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nano replication and 3D assembling techniques for scaffold fabrication
Materials Science and Engineering C 42 (2014) 615–621
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Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec
Review
Micro/nano replication and 3D assembling techniques for scaffold fabrication M.J. Lima, V.M. Correlo ⁎, R.L. Reis a
3B's Research Group — Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, 4806-909 Guimarães, Portugal ICVS/3B's, Associate Laboratory, PT Government Associate Laboratory, Guimarães, Braga, Portugal
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Article history: Received 22 January 2014 Received in revised form 19 May 2014 Accepted 30 May 2014 Available online 6 June 2014 Keywords: Scaffolds Micro/nanofabrication Hot embossing Soft lithography Patterning
a b s t r a c t The development of tissue engineering field entails the creation of micro/nanoscale features for cellular alignment and biocompatibility improvement. As replication techniques, hot embossing and soft lithography can be used to produce micro/nanoscale features on biodegradable membranes. Subsequently the generation of 3D scaffolds can be done by means of assembling techniques. Using the described techniques, high resolution of features, as small as 5 nm, can be achieved. Nevertheless membrane assembling must be fully studied to avoid feature fluctuations and even collapse of the scaffold. The present review focuses on the state-of-the-art in the replication techniques used to create micro/nanoscale features on biodegradable polymers and assembling approaches to construct scaffolds with the aim of exploring existing advances and limitations of the reported methods. © 2014 Elsevier B.V. All rights reserved.
Contents 1. 2.
Introduction . . . . . . . . . . . . . . . . . . . . . . . Replication technologies for tissue engineering applications . 2.1. Soft lithography . . . . . . . . . . . . . . . . . . 2.1.1. Replica molding . . . . . . . . . . . . . 2.1.2. Micromolding in capillaries . . . . . . . . 2.1.3. Microcontact printing . . . . . . . . . . . 2.2. Hot embossing . . . . . . . . . . . . . . . . . . 3. Soft lithography vs hot embossing . . . . . . . . . . . . . 4. 3D assembling approaches for tissue engineering applications 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction Organ failure and tissue loss are the major problems in human health care [1]. To circumvent these problems, surgical strategies, such as, organ transplantation, tissue transfer and prosthesis replacement are the most commonly used approaches [1,2]. Nevertheless, several
⁎ Corresponding author at: 3B's Research Group — Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, 4806-909 Guimarães, Portugal. E-mail address: [email protected] (V.M. Correlo).
http://dx.doi.org/10.1016/j.msec.2014.05.064 0928-4931/© 2014 Elsevier B.V. All rights reserved.
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disadvantages are associated with these therapies, namely, shortage of organ donors, disease transmission and biocompatibility issues [3]. In the past few years, tissue engineering emerged in the field of orthopedic surgery and biomedical engineering as a discipline able to offer promising alternatives to actual therapies [4,5]. This new field of research was defined by Langer and Vacanti as “an interdisciplinary field that applies the principles of engineering and of life science towards the development of biological substitutes that restore, maintain or improve tissue or organ function” [6]. Earlier, different approaches to create scaffolds, such as, compression molding followed by porogen leaching [7,8], gas foaming [9–11], fiberbonding [12–14], freeze-drying [15,16], and solvent casting [17] have
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been studied. Nevertheless, these methods are limited by their random micro-geometries, low-resolution features, random distribution of pores, residual particles and solvents in the polymer matrix and limited oxygen/nutrient supply [18]. Afterwards, machine-based processes, such as, micro injection molding [19] and rapid prototyping including fused deposition modeling (FDM) [20,21], stereolithography (SLA) [22] and 3D printing [23,24], were also used to produce biocompatible organized structures but the limited resolution is still a drawback. In the recent years, micro/nanofabrication technologies have emerged as versatile and powerful approaches for micro/nanoscale feature creation and can be broadly separated into direct methods and replication methods. As the name implies, the first method creates patterns directly on the substrate (e.g. photolithography) and the second one replicates features using several times the same master mold (that is usually produced by direct methods). Despite of direct methods being able to create patterns with good resolutions, they are usually more expensive methods than replication techniques [25]. Replication methods are emerging tools for tissue engineering applications since they can tailor biochemical cues and surface patterns capable of controlling cell adhesion or orientation producing precisely arranged co-culture systems [26–32] with lower associated costs. These technologies offer the possibility of building large-area stamps (from 4 to 100 cm2, [33,34]) with features at length scales from b5 nm to N1 cm creating feature scales smaller than those of cells [35,36]. A variety of different approaches has been successfully applied to produce different types of features on polymeric surfaces in the micrometer and submicrometer range [37–39] such as fibrillar ECM alignment [40,41], round features [42] and submicroscale textures and microgrooves [43]. Furthermore, the osteogenic differentiation of mesenchymal stem cells [44,45] and vascularization [46] were also reported to be promoted by micro/nanostructured substrates. This review will focus on the state-of-the art of replication methods and 3D assembling methodologies providing also a discussion of the advances and limitations of each technology and a perspective of the future trends regarding micro/nanofabrication techniques. 2. Replication technologies for tissue engineering applications Replication technologies, which allow the development of biofunctionalized surfaces with micro/nano patterned cues on both synthetic and natural based polymers become increasingly important to medical diagnostics, biochemical analysis, cell-based assays, sample preparation [47] and tissue engineering applications [48,49]. The use of these novel technologies, by achieving high resolution features at the nanoscale, improves the formation of new blood capillaries since cells attach to topographical cues avoiding the simple addition of cells to scaffold without any type of biochemical or physical cues that often leads to random and inadequate results [48,50]. Furthermore, synthetic and natural based biodegradable polymers can be cast onto micro/ nanofabricated molds to produce structures with small feature resolution [51–54]. Table 1 lists some of these replication technologies envisaging their application on the tissue engineering field.
Included on replication techniques, hot embossing (also known as nanoimprint lithography) and soft lithography (micro-casting) have been used to achieve patterns with dimensions as small as 5 nm [36, 55–58]. The master mold used for these replication techniques are usually produced using a hard or a soft material, being mold rigidity, the major difference between hot embossing and soft lithography. The following sub-chapters extensively describe the characteristics of each method. 2.1. Soft lithography Soft lithography, developed in 1997 by George Whitesides and coworkers, emerged as an alternative procedure to photolithographic techniques for micro/nanofabrication [59]. This method is included in replication methods and is characterized by using a patterned elastomer (usually made from PDMS) as a stamp or mold, to generate microstructures and a pre-polymer for posterior thermal or photo curable process [60]. Several elastomeric materials are used in the preparation of molds for soft lithography such as, poly(methylmethacrylate) (PMMA) [61], perfluoropolyether (SIFEL) [62] and polydimethilsiloxane (PDMS) [63]. Nevertheless, PDMS is the most widely used due to its transparency to visible wavelengths [64,65] and to its elastomeric characteristics providing also a low interfacial free energy on the surface and releasing easily from the substrate [66,67]. The schematic fabrication process of the elastomeric mold is shown in Fig. 1A. In this process, a master mold is usually made on a silicon wafer by photolithography. Afterwards, the PDMS pre-polymer is cast in the rigid master mold for further thermal curing and finally peeled off. As the fabrication of PDMS mold is based on replication process, multiple PDMS molds (or stamps) can be produced and each elastomeric stamp can be used for at least 50 times [60,68], depending on the replication technique conditions, mold material and feature patterns. This characteristic improves the productivity of the process with low associated costs. Nevertheless, the main disadvantage of using PDMS mold is the damage of the pattern height with consequent lower resolution of features [69] and even distortion/deformation of microstructures [70]. Soft lithographic techniques can be divided into: i) microcontact printing, ii) micromolding in capillaries, iii) microtransfer molding, iv) replica molding and v) solvent-assisted micromolding [56,59,71]. Up to now, only some of these techniques are being used for tissue engineering applications and are described as follows. 2.1.1. Replica molding The process of replica molding (REM) (Fig. 1B) consists of using a soft mold and a photo or thermally curable pre-polymer. The prepolymer is cast into the PDMS mold and solvents are photo or thermally removed to produce the micro/nano patterns on polymer substrate. With REM method it is possible to pattern features as small as the capillaries using different types of substrates. However, this technique uses solvents for polymer conformation into the mold.
Table 1 Replication techniques used in tissue engineering.
Soft lithography
Hot embossing
Method
Resolution
Main characteristics
References
Microcontact printing (μCP)
35 nm
[112–114]
Replica molding (REM)
30 nm
Micromolding in capillaries (MIMIC)
1 μm
Pattern substrates for cell culture to control the attachment of cells. Formation of self-assembled monolayers on an elastomeric mold to stamp the desired pattern and to create films. Uses PDMS mold to cast a pre polymer. After, the polymer is cured and detached from the mold. Ability to mold against nonplanar, rigid and soft topographic surfaces. Based on capillary force to fill the channels between the mold and the support. Uses a low viscosity polymer precursor and after, the PDMS mold is removed remaining only the molded polymer. Produces high-aspect-ratio structures. Utilizes temperature above Tg and vacuum conditions to prevent trapping of air in microstructures.
5–10 nm
[51,72–74] [82,83,86,115]
[36,98,116–119]
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Fig. 1. Schematic representation of micro/nanofabrication techniques: A) fabrication process of elastomeric molds for soft lithography applications; B) replica molding (REM); C) micromolding in capillaries (MIMIC); D) microcontact printing (μCP); and E) hot embossing.
Some pre-polymers can wear or dissolve the PDMS mold. Therefore, for REM, the mold can only be used for about 20 times. The advantage of using REM is the possibility to make patterns on large, nonplanar, rigid and soft substrates with low associated costs [51,67,72–74].
Polymer
Micro/nano fabrication technology
Several studies conducted in the tissue engineering field refer to REM as a low cost method to produce high aspect ratio structures [75, 76]. The method was used by Borenstein et al. [77] to construct microfabricated scaffolds in order to develop microvasculature enabling the
2D micro/nano fabricated membranes
Assembling methodology
3D scaffolds
Fig. 2. Methodology to achieve 3D scaffolds: the polymer is processed by micro/nanofabrication methods and 2D polymeric and biodegradable membranes were produced. After, a bottom-up methodology is applied to assemble those membranes. At the end 3D scaffolds were fabricated.
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development of bulk organ scaffolds. The development of the PDMS template was made by using a micromachined silicon mold. Moreover, the scaffold was successfully seeded with endothelial cells in channels with dimensions as small as the capillaries to promote vascularization. On the other hand, to control cell orientation and morphology by topographical patterning, poly (glycerol-sebacate) (PGS) on sucrose-coated microfabricated silicon was used by Bettinger et al. [42]. The fabricated microstructures were biocompatible, flexible and biodegradable with features in the range of 500 nm. The existing micro curvature in the fabricated structures was a stronger topographic cue in order to align and elongate aortic endothelial cells. In a different study, REM process was used for patterning poly(methyl methacrylate) (PMMA) and polydimethylsiloxane (PDMS) substrates to study the cell behavior, proliferation and morphology of pulmonary artery smooth muscle cells (SMC) [26]. The results have shown that more than 90% of cells, including the nuclei, aligned to the gratings [26]. REM technique is probably the most used among soft lithographic methods since it is simpler and requires almost no specific equipment to produce micro features on the PDMS master mold.
patterns which resulted in the modification of the morphology of the fibroblast cells indicating that this approach can be used in the future to control cell shape-functionality on-chip. Moreover, Baran et al. [18] used heparin as a biochemical cue and μCP as a technique to stamp the heparin patterns on membranes with previous topographical patterns. Fibroblast cell culture showed different grown patterns when using heparin printed surface. Also, only the heparin patterned membranes combined with topographical patterns induced the organization of fibroblasts [18]. In tissue engineering context, μCP can be seen as a complementary method to pattern not topographical features but biochemical cues to induce cell attachment and organization. In the future, the combination of μCP with other soft lithographic techniques for topographical feature production can be an increasing strategy for tissue engineering applications since it can improve cell adhesion and at the same time, promote cellular organization.
2.1.2. Micromolding in capillaries Micromolding in capillaries (MIMIC) (Fig. 1C) is a lithographic method based on microfluidics and is a suitable technique to generate patterned microstructures of organic polymers on the surface of solid substrates [78]. An empty network of channels (PDMS mold) is designed with the contact between mold and substrate. Then the channels can be filled with a polymer solution by capillary action [79,80]. The liquid flows in the capillaries due to pressure difference between two hydraulically connected regions of the liquid mass. After the channels are fulfilled, the polymer is cured and the PDMS mold can be removed from the substrate [81–83]. MIMIC, as an all soft lithographic method, has advantages such as, low cost and a wider range of polymers to pattern [84]. Yu et al. [85] describes MIMIC as a simple and multipurpose patterning method, capable to produce highly systematic and reproducible polymer patterns with tunable morphologies and sizes [85]. Moreover, Vozzi et al. [86] studied the use of three different methods based on soft lithography to prepare 3D scaffolds of poly(lactic-co-glycolic acid) (PLGA) with feature resolution of 10–30 μm. The techniques used include microfluidic molding (MIMIC), micromolding and spin coating however, limited geometry due to pressure drop was referred as a limitation of microfluidic molding. Folch et al. [87] developed microfluidic molding structures as models for scaffold production. Polyurethane (PU) precursor was injected into a network mold of PDMS and the obtained structures were described as inexpensive that can be implemented in biological applications using biodegradable polymers and serve as scaffolds. Therefore, MIMIC can produce patterns from different materials on several substrates filling the PDMS channels using the capillarity force. All these studies revealed that MIMIC is an inexpensive and high resolution method achieving resolution as small as 1 μm.
Hot embossing (Fig. 1E) is described as a process that uses temperature, pressure and vacuum conditions in order to mold polymer producing features as small as 5 nm. Initially, the polymer and the master mold are placed in contact and heated above the glass transition temperature (Tg) or melting temperature of the thermoplastic polymer (when the viscosity changes substantially and the material becomes a viscous mass) [93,94]. Then, a controlled force is applied under vacuum conditions, finally, the master mold and the polymer are cooled below the glass transition temperature and de-embossed [93]. The vacuum is needed to prevent the trapping of air in the microstructures and to remove water vapor driven out from the polymer substrate during the process. In addition, it is an important condition to increase the lifetime of metallic master molds by preventing corrosion at high temperatures [93]. Hot embossing is an extremely advantageous method producing features with excellent replication capabilities and well-defined shapes, exhibiting very low surface roughness of less than 5 nm [95]. It is a relatively simpler replication process, and possesses few variable parameters, producing structures with high accuracy and wide range of shapes and aspect ratios [96]. The method is well suited for a wide range of micro fluidic applications, material characteristics and biochemical compatibility [93]. The hot embossing is also described as a low-cost technique for producing pathways to control cell shape and alignment [97]. In literature, different terms are used to describe hot embossing process [98,99] depending on the scale and the material used as master mold. The method is described as nanoimprint lithography for patterns on the nanoscale that usually uses master molds made from silicon wafers since they can achieve high resolution structures; and embossing or micro hot embossing when the scale of the patterns are on μm. Nanoimprinting lithography was for the first time described by Chou et al. [100]. This method consists of using photolithographic methods to produce patterns on silicon wafer that are further used as a master mold to imprint micro/nano features through mechanical embossing. Hu et al. [101] fabricated nanostructured materials for applications in tissue engineering. Nanoimprinting lithography (NIL) was used to pattern features on polystyrene plates and subsequently, 3D scaffolds were constructed. Under cell culture studies, bovine pulmonary artery smooth muscle cells attached and proliferated to the patterns and cell alignment was observed. Aiming to build artificial capillaries, Wang et al. [48] fabricated vascular networks using polycarbonate (PC) and poly(lactic-co-glycolic acid) (PLGA) by hot embossing technique. It was concluded that the loading pressure and the embossing temperature were the main parameters affecting the structure's quality. Bovine endothelial cells (BCE) were seeded on the scaffolds using dynamic conditions demonstrating encouraging results. In another study, Mills et al. [35] produced
2.1.3. Microcontact printing Microcontact printing (μCP) technique (Fig. 1D) is one of the most used methods to pattern functional organic surfaces. For this purpose, an elastomeric stamp is used with relief on its surface to generate self-assembled monolayers (SAMs) on the surface of planar and curved substrates [59,60,88]. Specifically advantageous for tissue engineering applications, this methodology is used to tailor wettability, biocompatibility or reactivity of the surface by transferring organic coatings [67]. Several studies reported in the literature describe the use of μCP as a technique to create biochemical cues for cell alignment [89,90]. Mrksich et al. [91] used μCP to pattern the formation of SAMs at the micrometer scale in order to promote the attachment of mammalian cells. SAMs were coated with fibronectin and the preferential adhesion of the cells was observed. In a different study, Das et al. [92] also analyzes the interaction of the mammalian cells using μCP
2.2. Hot embossing
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structures on the surface of poly(lactic acid) — PLA by nanoembossing and the product features achieved dimensions smaller than cells. Furthermore, Charest et al. [97] used hot embossing method to prepare micro textured polymer substrates with grooves of approximately 5 μm deep, 4 μm wide, and a periodicity of 34 μm. The main objective was to study the response of osteoblast cells grown on these surfaces. Petronis et al. [102] also used hot embossing techniques to improve the fabrication method of micro structured ceramic scaffolds. It was created a well-defined surface morphology given the advantages such as simplicity and expandability for large areas compared to injection molding. In a recent study, Lima et al. [103] reported the use of hot embossing method to produce two-dimensional (2D) microfabricated membranes from polycaprolactone (PCL) and a biodegradable blend consisting of starch–polycaprolactone (SPCL (30% starch)) with accurately imprinted micro pillars and micro holes and further assembled for multi-layer scaffolds production. The stability of rigid molds as well as the solvent-free characteristic of embossing processes are advantageous since they allow maintaining the fabricated features for longer time with a single mold and avoid contamination of the polymer matrix due to the solvent usage. 3. Soft lithography vs hot embossing As described above, several micro/nanofabrication methods have been used to obtain micro/nanofabricated membranes for tissue engineering applications [104,105]. Among them, it is possible to evidence the major limitation of soft lithography techniques that concerns the deformation of the soft mold due to the high embossing pressure and the use of solvents that frequently causes distortion of the structures [103, 105,106]. Nevertheless, soft lithography is an advantageous process to produce low cost molds due to the easy processing and the low cost of the mold materials. On the other hand, when using hot embossing, the collapse of the membrane features can be avoided due to fabrication parameters inherent to the hot embossing process (solvent-free, pressure, temperature, time and vacuum conditions), and due to the rigid character of the master mold that preserved the micro architecture and can be used for a longer time (N1000). Although hot embossing process is more expensive than soft lithography, it overcomes the use of solvents in the process (not appropriate for tissue engineering applications since it may cause toxicity for the cells seeded on the scaffold) being only limited by the viscosity of the material at higher temperatures.
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scaffolds they utilized the membranes immediately after casting when the solvent residue still present to enable the bonding of layers. After the entire sample was created it has utilized phase separation to remove the solvent. On a simple method, Boike et al. [108] used the approach of bonding the polymers below Tg temperature although deformation of structures was observed. Moreover, the report study by Bao et al. [109] shows that 3D structures can be imprinted over the existing polymer patterns. The versatility of controlling the material selection and process condition and high resolution are the main advantages of this method. However, the process creates a residue film that is removed by Oxygen Reactive Ion Etching (O2 RIE). In addition, Bettinger et al. [110] create patterned silk fibroin layers and they were bound between rigid plates under mechanical pressure at 70 °C for 18 h to produce a water-insoluble silk fibroin interface. The method described by Bettinger et al. avoids the use of toxic solvents and harsh processing conditions nevertheless this method was only described to be applied to silk fibroin materials. Kehagias et al. [111] utilized a combination of nanoimprint lithography and contact printing lithography. To create scaffolds, certain areas of the layers were exposed to UV light. After, UV unexposed areas were dissolved in a solution and only the UV exposed areas were bounded creating a 3D structure. Recently, Lima et al. proposed a novel, easy, highly reproducible and inexpensive bottom-up approach for assembling scaffolds using microfabricated PCL and SPCL biodegradable membranes as base-units. Stable scaffolds of PCL, SPCL and combination of both, with the micro features of the membranes were obtained. The application of a small amount of PCL solution only on the top of the pillars to bind the membranes enabled to overcome the need for using large amounts of solvents as well as to maintain the integrity of the structure due to the low manipulation degree [103]. As described above, several approaches are being studied to create 3D structures from 2D micro/nano fabricated membranes (typical structure produced by replication techniques). Still, height scaffold limitations are still far from being eliminated during the assembling due to the collapsing of membranes and low adhesive forces between each layer. Indeed, several authors describe assembling from 3 to 12 layers of micro/nano fabricated membranes leading to scaffold heights from 0.1 to 0.4 cm, depending on the number of layers assembled [103,104, 109]. For 3D structure production, the choice of the best technique must be based on the clinical application and size of defects, robustness and precision combined with the use of low amounts of solvents to avoid the possible toxicity for cell seeding.
4. 3D assembling approaches for tissue engineering applications 5. Conclusions Despite the significant attainments in the creation of micro/ nanofabricated structures, soft lithography and hot embossing technologies produce 2D membranes. Nevertheless, scaffolds for tissue engineering applications are described as three-dimensional (3D) structures. To overcome this limitation, assembling methodologies emerged as a tool to construct 3D scaffolds from 2D membranes. Fig. 2 represents the procedure to produce the final 3D scaffold for tissue engineering applications. Several studies presented novel approaches to achieve 3D scaffolds from 2D membranes. Mata et al. [104] used a method of a dual sided molding system: a SU-8 and a PDMS mold to pattern features on PDMS membranes. Afterwards, the 3D assembling was accessed using a mechanical jig to control the alignment of the membranes. Still this procedure can be very expensive and it has not yet reported applications of biodegradable polymers for real tissue engineering applications. In a different study, Yang et al. [105] used a variety of microembossing processes to transfer the pattern to the poly(DL-lactide-co-glycolide) substrate. For membrane's assembly, CO2 bonding technique was used demonstrating to be a powerful method to assemble 3D scaffolds at low temperatures. Papenburg et al. [107] employed solvents to cast polymer into the mold, similar to the REM process. To create 3D
Regarding tissue engineering field, replication methods are able to create micro/nano features on 2D membranes for improvement of cellular alignment and biocompatibility. Comparing both reported replication techniques, soft lithography is described as an inexpensive technology that allows creating multiple elastomeric molds from a single master mold. Still, hot embossing uses a more stable rigid mold that creates more precise features with high aspect ratio resolution without the use of solvents. For concrete applications in tissue engineering, the application of 3D scaffolds for large tissue defects is unavoidable. For that reason, assembling 2D layers for creation of a 3D scaffold with good adherence between them is crucial. The use of large amounts of solvents and high temperatures during the assembling could take several scaffold deformation. Hence, assembling technique must be chosen depending on the application and the physical properties of the used materials. Replication methods including soft lithography and hot embossing coupled with assembling techniques can be used to construct highly precise scaffolds and that represents an advance in the tissue engineering field.
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References [1] S.J. Shieh, J.P. Vacanti, State-of-the-art tissue engineering: from tissue engineering to organ building, Surgery 137 (1) (2005) 1–7. [2] G. Chen, T. Ushida, T. Tateishi, Development of biodegradable porous scaffolds for tissue engineering, Mater. Sci. Eng. C 17 (1–2) (2001) 63–69. [3] L. De Bartolo, et al., Bio-hybrid organs and tissues for patient therapy: a future vision for 2030, Chem. Eng. Process. Process Intensif. 51 (2012) 79–87. [4] G.K. Sandor, R. Suuronen, Combining adipose-derived stem cells, resorbable scaffolds and growth factors: an overview of tissue engineering, J. Can. Dent. Assoc. 74 (2) (2008) 167–170. [5] I. Armentano, et al., Biodegradable polymer matrix nanocomposites for tissue engineering: a review, Polym. Degrad. Stab. 95 (11) (2010) 2126–2146. [6] R. Langer, J.P. Vacanti, Tissue engineering, Science 260 (5110) (1993) 920–926. [7] R.M. Allaf, I.V. Rivero, Fabrication and characterization of interconnected porous biodegradable poly(epsilon-caprolactone) load bearing scaffolds, J. Mater. Sci. Mater. Med. 22 (8) (2011) 1843–1853. [8] G.L. Converse, et al., Hydroxyapatite whisker-reinforced polyetherketoneketone bone ingrowth scaffolds, Acta Biomater. 6 (3) (2010) 856–863. [9] Y.S. Nam, J.J. Yoon, T.G. Park, A novel fabrication method of macroporous biodegradable polymer scaffolds using gas foaming salt as a porogen additive, J. Biomed. Mater. Res. 53 (1) (2000) 1–7. [10] J.J. Yoon, T.G. Park, Degradation behaviors of biodegradable macroporous scaffolds prepared by gas foaming of effervescent salts, J. Biomed. Mater. Res. 55 (3) (2001) 401–408. [11] A. Salerno, et al., Design of porous polymeric scaffolds by gas foaming of heterogeneous blends, J. Mater. Sci. Mater. Med. 20 (10) (2009) 2043–2051. [12] M.E. Gomes, et al., Starch-poly(epsilon-caprolactone) and starch-poly(lactic acid) fibre-mesh scaffolds for bone tissue engineering applications: structure, mechanical properties and degradation behaviour, J. Tissue Eng. Regen. Med. 2 (5) (2008) 243–252. [13] M.E. Gomes, et al., Effect of flow perfusion on the osteogenic differentiation of bone marrow stromal cells cultured on starch-based three-dimensional scaffolds, J. Biomed. Mater. Res. A 67 (1) (2003) 87–95. [14] A.G. Mikos, et al., Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation, J. Biomed. Mater. Res. 27 (2) (1993) 183–189. [15] Q. Lv, Q. Feng, Preparation of 3-D regenerated fibroin scaffolds with freeze drying method and freeze drying/foaming technique, J. Mater. Sci. Mater. Med. 17 (12) (2006) 1349–1356. [16] M.G. Haugh, C.M. Murphy, F.J. O'Brien, Novel freeze-drying methods to produce a range of collagen-glycosaminoglycan scaffolds with tailored mean pore sizes, Tissue Eng. Part C Methods 16 (5) (2010) 887–894. [17] D. Sin, et al., Polyurethane (PU) scaffolds prepared by solvent casting/particulate leaching (SCPL) combined with centrifugation, Mater. Sci. Eng. C 30 (1) (2010) 78–85. [18] E.T. Baran, et al., Microchannel-patterned and heparin micro-contact-printed biodegradable composite membranes for tissue-engineering applications, J. Tissue Eng. Regen. Med. 5 (6) (2011) e108–e114. [19] M.E. Gomes, et al., A new approach based on injection moulding to produce biodegradable starch-based polymeric scaffolds: morphology, mechanical and degradation behaviour, Biomaterials 22 (9) (2001) 883–889. [20] Z. Chen, et al., Fabrication of osteo-structure analogous scaffolds via fused deposition modeling, Scr. Mater. 52 (2) (2005) 157–161. [21] D.W. Hutmacher, et al., Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling, J. Biomed. Mater. Res. 55 (2) (2001) 203–216. [22] F.P. Melchels, J. Feijen, D.W. Grijpma, A poly(D,L-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography, Biomaterials 30 (23–24) (2009) 3801–3809. [23] C.X.F. Lam, et al., Scaffold development using 3D printing with a starch-based polymer, Mater. Sci. Eng. C 20 (1–2) (2002) 49–56. [24] B. Leukers, et al., Hydroxyapatite scaffolds for bone tissue engineering made by 3D printing, J. Mater. Sci. Mater. Med. 16 (12) (2005) 1121–1124. [25] S.P. Garland, T.M.M. Jr, T. Pan, Print-to-pattern dry film photoresist lithography, J. Micromech. Microeng. 24 (5) (2014) 057002. [26] E.K. Yim, et al., Nanopattern-induced changes in morphology and motility of smooth muscle cells, Biomaterials 26 (26) (2005) 5405–5413. [27] E. Tejeda-Montes, et al., Engineering membrane scaffolds with both physical and biomolecular signaling, Acta Biomater. 8 (3) (2012) 998–1009. [28] A. Bakry, et al., A new approach for the preparation of hydrophilic poly(L-lactide) porous scaffold for tissue engineering by using lamellar single crystals, Polym. Int. 61 (7) (2012) 1177–1185. [29] J. Mitra, et al., Scaffolds for bone tissue engineering: role of surface patterning on osteoblast response, RSC Adv. 3 (28) (2013) 11073–11094. [30] A.A.K. Moe, et al., Microarray with micro- and nano-topographies enables identification of the optimal topography for directing the differentiation of primary murine neural progenitor cells, Small 8 (19) (2012) 3050–3061. [31] M. Ahmed, et al., Nanostructured materials for cardiovascular tissue engineering, J. Nanosci. Nanotechnol. 12 (6) (2012) 4775–4785. [32] W. Chia-Wen, A. Tsuyoshi, K. Makoto, Electron-beam lithography assisted patterning of surfactant-templated mesoporous thin films, Nanotechnology 15 (12) (2004) 1886. [33] G.M. Whitesides, et al., Soft lithography in biology and biochemistry, Annu. Rev. Biomed. Eng. 3 (2001) 335–373. [34] J. Charest, W. King, Engineering biomaterial interfaces through micro and nanopatterning, in: P. Hesketh (Ed.), BioNanoFluidic MEMS, Springer, US, 2008, pp. 251–277.
[35] C.A. Mills, et al., Transparent micro- and nanopatterned poly(lactic acid) for biomedical applications, J. Biomed. Mater. Res. A 76 (4) (2006) 781–787. [36] M. Schvartzman, S.J. Wind, Robust pattern transfer of nanoimprinted features for sub-5-nm fabrication, Nano Lett. 9 (10) (2009) 3629–3634. [37] Geissler, M., 4.03 — Sub-micrometer patterning using soft lithography, in Comprehensive Nanoscience and Technology, L.A. Editors-in-Chief: David, D.S. Gregory, and P.W. Gary, Editors. 2011, Academic Press: Amsterdam. p. 63–81. [38] C. Acikgoz, et al., Polymers in conventional and alternative lithography for the fabrication of nanostructures, Eur. Polym. J. 47 (11) (2011) 2033–2052. [39] K.-L. Lai, et al., Patterning of polystyrene thin films by solvent-assisted imprint lithography and controlled dewetting, Microelectron. Eng. 94 (2012) 33–37. [40] P. Clark, et al., Cell guidance by ultrafine topography in vitro, J. Cell Sci. 99 (Pt 1) (1991) 73–77. [41] J. Wu, et al., The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells, Biomaterials 33 (5) (2012) 1343–1352. [42] C.J. Bettinger, et al., Microfabrication of poly (glycerol-sebacate) for contact guidance applications, Biomaterials 27 (12) (2006) 2558–2565. [43] Y. Wan, et al., Adhesion and proliferation of OCT-1 osteoblast-like cells on microand nano-scale topography structured poly(L-lactide), Biomaterials 26 (21) (2005) 4453–4459. [44] K.S. Brammer, et al., Hydrophobic nanopillars initiate mesenchymal stem cell aggregation and osteo-differentiation, Acta Biomater. 7 (2) (2011) 683–690. [45] G.J. Bakeine, et al., Design, fabrication and evaluation of nanoscale surface topography as a tool in directing differentiation and organisation of embryonic stem-cell-derived neural precursors, Microelectron. Eng. 86 (4–6) (2009) 1435–1438. [46] S. Fuchs, et al., Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds, Biomaterials 30 (4) (2009) 526–534. [47] K. Jörg, B. Stefanie, S. Martin, Low temperature adhesion bonding for BioMEMS, J. Micromech. Microeng. 16 (4) (2006) 802. [48] G.J. Wang, et al., Bio-MEMS fabricated artificial capillaries for tissue engineering, Microsyst. Technol. 12 (1–2) (2005) 120–127. [49] C.Y. Tay, et al., Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications, Small 7 (10) (2011) 1361–1378. [50] W. Ryu, et al., The construction of three-dimensional micro-fluidic scaffolds of biodegradable polymers by solvent vapor based bonding of micro-molded layers, Biomaterials 28 (6) (2007) 1174–1184. [51] Y. Xia, et al., Complex optical surfaces formed by replica molding against elastomeric masters, Science 273 (5273) (1996) 347–349. [52] E. Delamarche, et al., Patterned delivery of immunoglobulins to surfaces using microfluidic networks, Science 276 (5313) (1997) 779–781. [53] M. Emmelius, G. Pawlowski, H.W. Vollmann, Materials for optical data storage, Angew. Chem. Int. Ed. Engl. 28 (11) (1989) 1445–1471. [54] J. Kim, et al., Biologically inspired micro- and nanoengineering systems for functional and complex tissues, Tissue Eng. A (2014). [55] S.Y. Chou, et al., Sub-10 nm Imprint Lithography and Applications, AVS, Dana Point, California (USA), 1997. [56] S. Zhang, et al., Biological surface engineering: a simple system for cell pattern formation, Biomaterials 20 (13) (1999) 1213–1220. [57] M. Beck, et al., Improving stamps for 10 nm level wafer scale nanoimprint lithography, Microelectron. Eng. 61–62 (2002) 441–448. [58] H. Cao, et al., Fabrication of 10 nm enclosed nanofluidic channels, Appl. Phys. Lett. 81 (1) (2002) 174–176. [59] G. Cao, Nanostructures fabricated by physical techniques, Nanostructures and Nanomaterials, 2004, pp. 277–328. [60] S.S. Saliterman, Fundamentals of BioMEMS and Medical Microdevices, 2006, pp. 75–98. [61] S. Alom Ruiz, C.S. Chen, Microcontact printing: a tool to pattern, Soft Matter 3 (2) (2007) 168–177. [62] N.S. Devaraju, M.A. Unger, Multilayer soft lithography of perfluoropolyether based elastomer for microfluidic device fabrication, Lab Chip 11 (11) (2011) 1962–1967. [63] C.M. Bruinink, et al., Stamps for submicrometer soft lithography fabricated by capillary force lithography, Adv. Mater. 16 (13) (2004) 1086–1090. [64] H. Liu, et al., Thermal processing of starch-based polymers, Prog. Polym. Sci. 34 (12) (2009) 1348–1368. [65] D.K. Cai, et al., Optical absorption in transparent PDMS materials applied for multimode waveguides fabrication, Opt. Mater. 30 (7) (2008) 1157–1161. [66] W.M. Choi, O.O. Park, A soft-imprint technique for direct fabrication of submicron scale patterns using a surface-modified PDMS mold, Microelectron. Eng. 70 (1) (2003) 131–136. [67] B.D. Gates, et al., Unconventional nanofabrication, Annu. Rev. Mater. Res. 34 (1) (2004) 339–372. [68] O.C. Jeong, S. Konishi, Controlling the size of replicable polydimethylsiloxane (PDMS) molds/stamps using a stepwise thermal shrinkage process, Microelectron. Eng. 88 (8) (2011) 2286–2289. [69] N. Koo, et al., Improved mold fabrication for the definition of high quality nanopatterns by Soft UV-Nanoimprint lithography using diluted PDMS material, Microelectron. Eng. 84 (5–8) (2007) 904–908. [70] Q. He, et al., Angular evaluation to quantify planar distortions of PDMS stamps in soft lithography, Mater. Chem. Phys. 83 (1) (2004) 60–65. [71] Y. Xia, G.M. Whitesides, Soft lithography, Annu. Rev. Mater. Sci. 28 (1) (1998) 153–184. [72] T.-K. Shih, et al., Fabrication of various curved relief structures through concave surface forming and soft replica molding, Microelectron. Eng. 83 (3) (2006) 471–475. [73] D. Losic, et al., Rapid fabrication of micro- and nanoscale patterns by replica molding from diatom biosilica, Adv. Funct. Mater. 17 (14) (2007) 2439–2446.
M.J. Lima et al. / Materials Science and Engineering C 42 (2014) 615–621 [74] J.K.S. Poon, et al., Soft lithography replica molding of critically coupled polymer microring resonators, IEEE Photon. Technol. Lett. 16 (11) (2004) 2496–2498. [75] J.C. Charles, et al., Surface-enhanced Raman nanodomes, Nanotechnology 21 (41) (2010) 415301. [76] I.D. Block, L.L. Chan, B.T. Cunningham, Large-area submicron replica molding of porous low-k dielectric films and application to photonic crystal biosensor fabrication, Microelectron. Eng. 84 (4) (2007) 603–608. [77] J.T. Borenstein, et al., Microfabrication technology for vascularized tissue engineering, Biomed. Microdevices 4 (3) (2002) 167–175. [78] J. Chen, et al., Hybrid hierarchical patterns of gold nanoparticles and poly(ethylene glycol) microstructures, J. Mater. Chem. C 1 (46) (2013) 7709–7715. [79] M. Dong, F.A.L. Dullien, I. Chatzis, Imbibition of oil in film form over water present in edges of capillaries with an angular cross section, J. Colloid Interface Sci. 172 (1) (1995) 21–36. [80] L. Beria, et al., ‘Clickable’ hydrogels for all: facile fabrication and functionalization, Biomater. Sci. 2 (1) (2014) 67–75. [81] M.J. Park, W.M. Choi, O.O. Park, Patterning polymer light-emitting diodes by micromolding in capillary, Curr. Appl. Phys. 6 (4) (2006) 627–631. [82] K.-Y. Suh, M.C. Park, P. Kim, Capillary force lithography: a versatile tool for structured biomaterials interface towards cell and tissue engineering, Adv. Funct. Mater. 19 (17) (2009) 2699–2712. [83] E. Bystrenova, et al., Multiple length-scale patterning of DNA by stamp-assisted deposition, Angew. Chem. 118 (29) (2006) 4897–4900. [84] Y. Xia, E. Kim, G.M. Whitesides, Micromolding of polymers in capillaries: applications in microfabrication, Chem. Mater. 8 (7) (1996) 1558–1567. [85] X. Yu, et al., Fabrication of structures with tunable morphologies and sizes by soft molding, Appl. Surf. Sci. 252 (5) (2005) 1947–1953. [86] G. Vozzi, et al., Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition, Biomaterials 24 (14) (2003) 2533–2540. [87] A. Folch, et al., Stacks of microfabricated structures as scaffolds for cell culture and tissue engineering, Biomed. Microdevices 2 (3) (2000) 207–214. [88] S. Casimirius, et al., Microcontact printing process for the patterned growth of individual CNTs, Microelectron. Eng. 73–74 (2004) 564–569. [89] C.A. Trinkle, L.P. Lee, High-precision microcontact printing of interchangeable stamps using an integrated kinematic coupling, Lab Chip 11 (3) (2011) 455–459. [90] R.N. Orth, et al., Creating biological membranes on the micron scale: forming patterned lipid bilayers using a polymer lift-off technique, Biophys. J. 85 (5) (2003) 3066–3073. [91] M. Mrksich, et al., Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver, Exp. Cell Res. 235 (2) (1997) 305–313. [92] T. Das, et al., Microcontact printing of Concanavalin A and its effect on mammalian cell morphology, J. Colloid Interface Sci. 314 (1) (2007) 71–79. [93] P. Ian, Hot embossing for lab-on-a-chip applications, Bio-MEMS, CRC Press, 2006, pp. 117–140. [94] H. Becker, U. Heim, Hot embossing as a method for the fabrication of polymer high aspect ratio structures, Sensors Actuators A Phys. 83 (1–3) (2000) 130–135. [95] K. Mohamed, M.M. Alkaisi, R.J. Blaikie, Fabrication of Three Dimensional Structures for an UV Curable Nanoimprint Lithography Mold Using Variable Dose Control With Critical-energy Electron Beam Exposure, 2007. (AVS).
621
[96] N. Jagannathan, P. Ian, Polymer embossing tools for rapid prototyping of plastic microfluidic devices, J. Micromech. Microeng. 14 (1) (2004) 96. [97] J.L. Charest, et al., Hot embossing for micropatterned cell substrates, Biomaterials 25 (19) (2004) 4767–4775. [98] M.D. Austin, et al., Fabrication of 5 nm linewidth and 14 nm pitch features by nanoimprint lithography, Appl. Phys. Lett. 84 (26) (2004) 5299–5301. [99] S. Lan, et al., A parameter study on the micro hot-embossing process of glassy polymer for pattern replication, Microelectron. Eng. 86 (12) (2009) 2369–2374. [100] L.J. Guo, Recent progress in nanoimprint technology and its applications, J. Phys. D. Appl. Phys. 37 (11) (2004) R123. [101] W. Hu, et al., Effects of nanoimprinted patterns in tissue-culture polystyrene on cell behavior, J. Vac. Sci. Technol. A 23 (6) (2005) 2984–2989. [102] S. Petronis, et al., Microstructuring ceramic scaffolds for hepatocyte cell culture, J. Mater. Sci. Mater. Med. 12 (6) (2001) 523–528. [103] M.J. Lima, et al., Bottom-up approach to construct microfabricated multi-layer scaffolds for bone tissue engineering, Biomed. Microdevices (2013) 1–10. [104] A. Mata, et al., A three-dimensional scaffold with precise micro-architecture and surface micro-textures, Biomaterials 30 (27) (2009) 4610–4617. [105] Y. Yang, et al., Fabrication of well-defined PLGA scaffolds using novel microembossing and carbon dioxide bonding, Biomaterials 26 (15) (2005) 2585–2594. [106] J.A. Rogers, K.E. Paul, G.M. Whitesides, Quantifying distortions in soft lithography, J. Vac. Sci. Technol. B Microelectron. Nanometer Struct. 16 (1) (1998) 88–97. [107] B.J. Papenburg, et al., One-step fabrication of porous micropatterned scaffolds to control cell behavior, Biomaterials 28 (11) (2007) 1998–2009. [108] Y.M. Boiko, R.E. Prud'homme, Bonding at symmetric polymer/polymer interfaces below the glass transition temperature, Macromolecules 30 (12) (1997) 3708–3710. [109] L.R. Bao, et al., Nanoimprinting Over Topography and Multilayer Threedimensional Printing, AVS, Anaheim, California (USA), 2002. [110] C.J. Bettinger, et al., Silk fibroin microfluidic devices, Adv. Mater. 19 (5) (2007) 2847–2850. [111] N. Kehagias, et al., Reverse-contact UV nanoimprint lithography for multilayered structure fabrication, Nanotechnology 18 (17) (2007) 175303. [112] D. Wang, et al., Patterning of Gd2(WO4)3:Ln3+ (Ln = Eu, Tb) luminescent films by microcontact printing route, J. Colloid Interface Sci. 365 (1) (2012) 320–325. [113] A.M.C. Egea, C. Vieu, Microcontact printing of biomolecular gratings from SU-8 masters duplicated by Thermal Soft UV NIL, Microelectron. Eng. 88 (8) (2011) 1935–1938. [114] S.M. Giannitelli, et al., Surface decoration of electrospun scaffolds by microcontact printing, Asia Pac. J. Chem. Eng. (2014) (p. n/a-n/a). [115] B. Chelli, et al., Neural cell alignment by patterning gradients of the extracellular matrix protein laminin, Interface Focus 4 (1) (2014). [116] S.Y. Chou, P.R. Krauss, Imprint lithography with sub-10 nm feature size and high throughput, Microelectron. Eng. 35 (1) (1997) 237–240. [117] P. Linfa, et al., Micro hot embossing of thermoplastic polymers: a review, J. Micromech. Microeng. 24 (1) (2014) 013001. [118] A. Ifty, Hot topics in biomaterials, Future Science Book Series, Future Science Ltd, 2014. (116). [119] M. Elsayed, O.M. Merkel, Nanoimprinting of topographical and 3D cell culture scaffolds, Nanomedicine (London) 9 (2) (2014) 349–366.
Contents lists available at ScienceDirect
Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec
Review
Micro/nano replication and 3D assembling techniques for scaffold fabrication M.J. Lima, V.M. Correlo ⁎, R.L. Reis a
3B's Research Group — Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, 4806-909 Guimarães, Portugal ICVS/3B's, Associate Laboratory, PT Government Associate Laboratory, Guimarães, Braga, Portugal
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a r t i c l e
i n f o
Article history: Received 22 January 2014 Received in revised form 19 May 2014 Accepted 30 May 2014 Available online 6 June 2014 Keywords: Scaffolds Micro/nanofabrication Hot embossing Soft lithography Patterning
a b s t r a c t The development of tissue engineering field entails the creation of micro/nanoscale features for cellular alignment and biocompatibility improvement. As replication techniques, hot embossing and soft lithography can be used to produce micro/nanoscale features on biodegradable membranes. Subsequently the generation of 3D scaffolds can be done by means of assembling techniques. Using the described techniques, high resolution of features, as small as 5 nm, can be achieved. Nevertheless membrane assembling must be fully studied to avoid feature fluctuations and even collapse of the scaffold. The present review focuses on the state-of-the-art in the replication techniques used to create micro/nanoscale features on biodegradable polymers and assembling approaches to construct scaffolds with the aim of exploring existing advances and limitations of the reported methods. © 2014 Elsevier B.V. All rights reserved.
Contents 1. 2.
Introduction . . . . . . . . . . . . . . . . . . . . . . . Replication technologies for tissue engineering applications . 2.1. Soft lithography . . . . . . . . . . . . . . . . . . 2.1.1. Replica molding . . . . . . . . . . . . . 2.1.2. Micromolding in capillaries . . . . . . . . 2.1.3. Microcontact printing . . . . . . . . . . . 2.2. Hot embossing . . . . . . . . . . . . . . . . . . 3. Soft lithography vs hot embossing . . . . . . . . . . . . . 4. 3D assembling approaches for tissue engineering applications 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction Organ failure and tissue loss are the major problems in human health care [1]. To circumvent these problems, surgical strategies, such as, organ transplantation, tissue transfer and prosthesis replacement are the most commonly used approaches [1,2]. Nevertheless, several
⁎ Corresponding author at: 3B's Research Group — Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Taipas, 4806-909 Guimarães, Portugal. E-mail address: [email protected] (V.M. Correlo).
http://dx.doi.org/10.1016/j.msec.2014.05.064 0928-4931/© 2014 Elsevier B.V. All rights reserved.
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disadvantages are associated with these therapies, namely, shortage of organ donors, disease transmission and biocompatibility issues [3]. In the past few years, tissue engineering emerged in the field of orthopedic surgery and biomedical engineering as a discipline able to offer promising alternatives to actual therapies [4,5]. This new field of research was defined by Langer and Vacanti as “an interdisciplinary field that applies the principles of engineering and of life science towards the development of biological substitutes that restore, maintain or improve tissue or organ function” [6]. Earlier, different approaches to create scaffolds, such as, compression molding followed by porogen leaching [7,8], gas foaming [9–11], fiberbonding [12–14], freeze-drying [15,16], and solvent casting [17] have
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been studied. Nevertheless, these methods are limited by their random micro-geometries, low-resolution features, random distribution of pores, residual particles and solvents in the polymer matrix and limited oxygen/nutrient supply [18]. Afterwards, machine-based processes, such as, micro injection molding [19] and rapid prototyping including fused deposition modeling (FDM) [20,21], stereolithography (SLA) [22] and 3D printing [23,24], were also used to produce biocompatible organized structures but the limited resolution is still a drawback. In the recent years, micro/nanofabrication technologies have emerged as versatile and powerful approaches for micro/nanoscale feature creation and can be broadly separated into direct methods and replication methods. As the name implies, the first method creates patterns directly on the substrate (e.g. photolithography) and the second one replicates features using several times the same master mold (that is usually produced by direct methods). Despite of direct methods being able to create patterns with good resolutions, they are usually more expensive methods than replication techniques [25]. Replication methods are emerging tools for tissue engineering applications since they can tailor biochemical cues and surface patterns capable of controlling cell adhesion or orientation producing precisely arranged co-culture systems [26–32] with lower associated costs. These technologies offer the possibility of building large-area stamps (from 4 to 100 cm2, [33,34]) with features at length scales from b5 nm to N1 cm creating feature scales smaller than those of cells [35,36]. A variety of different approaches has been successfully applied to produce different types of features on polymeric surfaces in the micrometer and submicrometer range [37–39] such as fibrillar ECM alignment [40,41], round features [42] and submicroscale textures and microgrooves [43]. Furthermore, the osteogenic differentiation of mesenchymal stem cells [44,45] and vascularization [46] were also reported to be promoted by micro/nanostructured substrates. This review will focus on the state-of-the art of replication methods and 3D assembling methodologies providing also a discussion of the advances and limitations of each technology and a perspective of the future trends regarding micro/nanofabrication techniques. 2. Replication technologies for tissue engineering applications Replication technologies, which allow the development of biofunctionalized surfaces with micro/nano patterned cues on both synthetic and natural based polymers become increasingly important to medical diagnostics, biochemical analysis, cell-based assays, sample preparation [47] and tissue engineering applications [48,49]. The use of these novel technologies, by achieving high resolution features at the nanoscale, improves the formation of new blood capillaries since cells attach to topographical cues avoiding the simple addition of cells to scaffold without any type of biochemical or physical cues that often leads to random and inadequate results [48,50]. Furthermore, synthetic and natural based biodegradable polymers can be cast onto micro/ nanofabricated molds to produce structures with small feature resolution [51–54]. Table 1 lists some of these replication technologies envisaging their application on the tissue engineering field.
Included on replication techniques, hot embossing (also known as nanoimprint lithography) and soft lithography (micro-casting) have been used to achieve patterns with dimensions as small as 5 nm [36, 55–58]. The master mold used for these replication techniques are usually produced using a hard or a soft material, being mold rigidity, the major difference between hot embossing and soft lithography. The following sub-chapters extensively describe the characteristics of each method. 2.1. Soft lithography Soft lithography, developed in 1997 by George Whitesides and coworkers, emerged as an alternative procedure to photolithographic techniques for micro/nanofabrication [59]. This method is included in replication methods and is characterized by using a patterned elastomer (usually made from PDMS) as a stamp or mold, to generate microstructures and a pre-polymer for posterior thermal or photo curable process [60]. Several elastomeric materials are used in the preparation of molds for soft lithography such as, poly(methylmethacrylate) (PMMA) [61], perfluoropolyether (SIFEL) [62] and polydimethilsiloxane (PDMS) [63]. Nevertheless, PDMS is the most widely used due to its transparency to visible wavelengths [64,65] and to its elastomeric characteristics providing also a low interfacial free energy on the surface and releasing easily from the substrate [66,67]. The schematic fabrication process of the elastomeric mold is shown in Fig. 1A. In this process, a master mold is usually made on a silicon wafer by photolithography. Afterwards, the PDMS pre-polymer is cast in the rigid master mold for further thermal curing and finally peeled off. As the fabrication of PDMS mold is based on replication process, multiple PDMS molds (or stamps) can be produced and each elastomeric stamp can be used for at least 50 times [60,68], depending on the replication technique conditions, mold material and feature patterns. This characteristic improves the productivity of the process with low associated costs. Nevertheless, the main disadvantage of using PDMS mold is the damage of the pattern height with consequent lower resolution of features [69] and even distortion/deformation of microstructures [70]. Soft lithographic techniques can be divided into: i) microcontact printing, ii) micromolding in capillaries, iii) microtransfer molding, iv) replica molding and v) solvent-assisted micromolding [56,59,71]. Up to now, only some of these techniques are being used for tissue engineering applications and are described as follows. 2.1.1. Replica molding The process of replica molding (REM) (Fig. 1B) consists of using a soft mold and a photo or thermally curable pre-polymer. The prepolymer is cast into the PDMS mold and solvents are photo or thermally removed to produce the micro/nano patterns on polymer substrate. With REM method it is possible to pattern features as small as the capillaries using different types of substrates. However, this technique uses solvents for polymer conformation into the mold.
Table 1 Replication techniques used in tissue engineering.
Soft lithography
Hot embossing
Method
Resolution
Main characteristics
References
Microcontact printing (μCP)
35 nm
[112–114]
Replica molding (REM)
30 nm
Micromolding in capillaries (MIMIC)
1 μm
Pattern substrates for cell culture to control the attachment of cells. Formation of self-assembled monolayers on an elastomeric mold to stamp the desired pattern and to create films. Uses PDMS mold to cast a pre polymer. After, the polymer is cured and detached from the mold. Ability to mold against nonplanar, rigid and soft topographic surfaces. Based on capillary force to fill the channels between the mold and the support. Uses a low viscosity polymer precursor and after, the PDMS mold is removed remaining only the molded polymer. Produces high-aspect-ratio structures. Utilizes temperature above Tg and vacuum conditions to prevent trapping of air in microstructures.
5–10 nm
[51,72–74] [82,83,86,115]
[36,98,116–119]
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Fig. 1. Schematic representation of micro/nanofabrication techniques: A) fabrication process of elastomeric molds for soft lithography applications; B) replica molding (REM); C) micromolding in capillaries (MIMIC); D) microcontact printing (μCP); and E) hot embossing.
Some pre-polymers can wear or dissolve the PDMS mold. Therefore, for REM, the mold can only be used for about 20 times. The advantage of using REM is the possibility to make patterns on large, nonplanar, rigid and soft substrates with low associated costs [51,67,72–74].
Polymer
Micro/nano fabrication technology
Several studies conducted in the tissue engineering field refer to REM as a low cost method to produce high aspect ratio structures [75, 76]. The method was used by Borenstein et al. [77] to construct microfabricated scaffolds in order to develop microvasculature enabling the
2D micro/nano fabricated membranes
Assembling methodology
3D scaffolds
Fig. 2. Methodology to achieve 3D scaffolds: the polymer is processed by micro/nanofabrication methods and 2D polymeric and biodegradable membranes were produced. After, a bottom-up methodology is applied to assemble those membranes. At the end 3D scaffolds were fabricated.
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development of bulk organ scaffolds. The development of the PDMS template was made by using a micromachined silicon mold. Moreover, the scaffold was successfully seeded with endothelial cells in channels with dimensions as small as the capillaries to promote vascularization. On the other hand, to control cell orientation and morphology by topographical patterning, poly (glycerol-sebacate) (PGS) on sucrose-coated microfabricated silicon was used by Bettinger et al. [42]. The fabricated microstructures were biocompatible, flexible and biodegradable with features in the range of 500 nm. The existing micro curvature in the fabricated structures was a stronger topographic cue in order to align and elongate aortic endothelial cells. In a different study, REM process was used for patterning poly(methyl methacrylate) (PMMA) and polydimethylsiloxane (PDMS) substrates to study the cell behavior, proliferation and morphology of pulmonary artery smooth muscle cells (SMC) [26]. The results have shown that more than 90% of cells, including the nuclei, aligned to the gratings [26]. REM technique is probably the most used among soft lithographic methods since it is simpler and requires almost no specific equipment to produce micro features on the PDMS master mold.
patterns which resulted in the modification of the morphology of the fibroblast cells indicating that this approach can be used in the future to control cell shape-functionality on-chip. Moreover, Baran et al. [18] used heparin as a biochemical cue and μCP as a technique to stamp the heparin patterns on membranes with previous topographical patterns. Fibroblast cell culture showed different grown patterns when using heparin printed surface. Also, only the heparin patterned membranes combined with topographical patterns induced the organization of fibroblasts [18]. In tissue engineering context, μCP can be seen as a complementary method to pattern not topographical features but biochemical cues to induce cell attachment and organization. In the future, the combination of μCP with other soft lithographic techniques for topographical feature production can be an increasing strategy for tissue engineering applications since it can improve cell adhesion and at the same time, promote cellular organization.
2.1.2. Micromolding in capillaries Micromolding in capillaries (MIMIC) (Fig. 1C) is a lithographic method based on microfluidics and is a suitable technique to generate patterned microstructures of organic polymers on the surface of solid substrates [78]. An empty network of channels (PDMS mold) is designed with the contact between mold and substrate. Then the channels can be filled with a polymer solution by capillary action [79,80]. The liquid flows in the capillaries due to pressure difference between two hydraulically connected regions of the liquid mass. After the channels are fulfilled, the polymer is cured and the PDMS mold can be removed from the substrate [81–83]. MIMIC, as an all soft lithographic method, has advantages such as, low cost and a wider range of polymers to pattern [84]. Yu et al. [85] describes MIMIC as a simple and multipurpose patterning method, capable to produce highly systematic and reproducible polymer patterns with tunable morphologies and sizes [85]. Moreover, Vozzi et al. [86] studied the use of three different methods based on soft lithography to prepare 3D scaffolds of poly(lactic-co-glycolic acid) (PLGA) with feature resolution of 10–30 μm. The techniques used include microfluidic molding (MIMIC), micromolding and spin coating however, limited geometry due to pressure drop was referred as a limitation of microfluidic molding. Folch et al. [87] developed microfluidic molding structures as models for scaffold production. Polyurethane (PU) precursor was injected into a network mold of PDMS and the obtained structures were described as inexpensive that can be implemented in biological applications using biodegradable polymers and serve as scaffolds. Therefore, MIMIC can produce patterns from different materials on several substrates filling the PDMS channels using the capillarity force. All these studies revealed that MIMIC is an inexpensive and high resolution method achieving resolution as small as 1 μm.
Hot embossing (Fig. 1E) is described as a process that uses temperature, pressure and vacuum conditions in order to mold polymer producing features as small as 5 nm. Initially, the polymer and the master mold are placed in contact and heated above the glass transition temperature (Tg) or melting temperature of the thermoplastic polymer (when the viscosity changes substantially and the material becomes a viscous mass) [93,94]. Then, a controlled force is applied under vacuum conditions, finally, the master mold and the polymer are cooled below the glass transition temperature and de-embossed [93]. The vacuum is needed to prevent the trapping of air in the microstructures and to remove water vapor driven out from the polymer substrate during the process. In addition, it is an important condition to increase the lifetime of metallic master molds by preventing corrosion at high temperatures [93]. Hot embossing is an extremely advantageous method producing features with excellent replication capabilities and well-defined shapes, exhibiting very low surface roughness of less than 5 nm [95]. It is a relatively simpler replication process, and possesses few variable parameters, producing structures with high accuracy and wide range of shapes and aspect ratios [96]. The method is well suited for a wide range of micro fluidic applications, material characteristics and biochemical compatibility [93]. The hot embossing is also described as a low-cost technique for producing pathways to control cell shape and alignment [97]. In literature, different terms are used to describe hot embossing process [98,99] depending on the scale and the material used as master mold. The method is described as nanoimprint lithography for patterns on the nanoscale that usually uses master molds made from silicon wafers since they can achieve high resolution structures; and embossing or micro hot embossing when the scale of the patterns are on μm. Nanoimprinting lithography was for the first time described by Chou et al. [100]. This method consists of using photolithographic methods to produce patterns on silicon wafer that are further used as a master mold to imprint micro/nano features through mechanical embossing. Hu et al. [101] fabricated nanostructured materials for applications in tissue engineering. Nanoimprinting lithography (NIL) was used to pattern features on polystyrene plates and subsequently, 3D scaffolds were constructed. Under cell culture studies, bovine pulmonary artery smooth muscle cells attached and proliferated to the patterns and cell alignment was observed. Aiming to build artificial capillaries, Wang et al. [48] fabricated vascular networks using polycarbonate (PC) and poly(lactic-co-glycolic acid) (PLGA) by hot embossing technique. It was concluded that the loading pressure and the embossing temperature were the main parameters affecting the structure's quality. Bovine endothelial cells (BCE) were seeded on the scaffolds using dynamic conditions demonstrating encouraging results. In another study, Mills et al. [35] produced
2.1.3. Microcontact printing Microcontact printing (μCP) technique (Fig. 1D) is one of the most used methods to pattern functional organic surfaces. For this purpose, an elastomeric stamp is used with relief on its surface to generate self-assembled monolayers (SAMs) on the surface of planar and curved substrates [59,60,88]. Specifically advantageous for tissue engineering applications, this methodology is used to tailor wettability, biocompatibility or reactivity of the surface by transferring organic coatings [67]. Several studies reported in the literature describe the use of μCP as a technique to create biochemical cues for cell alignment [89,90]. Mrksich et al. [91] used μCP to pattern the formation of SAMs at the micrometer scale in order to promote the attachment of mammalian cells. SAMs were coated with fibronectin and the preferential adhesion of the cells was observed. In a different study, Das et al. [92] also analyzes the interaction of the mammalian cells using μCP
2.2. Hot embossing
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structures on the surface of poly(lactic acid) — PLA by nanoembossing and the product features achieved dimensions smaller than cells. Furthermore, Charest et al. [97] used hot embossing method to prepare micro textured polymer substrates with grooves of approximately 5 μm deep, 4 μm wide, and a periodicity of 34 μm. The main objective was to study the response of osteoblast cells grown on these surfaces. Petronis et al. [102] also used hot embossing techniques to improve the fabrication method of micro structured ceramic scaffolds. It was created a well-defined surface morphology given the advantages such as simplicity and expandability for large areas compared to injection molding. In a recent study, Lima et al. [103] reported the use of hot embossing method to produce two-dimensional (2D) microfabricated membranes from polycaprolactone (PCL) and a biodegradable blend consisting of starch–polycaprolactone (SPCL (30% starch)) with accurately imprinted micro pillars and micro holes and further assembled for multi-layer scaffolds production. The stability of rigid molds as well as the solvent-free characteristic of embossing processes are advantageous since they allow maintaining the fabricated features for longer time with a single mold and avoid contamination of the polymer matrix due to the solvent usage. 3. Soft lithography vs hot embossing As described above, several micro/nanofabrication methods have been used to obtain micro/nanofabricated membranes for tissue engineering applications [104,105]. Among them, it is possible to evidence the major limitation of soft lithography techniques that concerns the deformation of the soft mold due to the high embossing pressure and the use of solvents that frequently causes distortion of the structures [103, 105,106]. Nevertheless, soft lithography is an advantageous process to produce low cost molds due to the easy processing and the low cost of the mold materials. On the other hand, when using hot embossing, the collapse of the membrane features can be avoided due to fabrication parameters inherent to the hot embossing process (solvent-free, pressure, temperature, time and vacuum conditions), and due to the rigid character of the master mold that preserved the micro architecture and can be used for a longer time (N1000). Although hot embossing process is more expensive than soft lithography, it overcomes the use of solvents in the process (not appropriate for tissue engineering applications since it may cause toxicity for the cells seeded on the scaffold) being only limited by the viscosity of the material at higher temperatures.
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scaffolds they utilized the membranes immediately after casting when the solvent residue still present to enable the bonding of layers. After the entire sample was created it has utilized phase separation to remove the solvent. On a simple method, Boike et al. [108] used the approach of bonding the polymers below Tg temperature although deformation of structures was observed. Moreover, the report study by Bao et al. [109] shows that 3D structures can be imprinted over the existing polymer patterns. The versatility of controlling the material selection and process condition and high resolution are the main advantages of this method. However, the process creates a residue film that is removed by Oxygen Reactive Ion Etching (O2 RIE). In addition, Bettinger et al. [110] create patterned silk fibroin layers and they were bound between rigid plates under mechanical pressure at 70 °C for 18 h to produce a water-insoluble silk fibroin interface. The method described by Bettinger et al. avoids the use of toxic solvents and harsh processing conditions nevertheless this method was only described to be applied to silk fibroin materials. Kehagias et al. [111] utilized a combination of nanoimprint lithography and contact printing lithography. To create scaffolds, certain areas of the layers were exposed to UV light. After, UV unexposed areas were dissolved in a solution and only the UV exposed areas were bounded creating a 3D structure. Recently, Lima et al. proposed a novel, easy, highly reproducible and inexpensive bottom-up approach for assembling scaffolds using microfabricated PCL and SPCL biodegradable membranes as base-units. Stable scaffolds of PCL, SPCL and combination of both, with the micro features of the membranes were obtained. The application of a small amount of PCL solution only on the top of the pillars to bind the membranes enabled to overcome the need for using large amounts of solvents as well as to maintain the integrity of the structure due to the low manipulation degree [103]. As described above, several approaches are being studied to create 3D structures from 2D micro/nano fabricated membranes (typical structure produced by replication techniques). Still, height scaffold limitations are still far from being eliminated during the assembling due to the collapsing of membranes and low adhesive forces between each layer. Indeed, several authors describe assembling from 3 to 12 layers of micro/nano fabricated membranes leading to scaffold heights from 0.1 to 0.4 cm, depending on the number of layers assembled [103,104, 109]. For 3D structure production, the choice of the best technique must be based on the clinical application and size of defects, robustness and precision combined with the use of low amounts of solvents to avoid the possible toxicity for cell seeding.
4. 3D assembling approaches for tissue engineering applications 5. Conclusions Despite the significant attainments in the creation of micro/ nanofabricated structures, soft lithography and hot embossing technologies produce 2D membranes. Nevertheless, scaffolds for tissue engineering applications are described as three-dimensional (3D) structures. To overcome this limitation, assembling methodologies emerged as a tool to construct 3D scaffolds from 2D membranes. Fig. 2 represents the procedure to produce the final 3D scaffold for tissue engineering applications. Several studies presented novel approaches to achieve 3D scaffolds from 2D membranes. Mata et al. [104] used a method of a dual sided molding system: a SU-8 and a PDMS mold to pattern features on PDMS membranes. Afterwards, the 3D assembling was accessed using a mechanical jig to control the alignment of the membranes. Still this procedure can be very expensive and it has not yet reported applications of biodegradable polymers for real tissue engineering applications. In a different study, Yang et al. [105] used a variety of microembossing processes to transfer the pattern to the poly(DL-lactide-co-glycolide) substrate. For membrane's assembly, CO2 bonding technique was used demonstrating to be a powerful method to assemble 3D scaffolds at low temperatures. Papenburg et al. [107] employed solvents to cast polymer into the mold, similar to the REM process. To create 3D
Regarding tissue engineering field, replication methods are able to create micro/nano features on 2D membranes for improvement of cellular alignment and biocompatibility. Comparing both reported replication techniques, soft lithography is described as an inexpensive technology that allows creating multiple elastomeric molds from a single master mold. Still, hot embossing uses a more stable rigid mold that creates more precise features with high aspect ratio resolution without the use of solvents. For concrete applications in tissue engineering, the application of 3D scaffolds for large tissue defects is unavoidable. For that reason, assembling 2D layers for creation of a 3D scaffold with good adherence between them is crucial. The use of large amounts of solvents and high temperatures during the assembling could take several scaffold deformation. Hence, assembling technique must be chosen depending on the application and the physical properties of the used materials. Replication methods including soft lithography and hot embossing coupled with assembling techniques can be used to construct highly precise scaffolds and that represents an advance in the tissue engineering field.
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References [1] S.J. Shieh, J.P. Vacanti, State-of-the-art tissue engineering: from tissue engineering to organ building, Surgery 137 (1) (2005) 1–7. [2] G. Chen, T. Ushida, T. Tateishi, Development of biodegradable porous scaffolds for tissue engineering, Mater. Sci. Eng. C 17 (1–2) (2001) 63–69. [3] L. De Bartolo, et al., Bio-hybrid organs and tissues for patient therapy: a future vision for 2030, Chem. Eng. Process. Process Intensif. 51 (2012) 79–87. [4] G.K. Sandor, R. Suuronen, Combining adipose-derived stem cells, resorbable scaffolds and growth factors: an overview of tissue engineering, J. Can. Dent. Assoc. 74 (2) (2008) 167–170. [5] I. Armentano, et al., Biodegradable polymer matrix nanocomposites for tissue engineering: a review, Polym. Degrad. Stab. 95 (11) (2010) 2126–2146. [6] R. Langer, J.P. Vacanti, Tissue engineering, Science 260 (5110) (1993) 920–926. [7] R.M. Allaf, I.V. Rivero, Fabrication and characterization of interconnected porous biodegradable poly(epsilon-caprolactone) load bearing scaffolds, J. Mater. Sci. Mater. Med. 22 (8) (2011) 1843–1853. [8] G.L. Converse, et al., Hydroxyapatite whisker-reinforced polyetherketoneketone bone ingrowth scaffolds, Acta Biomater. 6 (3) (2010) 856–863. [9] Y.S. Nam, J.J. Yoon, T.G. Park, A novel fabrication method of macroporous biodegradable polymer scaffolds using gas foaming salt as a porogen additive, J. Biomed. Mater. Res. 53 (1) (2000) 1–7. [10] J.J. Yoon, T.G. Park, Degradation behaviors of biodegradable macroporous scaffolds prepared by gas foaming of effervescent salts, J. Biomed. Mater. Res. 55 (3) (2001) 401–408. [11] A. Salerno, et al., Design of porous polymeric scaffolds by gas foaming of heterogeneous blends, J. Mater. Sci. Mater. Med. 20 (10) (2009) 2043–2051. [12] M.E. Gomes, et al., Starch-poly(epsilon-caprolactone) and starch-poly(lactic acid) fibre-mesh scaffolds for bone tissue engineering applications: structure, mechanical properties and degradation behaviour, J. Tissue Eng. Regen. Med. 2 (5) (2008) 243–252. [13] M.E. Gomes, et al., Effect of flow perfusion on the osteogenic differentiation of bone marrow stromal cells cultured on starch-based three-dimensional scaffolds, J. Biomed. Mater. Res. A 67 (1) (2003) 87–95. [14] A.G. Mikos, et al., Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation, J. Biomed. Mater. Res. 27 (2) (1993) 183–189. [15] Q. Lv, Q. Feng, Preparation of 3-D regenerated fibroin scaffolds with freeze drying method and freeze drying/foaming technique, J. Mater. Sci. Mater. Med. 17 (12) (2006) 1349–1356. [16] M.G. Haugh, C.M. Murphy, F.J. O'Brien, Novel freeze-drying methods to produce a range of collagen-glycosaminoglycan scaffolds with tailored mean pore sizes, Tissue Eng. Part C Methods 16 (5) (2010) 887–894. [17] D. Sin, et al., Polyurethane (PU) scaffolds prepared by solvent casting/particulate leaching (SCPL) combined with centrifugation, Mater. Sci. Eng. C 30 (1) (2010) 78–85. [18] E.T. Baran, et al., Microchannel-patterned and heparin micro-contact-printed biodegradable composite membranes for tissue-engineering applications, J. Tissue Eng. Regen. Med. 5 (6) (2011) e108–e114. [19] M.E. Gomes, et al., A new approach based on injection moulding to produce biodegradable starch-based polymeric scaffolds: morphology, mechanical and degradation behaviour, Biomaterials 22 (9) (2001) 883–889. [20] Z. Chen, et al., Fabrication of osteo-structure analogous scaffolds via fused deposition modeling, Scr. Mater. 52 (2) (2005) 157–161. [21] D.W. Hutmacher, et al., Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling, J. Biomed. Mater. Res. 55 (2) (2001) 203–216. [22] F.P. Melchels, J. Feijen, D.W. Grijpma, A poly(D,L-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography, Biomaterials 30 (23–24) (2009) 3801–3809. [23] C.X.F. Lam, et al., Scaffold development using 3D printing with a starch-based polymer, Mater. Sci. Eng. C 20 (1–2) (2002) 49–56. [24] B. Leukers, et al., Hydroxyapatite scaffolds for bone tissue engineering made by 3D printing, J. Mater. Sci. Mater. Med. 16 (12) (2005) 1121–1124. [25] S.P. Garland, T.M.M. Jr, T. Pan, Print-to-pattern dry film photoresist lithography, J. Micromech. Microeng. 24 (5) (2014) 057002. [26] E.K. Yim, et al., Nanopattern-induced changes in morphology and motility of smooth muscle cells, Biomaterials 26 (26) (2005) 5405–5413. [27] E. Tejeda-Montes, et al., Engineering membrane scaffolds with both physical and biomolecular signaling, Acta Biomater. 8 (3) (2012) 998–1009. [28] A. Bakry, et al., A new approach for the preparation of hydrophilic poly(L-lactide) porous scaffold for tissue engineering by using lamellar single crystals, Polym. Int. 61 (7) (2012) 1177–1185. [29] J. Mitra, et al., Scaffolds for bone tissue engineering: role of surface patterning on osteoblast response, RSC Adv. 3 (28) (2013) 11073–11094. [30] A.A.K. Moe, et al., Microarray with micro- and nano-topographies enables identification of the optimal topography for directing the differentiation of primary murine neural progenitor cells, Small 8 (19) (2012) 3050–3061. [31] M. Ahmed, et al., Nanostructured materials for cardiovascular tissue engineering, J. Nanosci. Nanotechnol. 12 (6) (2012) 4775–4785. [32] W. Chia-Wen, A. Tsuyoshi, K. Makoto, Electron-beam lithography assisted patterning of surfactant-templated mesoporous thin films, Nanotechnology 15 (12) (2004) 1886. [33] G.M. Whitesides, et al., Soft lithography in biology and biochemistry, Annu. Rev. Biomed. Eng. 3 (2001) 335–373. [34] J. Charest, W. King, Engineering biomaterial interfaces through micro and nanopatterning, in: P. Hesketh (Ed.), BioNanoFluidic MEMS, Springer, US, 2008, pp. 251–277.
[35] C.A. Mills, et al., Transparent micro- and nanopatterned poly(lactic acid) for biomedical applications, J. Biomed. Mater. Res. A 76 (4) (2006) 781–787. [36] M. Schvartzman, S.J. Wind, Robust pattern transfer of nanoimprinted features for sub-5-nm fabrication, Nano Lett. 9 (10) (2009) 3629–3634. [37] Geissler, M., 4.03 — Sub-micrometer patterning using soft lithography, in Comprehensive Nanoscience and Technology, L.A. Editors-in-Chief: David, D.S. Gregory, and P.W. Gary, Editors. 2011, Academic Press: Amsterdam. p. 63–81. [38] C. Acikgoz, et al., Polymers in conventional and alternative lithography for the fabrication of nanostructures, Eur. Polym. J. 47 (11) (2011) 2033–2052. [39] K.-L. Lai, et al., Patterning of polystyrene thin films by solvent-assisted imprint lithography and controlled dewetting, Microelectron. Eng. 94 (2012) 33–37. [40] P. Clark, et al., Cell guidance by ultrafine topography in vitro, J. Cell Sci. 99 (Pt 1) (1991) 73–77. [41] J. Wu, et al., The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells, Biomaterials 33 (5) (2012) 1343–1352. [42] C.J. Bettinger, et al., Microfabrication of poly (glycerol-sebacate) for contact guidance applications, Biomaterials 27 (12) (2006) 2558–2565. [43] Y. Wan, et al., Adhesion and proliferation of OCT-1 osteoblast-like cells on microand nano-scale topography structured poly(L-lactide), Biomaterials 26 (21) (2005) 4453–4459. [44] K.S. Brammer, et al., Hydrophobic nanopillars initiate mesenchymal stem cell aggregation and osteo-differentiation, Acta Biomater. 7 (2) (2011) 683–690. [45] G.J. Bakeine, et al., Design, fabrication and evaluation of nanoscale surface topography as a tool in directing differentiation and organisation of embryonic stem-cell-derived neural precursors, Microelectron. Eng. 86 (4–6) (2009) 1435–1438. [46] S. Fuchs, et al., Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds, Biomaterials 30 (4) (2009) 526–534. [47] K. Jörg, B. Stefanie, S. Martin, Low temperature adhesion bonding for BioMEMS, J. Micromech. Microeng. 16 (4) (2006) 802. [48] G.J. Wang, et al., Bio-MEMS fabricated artificial capillaries for tissue engineering, Microsyst. Technol. 12 (1–2) (2005) 120–127. [49] C.Y. Tay, et al., Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications, Small 7 (10) (2011) 1361–1378. [50] W. Ryu, et al., The construction of three-dimensional micro-fluidic scaffolds of biodegradable polymers by solvent vapor based bonding of micro-molded layers, Biomaterials 28 (6) (2007) 1174–1184. [51] Y. Xia, et al., Complex optical surfaces formed by replica molding against elastomeric masters, Science 273 (5273) (1996) 347–349. [52] E. Delamarche, et al., Patterned delivery of immunoglobulins to surfaces using microfluidic networks, Science 276 (5313) (1997) 779–781. [53] M. Emmelius, G. Pawlowski, H.W. Vollmann, Materials for optical data storage, Angew. Chem. Int. Ed. Engl. 28 (11) (1989) 1445–1471. [54] J. Kim, et al., Biologically inspired micro- and nanoengineering systems for functional and complex tissues, Tissue Eng. A (2014). [55] S.Y. Chou, et al., Sub-10 nm Imprint Lithography and Applications, AVS, Dana Point, California (USA), 1997. [56] S. Zhang, et al., Biological surface engineering: a simple system for cell pattern formation, Biomaterials 20 (13) (1999) 1213–1220. [57] M. Beck, et al., Improving stamps for 10 nm level wafer scale nanoimprint lithography, Microelectron. Eng. 61–62 (2002) 441–448. [58] H. Cao, et al., Fabrication of 10 nm enclosed nanofluidic channels, Appl. Phys. Lett. 81 (1) (2002) 174–176. [59] G. Cao, Nanostructures fabricated by physical techniques, Nanostructures and Nanomaterials, 2004, pp. 277–328. [60] S.S. Saliterman, Fundamentals of BioMEMS and Medical Microdevices, 2006, pp. 75–98. [61] S. Alom Ruiz, C.S. Chen, Microcontact printing: a tool to pattern, Soft Matter 3 (2) (2007) 168–177. [62] N.S. Devaraju, M.A. Unger, Multilayer soft lithography of perfluoropolyether based elastomer for microfluidic device fabrication, Lab Chip 11 (11) (2011) 1962–1967. [63] C.M. Bruinink, et al., Stamps for submicrometer soft lithography fabricated by capillary force lithography, Adv. Mater. 16 (13) (2004) 1086–1090. [64] H. Liu, et al., Thermal processing of starch-based polymers, Prog. Polym. Sci. 34 (12) (2009) 1348–1368. [65] D.K. Cai, et al., Optical absorption in transparent PDMS materials applied for multimode waveguides fabrication, Opt. Mater. 30 (7) (2008) 1157–1161. [66] W.M. Choi, O.O. Park, A soft-imprint technique for direct fabrication of submicron scale patterns using a surface-modified PDMS mold, Microelectron. Eng. 70 (1) (2003) 131–136. [67] B.D. Gates, et al., Unconventional nanofabrication, Annu. Rev. Mater. Res. 34 (1) (2004) 339–372. [68] O.C. Jeong, S. Konishi, Controlling the size of replicable polydimethylsiloxane (PDMS) molds/stamps using a stepwise thermal shrinkage process, Microelectron. Eng. 88 (8) (2011) 2286–2289. [69] N. Koo, et al., Improved mold fabrication for the definition of high quality nanopatterns by Soft UV-Nanoimprint lithography using diluted PDMS material, Microelectron. Eng. 84 (5–8) (2007) 904–908. [70] Q. He, et al., Angular evaluation to quantify planar distortions of PDMS stamps in soft lithography, Mater. Chem. Phys. 83 (1) (2004) 60–65. [71] Y. Xia, G.M. Whitesides, Soft lithography, Annu. Rev. Mater. Sci. 28 (1) (1998) 153–184. [72] T.-K. Shih, et al., Fabrication of various curved relief structures through concave surface forming and soft replica molding, Microelectron. Eng. 83 (3) (2006) 471–475. [73] D. Losic, et al., Rapid fabrication of micro- and nanoscale patterns by replica molding from diatom biosilica, Adv. Funct. Mater. 17 (14) (2007) 2439–2446.
M.J. Lima et al. / Materials Science and Engineering C 42 (2014) 615–621 [74] J.K.S. Poon, et al., Soft lithography replica molding of critically coupled polymer microring resonators, IEEE Photon. Technol. Lett. 16 (11) (2004) 2496–2498. [75] J.C. Charles, et al., Surface-enhanced Raman nanodomes, Nanotechnology 21 (41) (2010) 415301. [76] I.D. Block, L.L. Chan, B.T. Cunningham, Large-area submicron replica molding of porous low-k dielectric films and application to photonic crystal biosensor fabrication, Microelectron. Eng. 84 (4) (2007) 603–608. [77] J.T. Borenstein, et al., Microfabrication technology for vascularized tissue engineering, Biomed. Microdevices 4 (3) (2002) 167–175. [78] J. Chen, et al., Hybrid hierarchical patterns of gold nanoparticles and poly(ethylene glycol) microstructures, J. Mater. Chem. C 1 (46) (2013) 7709–7715. [79] M. Dong, F.A.L. Dullien, I. Chatzis, Imbibition of oil in film form over water present in edges of capillaries with an angular cross section, J. Colloid Interface Sci. 172 (1) (1995) 21–36. [80] L. Beria, et al., ‘Clickable’ hydrogels for all: facile fabrication and functionalization, Biomater. Sci. 2 (1) (2014) 67–75. [81] M.J. Park, W.M. Choi, O.O. Park, Patterning polymer light-emitting diodes by micromolding in capillary, Curr. Appl. Phys. 6 (4) (2006) 627–631. [82] K.-Y. Suh, M.C. Park, P. Kim, Capillary force lithography: a versatile tool for structured biomaterials interface towards cell and tissue engineering, Adv. Funct. Mater. 19 (17) (2009) 2699–2712. [83] E. Bystrenova, et al., Multiple length-scale patterning of DNA by stamp-assisted deposition, Angew. Chem. 118 (29) (2006) 4897–4900. [84] Y. Xia, E. Kim, G.M. Whitesides, Micromolding of polymers in capillaries: applications in microfabrication, Chem. Mater. 8 (7) (1996) 1558–1567. [85] X. Yu, et al., Fabrication of structures with tunable morphologies and sizes by soft molding, Appl. Surf. Sci. 252 (5) (2005) 1947–1953. [86] G. Vozzi, et al., Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition, Biomaterials 24 (14) (2003) 2533–2540. [87] A. Folch, et al., Stacks of microfabricated structures as scaffolds for cell culture and tissue engineering, Biomed. Microdevices 2 (3) (2000) 207–214. [88] S. Casimirius, et al., Microcontact printing process for the patterned growth of individual CNTs, Microelectron. Eng. 73–74 (2004) 564–569. [89] C.A. Trinkle, L.P. Lee, High-precision microcontact printing of interchangeable stamps using an integrated kinematic coupling, Lab Chip 11 (3) (2011) 455–459. [90] R.N. Orth, et al., Creating biological membranes on the micron scale: forming patterned lipid bilayers using a polymer lift-off technique, Biophys. J. 85 (5) (2003) 3066–3073. [91] M. Mrksich, et al., Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver, Exp. Cell Res. 235 (2) (1997) 305–313. [92] T. Das, et al., Microcontact printing of Concanavalin A and its effect on mammalian cell morphology, J. Colloid Interface Sci. 314 (1) (2007) 71–79. [93] P. Ian, Hot embossing for lab-on-a-chip applications, Bio-MEMS, CRC Press, 2006, pp. 117–140. [94] H. Becker, U. Heim, Hot embossing as a method for the fabrication of polymer high aspect ratio structures, Sensors Actuators A Phys. 83 (1–3) (2000) 130–135. [95] K. Mohamed, M.M. Alkaisi, R.J. Blaikie, Fabrication of Three Dimensional Structures for an UV Curable Nanoimprint Lithography Mold Using Variable Dose Control With Critical-energy Electron Beam Exposure, 2007. (AVS).
621
[96] N. Jagannathan, P. Ian, Polymer embossing tools for rapid prototyping of plastic microfluidic devices, J. Micromech. Microeng. 14 (1) (2004) 96. [97] J.L. Charest, et al., Hot embossing for micropatterned cell substrates, Biomaterials 25 (19) (2004) 4767–4775. [98] M.D. Austin, et al., Fabrication of 5 nm linewidth and 14 nm pitch features by nanoimprint lithography, Appl. Phys. Lett. 84 (26) (2004) 5299–5301. [99] S. Lan, et al., A parameter study on the micro hot-embossing process of glassy polymer for pattern replication, Microelectron. Eng. 86 (12) (2009) 2369–2374. [100] L.J. Guo, Recent progress in nanoimprint technology and its applications, J. Phys. D. Appl. Phys. 37 (11) (2004) R123. [101] W. Hu, et al., Effects of nanoimprinted patterns in tissue-culture polystyrene on cell behavior, J. Vac. Sci. Technol. A 23 (6) (2005) 2984–2989. [102] S. Petronis, et al., Microstructuring ceramic scaffolds for hepatocyte cell culture, J. Mater. Sci. Mater. Med. 12 (6) (2001) 523–528. [103] M.J. Lima, et al., Bottom-up approach to construct microfabricated multi-layer scaffolds for bone tissue engineering, Biomed. Microdevices (2013) 1–10. [104] A. Mata, et al., A three-dimensional scaffold with precise micro-architecture and surface micro-textures, Biomaterials 30 (27) (2009) 4610–4617. [105] Y. Yang, et al., Fabrication of well-defined PLGA scaffolds using novel microembossing and carbon dioxide bonding, Biomaterials 26 (15) (2005) 2585–2594. [106] J.A. Rogers, K.E. Paul, G.M. Whitesides, Quantifying distortions in soft lithography, J. Vac. Sci. Technol. B Microelectron. Nanometer Struct. 16 (1) (1998) 88–97. [107] B.J. Papenburg, et al., One-step fabrication of porous micropatterned scaffolds to control cell behavior, Biomaterials 28 (11) (2007) 1998–2009. [108] Y.M. Boiko, R.E. Prud'homme, Bonding at symmetric polymer/polymer interfaces below the glass transition temperature, Macromolecules 30 (12) (1997) 3708–3710. [109] L.R. Bao, et al., Nanoimprinting Over Topography and Multilayer Threedimensional Printing, AVS, Anaheim, California (USA), 2002. [110] C.J. Bettinger, et al., Silk fibroin microfluidic devices, Adv. Mater. 19 (5) (2007) 2847–2850. [111] N. Kehagias, et al., Reverse-contact UV nanoimprint lithography for multilayered structure fabrication, Nanotechnology 18 (17) (2007) 175303. [112] D. Wang, et al., Patterning of Gd2(WO4)3:Ln3+ (Ln = Eu, Tb) luminescent films by microcontact printing route, J. Colloid Interface Sci. 365 (1) (2012) 320–325. [113] A.M.C. Egea, C. Vieu, Microcontact printing of biomolecular gratings from SU-8 masters duplicated by Thermal Soft UV NIL, Microelectron. Eng. 88 (8) (2011) 1935–1938. [114] S.M. Giannitelli, et al., Surface decoration of electrospun scaffolds by microcontact printing, Asia Pac. J. Chem. Eng. (2014) (p. n/a-n/a). [115] B. Chelli, et al., Neural cell alignment by patterning gradients of the extracellular matrix protein laminin, Interface Focus 4 (1) (2014). [116] S.Y. Chou, P.R. Krauss, Imprint lithography with sub-10 nm feature size and high throughput, Microelectron. Eng. 35 (1) (1997) 237–240. [117] P. Linfa, et al., Micro hot embossing of thermoplastic polymers: a review, J. Micromech. Microeng. 24 (1) (2014) 013001. [118] A. Ifty, Hot topics in biomaterials, Future Science Book Series, Future Science Ltd, 2014. (116). [119] M. Elsayed, O.M. Merkel, Nanoimprinting of topographical and 3D cell culture scaffolds, Nanomedicine (London) 9 (2) (2014) 349–366.