derived stromal cell differentiation on, biomimetic polycaprolactone nanofibrous scaffolds with graded insulin and beta-glycerophosphate concentrations, Tissue Eng. Part A 17 (2011) 1239 1252. [41] F.M. Chen, J. Zhang, M. Zhang, Y. An, F. Chen, Z.F. Wu, A review on endogenous regenerative technology in periodontal regenerative medicine, Biomaterials 31 (2010) 7892 7927. [42] P.X. Ma, Biomimetic materials for tissue engineering, Adv. Drug Deliv. Rev. 60 (2008) 184 198. [43] S. Srinivasan, R. Jayasree, K.P. Chennazhi, S.V. Nair, R. Jayakumar, Biocompatible alginate/nano bioactive glass ceramic composite scaffolds for periodontal tissue regeneration, Carbohydr. Polym. 87 (2012) 274 283.
511
512
CHAPTER 20 Biomimetics using nanotechnology/nanoparticles
[44] F. Yang, S.K. Both, X. Yang, X.F. Walboomers, J.A. Jansen, Development of an electrospun nano-apatite/PCL composite membrane for GTR/GBR application, Acta Biomater. 5 (2009) 3295 3304. [45] Z. Yuan, H. Nie, S. Wang, C.H. Lee, A. Li, S.Y. Fu, et al., Biomaterial selection for tooth regeneration, Tissue Eng. Part B Rev. 17 (2011) 373 388. [46] A.G. Fincham, J. Moradian-Oldak, J.P. Simmer, The structural biology of the developing dental enamel matrix, J. Struct. Biol. 126 (1999) 270 299. [47] Z. Huang, T.D. Sargeant, J.F. Hulvat, A. Mata, P. Bringas, C.H. Koh, et al., Bioactive nanofibers instruct cells to proliferate and differentiate during enamel regeneration, J. Bone Miner. Res. 23 (2008) 1995 2006. [48] H.F. Chen, B.H. Clarkson, K. Sun, J.F. Mansfield, Self-assembly of synthetic hydroxyapatite nanorods into enamel prism like structure, J. Colloid Interface Sci. 188 (2005) 97 103. [49] H.F. Chen, Z.Y. Tang, J. Liu, K. Sun, S.R. Chang, M.C. Peters, et al., Acellular synthesis of a human enamel-like microstructure, Adv. Mater. 18 (2006) 1846 1851. [50] Y. Fujishiro, A. Fujimoto, T. Sato, A. Okuwaki, Coating of hydroxyapatite on titanium plates using thermal-dissociation of calcium-EDTA chelate complex in phosphate solutions under hydrothermal conditions, J. Colloid Interface Sci. 173 (1995) 119 127. [51] W. Suchannek, M. Yoshimura, Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants, J. Mater. Res. 13 (1998) 94 117. [52] M. Cao, Y. Wang, C. Guo, Y. Qi, C. Hu, Preparation of ultrahigh-aspect-ratio hydroxyapatite nanofibers in reverse micelles under hydrothermal conditions, Langmuir 20 (2004) 4784. [53] L. Li, C. Mao, J. Wang, X. Xu, H. Pan, Y. Deng, et al., Bio-inspired enamel repair via Glu-directed assembly of apatite nanoparticle: an approach to biomaterials with optimal characteristic, Adv. Mater. 23 (2011) 4695 4701. [54] M. Hannig, C. Hannig, Nanomaterials in preventive dentistry, Nat. Nanotechnol. 5 (2010) 565 569. [55] K. Onuma, K. Yamagishi, A. Oyane, Nucleation and growth of hydroxyapatite nanocrystals for nondestructive repair of early caries lesions, J. Cryst. Growth 282 (2005) 199 207. [56] Y. Yamagishi, K. Onuma, T. Suzuki, F. Okada, J. Tagami, M. Otsuki, et al., A synthetic enamel for rapid tooth repair, Nature 433 (2005) 819. [57] K.L. Lv, J.X. Zhang, X.C. Meng, X.Y. Li, Remineralization effect of the nano-HA toothpaste on artificial caries, Key Eng. Mater. 330 332 (2007) 267 270. [58] M.Y. Kim, H.K. Kwon, C.H. Choi, B.I. Kim, Combined effects of nanohydroxyapatite and NaF on remineralization of early caries lesion, Key Eng. Mater. 330 332 (2007) 1347 1350. [59] N. Roveri, E. Battistella, I. Foltran, E. Foresti, M. Iafisco, M. Lelli, et al., Synthetic biomimetic carbonate-hydroxyapatite nanocrystals for enamel remineralization, Adv. Mater. Res. 47 50 (2008) 821 824. [60] N. Roveri, E. Battistella, C.L. Bianchi, I. Foltran, E. Foresti, M. Lafisco, et al., Surface enamel remineralization: biomimetic apatite nanocrystals and fluoride ions different effects, J. Nanomater. (2009) 746383. Available from: https://doi.org/ 10.1155.
References
[61] L. Li, H.H. Pan, J.H. Tao, X.R. Xu, C.Y. Mao, X.H. Gu, et al., Repair of enamel by using hydroxyapatite nanoparticles as the building blocks, J. Mater. Chem. 18 (2008) 4079 4084. [62] P. Tschoppe, D.L. Zandim, P. Martus, A.M. Kielbassa, Enamel and dentine remineralization by nano-hydroxyapatite toothpastes, J. Dent. 3 (2011) 430 437. [63] S.B. Huang, S.S. Gao, H.Y. Yu, Effect of nano-hydroxyapatite concentration on remineralization of initial enamel lesion in vitro, Biomed. Mater. 4 (2009) 034104. [64] S. Huang, S. Gao, L. Cheng, H. Yu, Remineralization potential of nanohydroxyapatite on initial enamel lesions: an in vitro study, Caries Res. 45 (2011) 460 468. [65] S. Huang, S. Gao, L. Cheng, H. Yu, Combined effects of nano-hydroxyapatite and Galla chinensis on remineralization of initial enamel lesion in vitro, J. Dent. 38 (2010) 811 819. [66] G. Balasundaram, M. Sato, T.J. Webster, Using hydroxyapatite nanoparticles and decreased crystallinity to promote osteoblast adhesion similar to functionalizing with RGD, Biomaterials 27 (2006) 2798 2805. [67] Q. Hu, Z. Tan, Y. Liu, J. Tao, Y. Cai, M. Zhang, et al., Effect of crystallinity of calcium phosphate nanoparticles on adhesion, proliferation, and differentiation of bone marrow mesenchymal stem cells, J. Mater. Chem. 17 (2007) 4690 4698. [68] S. Mai, Y.K. Kim, M. Toledano, L. Breschi, J.Q. Ling, D.H. Pashley, et al., Phosphoric acid esters cannot replace polyvinylphosphonic acid as phosphoprotein analogs in biomimetic remineralization of resin-bonded dentin, Dent. Mater. 25 (2009) 1230 1239. [69] A.W. Xu, Y.R. Ma, H. Colfen, Biomimetic mineralization, J. Mater. Chem. 17 (2007) 415 449. [70] E.C. Reynolds, Remineralization of enamel subsurface lesions by casein phosphopeptide-stabilized calcium phosphate solutions, J. Dent. Res. 76 (1997) 1587 1595. [71] M.V. Morgan, G.G. Adams, D.L. Bailey, C.E. Tsao, S.L. Fischman, E.C. Reynolds, The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography, Caries Res. 42 (2008) 171 184. [72] F. Cai, D.J. Manton, P. Shen, G.D. Walker, K.J. Cross, Y. Yuan, et al., Effect of addition of citric acid and casein phosphopeptide amorphous calcium phosphate to a sugar-free chewing gum on enamel remineralization in situ, Caries Res. 41 (2007) 377 383. [73] Y. Iijima, F. Cai, P. Shen, G. Walker, C. Reynolds, E.C. Reynolds, Acid resistance of enamel subsurface lesions remineralized by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate, Caries Res. 38 (2004) 551 556. [74] A.M. Al-Mullahi, K.J. Toumba, Effect of slow-release fluoride devices and casein phosphopeptide/amorphous calcium phosphate nanocomplexes on enamel remineralization in vitro, Caries Res. 44 (2010) 364 371. [75] J.D. Bader, Casein phosphopeptide-amorphous calcium phosphate shows promise for preventing caries, Evid. Based Dent. 11 (2010) 11 12. [76] G.D. Walker, F. Cai, P. Shen, G.G. Adams, C. Reynolds, E.C. Reynolds, Casein phosphopeptide-amorphous calcium phosphate incorporated into sugar confections
513
514
CHAPTER 20 Biomimetics using nanotechnology/nanoparticles
[77]
[78]
[79] [80]
[81]
[82] [83]
[84]
[85]
[86]
[87] [88]
[89]
[90] [91]
[92]
inhibits the progression of enamel subsurface lesions in situ, Caries Res. 44 (2010) 33 40. N. Srinivasan, M. Kavitha, S.C. Loganathan, Comparison of the remineralization potential of CPP ACP and CPP ACP with 900 ppm fluoride on eroded human enamel: an in situ study, Arch. Oral Biol. 55 (2010) 541 544. H. Hamba, T. Nikaido, G. Inoue, A. Sadr, J. Tagami, Effects of CPP ACP with sodium fluoride on inhibition of bovine enamel demineralization: a quantitative assessment using micro-computed tomography, J. Dent. 39 (2011) 405 413. E.C. Reynolds, Anticariogenic complexes of amorphous calcium phosphate stabilized by casein phosphopeptides: a review, Spec. Care Dentist. 18 (1998) 8 16. C. Llena, L. Forner, P. Baca, Anticariogenicity of casein phosphopeptide-amorphous calcium phosphate: a review of the literature, J. Contemp. Dent. Prac. 10 (2009) 1 9. V. Yengopal, S. Mickenautsch, Caries preventive effect of casein phosphopeptideamorphous calcium phosphate (CPP-ACP): a metaanalysis, Acta Odontol. Scand. 21 (2009) 1 12. N.J. Cochrane, F. Cai, N.L. Huq, M.F. Burrow, E.C. Reynolds, New approaches to enhanced remineralization of tooth enamel, J. Dent. Res. 89 (2010) 1187 1197. E.C. Reynolds, F. Cai, P. Shen, G.D. Walker, Retention in plaque and remineralization of enamel lesion by various forms of calcium in a mouthrinse or sugar-free chewing gum, J. Dent. Res. 82 (2003) 206 211. H.H.K. Xu, M.D. Weir, L. Sun, Nanocomposites with Ca and PO4 release: effects of reinforcement, dicalcium phosphate particle size and silanization, Dent. Mater. 23 (2007) 1482 1491. Y.W. Hong, J.H. Kim, B.H. Lee, Y.K. Lee, B.J. Choi, J.H. Lee, et al., The effect of nano-sized β-tricalcium phosphate on remineralization in glass ionomer dental luting cement, Key Eng. Mater. 361 363 (2008) 861 864. S. Nakashima, M. Yoshie, H. Sano, A. Bahar, Effect of a test dentifrice containing nano-sized calcium carbonate on remineralization of enamel lesions in vitro, J. Oral Sci. 51 (2009) 69 77. K. Kawasaki, J. Ruben, I. Stokroos, O. Takagi, J. Arends, The remineralization of EDTA-treated human dentine, Caries Res. 33 (1999) 275 280. Y. Shibata, L.H. He, Y. Kataoka, T. Miyazaki, M.V. Swain, Micromechanical property recovery of human carious dentin achieved with colloidal nano-beta-tricalcium phosphate, J. Dent. Res. 87 (2008) 233 237. M. Vollenweider, T.J. Brunner, S. Knecht, R.N. Grass, M. Zehnder, T. Imfeld, et al., Remineralization of human dentin using ultrafine bioactive glass particles, Acta Biomater. 3 (2007) 936 943. F.R. Tay, D.H. Pashley, Biomimetic remineralization of resin-bonded acid-etched dentin, J. Dent. Res. 88 (2009) 719 724. V.T. Sakai, Z. Zhang, Z. Dong, K.G. Neiva, M. Machado, S. Shi, et al., SHED differentiate into functional odontoblast and endothelium, J. Dent. Res. 89 (2010) 791 796. M.M. Cordeiro, Z. Dong, T. Kaneko, Z. Zhang, M. Miyazawa, S. Shi, et al., Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth, J. Endod. 34 (2008) 962 969.
References
[93] V. Rosa, T.M. Botero, J.E. No¨r, Regenerative endodontics in light of the stem cell paradigm, Int. Dent. J. 61 (2011) 23 28. [94] G. Huang, T. Yamaza, L.D. Shea, F. Djouad, N.Z. Kuhn, R.S. Tuan, et al., Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model, Tissue Eng. Part A 16 (2009) 605 615. [95] V. Rosa, A. Della Bona, B.N. Cavalcanti, J.E. No¨r, Tissue engineering: from research to dental clinics, Dent. Mater. 28 (2012) 341 348. [96] K.M. Galler, A. Cavender, V. Yuwono, H. Dong, S. Shi, G. Schmalz, et al., Selfassembling peptide amphiphile nanofibers as a scaffold for dental stem cells, Tissue Eng. Part A 14 (2008) 2051 2058.
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20
Shengbin Huang1,2, Tingting Wu1,2 and Haiyang Yu1,2 1
State Key Laboratory of Oral Diseases, Chengdu, P.R. China 2West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China
20.1 INTRODUCTION Tissue engineering is a multidisciplinary field by nature, bringing together biology, engineering, and clinical sciences with the goal of generating new tissues and organs [1]. This field builds on the interface between material science and biocompatibility, and integrates cells, natural or synthetic scaffolds, and specific signals to create new tissues. Nowadays, regenerative dentistry is viewed synonymous to tissue engineering in dentistry. Continuous research is going on in this field at both preclinical and clinical levels; remarkable and promising results are also being obtained. However, the high demand for aesthetics of dental tissue structures and the complex atmosphere poses special challenges in this area [2]. Nanotechnology is described as science and techniques which control and manipulate matter at a nanometric level. It has progressed tremendously in the last few decades. Nanomaterials are materials with basic structural units, grains, particles, fibers, or other constituent components smaller than 100 nm in at least one dimension [3] and have great potential in disease prevention, diagnosis, and treatment. To date, advances in this field have led to significant progress in tissue repair and regeneration. With the help of nanotechnology it is possible to interact with cell components, to manipulate cell proliferation and differentiation, and in the production and organization of extracellular matrices. New nanomaterials are leading to a range of emerging dental treatments that utilize more biomimetic materials that closely duplicate natural tooth structure. The uses of nanostructures that will work in harmony with the body’s own regenerative processes are moving into dental clinical practice. In this chapter, we will focus on the recent progress of the applications of nanotechnology in dental tissue regeneration, the contributions of these new technologies in the development of innovative biomimetic materials, and their potential clinical applications.
Nanobiomaterials in Clinical Dentistry. DOI: https://doi.org/10.1016/B978-0-12-815886-9.00020-6 © 2019 Elsevier Inc. All rights reserved.
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20.2 NANOTECHNOLOGY FOR CRANIOFACIAL BONE AND CARTILAGE TISSUE ENGINEERING Craniofacial bone defects secondary to trauma, infection, cancer, and congenital disorders represent a major health problem. Current strategies aimed at replacing bony defects include the utilization of autografts, allografts, and synthetic biomaterials. Despite the fact that these substitutes restore stability and function to a reasonable degree, however they still have limitations. Tissue engineering is considered as an optimal approach for various tissue repairs including craniofacial defect repairs [4]. Biomaterials, acting as scaffolds for tissue engineering, play an essential role in the process of tissue regeneration. Moreover, incorporation of nanotechnology into scaffold design and manufacture will further enhance the quality and function of regenerated tissues. Due to the biomimetic features and excellent physiochemical properties, nanomaterials have been shown to improve adhesion, proliferation, and differentiation of cells, which would finally guide tissue regeneration (Fig. 20.1) [5]. Within the craniofacial tissue engineering field, the major types of materials used are natural and synthetic polymers, ceramics, composite materials, and electrospun nanofibers. Synthetic and natural polymers are excellent candidates for bone/cartilage tissue engineering applications due to their biodegradability and ease of fabrication. Numerous studies have shown successful bone formation with nanofibrous synthetic and natural polymer scaffolds such as electrospun polycaprolactone [6], poly(lactic-co-glycolic acid) [7], polyvinyl alcohol/type I collagen blend [8], and many others [9]. Nanofibrous scaffolds would be an advantageous microenvironment for bone tissue formation by mimicking the type I collagen fibers that are a major component of bone and provide a cellular platform for bone formation [10]. Nanophase ceramics are popular as bone substitutes, coatings, and filler materials due to their dimensional similarity to bone/cartilage tissue and unique surface properties, including surface topography, surface chemistry, surface wettability, and surface energy. Numerous in vitro studies have revealed that nanohydroxyapatite (HA) significantly enhances osteoblast adhesion and function [11 13]. In vivo studies have also demonstrated that nanostructured HA can improve cell attachment and mineralization, suggesting that nanosized HA may be a better candidate for clinical use in terms of bioactivity [14 19]. In general, nanostructured ceramics offer much improved performances compared to their larger particle-sized counterparts due to their huge surface-to-volume ratio and unusual chemical synergistic effects. Nanosized HA is expected to have a better bioactivity than coarser crystals [12,20,21]. Similar tendencies have been reported for other nanoceramics including alumina, zinc oxide, and titania. Osteoblast adhesion increased by 146% and 200% on nanophase zinc oxide (23 nm) and titania (32 nm) compared to microphase zinc oxide (4.9 μm) and titania (4.1 μm), respectively [22,23].
FIGURE 20.1 The biomimetic advantages of nanomaterials. (A) The nanostructured hierarchal self-assembly of bone. (B) Nanophase titanium (top, the atomic force microscopy image) and nanocrystalline HA/HRN hydrogel scaffold (bottom, the SEM image). (C) Schematic illustration of the mechanism by which nanomaterials may be superior to conventional materials for bone regeneration. The bioactive surfaces of nanomaterials mimic those of natural bones to promote greater amounts of protein adsorption and efficiently stimulate more new bone formation than conventional materials. HA, Hydroxyapatite; SEM, Scanning Electron Microscope. Adapted from L.J. Zhang, T.J. Webster, Nanotechnology and nanomaterials: promises for improved tissue regeneration, Nano Today 4 (2009) 66 80, with permission from Elsevier.
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Commercial formulations (nanobone) have also been developed and extensively used in the clinic. nanOss bone void filler from Angstrom Medica Inc. is considered as the first nanotechnological medical device, and received clearance by the US Food and Drug Administration in 2005. Its major composition is calcium orthophosphate nanoparticles, which mimics the nanostructure, composition, and performance of human bone. nanOss is remodeled over time into human bone with applications in sports medicine, trauma, spine, and general orthopedics [24]. Ostim (Osartis GmbH & Co. KG, Obernburg, Germany) is another popular commercial formulation. It is a ready-to-use injectable paste that received Conformite Europeans approval in 2002. Ostim is a suspension of synthetic nano-HA in water, prepared by a wet chemical reaction [25]. Ostim can be used to treat metaphyseal fracture and cysts, alveolar ridge augmentation, osteotomies, etc. [24,26 36]. Although inorganic and organic substances show potential to promote bone regeneration, they have inferior mechanical properties. Bone is composed of both collagen (mainly type I) and mineralized substances (mainly HA), therefore, a biomimetic scaffold should contain both inorganic and organic components. Kim et al. demonstrated that a rapid screening tool for potential biomimetic analogs of collagen mineralization and the nanoscopic protocol could accelerate the application of collagen-HA in bone regeneration [37]. Recently, another study showed that chondroitin sulfate combined with nano-HA exhibited the potential to mimic native bone extracellular matrix (ECM) to promote bone regeneration [38]. These findings show that tissue engineering based on nanotechnology could become a breakthrough approach to reconstructing bone deformities in a more effective and less traumatic way. As it relates to craniofacial reconstruction, the design of polymer scaffolds with defined mechanical and degradative properties has opened a new avenue to cartilage reconstruction. Cartilage destruction is associated with trauma and with degenerative articular cartilage destruction at the temporomandibular joint. The limited capacity of cartilaginous tissue to regenerate and the lack of inductive molecules have focused interest among researchers and manufacturers in developing engineered cartilage. Cartilage itself is avascular and has relatively limited ability for intrinsic repair. A pilot clinical study showed that a newly developed biomimetic osteochondral scaffold with nucleating collagen fibrils along with HA nanoparticles could be used to repair femoral condyle defects of knee joints. Magnetic resonance imaging demonstrated good short-term stability of the scaffold. Histologic analysis showed the formation of subchondral bone without the presence of biomaterials. This result is encouraging and should be a cue for temporomandibular joint (TMJ) defect repair [39]. Gene therapy approaches based on nanotechnology are promising for growth factor signaling mediated cartilage regeneration. As shown by Erisken et al. [40], osteochondral tissue regeneration could be induced with nanofibrous scaffolds fabricated with two different layers that were respectively conjugated with insulin (for chondrogenic differentiation) or with A-glycerophosphate (for osteogenic differentiation). After
20.3 Nanotechnology for Periodontal Regeneration
being seeded on this mimetic scaffold, adipose-derived stem cells could be induced to chondrogenic cells at an insulin-rich location and to osteogenic cells at an A-glycerophosphate-released region. This approach may also be applied for regenerating complex craniofacial tissues such as the TMJ [40].
20.3 NANOTECHNOLOGY FOR PERIODONTAL REGENERATION Periodontal disease leads to destruction of the periodontium: alveolar bone, cementum, the periodontal ligament, and gingiva. Effective treatment for periodontal tissue regeneration plays an important role in the normal function of the craniofacial and systemic system. However, various conventional therapies [open flap debridement, guided tissue regeneration (GTR), and bone replacement grafts, provide either alone or in combination] for periodontal tissue regeneration have shown limited and variable clinical outcomes (Fig. 20.2) [41]. To accelerate clinical translation, there is an ongoing need to develop therapeutics based on endogenous regenerative technology (ERT), which can stimulate latent self-repair mechanisms in patients and harness the host’s innate capacity for regeneration. ERT in periodontics applies the patient’s own regenerative “tool,” that is, patient-derived growth factors and fibrin scaffolds, sometimes in association with commercialized products (e.g., Emdogain and Bio-OSS), to create a material niche in an injured site where the progenitor/stem cells from neighboring tissues can be recruited for in situ periodontal regeneration. The selection and design of materials influence the therapeutic potential and the number and invasiveness of the associated clinical procedures [41]. This has shifted the focus from the attempt to recreate tissue replacement/constructs ex vivo to the development of biofunctionalized biomaterials that incorporate and release regulatory signals in a precise and near-physiological fashion to achieve in situ regeneration. Therefore, certain artificially designed scaffold features, such as porosity, pore size, and interpore connectivity are necessary for optimal tissue engineering applications (accelerated/expedited tissue regeneration), no matter which biomaterial scaffold is proposed [42]. In this regard, a biomimetic scaffold mimicking certain features such as nanoscale topography and biological cues of natural ECM is advantageous for facilitating cell recruitment, seeding, adhesion, proliferation, differentiation, and neotissue genesis [41]. Thus, as mentioned above, biomimetic features and excellent physiochemical properties of nanomaterials play a key role in stimulating cell growth and guiding tissue regeneration. Nanotechnology is expected to play an important role in the design and application of biofunctionalized biomaterials in the periodontal tissue repair process. For example, alginate/nBGC (synthesis of nanobioactive glass ceramic particles) composite scaffolds were successfully fabricated using lyophilization technique and characterized. The scaffolds were found to have characteristic materialistic and biological properties essential to
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FIGURE 20.2 Schematic diagrams of several techniques commonly used in periodontal surgery. (A) OFD procedure involves the periodontal surgeon lifting the gum away from the tooth and surrounding bone, providing increased access for scaling and root planning. However, periodontal defects, if left empty after OFD, fill with the first cells to reach the area, that is, epithelial cells (1) and fibroblasts (2), after cell proliferation, which generates a core of fibroepithelial tissues that attach to the root surface, hence bone (3) and periodontal ligament (3) regeneration are encumbered. (B) GTR is a surgical procedure that utilizes a barrier membrane which is placed under the gum and over the remaining bone to prevent epithelial down-growth (1) and fibroblast trans-growth (2) into the wound space, thereby maintaining a space for true periodontal tissue regeneration (3 and 4). (C) The use of bone grafts is a surgical procedure that replaces missing bone with materials from the patient’s own body (autogenous bone) or an artificial, synthetic, or natural substitute. Bone growth may be stimulated by the grafts and new bone fills the defect which may provide support for the tooth. OFD, Open flap debridement; GTR, guided tissue regeneration. Adapted from F.M. Chen, J. Zhang, M. Zhang, Y. An, F. Chen, Z.F. Wu, A review on endogenous regenerative technology in periodontal regenerative medicine, Biomaterials 31 (2010) 7892 7927, with permission from Elsevier.
20.4 Nanotechnology for Tooth Regeneration
facilitate periodontal regeneration [43]. The composite scaffolds had a pore size of about 100 300 μm, controlled porosity and swelling ability, limited degradation and enhanced biomineralization, due to the presence of nBGC in the alginate scaffold. Incorporation of nBGC did not alter the viability of MG-63 and hPDLF cells and also helped to attain good protein adsorption, cell attachment, and cell proliferation onto the scaffolds. The hPDLF cells also showed distinct osteoblastlike behavior with enhanced alkaline phosphatase activity. All these results suggested that alginate/nBGC composite scaffold serves as an appropriate bioactive matrix for periodontal tissue regeneration, thus indicating signs of another successive outbreak in the field of periodontal tissue engineering. In another study, Fang Yang and colleagues developed an electrospun nanoapatite/PCL (polycaprolactone) composite membrane for GTR/GBR (guided bone regeneration) application, the results showed that the electrospun membrane incorporating nanoapatite is strong, enhances bioactivity, and supports osteoblast-like cell proliferation and differentiation. The membrane system can be used as a prototype for the further development of an optimal membrane for clinical use [44].
20.4 NANOTECHNOLOGY FOR TOOTH REGENERATION Tooth regeneration has long been the dental profession’s aspiration, however, the combination of tissue bioengineering along with the development of genetically designed trigger nanoparticles, which are biomimetic with mineralized tissues, has begun to bear fruit in the manufacturing of in vitro teeth. Jeremy J. Mao, the pioneer researcher in dental regeneration, suggested that the regeneration of teeth can be divided into several specific areas as follows [45]: 1. 2. 3. 4. 5. 6. 7. 8.
Regeneration or de novo formation of an entire, anatomically correct tooth; Regeneration of the root; Regeneration of dental pulp; Regeneration of dentin that may either act as reparative dentin to seal off an exposed pulp chamber or as a replacement of current synthetic materials; Regeneration of cementum as a part of periodontium regeneration or for loss of cementum and/or dentin resulting from orthodontic tooth movement; Regeneration of periodontium including cementum, periodontal ligament, and alveolar bone; Regeneration or synthesis of enamel-like structures that may be used as biological substitute for enamel; Remineralization of enamel and dentin.
For tooth regeneration, biomaterials have served primarily as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. It is indispensable for the regeneration of tooth root, tooth crown, dental pulp, or an
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entire tooth. Nanomaterials, which can mimic the surface properties of natural tissues, have been highlighted as promising candidates for improving traditional dental tissue engineering materials. The various forms of tooth tissue engineering related to nanotechnology and nanomaterials are described in the following sections.
20.4.1 NANOMATERIALS IN BIOMIMETIC ENAMEL REGENERATION Enamel is the hardest material formed by vertebrates and is the most highly mineralized skeletal tissue present in the body. Mature enamel is composed of 95% 97% carbonated HA by weight with less than 1% organic material. Mature dental enamel has a complex form, providing a striking example of a highly mineralized structure exquisitely adapted to absorb essential mechanical and abrasive stresses throughout the lifetime of the organism (Fig. 20.3) [46]. However, enamel cannot heal itself by a cellular repair as enamel is both acellular and avascular. It loses mineral substances due to caries, trauma, and erosion. Restorations of damaged tooth tissues with artificial materials represent the traditional therapeutic solutions. Although many sophisticated materials are now available for restoration, their use is not yet completely satisfactory. A combination of tissue bioengineering with the development of genetically designed trigger nanoparticles which are biomimetic with mineralized tissues, has begun to bear
FIGURE 20.3 The organization of dental enamel. Scanning electron micrograph of the surface of an acid-etched ground section of mature mouse incisal dental enamel. Ordered arrays of enamel prisms are each constructed of parallel bundles of carbonated hydroxyapatite enamel crystallites. Reproduced from A.G. Fincham, J. Moradian-Oldak, J.P. Simmer, The structural biology of the developing dental enamel matrix, J. Struct. Biol. 126 (1999) 270 299, with permission from Elsevier.
20.4 Nanotechnology for Tooth Regeneration
fruit in the manufacturing of in vitro teeth tissue, even whole teeth. For example, the amelogenin gene has been manipulated to adhere to HA nanoparticles. When these are directly shot to pluripotential cells encapsulated in nanohydrogels they begin to work on the formation of the enamel tissue [47]. Previous attempts to engineer enamel focused mainly on chemical synthesis. Chen and collaborators synthesized and modified the HA nanorod surface with monolayers of surfactants to create specific surface characteristics that allowed the nanorods to selfassemble into an enamel prism-like structure at the water air interface. The size of the synthetic HA nanorods can be controlled, and synthesized nanorods were similar in size to both human and rat enamel crystals [48]. In their other studies, prism-like structures, consisting of fluorapatite crystals similar to the dimensions of those seen in human enamel have been synthesized using hydrothermal method [49]. This method is a widely adopted nanotechnology to create nanorods, nanowires, and whiskers and has already been shown to be an effective way to create different kinds of nanomaterials [50 52]. However, the majority of these synthesis methods were developed use high temperature, high pressure, and extremely acidic pH, or in the presence of a concentrated solution of surfactants. It is generally accepted that the biomimetic synthesis of enamellike apatite structures under physiological conditions is an alternative restorative pathway. Recently, Lili et al. reported that a bio-inspired cooperative effect of an amino acid (glutamic acid, Glu) and nanoapatite particles can result in the regeneration of enamel-like structure under physiological conditions. Importantly, the mechanical characteristics of the repaired enamel are well maintained by using this feasible enamel remodel [53]. These successful approaches of enamel regeneration imply a potential of material-inspired strategy of nanoassembling in biomedical applications and open the possibility that in the future dental practice might drastically change, allowing the manufacturing of teeth in the dental practice office.
20.4.2 NANOMATERIAL IN ENAMEL AND DENTINE REMINERALIZATION The prevention of tooth decay and the treatment of lesions and cavities are ongoing challenges in dentistry. In recent years, biomimetic approaches have been used to develop nanomaterials for the remineralization of early enamel lesions [54]. Nowadays, nano-HA is widely studied as a biomimetic material for the reconstruction of tooth enamel suffering from mineral loss and as an effective anticaries agent because of its unique potential for remineralization [55 62]. Our previous studies demonstrated that nano-HA has the potential to remineralize initial enamel caries lesions under dynamic pH cycling conditions. In addition, a concentration of 10% nano-HA may be optimal for remineralization of early enamel caries in vitro [63]. In further research, however we found that nano-HA helped mineral deposition predominantly in the outer layer of the lesion and only
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had a limited capacity to reduce lesion depth. Nevertheless, the remineralization effect of nano-HA increased significantly when the pH was less than 7.0 [64]. Further, our research showed that there was a significant synergistic effect of combined galla chinensis (GCE) and nano-HA treatment on promoting the remineralization of initial enamel lesion [65]. When GCE was added with nano-HA, a significantly higher volume percent mineral was present in the body of the lesion, it would not completely inhibit the deposition of nano-HA on the out layer of lesion in the remineralization process, so full remineralization on the initial enamel lesion was obtained. The scanning electron microscope (SEM) images showed that the crystals of the surface layer in the GCE 1 nano-HA group were arranged regularly and a densely uniform structure was formed (Fig. 20.4E), whereas, irregularly arranged crystals were present in the nano-HA group (Fig. 20.4C). Accumulated evidence has demonstrated that the average size of the calcium phosphate crystals plays an essential role in the formation of hard tissues and has a significant influence on its intrinsic properties, including solubility and biocompatibility [66,67]. An in vitro study demonstrated that evenly sized nanoapatite particles (20 nm-sized HA and building blocks of biological apatite of dental enamel) could simultaneously repair and prevent initial erosive lesions in enamel compared with conventional HA crystals that are hundreds of nanometers in length [61]. Our in vitro study also demonstrated that nano-HA provides better remineralization than micro-HA. Generally, these studies suggest that analogues of nanobuilding blocks of biominerals should be highlighted in the entire subject of biomineralization. In summary, the remineralization effect of nano-HA on caries lesions is clear, but the mechanism of action is still open to debate. A number of researchers have proposed that nano-HA promotes remineralization through excellent deposition onto etched enamel [61] or by depositing apatite nanoparticles in the defects on demineralized enamel. Other researchers, however, have suggested that nano-HA acts to deliver a calcium source to the mouth, which can increase oral calcium levels, and has the potential to limit acid challenges by reducing enamel demineralization while promoting enamel remineralization [55 57]. Based on these theories combined with our current results, we propose that the mechanism of remineralization is that HA acts as a calcium phosphate reservoir, helping to maintain a state of supersaturation with respect to enamel minerals, thereby depressing enamel demineralization and enhancing remineralization; this is in accordance with the classic paradigm of “top-down” ion-mediated crystalline growth to account for the intricate biomineralization strategies identified in nature [68]. Nano-HA, on the other hand, shows promising remineralization efficacy on enamel lesions in view of its unique characteristics, including excellent deposition properties, which are in good agreement with the “bottom-up” concept of particle-mediated nanoprecursor assembly and mesocrystalline transformation in the biomineralization process [69].
FIGURE 20.4 SEM images of the enamel surfaces in different groups (60,000 3 ). Many micropores and honeycomb structures were apparently on enamel surface in DDW group (B), however, after application of nano-HA, acicular crystals had sedimented on the lesion surface and the cavities and microspores significantly decreased, meanwhile, the surface of the demineralized enamel appeared to be covered by crystal, arranged in a thick and homogeneous apatite layer (C). Some fingerlike crystals disorderly distributed on the surface of enamel after treated with GCE, a honeycomb structure still remained in some regions on the surface of the lesion (D). In GCE 1 nano-HA group, the surface morphology was similar to that in the nano-HA group, however, the crystals were arranged regularly and a dense layer was also obtained after addition of GCE (E). Different-sized globules were formed on the lesion surface in the NaF group (A). HA, Hydroxyapatite.
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Other biomimetic approaches for remineralization of initial submicrometer enamel erosions and lesions are based on nanosized casein phosphopeptide amorphous calcium phosphate (CPP ACP). The CPP ACP prevents demineralization and promotes remineralization of initial enamel lesions in laboratory, animal, and human experiments and in randomized, controlled clinical trials [70 78]. The CPP ACP literature has been reviewed by several authors [79 81] with the most recent being a systematic meta-analysis concluding that there is sufficient clinical evidence demonstrating enamel remineralization and caries prevention by regular use of products containing CPP ACP [82]. The CPPs stabilize calcium and phosphate ions through the formation of amorphous nanocomplexes, which would be expected to enter the porosities of an enamel subsurface lesion and diffuse down concentration gradients into the body of the subsurface lesion. Once present in the enamel subsurface lesion, the CPP ACP would release the weakly bound calcium and phosphate ions which then deposit into crystal voids [82]. Further, the CPP ACP nanocomplexes have also been demonstrated to bind onto the tooth surface and into supragingival plaque to significantly increase the level of bioavailable calcium and phosphate ion [83]. In all of the remineralization technologies currently available commercially, the CPP ACP and CPP ACFP (amorphous calcium fluoride phosphate) technology has the most evidence to support its use. Except for the nano-HA and CPP ACP, other nanosize calcium phosphates have also been considered as remineralization agents due to their unique properties. For nanodimensional dicalcium phosphate anhydrous (DCPA), decreasing of DCPA particle dimensions was found to increase the Ca21 and PO32 4 ions release from DCPA-based biocomposites. Nano-DCPA-based biocomposites, possessing both high strength and good release of Ca21 and PO32 4 ions, may therefore, provide the needed and unique combination of stress-bearing and caries-inhibiting capabilities suitable for dental applications [84]. A positive influence of adding nanodimensional β-TCP (tricalcium phosphate) against acid demineralization and promoted remineralization of enamel surface was also detected [85]. In another in vitro study, nanosized amorphous calcium carbonate particles applied twice a day for 20 days promoted remineralization of artificial white-spot enamel lesions [86]. Dentine remineralization is clinically significant for the prevention and treatment of dentine caries, root caries, and dentine hypersensitivity. Dentine remineralization is, however, more difficult than enamel remineralization due to the abundant presence of organic matrix in dentine. An accepted notion is that dentine remineralization occurs neither by the spontaneous precipitation nor by the nucleation of mineral on the organic matrix (mainly type I collagen) but by the growth of residual inorganic crystals in the lesions [87]. Reconstitution and remineralization of dentine using nanosized bioactive glass particles and betatricalcium phosphate was also tested in vitro, however, the mechanical properties
20.4 Nanotechnology for Tooth Regeneration
of original dentine could not be reproduced [88,89]. Fortunately, the biomimetic remineralization scheme provides a proof-of-concept for the adoption of nanotechnology as an alternative strategy to remineralization of dentine. Metastable ACP nanoprecursors were generated when polyacrylic acid was included in the phosphate-containing fluid. The nanoprecursors were attracted to the acid-demineralized collagen matrix and transformed into polyelectrolytestabilized apatite nanocrystals that assembled along the microfibrils (intrabrillar remineralization) and surface of the collagen fibrils (interfibrillar remineralization) to achieve dentine remineralization [90]. The results revealed that guided tissue remineralization based on nanotechnology is potentially useful in the remineralization of acid-etched dentine that is incompletely infiltrated by dentine adhesives, and partially demineralized caries-affected dentine.
20.4.3 NANOMATERIAL IN DENTIN PULP COMPLEX REGENERATION Restorative dentistry is looking for techniques and materials to regenerate the dentin pulp complex in a biological manner. This showed the great potential in the treatment of our most common oral health problem and cavities. There is evidence suggesting that odontoblasts (cells that produce dentin), dental pulp stem cells (DPSC), and stem cells from human exfoliated deciduous teeth (SHED) are able to produce pulp/dentin-like tissues when seeded on specific condition or scaffolds [91 94]. In the process, advanced biomimetic scaffolding materials are versatile enough to provide a suitable 3D network to accommodate these cells and guide their growth, organization, and differentiation. One important step toward regenerative endodontics was achieved when SHED mixed with nanofiber peptide scaffold and injected into full-length root canals were able to generate a dental pulp. Fig. 20.5 shows the presence of a pulp tissue fulfilling the hollow passageway of the root canal, with proliferative activity and blood network maturity comparable to those observed in a young human dental pulp [95]. Another in vitro study showed that peptide-amphiphile molecules provide a nanostructured, cell-responsive matrix that is specifically conducive to dental stem cells. The SHED and DPSC seeded in phosphate (PA) hydrogels show differences in morphology, proliferation, and differentiation behavior. SHED appears to be a suitable tool for soft tissue regeneration, such as dental pulp, whereas DPSC might be useful for engineering mineralized tissues like dentin [96]. Further development and successful application of these strategies to regenerate dentin and dental pulp could one day revolutionize the treatment of our most common oral health problem and cavities.
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FIGURE 20.5 Dental pulp tissue engineered for 35 days inside root canal using SHED cells (A) and natural dental pulp from premolar (B). It is possible to observe the formation of a healthy tissue without inflammatory signs and a densification of odontoblast-like cell along dentin walls in the SHED originated tissue similar to the control. The engineered tissue occupies the whole apical portion (C) and immunohistochemistry with PCNA and factor VIII shows a proliferative tissue with a well-established and mature blood network (D and E). PCNA, proliferating cell nuclear activity; SHED, Stem cells from human exfoliated deciduous teeth. Reproduced from V. Rosa, A. Della Bona, B.N. Cavalcanti, J.E. No¨r, Tissue engineering: from research to dental clinics, Dent. Mater. 28 (2012) 341 348, with permission from Elsevier.
References
20.5 CONCLUSIONS Despite the challenges in dental tissue regeneration that lie ahead, significant evidence exists to support the premise that recent advances in nanotechnology, acting as biomimetic tools, show great potential to overcome the challenges and promise for improved dental tissue regeneration. Nanomaterials tailored for engineering dental tissues are continually being introduced and yield numerous clinical dental benefits. These include improved treatments for periodontal defects, enhanced maxillary and mandibular bone regeneration, perhaps more biological methods to repair teeth after carious damage and possibly even regrowing lost teeth. In the near future, advances in bioengineering research will lead to wide application of regenerative dentistry into general dental practice to produce wonderful treatments and dramatically improve patients’ quality of life.
REFERENCES [1] R. Langer, J.P. Vacanti, Tissue engineering, Science 260 (1993) 920 926. [2] S. Yildirim, S.Y. Fu, K. Kim, H. Zhou, C.H. Lee, A. Li, et al., Tooth regeneration: a revolution in stomatology and evolution in regenerative medicine, Int. J. Oral Sci. 3 (2011) 107 116. [3] R.W. Siegel, G.E. Fougere, Mechanical properties of nanophase metals, Nanostruct. Mater. 6 (1995) 205. [4] S.M. Warren, K.D. Fong, C.M. Chen, E.G. Loboa, C.M. Cowan, H.P. Lorenz, et al., Tools and techniques for craniofacial tissue engineering, Tissue Eng. 9 (2003) 187 200. [5] L.J. Zhang, T.J. Webster, Nanotechnology and nanomaterials: promises for improved tissue regeneration, Nano Today 4 (2009) 66 80. [6] H. Yoshimoto, Y. Shin, H. Terai, J. Vacanti, A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering, Biomaterials 24 (2003) 2077 2082. [7] M. Jose, V. Thomas, Y. Xu, S. Bellis, E. Nyairo, D. Dean, Aligned bioactive multicomponent nanofibrous nanocomposite scaffolds for bone tissue engineering, Macromol. Biosci. 10 (2010) 433 444. [8] A. Asran, S. Henning, G. Michler, Polyvinyl alcohol-collagen-hydroxyapatite biocomposite nanofibrous scaffold: mimicking the key features of natural bone at the nanoscale level, Polymer 51 (2010) 868 876. [9] J. Venugopal, M. Prabhakaran, Y. Zhang, S. Low, A.T. Choon, S. Ramakrishna, Biomimetic hydroxyapatite-containing composite nanofibrous substrates for bone tissue engineering, Philos. Trans. A Math. Phys. Eng. Sci. 368 (2010) 2065 2081. [10] M.J. Gupte, P.X. Ma, Nanofibrous scaffolds for dental and craniofacial applications, J. Dent. Res. 91 (2012) 227 234. [11] T.J. Webster, C. Ergun, R.H. Doremus, R.W. Siegel, R. Bizios, Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics, J. Biomed. Mater. Res. 51 (2000) 475 483.
509
510
CHAPTER 20 Biomimetics using nanotechnology/nanoparticles
[12] T.J. Webster, C. Ergun, R.H. Doremus, R.W. Siegel, R. Bizios, Enhanced osteoclastlike cell functions on nanophase ceramics, Biomaterials 22 (2001) 1327 1333. [13] S.P. Nukavarapu, S.G. Kumbar, J.L. Brown, N.R. Krogman, A.L. Weikel, M.D. Hindenlang, et al., Polyphosphazene/nano-hydroxyapatite composite microsphere scaffolds for bone tissue engineering, Biomacromolecules 9 (2008) 1818 1825. [14] M. Sato, M.A. Sambito, A. Aslani, N.M. Kalkhoran, E.B. Slamovich, T.J. Webster, Increased osteoblast functions on undoped and yttrium-doped nanocrystalline hydroxyapatite coatings on titanium, Biomaterials 27 (2006) 2358 2369. [15] E.S. Thian, J. Huang, S.M. Best, Z.H. Barber, R.A. Brooks, N. Rushton, et al., The response of osteoblasts to nanocrystalline silicon-substituted hydroxyapatite thin films, Biomaterials 27 (2006) 2692 2698. [16] K.U. Lewandrowski, S.P. Bondre, D.L. Wise, D.J. Trantolo, Enhanced bioactivity of a poly(propylene fumarate) bone graft substitute by augmentation with nanohydroxyapatite, Biomed. Mater. Eng. 13 (2003) 115 124. [17] E.S. Thian, Z. Ahmad, J. Huang, M.J. Edirisinghe, S.N. Jayasinghe, D.C. Ireland, et al., Bioactivity of nanoapatite produced by electrohydrodynamic atomization, J. Bionanosci. 1 (2007) 60 63. [18] S. Pezzatini, R. Solito, L. Morbidelli, S. Lamponi, E. Boanini, A. Bigi, et al., The effect of hydroxyapatite nanocrystals on microvascular endothelial cell viability and functions, J. Biomed. Mater. Res. A 76A (2006) 656 663. [19] S. Pezzatini, L. Morbidelli, R. Solito, E. Paccagnini, E. Boanini, A. Bigi, et al., Nanostructured HA crystals up-regulate FGF-2 expression and activity in microvascular endothelium promoting angiogenesis, Bone 41 (2007) 523 534. [20] S.I. Stupp, G.W. Ciegler, Organoapatites: materials for artificial bone. I. Synthesis and microstructure, J. Biomed. Mater. Res. 26 (1992) 169 183. [21] J. Huang, S.M. Best, W. Bonfield, R.A. Brooks, N. Rushton, S.N. Jayasinghe, et al., In vitro assessment of the biological response to nanosized hydroxyapatite, J. Mater. Sci. Mater. Med. 15 (2004) 441 445. [22] G. Colon, B.C. Ward, T.J. Webster, Increased osteoblast and decreased Staphylococcus epidermidis functions on nanophase ZnO and TiO2, J. Biomed. Mater. Res. A 78 (2006) 595 604. [23] T.J. Webster, E.L. Hellenmeyer, R.L. Price, Increased osteoblast functions on theta 1 delta nanofiber alumina, Biomaterials 26 (2005) 953 960. [24] W. Paul, C.P. Sharma, Nanoceramic matrices: biomedical applications, Am. J. Biochem. Biotechnol. 2 (2006) 41 48. [25] F.X. Huber, N. McArthur, J. Hillmeier, H.J. Kock, M. Baier, M. Diwo, et al., Void filling of tibia compression fracture zones using a novel resorbable nanocrystalline hydroxyapatite paste in combination with a hydroxyapatite ceramic core: first clinical results, Arch. Orthop. Trauma Surg. 126 (2006) 533 540. [26] R. Smeets, G. Jelitte, M. Heiland, A. Kasaj, M. Grosjean, D. Riediger, et al., Hydroxylapatit-Knochenersatzmaterial (Ostim®) bei der Sinusbodenelevation, Schweiz Monatsschr. Zahnmed. 118 (2008) 203 208. [27] K.L. Gerlach, D. Niehues, Die Behandlung der Kieferzysten mit einem neuartigen nanopartikula¨ren Hydroxylapatit, Mund Kiefer GesichtsChir. 11 (2007) 131 137. [28] F. Schwarz, K. Bieling, T. Latz, E. Nuesry, J. Becker, Healing of intrabony periimplantitis defects following application of a nanocrystalline hydroxyapatite (Ostimt) or a bovine-derived xenograft (Bio-Osst) in combination with a collagen membrane (Bio-Gidet). A case series, J. Clin. Periodontol. 33 (2006) 491 499. Materials 2 (2009) 2037.
References
[29] F.P. Strietzel, P.A. Reichart, H.L. Graf, Lateral alveolar ridge augmentation using a synthetic nano-crystalline hydroxyapatite bone substitution material (Ostim®). Preliminary clinical and histological results, Clin. Oral Implants Res. 18 (2007) 743 751. [30] C. Spies, S. Schnu¨rer, T. Gotterbarm, S. Breusch, Tierexperimentelle Untersuchung des Knochenersatzstoffs Ostimt im kno¨chernen Lager des Go¨ttinger Miniaturschweins, Z. Orthop. Unfall. 146 (2008) 64 69. [31] M. Thorwarth, S. Schultze-Mosgau, P. Kessler, J. Wiltfang, K.A. Schlegel, Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite, J. Oral Maxillofac. Surg. 63 (2005) 1626 1633. [32] J. Brandt, S. Henning, G. Michler, M. Schulz, A. Bernstein, Nanocrystalline hydroxyapatite for bone repair, Key Eng. Mater. 361 363 (2008) 35 38. [33] F.X. Huber, J. Hillmeier, L. Herzog, N. McArthur, H.J. Kock, P.J. Meeder, Open reduction and palmar plate-osteosynthesis in combination with a nanocrystalline hydroxyapatite spacer in the treatment of comminuted fractures of the distal radius, J. Hand Surg. (Brit). 31B (2006) 298 303. [34] F.X. Huber, J. Hillmeier, N. McArthur, H.J. Kock, P.J. Meeder, The use of nanocrystalline hydroxyapatite for the reconstruction of calcaneal fractures: preliminary results, J. Foot Ankle Surg. 45 (2006) 322 328. [35] M.W. Laschke, K. Witt, T. Pohlemann, M.D. Menger, Injectable nanocrystalline hydroxyapatite paste for bone substitution: in vivo analysis of biocompatibility and vascularization, J. Biomed. Mater. Res. B Appl. Biomater. 82B (2007) 494 505. [36] C.K.G. Spies, S. Schnu¨rer, T. Gotterbarm, S. Breusch, The efficacy of Biobont and Ostimt within metaphyseal defects using the Go¨ttinger Minipig, Arch. Orthop. Trauma Surg. 129 (2009) 979 988. [37] Y.K. Kim, L.S. Gu, T.E. Bryan, J.R. Kim, L. Chen, Y. Liu, et al., Mineralisation of reconstituted collagen using polyvinylphosphonic acid/polyacrylic acid templating matrix protein analogues in the presence of calcium, phosphate and hydroxyl ions, Biomaterials 31 (2010) 6618 6627. [38] Y. Zhang, V.J. Reddy, S.Y. Wong, X. Li, B. Su, S. Ramakrishna, et al., Enhanced biomineralization in osteoblasts on a novel electrospun biocomposite nanofibrous substrate of hydroxyapatite/collagen/chitosan, Tissue Eng. Part A 16 (2010) 1949 1960. [39] E. Kon, M. Delcogliano, G. Filardo, D. Pressato, M. Busacca, B. Grigolo, et al., A novel nanocomposite multilayered biomaterial for treatment of osteochondral lesions: technique note and an early stability pilot clinical trial, Injury 41 (2010) 693 701. [40] C. Erisken, D.M. Kalyon, H. Wang, C. Ornek-Ballanco, J. Xu, Osteochondral tissue formation through adipose-derived stromal cell differentiation on, biomimetic polycaprolactone nanofibrous scaffolds with graded insulin and beta-glycerophosphate concentrations, Tissue Eng. Part A 17 (2011) 1239 1252. [41] F.M. Chen, J. Zhang, M. Zhang, Y. An, F. Chen, Z.F. Wu, A review on endogenous regenerative technology in periodontal regenerative medicine, Biomaterials 31 (2010) 7892 7927. [42] P.X. Ma, Biomimetic materials for tissue engineering, Adv. Drug Deliv. Rev. 60 (2008) 184 198. [43] S. Srinivasan, R. Jayasree, K.P. Chennazhi, S.V. Nair, R. Jayakumar, Biocompatible alginate/nano bioactive glass ceramic composite scaffolds for periodontal tissue regeneration, Carbohydr. Polym. 87 (2012) 274 283.
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512
CHAPTER 20 Biomimetics using nanotechnology/nanoparticles
[44] F. Yang, S.K. Both, X. Yang, X.F. Walboomers, J.A. Jansen, Development of an electrospun nano-apatite/PCL composite membrane for GTR/GBR application, Acta Biomater. 5 (2009) 3295 3304. [45] Z. Yuan, H. Nie, S. Wang, C.H. Lee, A. Li, S.Y. Fu, et al., Biomaterial selection for tooth regeneration, Tissue Eng. Part B Rev. 17 (2011) 373 388. [46] A.G. Fincham, J. Moradian-Oldak, J.P. Simmer, The structural biology of the developing dental enamel matrix, J. Struct. Biol. 126 (1999) 270 299. [47] Z. Huang, T.D. Sargeant, J.F. Hulvat, A. Mata, P. Bringas, C.H. Koh, et al., Bioactive nanofibers instruct cells to proliferate and differentiate during enamel regeneration, J. Bone Miner. Res. 23 (2008) 1995 2006. [48] H.F. Chen, B.H. Clarkson, K. Sun, J.F. Mansfield, Self-assembly of synthetic hydroxyapatite nanorods into enamel prism like structure, J. Colloid Interface Sci. 188 (2005) 97 103. [49] H.F. Chen, Z.Y. Tang, J. Liu, K. Sun, S.R. Chang, M.C. Peters, et al., Acellular synthesis of a human enamel-like microstructure, Adv. Mater. 18 (2006) 1846 1851. [50] Y. Fujishiro, A. Fujimoto, T. Sato, A. Okuwaki, Coating of hydroxyapatite on titanium plates using thermal-dissociation of calcium-EDTA chelate complex in phosphate solutions under hydrothermal conditions, J. Colloid Interface Sci. 173 (1995) 119 127. [51] W. Suchannek, M. Yoshimura, Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants, J. Mater. Res. 13 (1998) 94 117. [52] M. Cao, Y. Wang, C. Guo, Y. Qi, C. Hu, Preparation of ultrahigh-aspect-ratio hydroxyapatite nanofibers in reverse micelles under hydrothermal conditions, Langmuir 20 (2004) 4784. [53] L. Li, C. Mao, J. Wang, X. Xu, H. Pan, Y. Deng, et al., Bio-inspired enamel repair via Glu-directed assembly of apatite nanoparticle: an approach to biomaterials with optimal characteristic, Adv. Mater. 23 (2011) 4695 4701. [54] M. Hannig, C. Hannig, Nanomaterials in preventive dentistry, Nat. Nanotechnol. 5 (2010) 565 569. [55] K. Onuma, K. Yamagishi, A. Oyane, Nucleation and growth of hydroxyapatite nanocrystals for nondestructive repair of early caries lesions, J. Cryst. Growth 282 (2005) 199 207. [56] Y. Yamagishi, K. Onuma, T. Suzuki, F. Okada, J. Tagami, M. Otsuki, et al., A synthetic enamel for rapid tooth repair, Nature 433 (2005) 819. [57] K.L. Lv, J.X. Zhang, X.C. Meng, X.Y. Li, Remineralization effect of the nano-HA toothpaste on artificial caries, Key Eng. Mater. 330 332 (2007) 267 270. [58] M.Y. Kim, H.K. Kwon, C.H. Choi, B.I. Kim, Combined effects of nanohydroxyapatite and NaF on remineralization of early caries lesion, Key Eng. Mater. 330 332 (2007) 1347 1350. [59] N. Roveri, E. Battistella, I. Foltran, E. Foresti, M. Iafisco, M. Lelli, et al., Synthetic biomimetic carbonate-hydroxyapatite nanocrystals for enamel remineralization, Adv. Mater. Res. 47 50 (2008) 821 824. [60] N. Roveri, E. Battistella, C.L. Bianchi, I. Foltran, E. Foresti, M. Lafisco, et al., Surface enamel remineralization: biomimetic apatite nanocrystals and fluoride ions different effects, J. Nanomater. (2009) 746383. Available from: https://doi.org/ 10.1155.
References
[61] L. Li, H.H. Pan, J.H. Tao, X.R. Xu, C.Y. Mao, X.H. Gu, et al., Repair of enamel by using hydroxyapatite nanoparticles as the building blocks, J. Mater. Chem. 18 (2008) 4079 4084. [62] P. Tschoppe, D.L. Zandim, P. Martus, A.M. Kielbassa, Enamel and dentine remineralization by nano-hydroxyapatite toothpastes, J. Dent. 3 (2011) 430 437. [63] S.B. Huang, S.S. Gao, H.Y. Yu, Effect of nano-hydroxyapatite concentration on remineralization of initial enamel lesion in vitro, Biomed. Mater. 4 (2009) 034104. [64] S. Huang, S. Gao, L. Cheng, H. Yu, Remineralization potential of nanohydroxyapatite on initial enamel lesions: an in vitro study, Caries Res. 45 (2011) 460 468. [65] S. Huang, S. Gao, L. Cheng, H. Yu, Combined effects of nano-hydroxyapatite and Galla chinensis on remineralization of initial enamel lesion in vitro, J. Dent. 38 (2010) 811 819. [66] G. Balasundaram, M. Sato, T.J. Webster, Using hydroxyapatite nanoparticles and decreased crystallinity to promote osteoblast adhesion similar to functionalizing with RGD, Biomaterials 27 (2006) 2798 2805. [67] Q. Hu, Z. Tan, Y. Liu, J. Tao, Y. Cai, M. Zhang, et al., Effect of crystallinity of calcium phosphate nanoparticles on adhesion, proliferation, and differentiation of bone marrow mesenchymal stem cells, J. Mater. Chem. 17 (2007) 4690 4698. [68] S. Mai, Y.K. Kim, M. Toledano, L. Breschi, J.Q. Ling, D.H. Pashley, et al., Phosphoric acid esters cannot replace polyvinylphosphonic acid as phosphoprotein analogs in biomimetic remineralization of resin-bonded dentin, Dent. Mater. 25 (2009) 1230 1239. [69] A.W. Xu, Y.R. Ma, H. Colfen, Biomimetic mineralization, J. Mater. Chem. 17 (2007) 415 449. [70] E.C. Reynolds, Remineralization of enamel subsurface lesions by casein phosphopeptide-stabilized calcium phosphate solutions, J. Dent. Res. 76 (1997) 1587 1595. [71] M.V. Morgan, G.G. Adams, D.L. Bailey, C.E. Tsao, S.L. Fischman, E.C. Reynolds, The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography, Caries Res. 42 (2008) 171 184. [72] F. Cai, D.J. Manton, P. Shen, G.D. Walker, K.J. Cross, Y. Yuan, et al., Effect of addition of citric acid and casein phosphopeptide amorphous calcium phosphate to a sugar-free chewing gum on enamel remineralization in situ, Caries Res. 41 (2007) 377 383. [73] Y. Iijima, F. Cai, P. Shen, G. Walker, C. Reynolds, E.C. Reynolds, Acid resistance of enamel subsurface lesions remineralized by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate, Caries Res. 38 (2004) 551 556. [74] A.M. Al-Mullahi, K.J. Toumba, Effect of slow-release fluoride devices and casein phosphopeptide/amorphous calcium phosphate nanocomplexes on enamel remineralization in vitro, Caries Res. 44 (2010) 364 371. [75] J.D. Bader, Casein phosphopeptide-amorphous calcium phosphate shows promise for preventing caries, Evid. Based Dent. 11 (2010) 11 12. [76] G.D. Walker, F. Cai, P. Shen, G.G. Adams, C. Reynolds, E.C. Reynolds, Casein phosphopeptide-amorphous calcium phosphate incorporated into sugar confections
513
514
CHAPTER 20 Biomimetics using nanotechnology/nanoparticles
[77]
[78]
[79] [80]
[81]
[82] [83]
[84]
[85]
[86]
[87] [88]
[89]
[90] [91]
[92]
inhibits the progression of enamel subsurface lesions in situ, Caries Res. 44 (2010) 33 40. N. Srinivasan, M. Kavitha, S.C. Loganathan, Comparison of the remineralization potential of CPP ACP and CPP ACP with 900 ppm fluoride on eroded human enamel: an in situ study, Arch. Oral Biol. 55 (2010) 541 544. H. Hamba, T. Nikaido, G. Inoue, A. Sadr, J. Tagami, Effects of CPP ACP with sodium fluoride on inhibition of bovine enamel demineralization: a quantitative assessment using micro-computed tomography, J. Dent. 39 (2011) 405 413. E.C. Reynolds, Anticariogenic complexes of amorphous calcium phosphate stabilized by casein phosphopeptides: a review, Spec. Care Dentist. 18 (1998) 8 16. C. Llena, L. Forner, P. Baca, Anticariogenicity of casein phosphopeptide-amorphous calcium phosphate: a review of the literature, J. Contemp. Dent. Prac. 10 (2009) 1 9. V. Yengopal, S. Mickenautsch, Caries preventive effect of casein phosphopeptideamorphous calcium phosphate (CPP-ACP): a metaanalysis, Acta Odontol. Scand. 21 (2009) 1 12. N.J. Cochrane, F. Cai, N.L. Huq, M.F. Burrow, E.C. Reynolds, New approaches to enhanced remineralization of tooth enamel, J. Dent. Res. 89 (2010) 1187 1197. E.C. Reynolds, F. Cai, P. Shen, G.D. Walker, Retention in plaque and remineralization of enamel lesion by various forms of calcium in a mouthrinse or sugar-free chewing gum, J. Dent. Res. 82 (2003) 206 211. H.H.K. Xu, M.D. Weir, L. Sun, Nanocomposites with Ca and PO4 release: effects of reinforcement, dicalcium phosphate particle size and silanization, Dent. Mater. 23 (2007) 1482 1491. Y.W. Hong, J.H. Kim, B.H. Lee, Y.K. Lee, B.J. Choi, J.H. Lee, et al., The effect of nano-sized β-tricalcium phosphate on remineralization in glass ionomer dental luting cement, Key Eng. Mater. 361 363 (2008) 861 864. S. Nakashima, M. Yoshie, H. Sano, A. Bahar, Effect of a test dentifrice containing nano-sized calcium carbonate on remineralization of enamel lesions in vitro, J. Oral Sci. 51 (2009) 69 77. K. Kawasaki, J. Ruben, I. Stokroos, O. Takagi, J. Arends, The remineralization of EDTA-treated human dentine, Caries Res. 33 (1999) 275 280. Y. Shibata, L.H. He, Y. Kataoka, T. Miyazaki, M.V. Swain, Micromechanical property recovery of human carious dentin achieved with colloidal nano-beta-tricalcium phosphate, J. Dent. Res. 87 (2008) 233 237. M. Vollenweider, T.J. Brunner, S. Knecht, R.N. Grass, M. Zehnder, T. Imfeld, et al., Remineralization of human dentin using ultrafine bioactive glass particles, Acta Biomater. 3 (2007) 936 943. F.R. Tay, D.H. Pashley, Biomimetic remineralization of resin-bonded acid-etched dentin, J. Dent. Res. 88 (2009) 719 724. V.T. Sakai, Z. Zhang, Z. Dong, K.G. Neiva, M. Machado, S. Shi, et al., SHED differentiate into functional odontoblast and endothelium, J. Dent. Res. 89 (2010) 791 796. M.M. Cordeiro, Z. Dong, T. Kaneko, Z. Zhang, M. Miyazawa, S. Shi, et al., Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth, J. Endod. 34 (2008) 962 969.
References
[93] V. Rosa, T.M. Botero, J.E. No¨r, Regenerative endodontics in light of the stem cell paradigm, Int. Dent. J. 61 (2011) 23 28. [94] G. Huang, T. Yamaza, L.D. Shea, F. Djouad, N.Z. Kuhn, R.S. Tuan, et al., Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model, Tissue Eng. Part A 16 (2009) 605 615. [95] V. Rosa, A. Della Bona, B.N. Cavalcanti, J.E. No¨r, Tissue engineering: from research to dental clinics, Dent. Mater. 28 (2012) 341 348. [96] K.M. Galler, A. Cavender, V. Yuwono, H. Dong, S. Shi, G. Schmalz, et al., Selfassembling peptide amphiphile nanofibers as a scaffold for dental stem cells, Tissue Eng. Part A 14 (2008) 2051 2058.
515