Background:Rodent models have been widely used to investigate skin development,but do not account for significant differences in composition compared to human skin.On the other hand,two-dimensional and three-dimension...Background:Rodent models have been widely used to investigate skin development,but do not account for significant differences in composition compared to human skin.On the other hand,two-dimensional and three-dimensional engineered skin models still lack the complex features of human skin such as appendages and pigmentation.Recently,hair follicle containing skin organoids(SKOs)with a stratified epidermis,and dermis layer have been generated as floating spheres from human-induced pluripotent stem cells(hiPSCs).Methods:The current study aims to investigate the generation of hiPSCs-derived SKOs using an air-liquid interface(ALI)model on transwell membranes(T-SKOs)and compares their development with conventional floating culture in low-attachment plates(F-SKOs).Results:Mature SKOs containing an epidermis,dermis,and appendages are created in both T-SKO and F-SKO conditions.It was found that the hair follicles are smaller and shorter in the F-SKO compared with T-SKOs.Additionally,the ALI conditions contribute to enhanced hair follicle numbers than conventional floating culture.Conclusions:Together,this study demonstrates the significant influence of transwell culture on the morphogenesis of hair follicles within SKOs and highlights the potential for refinement of skin model engineering for advancing dermatology and skin research.展开更多
Pathological scarring imposes a major clinical and social burden worldwide.Human cutaneous wounds are responsive to mechanical forces and convert mechanical cues to biochemical signals that eventually promote scarring...Pathological scarring imposes a major clinical and social burden worldwide.Human cutaneous wounds are responsive to mechanical forces and convert mechanical cues to biochemical signals that eventually promote scarring.To understand the mechanotransduction pathways in cutaneous scarring and develop new mechanotherapy approaches to achieve optimal scarring,the current study highlights the mechanical behavior of unwounded and scarred skin as well as intra-and extracellular mechanisms behind keloid and hypertrophic scars.Additionally,the therapeutic interventions that promote optimal scar healing by mechanical means at the molecular,cellular or tissue level are extensively reviewed.The current literature highlights the significant role of fibroblasts in wound contraction and scar formation via differentiation intomyofibroblasts.Thus,understanding myofibroblasts and their responses to mechanical loading allows the development of new scar therapeutics.A review of the current clinical and preclinical studies suggests that existing treatment strategies only reduce scarring on a small scale after wound closure and result in poor functional and aesthetic outcomes.Therefore,the perspective of mechanotherapies needs to consider the application of both mechanical forces and biochemical cues to achieve optimal scarring.Moreover,early intervention is critical in wound management;thus,mechanoregulation should be conducted during the healing process to avoid scar maturation.Future studies should either consider combining mechanical loading(pressure)therapies with tension offloading approaches for scar management or developing more effective early therapies based on contraction-blocking biomaterials for the prevention of pathological scarring.展开更多
基金Metro North Hospital and Health Service(MNHHS),Queensland Health,Queensland,Australia.
文摘Background:Rodent models have been widely used to investigate skin development,but do not account for significant differences in composition compared to human skin.On the other hand,two-dimensional and three-dimensional engineered skin models still lack the complex features of human skin such as appendages and pigmentation.Recently,hair follicle containing skin organoids(SKOs)with a stratified epidermis,and dermis layer have been generated as floating spheres from human-induced pluripotent stem cells(hiPSCs).Methods:The current study aims to investigate the generation of hiPSCs-derived SKOs using an air-liquid interface(ALI)model on transwell membranes(T-SKOs)and compares their development with conventional floating culture in low-attachment plates(F-SKOs).Results:Mature SKOs containing an epidermis,dermis,and appendages are created in both T-SKO and F-SKO conditions.It was found that the hair follicles are smaller and shorter in the F-SKO compared with T-SKOs.Additionally,the ALI conditions contribute to enhanced hair follicle numbers than conventional floating culture.Conclusions:Together,this study demonstrates the significant influence of transwell culture on the morphogenesis of hair follicles within SKOs and highlights the potential for refinement of skin model engineering for advancing dermatology and skin research.
文摘Pathological scarring imposes a major clinical and social burden worldwide.Human cutaneous wounds are responsive to mechanical forces and convert mechanical cues to biochemical signals that eventually promote scarring.To understand the mechanotransduction pathways in cutaneous scarring and develop new mechanotherapy approaches to achieve optimal scarring,the current study highlights the mechanical behavior of unwounded and scarred skin as well as intra-and extracellular mechanisms behind keloid and hypertrophic scars.Additionally,the therapeutic interventions that promote optimal scar healing by mechanical means at the molecular,cellular or tissue level are extensively reviewed.The current literature highlights the significant role of fibroblasts in wound contraction and scar formation via differentiation intomyofibroblasts.Thus,understanding myofibroblasts and their responses to mechanical loading allows the development of new scar therapeutics.A review of the current clinical and preclinical studies suggests that existing treatment strategies only reduce scarring on a small scale after wound closure and result in poor functional and aesthetic outcomes.Therefore,the perspective of mechanotherapies needs to consider the application of both mechanical forces and biochemical cues to achieve optimal scarring.Moreover,early intervention is critical in wound management;thus,mechanoregulation should be conducted during the healing process to avoid scar maturation.Future studies should either consider combining mechanical loading(pressure)therapies with tension offloading approaches for scar management or developing more effective early therapies based on contraction-blocking biomaterials for the prevention of pathological scarring.
