Exploiting Meltable Protein Hydrogels to Encapsulate and Culture Cells in 3D.
Exploiting Meltable Protein Hydrogels to Encapsulate and Culture Cells in 3D.
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利用可熔蛋白质水凝胶封装和培养 3D 细胞。
DOI：
10.1002/mabi.202200134
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发表时间：
2022
影响因子：
4.6
通讯作者：
Dura G
中科院分区：
文献类型：
--
作者：
Dura G
人们越来越认识到，3D 细胞培养比 2D 更好地模拟复杂的体内环境，减少异常的细胞行为并最终改善实验结果。模仿天然细胞外基质 (ECM) 的化学交联水凝胶是经过验证的细胞培养平台，但将细胞封装在这些水凝胶网络内需要生物正交交联化学物质，这种化学物质可能具有细胞毒性、合成要求高且成本高昂。荚膜抗原片段 1 (Caf1) 是一种细菌聚合菌毛蛋白，可通过基因工程模拟 ECM。此外，即使在水凝胶网络内化学交联时，它也可以在其聚合形式和单体形式之间可逆地热相互转化。事实证明，Caf1 水凝胶的这种可熔化特性可用于以一定范围的细胞密度（水凝胶的 2 × 105–2 × 106 个细胞 mL−1）封装新生儿人类真皮成纤维细胞，从而避免化学细胞毒性问题。这些水凝胶支持细胞 3D 培养长达 21 天，成功诱导细胞功能，例如增殖和迁移。这项工作意义重大，因为它进一步凸显了简单、稳健、基于 Caf1 的水凝胶作为细胞培养平台的潜力。
There is a growing realization that 3D cell culture better mimics complex in vivo environments than 2D, lessening aberrant cellular behaviors and ultimately improving the outcomes of experiments. Chemically crosslinked hydrogels which imitate natural extracellular matrix (ECM) are proven cell culture platforms, but the encapsulation of cells within these hydrogel networks requires bioorthogonal crosslinking chemistries which can be cytotoxic, synthetically demanding, and costly. Capsular antigen fragment 1 (Caf1) is a bacterial, polymeric, fimbrial protein which can be genetically engineered to imitate ECM. Furthermore, it can, reversibly, thermally interconvert between its polymeric and monomeric forms even when chemically crosslinked within a hydrogel network. It is demonstrated that this meltable feature of Caf1 hydrogels can be utilized to encapsulate neonatal human dermal fibroblasts at a range of cell densities (2 × 105–2 × 106cells mL−1of hydrogel) avoiding issues with chemical cytotoxicity. These hydrogels supported cell 3D culture for up to 21 d, successfully inducing cellular functions such as proliferation and migration. This work is significant because it further highlights the potential of simple, robust, Caf1‐based hydrogels as a cell culture platform.