Micropatterned dermal-epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis.
Micropatterned dermal-epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis.
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DOI：
10.1016/j.actbio.2013.08.017
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发表时间：
2013-12
影响因子：
9.7
通讯作者：
Pins, George D.
中科院分区：
文献类型：
--
作者：
Clement, Amanda L.;Moutinho, Thomas J., Jr.;Pins, George D.
尽管组织工程皮肤替代品在治疗慢性伤口（如糖尿病和静脉溃疡）方面取得了一些临床成功，但移植物的持续使用和稳定性仍然令人担忧。目前的双层皮肤替代品缺乏真皮-表皮连接处特有的微地形，而真皮-表皮连接处能增强皮肤的机械稳定性，并产生细胞微生境，从而促进角质细胞的功能，形成皮肤附属物，促进伤口愈合。我们开发了一种新的微图案真皮-表皮再生基质（μDERM），它结合了这种复杂的地形，并大大增强了表皮形态。在这里，我们描述了使用这种3D体外培养模型来系统地评估不同的地形几何形状，以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化细胞功能壁龛：增殖壁龛（窄几何），基底膜蛋白合成壁龛（宽几何）和假定的角化细胞干细胞壁龛（窄几何和角）。其中，50 μm和100 μm通道的表皮厚度和角质细胞增殖显著（p<0.05）增加，400 μm通道的层粘连蛋白332沉积显著（p<0.05）增加。此外，β1brip63+角质形成细胞，假定的角质形成细胞干细胞，优先聚集在通道几何形状（类似于在天然皮肤中观察到的聚集），而不是随机分布在平地上。这项研究确定了特定的目标几何形状，以提高皮肤再生和移植物的性能。此外，这些结果表明μDERM微形貌在设计下一代皮肤替代品方面的重要性。最后，我们预计μDERMS上的3D器官型培养将为皮肤形态发生、伤口愈合和病理的体外研究提供一种新的组织工程皮肤替代品。
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 3D in vitro culture model to systematically evaluate different topographical geometries, 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, β1brip63+ 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 next generation skin substitutes. Finally, we anticipate that 3D organotypic cultures on μDERMS will provide a novel tissue engineered skin substitute for in vitro investigations of skin morphogenesis, wound healing and pathology.
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影响因子：
2.7
作者：
Auger, F. A.;Lacroix, D.;Germain, L.
通讯作者：
Germain, L.
影响因子：
10.3
作者：
El-Ghalbzouri, A;Gibbs, S;Ponec, M
通讯作者：
Ponec, M
DOI：
10.1038/jid.2008.265
发表时间：
2009-03
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.1
作者：
Bush, Katie A.;Pins, George D.
通讯作者：
Pins, George D.
影响因子：
4.6
作者：
Lammers, Gerwen;Roth, Guenter;van Kuppevelt, Toin H.
通讯作者：
van Kuppevelt, Toin H.