Valitor, Inc. Berkeley, California 94710, United States.
Department of Surgery, University of California San Francisco , San Francisco, California 94110, United States.
Biomacromolecules. 2017 Aug 14;18(8):2350-2359. doi: 10.1021/acs.biomac.7b00553. Epub 2017 Jul 21.
There is a clinical need for new therapeutics to improve healing of chronic impaired wounds. Thus, we investigated how biopolymer conjugation could be used to improve the wound healing performance of a key growth factor for tissue regeneration: Sonic hedgehog (Shh). We generated two multivalent Shh conjugates (mvShh) using hyaluronic acid with two different MWs, which exhibited equivalent potency and proteolytic protection in vitro. Using db/db diabetic mice, we showed that mvShh made with smaller HyA MW resulted in more rapid and robust neovascularization compared to mvShh made with larger MW HyA. Further, smaller mvShh conjugates resulted in faster wound resolution compared to the unconjugated Shh. This study is the first to show how the wound healing efficacy of multivalent protein-polymer conjugates is sensitive to the polymer MW, and our findings suggest that this parameter could be used to enhance the efficacy of growth factor conjugates.
临床上需要新的疗法来改善慢性受损伤口的愈合。因此，我们研究了如何通过生物聚合物缀合来提高组织再生的关键生长因子—— Sonic hedgehog（Shh）的伤口愈合性能。我们使用两种不同 MW 的透明质酸生成了两种多价 Shh 缀合物（mvShh），它们在体外表现出等效的效力和蛋白水解保护。使用 db/db 糖尿病小鼠，我们表明，与使用较大 MW 透明质酸的 mvShh 相比，MW 较小的 HyA 制成的 mvShh 导致更快和更强的血管生成。此外，较小的 mvShh 缀合物与未缀合的 Shh 相比，更快地解决了伤口。这项研究首次表明，多价蛋白-聚合物缀合物的伤口愈合功效对聚合物 MW 敏感，我们的研究结果表明，该参数可用于增强生长因子缀合物的功效。
