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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics.
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Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics.

机译:用于组织再生传导的合成基质金属蛋白酶敏感性水凝胶:工程细胞侵袭特性。

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摘要

Synthetic hydrogels have been molecularly engineered to mimic the invasive characteristics of native provisional extracellular matrices: a combination of integrin-binding sites and substrates for matrix metalloproteinases (MMP) was required to render the networks degradable and invasive by cells via cell-secreted MMPs. Degradation of gels was engineered starting from a characterization of the degradation kinetics (k(cat) and K(m)) of synthetic MMP substrates in the soluble form and after crosslinking into a 3D hydrogel network. Primary human fibroblasts were demonstrated to proteolytically invade these networks, a process that depended on MMP substrate activity, adhesion ligand concentration, and network crosslinking density. Gels used to deliver recombinant human bone morphogenetic protein-2 to the site of critical defects in rat cranium were completely infiltrated by cells and remodeled into bony tissue within 4 wk at a dose of 5 microg per defect. Bone regeneration was also shown to depend on the proteolytic sensitivity of the matrices. These hydrogels may be useful in tissue engineering and cell biology as alternatives for naturally occurring extracellular matrix-derived materials such as fibrin or collagen.
机译:合成水凝胶已进行分子工程化,以模拟天然临时细胞外基质的侵袭特性:需要整合素结合位点和基质金属蛋白酶(MMP)的底物的组合,以使网络可降解并通过细胞分泌的MMP侵袭细胞。从可溶形式的合成MMP底物的降解动力学(k(cat)和K(m))表征开始,然后交联到3D水凝胶网络中,即可对凝胶进行降解。初级人类成纤维细胞被证明可以蛋白水解地侵入这些网络,该过程取决于MMP底物活性,粘附配体浓度和网络交联密度。用于将重组人骨形态发生蛋白2传递至大鼠颅骨关键缺损部位的凝胶被细胞完全浸润,并在4周内重塑成骨组织,每次缺损为5微克。还显示了骨再生取决于基质的蛋白水解敏感性。这些水凝胶可用于组织工程和细胞生物学中,作为天然存在的细胞外基质衍生材料(如纤维蛋白或胶原蛋白)的替代品。

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