Fast-Curing Injectable Microporous Hydrogel for In Situ Cell Encapsulation.
Fast-Curing Injectable Microporous Hydrogel for In Situ Cell Encapsulation.
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DOI：
10.1021/acsabm.2c00214
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发表时间：
2022-06-20
影响因子：
4.7
通讯作者：
Jeong, Kyung Jae
中科院分区：
文献类型：
--
作者：
Edwards, Seth D;Hou, Shujie;Brown, Jason M;Boudreau, Ryann D;Lee, Yuhan;Kim, Young Jo;Jeong, Kyung Jae
可注射的水凝胶先前已经证明了作为组织再生的临时支架或作为细胞、生长因子或药物的递送载体的潜力。然而，大多数可注射水凝胶系统缺乏微孔结构，阻止宿主细胞迁移到水凝胶内部并限制包封细胞的扩散和增殖。本文描述了由明胶/明胶甲基丙烯酰基（GelMA）复合微凝胶组装的可注射微孔水凝胶。使用明胶/GelMA水性混合物通过油包水乳液制备微凝胶。这些微凝胶与仅含GelMA的微凝胶相比显示出改善的热稳定性，并且受益于在光引发剂（PI）存在下使用UV照射（365 nm）的组合光聚合和通过微生物转氨酶（mTG）的酶促反应，它们一起使得水凝胶能够快速固化和组织粘附。双交联方法还允许降低PI浓度并使光聚合期间的细胞毒性最小化。当应用于原位细胞包封时，包封的人真皮成纤维细胞（hDF）和人间充质干细胞（hMSC）能够在水凝胶的孔隙中快速扩散和增殖。这种水凝胶具有通过被封装的细胞分泌前列腺素E2（PGE 2）和白细胞介素-6（IL-6）来增强hMSC抗炎行为的潜力。总而言之，这种可注射制剂具有用作再生医学中各种应用的细胞递送载体的潜力。
Injectable hydrogels have previously demonstrated potential as a temporary scaffold for tissue regeneration, or as a delivery vehicle for cells, growth factors, or drugs. However, most injectable hydrogel systems lack a microporous structure, preventing host cell migration into the hydrogel interior and limiting spreading and proliferation of encapsulated cells. Herein an injectable microporous hydrogel assembled from gelatin/gelatin methacryloyl (GelMA) composite microgels is described. Microgels are produced by a water-in-oil emulsion using a gelatin/GelMA aqueous mixture. These microgels show improved thermal stability compared to GelMA-only microgels, and benefit from combined photopolymerization using UV irradiation (365 nm) in the presence of photoinitiator (PI) and enzymatic reaction by microbial transglutaminase (mTG), which together enable fast curing and tissue adhesion of the hydrogel. The dual-crosslinking approach also allows for the reduction of PI concentration and minimizes cytotoxicity during photopolymerization. When applied for in situ cell encapsulation, encapsulated human dermal fibroblasts (hDFs) and human mesenchymal stem cells (hMSCs) are able to rapidly spread and proliferate in the pore space of the hydrogel. This hydrogel has the potential to enhance hMSC anti-inflammatory behavior through the demonstrated secretion of prostaglandin E2 (PGE2) and interleukin-6 (IL-6) by encapsulated cells. Altogether, this injectable formulation has the potential to be used as a cell delivery vehicle for various applications in regenerative medicine.