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Synthetic and natural polymers (biopolymers) are commonly used in tissue engineering because of valuable properties eg. biocompatibility, biodegradability, good mechanical properties etc. For this reasons, a lot of current research studies for medicine is focused on this group of materials. Polymers, give the great opportunity to fulfill one of the main assumption of regenerative medicine and tissue engineering, which is formation of wholsome tissue in in vivo conditions.
Recent years polymers have become the most used and investigated materials for applications in medicine. In the case of tissue engineering the most important features of polymers are ability to be easily reproduced, their versatility, tuneable properties and biodegradability. Biomedical polymers can be divided into two main groups: naturally-occuring polymers and synthetic polymers.
Among natural polymers we can distinguish: proteins (e.g. silk, collagen, fibrin), polysaccharides (e.g. alginate, hyaluronic acid, chitosan) and polynucleotides (e.g. DNA, RNA). Proteins and polysaccharides are very often used in tissue engineering. The most common natural polymers are presented below.
Collagen is ECM protein. We know 27 types of collagen, wherein type I collagen is the most abundant. It is fibrillar, rod-shaped molecule, which can be found for example in tendon, ligament, bone, skin and cornea. Collagen fibers are the tissue structural framework and are responsible for suitable tensile strength. Great importance of collagen in tissue structure causes that this polymer is very often used as material for tissue engineering scaffolds.
Figure 1. Aligned (A) and randomly oriented (B) nanometer scaffolds.
Silks are proteins produced in fiber form by silkworms and spiders. They are generally composed of β-sheet structures. These structures allow to tight packing of stacked sheets of hydrogen bonded chains. The assembly of silk and the strength and resiliency of silk fibers are the result of large hydrophobic domains interspaced with smaller hydrophilic domains. Silks are used as biomaterials because of their biocompatibility, controlled proteolytic biodegradability, impressive mechanical properties, morphologic flexibility and the ability to immobilize growth factor.
Fibrin is a fibrous protein involved in the clotting of blood. It is formed by polymerization process with the action of thrombin and activated factor XIII, which convert fibrinogen into fibrin. Cross-linking is one method in which diverse microstructural and mechanical properties of fibrin networks can be achieved. What is interesting, by using fibrin made from a patient’s own blood, autologous scaffolds can be manufactured. The fibrin disadvantages are morphological deconfiguration and rapid degradation in physiological conditions, and thus combinations of fibrin with strength enhancers such as PCL/polyurethane, hyaluronic acid and PLGA are used.
Hyaluronic acid (HA) is a natural linear glycosaminoglycan, co-polymer of D-glucuronic acid and N-acetyl-D-glucosamine. Hyaluronic acid is present in connective, epithelial and neural tissue and synovial fluid. What important, HA is biocompatible, biodegradable and has important tissue healing properties, such as induction of angiogenesis, and the promotion of cell migration, adhesion, and proliferation. It has been suggested that this polymer display also anti-inflammatory and bacteriostatic action.
Alginates are a low-cost marine materials extracted from the cell walls of brown seaweed. Alginates are salts of alginic acid. Naturally, alginates occur as calcium, magnesium and sodium salts. The very important feature of alginates is that they can form hydrogel thanks to ion-crosslinking, for example Ca2+-crosslinking. Chemically, alginates are linear copolymers containing blocks of (1,4)-linked β-D-mannuronate (M) and α-L-guluronate (G) residues. The M/G ratio, G-block length and molecular weight affect the physical and mechanical properties of alginate and resultant hydrogel.
Chitosan is cationic polysaccharide obtained from deacetylation of chitin built from (beta-1,4-linked N-acetylglucosamine units. Deacetylation is used due to insolubility of chitin in common solvents and difficult processing. Degree of the deacetylation has impact on crystallinity and molecular weight of the chitosan. This cationic polymer can form electrostatic interactions with negatively charged cell surfaces and also display antimicrobial activity. Thanks to ability of chitosan to interact with glycosaminoglycans (GAGs) scaffolds based on chitosan can have a direct impact on the modulation of cytokines and growth factors and thus local tissue regeneration.
Synthetic polymers are also common used in tissue engineering. They are much more reproducible and have better mechanical properties in comparison to natural polymers. Examples of the most frequently studied synthetic biomedical polymers are presented below.
Poly(caprolactone) (PCL) is thesemi-crystalline aliphatic polyester. Properties such as great organic solvent solubility, a melting temperature of about 55–60∘C and glass transition temperature of −54∘C causes that this polymer is common used as tissue regeneration support structures. Due to relatively long degradation profile PCL is suitable for use in tissues with longer regeneration process.
Figure 2.Electrospun nanofibrous membrane made from PCL and collagen.
Poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and their copolymer poly(lactic-co-glycolic acid) (PLGA) are also polyesters. Furthermore, these polymers are poly(caprolactone) (PCL) is thesemi-crystalline aliphatic polyester. Properties such as great organic solvent solubility, a melting temperature of about 55–60∘C and glass transition temperature of −54∘C causes that this polymer is common used as tissue regeneration support structures. Due to relatively long degradation profile PCL is suitable for use in tissues with longer regeneration process.
Poly(lactic acid) (PLA), poly(glycolic acid) (PGA) and their copolymer poly(lactic-co-glycolic acid) (PLGA) are also polyesters. Furthermore, these polymers are poly(hydroxy acids). Hydrolysis of the ester bonds in the backbone of their chains causes breaking down of PLA, PGA and PLGA to their monomeric units - lactic acid and glycolic acid respectively. These breakdown products can be then simply cleared by natural metabolic pathways.
Poly(ethylene glycol) (PEG) is polyether. Its polymerization involves ethylene oxide condensation. Chains of PEG which are greater than 10 kDa are defined as poly(ethylene oxide) (PEO). Molecular weight, cross-linking and polymer concentration affect mechanical properties of PEG scaffolds in tissue engineering. These polymers are biocompatible, biodegradable, non-toxic, low-immunogenic. Despite the lack of natural ability of PEG
to binding proteins or cells, cell adhesion is possible thanks to incorporation of RGD peptides.
Poly(urethanes) are traditionally and most commonly formed by reacting a di- or polyisocyanate with a polyol. Therefore fundamental constituents of polyurethanes are: hard segment - diisocyanate, the soft segment - polyethers or polyesters and chain extenders. Properties of resultant polyurethane depend on the ratios of these components. Due to unfavorable degradation profiles combinations of polyurethanes with other biomaterials are made to improve degradation rate of polyurethane-based scaffolds.