Center for Minimally Invasive Therapeutics (C-MIT), University of California-Los Angeles, Los Angeles, CA 90095, United States of America.
Bioprocess and Biotechnology Department, Sãao Paulo State University (Unesp), School of Pharmaceutical Sciences, Km 01 Araraquara-Jau Road, Araraquara, SP 14801-902, Brazil.
Biofabrication. 2021 Apr 9;13(3). doi: 10.1088/1758-5090/aba503.
The skin serves a substantial number of physiological purposes and is exposed to numerous biological and chemical agents owing to its large surface area and accessibility. Yet, current skin models are limited in emulating the multifaceted functions of skin tissues due to a lack of effort on the optimization of biomaterials and techniques at different skin layers for building skin frameworks. Here, we use biomaterial-based approaches and bioengineered techniques to develop a 3D skin model with layers of endothelial cell networks, dermal fibroblasts, and multilayered keratinocytes. Analysis of mechanical properties of gelatin methacryloyl (GelMA)-based bioinks mixed with different portions of alginate revealed bioprinted endothelium could be better modeled to optimize endothelial cell viability with a mixture of 7.5% GelMA and 2% alginate. Matrix stiffness plays a crucial role in modulating produced levels of Pro-Collagen I alpha-1 and matrix metalloproteinase-1 in human dermal fibroblasts and affecting their viability, proliferation, and spreading. Moreover, seeding human keratinocytes with gelatin-coating multiple times proved to be helpful in reducing culture time to create multiple layers of keratinocytes while maintaining their viability. The ability to fabricate selected biomaterials for each layer of skin tissues has implications in the biofabrication of skin systems for regenerative medicine and disease modeling.
皮肤具有许多重要的生理功能，由于其表面积大且易于接触，因此会暴露于许多生物和化学制剂中。然而，由于在不同皮肤层的生物材料和技术优化方面缺乏努力，目前的皮肤模型在模拟皮肤组织的多种功能方面受到限制，无法构建皮肤框架。在这里，我们使用基于生物材料的方法和生物工程技术，开发了一种具有内皮细胞网络、真皮成纤维细胞和多层角质形成细胞层的 3D 皮肤模型。分析不同比例的海藻酸钠混合的明胶甲基丙烯酰（GelMA）基生物墨水的机械性能表明，生物打印的内皮细胞可以更好地建模，通过混合 7.5% GelMA 和 2%海藻酸钠来优化内皮细胞活力。基质硬度在调节人真皮成纤维细胞中产生的 I 型前胶原和基质金属蛋白酶-1 的水平方面起着至关重要的作用，并且会影响其活力、增殖和扩散。此外，多次用明胶涂层接种人角质形成细胞有助于减少培养时间，同时保持其活力，从而形成多层角质形成细胞。为皮肤组织的每一层制造选定的生物材料的能力对再生医学和疾病建模的皮肤系统的生物制造具有重要意义。
