Charles Institute of Dermatology, School of Medicine, University College Dublin, Dublin, Dublin 4, Ireland.
Blafar Limited, NovaUCD, Belfield Innovation Park Belfield, Dublin, Dublin 4, Ireland.
Macromol Biosci. 2021 Sep;21(9):e2100079. doi: 10.1002/mabi.202100079. Epub 2021 Jun 18.
Cell therapies have great potential for the treatment of many different diseases, while the direct application of cells to the targeted location leads to limited therapeutic outcomes due to the low cell engraftment and cell survival rate. Injectable hydrogels have been developed to facilitate cell delivery; however, those currently developed hydrogel systems still face the limited cell survival rate. Here, an injectable and self-healable hydrogel is reported through the combination of hyperbranched PEG-based multi-hydrazide macro-crosslinker (HB-PEG-HDZ) and aldehyde-functionalized hyaluronic acid (HA-CHO), with gelatin added to increase the crosslinking density and cell activity. The hydrogels can be formed only in 7 s due to the relatively high content of the functional end groups. The reversible crosslinking mechanism between the hydrazide and aldehyde groups endows the hydrogel with shear-thinning and self-healing properties. The hydrogels with gelatin exhibit relatively better mechanical properties and cell activity. The hydrogels can improve the survival, attachment, and engraftment of injected cells due to the rapid sol-gel transition, which can promote an enhanced regenerative response.
细胞疗法在治疗许多不同疾病方面具有巨大的潜力,而由于细胞的植入率和存活率低,直接将细胞应用于靶向位置导致治疗效果有限。已经开发出可注射水凝胶来促进细胞递送;然而,目前开发的水凝胶系统仍然面临细胞存活率有限的问题。在这里,通过超支化 PEG 基多酰肼大分子交联剂(HB-PEG-HDZ)和醛基化透明质酸(HA-CHO)的组合,报告了一种可注射和自修复水凝胶,加入明胶以增加交联密度和细胞活性。由于功能端基含量较高,水凝胶只能在 7 秒内形成。酰腙和醛基之间的可逆交联机制赋予水凝胶剪切稀化和自修复特性。含有明胶的水凝胶表现出相对更好的机械性能和细胞活性。由于快速的溶胶-凝胶转变,水凝胶可以提高注射细胞的存活率、附着率和植入率,从而促进增强的再生反应。