title: Collagen-gelatin mixtures as wound model, and substrates for VEGF-mimetic peptide binding and endothelial cell activation.
abstract: 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.
authors.affiliation: Department of Materials Science and Engineering, The Johns Hopkins University, 3400 N. Charles St, Baltimore, MD 21218, USA.
authors.forename: Tania R
authors.initials: TR
authors.lastname: Chan
authors.affiliation: Department of Materials Science and Engineering, The Johns Hopkins University, 3400 N. Charles St, Baltimore, MD 21218, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stahl
authors.affiliation: Department of Bioengineering, University of Utah, 36 S Wasatch Drive, 3100 SMBB, Salt Lake City, UT 84112, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Bioengineering, University of Utah, 36 S Wasatch Drive, 3100 SMBB, Salt Lake City, UT 84112, USA. Electronic address: michael.yu@utah.edu.
authors.forename: S Michael
authors.initials: SM
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002056:Burns / Q000473:pathology; D002417:Cattle; D024042:Collagen Type I / Q000737:chemistry / Q000494:pharmacology* / Q000648:ultrastructure; D005453:Fluorescence; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology* / Q000648:ultrastructure; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D011489:Protein Denaturation; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014947:Wounds and Injuries / Q000473:pathology*
chemical_list: D024042:Collagen Type I; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D005780:Gelatin
keywords: Angiogenesis; Collagen; Microvasculature; Tissue engineering; VEGF