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从天然无序区域筛选出的寡肽修饰小肠黏膜下层,以促进血管生成和加速伤口愈合。

Modification of the small intestinal submucosa membrane with oligopeptides screened from intrinsically disordered regions to promote angiogenesis and accelerate wound healing.

机构信息

Department of Stomatology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.

School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China.

出版信息

Biomater Adv. 2023 May;148:213360. doi: 10.1016/j.bioadv.2023.213360. Epub 2023 Mar 2.

Abstract

A slow vascularization rate is considered one of the major disadvantages of biomaterials used for accelerating wound healing. Several efforts, including cellular and acellular technologies, have been made to facilitate biomaterial-induced angiogenesis. However, no well-established techniques for promoting angiogenesis have been reported. In this study, a small intestinal submucosa (SIS) membrane modified by an angiogenesis-promoting oligopeptide (QSHGPS) screened from intrinsically disordered regions (IDRs) of MHC class II was used to promote angiogenesis and accelerate wound healing. Because the main component of SIS membranes is collagen, the collagen-binding peptide sequence TKKTLRT and the pro-angiogenic oligopeptide sequence QSHGPS were used to construct chimeric peptides to obtain specific oligopeptide-loaded SIS membranes. The resulting chimeric peptide-modified SIS membranes (SIS-L-CP) significantly promoted the expression of angiogenesis-related factors in umbilical vein endothelial cells. Furthermore, SIS-L-CP exhibited excellent angiogenic and wound-healing abilities in a mouse hindlimb ischaemia model and a rat dorsal skin defect model. The high biocompatibility and angiogenic capacity of the SIS-L-CP membrane make it promising in angiogenesis- and wound healing-related regenerative medicine.

摘要

血管生成速度缓慢被认为是用于加速伤口愈合的生物材料的主要缺点之一。已经做出了包括细胞和无细胞技术在内的多种努力来促进生物材料诱导的血管生成。然而,尚未报道用于促进血管生成的成熟技术。在这项研究中,使用从小肠黏膜下层(SIS)膜筛选出的源自 MHC Ⅱ类的内在无序区(IDR)的促进血管生成的寡肽(QSHGPS)来修饰 SIS 膜,以促进血管生成并加速伤口愈合。由于 SIS 膜的主要成分是胶原蛋白,因此使用胶原蛋白结合肽序列 TKKTLRT 和促血管生成寡肽序列 QSHGPS 来构建嵌合肽,以获得具有特定寡肽负载的 SIS 膜。所得的嵌合肽修饰的 SIS 膜(SIS-L-CP)可显著促进脐静脉内皮细胞中与血管生成相关的因子的表达。此外,SIS-L-CP 在小鼠后肢缺血模型和大鼠背部皮肤缺损模型中表现出出色的血管生成和伤口愈合能力。SIS-L-CP 膜具有的高生物相容性和血管生成能力使其在与血管生成和伤口愈合相关的再生医学中有很好的应用前景。

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