Role of Graphene Family Nanomaterials in Skin Wound Healing and Regeneration.

Owing to astonishing properties such as the large surface area to volume ratio, mechanical stability, antimicrobial property, and collagen crosslinking, graphene family nanomaterials (GFNs) have been widely used in various biomedical applications including tissue regeneration. Many review literatures are available to compile the role of GFNs in cardiac, bone, and neuronal tissue regeneration. However, the contribution of GFNs in skin wound healing and tissue regeneration was not yet discussed. In the present review, we have highlighted the properties of GFNs and their application in skin wound healing. In addition, we have included challenges and future directions of GFNs in skin tissue regeneration in the portion of conclusion and perspectives.

Chitosan based ethanolicAllium Sativumextract hydrogel film: a novel skin tissue regeneration platform for 2nd degree burn wound healing.

This study investigated the potential of ethanolic garlic extract-loaded chitosan hydrogel film for burn wound healing in an animal model. The ethanolic garlic extract was prepared by macerating fresh ground garlic cloves in ethanol for 24 h, followed by filtration and concentration using a rotary evaporator. Hydrogels were then prepared by casting a chitosan solution with garlic extract added at varying concentrations for optimization and, following drying, subjected to various characterization tests, including moisture adsorption (MA), water vapor transmission rate (WVTR), and water vapor permeability rate (WVPR), erosion, swelling, tensile strength, vibrational, and thermal analysis, and surface morphology. The optimized hydrogel (G2) was then analyzedin vivofor its potential for healing 2nd degree burn wounds in rats, and histological examination of skin samples on day 14 of the healing period. Results showed optimized hydrogel (G2; chitosan: 2 g, garlic extract: 1 g) had MA of 56.8% ± 2.7%, WVTR and WVPR of 0.00074 ± 0.0002, and 0.000 498 946 ± 0.0001, eroded up to 11.3% ± 0.05%, 80.7% ± 0.04% of swelling index, and tensile strength of 16.6 ± 0.9 MPa, which could be attributed to the formation of additional linkages between formulation ingredients and garlic extract constituents at OH/NH and C=O, translating into an increase in transition melting temperature and enthalpy (ΔT= 238.83 °C ± 1.2 °C, ΔH= 4.95 ± 0.8 J g-1) of the chitosan moieties compared with blank. Animal testing revealed G2 formulation significantly reduced the wound size within 14 d of the experiment (37.3 ± 6.8-187.5 ± 21.5 mm2) and had significantly higher reepithelization (86.3 ± 6.8-26.8 ± 21.5 and 38.2% ± 15.3%) compared to untreated and blank groups by hastening uniform and compact deposition of collagen fibers at the wound site, cementing developed formulation a promising platform for skin regeneration.

Studies on cytocompatibility of human dermal fibroblasts on carbon nanofiber nanoparticle-containing bioprinted constructs.

Functional nanocomposite-based printable inks impart strength, mechanical stability, and bioactivity to the printed matrix due to the presence of nanomaterials or nanostructures. Carbonaceous nanomaterials are known to improve the electrical conductivity, osteoconductivity, mechanical, and thermal properties of printed materials. In the current work, we have incorporated carbon nanofiber nanoparticles (CNF NPs) into methacrylated gelatin (GelMA) to investigate whether the resulting nanocomposite printable ink constructs (GelMA-CNF NPs) promote cell proliferation. Two kinds of printable constructs, cell-laden bioink and biomaterial ink, were prepared by incorporating various concentrations of CNF NPs (50, 100, and 150 µg/mL). The CNF NPs improved the mechanical strength and dielectric properties of the printed constructs. The in vitro cell line studies using normal human dermal fibroblasts (nHDF) demonstrated that CNF NPs are involved in cell-material interaction without affecting cellular morphology. Though the presence of NPs did not affect cellular viability on the initial days of treatment, it caused cytotoxicity to the cells on days 4 and 7 of the treatment. A significant level of cytotoxicity was observed in the highly CNF-concentrated bioink scaffolds (100 and 150 µg/mL). The unfavorable outcomes of the current work necessitate further study of employing functionalized CNF NPs to achieve enhanced cell proliferation in GelMA-CNF NPs-based bioprinted constructs and advance the application of skin tissue regeneration.

Aloe vera-based biomaterial ink for 3D bioprinting of wound dressing constructs.

This study emphasizes the development of a multifunctional biomaterial ink for wound healing constructs. The biomaterial ink benefits from Aloe vera's intrinsic biocompatible, biodegradable, antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory attributes, thus alleviating the need for supplementary substances employed to combat infections and stimulate tissue regeneration. Moreover, this biomaterial ink seeks to address the scarcity of standardized printable materials possessing adequate biocompatibility and physicochemical properties, which hinder its widespread clinical adoption. The biomaterial ink was synthesized via ionic crosslinking to enhance its rheological and mechanical characteristics. The findings revealed that Aloe vera substantially boosted the hydrogel's viscoelastic behavior, enabling superior compressive modulus and the extrusion of fine filaments. The bioprinted constructs exhibited desirable resolution and mechanical strength while displaying a porous microstructure analogous to the native extracellular matrix. Biological response demonstrated no detrimental impact on stem cell viability upon exposure to the biomaterial ink, as confirmed by live/dead assays. These outcomes validate the potential of the developed biomaterial ink as a resource for the bioprinting of wound dressings that effectively foster cellular proliferation, thereby promoting enhanced wound healing by leveraging Aloe vera's inherent properties.

Extracellular Matrix-Bioinspired Anisotropic Topographical Cues of Electrospun Nanofibers: A Strategy of Wound Healing through Macrophage Polarization.

The skin serves as the body's outermost barrier and is the largest organ, providing protection not only to the body but also to various internal organs. Owing to continuous exposure to various external factors, it is susceptible to damage that can range from simple to severe, including serious types of wounds such as burns or chronic wounds. Macrophages play a crucial role in the entire wound-healing process and contribute significantly to skin regeneration. Initially, M1 macrophages infiltrate to phagocytose bacteria, debris, and dead cells in fresh wounds. As tissue repair is activated, M2 macrophages are promoted, reducing inflammation and facilitating restoration of the dermis and epidermis to regenerate the tissue. This suggests that extracellular matrix (ECM) promotes cell adhesion, proliferation, migrationand macrophage polarization. Among the numerous strategies, electrospinning is a versatile technique for obtaining ECM-mimicking structures with anisotropic and isotropic topologies of micro/nanofibers. Various electrospun biomaterials influence macrophage polarization based on their isotropic or anisotropic topologies. Moreover, these fibers possess a high surface-area-to-volume ratio, promoting the effective exchange of vital nutrients and oxygen, which are crucial for cell viability and tissue regeneration. Micro/nanofibers with diverse physical and chemical properties can be tailored to polarize macrophages toward skin regeneration and wound healing, depending on specific requirements. This review describes the significance of micro/nanostructures for activating macrophages and promoting wound healing.

Natural Polymer-Based Thin Film Strategies for Skin Regeneration in Lieu of Regenerative Dentistry.

Wound healing (WH) is a complex and dynamic process that comprises of a series of molecular and cellular events that occur after tissue injury. The injuries of the maxillofacial and oral region caused by trauma or surgery result in undesirable WH such as delayed wound closure and formation of scar tissue. Skin tissue engineering (TE)/regeneration is an emerging approach toward faster, superior, and more effective resolution of clinically significant wounds effectively. A multitude of TE principles approaches are being put to action for the fabrication of hydrogels, electrospun sheets, 3D scaffolds, and thin films that can be used as wound dressings materials, sutures, or skin substitutes. Thin films are advantageous over other materials owing to their flexibility, ability to provide a barrier against external contamination, easy gaseous exchange, and easy monitoring of wounds. This review focuses on wound-dressing films and their significance and discusses various fabrication techniques. In addition, we explore various natural biopolymers that can be used for fabrication of skin TE materials. Impact Statement In this review article, critical evaluations of natural polymers used in skin regeneration were discussed. Further, the fabrication technology of the 2D and 3D material in wound healing were discussed.

Injectable gelatin/oxidized dextran hydrogel loaded with apocynin for skin tissue regeneration.

Acute skin injury should be treated in time, due to many factors will affect the normal healing process of wounds, hinder tissue regeneration, and eventually form chronic wounds. Herein, an injectable, in-situ gel-forming hydrogel has been fabricated. The hydrogel is stabilized by dynamic Schiff base and composed of gelatin (Gel), oxidized dextran (Odex) and apocynin (Apo). In vitro studies have shown that this hydrogel has good injectability, plasticity, self-healing and efficient hemostatic properties. The hydrogel has good cytocompatibility with HaCaT and L929 cells by the Live/Dead cell staining. Furthermore, in vivo studies have shown that hydrogel loaded with APO can accelerate angiogenesis and skin tissue regeneration by reducing wound inflammation. Therefore, the injectable Gel/Odex/Apo hydrogel has the advantages of simple preparation process, convenient use and multifunction, etc., it is a promising wound dressing for full-thickness skin repair and has great potential in the field of skin tissue regeneration.

3D bioprinted mesenchymal stromal cells in skin wound repair.

Skin tissue regeneration and repair is a complex process involving multiple cell types, and current therapies are limited to promoting skin wound healing. Mesenchymal stromal cells (MSCs) have been proven to enhance skin tissue repair through their multidifferentiation and paracrine effects. However, there are still difficulties, such as the limited proliferative potential and the biological processes that need to be strengthened for MSCs in wound healing. Recently, three-dimensional (3D) bioprinting has been applied as a promising technology for tissue regeneration. 3D-bioprinted MSCs could maintain a better cell ability for proliferation and expression of biological factors to promote skin wound healing. It has been reported that 3D-bioprinted MSCs could enhance skin tissue repair through anti-inflammatory, cell proliferation and migration, angiogenesis, and extracellular matrix remodeling. In this review, we will discuss the progress on the effect of MSCs and 3D bioprinting on the treatment of skin tissue regeneration, as well as the perspective and limitations of current research.

Proangiogenic Peptide Nanofiber Hydrogels for Wound Healing.

Rapid vascularization is vital for dermal regeneration, nutrient and nutrition transfer, metabolic waste removal, and prevention of infection. This study reports on a series of proangiogenic peptides designed to undergo self-assembly and promote angiogenesis and hence skin regeneration. The proangiogenic peptides comprised an angiogenic peptide segment, GEETEVTVEGLEPG, and a ß-sheet structural peptide sequence. These peptides dissolved easily in ultrapure water and rapidly self-assembled into hydrogels in a pH-dependent manner, creating three-dimensional fibril network structures and nanofibers as revealed by a scanning microscope and a transmission electron microscope. In vitro experiments showed that the peptide hydrogels favored adhesion and proliferation of mouse fibroblasts (L929) and human umbilical vein endothelial cells (HUVECs). In particular, many connected tubes were formed in the HUVECs after 8 h of culture on the peptide hydrogels. In vivo experiments demonstrated that new blood vessels grew into the proangiogenic peptide hydrogels within 2 weeks after subcutaneous implantation in mice. Moreover, the proangiogenic-combined hydrogels exhibited faster repair cycles and better healing of skin defects. Collectively, the results indicate that the proangiogenic peptide hydrogels are a promising therapeutic option for skin regeneration.

Fabrication of dual layered biocompatible herbal biopatch from biological waste for skin - tissue regenerative applications.

A dual layered herbal biopolymeric patch (biopatch) with enhanced wound healing efficiency and skin mimicking functions was fabricated for skin-tissue regenerative applications. In this study, hoof keratin (KE) extracted from biological waste and gelatin (GE) was employed for KE-GE biosheet fabrication using a simple casting method. Further, the top layer of the fabricated KE-GE biosheet was coated with bioactive Matricaria recutita (Chamomile flower) extract (CH) with gelatin through an electrospraying method. The optimized dual layered herbal biopatch (KE-GE/GE-CH) exhibits strong physiochemical (FTIR, XRD TG-DTA), mechanical (tensile strength) and biological (in vitro and in vivo) studies. Moreover, the morphology (SEM) of soft mimetic biopatch possesses excellent cell-material interaction and cell proliferation which accelerates the wound healing process. Biopatch demonstrates a proven degradation profile with good swelling features to achieve more than 80% herbal drug release in 96 h. Antimicrobial properties also reveal the potential activity of biopatch against bacterial microbes. In addition, in vitro cell viability using NIH 3T3 fibroblast cell lines and in vivo investigations revealed that the biopatch is non-cytotoxic, increases collagen deposition and shows rapid reepithelialization at the wound site as a potential wound dressing. We anticipated that the biological hoof keratin and bioactive herbal extract coated biopatch could serve as a desirable wound dressing candidate to suit various skin tissue regenerative applications.

Biomimetic Supramolecular Drug Delivery Hydrogels for Accelerated Skin Tissue Regeneration.

Skin tissue is regenerated by the combinational function of skin cells, extracellular matrix (ECM), and bioactive molecules. As an artificial ECM, supramolecular hydrogels exhibited outstanding capability to mimic the physical properties of ECM. However, the lack of biochemical function in supramolecular hydrogels has limited further tissue engineering applications. Here, we developed self-assembling supramolecular drug delivery hydrogels to mimic the skin tissue regeneration process. The supramolecular hydrogels were prepared to encapsulate fibroblasts by the host-guest interaction of cyclodextrin-modified gelatin (GE-CD) and adamantane-modified hyaluronate (Ad-HA) in conjugation with human growth hormone (hGH) for accelerated skin tissue regeneration. In vitro, GE-CD/Ad-HA-hGH hydrogels showed highly facilitated cell growth by the controlled hGH delivery. After a subcutaneous injection into the back of mice, IVIS imaging of bioengineered fibroblasts to express red fluorescence protein (RFP) revealed prolonged cell survival and proliferation in the supramolecular hydrogels for more than 21 days. We could also observe the improved skin tissue regeneration by the facilitated fibroblast proliferation with angiogenesis. Taken together, we could confirm the feasibility of biomimetic supramolecular drug delivery GE-CD/Ad-HA-hGH hydrogels for various tissue engineering applications.

Exosome loaded genipin crosslinked hydrogel facilitates full thickness cutaneous wound healing in rat animal model.

Full thickness cutaneous wound therapy and regeneration remains a critical challenge in clinical therapeutics. Recent reports have suggested that mesenchymal stem cells exosomes therapy is a promising technology with great potential to efficiently promote tissue regeneration. Multifunctional hydrogel composed of both synthetic materials and natural materials is an effective carrier for exosomes loading. Herein, we constructed a biodegradable, dual-sensitive hydrogel encapsulated human umbilical cord-mesenchymal stem cells (hUCMSCs) derived exosomes to facilitate wound healing and skin regeneration process. The materials characterization, exosomes identification, and in vivo full-thickness cutaneous wound healing effect of the hydrogels were performed and evaluated. The in vivo results demonstrated the exosomes loaded hydrogel had significantly improved wound closure, re-epithelialization rates, collagen deposition in the wound sites. More skin appendages were observed in exosomes loaded hydrogel treated wound, indicating the potential to achieve complete skin regeneration. This study provides a new access for complete cutaneous wound regeneration via a genipin crosslinked dual-sensitive hydrogel loading hUCMSCs derived exosomes.

Impact of exosome-loaded chitosan hydrogel in wound repair and layered dermal reconstitution in mice animal model.

Combat or burn injuries are associated with a series of risks, such as microbial infection, an elevated level of inflammatory response, and pathologic scar tissue formation, which significantly postpone wound healing and also lead to impaired repair. Skin engineering for wound healing requires a biomimetic dressing substrate with ideal hydrophilicity, holding antioxidant and antimicrobial properties. In addition, available bioactive specification is required to reduce scar formation, stimulate angiogenesis, and improve wound repair. In this study, we successfully fabricated chitosan (Ch)-based hydrogel enriched with isolated exosome (EXO) from easy-accessible stem cells, which could promote fibroblast cell migration and proliferation in vitro. Full-thickness excisional wound model was used to investigate the in vivo dermal substitution ability of the fabricated hydrogel composed Ch and EXO substrates. Our finding confirmed that the wounds covered with Ch scaffold containing isolated EXO have nearly 83.6% wound closure ability with a high degree of re-epithelialization, whereas sterile gauze showed 51.5% of reduction in wound size. In summary, obtained results imply that Ch-glycerol-EXO hydrogel construct can be utilized at the full-thickness skin wound substitution and skin tissue engineering.

High porous electrospun poly(ε-caprolactone)/gelatin/MgO scaffolds preseeded with endometrial stem cells promote tissue regeneration in full-thickness skin wounds: An in vivo study.

In the current study, electrospun poly(ε-caprolactone)-gelatin (PCL-Gel) fibrous scaffolds containing magnesium oxide (MgO) particles and preseeded with human endometrial stem cells (hEnSCs) were developed to use as wound care material in skin tissue engineering applications. Electrospun fibers were fabricated using PCL-Gel (1:1 [wt/wt]) with different concentrations of MgO particles (1, 2, and 4 wt%). The fibrous scaffolds were evaluated regarding their microstructure, mechanical properties, surface wettability, and in vitro and in vivo performances. The full-thickness excisional wound model was used to evaluate the in vivo wound healing ability of the fabricated scaffolds. Our findings confirmed that the wounds covered with PCL-Gel fibrous scaffolds containing 2 wt% MgO and preseeded with hEnSCs have nearly 79% wound closure ability while sterile gauze showed 11% of wound size reduction. Our results can be employed for biomaterials aimed at the healing of full-thickness skin wounds.

Fabrication of chitosan-polyvinyl alcohol and silk electrospun fiber seeded with differentiated keratinocyte for skin tissue regeneration in animal wound model.

Hybrid fibrous mat containing cell interactive molecules offers the ability to deliver the cells and drugs in wound bed, which will help to achieve a high therapeutic treatment. In this study, a co-electrospun hybrid of polyvinyl alcohol (PVA), chitosan (Ch) and silk fibrous mat was developed and their wound healing potential by localizing bone marrow mesenchymal stem cells (MSCs)-derived keratinocytes on it was evaluated in vitro and in vivo. It was expected that fabricated hybrid construct could promote wound healing due to its structure, physical, biological specifications. The fabricated fibrous mats were characterized for their structural, mechanical and biochemical properties. The shape uniformity and pore size of fibers showed smooth and homogenous structures of them. Fourier transform infrared spectroscopy (FTIR) verified all typical absorption characteristics of Ch-PVA + Silk polymers as well as Ch-PVA or pure PVA substrates. The contact angle and wettability measurement of fibers showed that mats found moderate hydrophilicity by addition of Ch and silk substrates compared with PVA alone. The mechanical features of Ch-PVA + Silk fibrous mat increase significantly through co-electrospun process as well as hybridization of these synthetic and natural polymers. Higher degrees of cellular attachment and proliferation obtained on Ch-PVA + Silk fibers compared with PVA and Ch-PVA fibers. In terms of the capability of Ch-PVA + Silk fibers and MSC-derived keratinocytes, histological analysis and skin regeneration results showed this novel fibrous construct could be suggested as a skin substitute in the repair of injured skin and regenerative medicine applications.

Engineered delivery strategies for enhanced control of growth factor activities in wound healing.

Growth factors (GFs) are versatile signalling molecules that orchestrate the dynamic, multi-stage process of wound healing. Delivery of exogenous GFs to the wound milieu to mediate healing in an active, physiologically-relevant manner has shown great promise in laboratories; however, the inherent instability of GFs, accompanied with numerous safety, efficacy and cost concerns, has hindered the clinical success of GF delivery. In this article, we highlight that the key to overcoming these challenges is to enhance the control of the activities of GFs throughout the delivering process. We summarise the recent strategies based on biomaterials matrices and molecular engineering, which aim to improve the conditions of GFs for delivery (at the 'supply' end of the delivery), increase the stability and functions of GFs in extracellular matrix (in transportation to target cells), as well as enhance the GFs/receptor interaction on the cell membrane (at the 'destination' end of the delivery). Many of these investigations have led to encouraging outcomes in various in vitro and in vivo regenerative models with considerable translational potential.

Combined chemical and structural signals of biomaterials synergistically activate cell-cell communications for improving tissue regeneration.

Biomaterials are only used as carriers of cells in the conventional tissue engineering. Considering the multi-cell environment and active cell-biomaterial interactions in tissue regeneration process, in this study, structural signals of aligned electrospun nanofibers and chemical signals of bioglass (BG) ionic products in cell culture medium are simultaneously applied to activate fibroblast-endothelial co-cultured cells in order to obtain an improved skin tissue engineering construct. Results demonstrate that the combined biomaterial signals synergistically activate fibroblast-endothelial co-culture skin tissue engineering constructs through promotion of paracrine effects and stimulation of gap junctional communication between cells, which results in enhanced vascularization and extracellular matrix protein synthesis in the constructs. Structural signals of aligned electrospun nanofibers play an important role in stimulating both of paracrine and gap junctional communication while chemical signals of BG ionic products mainly enhance paracrine effects. In vivo experiments reveal that the activated skin tissue engineering constructs significantly enhance wound healing as compared to control. This study indicates the advantages of synergistic effects between different bioactive signals of biomaterials can be taken to activate communication between different types of cells for obtaining tissue engineering constructs with improved functions. STATEMENT OF SIGNIFICANCE: Tissue engineering can regenerate or replace tissue or organs through combining cells, biomaterials and growth factors. Normally, for repairing a specific tissue, only one type of cells, one kind of biomaterials, and specific growth factors are used to support cell growth. In this study, we proposed a novel tissue engineering approach by simply using co-cultured cells and combined biomaterial signals. Using a skin tissue engineering model, we successfully proved that the combined biomaterial signals such as surface nanostructures and bioactive ions could synergistically stimulate the cell-cell communication in co-culture system through paracrine effects and gap junction activation, and regulated expression of growth factors and extracellular matrix proteins, resulting in an activated tissue engineering constructs that significantly enhanced skin regeneration.

A novel gellan-PVA nanofibrous scaffold for skin tissue regeneration: Fabrication and characterization.

In this investigation, we have introduced novel electrospun gellan based nanofibers as a hydrophilic scaffolding material for skin tissue regeneration. These nanofibers were fabricated using a blend mixture of gellan with polyvinyl alcohol (PVA). PVA reduced the repulsive force of resulting solution and lead to formation of uniform fibers with improved nanostructure. Field emission scanning electron microscopy (FESEM) confirmed the average diameter of nanofibers down to 50 nm. The infrared spectra (IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis evaluated the crosslinking, thermal stability and highly crystalline nature of gellan-PVA nanofibers, respectively. Furthermore, the cell culture studies using human dermal fibroblast (3T3L1) cells established that these gellan based nanofibrous scaffold could induce improved cell adhesion and enhanced cell growth than conventionally proposed gellan based hydrogels and dry films. Importantly, the nanofibrous scaffold are biodegradable and could be potentially used as a temporary substrate/or biomedical graft to induce skin tissue regeneration.

Naturally derived biofunctional nanofibrous scaffold for skin tissue regeneration.

Significant wound healing activity of Aloe vera (AV) and higher elastic strength of Silk fibroin (SF) along with mammalian cell compatibility makes AV and SF an attractive material for tissue engineering. The purpose of the present work was to combine their unique properties, with the advantage of electrospinning to prepare a hybrid transdermal biomaterial for dermal substitutes. The physico-chemical characterization of the developed scaffold showed finer morphology expressing amino and esteric groups with improved hydrophilic properties and favorable tensile strain of 116% desirable for skin tissue engineering. Their biological response showed favorable fibroblast proliferation compared to control which almost increased linearly by (p<0.01) 34.68% on day 3, (p<0.01) 19.13% on day 6, and (p<0.001) 97.86% on day 9 with higher expression of CMFDA, collagen and F-actin proteins. The obtained results prove that the nanofibrous scaffold with synergistic property of AV and SF would be a potential biomaterial for skin tissue regeneration.

Biocomposite nanofibrous strategies for the controlled release of biomolecules for skin tissue regeneration.

Nanotechnology and tissue engineering have enabled engineering of nanostructured strategies to meet the current challenges in skin tissue regeneration. Electrospinning technology creates porous nanofibrous scaffolds to mimic extracellular matrix of the native tissues. The present study was performed to gain some insights into the applications of poly(l-lactic acid)-co-poly-(ε-caprolactone) (PLACL)/silk fibroin (SF)/vitamin E (VE)/curcumin (Cur) nanofibrous scaffolds and to assess their potential for being used as substrates for the culture of human dermal fibroblasts for skin tissue engineering. PLACL/SF/VE/Cur nanofibrous scaffolds were fabricated by electrospinning and characterized by fiber morphology, membrane porosity, wettability, mechanical strength, and chemical properties by Fourier transform infrared (FTIR) analysis. Human dermal fibroblasts were cultured on these scaffolds, and the cell scaffold interactions were analyzed by cell proliferation, cell morphology, secretion of collagen, expression of F-actin, and 5-chloromethylfluorescein diacetate (CMFDA) dye. The electrospun nanofiber diameter was obtained between 198±4 nm and 332±13 nm for PLACL, PLACL/SF, PLACL/SF/VE, and PLACL/SF/VE/Cur nanofibrous scaffolds. FTIR analysis showed the presence of the amide groups I, II, and III, and a porosity of up to 92% obtained on these nanofibrous scaffolds. The results showed that the fibroblast proliferation, cell morphology, F-actin, CMFDA dye expression, and secretion of collagen were significantly increased in PLACL/SF/VE/Cur when compared to PLACL nanofibrous scaffolds. The accessibility of human dermal fibroblasts cultured on PLACL/SF/VE/Cur nanofibrous scaffolds proved to be a potential scaffold for skin tissue regeneration.