Chan Tania R, Stahl Patrick J, Li Yang, Yu S Michael
Department of Materials Science and Engineering, The Johns Hopkins University, 3400 N. Charles St, Baltimore, MD 21218, USA.
Department of Bioengineering, University of Utah, 36 S Wasatch Drive, 3100 SMBB, Salt Lake City, UT 84112, USA.
Acta Biomater. 2015 Mar;15:164-72. doi: 10.1016/j.actbio.2015.01.005. Epub 2015 Jan 10.
In humans, high level of collagen remodeling is seen during normal physiological events such as bone renewal, as well as in pathological conditions, such as arthritis, tumor growth and other chronic wounds. Our lab recently discovered that collagen mimetic peptide (CMP) is able to hybridize with denatured collagens at these collagen remodeling sites with high affinity. Here, we show that the CMP's high binding affinity to denatured collagens can be utilized to deliver angiogenic signals to scaffolds composed of heat-denatured collagens (gelatins). We first demonstrate hybridization between denatured collagens and QKCMP, a CMP with pro-angiogenic QK domain. We show that high levels of QKCMP can be immobilized to a new artificial matrix containing both fibrous type I collagen and heat denatured collagen through triple helix hybridization, and that the QKCMP is able to stimulate early angiogenic response of endothelial cells (ECs). We also show that the QKCMP can bind to excised tissues from burn injuries in cutaneous mouse model, suggesting its potential for promoting neovascularization of burn wounds.
在人类中，在诸如骨骼更新等正常生理过程以及诸如关节炎、肿瘤生长和其他慢性伤口等病理状况下，都能观察到高水平的胶原蛋白重塑。我们实验室最近发现，胶原蛋白模拟肽（CMP）能够在这些胶原蛋白重塑位点与变性胶原蛋白以高亲和力杂交。在此，我们表明CMP与变性胶原蛋白的高结合亲和力可用于将血管生成信号传递至由热变性胶原蛋白（明胶）组成的支架。我们首先证明了变性胶原蛋白与具有促血管生成QK结构域的CMP（QKCMP）之间的杂交。我们表明，通过三螺旋杂交，高水平的QKCMP能够固定到一种包含纤维状I型胶原蛋白和热变性胶原蛋白的新型人工基质上，并且QKCMP能够刺激内皮细胞（ECs）的早期血管生成反应。我们还表明，QKCMP能够结合皮肤小鼠模型中烧伤损伤的切除组织，这表明其具有促进烧伤创面新生血管形成的潜力。
