Vascular induction and cell infiltration into peptide-modified bioactive silk fibroin hydrogels
Vascular induction and cell infiltration into peptide-modified bioactive silk fibroin hydrogels
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DOI：
10.1039/c7tb02109g
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发表时间：
2017-09-28
影响因子：
7
通讯作者：
Yamaoka, Tetsuji
中科院分区：
文献类型：
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作者：
Kambe, Yusuke;Murakoshi, Akie;Yamaoka, Tetsuji
在基于水凝胶的软组织工程中，血管诱导到水凝胶中以及长期的体积保留对于维持组织形状和功能而不引起水凝胶的较深部分的坏死是必不可少的。丝素蛋白（SF）水凝胶显示出足够高的机械强度以在植入期间维持其形状一个月，但尚未很好地评估其是否具有血管诱导生物活性以实现其被血管化组织替代。在这里，我们产生了血管诱导肽（VIP）含有内皮细胞（EC）粘附REDV和血管内皮生长因子模拟QK肽修改SF水凝胶。体外实验表明，由于VIP的生物活性，用VIP修饰SF水凝胶仅改变水凝胶的生物学性质。SF水凝胶在大鼠皮下植入显示各向同性EC迁移到水凝胶中，随后是巨噬细胞和成纤维细胞的浸润。由于这些巨噬细胞和成纤维细胞似乎分别降解SF网络和产生胶原蛋白，因此SF水凝胶逐渐被再生组织取代。VIP加速细胞浸润，使再生组织中血管的形成加倍。这些结果表明VIP改性的SF水凝胶作为软组织工程应用的材料的潜力。
In hydrogel-based soft tissue engineering, vascular induction into a hydrogel as well as long-term volume retention is essential to maintain tissue shape and function without causing necrosis in the deeper part of the hydrogel. A silk fibroin (SF) hydrogel shows a sufficiently high mechanical strength to maintain its shape during implantation for a month, but it has not been well evaluated whether it has vascular-inducing bioactivity to achieve its replacement by vascularized tissues. Here, we produced a vascular-inducing peptide (VIP) containing an endothelial cell (EC)-adhesive REDV and vascular endothelial growth factor-mimicking QK peptides to modify the SF hydrogel. In vitro experiments showed that the modification of the SF hydrogel with VIP changed only biological properties of the hydrogel due to the bioactivity of VIP. Subcutaneous implantation of SF hydrogels in rats revealed isotropic EC migration into the hydrogels, which was followed by infiltration of macrophages and fibroblasts. Since these macrophages and fibroblasts appeared to degrade the SF network and to produce collagen, respectively, SF hydrogels were replaced gradually by regenerated tissues. VIP accelerated cell infiltration and doubled the formation of blood vessels in the regenerated tissue. These results suggest the potential of the VIP-modified SF hydrogel as a material for soft tissue engineering applications.