Field Of Skin Tissue Engineering Research Articles

Preparation, design, and characterization of an electrospun polyurethane/calcium chloride nanocomposite scaffold with improved properties for skin tissue regeneration

The present research paper explores the potential of electrospun nanofibers in the promising field of skin tissue engineering. Specifically, we propose an advanced preparation and characterization of an electrospun Polyurethane/Calcium Chloride (PU/CaCl2) nanocomposite scaffold, devised to boost the scaffold’s physicochemical and biological properties for skin tissue regeneration. By incorporating CaCl2 into the PU matrix using an electrospinning process, we were able to fabricate a novel nanocomposite scaffold. The morphological examination through Field Emission Scanning Electron Microscope (FESEM) revealed that the fiber diameter of the PU/CaCl2 (563 ± 147 nm) scaffold was notably smaller compared to the control (784 ± 149 nm). The presence of CaCl2 in the PU matrix was corroborated by Fourier-Transform Infrared Spectroscopy (FTIR) and Thermogravimetric Analysis (TGA). Furthermore, the PU/CaCl2 scaffold exhibited superior tensile strength (10.81 MPa) over pristine PU (Tensile −6.16 MPa, Contact angle - 109° ± 1° and Roughness - 854 ± 32 nm) and revealed enhanced wettability (72° ± 2°) and reduced surface roughness (274 ± 104 nm), as verified by Contact angle and Atomic Force Microscopy. The developed scaffold demonstrated improved anticoagulant properties, indicating its potential for successful integration within a biological environment. The improved properties of the PU/CaCl2 nanocomposite scaffold present a significant advancement in electrospun polymer nanofibers, offering a potential breakthrough in skin tissue engineering. However, additional studies are required to thoroughly evaluate the scaffold’s effectiveness in promoting cell adhesion, proliferation, and differentiation. We aim to catalyze significant advancements in the field by revealing the creation of a potent skin scaffold leveraging electrospun nanofibers. Encouraging deeper exploration into this innovative electrospun composite scaffold for skin tissue engineering, the PU/CaCl2 scaffold stands as a promising foundation for pioneering more innovative, efficient, and sustainable solutions in biomedical applications.

Fabrication and evaluation of poly(ε-caprolactone) based nanofibrous scaffolds loaded with homoeopathic mother tincture of Syzygium cumini for wound healing applications

Traditional wound healing substitutes loaded with bioactive molecules such as drugs, growth factors, and so on have been extensively researched in order to promote better wound healing and restore normal tissue function. The use of nanofibrous scaffolds has enhanced the biomaterial performance, thereby offering a promising solution as wound dressings in the field of skin tissue engineering. In the present study, the homoeopathic mother tincture extract of Syzygium cumini incorporated in poly(ε-caprolactone) nanofibrous scaffolds were fabricated in the concentration range of 5 %–20 % (w/w) and its various physicochemical and biological properties were evaluated. The fabricated nanofibers structurally mimicked the extracellular matrix, with enhanced hydrophilicity for better cellular attachment and proliferation. These scaffolds also showed anti-biofilm activity against P. aeruginosa and S. aureus and exhibited superior anti-oxidant activity. Furthermore, the extract incorporation was observed to be beneficial in cell adhesion, viability, growth and proliferation. This novel poly(ε-caprolactone) nanofibrous scaffold loaded with homoeopathic mother tincture extract of Syzygium cumini might be a suitable biomaterial for clinical management of wounds and reconstruction of damaged/diseased skin tissues.

Novel PLCL nanofibrous/keratin hydrogel bilayer wound dressing for skin wound repair

In this study, a novel poly(L-lactate-caprolactone) copolymer (PLCL) nanofibrous/keratin hydrogel bilayer wound dressing loaded with fibroblast growth factor (FGF-2) was prepared by the low-pressure filtration-assisted method. The ability of the keratin hydrogel in the bilayer dressing to mimic the dermis and that of the nanofibrous PLCL to mimic the epidermis were discussed. Keratin hydrogel exhibited good porosity and maximum water absorption of 874.09%. Compared with that of the dressing prepared by the coating method, the interface of the bilayer dressing manufactured by the low-pressure filtration-assisted method (filtration time: 20 min) was tightly bonded, and its bilayer dressing interface could not be easily peeled off. The elastic modulus of hydrogel was about 44 kPa, which was similar to the elastic modulus of the dermis (2–80 kPa). Additionally, PLCL nanofibers had certain toughness and flexibility suitable for simulating the epidermal structures. In vitro studies showed that the bilayer dressing was biocompatible and biodegradable. In vivo studies indicated that PLCL/keratin-FGF-2 bilayer dressing could promote re-epithelialization, collagen deposition, skin appendages (hair follicles) regeneration, microangiogenesis construction, and adipose-derived stem cells (ADSCs) recruitment. The introduction of FGF-2 resulted in a better repair effect. The bilayer dressing also solved the problems of poor interface adhesion of hydrogel/electrospinning nanofibers. This paper also explored the preliminary role and mechanism of bilayer dressing in promoting skin healing, showing that its potential applications as a biomedical wound dressing in the field of skin tissue engineering.

Three-layer core-shell structure of polypyrrole/polydopamine/poly(l-lactide) nanofibers for wound healing application

Poor wound healing is a very common clinical problem, so far there is no completely satisfactory treatment. Electropsun nanofibrous wound dressings may provide an ideal structure to improve wound healing. Therefore, development of nanofibrous wound dressings with rapid hemostasis, antibacterial and tissue regenerative multi-functions has been a hotspot in the field of skin tissue engineering. In this work, polydopamine (PDA) and polypyrrole (PPy) were uniformly coated onto the surface of poly(l-lactide) (PLLA) nanofibers by in-situ polymerization, forming a novel PPy/PDA/PLLA three-layer core-shell structure. The homogeneously coated PPy and PDA two layers could significantly increase the hydrophilicity, conductivity, near-infrared photothermal antibacterial property, the speed of wound hemostasis, antioxidant capacity and reactive oxygen species (ROS) scavenging capacity, respectively. In addition, PPy/PDA/PLLA nanofibers showed good biocompatibility. Rat wound healing model confirmed that PPy/PDA/PLLA nanofibers could significantly accelerate wound repair in vivo. Thus, this novel nanofibrous wound dressing is a promising candidate for clinical wound healing.

In Vivo Comparison of Synthetic Macroporous Filamentous and Sponge-like Skin Substitute Matrices Reveals Morphometric Features of the Foreign Body Reaction According to 3D Biomaterial Designs.

Synthetic macroporous biomaterials are widely used in the field of skin tissue engineering to mimic membrane functions of the native dermis. Biomaterial designs can be subclassified with respect to their shape in fibrous designs, namely fibers, meshes or fleeces, respectively, and porous designs, such as sponges and foams. However, synthetic matrices often have limitations regarding unfavorable foreign body responses (FBRs). Severe FBRs can result in unfavorable disintegration and rejection of an implant, whereas mild FBRs can lead to an acceptable integration of a biomaterial. In this context, comparative in vivo studies of different three-dimensional (3D) matrix designs are rare. Especially, the differences regarding FBRs between synthetically derived filamentous fleeces and sponge-like constructs are unknown. In the present study, the FBRs on two 3D matrix designs were explored after 25 days of subcutaneous implantation in a porcine model. Cellular reactions were quantified histopathologically to investigate in which way the FBR is influenced by the biomaterial architecture. Our results show that FBR metrics (polymorph-nucleated cells and fibrotic reactions) were significantly affected according to the matrix designs. Our findings contribute to a better understanding of the 3D matrix tissue interactions and can be useful for future developments of synthetically derived skin substitute biomaterials.

Novel bioactive adhesive dressing based on gelatin/ chitosan cross-linked cactus mucilage for wound healing.

The development of natural-based wound dressings is of great interest in the field of skin tissue engineering. Herein, different bioactive molecules such as gelatin (GEL), chitosan (CH) and mucilage (MU) were used to prepare a wound dressing. The physico-chemical and biological characterizations occurring after γ-irradiation were investigated. Results showed that Electron Paramagnetic Resonance (EPR) spectroscopy of un-irradiated GEL-CH-MU biomaterial showed two paramagnetic centers which correspond to g = 1.89 and g = 2.033. A generated new active center appeared at g = 2.003 at 25 kGy due to the interactions of gamma rays with the polymer chain creating signals at the absorbing functional groups. X-ray diffraction (XRD) spectra preserved the semi-crystalline structures between a range of 2θ (5° and 45°). Fourier Transform Infrared spectroscopy (FTIR) revealed that the initiation of cross linking phenomena. Moreover, γ-rays significantly increased antioxidant activity (9.1 ± 0.07%, p < 0.05) and exhibited a high anti-inflammatory activity (70%) at 25 kGy. Significant antibacterial activities in vitro liquid medium was observed. In addition GEL-CH-MU dressing exhibited high hemocompatibility. Conducted investigations state that such innovative dressing natural-based polymers for advanced wound care may be considered as useful for biomedical purposes.

3D-printed antioxidant antibacterial carboxymethyl cellulose/ε-polylysine hydrogel promoted skin wound repair

Developing a wound dressing for the treatment of large and irregular-shaped wounds remains a great challenge. Herein we developed novel printable bionic hydrogels with antibacterial and antioxidant properties which could effectively overcome the challenge by inhibiting inflammation and accelerating wound healing. The CMC/PL (CP) hydrogels were customized with glycidyl methacrylate (GMA) modified carboxymethyl cellulose (CMC) and ε-polylysine (ε-PL) via ultraviolet (UV) light polymerization using a 3D printer. Except for the high compression modulus (238 kPa), stable rheological properties, and effective degradability, these CP hydrogels also had an excellent inhibitory effect (95%) on both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Remarkably, CP hydrogels could remove the excessive reactive oxygen species (ROS) and protect the fibroblasts from damage. Compared with the commercial dressing (Tegaderm ™ film), CP hydrogels showed a better ability to increase the expression of VEGF and CD31, accelerate granulation tissue regeneration, and promote wound healing. This work provides a new strategy to fabricate on-demand multi-functional hydrogels in the field of skin tissue engineering.

Mechano-regulation of vascular network formation without branches in 3D bioprinted cell-laden hydrogel constructs.

Restoration of a wound is a common surgical procedure in clinic. Currently, the skin required for clinical use is taken from the patient's own body. However, it can be difficult to obtain enough skin sources for large-sized wounds and thus surgeons have started using commercial skin substitutes. The current commercial skin, which includes epidermis substitute, dermis substitute, and bilateral skin substitute, has been popularized in clinic. However, the application is limited by the occurrence of ischemia necrosis after transplantation. Recent studies suggest the use of pre-vascularized skin substitutes for wound healing is a promising area in the research field of skin tissue engineering. Pre-vascularization can be induced by changes in cultivation periods, exertion of mechanical stimuli, or coculture with endothelial cells and various factors. However, few methods could control the formation of vascular branches in engineering tissue in a self-assembly way. In this study, we use three-dimensional (3D) printing technology to confirm that a mechanical force can control the growth of blood vessels in the direction of mechanical stimulation with no branches, and that Yes-associated protein activity is involved in the regulatory progress. In vivo experiments verified that the blood vessels successfully function for blood circulation, and maintain the same direction. Results provide a theoretical basis for products of pre-vascularized skin tissues and other organs created by 3D bioprinting.

Electrospun wound dressings containing bioactive natural products: physico-chemical characterization and biological assessment

BackgroundCurrent research on skin tissue engineering has been focusing on novel therapies for the effective management of chronic wounds. A critical aspect is to develop matrices that promote growth and uniform distribution of cells across the wound area, and at the same time offer protection, as well as deliver drugs that help wound healing and tissue regeneration. In this context, we aimed at developing electrospun scaffolds that could serve as carriers for the bioactive natural products alkannin and shikonin (A/S).MethodsA series of polymeric nanofibers composed of cellulose acetate (CA) or poly(ε-caprolactone) (PCL) and varying ratios of a mixture of A/S derivatives, has been successfully fabricated and their physico-chemical and biological properties have been explored.ResultsScanning electron microscopy revealed a uniform and bead-free morphology for CA scaffolds, while for PCL beads along the fibers were observed. The average diameters for all nanofibers ranged between 361 ± 47 and 487 ± 88 nm. During the assessment of physicochemical characteristics, CA fiber mats exhibited a more favored profile, while the assessment of the biological properties of the scaffolds showed that CA samples containing A/S mixture up to 1 wt.% achieved to facilitate attachment, survival and migration of Hs27 fibroblasts. With respect to the antimicrobial properties of the scaffolds, higher drug-loaded (1 and 5 wt.%) samples succeeded in inhibiting the growth of Staphylococcus epidermidis and S. aureus around the edges of the fiber mats. Finally, carrying out a structure-activity relationship study regarding the biological activities (fibroblast toxicity/proliferation and antibacterial activity) of pure A/S compounds – present in the A/S mixture – we concluded that A/S ester derivatives and the dimeric A/S augmented cell proliferation after 3 days, whereas shikonin proved to be toxic at 500 nM and 1 μM and alkannin only at 1 μM. Additionally, alkannin, shikonin and acetyl-shikonin showed more pronounced antibacterial properties than the other esters, the dimeric derivative and the A/S mixture itself.ConclusionsTaken together, these findings indicate that embedding A/S derivatives into CA nanofibers might be an advantageous drug delivery system that could also serve as a potential candidate for biomedical applications in the field of skin tissue engineering.

Three dimensional spongy fibroin scaffolds containing keratin/vanillin particles as an antibacterial skin tissue engineering scaffold

Despite major progress in the field of skin tissue engineering and wound care products, reconstruction of skin defects still represents a significant challenge associated with impaired healing and wound infection. In the present study, a novel antibacterial 3 D spongy fibroin-based skin tissue engineering scaffold incorporated with vanillin-loaded keratin particles was fabricated through a freeze-drying process. The obtained scaffolds offered a well-connected porous structure with a pore size of higher than 100 nm, a high water uptake capacity (>700%) and slow in vitro degradation over 60 days, and drug release profile indicated a prolonged vanillin release up to 14 days from the scaffolds. Furthermore, anti-bacterial and in vitro cell experiments demonstrated a bactericidal activity by incorporating vanillin into the scaffolds, besides excellent cell attachment and cytocompatibility at lower vanillin concentrations (1, 5 and 10 mM, FKV1, FKV5 and FKV10, respectively); however, a significant cytotoxicity was observed at elevated vanillin concentration (20 mM, FKV20). Hence, these findings indicate that local delivery of incorporated vanillin within fibroin-based scaffolds presents promising potential for improving anti-bacterial biomaterials for skin tissue engineering.

Advanced Hydrogels as Wound Dressings.

Skin is the largest organ of the human body, protecting it against the external environment. Despite high self-regeneration potential, severe skin defects will not heal spontaneously and need to be covered by skin substitutes. Tremendous progress has been made in the field of skin tissue engineering, in recent years, to develop new skin substitutes. Among them, hydrogels are one of the candidates with most potential to mimic the native skin microenvironment, due to their porous and hydrated molecular structure. They can be applied as a permanent or temporary dressing for different wounds to support the regeneration and healing of the injured epidermis, dermis, or both. Based on the material used for their fabrication, hydrogels can be subdivided into two main groups—natural and synthetic. Moreover, hydrogels can be reinforced by incorporating nanoparticles to obtain “in situ” hybrid hydrogels, showing superior properties and tailored functionality. In addition, different sensors can be embedded in hydrogel wound dressings to provide real-time information about the wound environment. This review focuses on the most recent developments in the field of hydrogel-based skin substitutes for skin replacement. In particular, we discuss the synthesis, fabrication, and biomedical application of novel “smart” hydrogels.

Improvement of a Three-Layered in vitro Skin Model for Topical Application of Irritating Substances.

In the field of skin tissue engineering, the development of physiologically relevant in vitro skin models comprising all skin layers, namely epidermis, dermis, and subcutis, is a great challenge. Increasing regulatory requirements and the ban on animal experiments for substance testing demand the development of reliable and in vivo-like test systems, which enable high-throughput screening of substances. However, the reproducibility and applicability of in vitro testing has so far been insufficient due to fibroblast-mediated contraction. To overcome this pitfall, an advanced 3-layered skin model was developed. While the epidermis of standard skin models showed an 80% contraction, the initial epidermal area of our advanced skin models was maintained. The improved barrier function of the advanced models was quantified by an indirect barrier function test and a permeability assay. Histochemical and immunofluorescence staining of the advanced model showed well-defined epidermal layers, a dermal part with distributed human dermal fibroblasts and a subcutis with round-shaped adipocytes. The successful response of these advanced 3-layered models for skin irritation testing demonstrated the suitability as an in vitro model for these clinical tests: only the advanced model classified irritative and non-irritative substances correctly. These results indicate that the advanced set up of the 3-layered in vitro skin model maintains skin barrier function and therefore makes them more suitable for irritation testing.

Identification by next generation sequencing analysis of secreted small rnas from IL-1β-primed gingival mesenchymal stromal cells with pro-healing properties

Background & Aim In spite of several research advances in the field of skin tissue engineering and regenerative medicine, severe burns clinical management remains a major therapeutic issue. During the past few years, Mesenchymal Stromal Cells (MSCs) have become an attractive therapeutic option to improve tissue repair such as skin disorders. Several preclinical studies have highlighted their potential to reduce inflammation and promote reepithelialization through the secretion of bioactive molecules and extracellular vesicles containing proteins, mRNA and microRNAs. Recent discovery of their high plasticity to external stimuli has fostered the development of new targeted therapies known as “priming strategies”, that could orientate secretory products of MSCs. IL-1β is a molecule released early after an injury and can persist at high levels long after severe skin traumas such as burn. Therefore, IL-1β was used in a previous study as priming molecule and we found that IL-1β-primed gingival MSCs were superior to naive MSCs to improve wound healing and epidermal engraftment in vitro and in vivo. In the present study, we investigated the mechanism by which IL-1β-primed MSC promote a better wound healing. In particular, we wondered if some small RNAs are implicated in the activities of MSC. Methods, Results & Conclusion Therefore, we analyzed small RNAs with Next Generation Sequencing technic and PCR in conditioned media prepared from IL-1β-primed or naive gingival MSC culture. This analysis showed the down regulation and upregulation of several kind of small RNAs. We found that IL-1β-primed MSCs secrete higher level of miRNAs playing a role in inflammation such as miR-210-3p, and miR146-5p. This analysis also highlights a great number of other small RNAs that can be implicated in the pro-healing effect of primed MSC observed in our in vitro and in vivo models. To investigate their involvement in the wound healing process, mimics RNA corresponding to miRNA and other small RNA candidates will be used in models of inflammation, migration and dermal-epidermal junction formation in vitro. This study aims to better understand the mechanism of action of IL-1β primed MSC on wound healing, and the impact of the priming on the RNA secretion.

Polycaprolactone/Gelatin Nanofiber Membranes Containing EGCG-Loaded Liposomes and Their Potential Use for Skin Regeneration.

Polymeric scaffolds incorporating plant-derived compounds, produced by electrospinning, have attracted attention in the field of skin tissue engineering. This study evaluates the sustained antioxidant activity of polycaprolactone (PCL)/gelatin nanofibers prepared by electrospinning and incorporating loaded liposomes of epigallocatechin-3-gallate (EGCG), a strong antibacterial and antioxidant molecule found in green tea, that significantly accelerates the wound-healing process. The morphology and the structural properties of the membranes were characterized by scanning electron microscopy (SEM) and FTIR spectroscopy. Results revealed that the EGCG released from PCL+gelatin nanofibers scavenges the toxic ROS species generated by exposure to either H2O2 or UV radiation and slows down the oxidation events associated with damage. This study provides the basis for development of promising nanofiber formulations containing EGCG that might enhance repair/regeneration of skin tissue.

HGF, MMPs and TGF-β1 contribute to INTERLEUKIN-1β primed mesenchymal stromal cells effect on wound healing and epidermal substitute engraftment

Background & Aim In spite of several research advances in the field of skin tissue engineering and regenerative medicine, little progress has been made in the management of major burns. Since the 1980s, deep and extensive skin wounds and burns are treated with autologous Split-Thickness Skin Grafts, or Cultured Epidermal Autografts (CEAs) when donor sites are limited. While CEAs allow patient survival in most critical cases, poor engraftment rates and reduced skin functionality limit the clinical use of CEAs. In the past few decades, Mesenchymal Stromal Cells (MSCs) therapy has emerged as a new strategy to promote wound healing through anti-inflammatory, anti-microbial, pro-trophic and pro-remodeling effects. MSCs are also able to interact with their environment and modify their secretory profile depending on cellular, molecular or physical priming cues. Thus, the present work aims to assess the benefit and mechanism of action of Interleukin-1β (IL-1β) primed MSCs or their secretory products on wound healing and epidermal substitute engraftment. Methods, Results & Conclusion Naive and IL-1β-primed MSCs or their Conditioned Media (CM) were evaluated in in vitro models of migration, inflammation and Dermal-Epidermal Junction (DEJ) formation, and in an in vivo skin excisional and epidermal substitute grafting mouse model. We showed that the IL-1β priming potentiates the MSC efficacy through the reduction of inflammation and the promotion of cell migration, DEJ remodeling and epidermal substitute engraftment. These positive effects were partly mediated by MSC paracrine secretions which targeted downstream p38MAPK, SMAD and MMP signalings. Among priming-induced secreted factors, MMP-1, MMP-9, HGF and TGF-β1 were found to play key roles in the resolution of wound healing. These results underline the benefit of the IL-1β priming strategy in the treatment of severe skin defects using MSC and epidermal substitute. We hope that this approach could soon improve the current medical treatment of full-thickness burn wounds.

Characterization and Evaluation of Carboxymethyl Cellulose-Based Films for Healing of Full-Thickness Wounds in Normal and Diabetic Rats.

Artificial skin substitute made of polymeric films are of great demand in the field of skin tissue engineering. We report here the fabrication of carboxymethyl cellulose (CMC) and poly(ethylene glycol) (PEG) blend films by solution casting method for wound healing applications. The physicochemical characteristics and the thermal stability of the films were analyzed. The surface morphology shows crystalline structures with large hexagonal-like platelet crystals of CMC on the surface of the films. Pure CMC films exhibited higher tensile strength than the CMC/PEG blend films. The swelling ratio (SR) of the films was influenced by the pH of Tris–HCL buffer (2.0, 5.0, and 7.0), which increased with increase in pH. The hemocompatibility assay and cytotoxicity test using NIH 3T3 fibroblast cells showed that the films were biocompatible. To evaluate the wound healing efficacy, the films were applied in full-thickness wounds created in normal and diabetic Wistar albino rats. The wounds healed faster with pure CMC film compared to blend films in both normal and diabetic rats, evidenced by intensive collagen formation in histopathological analysis. Thus, the films have potential application in skin regeneration, thereby to restore the structural and functional characteristics of the skin.

Three-Dimensional Printing and Cell Therapy for Wound Repair.

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Progress and Future Prospectives in Skin-on-Chip Development with Emphasis on the use of Different Cell Types and Technical Challenges

Understanding the healthy and diseased state of skin is important in many areas of basic and applied research. Although the field of skin tissue engineering has advanced greatly over the last years, current in vitro skin models still do not mimic the complexity of the human skin. Skin-on-chip and induced pluripotent stem cells (iPSC) might be key technologies to improve in vitro skin models. This review summarizes the state of the art of in vitro skin models with regard to cell sources (primary, cell line, iPSC) and microfluidic devices. It can be concluded that iPSC have the potential to be differentiated into many kinds of immunologically matched cells and skin-on-chip technology might lead to more physiologically relevant skin models due to the controlled environment, possible exchange of immune cells, and an increased barrier function. Therefore the combination of iPSC and skin-on-chip is expected to lead to superior healthy and diseased in vitro skin models.

Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review.

Over centuries, the field of regenerative skin tissue engineering has had several advancements to facilitate faster wound healing and thereby restoration of skin. Skin tissue regeneration is mainly based on the use of suitable scaffold matrices. There are several scaffold types, such as porous, fibrous, microsphere, hydrogel, composite and acellular, etc., with discrete advantages and disadvantages. These scaffolds are either made up of highly biocompatible natural biomaterials, such as collagen, chitosan, etc., or synthetic materials, such as polycaprolactone (PCL), and poly-ethylene-glycol (PEG), etc. Composite scaffolds, which are a combination of natural or synthetic biomaterials, are highly biocompatible with improved tensile strength for effective skin tissue regeneration. Appropriate knowledge of the properties, advantages and disadvantages of various biomaterials and scaffolds will accelerate the production of suitable scaffolds for skin tissue regeneration applications. At the same time, emphasis on some of the leading challenges in the field of skin tissue engineering, such as cell interaction with scaffolds, faster cellular proliferation/differentiation, and vascularization of engineered tissues, is inevitable. In this review, we discuss various types of scaffolding approaches and biomaterials used in the field of skin tissue engineering and more importantly their future prospects in skin tissue regeneration efforts.

Preparation and properties of PLGA nanofiber membranes reinforced with cellulose nanocrystals

Although extensively used in the fields of drug-carrier and tissue engineering, the biocompatibility and mechanical properties of polylactide–polyglycolide (PLGA) nanofiber membranes still limit their applications. The objective of this study was to improve their utility by introducing cellulose nanocrystals (CNCs) into PLGA nanofiber membranes. PLGA and PLGA/CNC composite nanofiber membranes were prepared via electrospinning, and the morphology and thermodynamic and mechanical properties of these nanofiber membranes were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). The cytocompatibility and cellular responses of the nanofiber membranes were also studied by WST-1 assay, SEM, and confocal laser scanning microscopy (CLSM). Incorporation of CNCs (1, 3, 5, and 7wt.%) increased the average fiber diameter of the prepared nanofiber membranes from 100nm (neat PLGA) to ∼400nm (PLGA/7wt.% CNC) and improved the thermal stability of the nanofiber membranes. Among the PLGA/CNC composite nanofiber membranes, those loaded with 7wt.% CNC nanofiber membranes had the best mechanical properties, which were similar to those of human skin. Cell culture results showed that the PLGA/CNC composite nanofiber membranes had better cytocompatibility and facilitated fibroblast adhesion, spreading, and proliferation compared with neat PLGA nanofiber membranes. These preliminary results suggest that PLGA/CNC composite nanofiber membranes are promising new materials for the field of skin tissue engineering.