Table 1.

Properties and recent wound healing action of different polymeric biomaterials

Types	Sl. No.	Name of the polymer	Details	Properties	Recent wound healing application	Reference
Synthetic Biomaterials	1.	Polyurethane and its derivatives	• Organic homopolymer macromolecule linked together by carbamate (-O-CO-NH-) linkages • Thermosetting polymers or thermoplastic polyurethanes [18]	• Highly biocompatible and haemocompatible • High material strength and durability • Biodegradable with few exceptions • Highly elastic	A composite of polyurethane and gelatin was fabricated to act as an artificial skin scaffold for wound healing. Ciprofloxacin HCl was incorporated to avoid infection, thus promoting rapid wound healing. The electrospun scaffold was mechanically and thermally stable and pointed out to be a promising candidate for wound healing scaffold. In-vitro studies were conducted to evaluate the efficacy of the composite scaffolds.	[19]
	2.	Poly caprolactone	• Semicrystalline linear polyester • Partially crystalline • Synthesized by ring-opening polymerization of ε-caprolactone • The low melting point of ~60°C. Used in making specialized polyurethane that is resistant to water, oil, solvent and chlorine [20]	• Bio-degradable • Non-toxic • Semi-crystalline • Hydrophobic in nature • Slow degradation rate • Good elastic property	Electrospun nanofibrous scaffold composed of polycaprolactone and co-doped hydroxyapatite has been used as a material for wound healing. Aluminium/vanadate ions were incorporated for further modification. The scaffold was mechanically stable and contributed to cellular proliferation. The in vitro studies conducted using human fibroblasts indicated that the nanofibres could be a promising biomaterial for wound healing applications.	[21]
	3.	Polyvinyl alcohol	• Colourless, odourless, water-soluble synthetic polymer • Biodegradable, both in aerobic and anaerobic conditions • Synthesized using free-radical polymerization of vinyl acetate • Highly crystalline [22]	• pH-sensitive • film-forming capability • Water soluble • Bio-compatible • Hydrophilic	A very recent study showed the development of a polymeric nano-fibrous wound dressing of polyvinyl alcohol and propolis (a natural product with wound healing properties). The resulting scaffold exhibited excellent wound healing properties when tested on fibroblast cells and diabetic wounded mouse models. The scaffolds also supported tissue regeneration. The nano-scaffold turned out to be highly efficient in both in vitro and in vivo models using diabetes-induced male Swiss mice.	[23]
	4.	Silicone	• Inert synthetic compound • Colourless, oily or rubber-like polymers • Composed of siloxane. • Heat-resistant • Used in implants for tissue engineering • Soluble in non-polar solvents, including heptane, chloroform, toluene, benzene, etc. [24]	• Resistance to cold and heat • Good electrical conductivity • Good stability • Flexibility • Biocompatible	A novel multifunctional wound healing and dressing material was fabricated using poly(ε-caprolactone) quaternized silicone, outer layer and polyvinyl alcohol/collagen/quaternized chitosan, inner layer. The electrospinning technique was used for the fabrication. The membranes showed both antibacterial activity and cellular proliferation. The membranes exhibited excellent antibacterial activity, haemostatic performance, hydrophilicity, scar inhibition and wound healing properties. Experiments were conducted both in vitro and in vivo. The in vivo wound, healing and estimation of scar inhibition were evaluated using a rabbit ear full-thickness skin defect model.	[25]
	5.	Poly (lactide-co-glycolide) (PLGA)	• Co-polymer is composed of two different monomers, the cyclic dimers of glycolic acid and lactic acid • Food and Drug Administration (FDA) approved to be used in therapeutic devices • Glass transition temperature in the range of 40–60°C • Undergoes hydrolysis in the body • Soluble in solvents like chlorinated solvents, ethyl acetate tetra-hydro furan or acetone [26]	• Biocompatible • Biodegradable • FDA approved • Tuneable mechanical properties	Curcumin-loaded poly (PLGA) nanofibre membrane incorporated with growth factors (heparin) was fabricated for wound dressing as well as for the sustained release of the exogenous factor. The membrane was found to be highly biocompatible and also exhibited high tensile strength. The in vivo study showed fast wound closure, accelerated re-epithelisation rate, higher angiogenesis rate and more collagen deposition at the wound site. The nanofibrous scaffolds were tested using a streptozotocin-induced diabetic wound model in Sprague–Dawley rats.	[27]
	6.	Poly-lactic acid	• Aliphatic ester • Monomer connected with an ester bond • Naturally degradable • Used in various biomedical application • complex structures assembly like branched, star-shaped or grafted • Lacks mechanical toughness [28]	• Biocompatible • Non-toxic • Highly stable • Naturally biodegradable • Hydrophobic • Chemically inert • Tuneable mechanical property	Nanofibres consisting of polylactic acids were fabricated with the inclusion of black pepper essential oil or limonene and was coated with medium molecular weight chitosan. The fibres showed an enhanced anti-bacterial effect along with good mechanical properties. The fibres were found to be biocompatible and also promoted cellular adhesion and proliferation in vitro.	[29]
	7.	Poly ethylene glycol(PEG)	• Synthesized using low molecular weight polyether monomers derived from ethylene oxide • Repeating unit of ethylene glycol, −(O–CH2–CH2)– • Water-soluble polymer • Reported Tg and Tm are around −54°C and 74°C, respectively • Semicrystalline [30]	• Flexible • Non-toxic • Biocompatible	Injectable and degradable PEG hydrogel was synthesized using complex chemical routes with uniform pore size. The hydrogel showed superior biocompatibility with natural degrading capability. Both in vitro and in vivo results in the rat wound model showed that the injectable PEG could be considered to be a suitable candidate for wound healing applications.	[31]
Natural biomaterials	8.	Collagen	• Naturally occurring proteins are commonly found in the extracellular matrix of connective tissue • Consists of amino acids bound together to form a triple helix of elongated fibril [32]	• Biocompatible • Biodegradable • Strong • Permeable • Stable	A study showed the use of collagen and sodium alginate for the fabrication of a tissue scaffold to improve the effectiveness of stem cells in a full-thickness excision mice wound model. The scaffold was injectable, biodegradable and highly biocompatible with low immunogenicity. The scaffold loaded with human umbilical cord mesenchymal stem cells helps skin wound healing via partly inhibiting the NLRP3 pathway, hence a potential treatment for wound healing.	[33]
	9.	Chitin	• Hard naturally occurring polysaccharides, • long-chain polymer of N-acetylglucosamine [34] • Present in cell walls of fungi, the exoskeletons of arthropods, such as crustaceans and insects, the radulae of molluscs, cephalopod beaks, and the scales of fish and skin of lissamphibians [35]	• Translucent • Pliable • Resilient • Biocompatible • Biodegradable • Good tensile strength	Chitin, along with loose corn stalk and silver nanoparticles, was used to fabricate a sponge. The sponge was biocompatible and also exhibited a haemostatic effect when tested in vivo using a liver injury model of rats. The sponge also showed an excellent antibacterial effect and was also effective as a good wound closure agent when tested in vivo in male rats.	[36]
	10.	Chitosan	• Linear polysaccharide with randomly arranged • β-(1 → 4)-link • D-Glucosamine (deacetylated unit) and N-acetyl-D-glucosamine • Made from chitin shells of shrimp or dead crustaceans [37]	• Biodegradability • Non-toxic • Antifungal property • Can stimulate the immune system • Accelerates wound healing	Chitosan and nano-cellulose-based freeze-dried sponges were fabricated using EDC/NHS as a cross-linker. The sponges exhibited superior anti-bacterial efficacy owing to the inclusion of Lawson’s solution. The engineered scaffolds showed good wound healing activity as well as good haemostatic activity. The rat tail amputation model (amputation of tail caused due to wound) was used to check for the haemostatic the potential of the sample, and the rat full-thickness excisional cutaneous wound model were used to examine the wound healing assay.	[38]
	11.	Alginate	• Linearly arranged anionic biopolymer that is found in brown algae and bacteria • Consisting of α-l-guluronic acid (G) and β-d-mannuronic acid (M) residues arranged linearly in 1,4-glycosidic linkages • Biocompatible, biodegradable, low cost and readily available [39]	• Alginate is highly stable in both its solid and solution form • Water solubility • Viscous • High tensile strength • Flexible	A recent interesting study proposed the incorporation of Raphanus sativus L. Seed extracts in sodium alginate for wound healing application. The hydrogel was thermally and mechanically stable with proper angiogenic capability. The study pointed out the use of extract-loaded sodium alginate hydrogel as a potential candidate for wound healing application. The material was tested using the chick chorioallantoic membrane of fertilized chick eggs.	[40]
	12.	Gellan	• Linear, negatively charged polysaccharide. • Biodegradable and non-toxic • Poor mechanical strength • Needs blending with other naturally occurring polymers such as agar, chitosan, cellulose, sodium alginate, starch, pectin, polyaniline, pullulan, polyvinyl chloride and xanthan gum [41]	• Gellan is known for its stability, elasticity and ductility • Malleable • Biocompatible • Biodegradable • Flexibility	Recent research aimed at developing a novel bilayer wound dressing material using gellan gum and gelatin. Antibiotics were incorporated to increase the antimicrobial efficacy. The material showed good cellular proliferation when tested in vitro.	[42]
	13.	Gelatin	• Product of partial hydrolysis of collagen extracted from the skin, bones and connective tissues of animals • Gel-forming property • Translucent, colourless, flavourless [43]	• Good water-retention property • Dispersion stability • High dispersibility • Low viscosity	A composite of gelatin loaded with polysialic acid (a natural product with good wound healing properties) and crosslinked with tannic acid was constructed for wound dressing application with the ability to prevent bacterial infection. The fabricated material showed low toxicity and also exhibited a superior wound healing rate when tested using an excision wound model in rats.	[44]
	14.	Fibrin	• Natural fibres are formed when there is a healing injury in mammalian tissue. • Helps in blood clots and wound healing [45]	• Has both viscous and elastic properties • Withstands mechanical deformation • Biocompatible • Biodegradable	Liquid-type nonthermal atmospheric plasma (LTP) incorporated into a silk–fibrin composite gel was investigated for wound healing effect. The controlled release of LTP from the composite induced favorable cellular events in an irradiated wound bed. The different biological assays showed improved cellular viability and extracellular matrix deposition. In-vivo studies using full-thickness skin flap wounds on C57/BL6 mice also showed enhanced wound healing and regenerative properties.	[46]
	15.	Hyaluronic acid	• Naturally occurring chemicals are found abundantly in articular cartilage and synovial fluid • Non-protein-based glycosaminoglycan with characteristic physiochemical properties [47]	• Being one of the natural compounds of our body, it is highly biocompatible • Biodegradable • Clear/Translucent • Good fluid retention property	Combinational nanofibres consisting of hyaluronic acid/polyvinyl alcohol/polyethylene oxide blend and incorporated with ZnO NPs/cinnamon essential oil (CEO) antimicrobial combination exhibited both antimicrobial properties as well as superior wound healing. Physiochemical characterization and electron microscopy confirmed the presence of hyaluronic acid and ZnO NPs and CEO. The nanofibres inhibited the growth of Staphylococcus aureus. The in vitro and in vivo studies exhibited superior bio-compatibility and wound healing effects of the nanofibres.	[48]
	16.	Silk fibroin	• The major structural component of silk is produced by the silkworm • Composed of alternatively repeating units of hydrophobic heavy chains and hydrophilic light chains [49]	• Silk fibroin is known for its robust mechanical strength • High tensile strength • Stiff • Extensible • Flexible and malleable • Biodegradable and biocompatible	Silk fibroin-based scaffold incorporated with hyaluronic acid and natural silk fibroin nanofibres was constructed to serve as a novel scaffold for wound healing. The scaffold had high porosity (~92.5%), water-uptake ratio (~96%) and swelling ratio (~90%). The scaffold exhibited superior biocompatibility and cellular proliferation. In-vivo studies showed accelerated wound healing (up to 98.2 ± 0.5% within 4 weeks) and can also regulate collagen arrangement by nanofibres as a template to inhibit scar formation.	[50]