Lin Hang, Chen Bing, Sun Wenjie, Zhao Wenxue, Zhao Yannan, Dai Jianwu
Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100080, People's Republic of China.
Biomaterials. 2006 Nov;27(33):5708-14. doi: 10.1016/j.biomaterials.2006.07.023. Epub 2006 Aug 9.
Platelet-derived growth factor BB (PDGF-BB) was an important inductive factor during wound healing, but the lack of efficient delivery system limited its clinical application. Here, a peptide of seven amino acids was firstly utilized to engineer PDGF-BB to construct a collagen-targeting system. This peptide functioned as collagen-binding domain (CBD) to specially target the PDGF-BB to the collagen and restrict its diffusion. In our study, in vitro activity assay showed that the CBD-fused PDGF (CBD-PDGF) and native PDGF (NAT-PDGF) possessed similar activity to stimulate the human fibroblast proliferation. As expected, this peptide promoted the binding of PDGF to collagen scaffolds, and CBD-PDGF caused more cells to proliferate on the collagen gel than NAT-PDGF when the same amounts of PDGF were added. In the in vivo experiment, CBD-PDGF-loaded collagen scaffolds were uniformly cellularized and vascularized compared to that of NAT-PDGF-loaded scaffolds. Our study demonstrated that the CBD targeted PDGF to the collagen scaffold to exert its functions, and it suggested this could be an effective system for targeting tissue regeneration and wound repair.
血小板衍生生长因子BB(PDGF-BB)是伤口愈合过程中的一种重要诱导因子,但缺乏有效的递送系统限制了其临床应用。在此,首先利用一种七氨基酸肽对PDGF-BB进行工程改造,构建了一种胶原靶向系统。该肽作为胶原结合结构域(CBD)发挥作用,将PDGF-BB特异性靶向到胶原上并限制其扩散。在我们的研究中,体外活性测定表明,融合CBD的PDGF(CBD-PDGF)和天然PDGF(NAT-PDGF)在刺激人成纤维细胞增殖方面具有相似的活性。正如预期的那样,该肽促进了PDGF与胶原支架的结合,并且当添加相同量的PDGF时,CBD-PDGF比NAT-PDGF在胶原凝胶上使更多细胞增殖。在体内实验中,与负载NAT-PDGF的支架相比,负载CBD-PDGF的胶原支架细胞均匀化且血管化。我们的研究表明,CBD将PDGF靶向到胶原支架以发挥其功能,并且表明这可能是一种用于靶向组织再生和伤口修复的有效系统。