In Situ Sodium Chloride Cross-Linked Fish Skin Collagen Scaffolds for Functional Hemostasis Materials.

Current fish collagen hemostasis for wound healing products is commonly obtained by electrospinning or artificial cross-linking fish collagen fibers which lacks mechanical properties, and biofunctions. Here, a new bio-active fish skin scaffold (FSS) is shown using in situ cross-linked scaleless freshwater fish skin adding adipose-derived stem cells (ASCs)-produced exosomes for hemostasis and wound healing. The structure, pore size, and the thickness of FSS is studied by swelling test, Fourier-transform infrared (FT-IR) spectra, scanning electron microscope (SEM) images, and histological analysis. The biofunctions of the FSS are also tested in vitro and in vivo. FSS keeps two functional layers: The dermis layer collagen forms a sponge like structure after swelling and in situ cross-linking treatments. The pore size of the FSS is ≈152 ± 23.54 µm, which is suitable for cells growing, angiogenesis and ASCs exosomes accelerate wound healing. The fat-rich epidermis layer can keep the wound moisty and clean before completely healed. In vitro and in vivo experimental results indicate that FSS+Exosomes enhances rat skin cavity wound healing. In situ sodium chloride cross-linked FSS+Exosomes provides a new strategy as functional hemostatic dressing scaffold for wound healing.

Evaluation of an antibacterial peptide-loaded amniotic membrane/silk fibroin electrospun nanofiber in wound healing.

Antimicrobial peptides (AMPs) are among the compounds that have significant potential to deal with infectious skin wounds. Using wound dressings or skin scaffolds containing AMPs can be an effective way to overcome infections caused by antibiotic-resistant strains. In this study, we developed an amniotic membrane-based skin scaffold using silk fibroin to improve mechanical properties and CM11 peptide as an antimicrobial peptide. The peptide was coated on the scaffold using the soaking method. The fabricated scaffold was characterised by SEM and FTIR, and their mechanical strength, biodegradation, peptide release, and cell cytotoxicity analyses were performed. Then, their antimicrobial activity was measured against antibiotic-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. The in vivo biocompatibility of this scaffold was evaluated by subcutaneously implanting it under the skin of the mouse and counting lymphocytes and macrophages in the implanted area. Finally, the regenerative ability of the scaffold was analyzed in the mouse full-thickness wound model by measuring the wound diameter, H&E staining, and examining the expression rate of genes involved in the wound healing process. The developed scaffolds exerted an inhibiting effect on the bacteria growth, indicating their proper antimicrobial property. In vivo biocompatibility results showed no significant count of macrophages and lymphocytes between the test and control groups. The wound closure rate was significantly higher in the wound covered with fibroin electrospun-amniotic membrane loaded with 32 µg/mL CM11, where the relative expression rates of collagen I, collagen III, TGF-ß1 and TGF-ß3 were higher compared with the other groups.

Comparison of Type I and Type III Collagen Concentration between Oreochromis mossambicus and Oreochromis niloticus in Relation to Skin Scaffolding.

Background and Objectives: Skin scaffolding can be done using allografts and autografts. As a biological allograft, the skin of Oreochromis niloticus (ON) has been used due to its high type I and III collagen content. Oreochromis mossambicus (OM) is also a member of the Oreochromis family, but not much is known regarding its collagen content. As such, this study aimed to assess and compare the collagen content of the two fish species. Materials and Methods: This is a crossover study comparing the skin collagen contents of the two fish. Young fish were chosen, as they tend to have higher collagen concentrations. The skin samples were sterilized in chlorhexidine and increasing glycerol solutions and analyzed histochemically with Sirius red picrate under polarized light microscopy. Results: 6 young ON and 4 OM specimens were used. Baseline type I collagen was higher for OM, but at maximum sterilization it was higher for ON, with no differences in between Type III collagen was higher for OM across all comparisons with the exception of the last stage of sterilization. Generally, collagen concentrations were higher in highly sterilized samples. Conclusions: OM skin harvested from young fish, with its greater collagen III content may be a better candidate for use as a biological skin scaffold in the treatment of burn wounds, compared to ON.

3D bioprinting of Salvianolic acid B-sodium alginate-gelatin skin scaffolds promotes diabetic wound repair via antioxidant, anti-inflammatory, and proangiogenic effects.

In patients with diabetic wounds, wound healing is impaired due to the presence of persistent oxidative stress, an altered inflammatory response, and impaired angiogenesis and epithelization. Salvianolic acid B (SAB), which is derived from the Chinese medicinal plant Salvia miltiorrhiza, has been found to exhibit antioxidant, anti-inflammatory, and proangiogenic effects. Previous studies have used 3D bioprinting technology incorporating sodium alginate (SA) and gelatin (Gel) as basic biomaterials to successfully produce artificial skin. In the current study, 3D bioprinting technology was used to incorporate SAB into SA-Gel to form a novel SAB-SA-Gel composite porous scaffold. The morphological characteristics, physicochemical characteristics, biocompatibility, and SAB release profile of the SAB-SA-Gel scaffolds were evaluated in vitro. In addition, the antioxidant, anti-inflammatory, and proangiogenic abilities of the SAB-SA-Gel scaffolds were evaluated in cells and in a rat model. Analysis demonstrated that 1.0 wt% (the percentage of SAB in the total weight of the solution containing SA and Gel) SAB-SA-Gel scaffolds had strong antioxidant, anti-inflammatory, and proangiogenic properties both in cells and in the rat model. The 1.0% SAB-SA-Gel scaffold reduced the expression of tumor necrosis factor-α, interleukin-6, and interluekin-1ß and increased the expression of transforming growth factor-ß. In addition, this scaffold removed excessive reactive oxygen species by increasing the expression of superoxide dismutase, thereby protecting fibroblasts from injury. The scaffold increased the expression of vascular endothelial growth factor and platelet/endothelial cell adhesion molecule-1, accelerated granulation tissue regeneration and collagen deposition, and promoted wound healing. These findings suggest that this innovative scaffold may have promise as a simple and efficient approach to managing diabetic wound repair.

Electrospinning/3D printing drug-loaded antibacterial polycaprolactone nanofiber/sodium alginate-gelatin hydrogel bilayer scaffold for skin wound repair.

Skin injuries and defects, as a common clinical issue, still cannot be perfectly repaired at present, particularly large-scale and infected skin defects. Therefore, in this work, a drug-loaded bilayer skin scaffold was developed for repairing full-thickness skin defects. Briefly, amoxicillin (AMX) was loaded on polycaprolactone (PCL) nanofiber via electrospinning to form the antibacterial nanofiber membrane (PCL-AMX) as the outer layer of scaffold to mimic epidermis. To maintain wound wettability and promote wound healing, external human epidermal growth factor (rhEGF) was loaded in sodium alginate-gelatin to form the hydrogel structure (SG-rhEGF) via 3D printing as inner layer of scaffold to mimic dermis. AMX and rhEGF were successfully loaded into the scaffold. The scaffold exhibited excellent physicochemical properties, with elongation at break and tensile modulus were 102.09 ± 6.74% and 206.83 ± 32.10 kPa, respectively; the outer layer was hydrophobic (WCA was 112.09 ± 4.67°), while the inner layer was hydrophilic (WCA was 48.87 ± 5.52°). Meanwhile, the scaffold showed excellent drug release and antibacterial characteristics. In vitro and in vivo studies indicated that the fabricated scaffold could enhance cell adhesion and proliferation, and promote skin wound healing, with favorable biocompatibility and great potential for skin regeneration and clinical application.

Multi-variate multi-objective optimization of production conditions for electro-spun skin scaffold using RSM and investigation of gamma irradiation effects on the properties of the optimized sample.

Developing electro-spun scaffolds with ideal mechanical properties for skin purposes can profit from using the Response Surface Methodology technique to define and optimize the outcome quality and required sterilization for use in vivo. This study investigated the effects of four main independent electrospinning variables for polycaprolactone nanofibers scaffold using multi-variable and multi-objective optimization. It was done to determine significant parameters on responses and find optimal conditions to reach the preferred properties. Young's modulus, elongation-at-break, and tensile strength were the responses. After obtaining appropriate models, the impact share of variables on the responses was determined using Sobol sensitivity analysis. The results showed that flow rate is the most significant parameter of elastic modulus and tensile strength responses, with 76.45 % and 41.27 % impact shares, respectively. The polymer concentration is the following significant parameter on elongation at break, tensile strength and, Young's modulus responses with 64.35 %, 39.485 and, 14.28 % impact share, respectively. Based on the optimized results, a skin scaffold with desired mechanical properties was achieved (under solution concentration of 10 % w/v, flow rate of 2 mL/h, nuzzle-collector distance of 15 cm, and applied voltage of 20 kV). Then it was sterilized with gamma radiation of various doses (25, 40, and 55 kGy) to use in vivo. The SEM analysis indicated no significant change in fibrous morphology due to gamma irradiation at any dosage. FTIR analysis demonstrated the breakup of ester bonds due to gamma irradiation. For samples irradiated by 25 kGy, the crystallinity percentage decreased and chains crosslinking without losing the mechanical stability was dominant. The studies demonstrated that 25 kGy of gamma irradiation could improve the mechanical properties of the optimized PCL skin scaffold, which is very promising for wound healing.

Fabrication and characterization of an antibacterial chitosan-coated allantoin-loaded NaCMC/SA skin scaffold for wound healing applications.

The field of tissue engineering has recently emerged as one of the most promising approaches to address the limitations of conventional tissue replacements for severe injuries. This study introduces a chitosan-coated porous skin scaffold based on sodium carboxymethyl cellulose (NaCMC) and sodium alginate (SA) hydrogels, incorporating allantoin (AL) as an antibacterial agent. The NaCMC/SA hydrogel was cross-linked with epichlorohydrin (ECH) and freeze-dried to obtain a three-dimensional porous structure. The coated and non-coated scaffolds underwent comprehensive evaluation and characterization through various in-vitro analyses, including SEM imaging, swelling, degradation, and mechanical assessments. Furthermore, the scaffolds were studied regarding their allantoin (AL) release profiles, antibacterial properties, cell viability, and cell adhesion. The in-vitro analyses revealed that adding a chitosan (CS) coating and allantoin (AL) to the NaCMC/SA hydrogel significantly improved the scaffolds' antibacterial properties and cell viability. It was observed that the NaCMC:SA ratio and ECH concentration influenced the swelling capacity, biodegradation, drug release profile, and mechanical properties of the scaffolds. Samples with higher NaCMC content exhibited enhanced swelling capacity, more controlled allantoin (AL) release, and improved mechanical strength. Furthermore, the in-vivo results demonstrated that the proposed skin scaffold exhibited satisfactory biocompatibility and supported cell viability during wound healing in Wistar rats, highlighting its potential for clinical applications.

3D-Printed Auxetic Skin Scaffold for Decreasing Burn Wound Contractures at Joints.

For patients with severe burns that consist of contractures induced by fibrous scar tissue formation, a graft must adhere completely to the wound bed to enable wound healing and neovascularization. However, currently available grafts are insufficient for scar suppression owing to their nonuniform pressure distribution in the wound area. Therefore, considering the characteristics of human skin, which is omnidirectionally stretched via uniaxial stretching, we proposed an auxetic skin scaffold with a negative Poisson's ratio (NPR) for tight adherence to the skin scaffold on the wound bed site. Briefly, a skin scaffold with the NPR effect was fabricated by creating a fine pattern through 3D printing. Electrospun layers were also added to improve adhesion to the wound bed. Fabricated skin scaffolds displayed NPR characteristics (-0.5 to -0.1) based on pulling simulation and experiment. Finger bending motion tests verified the decreased marginal forces (<50%) and deformation (<60%) of the NPR scaffold. In addition, the filling of human dermal fibroblasts in most areas (>95%) of the scaffold comprising rarely dead cells and their spindle-shaped morphologies revealed the high cytocompatibility of the developed scaffold. Overall, the developed skin scaffold may help reduce wound strictures in the joints of patients with burns as it exerts less pressure on the wound margin.

Fabrication of Fibrin/Polyvinyl Alcohol Scaffolds for Skin Tissue Engineering via Emulsion Templating.

In the search for a novel and scalable skin scaffold for wound healing and tissue regeneration, we fabricated a class of fibrin/polyvinyl alcohol (PVA) scaffolds using an emulsion templating method. The fibrin/PVA scaffolds were formed by enzymatic coagulation of fibrinogen with thrombin in the presence of PVA as a bulking agent and an emulsion phase as the porogen, with glutaraldehyde as the cross-linking agent. After freeze drying, the scaffolds were characterized and evaluated for biocompatibility and efficacy of dermal reconstruction. SEM analysis showed that the formed scaffolds had interconnected porous structures (average pore size e was around 330 µm) and preserved the nano-scale fibrous architecture of the fibrin. Mechanical testing showed that the scaffolds' ultimate tensile strength was around 0.12 MPa with an elongation of around 50%. The proteolytic degradation of scaffolds could be controlled over a wide range by varying the type or degree of cross-linking and by fibrin/PVA composition. Assessment of cytocompatibility by human mesenchymal stem cell (MSC) proliferation assays shows that MSC can attach, penetrate, and proliferate into the fibrin/PVA scaffolds with an elongated and stretched morphology. The efficacy of scaffolds for tissue reconstruction was evaluated in a murine full-thickness skin excision defect model. The scaffolds were integrated and resorbed without inflammatory infiltration and, compared to control wounds, promoted deeper neodermal formation, greater collagen fiber deposition, facilitated angiogenesis, and significantly accelerated wound healing and epithelial closure. The experimental data showed that the fabricated fibrin/PVA scaffolds are promising for skin repair and skin tissue engineering.

The efficacy of a paeoniflorin-sodium alginate-gelatin skin scaffold for the treatment of diabetic wound: An in vivo study in a rat model.

OBJECTIVE: To investigate the efficacy of a paeoniflorin-sodium alginate (SA)-gelatin skin scaffold for treating diabetic wound in a rat model. METHODS: Bioinks were prepared using various percentages of paeoniflorin in the total weight of a solution containing SA and gelatin. Skin scaffolds containing 0%, 1%, 3%, 5%, and 10% paeoniflorin were printed using 3D bioprinting technology, and scaffold microstructure was observed with scanning electron microscopy. Skin scaffolds were then used in rats with diabetic wounds. H&E staining, Masson staining, and immunohistochemical staining for IL-1ß and CD31 were performed on days 7 and 14. RESULTS: All skin scaffolds had a mesh-like structure with uniform pore distribution. Wounds healed well in each group, with the 1% and 3% groups demonstrating the most complete healing. H&E staining showed that skin accessory organs had appeared in each group. On day 7, collagen deposition in the 3% group was higher than in the other groups (P＜0.05), and IL-1ß infiltration was lower in the 10% group than in the 3% group (P = 0.002). On day 14, IL-1ß infiltration was not significantly different between the 10% and 3% groups (P = 0.078). The CD31 level was higher in the 3% group than in the other groups on days 7 and 14 (P＜0.05). CONCLUSION: A 3% paeoniflorin-SA-gelatin skin scaffold promoted the healing of diabetic wounds in rats. This scaffold promoted collagen deposition and microvascular regeneration and demonstrated anti-inflammatory properties, suggesting that this scaffold type could be used to treat diabetic wounds.

Fabrication of SA/Gel/C scaffold with 3D bioprinting to generate micro-nano porosity structure for skin wound healing: a detailed animal in vivo study.

Bioprinting has exhibited remarkable promises for the fabrication of functional skin substitutes. However, there are some significant challenges for the treatment of full-thickness skin defects in clinical practice. It is necessary to determine bioinks with suitable mechanical properties and desirable biocompatibilities. Additionally, the key for printing skin is to design the skin structure optimally, enabling the function of the skin. In this study, the full-thickness skin scaffolds were prepared with a gradient pore structure constructing the dense layer, epidermis, and dermis by different ratios of bioinks. We hypothesized that the dense layer protects the wound surface and maintains a moist environment on the wound surface. By developing a suitable hydrogel bioink formulation (sodium alginate/gelatin/collagen), to simulate the physiological structure of the skin via 3D printing, the proportion of hydrogels was optimized corresponding to each layer. These results reveal that the scaffold has interconnected macroscopic channels, and sodium alginate/gelatin/collagen scaffolds accelerated wound healing, reduced skin wound contraction, and re-epithelialization in vivo. It is expected to provide a rapid and economical production method of skin scaffolds for future clinical applications.

Ciprofloxacin-Modified Degradable Hybrid Polyurethane-Polylactide Porous Scaffolds Developed for Potential Use as an Antibacterial Scaffold for Regeneration of Skin.

The aim of the performed study was to fabricate an antibacterial and degradable scaffold that may be used in the field of skin regeneration. To reach the degradation criterion for the biocompatible polyurethane (PUR), obtained by using amorphous α,ω-dihydroxy(ethylene-butylene adipate) macrodiol (PEBA), was used and processed with so-called "fast-degradable" polymer polylactide (PLA) (5 or 10 wt %). To meet the antibacterial requirement obtained, hybrid PUR-PLA scaffolds (HPPS) were modified with ciprofloxacin (Cipro) (2 or 5 wt %) and the fluoroquinolone antibiotic inhibiting growth of bacteria, such as Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, which are the main causes of wound infections. Performed studies showed that Cipro-modified HPPS, obtained by using 5% of PLA, possess suitable mechanical characteristics, morphology, degradation rates, and demanded antimicrobial properties to be further developed as potential scaffolds for skin tissue engineering.

Development of nanofibrous collagen-grafted poly (vinyl alcohol)/gelatin/alginate scaffolds as potential skin substitute.

The main objective of this work is to fabricate a nanofibrous scaffold to regenerate skin tissue. A scaffold composed of poly (vinyl alcohol)/gelatin/alginate was prepared using electrospinning method. To improve scaffold biocompatibility and wound healing properties, collagen, extracted from rat tail, was grafted on as-prepared nanofibers. The prepared scaffolds were characterized by SEM, FTIR, swelling ratio test, and water vapor transmission rate (WVTR) measurement. Cytotoxicity of the scaffolds against human fibroblasts and L929 (NCBI C161) cells were tested using direct and indirect methods, respectively. Fibroblast cell adhesion and proliferation on the scaffold were also investigated. Results of morphological studies showed that beadless nanofibers with 229 nm diameter were prepared. ATR-FTIR spectra of collagen grafted nanofiber mats confirmed presence of the collagen on their surface. Collagen grafted nanofibers showed higher swelling ratio than nanofibers without collagen graft. Collagen grafting decreased VWTR. Collagen grafting decreased both tensile strength and Young's modulus of the nanofibrous scaffolds while increased their elongation at break. MTT results showed that both scaffolds are biocompatible with higher cell viability for nanofibers with collagen grafting. Fibroblast cell culture on the scaffolds demonstrated that both of scaffolds have good cell viability and proliferation while collagen grafted scaffold showed better results.

Chitosan/Glycosaminoglycan Scaffolds: The Role of Silver Nanoparticles to Control Microbial Infections in Wound Healing.

Cutaneous wounds represent a major issue in medical care, with approximately 300 million chronic and 100 million traumatic wound patients worldwide, and microbial infections slow the healing process. The aim of this work was to develop electrospun scaffolds loaded with silver nanoparticles (AgNPs) to enhance cutaneous healing, preventing wound infections. AgNPs were directly added to polymeric blends based on chitosan (CH) and pullulan (PUL) with hyaluronic acid (HA) or chondroitin sulfate (CS) to be electrospun obtaining nanofibrous scaffolds. Moreover, a scaffold based on CH and PUL and loaded with AgNPs was prepared as a comparison. The scaffolds were characterized by chemico-physical properties, enzymatic degradation, biocompatibility, and antimicrobial properties. All the scaffolds were based on nanofibers (diameters about 500 nm) and the presence of AgNPs was evidenced by TEM and did not modify their morphology. The scaffold degradation was proven by means of lysozyme. Moreover, the AgNPs loaded scaffolds were characterized by a good propensity to promote fibroblast proliferation, avoiding the toxic effect of silver. Furthermore, scaffolds preserved AgNP antimicrobial properties, although silver was entrapped into nanofibers. Chitosan/chondroitin sulfate scaffold loaded with AgNPs demonstrated promotion of fibroblast proliferation and to possess antimicrobial properties, thus representing an interesting tool for the treatment of chronic wounds.

3D printing process of gelatin/oxidized nanocellulose skin scaffold with high elastic modulus and high porosity / 中国组织工程研究

BACKGROUND:In the treatment of skin trauma with active repair,tissue engineering techniques are needed to generate new tissue to replace necrotic tissue.Skin scaffolds have a good application prospect in the field of wound repair.Skin scaffolds need to present three-dimensional porous structures with certain mechanical strength to meet the needs of cell proliferation and division.However,the mechanical strength of the currently used gelatin-based biomaterials is weak and cannot meet the requirements of the use of skin scaffolds. OBJECTIVE:To study the 3D printing process used in the preparation of tissue engineering skin scaffolds by gelatin/oxidized nanocellulose composites,and focus on the relationship between the porosity and mechanical strength of the scaffolds prepared under different process parameters. METHODS:Oxidized nanocellulose whiskers at 10%concentration were extracted from Humulus scandens and then compounded with 5%gelatin to obtain gelatin/oxidized nanocellulose composites.The elastic modulus of gelatin and gelatin/oxidized nanocellulose composite was determined.Skin scaffolds were prepared by 3D printing extrusion molding using gelatin/oxidized nanocellulose composite as the base material.Mechanical and rheological properties of the composite were tested to determine extrusion molding parameters(filling gap 1.5-2.5 mm,uniform distribution of 0.1 mm;air pressure of 160-200 kPa),and the skin scaffold with a three-dimensional porous structure was prepared.The compressive performance of the skin scaffold was tested and compared with the finite element analysis results.The relationship between the filling gap and the porosity and mechanical strength of the scaffold was demonstrated. RESULTS AND CONCLUSION:(1)The elastic modulus of 5%gelatin was increased by 8.84 times by adding 10%oxidized nanocellulose whisker.A gel filament with a diameter of 1 mm was obtained by extrusion at the air pressure of 160 kPa.When the filling gap increased from 1.5 mm to 2.5 mm,the theoretical porosity of the scaffold increased from 33%to 60%,but the compressive strength decreased from 230 000 Pa to 95 000 Pa.(2)These findings showed that the skin scaffold with theoretical porosity of 50%and elastic modulus of 160 000 Pa was prepared by using 2 mm filling gap.The scaffold had a clear three-dimensional porous structure.

Fabrication and In Vitro Characterization of Electrochemically Compacted Collagen/Sulfated Xylorhamnoglycuronan Matrix for Wound Healing Applications.

Skin autografts are in great demand due to injuries and disease, but there are challenges using live tissue sources, and synthetic tissue is still in its infancy. In this study, an electrocompaction method was applied to fabricate the densely packed and highly ordered collagen/sulfated xylorhamnoglycuronan (SXRGlu) scaffold which closely mimicked the major structure and components in natural skin tissue. The fabricated electrocompacted collagen/SXRGlu matrices (ECLCU) were characterized in terms of micromorphology, mechanical property, water uptake ability and degradability. The viability, proliferation and morphology of human dermal fibroblasts (HDFs) cells on the fabricated matrices were also evaluated. The results indicated that the electrocompaction process could promote HDFs proliferation and SXRGlu could improve the water uptake ability and matrices' stability against collagenase degradation, and support fibroblast spreading on the ECLCU matrices. Therefore, all these results suggest that the electrocompacted collagen/SXRGlu scaffold is a potential candidate as a dermal substitute with enhanced biostability and biocompatibility.

Creation of a Bioengineered Skin Flap Scaffold with a Perfusable Vascular Pedicle.

Full-thickness skin loss is a challenging problem due to limited reconstructive options, demanding 75 million surgical procedures annually in the United States. Autologous skin grafting is the gold standard treatment, but results in donor-site morbidity and poor aesthetics. Numerous skin substitutes are available on the market to date, however, none truly functions as full-thickness skin due to lack of a vascular network. The creation of an autologous full-thickness skin analogue with a vascular pedicle would result in a paradigm shift in the management of wounds and in reconstruction of full-thickness skin defects. To create a clinically relevant foundation, we generated an acellular skin flap scaffold (SFS) with a perfusable vascular pedicle of clinically relevant size by perfusion decellularization of porcine fasciocutaneous flaps. We then analyzed the yielded SFS for mechanical properties, biocompatibility, and regenerative potential in vitro and in vivo. Furthermore, we assessed the immunological response using an in vivo model. Finally, we recellularized the vascular compartment of an SFS and reconnected it to a recipient's blood supply to test for perfusability. Perfusion decellularization removed all cellular components with preservation of native extracellular matrix composition and architecture. Biaxial testing revealed preserved mechanical properties. Immunologic response and biocompatibility assessed via implantation and compared with native xenogenic skin and commercially available dermal substitutes revealed rapid neovascularization and complete tissue integration. Composition of infiltrating immune cells showed no evidence of allorejection and resembled the inflammatory phase of wound healing. Implantation into full-thickness skin defects demonstrated good tissue integration and skin regeneration without cicatrization. We have developed a protocol for the generation of an SFS of clinically relevant size, containing a vascular pedicle, which can be utilized for perfusion decellularization and, ultimately, anastomosis to the recipient vascular system after precellularization. The observed favorable immunological response and good tissue integration indicate the substantial regenerative potential of this platform.

Rheological studies of polysaccharides for skin scaffolds.

Polysaccharide hydrogels are good candidates for skin scaffolds because of their inherent biocompatibility and water transport properties. In the current study, hydrogels were made from a mixture of four polysaccharides: xanthan gum, konjac gum, iota-carrageenan, and kappa-carrageenan. Gel formation, strength, and structure of these polysaccharides were studied using rheological and thermal techniques. All gel samples studied were strong gels at all times because of the gradual water loss. However, after 12 h of storage, elastic (G') and loss (G'') moduli of hydrogel mixture containing all the ingredients is of one to two orders of magnitude greater than that of mixtures not containing either xanthan gum or iota-carrageenan, which confirmed the varied levels of gel strength. This is mainly due to the rate of water loss in each of these mixtures, resulting in gels of varying structures and dynamic moduli over a period of time. Iota-carrageenan and xanthan gum differ in their effect on gel strength and stability in combination with konjac gum and kappa-carrageenan.