Collagen–gelatin mixtures as wound model, and substrates for VEGF-mimetic peptide binding and endothelial cell activation

• Published in: Acta biomaterialia 2015-03, Vol.15, p.164-172
• Main Authors: Chan, Tania R., Stahl, Patrick J., Li, Yang, Yu, S. Michael
• Format: Article
• Language: English
• Subjects: Affinity; Amino Acid Sequence; Angiogenesis; Animals; Binding; Bones; Burns - pathology; Cattle; Collagen; Collagen Type I - chemistry; Collagen Type I - pharmacology; Collagen Type I - ultrastructure; Collagens; Endothelial cells; Fluorescence; Gelatin - chemistry; Gelatin - pharmacology; Gelatin - ultrastructure; Human; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Level (quantity); Mice; Microvasculature; Molecular Sequence Data; Molecular Weight; Peptides; Peptides - pharmacology; Protein Binding; Protein Denaturation; Rats; Remodeling; Tissue engineering; Vascular Endothelial Growth Factor A - pharmacology; VEGF; Wounds and Injuries - pathology
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2015.01.005

[Display omitted] 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.