Alginate has been used for skin regeneration for several years (Barbu, 2021). Alginate is a linear anionic polymer consisting of mannuronic acid (M blocks) and guluronic acid (G blocks) units. Alginate can be obtained from some bacteria, brown algae and kelp (ref). Alginate is a versatile polymer, that can form hydrogels and its mechanical properties can be easily adapted by the type and concentration of a cross-linker (ter Horst et al., 2019), (Augst et al., 2006). Alginate has several advantageous properties, such as biocompatibility, biodegradability, low-immunogenicity, simple gelation, ability to control its degradation, and relatively low cost (Suamte et al., 2023), (ter Horst et al., 2019), (Ceccaldi et al., 2017). When this polymer has a higher ratio of G blocks it is easier to process and it seems to have lower immunogenicity (ter Horst et al., 2019), (Aravamudhan et al., 2014). This polymer also has antiseptic properties, low toxicity, conformability, good water absorption and optimal water vapor transmission rate, which are some of the main characteristics required for wound dressings (Suamte et al., 2023), (Barnett and Varley, 1987). Given its beneficial properties, alginate can also be used in the creation of scaffolds for tissue engineering. Indeed, scaffolds consisting of alginate microspheres, alginate-chitosan, chito-oligosaccharides (COS) with collagen (alginate–chitosan–COS–collagen) and a combination of alginate, chitosan and COS (alginate–chitosan–COS) have been applied as a skin substitute, revealing improved biocompatibility and replicating the skin microenvironment (Suamte et al., 2023), (Chandika et al., 2015). Mobaraki et al. (2021) developed a drug delivery scaffold by conjugating alginate and collagen and incorporated curcumin nanoparticles to enhance wound healing properties. The results showed that wound healing increased by over 90% within 14 days. This study also demonstrated the ability of an alginate/collagen scaffold to incorporate curcumin nanoparticles and consequently improve skin healing. Gao et al. (2022) developed an innovative 3D culture system using an alginate microsphere-collagen hydrogel, which demonstrated the ability to enhance human umbilical cord mesenchymal stem cell survival, allowing their sustained release to boost wound healing.

Cellulose is an abundant polymer in nature and can be obtained from plants (vascular plants or algae) and bacteria (Acetobacter xylinum) (ter Horst et al., 2019). This polymer offers a stable matrix necessary for tissue engineering purposes and is available in diverse forms with exceptional biocompatibility, as is the case of viscose cellulose sponge (Suamte et al., 2023), (Märtson et al., 1998).

Bacterial cellulose has an interesting feature, a porous structure similar to skin. It is a highly hydrophilic material, which is a very important feature for a wound dressing, as a wound requires a moist environment (Kucińska-Lipka et al., 2015). Diaz-Gomez et al. (2022) developed a 3D printed carboxymethyl cellulose scaffold loaded with platelet rich plasma for the treatment of diabetic wounds. This scaffold revealed a sustained release of growth factors and boosted angiogenesis, granulation, and re-epithelialization in skin defects, highlighting its suitability to act as an active dressing for patients with diabetes (Diaz-Gomez et al., 2022). Cellulose can also be associated with different components to further enhance its effect, as demonstrated by Alavi and Nokhodchi (2020). The authors combined cellulose with zinc oxide nanoparticles and reported that this combination improves the mechanical and anti-bacterial properties of the wound dressing. Additionally, Madub et al. (2021) reported the possibility to prepare a nanofibrous scaffold using ulvan cellulose. Using an in vitro assay with fibroblast cells, the study demonstrated that the scaffold enhanced cell growth and accelerated angiogenesis without foreign body response in an in vitro biocompatibility test. Xu et al. (2022) prepared a chitosan-cellulose hydrogel dressing integrating microspheres for wound healing. This hydrogel exhibited good drug release performance, improved antibacterial activity, and had the ability to support the survival and proliferation of human adipose-derived stem cells. The main limitation of this natural polymer is the high cost associated with its purification process.

Chitosan is a polysaccharide obtained from the deacetylation of chitin. Chitin is the structural element crustaceans or fungi exoskeleton (ter Horst et al., 2019), (Ahmadi et al., 2015). The main limitation of chitosan/chitin is its poor stability. As it is a weak base, chitosan/chitin is soluble in an acidic solution, but is not soluble in a neutral solution (ter Horst et al., 2019). This polymer has several beneficial properties, such as homeostasis, mucoadhesion, hydrophilicity and non-toxicity. Its similarity to the ECM structure improves cell adhesion and proliferation, making chitosan/chitin an auspicious candidate for tissue engineering applications (Suamte et al., 2023), (Amado et al., 2008). Indeed, studies have shown that chitosan can improve the function of inflammatory cells during wound healing (Feng et al., 2021). Moreover, it has been reported that a chitosan coating enhances the biocompatibility and hydrophilicity of different biomaterials (Kweon et al., 2003), (Shalumon et al., 2011). Fujita et al. (2004) developed a chitosan hydrogel cross-linked by UV light irradiation that revealed resistance against Escherichia coli growth. Dacron grafts combined with this chitosan hydrogel demonstrated antibacterial activity with considerable local infection inhibition. A study with diabetic rats demonstrated that a chitosan/collagen scaffold fused with Thymosin beta-4 (TB4) presented a sustained release of TB4 leading to faster proliferation and migration of glucose-treated human umbilical vein endothelial cells with heightened angiogenesis (Ti et al., 2014). Rezaii et al. also prepared a chitosan-collagen scaffold with the incorporation of curcumin nanoparticles. This scaffold led to the successful healing of full-thickness punch wounds on a Wistar rat model (Rezaii et al., 2019). The developed scaffold revealed an excellent wound-healing potential since it allowed new blood vessel formation and increased collagen production. Additionally it led to changes at the wound site regarding the granulation tissue density and epidermis thickness (Rezaii et al., 2019). A porous 3D scaffold composed of chitosan hydrochloride, collagen, carboxymethyl cellulose and β-glycerophosphate presented water absorption capacity and sustained released of rosuvastatin. Maged et al. also reported that the loading of mesenchymal stem cells into the scaffold further enhanced fibroblast proliferation and skin regeneration in a wound-healing model of Albino rats (Maged et al., 2019). Vakilian et al. (2021) produced a three-layered scaffold based on chitosan and alginate, which demonstrated excellent biocompatibility and the capacity to promote tissue regeneration.

Dextran is a hydrophilic natural polysaccharide with linear chains containing α-1,6 linked D-glucopyranose residues produced by several strains of bacteria. This polymer contains a large number of hydroxyl groups that can be easily conjugated to drugs and proteins by either direct attachment or through a linker, and its degradation occurs via phagocytosis (Suamte et al., 2023), (Mehvar, 2000). These polymer properties are described in Figure 2. Dextran-derived hydrogels can be prepared by chemical or physical cross-linking or even by radical polymerization (ter Horst et al., 2019). These hydrogels have restricted cell adhesivity and do not appear to influence cell viability, so they are normally used for drug delivery. In addition, dextran has a slow degradation rate, which limits its application for wound healing (ter Horst et al., 2019). Researchers have tried to alter dextran hydrogels properties to enhance cell adhesion (Massia and Stark, 2001) and improve biocompatibility (Sun et al., 2010). For that Möller et al. (2007) modified a dextran degradation profile by treating dextran with glycidyl methacrylate to improve its functionality as a tissue engineered scaffold for burn wound healing (Sun et al., 2011). Sun et al. (2011) developed an acellular dextran hydrogel and studied its application in full thickness burns using a mice model. This study revealed that the prepared hydrogel stimulates angiogenesis and skin regeneration. Shen et al. (2015) reported similar results in a full thickness porcine model, demonstrating an additional improvement in dermal reconstruction and reinnervation. Furthermore, Park et al. (2014) evidenced the capacity of a hypoxia-inducible dextran hydrogel to promote neovascularization. Regarding cell delivery to wounds, Voigt et al. (1999) seeded keratinocytes into collagen-coated dextran microspheres. These microspheres were transplanted as micrograft’s to full thickness wounds in an athymic nude mouse model, revealing the reconstitution of the epithelium, which was multi-layered and keratinized within 14 days. Yang et al. (2022) fabricated a multifunctional hydrogel created through polylysine-graft-cysteine/oxidized dextran for supporting skin tissue regeneration. This hydrogel exhibited not only good antibacterial and free radical scavenging capacity, but also a better efficacy for promoting wound repair than commercial dressing.

Hyaluronic acid is a non-sulfated glycosaminoglycan consisting of repeating polymeric disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine linked by a glucuronidic β (1→3) bond (Weissmann and Meyer, 1954). It is an anionic, linear polymer that exists in all living organisms and can be found in connective tissue particularly in the dermis of the skin (ter Horst et al., 2019). This polymer has several beneficial properties that are described in Figure 3. Hyaluronic acid plays important roles in cell growth and differentiation, and it facilitates early inflammation, which is essential for wound healing (Suamte et al., 2023), (Chen et al., 2002). However, its main limitation is due to its rapid enzymatic degradation in physiological media (Negut et al., 2020). Due to its properties, easy preparation and modification, hydrophilicity, biodegradability and non-adhesiveness, this polymer is normally used for the development of cosmetic products, as well as, tissue scaffolds (Suamte et al., 2023), (Gravante et al., 2007). In addition, hyaluronic acid has physical and biochemical features either in solution or hydrogel form that improves body repair (Collins and Birkinshaw, 2013). Su et al. developed a decellularized scaffold of hyaluronic acid loaded with epidermal growth factor, which exhibited good healing rates (over 87%) on wounds with thick epidermis and skin appendage formation (Su et al., 2014). A study conducted by Sanad and co-workers demonstrated the potential of a novel chitosan–hyaluronic acid composite sponge scaffold enriched with andrographolide lipid nanocarriers for use in wound treatment. Indeed, it has been demonstrated by in vivo evaluation using a rat model that the developed scaffold heightened wound healing with no scar formation and improved tissue quality (Sanad and Abdel-Bar, 2017). Chang et al. developed an enzyme-crosslinked hyaluronic acid-tyramine hydrogel loaded with antioxidant and photothermal silver nanoparticles to be used as a functional wound dressing. This nanocomposite hydrogel has good antibacterial and antioxidant properties, decreases inflammation, supports angiogenesis, and accelerates the healing process. This study demonstrates the great potential of the developed hydrogel for the treatment of infected skin wounds (Chang et al., 2022).

Starch is a storage polysaccharide that has interesting properties, such as biodegradability, non-cytotoxicity, and renewability (MORRISON et al., 1990). Starch is also easily modified by chemical procedures opening the door to its use for drug delivery and tissue engineering. Indeed, Ngoenkam et al. (2010) developed an injectable starch-chitosan hydrogel for the delivery of chondrocytes. Starch can be easily blended with other polymers due to its non-ionic nature. It can increase pore size and water uptake of the resulting polymer blend, as demonstrated in this study. Sundaram et al. also reported excellent mechanical properties with increased porosity (82.51%) of a gelatine-starch scaffold making it suitable for cell growth, vascularization and cellular interaction (Sundaram et al., 2008). Starch-based scaffolds have a good biodegradation rate and can act as a substrate for cell adhesion (Roslan et al., 2016). The potential for these scaffolds in wound healing applications has been highlighted by Waghmare et al. (2018) who showed an increase in mouse fibroblast cells (L929), growth and proliferation with low toxicity. Salehi et al. (2017) prepared starch-based nanocomposite hydrogel scaffolds with zeolite nanoparticles and chamomile extracts for the treatment of chronic ulcers. They demonstrated the successful healing of the refractory ulcers without any hypersensitivity reaction towards the scaffold. Chhabra et al. (2020) reported the development of starch-gelatine scaffolds for wound healing applications. This study revealed the ability of the scaffold to accelerate wound closure and promote tissue reorganization and remodelling.

Agar is a polymer with high biocompatibility and non-immunogenicity (Zarrintaj et al., 2018), which can form a gel that mimics ECM physical characteristics of the tissue with the ability to transport cell growth factors to injured tissues and organs (Lewitus et al., 2011). Nayak and Gupta (2015) demonstrated that a binary blend of agar with keratin is non-toxic and allows cell growth, which makes it appropriate to be used in wound healing and skin regeneration. Furthermore, it has been confirmed that a novel squalene loaded agar-based emulgel scaffold can accelerate the healing of burn wounds by significantly contracting the wound area with high re-vascularization and macrophage polarization (Shanmugarajan et al., 2020). Eivazzadeh-Keihan et al. (2021) developed a nanobiocomposite scaffold based on cross-linked lignin-agarose hydrogel, extracted silk fibroin solution, and zinc chromite nanoparticles for wound healing applications. This study revealed that mice wounds treated with this nanobiocomposite were almost completely healed in 5 days. Basha et al. (2020) synthesized fumaric acid and incorporated it into an agar-silver hydrogel to tackle wound healing. This hydrogel showed a synergistic antibacterial effect against microbes, a quicker rate of wound healing, and augmented collagen deposition and angiogenesis.

Silk is a natural fibrous protein acquired from the larvae of Lepidoptera, consisting of two key proteins: a fibrous protein and sericin which is soluble in water (Suamte et al., 2023), (Reddy et al., 2021). This biopolymer has several beneficial properties such as low weight, high strength, excellent elasticity and durability; and it can be used as a coating material or support for the development of biocompatible scaffolds (Choi et al., 2018). Wang et al. (2021) developed a bioactive scaffold composed of hyaluronic acid and natural silk fibroin nanofiber, which has a similar chemical and biophysical composition, as well as, a similar nanostructure to the ECM. This study revealed the cytocompatibility of the scaffold with cell proliferation and differentiation. The presence of this material increased wound healing with collagen assembly and inhibited scar formation. Babu et al. (2018) conducted a study involving the use of silk fibroin with silver oxide nanoparticles to evaluate their synergistic effect on wound healing. The developed biomaterial revealed a noteworthy antibacterial activity against pathogenic and non-pathogenic bacteria and demonstrated through an in vitro scratch assay that the T3T fibroblast cells quickly migrated to the scratch area with complete coverage of the area upon 24 h. This study also confirmed the biocompatibility of the scaffold through a cytotoxicity assay highlighting its potential for wound healing applications (Babu et al., 2018). Xie et al. (2022) developed an allantoin-functionalized silk fibroin-sodium alginate composite scaffold for the treatment of cutaneous wounds. The scaffolds revealed excellent biocompatibility and enabled the wound healing process by boosting collagen deposition, re-epithelialization, and vascularization at the wound site.

Fibrin is an insoluble protein, formed by the cleavage of soluble fibrinogen by the proteolytic thrombin, which is activated upon tissue injury. Given the ability of fibrin to act as a blood clotting agent, it is natural that it forms a fibrous mesh (ter Horst et al., 2019). This polymer has been widely studied for wound healing applications (ter Horst et al., 2019). Fibrin-based scaffolds have demonstrated that they let binding of a series of active biological molecules to themselves which in turn enables specified cell matrix relations and augments tissue regeneration (Suamte et al., 2023). These scaffolds offer the required time for the development of neo matrix with a gradual reassimilation through proteases (Bencherif et al., 2017). Fibrin can also be used in combination with distinct polymers, as a biological scaffold, with potential biomaterial for the regeneration of primary cells, skin, and bones (Ahmed et al., 2008). The use of this polymer in the design of scaffolds, may not be ideal, as fibrin can be rapidly degraded (SAKIYAMA et al., 1999). Bastidas et al. (2020) prepared a fibrin-based scaffold composed of poly (lactic-co-glycolic acid) (PLGA) by electrospinning. They evaluated its potential to be used as a skin substitute, and results demonstrated that this scaffold presents blood compatibility and incorporation of fibrin improved cell adhesion and viability. Furthermore, the effect of an injectable fibrin scaffold loaded with growth factors for the repair of full thickness skin defects was assessed (Shao et al., 2021). Shao et al. (2021) showed that this scaffold, which has a fine network of platelets and white blood cells, allowed a sustained release of growth hormones, facilitating the cellular proliferation, revascularization and deposition of collagen. These results highlighted the potential of the scaffold to promote skin repair. Mirhaj et al. (2022) fabricated a polycaprolactone/keratin/platelet-rich fibrin fibrous scaffold by electrospinning and demonstrated its angiogenic potential, as well as its ability to accelerate wound healing, collagen deposition and formation of skin appendages.

Collagen is the most abundant protein in the human body and the major component of the extracellular matrix (Sherman et al., 2015). It is the main structural protein in the dermis, having an important role in wound healing. Thereby, collagen has been employed in the development of several skin scaffolds (Chattopadhyay and Raines, 2014). Collagen type I is the most used in skin scaffolds, since it is the most abundant protein in native dermal tissue (ter Horst et al., 2019). This polymer can easily be blended with other polymers such as chitosan, hyaluronic acid, and chondroitin sulfate to obtain improved biological and mechanical features (Matsiko et al., 2012). The properties of the scaffolds can be modulated by varying the concentration of collagen (Wozney et al., 1988). Collagen presents excellent properties, such as biocompatibility, low antigenicity, and high mechanical strength, and it facilitates cell binding, proliferation, differentiation, and production of ECM (Figure 4), which make it suitable for wound healing applications (Reis et al., 2008). Natarajan and co-workers developed tannic acid cross-linked collagen scaffold using a casting technique and evaluated its effects on wound healing (Natarajan et al., 2013). The study included an in vivo test using excision wound model rats, demonstrating improved healing rates, and an efficient wound closure. This new biomaterial also revealed the potential for controlled drug release. Indeed, Tezgel et al. (2020) loaded nanostructured lipid carriers and siRNA complexes in collagen scaffolds and coated them with a 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) shell. This study showed a prolonged release of siRNA with good transfection efficiency and a prolonged downregulation of ERK-1 protein for 7 days. These results confirmed that the developed collagen scaffolds are promising materials to be applied into wounds to promote healing through controlling the expression of proteins involved in this complex process (Tezgel et al., 2020). Kumar Reddy Sanapalli et al. (2022) developed an L-Glutamic acid loaded collagen/chitosan composite scaffold for the faster healing of diabetic wounds. The scaffolds have not exhibited any toxicity and showed higher rates of wound contraction, having also a modulatory effect on the inflammatory biomarker MMP-9.

Fibronectin is a high molecular weight glycoprotein obtained from human and bovine plasma that can be used as a scaffold to assist cell adherence and migration, thus regulating cell proliferation and differentiation (Suamte et al., 2023), (Pankov and Yamada, 2002). Chantre et al. (2018) produced scaffolds based on fibronectin nanofibers for wound healing applications. The obtained results revealed that this scaffold has the ability to accelerate wound closure, as well as, to increase tissue restoration and recovery of dermal and epidermal constructs including adipose tissue and skin appendages. Jara et al. (2020) synthesized a novel fibrin matrix composed of fibronectin and plasma fibrinogen combined with fibrin nanofibers with fibronectin nanoclusters. These nanoclusters stimulated the pro-healing cells such as endothelial cells, fibroblasts and keratinocytes and promoted their migration, survival, proliferation and function, resulting in quicker and improved wound healing.

Elastin is another ECM protein that is hydrophobic and insoluble in nature. This polymer can be used in the development of biomaterials in its different forms: hydrolyzed soluble elastin, insoluble elastin fibres, recombinant tropoelastin, block copolymers of elastin, repeats of synthetic peptide sequences and in combination with other polymers (Suamte et al., 2023), (Daamen et al., 2007). Boekema et al. (2014) developed a novel collagen-elastin scaffold to be used as a dermal replacement for treating full-thickness skin defects such as burn wounds. Furthermore, a study reported that a triple-polymer scaffold made of a collagen-elastin-polycaprolactone composite was developed (Chong et al., 2019). The inclusion of elastin was revealed to decrease the stiffness of the scaffold, while also decreasing hysteresis and increasing elasticity. Additionally, the developed scaffold promoted keratinocyte and fibroblast proliferation, tissue integration and accelerated early-stage angiogenesis. Thus, this study revealed the potential use of the triple-polymer scaffold in supporting full growth with tissue regeneration in a severe burn injury (Chong et al., 2019).

Keratin is a fibrous protein present in skin, nails and hair. It has interesting properties, like good biocompatibility and the ability to form self-organized structures that synchronize cellular recognition and behavior (Bragulla and Homberger, 2009), (Rouse and Van Dyke, 2010). Moreover, wool keratin has shown its ability to promote cell adhesion, due to the presence of the cell adhesion sequences, arginine-glycine-aspartic acid and leucine-aspartic acid-valine (Tachibana et al., 2002). Xu et al. (2013) prepared a human hair keratin scaffold by freeze-dying and demonstrated its ability for subcutaneous implantation and for treating full-thickness skin defects in rats. Indeed, this study confirmed the potential of keratin for skin regeneration since the scaffold provided a more rapid vascularization, thicker epidermis, lower contractions and formation of new hair follicles. A study involving the preparation of a porous keratin/chitosan scaffold by lyophilization revealed enhanced antibacterial activity and cell proliferation rates, highlighting its promising use for wound dressings (TAN et al., 2015). The development of an in situ forming keratin hydrogel and its application as a drug depot for wound repair revealed that the deferoxamine-loaded scaffold accelerated healing in the full-thickness wounds of streptozotocin-induced diabetic rats by raising angiogenesis and neovascularization in wounds (Chen et al., 2021).

Gelatine is a natural polymer obtained from collagen and it has beneficial features such as low antigenicity, biocompatibility and biodegradability making it suitable for medicinal and pharmaceutical applications (Young et al., 2005). This polymer has acidic and basic groups giving it a high flexibility in terms of its structure in comparison to other polymers. Gelatine can be processed in several forms, for example as injectable hydrogels, sponges and microspheres, given its gelation abilities and ease of processibility (Malafaya et al., 2007). Moreover, other peptides and cell adhesion molecules can be incorporated into gelatine for its use in distinct tissue engineering approaches (Ito et al., 2003). Ninan and co-workers developed porous gelatine/zeolite scaffolds by freeze drying, revealing their cytocompatibility and antibacterial activity, as well as, their ability to improve wound healing in Sprague Dawley rats (Ninan et al., 2014). A study described the development of a gelatine-based scaffold combined with alginate hollow fibers, to attain a vascular network for nutrients and oxygen supply for embedded cells. In this study, human umbilical vein endothelial cells were embedded into the scaffolds and the network formed by the hollow fibers supplied the oxygen and required nutrients and aided the waste removal (Li et al., 2020). Sadeghi et al. (2023) developed a gelatine/alginate sulfate hybrid scaffold as a dermal substitute to hasten the healing of full-thickness diabetic ulcers in a diabetic mouse model. The scaffolds revealed no cytotoxicity, as well as, an increase in cell growth. This increase was related to the increase in the alginate sulfate content. Additionally, this study confirmed the potential of hybrid scaffolds to act as dermal substitutes, as they lead to the formation of an epidermal layer with a homogeneous distribution of collagenous tissue and low penetration of immune cells.

Polydimethylsiloxane (PDMS) is a part of the siloxane (silicone) family and is the most commonly silicone elastomer used (Kohli et al., 2019). This polymer has several properties, including its inertia, compatibility with blood, low toxicity, low glass transition temperature, among others (Figure 5) (Akhtar et al., 2016), (Polmanteer, 1988). Given its beneficial features, PDMS is used in several applications, like in cardiac pacemaker leads, artificial skin, contact lenses, medical adhesives, finger joints, catheters and drug delivery systems (Akhtar et al., 2016)– (Leeper and Wright, 1983). Regarding the tissue engineering field, Nikpour and co-workers developed a curcumin-loaded Fe(II) metal–organic framework/polydimethylsiloxane sponge that showed its ability to enhance healing and revascularization, highlighting its potential to be used as a 3D porous substrate for tissue engineering and regenerative medicine (Nikpour et al., 2022).

Polyvinyl Alcohol (PVA) is a water-soluble polymer with a repeating hydroxyl group in its backbone (Kohli et al., 2019). This polymer has desirable features such as biodegradability, biocompatibility, and non-toxicity which make them suitable to be used in several biomedical applications (Allen et al., 2004). PVA is frequently used in conjugation with other polymers, such as chitosan and polyhydroxy butyrate, for the production of nanofibers that can be used in tissue engineering applications (e.g., wound healing) (Rahmani Del Bakhshayesh et al., 2018). Ahlawat et al. (2019) developed Carica papaya-loaded PVA/Gelatine nanofibers for wound dressing application. This study revealed that the fabricated material provided a moist environment at the wound site, allowing re-epithelialization. In addition, the cytotoxicity assay performed on NIH 3T3 fibroblast cells demonstrated that the nanofibers have good compatibility with no cytotoxic effects. It is also worth noting the excellent antibacterial activity of the material against gram-positive and gram-negative bacteria, evidencing the promising use of these nanofibers in wound healing applications. Rajora and colleagues prepared a nanofiber mat of neem gum polysaccharide with PVA using an electrospinning technique (Rajora and Bal, 2022). This nanofiber showed hemocompatibility, as well as, biodegradability having antimicrobial activity against Escherichia coli and Staphylococcus aureus. Furthermore, this study revealed that the prepared device speed up wound healing in mice with dense collagen and fibroblasts highlighting.

Poly-N-vinylpyrrolidone (PVP) is a biocompatible, water-soluble, and biodegradable polymer extensively used as a hydrogel membrane for skin alternative products, since it is no irritating to the skin (Kamoun et al., 2017). PVP also has other beneficial features, such as its environmental stability, low cytotoxicity, high chemical and thermal resistance, affinity to complex hydrophilic and hydrophobic substances and very good solubility in organic solvents (Negut et al., 2020). Moreover, the treatment of PVP through coating methods and copolymers combination gives it a variety of features (e.g., prevention of microbial penetration) useful for wound healing applications (Kohli et al., 2019). A study reported the development of a phlorizin-loaded silk protein/PVP composite nanofibrous membrane to be used as a wound dressing. The study demonstrated its ability to promote collagen deposition and angiogenesis in the wound site, as well as, its capacity to increase autophagy, accelerating wound repair (Sun et al., 2022). Zhang and co-workers prepared a chitosan, PVP, and dihydroquercetin nanofiber film to be used as wound excipients. The fibre film showed antioxidant and antibacterial activity, acceleration of the healing process and promotion of wound healing by inducing the autophagy pathway. The cytotoxicity assay performed on keratinocytes (HaCat cells) proved that the film is non-toxic (Zhang et al., 2022).

Polyurethane (PU) has versatile features such as toughness, durability, biocompatibility, and degradation rates which can be customized depending on the application (Zhang et al., 2016). PU can be employed in several combinations such as with olive oil to obtain antioxidant properties and a photoprotective mechanism or combined with propolis to enhance antibacterial activity and mechanical strength (Amna et al., 2014), (Kim et al., 2014). The combination of PU with dextran fibres through electrospinning revealed good angiogenesis activity alongside high anti-inflammatory action leading to the acceleration of cutaneous wound healing (Unnithan et al., 2015). A study, in which a nanocomposite PU/polycaprolactone scaffold with graphene oxide was developed through electrospinning, revealed great biocompatibility in contact with skin fibroblast cells and improved hydrophilicity (Sadeghianmaryan et al., 2020). Jaganathan et al. fabricated an electrospun PU scaffold loaded with nanofibers of zinc nitrate and evaluated its use as a wound dressing material (Jaganathan and Mani, 2019). The cytocompatibility and hemolytic study demonstrated a lower hemolytic index with increased fibroblasts proliferation. The developed material also exhibited enhanced physiochemical properties. Therefore, this material seems to be a good alternative for wound dressing materials. A PU cellulose acetate electrospun fibbers loaded with rosemary essential oil and adsorbed silver nanoparticles exhibited antibacterial activity and improved hydrophilicity of the fibbers, leading to a better attachment of cells to the micro-nanofibers, similar to the natural ECM (Rather et al., 2023).

Polylactic acid (PLA) is a biodegradable polyester obtained from renewable sources, like corn, starch, or sugar cane (Kohli et al., 2019), (Avinc and Khoddami, 2009). This polymer has several characteristics: inexpensive, non-toxic, hydrophobic, structurally stable, and excellent biocompatibility and mechanical integrity making it suitable for medical applications. PLA is an aliphatic polyester of naturally occurring lactic acid, thus, its degradation by enzymes or hydrolysis under physiological conditions originate products that are easily absorbed by the body (Avinc and Khoddami, 2009; Ulery et al., 2011; Sin et al., 2013; Yoon et al., 2017). Regarding tissue engineering applications, a novel dressing scaffold composed of Polyvinylpyrrolidone/PLA-Polyethylene oxide fibers with encapsulated collagen and cefazolin was evaluated as a wound healing material. Different scaffolds were prepared by varying the collagen concentration (10%, 20%, and 40% w/w based on PVP). The study showed that the scaffold adhesion rises with collagen increase boosting the healing effect. Moreover, the fabricated material exhibited antimicrobial activity and in vivo histological tests revealed that 10% and 20% collagen doses had the highest healing rate (Hajikhani et al., 2021). Another study reported the encapsulation of hydroxyapatite, zirconia, and graphene oxide nanosheets in mono, di, or tri phases, into nanofibrous scaffolds of PLA. It has been demonstrated that the scaffolds exhibited enhanced antibacterial activity and promoted cell viability. In addition, human fibroblasts proliferate on its surface, as well as, in the pores of the nanofibrous scaffold (Al-Wafi et al., 2021).

Polyglycolic acid (PGA) is a biodegradable polymer that belongs to the family of linear aliphatic polyesters (Kohli et al., 2019). This polymer is biocompatible, more hydrophilic than PLA and has high tensile strength (Negut et al., 2020). However, the use of PGA in biomedical applications is limited by its rapid degradation through hydrolysis, which results in a pH decrease in its microenvironment due to carbon dioxide production, leading to local cell and tissue necrosis. Additionally, the excess glycolic acid production from PGA degradation can elicit an inflammatory response (Ceonzo et al., 2006), (Pihlajamäki et al., 2006). Sekiya and collaborators reported that fusing PGA with collagen decreased inflammation and induced neovascularization in a mouse skin defect model (Sekiya et al., 2013). The incorporation of sodium tripolyphosphate into PGA scaffolds fillers via CO₂ foaming relieved inflammation and enhanced phagocytosis in a porcine model (Zhang et al., 2020).

Poly(lactic-co-glycolic) acid (PLGA) is a biodegradable polyester copolymer manufactured from random copolymerization of PLA and PGA (Kohli et al., 2019). The main properties of this polymer are described in Figure 6 (Negut et al., 2020). Given its beneficial features, it has been extensively used for sutures, drug delivery devices, and tissue engineering scaffolds (Maitz, 2015), (Pan and Ding, 2012). The preparation of a PLGA-liposome scaffold loaded with microRNA 145 and platelet-derived growth factor promoted angiogenesis in vitro and wound healing in vivo (Hu et al., 2021). Silk sericin-PLGA scaffolds obtained by electrospinning with ketoprofen for the treatment of periodontal diseases were developed by Chachlioutaki et al. (2022). The scaffold had enhanced hydrophilicity and mechanical strength, as well as, an anti-inflammatory effect on LPS-stimulated RAW-264.7 cells. Additionally, the developed material favours attachment and proliferation of human gingival fibroblasts (Chachlioutaki et al., 2022).

Poly-ε-caprolactone (PCL) is an extremely tough aliphatic polymer with good solubility, biocompatibility, exceptional elasticity and mechanical characteristics, low melting point and low decomposition rates along with non-toxicity and cost-effectiveness (Suamte et al., 2023), (Woodruff and Hutmacher, 2010). However, the main limitation of PCL is its low bioactivity and high hydrophobicity leading to the decrease of cell affinity with minimal tissue regeneration. Aiming to minimize these limitations PCL can be combined with other polymers like PLA to form a lesser hydrophobic construct with better degradability and mechanical properties (Patrício et al., 2013). For tissue engineering applications, a bilayer nanofibrous scaffold consisting of fish collagen and PCL produced using electrospinning, with the covalent attachment of chitooligosaccharides via carbodiimide chemistry demonstrated in vitro and in vivo assays and enhanced healing process (Chandika et al., 2021). Ekambaram et al. (2022) developed a novel wheatgrass extract infused PCL/chitosan nanofibrous scaffold through electrospinning for wound infections treatment and enhanced wound healing. The material revealed cytocompatibility against vero cells and exhibited higher anti-bacterial activity than commercial anti-biotic gentamicin. Additionally, the scaffold exhibited higher affinity with binding energy of−9.6 kcal/mol towards wound the healing receptor COX-2. This fact is very important as COX-2 induction enhances faster wound healing.

Polyethylene Glycol (PEG) is a biocompatible, nonbiodegradable, bioinert and hydrophilic polymer that has optimal biological and physicochemical properties, as well as, resistance to protein adsorption (Kohli et al., 2019), (Negut et al., 2020). Given the easiness to control its architecture along with its chemical composition, this polymer is an attractive scaffold material for tissue engineering applications (Suamte et al., 2023). A study in which an exosome secreted by adipose-derived stem cell was loaded into the matrix of a metalloproteinase degradable PEG smart hydrogel promoted diabetic wound healing by improving cellular functions (Jiang et al., 2022). Jin et al. (2021) developed a hybrid hydrogel composed of chitosan and poly (D,l-lactide)-PEG-poly (D,l-lactide) that tightly adhered to the skin with good antibacterial properties and accelerated the wound healing process.