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首页> 外文期刊>Acta biomaterialia >Micropatterned dermal-epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis
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Micropatterned dermal-epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis

机译：微图案化的真皮-表皮再生基质产生功能性壁ni，可增强表皮形态发生

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Although tissue engineered skin substitutes have demonstrated some clinical success for the treatment of chronic wounds such as diabetic and venous ulcers, persistent graft take and stability remain concerns. Current bilayered skin substitutes lack the characteristic microtopography of the dermal-epidermal junction that gives skin enhanced mechanical stability and creates cellular microniches that differentially promote keratinocyte function to form skin appendages and enhance wound healing. We developed a novel micropatterned dermal-epidermal regeneration matrix (μDERM) which incorporates this complex topography and substantially enhances epidermal morphology. Here, we describe the use of this three-dimensional (3-D) in vitro culture model to systematically evaluate different topographical geometries and to determine their relationship to keratinocyte function. We identified three distinct keratinocyte functional niches: the proliferative niche (narrow geometries), the basement membrane protein synthesis niche (wide geometries) and the putative keratinocyte stem cell niche (narrow geometries and corners). Specifically, epidermal thickness and keratinocyte proliferation is significantly (p 0.05) increased in 50 and 100 μm channels while laminin-332 deposition is significantly (p 0.05) increased in 400 μm channels compared to flat controls. Additionally, β1 brip63+ keratinocytes, putative keratinocyte stem cells, preferentially cluster in channel geometries (similar to clustering observed in native skin) compared to a random distribution on flats. This study identifies specific target geometries to enhance skin regeneration and graft performance. Furthermore, these results suggest the importance of μDERM microtopography in designing the next generation of skin substitutes. Finally, we anticipate that 3-D organotypic cultures on μDERMS will provide a novel tissue engineered skin substitute for in vitro investigations of skin morphogenesis, wound healing and pathology.
机译：尽管组织工程皮肤替代品已显示出在治疗诸如糖尿病和静脉溃疡等慢性伤口方面的一些临床成功，但持续移植物的摄取和稳定性仍然令人担忧。当前的双层皮肤替代品缺乏真皮-表皮连接的特征性微观形貌，该特征使皮肤增强了机械稳定性并产生了细胞微生态位，其差异性地促进了角质形成细胞的功能以形成皮肤附件并促进伤口愈合。我们开发了一种新型的微模式真皮-表皮再生基质（μDERM），该基质结合了这种复杂的形貌并大大增强了表皮形态。在这里，我们描述了使用此三维（3-D）体外培养模型来系统地评估不同的地形几何形状，并确定它们与角质形成细胞功能的关系。我们确定了三个不同的角质形成细胞功能壁ches：增生利基（狭窄的几何形状），基底膜蛋白合成利基（宽的几何形状）和假定的角质形成细胞干细胞利基（狭窄的几何形状和角落）。具体而言，与平坦对照组相比，在50和100μm通道中表皮厚度和角质形成细胞增殖显着（p <0.05）增加，而层粘连蛋白332沉积在400μm通道中显着（p <0.05）增加。此外，与公寓中的随机分布相比，β1brip63 +角质形成细胞，假定的角质形成干细胞优先聚集在通道几何结构中（类似于在天然皮肤中观察到的聚集）。这项研究确定了特定的目标几何形状，以增强皮肤再生和移植性能。此外，这些结果表明，μDERM微观形貌在设计下一代皮肤替代品中的重要性。最后，我们预期在μDERMS上进行的3-D有机型培养将为皮肤形态发生，伤口愈合和病理学的体外研究提供一种新型的组织工程皮肤替代品。

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