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Microfluidic Synthesis of Injectable Angiogenic Microgels
Cell Reports Physical Science ( IF 8.9 ) Pub Date : 2020-04-29 , DOI: 10.1016/j.xcrp.2020.100047
Haoran Zhao , Zitian Wang , Shengwei Jiang , Jiaqi Wang , Zhiwei Hu , Peter E. Lobie , Shaohua Ma

Implanting cell-laden microgels repairs soft tissue injuries, with the co-occurrence of tissue remodeling and angiogenesis in the engrafts. Engineering microgels using native-tissue derived materials, such as collagen, remains a challenge because they are mostly slow gelling and not angiogenic. Herein, we report a fast-gelling and angiogenic collagen scaffold interlocked by ultra-long DNA (>100,000 nt) programmed with vascular endothelial growth factor (VEGF) aptamers. The DNA interlocking shortens the collagen gelation time by >30-fold, to 40 s and modulated by the microfluidic flows, but the viscoelasticity, biodegradability, and biochemical properties of native collagen remain unaltered. When encapsulated with cells, the angiogenic microgels improve wound healing and liver regeneration, compared with the non-angiogenic or acellular microgels. After cryopreservation, the cell-laden microgels are retrieved with >80% of the cells viable, and they retain their therapeutic potential. These angiogenic, fast-gelling, and ultra-soft cell-laden microgels may be promising candidates as injectable therapeutics in regenerative medicine.



中文翻译:

注射用血管生成微凝胶的微流合成

植入充满细胞的微凝胶可修复软组织损伤,并在植入物中同时发生组织重塑和血管生成。使用天然组织衍生的材料(例如胶原蛋白)工程化微凝胶仍然是一个挑战,因为它们大多是缓慢的胶凝而不是血管生成的。在本文中,我们报道了由超长DNA(> 100,000 nt)与血管内皮生长因子(VEGF)适配子联锁的快速胶凝和血管生成胶原蛋白支架。DNA互锁将胶原蛋白的凝胶化时间缩短了30倍以上,达到40 s,并通过微流体流动进行了调节,但天然胶原蛋白的粘弹性,生物降解性和生化特性保持不变。当被细胞包裹时,血管生成微凝胶可改善伤口愈合和肝脏再生,与非血管生成或无细胞微凝胶相比。冷冻保存后,充满细胞的微凝胶可回收> 80%的活细胞,并且它们保留了其治疗潜力。这些血管生成的,快速胶凝的和超软的充满细胞的微凝胶有望成为再生医学中可注射的治疗药物。

更新日期:2020-04-29
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