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首页> 外文期刊>Science Advances >Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization
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Evolutionarily conserved sequence motif analysis guides development of chemically defined hydrogels for therapeutic vascularization

机译：进化水保守的序列基序分析指导化学定义水凝胶治疗血管化的开发

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Biologically active ligands (e.g., RGDS from fibronectin) play critical roles in the development of chemically defined biomaterials. However, recent decades have shown only limited progress in discovering novel extracellular matrix–protein–derived ligands for translational applications. Through motif analysis of evolutionarily conserved RGD-containing regions in laminin (LM) and peptide-functionalized hydrogel microarray screening, we identified a peptide (a1) that showed superior supports for endothelial cell (EC) functions. Mechanistic studies attributed the results to the capacity of a1 engaging both LM- and Fn-binding integrins. RNA sequencing of ECs in a1-functionalized hydrogels showed ~60% similarities with Matrigel in “vasculature development” gene ontology terms. Vasculogenesis assays revealed the capacity of a1-formulated hydrogels to improve EC network formation. Injectable alginates functionalized with a1 and MMPQK (a vascular endothelial growth factor–mimetic peptide with a matrix metalloproteinase–degradable linker) increased blood perfusion and functional recovery over decellularized extracellular matrix and (RGDS + MMPQK)–functionalized hydrogels in an ischemic hindlimb model, illustrating the power of this approach.
机译：生物活性配体（例如，来自Fibronectin的RGDS）在化学定义的生物材料的发展中起着关键作用。然而，近几十年已经显示出发现新型细胞外基质蛋白衍生配体的有限进展，用于转化应用。通过基因蛋白（LM）和肽官能化水凝胶微阵列筛选的进化含RGD区的基序分析，我们鉴定了一种肽（A1），其显示出用于内皮细胞（EC）功能的优异支持。机械研究将结果归因于A1接合LM和FN结合整合蛋白的容量。 A1官能化水凝胶中的ECS的RNA测序显示与“脉管系统发育”基因本体论术语中的matrigel相似〜60％。血管生成测定显示A1配方水凝胶的能力，以改善EC网络形成。用A1和MMPQK（具有基质金属蛋白酶 - 可降解的接头的血管内皮生长因子 - 可降解接头）官能化的可注射藻酸盐在缺血性后肢模型中增加了血液灌注和（RGDS + MMPQK） - 官能化水凝胶的血液灌注和功能恢复这种方法的力量。

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