Textile Technologies and Tissue Engineering: A Path Toward Organ Weaving
Mohsen Akbari , Ali Tamayol , Sara Bagherifard , Ludovic Serex , Pooria Mostafalu , Negar Faramarzi , Mohammad Hossein Mohammadi , and Ali Khademhosseini *
DOI: 10.1002/adhm.201500517
commonly utilized to provide mechanical support and 3D environments for cellular growth and function. Traditional methods for creating scaffolds including freeze-drying, [ 2 ] particle leaching, [ 3 ] and solvent casting [ 4 ] generate porous constructs with interconnected pores that are suitable for delivery of nutrients to the cells. However, the ability of these approaches for precise control over the spatial distribution of pore size and interconnectivity, mechan-ical properties, and structural properties is limited. Recently, advanced biofabrica-tion methods such as bioprinting, [ 5–8 ] ste-reolithography, [ 9–11 ] self-assembly of microgels, [ 12,13 ] and biotextiles [ 14–16 ] have
emerged to produce complex 3D-engineered tissues from living and nonliving elements with exquisite control over the resulting scaffold microarchitecture and cellular distribution.
Commercial biotextiles (e.g., TIGR Matrix, ULTRAPRO, and INTERGARD) are currently used as medical implants for treating pelvic organ prolapse, hernia, and vascular diseases. Recently, textile technologies have been utilized for biofabrica-tion of fi brous scaffolds for various tissue-engineering appli-cations. [ 14,16–18 ] Such technologies include weaving, knitting,
Textile technologies have recently attracted great attention as potential biofabrication tools for engineering tissue constructs. Using current textile technologies, fi brous structures can be designed and engineered to attain the required properties that are demanded by different tissue engineering applications. Several key parameters such as physiochemical characteristics of fi bers, microarchitecture, and mechanical properties of the fabrics play important roles in the effective use of textile technologies in tissue engi-neering. This review summarizes the current advances in the manufacturing of biofunctional fi bers. Different textile methods such as knitting, weaving, and braiding are discussed and their current applications in tissue engi-neering are highlighted.
Prof. M. Akbari, Dr. A. Tamayol, Dr. S. Bagherifard, Mr. L. Serex, Dr. P. Mostafalu, Dr. N. Faramarzi, Prof. A. Khademhosseini Department of Medicine Brigham and Women’s Hospital Biomaterials Innovation Research Center Harvard Medical School Cambridge , MA 02139 , USA E-mail: [email protected] Prof. M. Akbari, Dr. A. Tamayol, Dr. S. Bagherifard, Mr. L. Serex, Dr. P. Mostafalu, Dr. N. Faramarzi, Mr. M. H. Mohammadi, Prof. A. Khademhosseini Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute of Technology Cambridge , MA 02139 , USA Prof. M. Akbari, Dr. A. Tamayol, Dr. P. Mostafalu, Prof. A. Khademhosseini Wyss Institute for Biologically Inspired Engineering Harvard University Boston , MA 02115 , USA Prof. M. Akbari Department of Mechanical Engineering University of Victoria Victoria , BC V8P 5C2 , Canada
Dr. S. Bagherifard Department of Mechanical Engineering Politecnico di Milano Milan 20156 , Italy Dr. S. Bagherifard David H. Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology Cambridge , MA 02139 , USA Prof. A. Khademhosseini Department of Physics King Abdulaziz University Jeddah 21569 , Saudi Arabia Prof. A. Khademhosseini Department of Bioindustrial Technologies College of Animal Bioscience and Technology Konkuk University Hwayang-dong, Gwangjin-gu Seoul 143-701 , Republic of Korea
1. Introduction
Tissue engineering is a multidisciplinary enterprise that com-bines the principles of cellular biology, biomaterials, and engineering to address the current unmet demands for organ transplantation. [ 1 ] Fabrication of constructs with controlled mechanical properties, microstructure, and cellular distribu-tion plays a crucial role in the engineering of functional tis-sues. Scaffolds made from synthetic or natural biomaterials are
IEW braiding, embroidering, and electrospinning. The versatility of
textile structures enables tailoring their architecture by control-ling the fi ber size and orientation, pore size and geometry, pore interconnectivity, total porosity, and surface topography. All these properties are important for controlling the physical prop-erties and cellular behavior of the engineered constructs. In addition, by utilization of cell-laden fi bers during the assembly process, the cellular distribution can be fi nely controlled. In this review, we will primarily focus on the current advances in the textile-based fabrication methods for tissue engineering. Recent technological advances in the manufacturing of biofi bers as building blocks of biotextiles will be highlighted. We will then explore emerging applications of biotextiles for tissue engi-neering and regenerative medicine.
2. Biofunctional Fibers
Fibers are building blocks of biotextiles and their properties play an important role in controlling physiochemical properties of the fi nal construct. In this section, we grouped biofunctional fi bers into four major categories of synthetic, hydrogel, natural, and composite fi bers. Table 1 summarizes these categories and provides a comparison between them.
2.1. Synthetic Fibers
Synthetic polymers are widely used for the fabrication of scaffolds in tissue engineering and regenerative medicine. Examples include vascular prostheses that were made from poly(tetrafl uoroethylene) (PTFE) seeded with bone marrow stem cells, [ 19 ] cartilage scaffolds made from poly(glycolic acid) (PGA) yarns and seeded with porcine articular chon-drocytes, [ 14 ] and tissue engineered bladders fabricated from poly( DL -lactic-co-glycolic acid) (PLGA) matrix. [ 20 ] Synthetic materials have also been used in the form of micro- and nano-fi bers as they mimic the intricate fi brillar microstructure of the natural extracellular matrix (ECM). [ 21 ] Several approaches have been developed for creating micro- and nanofi brillars from synthetic biomaterials. Electrospinning and blow spinning are low-cost and robust methods for creating nanofi bers with diameters as small as 10 nm. [ 22,23 ] Electrospun nonwoven mats have been used to create biodegradable nanofi brous structures for cardiovascular tissue engineering, [ 24 ] fl exible electronics, [ 18 ] and skin tissue engineering. [ 25 ] Blow spinning is an alterna-tive method for making nonwoven fi brous structures with nanometer diameter fi bers. [ 26 ] This method offers the advan-tage of higher production rate compared to electrospinning. [ 26 ] Both electrospinning and blow spinning approaches can be used to generate scaffolds with pore dimensions that are much smaller than the average size of the cells; thus, limiting cel-lular infi ltration. [ 27 ]
Inspired by the process of protein self-assembly, nanofi bers are now being formed from oligomeric peptide, nucleotide, and nonbiological amphiphilic building blocks. [ 28 ] Although this is a promising approach, the self-assembly process occurs under conditions that are intolerable to cells, impeding the incorpora-tion of cells during the fabrication process.
Mohsen Akbari is an assis-tant professor of Mechanical Engineering, a member of the Center for Biomedical Research (CBR), and Center for Advanced Materials and Related Technology (CAMTEC) at University of Victoria, Canada. He is also affi liated with Brigham and Women’s Hospital at Harvard Medical School. Dr. Akbari’s research interests include the develop-
ment of fi ber-based technologies for tissue engineering, thread-based biosensors, smart wound dressings, and advanced drug-delivery systems.
Ali Tamayol is an instructor at the Harvard-MIT Division of Health Sciences at Massachusetts Institute of Technology. He is also affi liated to the Brigham and Women’s Hospital at Harvard Medical School. Prior to starting this appointment, he was a post-doctoral fellow at McGill University and a researcher at Simon Fraser University. His
research involves design, fabrication, and characterization of microsystems and fi brous biomaterials for emerging applications such as tissue engineering and drug testing platforms. He has developed advanced composite reinforced cell-laden fi bers with controlled physical and biological properties as well as substrates for biodegradable electronics and smart wound dressings.
Ali Khademhosseini is a pro-fessor at Harvard University and holds appointments at the Harvard-MIT Division of Health Sciences Technology, Brigham and Women’s Hospital. Additionally, he is on the faculty of the Wyss Institute for Biologically Inspired Engineering at Harvard University and the World Premier International-Advanced
Institute for Materials Research (WPI-AIMR), Tohoku University. He is an internationally recognized bioengineer regarded for his contributions and research in the areas of biomaterial synthesis, microscale technologies, and tissue engineering. His research involves the development of micro- and nanoscale technologies to control cellular behavior, fabrication of microscale biomaterials, and engineering systems for tissue engineering, drug discovery, and cell-based biosensing.
To fabricate fi bers with micron-size dimensions, other methods including meltspinning [ 29,30 ] and microfl uidic spin-ning [ 31,32 ] have been utilized. Such methods enable generating grooves on the surface of the fi bers, making them suitable for directing cellular alignment and growth. [ 30 ]
The choice of materials varies from nondegradable poly-mers such as polypropylene (PP) [ 33 ] and PTFE [ 34 ] to degradable polymers such as PGA [ 35 ] and PLGA. [ 31 ] These fi bers can be used in the form of monofi lament or multifi lament twisted or braided yarns for the biofabrication of scaffolds and biotex-tiles. It has been shown that the size and surface topology of monofi lament fi bers can modulate the orientation and organi-zation of cells. [ 30,31 ] Cells have shown to respond to the surface morphologies in nano- and microscales. [ 36–39 ] For instance, cells grown on PLGA fi bers were mostly aligned along the fi ber axis when seeded on smaller diameter fi bers (<30 µm) ( Figure 1 ). [ 31 ] Moreover, the surface topography on the fabricated fi bers can control the cellular orientation and alignment. [ 38 ] It has been shown that the fabrication of monofi lament fi bers with micro-grooves on their surface enhanced cellular orientation along the direction of the grooves. [ 30 ] Multifi lament yarns, with similar surface topography as threads used in textile industry, have been assembled by means of commercial textile instruments for the fabrication of load-bearing tissue scaffolds and used in cartilage [ 40 ] and cardiac muscle tissue engineering. [ 41 ]
Due to their high mechanical properties, synthetic biofi bers are great candidates for creating load-bearing scaffolds for tissue engineering. In addition, the high strength allows their assembly using commercial textile machines. By varying the surface morphology and fi ber diameter, cellular alignment and functions can be modulated. Key challenges toward cells encap-sulation within these synthetic fi bers include the harsh fabrica-tion process of synthetic fi bers and their commonly small pore sizes. Another major challenge for the use of synthetic fi bers in tissue engineering is the lack of binding sites on the surface of these fi bers, which makes them not cell adhesive. Thus, surface treatment strategies such as adsorption of proteins, tuning the surface characteristics such as topography, energy, and hydro-philicity, as well as coating the surface of fi bers with ECM-based materials should be used to promote cellular attachment.
2.2. Hydrogel-Based Fibers
Hydrogels are 3D polymeric networks with high water content, which are formed from hydrophilic polymer chains. These materials have found many applications in tissue engineering as they provide a nurturing environment for cells to proliferate and grow. [ 42–44 ] Considering the importance of hydrogel-based constructs in tissue engineering, multiple fabrication processes have been developed to create hydrogel fi bers with a wide variety of physical and biological characteristics.
Wetspinning is a technique to fabricate hydrogel based fi bers and consists of injecting a prepolymer into a crosslinking solution to create continuous solid fi bers with diameters as small as 50 µm. [ 45 ] The fi ber diameter can be controlled by changing the injection fl ow rate and the needle diameter. In general, a quick crosslinking process is desired if the crosslinker and prepolymer are both hydrophilic, else the prepolymer can diffuse into the crosslinking solution pre-venting the formation of mechanically stable fi bers. Alginate is the most employed hydrogel for the fabrication of wetspun hydrogel fi bers due to its rapid crosslinking process by cal-cium chloride (CaCl 2 ). [ 46,47 ]
Microfl uidic spinning is an alternative approach, which has been recently used for fabrication of biofi bers. [ 15,48–50 ] Its operation mechanism is similar to that of wetspinning, with the difference of co-fl owing the prepolymer and crosslinker co-axially in a microchannel. The hydrogel crosslinks as it fl ows through the channel and the fi ber is completely formed at the exit of the microfl uidic device. In this approach, fi bers with diameters ranging from 10 to a few hundred microm-eters can be fabricated. Generally microfl uidic spinning offers a better control over the fi ber size and shape in comparison to wetspinning. [ 42,49,51 ]
Microfl uidic systems are robust and capable of fabricating multicomponent fi bers. For example, core shell fi bers have been fabricated with this approach with the core containing cell-laden ECM-based proteins and the shell consisting of an alginate layer to protect the cells ( Figure 2 a–c). [ 15 ] In another study, the position of the cells across the fi ber cross-section was precisely controlled and hepatocytes were positioned between
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Table 1. Summary of different fi bers used in tissue engineering applications and their advantages and disadvantages.
Type of biofi bers Advantages Disadvantages
Synthetic • High mechanical strength • Harsh fabrication process for cells
• Tunable mechanical properties • Inability to encapsulate cells
• Controllable surface morphology • Lack of binding sites for cells on these fi bers’ surface
endothelial cells (ECs) to mimic the native cellular distribution in human liver (Figure 2 d,e). [ 48 ]
A typical challenge of working with hydrogel fi bers is that they are not mechanically strong and rapidly dehydrate. How-ever, overall hydrogel fi bers hold great promise for fabrication of tissue constructs. These fi bers can contain cells, bioactive molecules, and drugs, making them useful for many applica-tions such as soft tissue engineering, drug and cell delivery, and as implantable sensors. However, due to their limited mechanical strength, handling and assembly of hydrogel fi bers using current textile technologies is not trivial. Strategies such as the use of reinforcing materials for enhancing the mechan-ical properties of the fi bers have to be pursued to address this challenge.
2.3. Fibers from Natural Materials
Naturally derived biomaterials such as proteins and polysaccha-ride-based materials have found extensive applications in tissue engineering due to their superior biocompatibility as compared to the synthetic materials. Collagen is the most abundant pro-tein in the human body and is the main component of the ECM in connective tissues. Because of its unique properties such as excellent biocompatibility and tunable biodegradability, col-lagen has been used as a popular naturally derived material in tissue engineering. The fi rst known degradable sutures (catgut sutures) were made from purifi ed collagen taken from the small intestine of ruminants. [ 52 ] Recently, collagen threads were
manufactured by wetspinning and meltspinning methods. [ 53–56 ] The fabricated fi bers were used in neural and bone tissue engineering.
Chitosan is another attractive material that has a wide range of applications in tissue engineering due to its unique biolog-ical properties that include biocompatibility, biodegradability to harmless products, physiological inertness, and excellent protein affi nity. [ 57,58 ] Chitosan also has antibacterial, hemo-static, fungistatic, antitumoral, and anticholesteremic proper-ties, which make it an excellent candidate for drug delivery and wound healing applications. [ 59 ] Wetspinning has been the main approach for fabricating chitosan fi bers. [ 60–62 ] However other methods including electrospinning [ 63,64 ] and interfacial compl-exation [ 65 ] have also been used for creating scaffolds made from chitosan.
Silk is a protein-based polymer that is spun into fi bers by silkworms, spiders, scorpions, mites, and fl ies. [ 66 ] Due to their high tensile strength, sutures made from silk have been used for a long time in ocular, neural, and cardiovascular surgeries. For tissue engineering applications, silk fi bers were braided and used as an autologous tissue engineered anterior cruciate ligament (ACL). [ 67 ] Using microfl uidic spinning technique, silk fi bers have been fabricated with similar mechanical properties of the naturally drawn silk fi bers. [ 68 ] Naturally derived fi bers are attractive materials for tissue engineering applications because of their excellent biocompatibility and inherent properties of biological recognition. [ 21 ] However, complexities associated with purifi cation, immunogenicity, and potential pathogen transmis-sion still remain major challenges for use of these materials
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Figure 1. Controlling the orientation of cells on microfi bers by changing the fi ber diameter. a–f) L929 fi broblast morphology on a PLGA fi ber with diameters ranging from 10 to 242 µm. g–i) Immunostained cells oriented along 30 µm diameter fi ber direction. Reproduced with permission. [ 31 ] Copyright 2009, Springer.
in tissue engineering. Some of these challenges could be over-come by using recombinant protein expression technologies. [ 69 ] Moreover, combining naturally derived polymers together with synthetic materials can be another approach for addressing some of these limitations.
2.4. Composite and Hybrid Reinforced Fibers
Composite and hybrid fi bers generally refer to a class of fi bers that are fabricated from two or more individual constituent materials. In composite assembly, each material remains dis-tinct and contributes to a specifi c function. In hybrid systems, however, the constituents can be mixed throughout the con-struct. [ 46,70,71 ] An example is hybrid fi bers that were made from ultrahigh molecular weight polyethylene (UHMWPE) and poly-vinyl alcohol (PVA). [ 70 ] The prominent elastic properties and fatigue strength of UHMWPE enhanced the limited strength of the PVA hydrogel in tension, while the hydrogel itself contrib-uted to the signifi cant biocompatibility and resistance to wear which is in turn essential to withstand the hoop stresses applied during frequent loading cycles. In a notable study, gold nano-wires were added to the matrix of alginate scaffolds to enhance electrical conductivity ( Figure 3 a–d). [ 71 ] It has been shown that such composite material promotes the cardiomyocytes func-tion. As mentioned before, alginate is a strong hydrogel with
considerable water uptake capacity that has been widely used for fabrication of hydrogel fi bers using wetspinning or micro-fl uidic spinning. [ 47,48,51 ] However, this material does not provide a nurturing environment for the cells to spread and function. To overcome this issue, more cell friendly materials such as chitosan, [ 72 ] fi brin [ 73 ] and gelatin-based materials [ 16 ] have been blended with alginate to improve the cellular activity.
To overcome the challenge of low mechanical stability of cell friendly hydrogels, reinforcing materials such as carbon nano-tubes and graphene oxide have also been used. [ 74,75 ] An alterna-tive approach is to create composite fi bers with a load-bearing component. In one study, composite fi bers were made from a load-bearing core material, which was coated with a cell-laden hydrogel layer. Such fi bers possessed the mechanical strength of the synthetic material while still providing the favorable envi-ronment for the cells to grow. [ 16 ] The method was cytocompat-ible and was utilized to coat single and multilayers of particle- and cell-encapsulated hydrogels on a mechanically strong core fi ber (Figure 3 e–i). The fabricated fi bers were strong enough to be assembled using textile techniques and the cells remained functional during the fabrication and assembly process.
Although the higher mechanical strength of composite fi bers compared to pure hydrogel fi bers allows assembling them using textile methods, the presence of two distinct phases may result in delamination at the interface of its com-ponents. In addition, different degradation rates between the
Figure 2. Manufacturing of cell-laden hydrogel microfi bers using double co-axial fl ow microfl uidics. a) Cell-laden ECM proteins are entrapped in a calcium–alginate shell to form various types of functional fi bers. b) Cellular growth in ECM-based proteins. c) Long cell fi bers after culture and removal of the alginate layer. d) Co-culture of hepatocytes and fi broblasts on a single multilayer hydrogel microfi ber. e) Comparison of cellular viability in co-culture and single culture. Reproduced with permission. [ 15 ] Copyright 2013, Nature Publishing Group. Reproduced with permission. [ 48 ] Copyright 2011, Nature Publishing Group.
core and sheath layers can also affect the physical properties of the construct and can interfere with cellular migration and distribution.
3. Textile Technologies in Tissue Engineering
Textile technologies have re-emerged as promising approaches for creating complex constructs from monofi lament fi bers and multifi lament threads for various tissue engineering applica-tions. In this section, a summary of three textile methods that enable controlling the microstructure, mechanical properties, and cellular distribution of the tissue construct is provided. Table 2 summarizes these methods and highlights the advan-tages and drawbacks of each method. It is worth noting that nonwoven constructs that are widely used in many areas of tissue engineering are out of the scope of this review. Compre-hensive reviews on the application of nonwoven constructs in tissue engineering are provided by Hasan et al. [ 76 ] and Pham et al. [ 77 ]
3.1. Knitting
Knitting is a well-established textile method for creating com-plex 2D and 3D structures from yarns that are interlaced in a highly ordered arrangement of connected loops. In the knit-ting process, yarns are drawn through a previous loop to form interconnected loops. Depending on the direction of the loops, the knitting process is classifi ed into two major categories of weft and warp knitting. [ 78 ] In weft knitting, stitches from the same yarn are arranged horizontally ( Figure 4 a), while in warp knitting, stitches from the same yarn are arranged vertically (Figure 4 b). Knitted constructs can be characterized by their course and wale, which are the number of rows passing across the width and length of the fabric, respectively. The number of wale per unit length of the fabric is a function of the density of needles (“gauge”), yarn size and type, and the applied yarn tension.
Depending on the knitting process, types of stitches, and the yarn material, fabricated constructs possess different mechanical and physical properties. Fabrics made from tuck stitches have larger pore size and are wider, thicker, and slightly less extendable
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Figure 3. Composite materials showing superior mechanical and electrical characteristics. Incorporation of a) gold nanowires within b) alginate matrix improved the electrical conductivity of the composite material and promoted cardiomyocyte function. Expression of c) connexin 43 and d) actinin for alginate (Alg) and composite alginate–nanowire (NW) on days 3 and 8. Reproduced with permission. [ 16 ] Copyright 2014, Wiley-VCH. e) Fabrication of composite living fi bers made from a mechanically strong core material and a hydrogel layer. Encapsulation of cells on a f) nonabsorbable monofi lament suture and g) catgut suture. h,i) Multilayers of cells and biomolecules (represented by fl uorescently labeled beads). Reproduced with permission. [ 71 ] Copyright 2011, Nature Publishing Group.
than fabrics generated from regular stitches. Float stitches on the other hand provide directionality to the structure of the knitted fabrics. [ 78,80 ] The warp-knitted structures show more fl exibility and extendibility compared to the weft-knitted constructs. [ 80 ] However, the weft knitting offers superior control over pore size, porosity, and fi ber alignment in the construct. [ 81 ] Currently, there are automated and programmable machines that are capable of creating complex 2D and 3D fabrics in large scale. For example, “Tricot” and “Raschel” machines perform warp knitting while “fl atbed” and “circular” machines perform weft knitting.
Knitted scaffolds have been extensively used to engineer or to repair damaged tissues and organs. [ 16,79,81–85 ] Mechanical prop-erties and microstructure of the knitted structure are the two important parameters affecting the scaffold functionality. The pore size of the knitted fabric should be large enough (≈100 µm) to allow cellular ingrowth while maintaining the mechan-ical strength of the construct under applied stresses. Knitted
fabrics have also been employed as a reinforcing skeleton to provide structural support for a collagen or silk sponge with proper biological environment for tissue growth (Figure 4 c–e). For example, knitted silk-collagen sponge scaffolds have been seeded with human embryonic stem cells (hESC) and human mesenchymal stem cells (hMSCs) for tendon and ligament regeneration, respectively. [ 79,82 ] In another study, scaffolds knitted from hydroxyapatite-coated silk yarns have shown enhanced osteoinductivity and osteoconductivity. [ 84 ] Although knitted constructs have been mostly used as a reinforcing struc-ture, there are also reports of their use as a selectively remov-able template for creating autologous ECM scaffolds. [ 86 ] The process includes culturing cells on a knitted construct with desired microstructure and removing the knitted template after the ECM deposition of the cells. With the recent advances in the development of novel biomaterials, yarns can be made with controlled degradation profi les and mechanical properties.
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Table 2. Summary of textile methods for fabricating tissue constructs and their advantages and disadvantages.
Textile method Advantages Disadvantages
Knitting • High fl exibility • Adjusting properties in different directions is diffi cult
• Ability to create 3D complex structures using CAD systems
Weaving • Ability to create constructs with anisotropic properties • Less fl exibility compared to knitting
• Process is less mechanically harsh compared to knitting • Low porosity
Figure 4. Fabrication of knitted fabrics and their tissue engineering applications. a,b) Schematic diagrams of various knitting processes and stitches; a) Weft and b) warp knitting. c) Combined knitted silk scaffold and collagen sponge. d) Knitted silk scaffold. e) hMSCs grown on the combined knitted scaffold with high viability and proliferation rate. Reproduced with permission. [ 78 ] Copyright 2000, Elsevier. Reproduced with permission. [ 79 ] Copyright 2008, Elsevier.
most biotextiles, which enables higher com-plexity and performance capabilities in the construct. The ability of the knitted construct to stretch, makes knitted fabrics a great candi-date for engineering of load-bearing tissues. With the advent of new knitting machines equipped with computer-aided design (CAD) systems, 3D structures with exquisite control on their microstructure can be fabricated. Nonetheless, creating constructs with adjust-able properties in different directions is still diffi cult with knitting.
3.2. Weaving
Weaving is one of the most ancient technolo-gies developed by man for creating clothing. [ 87 ] In this textile method, the fabric is formed from two distinct sets of yarns, which are interlaced normally. [ 88 ] The lengthwise yarns are called warps and the weft (fi lling) passes through them in the lateral direction. The most common weaves include plain, satin, and twill ( Figure 5 a). In plain weave, each weft passes over one warp and then under the following warp and this trend will be reversed in the following row. In satin weave, warps are fl oating on top of a number of wefts and are more exposed in comparison to plain weave. In twill weave, on the other hand, the wefts are passed through the warps in a way that they are exposed in a diagonal fashion. Dif-ferent weaves can change the fl exibility and smoothness of the fabric. Another important factor that affects the looseness as well as the porosity of the generated fabric is the number of warps and wefts per square inch. [ 89 ]
Weaving looms are simple and easy-to-use and are compatible with a wide range of materials. Consequently, the application of woven constructs has extended to multiple engineering applications including com-posite fabrication, fuel cell technology, and biomedical engineering. Woven structures are more fl exible than knitted constructs but can endure less force in the in-plane direc-tion. Moreover, woven fabrics are less porous than knitted structures and possess smaller pores. The in-plane mechanical properties can be improved by interlocking multiple layers of woven fabrics for the applications that require load-bearing characteristics. [ 90 ] Moreover, the use of multiple layers allows for the fabrication of thick 3D structures.
Woven fabrics have been utilized as tissue engineering scaffolds or reinforcement mats
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Figure 5. Woven fabrics and their use in tissue engineering. a) Various common weaves including i) plain, ii) twill, and iii) satin. b) 3D woven scaffold generated with interlocking several layers for cartilage tissue engineering, i) schematic, ii) a representative SEM image of woven PGA scaffolds, iii) a typical scaffold covered with chondrocyte-laden agarose. Repro-duced with permission. [ 14 ] Copyright 2007, Nature Publishing Group. c) Weaving hydrogel fabrics using a microweaving loom (i), the loom was employed to create a patterned hydrogel fabric. Reproduced with permission. [ 15 ] Copyright 2013, Nature Publishing Group. d) Assembly of CLFs i,ii) using an off the shelf weaving loom, iii,iv) representative micro-graph demonstrating a typical fabricated cell-laden fabric. Reproduced with permission. [ 16 ] Copyright 2014, Wiley-VCH.
in hydrogels to tune the mechanical properties of the construct. In a pioneering study, Moutos et al. developed a microweaving loom to assemble PGA yarns into fabrics. [ 14 ] They also inter-locked several layers to create a load-bearing 3D structure. The reinforcement mat was embedded within chondrocyte-laden agarose gels for cartilage tissue engineering (Figure 5 b). This work was later adopted by a number of groups which fabricated reinforcing structures from silk, poly(caprolactone) (PCL), and polypropylene. [ 17,91–95 ] These studies have been mostly focused on mimicking the biomechanical properties of native tissues through the utilization of woven fabrics. Recently, researchers have tried to use weaving looms for controlling cellular pattern within a construct. For example, Onoe et al. devised a micro-weaving machine and assembled cell-laden hydrogel fi bers to create complex constructs with controlled cell distribution (Figure 5 c). [ 15 ] In another study, wetspun cell- and bead-laden hydrogel fi bers were created and then assembled using a custom-built weaving loom. [ 46 ]
Hydrogel fi bers are usually not mechanically strong, thus, the mechanical properties of the fabricated constructs will not be suitable for applications that require load-bearing charac-teristics. Our group has introduced the concept of composite living fi bers (CLFs) with a load-bearing core and cell-laden hydrogel shell. [ 16 ] We assembled these CLFs using a weaving loom to create cell-laden fabrics. Weaving CLFs with mechani-cally strong core enabled us to control both cellular distribution and mechanical properties (Figure 5 d).
Weaving enables fabrication of 3D constructs with tunable anisotropic mechanical properties that mimic the properties of several native tissues such as cardiac and cartilage. Weaving looms are easier to design in comparison to knitting systems for creating cell-laden structures with controlled mechanical characteristics and cell distribution. In addition, the weaving process is less mechanically harsh compared to other textile processes.
3.3. Braiding
A braided structure is comprised of three or more strands inter-twined in overlapping patterns. A wide variety of 3D geomet-rical shapes with fi ne-tuned stable properties can be obtained through varying the arrangements of diagonally intertwined strands. Complex structures fabricated through braiding are dif-ferentiated from knitted or woven counterparts by the versatility they offer in axial and radial load-bearing properties, enhanced physical stability, damage tolerance and fatigue resistance in bending, torsion and traction, as well as improved abrasion resistance. [ 51,96–98 ] A wide range of the medical textiles are man-ufactured using braiding technology including sutures, stents, nerve regeneration conduits, braided composite bone plates, scaffolds for ligaments tendons, and artifi cial cartilages. [ 51,98 ]
The high tensile strength and mechanical fl exibility of braided structures have made them an excellent candidate for engineering of articular and connective tissues such as carti-lage, tendon, and ligament. ACL is the most commonly injured intra-articular ligament of the knee. [ 99 ] Braiding technique has been used to develop numerous ACL grafts with biomi-metic characteristics. [ 34,99–101 ] It has been shown that the fi ber
materials, morphology of the scaffold, and the interactions between the fi bers play critical roles in the proper function of the engineered grafts. [ 102,103 ] A major challenge in ACL tissue engineering is regenerating articular cartilage with anisotropic and heterogeneous mechanical properties. Varying braiding angle, fi ber density, and number of layers, enable developing anisotropic mechanical and physical properties with adjustable gradient along any desired direction. By changing the porosity of the engineered graft from the two ends toward the middle region, cellular ingrowth can be enhanced while the mechan-ical properties of the engineered tissue are maintained. [ 103 ] Utilizing numerical tools, optimized fi ber confi gurations that provide the biomechanical requirements needed to restore the knee function were determined. [ 102 ]
Selection of proper fi ber material is another important parameter that has to be considered in the fabrication of braided tissue constructs. Synthetic materials such as poly(lactic acid-co-ε-caprolactone (PLCL) [ 101 ] and poly( L -lactic acid) (PLLA) [ 99 ] or composite fi bers made from synthetic and natural mate-rials such as 50% type I collagen and 50% PVA [ 100 ] have been used for ACL tissue engineering. Synthetic materials provide mechanical strength while the natural materials provide a more nurturing environment for the cells to grow and function.
Another well-recognized approach to enhance and direct cel-lular activities is to create nano features on the constructs. [ 105,106 ] Electrospinning is a powerful tool for creating fi bers with nano-meter sizes. Yarns made from a bundle of aligned fi bers can be created using electrospinning and can be intertwined to form braided scaffolds. [ 105 ] It has been shown that the mechanical properties of such constructs mimic the mechanical behavior of native tissue and also can enhance the cellular activity when seeded with hMSCs. [ 105 ] Moreover, such scaffolds have been modifi ed with antibacterial biomaterials such as chitosan and used as suturing thread that were bacterial resistance [ 104,107 ] ( Figure 6 ).
Due to their fl exibility and ability to maintain dimensional stability as well as improved radial compressive strength, braided constructs are ideal scaffolds for engineering nerve conduits. [ 96,108 ] A biodegradable multilayer-braided PLA fi ber-reinforced conduit has been fabricated to treat a 10 mm nerve gap in the rat sciatic nerve. [ 109 ] The results indicated that after 8 weeks of implantation, the scaffold was well integrated and encapsulated by the surrounding tissue. Recently, a novel tab-ular PLGA construct, consisting of a dense outer tube and a porous inner tube, has been developed to guide and support peripheral nerve regeneration. [ 108 ] Higher braiding density was used for the outside tube in order to serve as support for the space of the nerve regeneration and provide the required compression performance while the interior scaffold had lower PLGA fi ber density to function as the matrix bridge in the nerve regeneration process.
Overall, braided constructs offer enhanced mechanical prop-erties under various loading conditions, good fl exibility, and structural stability, as well as controlled tissue regeneration. These parameters make them an apt choice for tissue rein-forcement, grafts in load-bearing fi xations and wound closure and support. However, a key challenge associated with braided tissue scaffolds is their low porosity, which can limit cellular penetration and proliferation. Nevertheless, strategies that
allow for the incorporation of cells into the fi bers prior to their assembly can overcome this challenge.
4. Emerging Applications of Biotextiles
With the advent of textile technologies as biofabrication methods for creating biofabrics and tissue constructs, different applications of such structures have been emerged. The fabrics made from advanced biomaterials have been mainly used for three major applications including cardiovascular and muscu-loskeletal tissue engineering, wound dressings, and wearable electronics. However, few recent studies have reported the use of textile methods for neural tissue engineering, engineering of bladder, and for drug delivery applications.
4.1. Cardiovascular Tissue Engineering
Cardiovascular diseases such as congestive heart failure, coro-nary artery diseases, and heart valve dysfunction are respon-sible for ≈17 million deaths per year globally and this number is predicted to reach 23.3 million by 2030. [ 110 ] In the case of heart diseases, due to the lack of self-repair and renewal char-acteristics of the heart, organ transplantation is the only solu-tion. However, there is an unmet demand as the number of donors and patients do not match. Tissue engineering holds a great promise to overcome this health barrier by creating func-tional organs that can replace the injured organ. The fabrication of functional cardiac tissues using current tissue engineering techniques faces key challenges including the ability to i) mimic the cardiac-like molecular composition, structure, electrochem-ical, and mechanical properties of native tissue and ii) effec-tively vascularize tissues with clinically relevant dimensions. [ 111 ] Thus, a new paradigm for the treatment of cardiovascular tissue
damage is needed to provide an effective and long-term therapy for most patients.
Textile technologies are powerful tools for producing fi nely tuned 2D and 3D constructs from natural or synthetic fi bers. Textile manufacturing platforms offer unique advantages over existing scaffold fabrication methods (e.g., salt-leaching, [ 3 ] bio-printing, [ 5,47 ] and micropatterning [ 112 ] ), including fi ne control over the size, shape, porosity, and mechanical properties of the fabricated constructs. [ 14,40,51 ] Proper function of myocardial tissue requires anisotropic mechanical properties and direc-tional cellular alignment ( Figure 7 a–c). The heart is comprised of long, fi brous muscle cells wrapped in collagen sheaths and interwoven with blood vessels. [ 112 ] The shape and orientation of muscle cells within the heart tissue are therefore critical to their electrical and mechanical properties. Thus, fi bers can be loaded with different cell types such as hMSCs, ECs, and human car-diomyocytes (hCMs) as well as growth factors and drugs that augment cellular function. These fi bers can be then assembled to mimic the microarchitecture of the native tissue.
Currently, there are several US Food and Drug Administra-tion (FDA)-approved biotextiles available for the treatment of cardiovascular diseases and disorders. CorCap Cardiac Sup-port Device (CSD) from Acorn Cardiovascular, Inc. is a surgical mesh that is implanted around the heart to provide circum-ferential myocardial wall support and to reduce the wall stress and myocyte stretch. Vascular grafts such as Gelsoft [ 113 ] and Gelweave, [ 114–116 ] from VASCUTEK are also being used for the treatment of diseased aortic vessels.
Biofabrication of scaffolds for cardiovascular tissue engi-neering using textile methods has been demonstrated by sev-eral researchers in the past few years. In an interesting study, a knitted mesh made from hyaluronan benzyl ester (Hyaff-11; Fidia Advanced Biopolymers, AbanoTerme, Italy) was used to create a hybrid cardiac construct. [ 41 ] The knitted structure was used to improve the mechanical properties of the engineered
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Figure 6. Fabrication of braided constructs using electrospun nanofi bers. a) Schematic showing the process of fabricating aligned electrospun fi bers. b) Aligned electrospun fi bers. c) Braid the aligned multifi lament fi bers into a scaffold. Braided construct implanted in a rat forelimb after d) 1 day and e) 28 days showing smooth healing. Reproduced with permission. [ 104 ] Copyright 2010, Wiley.
construct that underwent cyclic mechanical loads during in vitro and in vivo studies. The hybrid construct exhibited higher tensile strength and stiffness compared to the native myocar-dium and remodeled in response to cyclic stretches in vivo and in vitro. Textile techniques have been combined with other bio-fabrication methods to create scaffolds that better mimic the microstructure and mechanical properties of the native car-diac tissue. For example, a hybrid-knitted electrospun scaffold has been fabricated to recapitulate the anisotropic mechanical properties of the native myocardium. [ 117 ] The results showed
signifi cant differences between the surface topology and mechanical properties of the hybrid scaffold and the electro-spun construct. The hybrid scaffold contained macroscopic patterns, which assisted cellular alignment, elongation, and cardiac-like organization. [ 117 ]
With the increasing rate of valvular dysfunction, utilization of textile approaches for biofabrication of scaffolds for heart valve engineering has attracted much attention in the past few years. In this context, biotextiles have been mostly used as a reinforcing skeleton for the scaffold. It has been shown that knitted scaffolds developed for tissue engineering of aortic valves had superior resistance against physiological fl ows compared to their electrospun counterparts. [ 118,119 ] Moreover, knitted scaffolds with micron size pores showed higher cellular infi ltration in comparison to electrospun structures. [ 118 ]
4.2. Musculoskeletal Tissue Engineering
Musculoskeletal diseases caused by trauma, infl ammation, or genetic disorders have a high prevalence. Severe long-term pain and mobility restriction impair the welfare and quality of life of patients with musculoskeletal disease. Current treatments often include the management of symptoms or replacement of the impaired tissue with inert materials. Indeed, tissue engineering is an alternative approach that enables creating functional tis-sues for organ replacement.
The majority of studies in this area have been focused on the development of engineered ligament and tendon. Braided and knitted constructs have been used alone [ 105,120 ] as scaffolds or reinforcing structures for scaffolds made from other polymers such as collagen [ 82,85 ] or silk. [ 84 ] In a notable study, electrospun fi bers were braided and seeded with hMSCs to engineer a tendon-like construct. [ 105 ] Results showed that nanofi bers improved the mechanical strength of the construct and enhanced the cellular function by mimicking the dimensionality of collagen fi brils in native tissue. [ 105 ] In another study, it was shown that a woven scaffold made from collagen threads with densely compacted and anisotropically aligned substrate textures stimulated tenogenesis topographically. [ 120 ] Therefore, such scaffolds can serve as a sub-strate for functional repair of ligaments and tendons.
4.3. Wound Dressing
Wound is defi ned as a break or cut in any tissue. [ 121 ] Manage-ment of skin wounds is one of the earliest medical activities of humans. During the past centuries, aligned with advances in biological and material sciences, more effective technologies have emerged for treating various wound types. [ 122 ] New devel-opments have also been boosted by the market size of wound management products ($28.7 billion in 2013). [ 123 ] Ideal wound dressings should: i) permeate oxygen; ii) keep the area moist; iii) remove excess exudates; iv) be biocompatible and nonal-lergenic; v) inhibit microorganisms growth; vi) provide appro-priate stimulation and growth factors during different stages of wound healing; and vii) possess suitable mechanical properties that prevent any potential discomfort while maintaining con-formal contact between the dressing and the wound.
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Figure 7. Textile-based methods for engineering of cardiac tissues. a) Microstructure of cardiac muscle with preferentially oriented cardiac muscle fi bers. b,c) Anisotropic mechanical properties of right ventricular myocardium showing the directionality of uniaxial tensile strength. Repro-duced with permission. [ 112 ] Copyright 2008, Nature Publishing Group.
IEW Textile systems have been widely used as wound dressings
since they possess oxygen permeable porous microstructure with the ability to wick exudates. The scalability of textile fabrics also adds to their robustness for use in wounds with different sizes. The ability of textile systems for tuning the mechanical properties of the generated constructs is another key advantage that enables the fabrication of elastic and fl exible dressings that maintain their contact with the wound. Traditionally, tex-tile dressings in the form of medical gauze and bandage have been fabricated from a range of natural and synthetic materials including cotton, silk, PGA, polyester, and polyurethane. [ 124 ] Conventional dressings can provide support to the wound during the healing process and are air and exudates permeable. Textile-based wound dressings can offer hemostatic properties by incorporation of proper reagents or applying mechanical force to physically close the wound. [ 125,126 ]
These conventional textile systems, however, cannot main-tain moisture in the wound area and fail to inhibit bacterial growth. [ 124 ] To solve the later challenge, fi bers or fabrics have been coated with antibacterial reagents such as silver and honey. [ 123,127,128 ] However, the generation of wet textile-based wound dressings has been impossible due to the insuffi cient mechanical strength of hydrogels and hydrocolloidic fi bers. Recent advancements in fabrication of hydrogel fabrics [ 15 ] (Figure 5 ) and the introduction of CLFs [ 16 ] (Figure 3 ) have paved the path towards creating wet fabrics that can potentially be used as wound dressings. For example, Knill et al. fabricated bi-layer alginate and chitosan hydrogel fi bers with antibacte-rial properties and randomly assembled them as a wet wound dressing ( Figure 8 ). [ 129 ] Another important characteristic of wet wound dressings is their ability for drug and growth factor delivery to the wound area to promote the healing process. [ 130 ] Recent advancements of textile-based electronics can also potentially lead to the development of dressings for sensing and stimulating the wound area to improve the healing rate. Thus, development of scalable techniques for generation of mechani-cally robust wet fabrics could potentially have an enormous impact on the advancement of wound management systems.
Biotextile, with a long history of being used as dressings for wound management, are promising substrates for advanced wound healing applications. Biotextiles combined with recent advances in biomaterials, drug delivery and fi ber-based elec-tronics hold a great promise for developing smart fabrics with the capability of monitoring the wound condition and per-forming suitable treatments.
4.4. Wearable Electronics
Recent advances in micro and nanofabrication technologies combined with progresses in the area of polymeric sciences have enabled the development of a new class of electrical sys-tems that are fl exible, elastic, and even biodegradable. [ 18 ] One area that has received noticeable attention for the fabrication of such systems is textile-based approach, specifi cally due to the tunable physical characteristics of the generated fabrics and their hierarchical nature. [ 131 ] This new class of electronics is wearable and can form conformal contact with skin. [ 132,133 ] In addition, electrically enabled fabrics have been made from poly-meric materials that are implantable as sensors or actuators. [ 133 ] In general, electrically enabled fabrics have been employed for various applications including fl exible circuits, [ 134 ] radio-fre-quency identifi cation tags, [ 135 ] wearable energy harvesting sys-tems, [ 136 ] and tissue engineering scaffolds. [ 137 ]
An important factor in design of fi ber-based electronics is the selection and introduction of the conductive materials into the system. The selected material should possess electrical con-ductivity and mechanical properties that suit specifi c applica-tions. For example, the conductive material should be fl exible to allow its incorporation into the fabric and should maintain its normal function once worn or implanted. [ 133 ] The conductive material can be selected from metallic fi bers, metallic particles and nanowires, carbon nanotubes, graphene, reduced graphene oxide, or conductive polymers. [ 133 ]
Conductive fi bers can be used either directly or in combi-nation with nonconductive threads for making wearable fab-rics. [ 138,139 ] In addition, conductive fi bers or yarns can be cre-ated by coating a core fi ber with a layer of conductive ink or polymer. [ 140,141 ] These fi bers or yarns are then interweaved or knitted into a fabric or can be added through an embroidery process to create conductive patterns. [ 138,142 ] It is also possible to render a regular fabric electrically conductive by simply coating it with or dipping it into a solution containing nanoparticles or nanowires. [ 143 ] Conventional patterning methods including screen printing by means of a shadow mask, applying the ink using a brush, spin coating, or spraying can also be used to create conductive patterns on textiles. Textile fabrics are also compatible with inkjet and contact printing, which possess a higher resolution in comparison to screen printing. Our group has recently introduced a biodegradable nanofi brous mat of PGS–PCL as a suitable substrate for fl exible and elastic sensors ( Figure 9 a–c). [ 18 ] Temperature and strain sensors were screen
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Figure 8. Bilayer hydrogel fi bers for antibacterial wound dressing. a) Schematic of the fi ber microarchitecture. b) A representative micrograph of fab-ricated alginate–chitosan hydrogel fi bers. Reproduced with permission. [ 129 ] Copyright 2004, Elsevier.
printed on top of the substrate and it was shown that the elec-trical functionality of the created patterns was maintained over a range of tensile strains and radii of curvature.
Biodegradable fabrics with embedded electronics have sev-eral applications in the fi eld of tissue engineering and regen-erative medicine. For example, it is now well documented that electrical stimulation can affect cellular behavior of muscles and neurons and thus can be used to control their alignment and function. [ 144,145 ] In addition, it has been demonstrated that proper electrical stimulation promotes synchronized beating of cardiomyocyte cultures, which is an important step toward engineering functional cardiac tissues. [ 146 ] These observations combined with tunable mechanical properties and biomimetic microarchitecture offered by textiles have motivated researchers to design electrically enabled tissue engineering scaffolds. In a notable study, a network of nanowires were fabricated and used to create tissue engineering scaffolds for both stimulating cel-lular cultures and sensing their activity in situ (Figure 9 d). [ 137 ] In particular, the scaffolds enabled monitoring the local elec-trical activity of cardiomyocytes and neurons and their response to drugs.
Overall, the integration of sensors with textiles is an exciting approach for developing wearable devices for continuous moni-toring of the human body health. Electrically conductive fab-rics combine the physical characteristics of textiles (tunable mechanical properties and high porosity) with advanced elec-tronics and sensors to create multifunctional scaffolds for car-diac and neural tissue engineering. In addition, by utilization of resorbable metals such as Mg and Zn, fully degradable sys-tems can be realized and implanted avoiding the necessity of a second retrieval surgery.
5. Challenges and Future Prospects
Biotextiles hold a great promise for various applications in tissue engineering and regenerative medicine. The versatility of textile techniques provides exciting opportunities in engi-neering scaffolds and tissue-like structures with controlled microarchitecture and cellular distribution. Textiles are highly porous and permeable to nutrients, oxygen, and growth fac-tors. Textile tissue engineering allows simultaneous control of mechanical properties and cell distribution within a construct. Thanks to their one directional features, fi bers can provide directionality to the cells which can lead to improved cellular alignment, and controlled differentiation during tissue forma-tion and remodeling. Additionally, fi bers can carry cells, drugs, and growth factors into the construct. Moreover, sacrifi cial fi bers can be interwoven to facilitate the generation of prevascu-larized tissue constructs.
Despite numerous advantages offered by textile technology, there are still several challenges that have to be addressed to use this technology up to its full potential. The main obstacle for the use of biotextiles for tissue engineering and regenera-tive medicine is combining state-of-the-art textile machinery, novel biomaterials, and biological advances to create tissues and organs automatically. Although fi bers made from synthetic materials are mechanically strong and can be assembled into complex structures using textile approaches, the harsh manu-facturing process hampers the ability to encapsulate cells inside them. Current methods for creating cell-laden fi bers yield to the fabrication of fi bers that are not mechanically strong to withstand the mechanical loads exerted during the manufac-turing process. Such challenge has been recently addressed by
Figure 9. Engineering fi ber-based implantable electronics. a) A typical PGS–PCL nanofi brous substrate with a conductive silver pattern. b) A micro-graph showing the microstructure of the sheet and the patterned conductive lines. c) Image of the conductive microstructure after complete degrada-tion of the substrate. [ 13 ] d) SEM image of electrical system formed from a network of nanowires engineered for creating electrically enabled scaffolds. e) Micrograph showing a hybrid multilayered PLGA scaffold. The inset shows the photograph of a typical hybrid scaffold. Scale bars: 200 µm and 5 mm (inset). f) Electrical measurement of extracellular fi eld potentials using the hybrid mesh. [ 88 ] Reproduced with permission. [ 18 ] Copyright 2014, Wiley-VCH. Reproduced with permission. [ 137 ] Copyright 2012, Nature Publishing Group.
developing cell-laden fi bers composed of a mechanically strong core material coated with a cell-laden hydrogel layer. However, the surface of cell-laden fi bers is also slippery which can make their assembly challenging. Thus, more advanced fi ber fabrica-tion techniques should be developed to allow the fabrication of cell-laden fi bers with properties comparable to the currently used threads. Accordingly, it is expected that the fi eld of textile tissue engineering will signifi cantly move toward this direc-tion. To enable the assembly of cell-laden fi bers, new textile machines that can control humidity, oxygen, and CO 2 level, create a sterile environment, and facilitate nutrient access to cells within the fi bers and generated fabrics is required.
While great advancements have been made in the fi eld of biotextiles, implantable fabrics are in use for limited applica-tions. The main challenge is the inability to capture the in vivo mechano-biological properties of different organs and tissues. This challenge can be addressed by creating different fi bers from advanced biomaterials with tunable physico-chemical properties capable of delivering growth factors and chemokines.
Another potential direction for the use of textile-based tis-sues is creating in vitro disease models and drug testing plat-forms. By assembly of cell-laden fi bers, different cells can be interfaced to facilitate the cross-talk between multiple cell types within a tissue. These advanced living fabrics can be combined with current organ-on-a-chip platforms. Flexible and wearable electronics and sensors are other areas that have been ben-efi tted from advances in biotextile engineering. It is expected that the fi eld will grow toward engineering implantable and biodegradable sensors and devices fabricated from textiles. One area that can likewise see a noticeable attention is the incorpo-ration of electronics within tissue scaffolds for monitoring cel-lular activity or stimulating them.
Acknowledgements The authors declare no confl ict of interests in this work. The fi nancial support from the National Science Foundation (EFRI-1240443), the offi ce of Naval Research Young National Investigator Award, and the National Institutes of Health (HL092836, DE019024, EB012597, AR057837, DE021468, HL099073, EB008392) is gratefully acknowledged. SB acknowledges funding from MIT-Italy program (Progetto Rocca) and Polimi International Fellowship (PIF).
Received: July 5, 2015 Revised: September 7, 2015
Published online: February 29, 2016
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