Development of Microfabricated Dermal Epidermal Regenerative Matrices to Evaluate the Role of Cellular Microenvironments on Epidermal Morphogenesis
Development of Microfabricated Dermal Epidermal Regenerative Matrices to Evaluate the Role of Cellular Microenvironments on Epidermal Morphogenesis
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DOI：
10.1089/ten.tea.2011.0479
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发表时间：
2012-11-01
影响因子：
4.1
通讯作者：
Pins, George D.
中科院分区：
文献类型：
--
作者：
Bush, Katie A.;Pins, George D.
真皮-表皮交界处（DEJ）的地形特征提供了对调节角质形成细胞功能和增强皮肤整体结构和组织至关重要的指导性线索。这种交叉的界面符合真皮上的一系列网脊和乳头状突起，其提供三维（3D）细胞微环境以及在机械负载期间真皮层和表皮层之间的结构稳定性。这些细胞微环境的尺寸在身体表面上表现出区域差异，并且定量组织学分析表明，根据这些微环境的区域几何形状，高度增殖的角质形成细胞的定位也不同。在这项研究中，我们结合了光刻，胶原蛋白处理和生化缀合技术，以创建微制造的真皮表皮再生基质（mDERM），其特征是模仿DEJ的天然3D细胞微环境。我们使用该模型系统来研究3D细胞微环境对上皮形成和基底角质形成细胞与mDERM表面上的微环境相互作用的影响。我们发现，与身体高摩擦区域（深而窄的通道）的特征非常相似的特征比与低摩擦区域相似的特征上皮化得更快。此外，当评估β 1表达（一种参与表皮形态发生的整合素）时，发现整合素bright表达定位于特征的深处，表明mDERM可能在定义细胞微环境以及角质形成细胞再生群体的保护环境中发挥作用。本研究的结果表明，mDERM可以作为一个强大的仿生模型系统来评估3D微环境在增强生物工程皮肤替代品的再生能力和结构稳定性方面的作用。
Topographic features at the dermal-epidermal junction (DEJ) provide instructive cues critical for modulating keratinocyte functions and enhancing the overall architecture and organization of skin. This interdigitated interface conforms to a series of rete ridges and papillary projections on the dermis that provides three-dimensional (3D) cellular microenvironments as well as structural stability between the dermal and epidermal layers during mechanical loading. The dimensions of these cellular microenvironments exhibit regional differences on the surface of the body, and quantitative histological analyses have shown that localization of highly proliferative keratinocytes also varies, according to the regional geometries of these microenvironments. In this study, we combined photolithography, collagen processing, and biochemical conjugation techniques to create microfabricated dermal epidermal regeneration matrices (mDERMs) with features that mimic the native 3D cellular microenvironment at the DEJ. We used this model system to study the effect of the 3D cellular microenvironment on epithelialization and basal keratinocyte interaction with the microenvironment on the surface of the mDERMs. We found that features closely mimicking those in high-friction areas of the body (deep, narrow channels) epithelialized faster than features mimicking low-friction areas. Additionally, when evaluating beta 1 expression, an integrin involved in epidermal morphogenesis, it was found that integrin-bright expression was localized in the depths of the features, suggesting that the mDERMs may play a role in defining cellular microenvironments as well as a protective environment for the regenerative population of keratinocytes. The outcomes of this study suggest that mDERMs can serve as a robust biomimetic model system to evaluate the roles of the 3D microenvironment on enhancing the regenerative capacity and structural stability of bioengineered skin substitutes.