Site metadata: {"citation_lastpage":"256","robots":"INDEX,FOLLOW,NOARCHIVE,NOCACHE,NOODP,NOYDIR","citation_article_type":"Review article","og:image":"https://ars.els-cdn.com/content/image/1-s2.0-S2590183422X00021-cov150h.gif","citation_firstpage":"243","citation_publisher":"Elsevier","citation_title":"Design of 3D smart scaffolds using natural, synthetic and hybrid derived polymers for skin regenerative applications","citation_fulltext_world_readable":"","dc.identifier":"10.1016/j.smaim.2022.09.005","citation_volume":"4","citation_type":"JOUR","tdm-policy":"https://www.elsevier.com/tdm/tdmrep-policy.json","citation_doi":"10.1016/j.smaim.2022.09.005","favicon":"https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/103/images/favSD.ico","ogDescription":"Effective wound care is a major concern as many conventional wound healing methods and materials have failed in facilitating proper healing, instead d…","language":"en-US","citation_pii":"S2590183422000473","ogTitle":"Design of 3D smart scaffolds using natural, synthetic and hybrid derived polymers for skin regenerative applications","citation_journal_title":"Smart Materials in Medicine","og:title":"Design of 3D smart scaffolds using natural, synthetic and hybrid derived polymers for skin regenerative applications","title":"Design of 3D smart scaffolds using natural, synthetic and hybrid derived polymers for skin regenerative applications - ScienceDirect","ogImage":"https://ars.els-cdn.com/content/image/1-s2.0-S2590183422X00021-cov150h.gif","citation_online_date":"2022/09/24","og:type":"article","og:description":"Effective wound care is a major concern as many conventional wound healing methods and materials have failed in facilitating proper healing, instead d…","citation_publication_date":"2023/01/01","citation_issn":"2590-1834","tdm-reservation":"1","viewport":"initial-scale=1","SDTech":"Proudly brought to you by the SD Technology team","scrapeId":"45cbfbe5-f9d8-4bbc-86f4-044ff8448648","sourceURL":"https://www.sciencedirect.com/science/article/pii/S2590183422000473","url":"https://www.sciencedirect.com/science/article/pii/S2590183422000473","statusCode":200} [Skip to main content](https://www.sciencedirect.com/science/article/pii/S2590183422000473#screen-reader-main-content) [Skip to article](https://www.sciencedirect.com/science/article/pii/S2590183422000473#screen-reader-main-title) - [View **PDF**](https://www.sciencedirect.com/science/article/pii/S2590183422000473/pdfft?md5=ffbf5e0b4761b1a328c5d8c7f0472b8f&pid=1-s2.0-S2590183422000473-main.pdf) - Download full issue Search ScienceDirect ## Outline 1. [Highlights](https://www.sciencedirect.com/science/article/pii/S2590183422000473#abs0015 "Highlights") 2. [Abstract](https://www.sciencedirect.com/science/article/pii/S2590183422000473#abs0010 "Abstract") 3. [Keywords](https://www.sciencedirect.com/science/article/pii/S2590183422000473#kwrds0010 "Keywords") 4. [1\. Introduction](https://www.sciencedirect.com/science/article/pii/S2590183422000473#sec1 "1. Introduction") 5. [2\. Different types of scaffolds](https://www.sciencedirect.com/science/article/pii/S2590183422000473#sec2 "2. Different types of scaffolds") 6. [3\. Conclusion and future prospective](https://www.sciencedirect.com/science/article/pii/S2590183422000473#sec3 "3. Conclusion and future prospective") 7. [Declaration of competing interest](https://www.sciencedirect.com/science/article/pii/S2590183422000473#coi0010 "Declaration of competing interest") 8. [Acknowledgement](https://www.sciencedirect.com/science/article/pii/S2590183422000473#ack0010 "Acknowledgement") 9. [References](https://www.sciencedirect.com/science/article/pii/S2590183422000473#cebib0010 "References") Show full outline ## [Cited by (57)](https://www.sciencedirect.com/science/article/pii/S2590183422000473\#section-cited-by) ## Figures (3) 1. [![Fig.1. Four different stages (haemostasis, inflammation, proliferation, and…](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr1.sml)](https://www.sciencedirect.com/science/article/pii/S2590183422000473#fig1) 2. [![Fig.2. Pictorial representation of use of different polymer-based scaffolds for wound…](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr2.sml)](https://www.sciencedirect.com/science/article/pii/S2590183422000473#fig2) 3. [![Fig.3. Pictorial representation of scaffold fabrication using electrospinning method](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr3.sml)](https://www.sciencedirect.com/science/article/pii/S2590183422000473#fig3) ## Tables (5) 1. [Table 1](https://www.sciencedirect.com/science/article/pii/S2590183422000473#tbl1 "Different commercially available scaffolds used in skin regeneration.") 2. [Table 2](https://www.sciencedirect.com/science/article/pii/S2590183422000473#tbl2 "Different polymers used for the designing of scaffolds.") 3. [Table 3](https://www.sciencedirect.com/science/article/pii/S2590183422000473#tbl3 "Different natural polymers used as scaffolds for wound healing applications.") 4. [Table 4](https://www.sciencedirect.com/science/article/pii/S2590183422000473#tbl4 "Different synthetic polymers used as scaffolds for wound healing and skin tissue engineering applications.") 5. [Table 5](https://www.sciencedirect.com/science/article/pii/S2590183422000473#tbl5 "Different hybrid polymers used as scaffolds for wound healing and skin tissue engineering applications.") [![Smart Materials in Medicine](https://ars.els-cdn.com/content/image/DKEAI.gif)](https://www.sciencedirect.com/journal/smart-materials-in-medicine "Go to Smart Materials in Medicine on ScienceDirect") ## [Smart Materials in Medicine](https://www.sciencedirect.com/journal/smart-materials-in-medicine "Go to Smart Materials in Medicine on ScienceDirect") [Volume 4](https://www.sciencedirect.com/journal/smart-materials-in-medicine/vol/4/suppl/C "Go to table of contents for this volume/issue"), 2023, Pages 243-256 [![Smart Materials in Medicine](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422X00021-cov150h.gif)](https://www.sciencedirect.com/journal/smart-materials-in-medicine/vol/4/suppl/C) # Design of 3D smart scaffolds using natural, synthetic and hybrid derived polymers for skin regenerative applications Author links open overlay panelLaldinthariSuamte, AkritiTirkey, Punuri JayasekharBabu Show more Outline Add to Mendeley Cite [https://doi.org/10.1016/j.smaim.2022.09.005](https://doi.org/10.1016/j.smaim.2022.09.005 "Persistent link using digital object identifier") [Get rights and content](https://s100.copyright.com/AppDispatchServlet?publisherName=ELS&contentID=S2590183422000473&orderBeanReset=true) Under a Creative Commons [license](http://creativecommons.org/licenses/by-nc-nd/4.0/) Open access ## Highlights - • In this Review, we disserted the various natural polymers for scaffolds design. - • We have highlighted the degradable and non-degradable synthetic polymers for scaffolds design. - • We have focused on the use of hybrid polymers for skin tissue engineering. - • Hybrid polymers showed better mechanical strength, fibroblast proliferation and epithelization that its individual counter parts. ## Abstract Effective [wound](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/wound "Learn more about wound from ScienceDirect's AI-generated Topic Pages") care is a major concern as many conventional [wound healing](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/wound-healing "Learn more about wound healing from ScienceDirect's AI-generated Topic Pages") methods and materials have failed in facilitating proper healing, instead disrupts the overall healing process, leading to the development of chronic wounds. Advancement in [tissue engineering](https://www.sciencedirect.com/topics/engineering/tissue-engineering "Learn more about tissue engineering from ScienceDirect's AI-generated Topic Pages") has led to the development of scaffolds; a 3D construct which can be utilized as a template for cell growth and regeneration while preventing infection along with acceleration of the wound healing process. Natural and [synthetic polymers](https://www.sciencedirect.com/topics/engineering/synthetic-polymer "Learn more about synthetic polymers from ScienceDirect's AI-generated Topic Pages") are used extensively for scaffold production and hybrid scaffolds are also introduced which constitutes a combination of natural and [synthetic polymers](https://www.sciencedirect.com/topics/materials-science/synthetic-polymer "Learn more about synthetic polymers from ScienceDirect's AI-generated Topic Pages"). This review highlights the design of scaffolds using different kinds of polymers for [skin tissue engineering](https://www.sciencedirect.com/topics/engineering/skin-tissue-engineering "Learn more about skin tissue engineering from ScienceDirect's AI-generated Topic Pages"). - [Previous article in issue](https://www.sciencedirect.com/science/article/pii/S2590183422000503) - [Next article in issue](https://www.sciencedirect.com/science/article/pii/S2590183422000527) ## Keywords Wound Polymers Healing Dressing materials Scaffolds ## 1\. Introduction [Wound healing](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/wound-healing "Learn more about Wound healing from ScienceDirect's AI-generated Topic Pages") is an intricate biological process of tissue repair, comprising a sequence of cellular events that eventually give rise to new healthy tissue \[ [1](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib1)\]. It occurs through four highly organized phases, namely [haemostasis](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/blood-stasis "Learn more about haemostasis from ScienceDirect's AI-generated Topic Pages"), inflammation, proliferation, and remodelling or maturation as depicted in [Fig. 1](https://www.sciencedirect.com/science/article/pii/S2590183422000473#fig1) \[ [2](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib2)\]. The sequential occurrence and duration of these phases plays a vital role in proper healing \[ [3](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib3)\]. Haemostasis is the first phase of [wound](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/wound "Learn more about wound from ScienceDirect's AI-generated Topic Pages") healing which occurs immediately after [injury](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/injury "Learn more about injury from ScienceDirect's AI-generated Topic Pages") and involves coagulation and vasoconstriction \[ [4](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib4)\]. The second phase is characterized by the arrival of [neutrophils](https://www.sciencedirect.com/topics/engineering/neutrophil "Learn more about neutrophils from ScienceDirect's AI-generated Topic Pages"), [monocytes](https://www.sciencedirect.com/topics/engineering/monocyte "Learn more about monocytes from ScienceDirect's AI-generated Topic Pages") and macrophages at the site of injury \[ [5](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib5)\]. Neutrophils play an important role in the removal of non-viable cells and [bacterial contaminants](https://www.sciencedirect.com/topics/engineering/bacterial-contaminant "Learn more about bacterial contaminants from ScienceDirect's AI-generated Topic Pages") from the wound site while macrophages are responsible for the release of different growth factors which promote the proliferation of new tissue \[ [6](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib6)\]. The [proliferative phase](https://www.sciencedirect.com/topics/engineering/proliferative-phase "Learn more about proliferative phase from ScienceDirect's AI-generated Topic Pages") includes epithelialization, proliferation of endothelial and fibroblasts cells and formation of blood vessels and granulation tissue \[ [\[7\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib7), [\[8\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib8), [\[9\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib9)\]. Granulation tissue serves as a [support system](https://www.sciencedirect.com/topics/engineering/support-system "Learn more about support system from ScienceDirect's AI-generated Topic Pages") for fibroblasts and other migrating cells which lasts for 4–14 days. Maturation is the final phase in which the extracellular matrix is reorganised, degraded and resynthesized to attain peak [tensile strength](https://www.sciencedirect.com/topics/materials-science/ultimate-tensile-strength "Learn more about tensile strength from ScienceDirect's AI-generated Topic Pages") \[ [10](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib10)\]. Clinically, wounds are classified into acute and chronic wounds \[ [11](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib11)\]. [Acute wounds](https://www.sciencedirect.com/topics/engineering/acute-wound "Learn more about Acute wounds from ScienceDirect's AI-generated Topic Pages") follow a normal wound healing process with no disruption eventually restoring the skin's function and anatomy whereas chronic wounds fail to follow the normal wound healing process due to the prolongation of any of the phases in the healing process \[ [12](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib12), [13](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib13)\]. ![Fig. 1](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr1.jpg) 1. [Download: Download high-res image (928KB)](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr1_lrg.jpg "Download high-res image (928KB)") 2. [Download: Download full-size image](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr1.jpg "Download full-size image") Fig. 1. Four different stages (haemostasis, inflammation, proliferation, and remodelling or maturation) of wound healing mechanism. Different conventional methods have consistently employed materials such as skin grafts, stitches, dressings and flaps for wound healing \[ [\[14\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib14), [\[15\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib15), [\[16\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib16)\]. The wound site requires optimum parameters in terms of moisture, temperature and oxygen to promote and facilitate proper blood flow, granulation and epithelialization \[ [\[17\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib17), [\[18\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib18), [\[19\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib19), [\[20\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib20)\]. Conventional wound healing often fails to prevent infection which disrupts the wound healing process. Moreover, these methods have limitations such as donor site morbidity, graft donor scarcity, wound contraction and scarring \[ [21](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib21), [22](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib22)\]. These drawbacks can be effectively managed or overcome with the use of alternative materials such as scaffolds which can meet the optimum parameters and requirements specific for wound healing and [tissue engineering](https://www.sciencedirect.com/topics/engineering/tissue-engineering "Learn more about tissue engineering from ScienceDirect's AI-generated Topic Pages") applications. Advances in different fields of technology over the past three decades have led us to impressive achievements in the field of tissue engineering for wound healing \[ [23](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib23)\]. [Skin tissue engineering](https://www.sciencedirect.com/topics/engineering/skin-tissue-engineering "Learn more about Skin tissue engineering from ScienceDirect's AI-generated Topic Pages") is a process of producing skin substitutes capable of renewing the framework and function of an injured tissue \[ [24](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib24)\]. One of the most vital components of skin tissue engineering is a scaffold, a 3D construct which serves as a platform for the proliferation of cells that finally result in the formation of a healthy tissue \[ [25](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib25)\]. An ideal scaffold for wound healing should have certain properties such as [bioactivity](https://www.sciencedirect.com/topics/engineering/bioactivity "Learn more about bioactivity from ScienceDirect's AI-generated Topic Pages") (to effect, respond and interact with its biological surroundings), [biocompatibility](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/biocompatibility "Learn more about biocompatibility from ScienceDirect's AI-generated Topic Pages") (it must not elicit an unwanted immune response), biodegradability (ability to degrade into harmless substances), high porosity (for providing consistent cell circulation, [cell proliferation](https://www.sciencedirect.com/topics/materials-science/cell-proliferation "Learn more about cell proliferation from ScienceDirect's AI-generated Topic Pages"), cell migration, diffusion of oxygen and water, etc.), have proteolytic activity (to break down the damaged proteins for formation of new tissue) and antioxidant property (to neutralize the free radicals) for proper facilitation of cells \[ [\[26\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib26), [\[27\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib27), [\[28\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib28), [\[29\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib29), [\[30\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib30), [\[31\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib31), [\[32\]](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib32)\]. Moreover, scaffolds should display favourable mechanical properties resembling the host tissue to provide structural integrity as well as to regulate cellular functions such as cell differentiation, cell phenotype and cell-matrix interaction \[ [33](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib33), [34](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib34)\]. In addition to being a support system, scaffolds are also used as a carrier for drugs or growth factors, which can deliver these therapeutic molecules to the wound site thus, enhancing the rate of wound healing \[ [35](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib35)\]. Apart from maintaining optimum moisture, temperature and oxygen concentration, they can also act as a shield for protection at the wound site \[ [36](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib36)\] and interact with their surrounding environment to expedite the healing process \[ [37](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib37)\]. Owing to these features scaffolds can effectively address the limitations of conventional methods. Numerous FDA approved scaffolds such as Dermafill™, OrcelTM, Apligraf®, etc. have been fabricated using tissue engineering \[ [38](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib38)\]. Different commercially available scaffolds used in skin regeneration are listed below in [Table 1](https://www.sciencedirect.com/science/article/pii/S2590183422000473#tbl1). Table 1. Different commercially available scaffolds used in skin regeneration. | Trade Name | Polymer source | Application | Reference | | --- | --- | --- | --- | | Apligraft | Collagen | Growth factor activation | \[ [38](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib38)\] | | Biobrane | Collagen | Promotion of cell adherence with fluid drainage | \[ [39](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib39)\] | | Epicite | Cellulose | High wound healing rates | \[ [40](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib40)\] | | Vicryl Mesh | Polylactic- _co_-glycolic acid | Skin graft | \[ [41](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib41)\] | The surface of a scaffold is the primary site for interaction with the surrounding environment which in turn affects the adhesion, growth and maturation of cells \[ [42](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib42)\] therefore, surface modification of scaffolds can be done to improve their cellular functions \[ [43](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib43)\]. In this process, specific biological and chemical cues can be incorporated into the scaffolds which can regulate the seeded cells’ activity by manipulating their signal transduction pathways \[ [44](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib44)\]. Different methods are used to achieve surface modification such as optimization of [incubation period](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/incubation-time "Learn more about incubation period from ScienceDirect's AI-generated Topic Pages"), pH value and pre-treatment by aqueous solution \[ [45](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib45)\]. Most surface modifications are usually done in case of synthetic and hybrid polymer scaffolds in order to improve surface interactions and biocompatibility \[ [46](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib46)\]. Apart from the ease of modification, there are numerous natural and [synthetic polymer](https://www.sciencedirect.com/topics/materials-science/synthetic-polymer "Learn more about synthetic polymer from ScienceDirect's AI-generated Topic Pages") materials which can be used for the fabrication of scaffolds. Introduction of [nanomaterials](https://www.sciencedirect.com/topics/engineering/nanomaterial "Learn more about nanomaterials from ScienceDirect's AI-generated Topic Pages") into scaffolds can impart unique properties to it such as enhanced physicochemical features, biocompatibility, antimicrobial activity and many more. These [nanofillers](https://www.sciencedirect.com/topics/engineering/nanofiller "Learn more about nanofillers from ScienceDirect's AI-generated Topic Pages") can be easily synthesized using different physical (sonication \[ [196](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib196)\], microwave-mediated \[ [197](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib197), [198](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib198)\], heating \[ [199](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib199)\], [laser ablation](https://www.sciencedirect.com/topics/materials-science/laser-ablation "Learn more about laser ablation from ScienceDirect's AI-generated Topic Pages") \[ [200](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib200)\], [UV irradiation](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/ultraviolet-irradiation "Learn more about UV irradiation from ScienceDirect's AI-generated Topic Pages") \[ [201](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib201)\]), chemical reduction \[ [202](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib202)\] and biological (plant-mediated \[ [203](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib203)\], microbe-mediated \[ [204](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib204)\]) methods. Studies have shown that [nanocomposite](https://www.sciencedirect.com/topics/engineering/nanocomposite "Learn more about nanocomposite from ScienceDirect's AI-generated Topic Pages") scaffolds embedded with [nanomaterials](https://www.sciencedirect.com/topics/materials-science/nanocrystalline-material "Learn more about nanomaterials from ScienceDirect's AI-generated Topic Pages") show promising results for wound healing and tissue [engineering applications](https://www.sciencedirect.com/topics/engineering/engineering-application "Learn more about engineering applications from ScienceDirect's AI-generated Topic Pages") \[ [47](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib47)\]. In addition, several methods are available for the facile fabrication of scaffolds. Different methods used for fabricating scaffolds are conventional methods like gas foaming, [melt molding](https://www.sciencedirect.com/topics/engineering/melt-molding "Learn more about melt molding from ScienceDirect's AI-generated Topic Pages"), freeze drying, solvent casting, etc., and advanced methods such as electrospinning, [3D printing](https://www.sciencedirect.com/topics/materials-science/three-dimensional-printing "Learn more about 3D printing from ScienceDirect's AI-generated Topic Pages") and [selective laser sintering](https://www.sciencedirect.com/topics/engineering/selective-laser-sintering "Learn more about selective laser sintering from ScienceDirect's AI-generated Topic Pages") etc. \[ [26](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib26)\]. An overall representation of how scaffolds are utilized is shown in [Fig. 2](https://www.sciencedirect.com/science/article/pii/S2590183422000473#fig2). Hence, it can be summarized that scaffolds are a potential alternative to the existing conventional materials for wound healing and tissue engineering applications as they provide the required optimum parameters, are biocompatible, offer ease of modification and can be synthesized from a wide range of polymers. Therefore, this review aims to introduce the extensive process of wound healing and describe in detail the role of scaffolds for wound healing. Also, it presents the use of natural, synthetic and hybrid-based polymers for scaffold production. [Natural polymers](https://www.sciencedirect.com/topics/chemical-engineering/natural-polymer "Learn more about Natural polymers from ScienceDirect's AI-generated Topic Pages") used as scaffolds have been further classified into [polysaccharide](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/polysaccharide "Learn more about polysaccharide from ScienceDirect's AI-generated Topic Pages") and protein-based polymers whereas the synthetic polymers have been sub-divided into degradable and non-degradable polymers and hybrid polymer-based scaffolds have been categorized on the basis of the [synthesis methods](https://www.sciencedirect.com/topics/engineering/synthesis-method "Learn more about synthesis methods from ScienceDirect's AI-generated Topic Pages") with a special attention to their use as scaffolds for wound healing and tissue engineering applications. ![Fig. 2](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr2.jpg) 1. [Download: Download high-res image (325KB)](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr2_lrg.jpg "Download high-res image (325KB)") 2. [Download: Download full-size image](https://ars.els-cdn.com/content/image/1-s2.0-S2590183422000473-gr2.jpg "Download full-size image") Fig. 2. Pictorial representation of use of different polymer-based scaffolds for wound healing. ## 2\. Different types of scaffolds Scaffolds are prepared from naturally occurring polymers, [synthetic polymers](https://www.sciencedirect.com/topics/materials-science/synthetic-polymer "Learn more about synthetic polymers from ScienceDirect's AI-generated Topic Pages") (which may be degradable or non-degradable) and hybrid polymers \[ [48](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib48)\]. Different kinds of polymers used in the designing of scaffolds are listed in [Table 2](https://www.sciencedirect.com/science/article/pii/S2590183422000473#tbl2). Table 2. Different polymers used for the designing of scaffolds. | Types | Polymers | Advantages | Disadvantages | Reference | | --- | --- | --- | --- | --- | | Natural polymer based scaffold | - ⁃
Cellulose

- ⁃
Alginate

- ⁃
Agar

- ⁃
Chitin

- ⁃
Hyaluronic acid

- ⁃
Dextran

- ⁃
Starch

- ⁃
Collagen

- ⁃
Fibronectin

- ⁃
Gelatin

- ⁃
Elastin

- ⁃
Silk

- ⁃
Keratin

- ⁃
Fibrin | - ⁃
Biocompatibility

- ⁃
Non-toxicity

- ⁃
Easy availability

- ⁃
Cost-effective | - ⁃
Poor mechanical properties

- ⁃
Low reproducibility due to variations in composition | \[ [49](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib49)\] | | \[ [50](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib50)\] | | \[ [51](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib51)\] | | \[ [52](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib52)\] | | \[ [53](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib53)\] | | \[ [54](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib54)\] | | \[ [55](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib55)\] | | \[ [56](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib56)\] | | \[ [57](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib57)\] | | \[ [58](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib58)\] | | \[ [59](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib59)\] | | \[ [60](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib60)\] | | \[ [61](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib61)\] | | \[ [62](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib62)\] | | Synthetic polymer based scaffold | - ⁃
Polyethylene glycol (PEG)

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Poly-β-hydroxybutyrate (PHB)

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Poly propylenefumarate (PPF)

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Polycaprolactone (PCL)

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Poly hydroxyortho esters

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Poly vinyl alcohol (PVA)

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Polyurethane (PU)

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Poly methyl methacrylate (PMMA)

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Polystyrene (PS)

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Polyethylene terephthalate (PET)

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Polyethersulfone (PES)

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Polyacrylic acid (PAA)

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Poly di ethylene glycol methyl ether methacrylate (PDEGMA) | - ⁃
Mechanically stable

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Ease of modification

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Consistent reproducibility due to uniform chemical composition | - ⁃
Lack of cell adhesion sites

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Less biocompatible

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Expensive | \[ [63](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib63)\] | | \[ [64](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib64)\] | | \[ [65](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib65)\] | | \[ [66](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib66)\] | | \[ [67](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib67)\] | | \[ [68](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib68)\] | | \[ [69](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib69)\] | | \[ [70](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib70)\] | | \[ [71](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib71)\] | | \[ [72](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib72)\] | | \[ [73](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib73)\] | | \[ [74](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib74)\] | | \[ [75](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib75)\] | | Hybrid scaffold | - ⁃
PCL Collagen

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PCL/Collagen/Titanium oxide

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hEnSCs/PCL/Collagen

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PEO/Chitosan/Collagen

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PEO/Chitosan

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PLLA/Chitosan

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Pullulan/Collage

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Collagen/elastin

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Chitosan/Silk

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Silk/Gelatin/Alginate

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AgNPs/Chitosan

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Carboxyethyl chitosan/PVA

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Silk fibroin/hyaluronic acid/sodium alginate | - ⁃
Increased mechanical strength

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Good tensile strength

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Regulated biocompatibility, degradation rates, cytotoxicity and thermostability | - ⁃
Non-facile fabrication methods

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Often require sophisticated instruments

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Expensive | \[ [76](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib76)\] | | \[ [77](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib77)\] | | \[ [78](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib78)\] | | \[ [79](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib79)\] | | \[ [80](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib80)\] | | \[ [81](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib81)\] | | \[ [82](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib82)\] | | \[ [83](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib83)\] | | \[ [84](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib84)\] | | \[ [85](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib85)\] | | \[ [86](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib86)\] | | \[ [87](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib87)\] | | \[ [88](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib88)\] | ### 2.1. Natural polymers [Natural polymers](https://www.sciencedirect.com/topics/materials-science/natural-polymer "Learn more about Natural polymers from ScienceDirect's AI-generated Topic Pages") are acquired from natural materials and provide an assurance of natural restructure, [biomimetic](https://www.sciencedirect.com/topics/engineering/biomimetics "Learn more about biomimetic from ScienceDirect's AI-generated Topic Pages") nature and [bioactivity](https://www.sciencedirect.com/topics/engineering/bioactivity "Learn more about bioactivity from ScienceDirect's AI-generated Topic Pages") \[ [89](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib89)\]. [Biocompatibility](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/biocompatibility "Learn more about Biocompatibility from ScienceDirect's AI-generated Topic Pages"), 3D geometry, nontoxic biodegradation and intrinsic structural resemblance are the key features obtained from natural polymers \[ [90](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib90)\]. Owing to these advantageous properties, scaffolds produced from different biodegradable and eco-friendly materials are extensively used in multiple aspects of [tissue engineering](https://www.sciencedirect.com/topics/engineering/tissue-engineering "Learn more about tissue engineering from ScienceDirect's AI-generated Topic Pages"). These polymers are roughly categorized on the basis of their monomeric units and structure into [polysaccharide](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/polysaccharide "Learn more about polysaccharide from ScienceDirect's AI-generated Topic Pages") and protein-based polymers \[ [91](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib91)\]. #### 2.1.1. Polysaccharide based polymers Polysaccharides offer good biodegradability, biocompatibility, ease in derivatization and low production cost along with their similarity to the extra cellular matrix (ECM) \[ [92](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib92)\]. These polysaccharides can be categorized on the basis of their functions which are structure or storage. An example of a structural [polysaccharide](https://www.sciencedirect.com/topics/chemical-engineering/polysaccharide "Learn more about polysaccharide from ScienceDirect's AI-generated Topic Pages") is [chitin](https://www.sciencedirect.com/topics/chemical-engineering/chitin "Learn more about chitin from ScienceDirect's AI-generated Topic Pages") obtained from crustacean shells while, glycogen and starch are examples of storage polysaccharides \[ [93](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib93)\]. Despite their several benefits, natural polymers have certain drawbacks associated with their branching, distribution, sequence and [molecular weight](https://www.sciencedirect.com/topics/engineering/molecular-weight "Learn more about molecular weight from ScienceDirect's AI-generated Topic Pages") which leads to preparation of inconsistent scaffolds resulting in [detrimental effects](https://www.sciencedirect.com/topics/engineering/detrimental-effect "Learn more about detrimental effects from ScienceDirect's AI-generated Topic Pages") on biorecognition events and rheology \[ [94](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib94)\]. Cellulose, [alginate](https://www.sciencedirect.com/topics/engineering/alginate "Learn more about alginate from ScienceDirect's AI-generated Topic Pages"), agar, [chitin](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/chitin "Learn more about chitin from ScienceDirect's AI-generated Topic Pages"), [hyaluronic acid](https://www.sciencedirect.com/topics/chemical-engineering/hyaluronic-acid "Learn more about hyaluronic acid from ScienceDirect's AI-generated Topic Pages"), [dextran](https://www.sciencedirect.com/topics/chemical-engineering/dextran "Learn more about dextran from ScienceDirect's AI-generated Topic Pages") and starch are the various polysaccharide-based polymers discussed in this study. _Cellulose_ is the most widely present [biopolymer](https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/biopolymer "Learn more about biopolymer from ScienceDirect's AI-generated Topic Pages") in the cell wall of plants offering beneficial key features over conventional synthetic materials \[ [49](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib49)\]. It provides a [stable matrix](https://www.sciencedirect.com/topics/engineering/stable-matrix "Learn more about stable matrix from ScienceDirect's AI-generated Topic Pages") required for tissue [engineering applications](https://www.sciencedirect.com/topics/engineering/engineering-application "Learn more about engineering applications from ScienceDirect's AI-generated Topic Pages") and is available in different forms with excellent biocompatibility \[ [95](https://www.sciencedirect.com/science/article/pii/S2590183422000473#bib95)\]. [Bacterial cellulose](https://www.sciencedirect.com/topics/engineer