Nanoengineered biomaterials for bladder regeneration

Nanoengineered biomaterials for bladder regeneration

CHAPTER Nanoengineered biomaterials for bladder regeneration 20 Farshid Sefat*, Tehmeena Israr Raja*, Zoha Salehi Moghadam†, Peiman Brouki Milan‡,§...

600KB Sizes 0 Downloads 76 Views

CHAPTER

Nanoengineered biomaterials for bladder regeneration

20

Farshid Sefat*, Tehmeena Israr Raja*, Zoha Salehi Moghadam†, Peiman Brouki Milan‡,§, Ali Samadikuchaksaraei‡,§, Masoud Mozafari†,‡,§ School of Engineering, Design and Technology-Medical Engineering, University of Bradford, Bradford, United Kingdom* Bioengineering Research Group, Department of Nanotechnology and Advanced Materials, Materials and Energy Research Center (MERC), Tehran, Iran† Cellular and Molecular Research Center (CMRC), Iran University of Medical Sciences (IUMS), Tehran, Iran‡ Department of Tissue Engineering & Regenerative Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran§

1 INTRODUCTION TO THE ANATOMY AND PHYSIOLOGY OF THE BLADDER The bladder is a hollow, very complex, semi-spherical organ that consists of multiple layers. The largest area of the bladder efficiently accumulates, stores, and releases urine produced by the kidneys, as directed by the central nervous system [1–4]. The bladder’s anatomical structure is described as being complex because of the presence of multiple, diverse layers, including the urothelium (the innermost layer), the lamina propria, the longitudinal muscle layer, and the circular muscle layer (on the outer end), as shown in Fig. 1 [2,5].

1.1 UROTHELIUM The urothelium has an internal mucosa layer that is in direct contact with urine. It contains three main types of cells (binuclear umbrella cells, intermediate cells, and basal cells) followed by a basement membrane that separates it from the lamina propria [2,6]. The surface of the mucosa contains multiple small structures known as rugae and transitional epithelial cells that allow resilient protection from the acidity and alkalinity of the urine, as well as an increase in both elasticity and surface area in order to accommodate up to approximately 800 mL of urine [2,5]. Other functions of the urothelium include utilizing paracrine signaling to nerve fibers, which in effect lets us know when the bladder is full and provides an eased sensation when urine is released [7]. Nanoengineered Biomaterials for Regenerative Medicine. https://doi.org/10.1016/B978-0-12-813355-2.00020-X # 2019 Elsevier Inc. All rights reserved.

459

460

CHAPTER 20 Nanoengineered biomaterials for bladder regeneration

Kidney

(B)

Urothelium Lamina propia Longitudinal muscle layer Circular muscle layer

Ureter Umbrella cells Intermediate cells Basal cells Basement membrane

Bladder Urethra

(C)

(A) FIG. 1 (A) Native urinary organs. (B) Native bladder tissue in a layer-by-layer arrangement. (C) Typical epithelium in the bladder. Reproduced with permission from A. Singh, T.J. Bivalacqua, N. Sopko, Urinary tissue engineering: challenges and opportunities, Sex. Med. Rev. 9 (2017) 35–44.

1.2 LAMINA PROPRIA The urothelium is surrounded by the lamina propria, a form of loose areolar connective tissue that lies under the basement membrane. The lamina propria is rich in blood vessels that enable innervation and vascularization and provide protection. The lamina propria is also rich in nervous tissue, which aids in controlling adjacent tissues. In particular, the efferent and afferent nerve endings allow sensory input, which helps the bladder maintain control of urine expelled out of the urethra [8]. In terms of physiology, the lamina propria consists of fibroblasts and interstitial and adipocyte cells [7,9]. Also, elastin, fibronectin, laminin, and collagen type III are prominent, along with various growth factors such as bFGF, PDGF, EGF, and VEGF. This highly vascularized, ECM-rich layer plays a significant role in involuntary transfer of information between the urothelium and the detrusor muscle [10–12].

1.3 DETRUSOR MUSCLE The submucosa surrounding the lamina propria is in contact with an external muscularis layer, known as the detrusor muscle. The detrusor muscle is a combination of the longitudinal muscle layer and the circular muscle layer. This muscle’s main function is to store urine; it expands (relaxes) to store urine and contracts to expel urine. The detrusor muscle extends to the urethral sphincter, the opening through which urine is expelled. These functions are controlled by the autonomic, efferent sympathetic and parasympathetic nervous systems [2,13].

2 Bladder and the need for tissue engineering

2 BLADDER AND THE NEED FOR TISSUE ENGINEERING People across the world suffer from degradation of the bladder, and because of the of the bladder’s great ability to regenerate, this organ is commonly overlooked in terms of tissue engineering. That said, although some of this organ’s tissue can regenerate, this scenario is not always the case. The latter situation leaves individuals without a functioning bladder, and often these people have long-term pain as result of infection, chronic inflammation, trauma, disease, injury, central or peripheral nervous systems dysfunction, and cancer [14–16]. With cancer of the bladder, in particular, the normal turnover rate of urothelium cells tends to be significantly lower than in healthy bladder tissue, whereas the rate increases substantially in cases of bladder tissue impairments caused by infection and injury [17,18]. Replacement options that allow full restoration of the bladder’s functions are limited. Therefore bladder tissue engineering is seen as a promising alternative. Typically, this process includes creating three-dimensional porous scaffolds that can maximize the activity of extracellular matrices and promote cellular growth and tissue regeneration. Because this is a fairly novel approach in bladder regeneration, complications can arise in terms of the cytotoxicity of the materials used to build the scaffolds, their biocompatibility, the optimization of the synthetic surfaces to maximize integration and vascularization, and the choice of cells (stem cells or differentiated cells) [19,20].

2.1 DECELLULARIZED SCAFFOLDS These scaffolds are obtained mostly from decellularized tissue, including tissue from oral mucosa, small intestinal submucosa, and bladder-decellularized matrixes, which offer natural and optimal integration properties to the extracellular matrix [21]. The main drawbacks to these scaffolds are possible contraction and transmission of various diseases [22]. In addition, these scaffolds are difficult to obtain compared to synthetic scaffolds created with readily available polymers [23].

2.2 SYNTHETIC SCAFFOLDS Various methods can be used to produce a range of synthetic biomaterials. Although they lack molecular signaling to increase cellular activity within the ECM, polymers such as poly(lactic acid-co-glycolic acid) (PLGA), poly(glycolic acid) (PGA), poly(caprolactone) (PCL), and poly(L-lactic acid) (PLLA), have physical properties such as controllable biodegradability. There is a minimal risk of infection if aseptic laboratory practices are followed, and the transmission of diseases such as hepatitis and HIV is prevented [23,24]. Creating an optimum synthetic scaffold for tissue regeneration—one that will allow the best cellular attachment, final graft cell proliferation, viability, and behavior—means that many factors must be taken into account, including substrate stiffness, bulk and surface chemistry (charge,

461

462

CHAPTER 20 Nanoengineered biomaterials for bladder regeneration

hydrophilicity), surface properties, and topological optimization [14,25]. To achieve better results, the next generation of scaffolds should be able to communicate with cells via the use of growth factors and cytokines, which emphasizes the importance of design and appropriate materials. Further research is needed to provide new, innovative ideas and requirements for scaffolds through, for example, studying the molecular size and properties (physical, chemical) of polymers with a potential to be used to create scaffolds [26–28]. The cohort of tissue engineering and regenerative medicine poses ample potential to utilize and further advance nanoscale characteristics and synthetic production of regenerative biocomponents. Research in nanomaterials has shown how alterations in terms of how reducing the size of objects (on nano and submicron scales) to a molecular scale can have a great impact on a material’s overall properties. It has been widely noted that the greatest bladder tissue response to synthetic materials can be accomplished by improving the interactions between biomaterials and bladder cells through the use of nanotechnology [14,29,30]. The subject of nanotechnology grew in public awareness in the early 2000s, and that interest and the development of that technology has continued ever since [31,32]. Recent ingenious discoveries in this field have provided information that enhances our understanding of how to control primary protein interactions, including cellular adhesions and growth on both biological and synthetic scaffolds [33]. Also, the adoption of nanotechnology-based methods in the medical sphere has led to the creation of improved implant devices and scaffolds with the desired level of surface roughness, thus simulating the proactive effects of the physical surface features of various tissues, including native bladder tissue [30,34–36]. In the rest of this chapter, we will discuss the reasons why nanomaterials are of such importance in tissue regeneration and the various methods used to fabricate scaffolds for bladder tissue regeneration.

3 NANOTECHNOLOGY MEETS MEDICINE Nanotechnology is referred to particle size manipulation of on an atomic, molecular, and supramolecular scale, which in turn allow adjustment of materials’ properties on a nanoscale level (100 nm and less). Here we consider the formation of numerous surfaces whose mechanical, biological, photochemical, and electrical properties are directly influenced by their nanoscale sizes and the structure of connected atoms [14]. Nanoparticles can be composed of only a few atoms or up to a few thousand atoms, whereas bulk materials usually contain billions of atoms; this difference leads to these counterparts having dissimilar properties [36]. Nanoparticles of certain materials react differently in terms of chemical reactions as compared to their counterpart bulk material. For example, gold is a chemically inactive material that is known for its resistance to discoloration and corrosion. As a bulk material, gold acts poorly as a catalyst; however, research has shown that gold nanoparticles approximately 5 nm in size behave as effective catalysts.

3 Nanotechnology meets medicine

The change in chemical behavior is thought to be caused by the crystalline structure of gold on an atomic scale—exposed atoms are more reactive toward free radicals compared to the internal gold particles within the bulk (as these bond with the surrounding gold particles) [37,38]. Silica surrounded by a thin shell of gold is a modern form of cancer treatment that can localize the targeting and death of cancer cells. For example, integrating the use of nanoparticles, because they are able to control reactivity, and fine-tuning the results as needed would be more beneficial than using the bulk material [39]. It is now commonly known that surface properties and that a material’s chemistry, roughness, and topography have a direct effect on protein adsorption and ultimately lead to cellular reactions with the related implant. All these factors can be modified by nanoscale alterations, which is why the consideration of nanomaterials is almost obligatory [40–42]. To increase protein absorption on tissue engineering scaffolds, the surface wettability must be optimized. In addition, cellular solutions should be attracted to the hydrophilic solid surface of the scaffolds to achieve increased protein attachment [42,43]. The contact angle has a direct effect on the wetting characteristics and surface energy of scaffolds; therefore changing the surface topography or chemistry by coating the surfaces with nanoparticles can potentially change the contact angle and surface energy, thus increasing the absorption of proteins. Khang et al. supported this idea by demonstrating a positive correlation between increased surface roughness on a nanometer scale and absorption of proteins, which is significant for bladder cell functions. In this study, polycarbonate-urethane (PCU) bladder stents with titanium-coated surfaces increased the roughness and produced optimal integration of cells. Also, by adding carbon nanotubes (CNTs), the absorption of fibronectin can be enhanced and thus produce an upsurge in the attachment of bladder cells. Therefore, nanomaterials can be used to create nanostructured roughness and to enhance bladder tissue regeneration processes [44]. A study in which cystectomy-induced rat models were used also illustrated the role of nanotechnology in bladder regeneration. Scaffolds composed of fibrogen nanofibers, collagen nanofibers, or electrospun poly (1, 8-octanediol-co-citrate) nanofibers were tested. Compared to the controls, these scaffolds showed significant regeneration of bladder tissues and considerable improvement in graft angiogenesis and scar formation [45–47]. Further studies have increased awareness of the importance of integrating growth factors to improve the properties of scaffolds. For example, a study in which VEGF (vascular endothelial growth factor) was incorporated into a scaffold improved innervation, muscularity, and angiogenesis. Jiang et al. used a biological scaffold of a decellularized rabbit bladder matrix and impregnated it with poly(lactic-coglycolic-acid) (PLGA) nanoparticles, which altered the surface roughness and extended the release of VEGF. The results showed a decrease in collagen content and scaffold contraction and an improvement in microvessel density. Also, the mechanical tests conducted on the scaffold demonstrated similar physical characteristics to those of the native bladder, such as elasticity and strength [48–50]. Physical optimizations of both biological and synthetic scaffolds are also thought to be important factors in regenerative medicine because of their adjustable

463

464

CHAPTER 20 Nanoengineered biomaterials for bladder regeneration

functionality, which is not usually achieved with traditional manufacturing techniques. It is evident how the use of nanotechnology can also change the surface chemistry, as well. By utilizing microinjection molding and electrospinning, it is possible to create complex nanostructures, with the latter having the ability to produce complex collagen structure forms as a triple helix to create nanoscale fibrils [14,51]. Unlike the production conventional materials, nanotechnology has made advancements in medical engineering. As a result, it is now understood that several nanomaterials are formulated chemically from miniscule molecules, e.g., secondary structures and noncovalent interactions. Some triggers, for instance, ionic gradient and pH changes, promote rapid variations in the surface display and the combination state to the such an extent that even supermolecular polymers are understood to be made via directional noncovalent bonds [51]. Design, structure, and synthetic processes are each fundamental parts in the final functioning of nanoengineered biomaterials, all of which we further discuss in this chapter.

4 METHODS FOR NANOSCALE SYNTHESIS: BOTTOM-UP VERSUS TOP-DOWN The bottom-up and top–down methods are often used to create synthetic structures in sizes ranging from 1 to 100 nm. These two methods were introduced in 1989 to classify molecular manufacturing in the field of nanotechnology [52]. In bottom-up synthesis, separate molecules are activated to self-assemble into larger structures with nanoscale sizes; whereas in top-down synthesis, a bulk material deteriorates to make smaller, frequently patterned features. Fig. 2 shows the eight general types of bottom-up and top-down synthesis [52].

4.1 BOTTOM-UP STRATEGIES In bottom-up strategies, atoms and molecules are self-assembled so that larger structures with nanoscale features are created. For example, self-assembled, charged lipids bond to create micelles (Fig. 2A) [51,53,54]. Peptide amphiphiles attach to bone, creating nanofibers that are chemically treated in such a way that ß-sheet surfaces are formed in block-like shapes (Fig. 2B). Nanoscale domains are formed from segregated polymer segments (Fig. 2C). Thus, in the bottom-up process, the structure and assembly of surface topologies can be managed (Fig. 2D) [53].

4.2 TOP-DOWN STRATEGIES One of the most-used top-down nano fabrication techniques is lithography. With this method, UV light is applied to a sample to engrave a pattern. The bulk surface has a stencil with either a negative or a positive pattern. The exposed surface is coated with a chemical that is reactive to UV light, and the stencil shelters the rest of the material.

4 Methods for nanoscale synthesis: Bottom-Up versus Top-Down

Trigger assembly

Expose

Develop, wash

(E)

(A)

Chemical treatment

Trigger assembly

(F)

(B) Trigger assembly

(C)

Dissolve template

Fill pores

(G) Surface assembly Collect

(D)

(H)

FIG. 2 Techniques for synthesis of surface topographies and nanoscale objects. Double-headed arrows show nanoscale objects. (A, B, C, D) Bottom-up designs. (E, F, G, H) Top-down designs. Reproduced with permission from D.A. Harrington, et al., Bladder Tissue Engineering Through Nanotechnology. World J. Urol. 26 (4) (2008) 315.

The UV light degrades the exposed chemically treated polymer, resulting in the desired microscopic topography (Fig. 2E) [14,53]. Chemical treatments, in which the properties of the bulk material are considered, create nanoscale features; and the desired surface topography is created through the chemical etching process previously described (Fig. 2F) [14,55]. Pattering is accomplished by filling pores and dissolving the template (template-assisted) in which nano objects are used as a dissolving mold to either surround or collect another degrading substance. Finally, the required nanoscale structures, such as nanorods, are created by utilizing anodic aluminum oxide (Fig. 2G) [56]. Another method for producing microfibers and nanofibers is electrospinning. In this method, various polymers are dissolved to create a solution that is loaded into syringes and, with the use of a high-voltage power supply, is forcibly extruded from the tip of the syringe into a collector at a constant rate, where they settle and entangle. Fibers with diameters ranging from 100 to 3000 nm can be created. From these fibers, porous scaffolds with potential applications in regenerative medicine can be built (Fig. 2H). Some methods fall midway between top-down and bottom-up processes, as discussed below. In these methods, various mechanical means are used in bulk materials to create nanoscale products [14,56].

465

466

CHAPTER 20 Nanoengineered biomaterials for bladder regeneration

5 APPLICATIONS OF NANOTECHNOLOGY IN THE BLADDER Nanotechnology has developed considerably in several areas and particularly in regard to the bladder—for example, basic research focused on understanding the fundamentals of the bladder; the diseases and disorders related to the bladder, such as their traumatic effects on the tissue; infections caused by ulcers, cancer, and so on; studies about the fate of cells; and the use of imaging techniques to determine the topography of bladder tissues and for replication of the structure and regeneration of the bladder epithelium [57–60]. Knowing how the bladder functions and being able to comprehend the various mechanical properties of the bladder’s tissues on a nanoscale level, such as surface reactions, elasticity, and even being able to view the rugae on a nanoscale level, are the first steps toward creating an innovative and advanced era in the medical industry. These innovations have already commenced in terms of utilizing nanotechnology for bladder regeneration. However, this area of research is neither fully explored nor applied, including utilization of nanostructures and nanoparticles such as antibacterial surfaces; utilization of nanoparticles for delivery agents; use of diverse combinations and geometries of nanoparticles derived from diverse bulk materials (e.g., combining silver nanoparticles with nanoparticle drugs in polymers to enhance healing properties); and creation of gene-delivery tools, cancer-killing agents, and drug-delivery agents [61–63]. Del Gaudio et al. [64] examined the bladder augmentation effect of an electrospun mat consisting of poly(ε-caprolactone) combined with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) on a female Wistar rat model. This study reported that urothelium formed with a lining up to 100% one month post-transplantation, and their 90-day follow-up showed that augmentation and migration of smooth muscles into the scaffold (representing the formation of muscle fibers) occurred (Fig. 3) [64].

FIG. 3 Pictures of the surgical procedure for rat bladder augmentation. (A) Bladder cystotomy. (B) The scaffold anastomosed with two running resorbable sutures. (C) The scaffold anastomosed to the native bladder 3 months after surgery. Reproduced with permission from C. Del Gaudio, et al., Evaluation of electrospun bioresorbable scaffolds for tissue-engineered urinary bladder augmentation, Biomed. Mater. 8 (4) (2013) 045013.

6 Bladder regeneration through nanotechnology

6 BLADDER REGENERATION THROUGH NANOTECHNOLOGY The bladder tissue, although having a nature which allows for healing, with the aid of nanoscale scaffolds will ensure the regenerated tissue has the correct mechanical properties to withstand the pressures and loads applied by the human body, in essence, re-establishing, preserving or refining tissue function [65].

6.1 TOP-DOWN PROCESSING OF NANOSCALE SCAFFOLDS A significant amount of research has focused on the use of nanoscale scaffolds in a range of organs, including the bladder [66,67]. Since the late 1900s, it has been known that surface patterning plays an important role in cellular attachment and interaction [65]. Various top-down methods can be utilized to create nanoscale surface patterns [68]. In addition, various polymers have been used to produce textured bladder scaffolds, including PLGA, PCL, and polyurethane [69]. A selective topdown degradation method enabled the production of nanoscale surface features ranging from 50 to 100 nm, which improved attachment of the smooth muscle cells present in the bladder [70]. In this work, the use of chemicals such as NaOH and HNO3 caused alterations in the surface chemistry of the degraded polymer. It was hypothesized that an increase in oxygen concentrations would be present through the use of such chemicals, thus creating surface hydroxyls and carbonyls. A silastic mold was used to replicate the surface features on untreated polymers, excluding the surface chemistry, and it was confirmed that the optimized topography produced by this degradation method significantly increased cellular adhesion [30]. The same type of technology was applied to create a porous 3D scaffold, further validating the results showing increased smooth muscle cell adhesion along with further proliferations in the overall elastin and collagen content [14]. Gaps in knowledge have surfaced as the mechanisms behind the upregulation in adhesion remain blurred, and the prospective use of nanotextured surfaces to affect adsorption for organic scaffolds is not yet fully explored [71].

6.2 COMBINING TOP-DOWN AND BOTTOM-UP PROCESSING OF NANOSCALE SCAFFOLDS Electrospinning is a processing method applied in both the top-down and the bottomup systems, and it allows extrusions of polymers beneath an electric weld. The nanoscale fibers are produced because of a magnetic field in which highly charged polymer solutions are forced through a nozzle [32,72]. Electrospun scaffolds, well known for their highly porous characteristics, are becoming more and more common as the technology advances and have resulted in creating diameters of randomly oriented fibers, both nanoscale and microscale [67,73]. Electrospun scaffolds offer benefits over conventional microfiber polymer scaffolds, such as increased control over a fiber’s alignment and diameter. Because electrospinning can create scaffolds

467

468

CHAPTER 20 Nanoengineered biomaterials for bladder regeneration

on a nanoscale, the produced matrices may have an increased influence on the cellular alignment of the attached cells. As a result, phenotype expression, skeletal muscle cells, vascular cells, and endothelial cells have been studied in terms of their application to electrospun surfaces; and these surfaces were shown to cause significant increases in attachment and alignment along the fibers [74,75]. Wellestablished pioneer groups such as Baker et al. expanded the research of polymers in the bladder tissue engineering field by investigating electrospun polystyrene, fibrogen, and cellulose acetate in relation to smooth muscle cells’ attachment and proliferation on scaffolds [76]. Assays were utilized in order to determine the efficacy of adherence between the scaffold and the smooth muscle cells, and a statistically significant increase in attachment was observed [76]. Biocompatibility is a preferred characteristic in the production of scaffolds. Biodegradable electrospun scaffolds created from biological proteins were created and tested over a period of 14 days, where it was observed that the fibronectin scaffold degraded, only to be replaced by a newly composed collagen matrix [77]. In this study, cardiac myocyte cells, primarily derived from a rat and followed by human bladder myocytes, were embedded on a fibronectin scaffold, which had an nonwoven architecture [78].

6.3 BOTTOM-UP PROCESSING OF NANOSCALE SCAFFOLDS Bottom up-processing methods for creating a nanoscale scaffold nanoscale include self-assembling peptide-amphiphile systems, which work by covalent attachment of highly charged hydrophilics to hydrophobic segments [14,79]. The hydrophilic peptide segment contains amino acid residues, which are selected to induce the formation of molecular sheets. The terminal ends of a single peptide-amphiphile system may include an epitope responsible for cellular signaling and binding, thus yielding additional cellular functions. When placed in a solution of a selected pH, each molecule in the system may also activate self-assembly as a result of an ionic alteration, which causes hydrophobic failure. This process enables the production of long nanofibers with diameters ranging from 6 to 8 nm, and when the concentration is adequate, interactions between the nanofibers cause an aqueous gel to form [79–81]. In terms of nanoscale bladder tissue engineering, the previously described system was used to create linked peptide-amphiphile molecules inscribed with G2 lysine dendrons, and selected expansions from the lysine extended to various sequences such as RGDS and PHSRN, which aided in mediating cellular adhesion. This process was continued by finely coating conventional microfiber scaffolds created from PGA, which, when triggered, created a complex arrangement of the nanofibers, including positively charged lysine segments between the peptide-amphiphile complexes. Combining the peptide-amphiphile system with the conventional scaffold enhanced smooth muscle cell attachment and enabled infiltration throughout the entire scaffold and matrix deposition [82,83]. Contrary to using peptide-amphiphile nanofibers as coatings for conventional scaffolds, this system can also be used to produce dense hydrogel encapsulate cells

7 Potential for further applications in bladder regeneration

in scaffolds with widely spaced pores [14]. In this way, beneficial growth factors can be introduced in bladder tissues to increase their regenerative properties. The terminal ends of the peptide-amphiphile systems can be optimized so that they comprise binding sites for the growth factors [84]. The hydrogel concept was tested in vivo when smooth muscle cells and urothelial cells were extracted from a human bladder and embedded in a scaffold created from polyamide composite with a basic fibroblast growth factor; a previous experiment without the peptide-amphiphile system showed positive results in terms of proliferation of smooth muscle cells and construction of matrix [85]. After 3 weeks, the human cells inserted into the subcutaneous rat model were well retained throughout the scaffold, a coating of urothelial cells was detected in the muscle cells and urothelial bilayer system, and, most important, there was a significant increase in phenotypic smooth muscle cells in the variable containing the peptide-amphiphile hydrogel system, as compared to the control [85]. Other self-assembling systems that work in a similar manner include the triblock polymer system, a biocompatible structure introduced by Guvendiran and Shull. Once again, hydrophobicity and hydrophilicity highly influence functionality, because this system is composed of hydrophobic poly(methyl methacrylate) and hydrophilic poly(methacrylic acid) blocks. The triblock polymer system is arranged in three aliquots, PMMA, PMAA, and PMMA [86]. When they are triggered in an aqueous solution, self-assembly occurs to assemble triblocks in distinctive nanoscale realms that act as cross-link points, thus creating a hydrogel. The cross-link points may also act as sockets to contain molecules such as hydrophobic fluorophores. This system is yet to be applied in tissue engineering of the bladder [86].

7 POTENTIAL FOR FURTHER APPLICATIONS IN BLADDER REGENERATION Interdisciplinary research combining biological complexity with refined biomaterials has brought about a new era in regenerative medicine. On the other hand, although technological advances in medical engineering have increased, their use in the urological sector has not been fully researched [65]. The reasons for this lack of research in terms of synthetic scaffolds and implants are uncertain; however, it is thought that tissues with the inability to naturally regenerate have been the focus of tissue engineering. Regardless of the fact that the bladder contains matrices that are regenerative, abnormal congenital ailments such as cancer, interstitial cystitis, and cystocele or physical problems such as reduced elasticity and trauma can cause symptoms such as pain and dysfunctionality that might be reduced or eliminated through the use of nanotechnology in the regeneration of the bladder [65,87,88]. Novel applications intended for the delivery of drugs, such as electrospun scaffolding and lithography on microscale, nanoscale, and near-nanoscale levels, have been researched for the relief of various problems. Long-term scaffold implants, however, have only recently been applied in the field of urology, briefly taking into account bladder derived cells, with their formation complexes to varying optimized

469

470

CHAPTER 20 Nanoengineered biomaterials for bladder regeneration

surfaces [14]. Bladder-derived cells such as smooth muscle cells and urothelial cells as well as progenitor stem cells can be easily obtained; therefore limited biological sources cannot be a justification for the lack of research in this field [89–91]. The notion of using stem cells as another means for bladder regeneration is based on the results of extensive research showing that this method creates tissue that comes close to matching the natural mechanical properties of bladder tissue [90]. Mesenchymal cells derived from adipose tissue and bone marrow have been experimented with, and the results have shown that transdifferentiation of these cells enables their conversion into a smooth muscle cell phenotype. Moreover, utilizing mesenchymal stem cells with the aid of growth factors and biological matrices can partially reduce the symptoms of various diseases, including those of the spine (spinal bifida) and vital organs, such as the liver and brain (which in turn affect the bladder, either structurally or physiologically), as well as the bladder by restructuring its tissue [87,89].

8 CONCLUSIONS Although tissue engineering surfaced only fairly recently through in vitro testing of organs, research being carried out in the medical devices industry holds promise for the future use of such engineering. Because of the regenerative nature of bladder tissue, this organ has previously been overlooked or disregarded in terms of synthetic aid for repair; however, advances in this field are being made, and the use of nanotechnology to enhance scaffolds is optimizing medical care. For example, various approaches to producing nanoscale scaffolds, such as the use of stem cells and top-down and bottom-up methods (including electrospinning and lithography), may play a positive role in creating enhanced bladder tissue and improving bladder regeneration.

REFERENCES [1] S. Bouhout, et al., Potential of different tissue engineering strategies in the bladder reconstruction, in: Regenerative Medicine and Tissue Engineering, InTech, 2013. [2] J. Smolar, et al., Stem cells in functional bladder engineering, Transfus. Med. Hemother. 43 (5) (2016) 328–335. [3] P. Ochodnicky, et al., Neurotrophins as regulators of urinary bladder function, Nat. Rev. Urol. 9 (11) (2012) 628. [4] T.C. Chai, et al., Mucosal signaling in the bladder, Auton. Neurosci. 200 (2016) 49–56. [5] R.V. Krstic, Human Microscopic Anatomy: An Atlas for Students of Medicine and Biology, Springer Science & Business Media, 2013. [6] A. Singh, T.J. Bivalacqua, N. Sopko, Urinary tissue engineering: challenges and opportunities, Sex. Med. Rev. 6 (1) (2018) 35–44. [7] G. Apodaca, E. Balestreire, L. Birder, The uroepithelial-associated sensory web, Kidney Int. 72 (9) (2007) 1057–1064.

References

[8] L.P. Gartner, J.L. Hiatt, Color Textbook of Histology E-Book, Elsevier Health Sciences, 2006. [9] K.E. Andersson, K.D. McCloskey, Lamina propria: the functional center of the bladder? Neurourol. Urodyn. 33 (1) (2014) 9–16. [10] K.J. Aitken, D.J. B€agli, The bladder extracellular matrix. Part I: architecture, development and disease, Nat. Rev. Urol. 6 (11) (2009) 596. [11] S.Y. Chun, et al., Identification and characterization of bioactive factors in bladder submucosa matrix, Biomaterials 28 (29) (2007) 4251–4256. [12] R. Soler, et al., The effect of lamina propria cells on the growth of urothelial and smooth muscle cells, J. Urol. 181 (4) (2009) 78. [13] W.C. de Groat, N. Yoshimura, Afferent nerve regulation of bladder function in health and disease, in: Sensory Nerves, Springer, 2009, pp. 91–138. [14] D.A. Harrington, et al., Bladder tissue engineering through nanotechnology, World J. Urol. 26 (4) (2008) 315. [15] G. Siracusa, A. Sparacino, V. Lentini, Neurogenic bladder and disc disease: a brief review, Curr. Med. Res. Opin. 29 (8) (2013) 1025–1031. [16] N. Montalbetti, et al., Increased urothelial paracellular transport promotes cystitis, Am. J. Physiol. Renal Physiol. 309 (12) (2015) F1070–F1081. [17] E.A. Kurzrock, et al., Label-retaining cells of the bladder: candidate urothelial stem cells, Am. J. Physiol. Renal Physiol. 294 (6) (2008) F1415–F1421. [18] K. Shin, et al., Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder, Nature 472 (7341) (2011) 110. [19] C. Alberti, Outlines on nanotechnologies applied to bladder tissue engineering, G. Chir. 33 (6/7) (2012) 235. [20] L. Zhou, et al., Autologous smooth muscle progenitor cells enhance regeneration of tissue-engineered bladder. Tissue Eng. (2018) https://doi.org/10.1089/ten.tea.2017.0376. [21] P.B. Milan, et al., Accelerated wound healing in a diabetic rat model using decellularized dermal matrix and human umbilical cord perivascular cells, Acta Biomater. 45 (2016) 234–246. [22] J.J. Song, H.C. Ott, Organ engineering based on decellularized matrix scaffolds, Trends Mol. Med. 17 (8) (2011) 424–432. [23] F.J. O’brien, Biomaterials & scaffolds for tissue engineering, Mater. Today 14 (3) (2011) 88–95. [24] M. Mozafari, The critical impact of controlled drug delivery in the future of tissue engineering, Trends Biomater. Artif. Organs 28 (3) (2014) 124–126. [25] S. Gurocak, et al., Bladder augmentation: review of the literature and recent advances, Indian J. Urol. 23 (4) (2007) 452. [26] Z. Zarekhalili, et al., Fabrication and characterization of PVA/gum tragacanth/PCL hybrid nanofibrous scaffolds for skin substitutes, Int. J. Biol. Macromol. 94 (2017) 679–690. [27] M. Rahmati, et al., Ionically crosslinked thermoresponsive chitosan hydrogels formed in situ: a conceptual basis for deeper understanding, Macromol. Mater. Eng. 302 (11) (2017) 1700227. [28] M. Gholipourmalekabadi, et al., Oxygen-generating biomaterials: a new, viable paradigm for tissue engineering? Trends Biotechnol. 34 (12) (2016) 1010–1021. [29] A. Kanematsu, S. Yamamoto, O. Ogawa, Changing concepts of bladder regeneration, Int. J. Urol. 14 (8) (2007) 673–678.

471

472

CHAPTER 20 Nanoengineered biomaterials for bladder regeneration

[30] Y.W. Chun, et al., Nanostructured bladder tissue replacements, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 3 (2) (2011) 134–145. [31] A. Ramedani, Y. Hatefi, M. Mozafari, Controlled delivery of cefixime trihydrate from organic-inorganic nanofiber composites, Biointerface Res. Appl. Chem. 6 (3) (2016). [32] M. Ghaffari, et al., Nanobiomaterials for bionic eye: vision of the future, in: Engineering of Nanobiomaterials, Elsevier, 2016, pp. 257–285. [33] N. Alasvand, et al., Therapeutic nanoparticles for targeted delivery of anticancer drugs, in: Multifunctional Systems for Combined Delivery, Biosensing and Diagnostics, Elsevier, 2017, pp. 245–259. [34] M. Ferrari, Cancer nanotechnology: opportunities and challenges, Nat. Rev. Cancer 5 (3) (2005) 161. [35] J.K. Vasir, M.K. Reddy, V.D. Labhasetwar, Nanosystems in drug targeting: opportunities and challenges, Curr. Nanosci. 1 (1) (2005) 47–64. [36] M.R. Mohammadi, et al., Nanomaterials engineering for drug delivery: a hybridization approach, J. Mater. Chem. B 5 (22) (2017) 3995–4018. [37] N. Jalali, et al., Synthesis and characterization of surface-modified poly (lactide-coglycolide) nanoparticles by chitosan molecules for on-demand drug delivery applications, Biointerface Res. Appl. Chem. 6 (3) (2016). [38] K. Nazemi, et al., Tissue-engineered chitosan/bioactive glass bone scaffolds integrated with PLGA nanoparticles: a therapeutic design for on-demand drug delivery, Mater. Lett. 138 (2015) 16–20. [39] L.R. Hirsch, et al., Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance, Proc. Natl. Acad. Sci. U. S. A. 100 (23) (2003) 13549–13554. [40] M. Mozafari, Editorial preface: special issue on functional surface for tissue engineering and regenerative medicine, Biointerface Res. Appl. Chem. 6 (3) (2016) 1183–1184. [41] C. Escobar, et al., Design of hard surfaces with metal (Hf/V) nitride multinanolayers, J. Superhard Mater. 36 (6) (2014) 366–380. [42] M. Mozafari, et al., Innovative surface modification of orthopaedic implants with positive effects on wettability and in vitro anti-corrosion performance, Surf. Eng. 30 (9) (2014) 688–692. [43] V. Shabafrooz, et al., The effect of hyaluronic acid on biofunctionality of gelatin– collagen intestine tissue engineering scaffolds, J. Biomed. Mater. Res. A 102 (9) (2014) 3130–3139. [44] D. Khang, et al., The role of nanometer and sub-micron surface features on vascular and bone cell adhesion on titanium, Biomaterials 29 (8) (2008) 970–983. [45] J. Adamowicz, T. Kowalczyk, T. Drewa, Tissue engineering of urinary bladder–current state of art and future perspectives, Cent. European J. Urol. 66 (2) (2013) 202. [46] A.K. Sharma, et al., Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly (1, 8-octanediol-co-citrate) based thin films, Biomaterials 31 (24) (2010) 6207–6217. [47] D. Rickert, et al., The importance of angiogenesis in the interaction between polymeric biomaterials and surrounding tissue, Clin. Hemorheol. Microcirc. 28 (3) (2003) 175–181. [48] B.C. Gill, M.S. Damaser, C.J. Chermansky, Future perspectives in bladder tissue engineering, Curr. Bladder Dysfunct. Rep. 10 (4) (2015) 443–448. [49] X. Jiang, et al., VEGF-loaded nanoparticle-modified BAMAs enhance angiogenesis and inhibit graft shrinkage in tissue-engineered bladder, Ann. Biomed. Eng. 43 (10) (2015) 2577–2586.

References

[50] M. Youssif, et al., Effect of vascular endothelial growth factor on regeneration of bladder acellular matrix graft: histologic and functional evaluation, Urology 66 (1) (2005) 201–207. [51] P.Y. Dankers, E. Meijer, Supramolecular biomaterials. A modular approach towards tissue engineering, Bull. Chem. Soc. Jpn. 80 (11) (2007) 2047–2073. [52] J. Saghaei, A. Fallahzadeh, T. Saghaei, Vapor treatment as a new method for photocurrent enhancement of UV photodetectors based on ZnO nanorods, Sensors Actuators A Phys. 247 (2016) 150–155. [53] G.A. Silva, et al., Selective differentiation of neural progenitor cells by high-epitope density nanofibers, Science 303 (5662) (2004) 1352–1355. [54] S. Zhang, Fabrication of novel biomaterials through molecular self-assembly, Nat. Biotechnol. 21 (10) (2003) 1171. [55] H. Lee, B.P. Lee, P.B. Messersmith, A reversible wet/dry adhesive inspired by mussels and geckos, Nature 448 (7151) (2007) 338. [56] S.J. Hurst, et al., Multisegmented one-dimensional nanorods prepared by hard-template synthetic methods, Angew. Chem. Int. Ed. 45 (17) (2006) 2672–2692. [57] P. Kreunin, et al., Bladder cancer associated glycoprotein signatures revealed by urinary proteomic profiling, J. Proteome Res. 6 (7) (2007) 2631–2639. [58] A. Vlahou, et al., Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine, Am. J. Pathol. 158 (4) (2001) 1491–1502. [59] G.A. Abrams, et al., Ultrastructural basement membrane topography of the bladder epithelium, Urol. Res. 31 (5) (2003) 341–346. [60] C.R. Estrada, et al., Behavioral profiling of human transitional cell carcinoma ex vivo, Cancer Res. 66 (6) (2006) 3078–3086. [61] Z. Cao, et al., Preparation and feasibility of superparamagnetic dextran iron oxide nanoparticles as gene carrier, Ai Zheng 23 (10) (2004) 1105–1109. [62] P. Tyagi, et al., Recent advances in intravesical drug/gene delivery, Mol. Pharm. 3 (4) (2006) 369–379. [63] Z. Lu, et al., Paclitaxel-loaded gelatin nanoparticles for intravesical bladder cancer therapy, Clin. Cancer Res. 10 (22) (2004) 7677–7684. [64] C. Del Gaudio, et al., Evaluation of electrospun bioresorbable scaffolds for tissueengineered urinary bladder augmentation, Biomed. Mater. 8 (4) (2013) 045013. [65] C.M. Kelleher, J.P. Vacanti, Engineering extracellular matrix through nanotechnology, J. R. Soc. Interface 7 (2010) S717–29. [66] M.A. Pattison, et al., Three-dimensional, nano-structured PLGA scaffolds for bladder tissue replacement applications, Biomaterials 26 (15) (2005) 2491–2500. [67] A.M. Ghafari, et al., Mechanical reinforcement of urinary bladder matrix by electrospun polycaprolactone nanofibers, Sci. Iran. 24 (6) (2017) 3476–3480. [68] H.M. Smilowitz, et al., Biodistribution of gold nanoparticles in BBN-induced muscleinvasive bladder cancer in mice, Int. J. Nanomedicine 12 (2017) 7937. [69] M. Horst, et al., Polyesterurethane and acellular matrix based hybrid biomaterial for bladder engineering, J Biomed Mater Res B Appl Biomater 105 (3) (2017) 658–667. [70] L. Zhang, T.J. Webster, Nanotechnology and nanomaterials: promises for improved tissue regeneration, Nano Today 4 (1) (2009) 66–80. [71] C.E. Ayres, et al., Nanotechnology in the design of soft tissue scaffolds: innovations in structure and function, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2 (1) (2010) 20–34.

473

474

CHAPTER 20 Nanoengineered biomaterials for bladder regeneration

[72] A. Yazdanpanah, et al., Fabrication and characterization of electrospun poly-L-lactide/ gelatin graded tubular scaffolds: toward a new design for performance enhancement in vascular tissue engineering, Prog. Nat. Sci. Mater. Int. 25 (5) (2015) 405–413. [73] M. Mozafari, Synthesis and characterisation of poly (lactide-co-glycolide) nanospheres using vitamin E emulsifier prepared through one-step oil-in-water emulsion and solvent evaporation techniques, IET Nanobiotechnol. 8 (4) (2014) 257–262. [74] S. Ribeiro, et al., Electrospun polymeric smart materials for tissue engineering applications, in: Electrospun Biomaterials and Related Technologies, Springer, 2017, pp. 251–282. [75] S.K. Nune, et al., Electrospinning of collagen nanofiber scaffolds for tissue repair and regeneration, in: Nanostructures for Novel Therapy, Elsevier, 2017, pp. 281–311. [76] S.C. Baker, et al., Characterisation of electrospun polystyrene scaffolds for threedimensional in vitro biological studies, Biomaterials 27 (16) (2006) 3136–3146. [77] M.C. McManus, et al., Electrospun fibrinogen: feasibility as a tissue engineering scaffold in a rat cell culture model, J. Biomed. Mater. Res. A 81 (2) (2007) 299–309. [78] H.H. Ahvaz, et al., Mechanical characteristics of electrospun aligned PCL/PLLA nanofibrous scaffolds conduct cell differentiation in human bladder tissue engineering, J. Nanosci. Nanotechnol. 13 (7) (2013) 4736–4743. [79] H. Cui, M.J. Webber, S.I. Stupp, Self-assembly of peptide amphiphiles: from molecules to nanostructures to biomaterials, Pept. Sci. 94 (1) (2010) 1–18. [80] Y. Zhou, et al., Self-assembly of hyperbranched polymers and its biomedical applications, Adv. Mater. 22 (41) (2010) 4567–4590. [81] T. Lin, et al., Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer, Acta Biomater. 53 (2017) 427–438. [82] K. Jakab, et al., Tissue engineering by self-assembly and bio-printing of living cells, Biofabrication 2 (2) (2010)022001. [83] X. Zhao, et al., Molecular self-assembly and applications of designer peptide amphiphiles, Chem. Soc. Rev. 39 (9) (2010) 3480–3498. [84] K. Jakab, et al., Tissue engineering by self-assembly of cells printed into topologically defined structures, Tissue Eng. A 14 (3) (2008) 413–421. [85] S.H. Beqaj, et al., Role of basic fibroblast growth factor in the neuropathic bladder phenotype, J. Urol. 174 (4) (2005) 1699–1703. [86] M. Guvendiren, K.R. Shull, Self-assembly of acrylic triblock hydrogels by vapor-phase solvent exchange, Soft Matter 3 (5) (2007) 619–626. [87] A. Kanematsu, et al., Bladder regeneration by bladder acellular matrix combined with sustained release of exogenous growth factor, J. Urol. 170 (4) (2003) 1633–1638. [88] R. Birla, Introduction to Tissue Engineering: Applications and Challenges, John Wiley & Sons, 2014. [89] S.Y. Chung, et al., Bladder reconstitution with bone marrow derived stem cells seeded on small intestinal submucosa improves morphological and molecular composition, J. Urol. 174 (1) (2005) 353–359. [90] H.-S. Hung, et al., Novel approach by nanobiomaterials in vascular tissue engineering, Cell Transplant. 20 (1) (2011) 63–70. [91] N. Alobaid, et al., Nanocomposite containing bioactive peptides promote endothelialisation by circulating progenitor cells: an in vitro evaluation, Eur. J. Vasc. Endovasc. Surg. 32 (1) (2006) 76–83.