Biodegradable and biocompatible polymers for tissue engineering application: a review

Abstract

Since so many years ago, tissue damages that are caused owing to various reasons attract scientists’ attention to find a practical way to treat. In this regard, many studies were conducted. Nano scientists also suggested some ways and the newest one is called tissue engineering. They use biodegradable polymers in order to replace damaged structures in tissues to make it practical. Biodegradable polymers are dominant scaffolding materials in tissue engineering field. In this review, we explained about biodegradable polymers and their application as scaffolds.

Keywords:

• Biodegradable polymers
• electrospinning
• nanofiber
• scaffold
• tissue engineering

Introduction

Tissue engineering is an interdisciplinary science that applies chemistry, material science, engineering, and medicine aiming to repair and replace tissues and organs (Cui et al. 2010, Walmsley et al. 2015). Tissue engineering strategies are classified into three main components containing scaffold, cells (differentiated or undifferentiated), and biological signaling molecules such as growth factors (GFs) (Pereira et al. 2011). The overall regeneration strategy based on the principles is shown in Figure 1. Scaffolds are three-dimensional (3D) structure that can be produced by synthetic polymers, natural polymers and purely biological molecules, such as collagen, elastin, hyaluronic acid, and other extracellular matrix (ECM) molecules (Bačáková et al. 2014). The scaffold must be able to mime the structure and biological function of natural extracellular matrix (ECM) in terms of both chemical composition and physical structure (Zhou and Lee 2011). The extracellular matrix (ECM) is a various composition of proteoglycans, proteins, and signaling molecules. ECM is originally known for its role in providing structural support to cells and as a location for cell migration (Owen and Shoichet 2010). Appropriate scaffolds for tissue engineering applications should be biodegradable, biocompatible, nontoxic, nonmutagenic, and nonimmunogenic. Furthermore, they should be able to provide appropriate mechanical support and show favorable surface properties, such as helping adhesion, proliferation and differentiation of cells (Bačáková et al. 2014, Zhou and Lee 2011). Polymeric scaffolds play a main role in tissue engineering through cell seeding, proliferation, and new tissue formation in three dimensions. These scaffolds have shown great ability in the research of tissue engineering (Sakai et al. 2013). Biodegradable polymers due to reducing inflammatory reactions, nontoxic and degradation by enzymes in the body have many applications in medicine and pharmacy. Biodegradable polymers are generally classified into two types, namely synthetic polymers and natural polymers (Liu et al. 2012). Synthetic polymers are compatible with body, biodegradable, and absorbable. These polymers are easily changed into different 3D matrix structure. Natural polymers are metabolized into metabolites that could be used or is easily removed by kidney clearance (Tian et al. 2012). Natural polymers are originated from both tissues like collagen and plants like lactic acid (Abbasi et al. 2016).

Figure 1. The schematic of tissue engineering strategies for damaged tissue.

Synthetic polymers

Synthetic polymers can be obtained by polymerization of monomers. Porous scaffolds fabricated from biocompatible and biodegradable polymers play vital roles in tissue engineering and regenerative medicine. The development of tissue engineering, tissue induction, and other types of regenerative medicine depend strongly upon the techniques of 3D porous scaffolds composed of organic and inorganic substrates, very frequently, biocompatible and biodegradable polymers. Synthetic polymers, such as polyglycolic acid, polylactic acid, polycaprolactone, poly (N-isopropylacrylamide), and their copolymers have been used in tissue engineering science. Synthetic polymers have acceptable processing flexibility and no immunological concerns compared with natural ECM proteins (Liu et al. 2012). Polylactic acid (PLA) and its copolymers, such as polylactide-co-glycolide (PLGA), PLGA–PEG. The biodegradable polyester family has been regarded as one of the few synthetic biodegradable polymers with controllable biodegradability, excellent biocompatibility, and high safety. Some properties of synthetic biodegradable polymers are shown in Table 1 (Eatemadi et al. 2016).

Table 1. Properties of synthetic biodegradable polymers.

Polymers	Molecular formula	Melting point	Abbreviation	Glass Transition temperature	Image
Polyglycolic acid	(C2H2O2)n	225–230 °C	(PGA)	35–40 °C
Polylactic acid	(C3H4O2)n	150–160 °C	(PLA)	60–65 °C
Polycaprolactone	(C6H10O2)n	60 °C	(PCL)	−60 °C
Poly (lactic-co-glycolic acid)		Depend on the percent composition (PLA, PGA)	(PLGA)	40–60 °C
Poly(N-isopropylacrylamide)	(C6H11NO)n	96 °C	(PNIPAAm)	32–34 °C

Polyglycolic acid (PGA)

Polyglycolic acid/or polyglycolide (PGA) is one of biodegradable and biocompatible aliphatic polyesters, that is, widely used in medical applications. PGA can be prepared starting from glycolic acid by ring-opening polymerization (Ikada and Tsuji 2000, Middleton and Tipton 2000). Common role of PGA as a biodegradable structure material has led to its assessment in other biomedical fields. Tissue engineering scaffolds, which are made of PGA, have been used in medical applications. Many studies in the field of tissue engineering are done using the PGA nanofibers (Boland et al. 2001). Kobayashi et al. prepared the nanocomposite combined of PGA and collagen. Their results of the animal models showed that the PGA-collagen nanocomposites were completely occupied and vascularized within 5 days after the implantation (Kobayashi et al. 2013). Patrascu et al. produced polyglycolic acid-hyaluronan (PGA-HA) scaffolds and analyze chondrogenic potential of freeze-dried (PGA-HA) implants preloaded with mesenchymal stem cells (MSCs) in vitro and in a rabbit articular cartilage defect model. Results demonstrated that MSC-loaded PGA-HA scaffolds have chondrogenic stimulation and are a good option for stem cell-mediated cartilage renewal (Patrascu et al. 2013). In studies based on tissue engineering, it can be concluded that using PGA polymers could be suitable scaffold for the regeneration of cartilage and blood vessels. Kobayashi et al. combined PGA and collagen to produce nanocomposite as scaffolds to be used in inducing vascularization, but another study is on cartilage regeneration. Patrascu et al. used polyglycolic acid and hyaluronan to prepare scaffolds-stimulating cartilage. Mesenchymal stem cells were cultured on the scaffold, and the results showed that the mesenchymal stem cell growth and differentiation are performed well enough so that mentioned scaffold is suitable for cartilage regeneration.

Polylactic acid

Polylactic acid or polylactide (PLA) is a biodegradable, bioadsorbable, thermoplastic aliphatic polyester, that is, derived from renewable resources. Lactic acid has two optical isomers, L- and D-lactic acid. PLA can be prepared from lactide by ring-opening polymerization (Middleton and Tipton 2000). PLA is used as medical implants in the form of screws, pins, rods, orthopedic device, and as a mesh (Lasprilla et al. 2012). One of the medical applications of polylactic acid in Chang’s study was conducted. In this study, polylactic acid has been used as a semipermeable microcapsule containing enzymes, hormones, vaccines, and other biological products. The reasons for using polylactic acid as semipermeable microcapsules are its biodegradability and also it produced nontoxic metabolite in the body after destroyed (Chang 1976). PLA is also used as a biodegradable and biocompatible material in tissue engineering science. Lin et al. produced hydroxyapatite (HA) mineralized on chitosan (CS)-coated poly (lactic acid) (PLA) nanofibers for bone regeneration. Their results show that this composite has similar structural, combination, and biological functions of natural bone and can help as a good choice for bone regeneration (Lin et al. 2014). In another study in the field of tissue engineering, Hao-Yang Mi et al. prepared composed thermoplastic polyurethane (TPU) and polylactic acid (PLA) tissue engineering scaffolds at different ratios. PLA was diffused as spheres into the TPU matrix. Their results show that the nanocomposite scaffolds PLA/TPU with surface roughness, biocompatibility, and mechanical properties that have the possible to be used as synthetic scaffolds in tissue engineering science (Mi et al. 2013). Based on these studies, it can be concluded that polylactic acid can be used as scaffolds for bone regeneration and other tissues. As noted above, Lin et al. used lactic acid to produce nanofibers containing hydroxyapatite, which is useful for bone mineralization. The nanofibers can be used as a scaffold for the growth and differentiation of osteoblast. These scaffolds can be a good choice for bone regeneration. But Hao-Yang Mi et al. combined polylactic acid and polyurethane to design scaffold that has good features such as surface roughness and being tunable. This scaffold with characteristics such as roughness and being tunable is a suitable candidate for soft and hard tissue regeneration (Ebrahimi et al. 2016).

Polycaprolactone

Polycaprolactone (PCL) is a biocompatible, bioadsorbable, and biodegradable polyester. PCL is synthesized by ring-opening polymerization of ɛ-caprolactone using a catalyst (SnO2) and heat (Middleton and Tipton 2000). PCL is used as medical implant, dental splints, and targeted drug delivery. PCL is also used in tissue engineering. Zheng R et al. produced electrospun membranes with different GT/PCL ratios. Results show that three kind of membranes with various GT/PCL ratios exhibited biocompatibility with chondrocytes. They also demonstrated that the high PCL content was unfavorable for 3D cartilage regeneration. It can be concluded from their studies that electrospun GT/PCL is a good candidate for cartilage and other tissue regenerations (Zheng et al. 2014). Uma Maheshwari et al. (2014) produced a polymer–ceramic bilayer nanocomposite scaffold based on electrospun polycaprolactone (PCL)/polyvinyl alcohol (PVA) bilayer nanofibers mixed with hydroxyapatite nanoparticles (HAp) for bone regeneration. Results demonstrated that (PVA/HAp/PCL) nanofibers are biocompatible scaffolds for bone tissue engineering application (Uma Maheshwari et al. 2014). Nanofibers are prepared from polycaprolactone in combination with other polymers provide suitable scaffolds for tissue engineering. Recent studies show that polycaprolactone is a biocompatible scaffold to be used in regeneration of bone and cartilage.

Poly (lactic-co-glycolic acid)

Poly (lactic-co-glycolic acid) or PLGA is a biodegradable and biocompatible copolymer, which is used in medical application, therapeutic tools, and drug delivery systems. PLGA is synthesized by ring-opening copolymerization of two different monomers of glycolic acid and lactic acid (Middleton and Tipton 2000). PLGA is used in tissue engineering. Junmin Qian et al. prepared poly (dl-lactic-coglycolic acid)/nano-hydroxyapatite (PLGA/nHA) scaffolds. Results showed that the combination of nHA into PLGA reduced the degree of crystallinity of PLGA and significantly enhanced the compactive modulus of biomorphic scaffolds. It can be concluded from their studies that the biomorphic PLGA/nHA composite scaffolds are useful for bone tissue engineering (Qian et al. 2014). Scaffolds made of polylactic-containing hydroxyapatite can stimulate osteoblasts, which is important for bone regeneration.

Poly (N-isopropylacrylamide)

Poly(N-isopropylacrylamide) (PNIPAAm) is a thermosensitive polymer. It is synthesized by free-radical polymerization from N-isopropylacrylamide monomers in the presence of the initiator (Schild 1992). Due to unique physical and chemical properties, it has many applications, such as biosensors, tissue engineering, and drug delivery. In studies, PNIPAAm is used to regenerate damaged tissue. For example, Sá-Lima H and et al. prepared scaffolds based on PNIPAAm polymers and studied capacity of poly (N-isopropylacrylamide)-g-methylcellulose (PNIPAAmg-MC) thermoreversible hydrogel as a 3D support for the regeneration of articular cartilage. They proved the feasibility of using PNIPAAm-g-MC thermoresponsive hydrogel as a 3D scaffold for cartilage regeneration by minimal-invasive approaches and also demonstrated an increase in synthesis of glycosoaminoglycans during culture time (Sá-Lima et al. 2011). It can be obtained that use of (PNIPAAm-g-MC) as thermosensitive scaffolds can be effective in regenerating cartilage and combination of PNIPAAm with other biological materials can be a suitable scaffold for tissue engineering applications.

Poly ((DL-lactic acid-co-glycolic acid)-g-ethylene glycol) (PLGA-g-PEG))

Poly((DL-lactic acid-co-glycolic acid)-g-ethylene glycol) (PLGA-g-PEG) is a copolymer of Poly (DL-lactic acid-co-glycolic acid) and poly (ethylene glycol). PLGA-g-PEG that is another biodegradable and bioadsorbable polymer used in tissue engineering and drug delivery systems. Sidney et al. (2014) prepared porous scaffolds composed of poly (DL-lactic acid-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) with and without the anti-inflammatory drug named diclofenac sodium for bone regeneration with the ability to release anti-inflammatory drugs. Produced scaffold was loaded with the various concentration of diclofenac sodium. The results of these studies suggest the possible use of PLGA/PEG scaffolds for the localized delivery of anti-inflammatory drugs in bone regeneration (Sidney et al. 2014).

Poly(caprolacton/ethylene glycol) copolymer

PCL–PEG copolymer is another biodegradable and biocompatible polymer, which is synthesized by ring-opening polymerization in the presence of catalyzer. PCL–PEG is used in tissue engineering to regenerate damaged tissue. In a recent study conducted by Niu et al. (2014) scaffolds were prepared from copolymers of poly (ɛ-caprolactone) (PCL) and polyethylene glycol (PEG) for peripheral nerve regeneration. In this study, Niu et al. (2014) prepared scaffolds of block polymers based on poly (ɛ-caprolactone) and polyethylene glycol (PEG) with high surface area porosity for cell adhesion and cell differentiation that would be a suitable environment for the regeneration of damaged tissue. The results of these studies on the peripheral nerves in animal models suggest that nerve guide scaffolds of poly (ɛ caprolactone) and poly(ethylene glycol) (PEG) have better peripheral nerve regeneration (Niu et al. 2014).

Poly(caprolacton/lactide) copolymer

PCL–PLA copolymer is another biodegradable, biocompatible, and bioadsorbable polymer that has many applications in tissue engineering. PCL–PLA copolymer is synthesized by ring-opening polymerization. In recent years, PCL–PLA copolymer nanofiber has many applications in the regeneration of damaged tissue and drug delivery systems based on nanofiber. A study by Karami et al (2013) has been performed that they used PCL/PLA hybrid nanofibers containing herbal drug for the treatment of wounds. In this study, Karami et al. prepared PCL/PLA hybrid nanofibers containing the herbal drug Thymol (Dorman and Deans 2000). Thymol has antimicrobial (Dorman and Deans 2000), antibacterial effects (Zarrini et al. 2010), and antifungal activity (Numpaque et al. 2011). Because of these properties, it can be used as a wound-healing agent. The results of these studies indicate that the electrospun PCL/PLA hybrid nanofibers containing Thymol had led to notable wound healing (Karami et al. 2013).

Natural polymers

Natural polymers are polymers produced by biological systems, such as microorganisms, plants, and animals. Natural polymers have many uses, such as an adhesive bandage, absorbent, prepared cosmetics, drug delivery, and medical scaffolds (Malafaya et al. 2007, Shanmugam et al. 2005). Natural polymers have a number of advantages and disadvantages. Similar to the host tissue, ability to communicate with the biological systems, metabolic compatibility, being nontoxic and low inflammatory reactions, ability to degrade by enzyme, use of heir degradation products in cellular metabolism are some of the advantages. On the other hand, due to temperature sensitivity, natural polymers are destroyed before they reach the melting point, and its complex structure makes it difficult to process. The possibility of disease transmission to human from other species due to preparation of a variety of natural polymers by plant and animal resources are known disadvantages of these polymers (Sonia and Sharma 2012). The following two types of natural polymers are available: (1) polysaccharides such as chitin, chitosan, and alginate; (2) proteins such as collagen and gelatin (Leach et al. 2003).

Polysaccharide-originated polymers

Chitin

Chitin exists in animal skeletal system, the lens of the eye, tendons, the outer layer of arthropods and insects and arachnids and crustaceans body (crab, shrimp, and lobster) and the internal parts of body in some animals, such as mollusks and plants, as well as in the cell wall of fungus (Malafaya et al. 2007, Ravi Kumar 2000). Chitin and chitosan (derivative of chitin) have many chemical and physical properties, such as high strength, biodegradability, and nontoxic. Chitin has a white appearance. Chitin has many applications in tissue engineering. Chitin can be used for wound healing because of biodegradability (Arun Kumar et al. 2015, Krajewska 2004).

Chitosan

Chitosan is a derivative of Glocan which is produced by repeated monomers of chitin. Boiling chitin in potassium hydroxide results in chitosan. Indeed, it is the deacetylated chitin and it is the most natural aminopolysaccharide (Malafaya et al. 2007). Chitosan has features, such as biocompatibility, being nontoxic and biodegradability. Chitosan has high blood compatibility and macrophages are less active (Khor and Lim 2003). It has many applications in the field of medical and pharmaceutical sciences (Jing et al. 2015, Şenel and McClure 2004). It is also widely used in tissue engineering. Chitosan without the use of toxic solution can be prepared in injectable form. This material is made as porous scaffold, hydrogel, and microspheres (Drury and Mooney 2003).

Alginate

Alginate is polysaccharide linear, homogeneous, and natural.Alginate mainly is prepared by dark and brown algae (George and Abraham 2006, Shanmugam et al. 2005). Because of its natural structure, it has many applications in the medical field, such as detoxifying in blood to absorb toxic metals (De Carvalho et al. 2004), assisting in the processing of many drugs (Patel et al. 2006), as molding materials in dental prosthetics (Rubel 2007), stabilizing cells and cell encapsulation (Smidsrød and Skja˚k-Br˦k 1990), healing of burns and reducing pain (Kneafsey et al. 1996), and tissue Engineering (Lee and Mooney 2001). Alginate scaffolds containing stem cells have been used to treat many diseases (Zhao et al. 2010).

Protein-originated polymers

Collagen

Collagen is a protein found in the extracellular matrix of animals. Collagen molecule is composed of three polypeptide chains. Three separate polypeptide chains called alpha, which is called tropocollagen involved in the collagen formation (Myllyharju 2003). Collagen of the skin, tendons, cartilage, and bone of animals are extracted. Collagen has features such as being biodegradable and easily destroyed by enzymes in the body, biocompatibility, low stimulation of the immune system and high cell binding (Lynn et al. 2004, Malafaya et al. 2007). Collagen has many applications in medical science including delivery systems, burn and wound healing (Doillon and Silver 1986), and tissue engineering (Glowacki and Mizuno 2008). Collagen is widely applied in the preparation of tissue engineering scaffolds.

Gelatin

Gelatin is solid substance, that is, translucent and colorless obtained from the hydrolysis of collagen inside animals' skin and bones (Malafaya et al. 2007, Shanmugam et al. 2005). Gelatin forms colloid and gel in water. Many chemical properties of gelatin are like collagen and mechanical properties of collagen are temperature dependent (Ross-Murphy 1992). Gelatin also has many applications in the field of medical sciences such as drug delivery systems (Olsen et al. 2003), shells of pharmaceutical capsules (Digenis et al. 1994), cell culture (Paguirigan and Beebe 2006), and preparation of tissue engineering scaffolds. Gelatin is widely applied in the field of tissue engineering.

Nanofiber scaffold preparation methods

To prepare a suitable scaffold for tissue engineering, a variety of methods can be used. Scaffolds used in tissue engineering have a high porosity, biodegradable, and nontoxic, and it can also be able to increase the growth and cell differentiation. Methods that are used for preparing scaffolds include electrospinning method, solvent casting, freeze drying and gas foaming. Electrospinning technique is most commonly used techniques, which are widely used in the preparing scaffold in nanotechnology. Electrospinning as a simple and inexpensive method to produce very thin fibers from polymer solution. Figure 2 shows the PCL/PLA nanofiber produced by electrospinning device.

Figure 2. SEM image of PCL/PLA nanofibers.

Synthesis method of nanofibers by electrospinning

Nanofibers are fibers with a diameter of less than 100 nm, which can be used as scaffolds in tissue engineering (Li and Xia 2004). Polymeric nanofibers have dramatically been considered due to their properties in nanoscale dimensions. Electrospinning is one of the most common methods for producing nanofibers. Electrospinning is a method for producing polymer fibers in nm diameters. In this way, the liquid solution and the polymer solution can be used (Huang et al. 2003). Electrospinning method for producing nanofibers consists of three components: a high voltage supply, small diameter capillary needle, and collector. In this process, the high voltage causes the jet of polymer solution. Before reaching the collector, jet solution is vapor or solid and the small fibers are collected. The electric field is applied through the electrode into the solution and collector. By increasing field intensity, fluid is drawn in hemispherical shape from tip of syringe and tends to form a cone which is known as the Taylor cone. With further increase in the electric field due to reaching the critical value, a jet is formed at the tip of the Taylor cone. In the low electrical potential, electrostatic repulsive force is balanced with the surface tension force. But, in the high electrical potential, electrostatic force overcomes the surface tension of the liquid and causing the formation of the jet. The jet is moving a certain distance in a straight way and then it is curved and moves spiral path through it. Jets instability and tension in the spiral path lead to thinning and evaporation of the solvent to produce nanofibers that finally reach collector (Agarwal et al. 2008, Pham et al. 2006). Figure 3 shows a schematic of the electrospinning device (Fallahzadeh et al. 2010).

Figure 3. Schematic view of electrospinning device.

Solvent casting

Solvent casting property for the scaffolds preparation is extremely simple and easy. It is totally based on leading the evaporation of some solvent in order to form scaffolds by one of the two routes. One method is to the dip the mold into polymeric solution and to permit enough time to draw off the solution. As a result, a layer of polymeric membrane is shaped. Other method is to add the polymeric solution in to a mold and provided the enough time to evaporate the solvent that make a layer of polymeric membrane, which adhere to the mold (Mikos and Temenoff 2000). One of the major disadvantages of this technique is the toxic solvent denatures the protein and may affect other solvent. To overcome these problems, scaffolds are completely dried by vacuum procedure to eliminate toxic solvent. In solvent casting method, a polymer is dissolved in an organic solvent, particles, mainly salts, with specific dimensions are then added to the solution, The mixture is shaped into its final geometry. For example, it can be cast onto a glass plate to produce a membrane or in a 3D mold to produce a scaffold. When the solvent evaporates, it creates a structure of composite material consisting of the particles together with the polymer and the composite material is then placed in a bath which dissolves the particles, leaving behind a porous structure.

Freeze drying

Freeze-drying technique is used for the production of porous scaffold. This technique is based on leading the principle of sublimation. Polymer is first dissolved in a solvent to form a solution of preferred concentration. The solution is frozen and solvent is removed by lyophilization under the high vacuum that fabricates the scaffold with high porosity and inter connectivity (Haugh et al. 2009). The pore size can be controlled by the freezing rate and pH. A fast freezing rate produces smaller pores. Controlled solidification in a single direction has been used to create a homogeneous 3D pore structure. Main advantage of this technique is that it does not require high temperature (von Heimburg et al. 2001).

Gas foaming

This technique uses high-pressure carbon dioxide gas for the fabrication of highly porous scaffolds. The porosity and porous structure of the scaffold depend upon the amount of gas dissolvent in the polymer. This process involves exposing highly porous polymer with carbon dioxide at high pressure to saturate the polymer with gas (Sachlos and Czernuszka 2003). Under this condition, dissolved carbon dioxide becomes unstable and will phase separates from the polymer. The carbon dioxide molecule becomes cluster to minimize the free energy, as a result pore nucleation is created. These pores cause the significant expansion of polymeric volume and decrease in polymeric density. A 3D scaffold is formed after completion of foaming process. The gas-foaming scaffold fabrication techniques do not require the utilization of organic solvent and high temperature.

In vivo and in vitro application of nanofibers

Nanofibers are widely used in in vitro and in vivo application. In a study that was conducted by Zong et al. (2015), nanofibers have been used as drug delivery systems to cancer cells. In this study (Zong et al. 2015), cisplatin loaded on nanofibers poly(ethylene oxide)/polylactide and its effect on cervical cancer cells examined. The experimental results showed that the antitumor effect and safety are in balance and this nanofibers are a good candidate for in vivo drug release in cancer cells (Zong et al. 2015). Another study on the use of nanofibers in bone conductivity investigated. The study was conducted by Ardeshirylajimi et al. (2015) prepared nanofibers and coated with bioactive glass.They in vitro studies were performed on MG-63 cells and results showed that nanofibers polyethersulfone coated with bioactive glass increases bone growth markers and the scaffolds is biocompatible with the media (Ardeshirylajimi et al. 2015). Damaged nerve regeneration is important for nerve function. In a study conducted by Su and Shih (2015) prepared polycaprolactone nanofiber with or without carbon nanotubes by electrospinning method. Studies for the growth and differentiation of nerve were performed on PC12 cell line by electric stimulation. The results showed that when carbon nanotubes are used in the scaffold structure differentiation of nerve cells in the scaffold increases. It can be concluded that carbon nanotubes because of their high electrical conductivity led to the rapid growth of nerve cells in the scaffold (Su and Shih 2015). These are just a sample of in vivo and in vitro studies was nanofibers. These studies can be understood that nanofibers due to mimic the extracellular matrix can be a good candidate for the reconstruction of damaged tissue in medical applications.

Conclusion

In brief, the main goal of tissue engineering is to repair damaged tissues. In this regard, we need some physical structures with possibility cell attachment, cell migration, cell culture, cell differentiation and finally to be replaced in tissues. These structures are produced by biodegradable polymers that play external matrix role in bioengineering. Different methods are used to make scaffolds, such as solvent casting, gas foaming, freeze drying, and electrospinning. Electrospinning is the most common method due to resulting in nanofibers in different sizes.

Funding information

This work is funded by a 2015 grant Drug Applied Research Center, Tabriz University of Medical Sciences.

Disclosure statement

The authors report no declaration of interest. The authors alone are responsible for the content and writing of the article.