Vascular induction and cell infiltration into peptide-modified bioactive silk fibroin hydrogels,Journal of Materials Chemistry B

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Vascular induction and cell infiltration into peptide-modified bioactive silk fibroin hydrogels
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2017-08-29 00:00:00 , DOI: 10.1039/c7tb02109g
Yusuke Kambe _{1,

2,

3,

4} , Akie Murakoshi _{1,

2,

3,

4,

5} , Hiroshi Urakawa _{4,

5,

6,

7} , Yoshiharu Kimura _{4,

6,

7,

8} , Tetsuji Yamaoka _{1,

2,

3,

4}

Affiliation

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.

中文翻译：

血管诱导和细胞浸润到肽修饰的生物活性丝素蛋白水凝胶中

在基于水凝胶的软组织工程中，将血管引入水凝胶以及长期保持体积对于维持组织的形状和功能而不会在水凝胶的较深部分造成坏死是必不可少的。丝素蛋白（SF）水凝胶显示出足够高的机械强度，可在植入过程中维持一个月的形状，但尚未对其是否具有血管诱导生物活性以被血管化组织替代进行评估。在这里，我们生产了包含诱导内皮细胞（EC）粘附性REDV和模仿血管内皮生长因子的QK肽的血管诱导肽（VIP），以修饰SF水凝胶。体外实验表明，由于VIP的修饰，SF水凝胶仅因其VIP的生物活性而改变了水凝胶的生物学特性。在大鼠皮下植入SF水凝胶后，各向同性EC迁移到水凝胶中，随后巨噬细胞和成纤维细胞浸润。由于这些巨噬细胞和成纤维细胞分别降解了SF网络并产生了胶原蛋白，因此SF水凝胶逐渐被再生组织取代。VIP加速了细胞浸润，并使再生组织中血管的形成增加了一倍。这些结果表明VIP修饰的SF水凝胶作为软组织工程应用材料的潜力。

更新日期：2017-09-20

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