Large full-thickness wounded skin regeneration using 3D-printed elastic scaffold with minimal functional unit of skin.

Traditional tissue engineering skin are composed of living cells and natural or synthetic scaffold. Besize the time delay and the risk of contamination involved with cell culture, the lack of autologous cell source and the persistence of allogeneic cells in heterologous grafts have limited its application. This study shows a novel tissue engineering functional skin by carrying minimal functional unit of skin (MFUS) in 3D-printed polylactide-co-caprolactone (PLCL) scaffold and collagen gel (PLCL + Col + MFUS). MFUS is full-layer micro skin harvested from rat autologous tail skin. 3D-printed PLCL elastic scaffold has the similar mechanical properties with rat skin which provides a suitable environment for MFUS growing and enhances the skin wound healing. Four large full-thickness skin defects with 30 mm diameter of each wound are created in rat dorsal skin, and treated either with tissue engineering functional skin (PLCL + Col + MFUS), or with 3D-printed PLCL scaffold and collagen gel (PLCL + Col), or with micro skin islands only (Micro skin), or without treatment (Normal healing). The wound treated with PLCL + Col + MFUS heales much faster than the other three groups as evidenced by the fibroblasts migration from fascia to the gap between the MFUS dermis layer, and functional skin with hair follicles and sebaceous gland has been regenerated. The PLCL + Col treated wound heals faster than normal healing wound, but no skin appendages formed in PLCL + Col-treated wound. The wound treated with micro skin islands heals slower than the wounds treated either with tissue engineering skin (PLCL + Col + MFUS) or with PLCL + Col gel. Our results provide a new strategy to use autologous MFUS instead "seed cells" as the bio-resource of engineering skin for large full-thickness skin wound healing.

Human umbilical cord mesenchymal stem cells implantation accelerates cutaneous wound healing in diabetic rats via the Wnt signaling pathway.

OBJECTIVE: Difficulty in wound healing is one common complication of diabetes mellitus. The study explored whether the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic ulcer wound was enhanced by the activation of the Wnt signaling pathway. METHODS: Rat diabetic model was established by intraperitoneal injection of Streptozotocin (STZ). hUCMSCs were purified and seeded on the collagen-chitosan laser drilling acellular dermal matrix (CCLDADM) scaffold, which was subsequently implanted into the cutaneous wound of normal and diabetic rats, followed by daily injection of Wnt signaling pathway agonist (Wnt3a) or antagonist (sFRP3) at the edge of the scaffold. Wound healing was checked on days 7, 14, and 21, and the fibrous tissue deposition, capillaries, and epidermal regeneration at the wound were examined by hematoxylin-eosin staining. The hUCMSCs-CCLDADM scaffold was cultured in vitro and treated with Wnt3a or sFRP3, followed by evaluation of cell proliferation, cell proliferation rate, survival status, and altered protein levels in the Wnt signaling pathway using BrdU staining, CCK-8 assay, live/dead staining, and Western blotting, respectively. RESULTS: On days 7 and 14 postoperatively, the speed of wound healing was significantly lower in diabetic rats than that in normal control rats. This phenomenon was significantly improved by the activation of the Wnt signaling pathway that also elevated the fibrous protein deposition and the abundance of capillary in the granulation tissue. Conversely, blockade of Wnt signaling slowed the healing of skin wound in diabetic rats. The activation of Wnt signaling pathway promoted the proliferation and differentiation and decreased the apoptosis of hUCMSCs, thereby elevating the number of living hUCMSCs on the CCLDADM scaffold, while the suppression exerted a contrary effect. CONCLUSION: The activation of the Wnt signaling pathway promotes the healing of diabetic skin wound by the regulation of proliferation and differentiation of hUCMSCs on the CCLDADM scaffold.

[Utilization of three-dimensional printing technology for repairing skin tissue].

Three-dimensional (3D) printing is a low-cost, high-efficiency production method, which can reduce the current cost and increase the profitability of skin repair material industry nowadays, and develop products with better performance. The 3D printing technology commonly used in the preparation of skin repair materials includes fused deposition molding technology and 3D bioprinting technology. Fused deposition molding technology has the advantages of simple and light equipment, but insufficient material selection. 3D bioprinting technology has more materials to choose from, but the equipment is cumbersome and expensive. In recent years, research on both technologies has focused on the development and application of materials. This article details the principles of fused deposition modeling and 3D bioprinting, research advances in wound dressings and tissue engineering skin production, and future developments in 3D printing on skin tissue repair, including cosmetic restoration and biomimetic tissue engineering. Also, this review prospects the development of 3D printing technology in skin tissue repairment.

[Development and progress of sixty years and stepping firmly to the future].

Since its establishment for 60 years, Department of Burns of the Second Affiliated Hospital of Zhejiang University School of Medicine has grown into a famous regional burn center in China under the leading of the pioneers and through the efforts of several generations. The department has distinctive disciplinary features in burn care, nutritional support, scar prevention and treatments, standard management of chronic wound, and skin tissue engineering research, making positive contribution to the development of burn medicine in China.

[Advances in the research of the application of induced pluripotent stem cells in tissue engineering skin as seed cells].

Tissue engineering skin has a wide application prospect on the clinical treatment of all sorts of skin defect, especially large area burn. The shortage of seed cells and their function improvement are the main problems in this field. The existing seed cells of tissue engineering skin are difficult to meet the needs of clinical application due to the limitations of acquisition, proliferation, and aging. Subsequently, the generation of induced pluripotent stem cells (iPSCs) provides a safe and efficient cell source for tissue engineering skin. Our article focuses on the origin of iPSCs and its characteristics of differentiating into keratinocytes, fibroblasts, melanocytes, vascular smooth muscle cells, nerve cells, and hair follicle, and discusses the main problems and prospects of iPSCs in establishment of tissue engineering skin and application in wound repair.

Advances in the research of the application of induced pluripotent stem cells in tissue engineering skin as seed cells / 中华烧伤杂志

Tissue engineering skin has a wide application prospect on the clinical treatment of all sorts of skin defect, especially large area burn. The shortage of seed cells and their function improvement are the main problems in this field. The existing seed cells of tissue engineering skin are difficult to meet the needs of clinical application due to the limitations of acquisition, proliferation, and aging. Subsequently, the generation of induced pluripotent stem cells (iPSCs) provides a safe and efficient cell source for tissue engineering skin. Our article focuses on the origin of iPSCs and its characteristics of differentiating into keratinocytes, fibroblasts, melanocytes, vascular smooth muscle cells, nerve cells, and hair follicle, and discusses the main problems and prospects of iPSCs in establishment of tissue engineering skin and application in wound repair.

Development and progress of sixty years and stepping firmly to the future / 中华烧伤杂志

Since its establishment for 60 years, Department of Burns of the Second Affiliated Hospital of Zhejiang University School of Medicine has grown into a famous regional burn center in China under the leading of the pioneers and through the efforts of several generations. The department has distinctive disciplinary features in burn care, nutritional support, scar prevention and treatments, standard management of chronic wound, and skin tissue engineering research, making positive contribution to the development of burn medicine in China.

Utilization of three-dimensional printing technology for repairing skin tissue / 生物医学工程学杂志

Three-dimensional (3D) printing is a low-cost, high-efficiency production method, which can reduce the current cost and increase the profitability of skin repair material industry nowadays, and develop products with better performance. The 3D printing technology commonly used in the preparation of skin repair materials includes fused deposition molding technology and 3D bioprinting technology. Fused deposition molding technology has the advantages of simple and light equipment, but insufficient material selection. 3D bioprinting technology has more materials to choose from, but the equipment is cumbersome and expensive. In recent years, research on both technologies has focused on the development and application of materials. This article details the principles of fused deposition modeling and 3D bioprinting, research advances in wound dressings and tissue engineering skin production, and future developments in 3D printing on skin tissue repair, including cosmetic restoration and biomimetic tissue engineering. Also, this review prospects the development of 3D printing technology in skin tissue repairment.

Characteristics and in vitro cell compatibility of human acellular dermal matrix with improved method / 中华医学美学美容杂志

Objective To detect the characteristics and in vitro cell compatibility of human acellular dermal matrix (ADM) with the improved method.Methods Cell components of healthy human skins were removed by the improved method and the traditional method respectively.The porosity, degradation time in vitro of the ADM prepared by two methods and the cytotoxicity of the material infiltration liquid with the improved method on the adipose derived stem cells were detected.HE staining was used to detect the residual of the cells, the integrity of collagen and cell biocompatibility.Scanning electron microscopy (SEM) was used to detect the pore size.Results Both the two methods could completely remove the cells, and maintain the integrity of the collagen scaffold;The porosity of ADM with the improved method was higher (93.1±1.02)% than that of traditional method (74.27±2.04)% (P<0.05);There was no significant difference in the cytotoxicity and in vitro degradation time between the two kinds of ADM;While pore diameter of the improved method was significantly higher [(181.21±66.9) μm] than that [(102.38±15.63) μm] in dermal reticular surface with the traditonal method (P<0.05).Conclusions There is no obvious cytotoxicity of the ADM with the improved method, and therefore it is more suitable for cell adhesion growth with higher porosity and larger pore size.

The establishment of the three-dimensional culture model of the human skin squamous-celled carcinoma and their biological evaluation of the high-invasive squamous carcinoma cells / 重庆医学

Objective To establish the three-dimensional culture model of the human skin squamous-celled carcinoma ,and isolate the highly invasive cell subsets ,and compare their biological characteristics .Methods By using the composite chitosan tissue engi-neering skin ,the three-dimensional culture model of the human skin squamous-celled carcinoma was successfully established , through digestion ,we divided and got the high-invasive squamous carcinoma cells subsets .After that ,the different invasive proper-ties of subpopulations of cells in nude mice tumor effects were compared .Results Different concentrations of cinnamaldehyde and interferon on skin squamous-celled carcinoma cell proliferation inhibition had statistical significance (P<0 .01) ,the different invasive characteristics of skin squamous cells carcinoma between subpopulations of cells proliferation inhibition also was statistically signifi-cant(P<0 .01) ,and the two different invasive properties of subpopulations of cells in the tumor characteristics also had statistical significance(P<0 .01) .Conclusion We established the three-dimensional culture model of the human skin squamous-celled carcino-ma successfully ,by using this model ,we could screen the higher invasive cells subsets .

Reconstruction of Tissue Engineering Skin by Epidermal Cells and Fibroblasts Combined with Modified Polymer of Lactic Acid / 现代生物医学进展

Objective: To investigate the applied feasibility of scaffold with modified PLA (Polymer of lactic acid) in tissue engineering. Methods:First, we adopted salting-in method to prepare porous foam scaffold. Then, we reconstructed tissue engineering skin by epidermal cells and fibroblasts combined with modified PLA. On the 14th day of cell culturing in vitro, we was a control. Results:The arfificial skin is composed of epidermis and dermis and similar to natural skin in appearance. The skin consists of fibroblasts and keratinocytes, which are in various proliferation and differentiation stages. Fibroblasts and keratinocytes distribute on the surface of polymer of lactic acid (PLA) and the number of fibroblast and keratinocyte increase. Conclusion:Dialdehyde starches (DAS) not only improve the function of PLA but also have good effects on cells. Moreover, it does not affect the growth and the metabolism of the cells. So it is feasible to use modified scaffold to construct tissue engineering skin.

Reconstruction of Tissue Engineering Skin by Epidermal Cells and Fibroblasts Combined with Modified Polymer of Lactic Acid / 现代生物医学进展

Objective: To investigate the applied feasibility of scaffold with modified PLA (Polymer of lactic acid) in tissue engineering. Methods:First, we adopted salting-in method to prepare porous foam scaffold. Then, we reconstructed tissue engineering skin by epidermal cells and fibroblasts combined with modified PLA. On the 14th day of cell culturing in vitro, we was a control. Results:The arfificial skin is composed of epidermis and dermis and similar to natural skin in appearance. The skin consists of fibroblasts and keratinocytes, which are in various proliferation and differentiation stages. Fibroblasts and keratinocytes distribute on the surface of polymer of lactic acid (PLA) and the number of fibroblast and keratinocyte increase. Conclusion:Dialdehyde starches (DAS) not only improve the function of PLA but also have good effects on cells. Moreover, it does not affect the growth and the metabolism of the cells. So it is feasible to use modified scaffold to construct tissue engineering skin.

Reconstruction of Tissue Engineering Skin by Epidermal Cells and Fibroblasts Combined with Modified Polymer of Lactic Acid / 现代生物医学进展

Objective: To investigate the applied feasibility of scaffold with modified PLA (Polymer of lactic acid) in tissue engineering. Methods:First, we adopted salting-in method to prepare porous foam scaffold. Then, we reconstructed tissue engineering skin by epidermal cells and fibroblasts combined with modified PLA. On the 14th day of cell culturing in vitro, we was a control. Results:The arfificial skin is composed of epidermis and dermis and similar to natural skin in appearance. The skin consists of fibroblasts and keratinocytes, which are in various proliferation and differentiation stages. Fibroblasts and keratinocytes distribute on the surface of polymer of lactic acid (PLA) and the number of fibroblast and keratinocyte increase. Conclusion:Dialdehyde starches (DAS) not only improve the function of PLA but also have good effects on cells. Moreover, it does not affect the growth and the metabolism of the cells. So it is feasible to use modified scaffold to construct tissue engineering skin.