Spatially Guided Construction of Multilayered Epidermal Models Recapturing Structural Hierarchy and Cell–Cell Junctions
Spatially Guided Construction of Multilayered Epidermal Models Recapturing Structural Hierarchy and Cell–Cell Junctions
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DOI：
10.1002/smsc.202200051
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发表时间：
2022-09
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影响因子：
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通讯作者：
Haiwei Zhai;Xiaowei Jin;Grayson Minnick;J. Rosenbohm;Mohammed Abdul Haleem Hafiz;Ruiguo Yang;Fanben Meng
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文献类型：
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作者：
Haiwei Zhai;Xiaowei Jin;Grayson Minnick;J. Rosenbohm;Mohammed Abdul Haleem Hafiz;Ruiguo Yang;Fanben Meng
当前皮肤等效物 3D 生物打印面临的挑战是重建独特的基底层和基底上层并促进它们的直接相互作用。这种结构排列对于建立 3D 分层表皮疾病模型至关重要，例如自身免疫性皮肤病寻常型天疱疮 (PV)，其目标是基底层和基底上层界面的细胞-细胞连接。受伤口愈合中上皮再生的启发，开发了一种结合 3D 生物打印和角化细胞空间引导自我重组的方法，以重新捕获表皮深层的精细结构层次。在此，载有角质形成细胞的纤维蛋白水凝胶被生物打印以产生地理线索，通过集体迁移、角质形成细胞分化和垂直扩张来指导细胞的动态自我重组。这个过程产生了一个自组织多层 (SOM) 区域，其中包含基底层到上基底层的转变，以指示分化的不同类型角蛋白的表达水平为标志。最后，证明了重建皮肤组织作为研究PV致病作用的体外平台，阐明了不同表皮层中PV抗体诱导的细胞-细胞连接解离的显着差异，这表明它们在可能疗法的临床前测试中的应用。
A current challenge in 3D bioprinting of skin equivalents is to recreate the distinct basal and suprabasal layers and promote their direct interactions. Such a structural arrangement is essential to establish 3D stratified epidermis disease models, such as for the autoimmune skin disease pemphigus vulgaris (PV), which targets the cell–cell junctions at the interface of the basal and suprabasal layers. Inspired by epithelial regeneration in wound healing, a method that combines 3D bioprinting and spatially guided self‐reorganization of keratinocytes is developed to recapture the fine structural hierarchy that lies in the deep layers of the epidermis. Herein, keratinocyte‐laden fibrin hydrogels are bioprinted to create geographical cues, guiding dynamic self‐reorganization of cells through collective migration, keratinocyte differentiation, and vertical expansion. This process results in a region of self‐organized multilayers (SOMs) that contain the basal‐to‐suprabasal transition, marked by the expressed levels of different types of keratins that indicate differentiation. Finally, the reconstructed skin tissue as an in vitro platform to study the pathogenic effects of PV is demonstrated, illuminating a significant difference in cell–cell junction dissociation induced by PV antibodies in different epidermis layers, which indicates their applications in the preclinical test of possible therapies.