This proposal addresses PHS 2009-02 Omnibus Solicitation of the NIH, CDC, FDA and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44]). Hypertrophic scars commonly form during healing of deep dermal wounds and are characterized as bulky, inelastic scars, which can restrict mobility, constrict orifices, and severely compromise physical appearance. According to Aetna, 10-15% of dermal wounds result in hypertrophic or keloid scars. The abnormal healing mechanism giving rise to hypertrophic scars is not fully understood, however advances in the understanding of biochemical differences between healthy and hypertrophic tissue, such as extracellular matrix components and how they affect fibroblast behavior, provide insights for development of therapeutic approaches for improving healing and reducing or eliminating scarring. Glytrix has designed a novel collagen-binding peptidoglycan, inspired by decorin, which regulates collagen fibril formation and increases collagen gel stiffness as decorin does. Using adult primary smooth muscle cells, higher elastin production was found in type I collagen gels in the presence of the peptidoglycan relative to collagen gels alone, thus demonstrating a positive impact of peptidoglycans on adult cell healing. Recently, Glytrix has shown that one time introduction of the peptidoglycan into a full thickness dermal wound in a rat results in improved healing as determined by reduction in visible scar and improved wound tensile strength. Glytrix hypothesizes that introduction of collagen binding peptidoglycan into deep dermal wounds in a Red Duroc pig model will inhibit hypertrophic scar formation, reduce overall scarring and improve healing of the wounds. In addition, a functional assay for determining synthesis criteria of the peptidoglycan will be developed. At the completion of the 6 month project, Glytrix will be poised to scale up production with a contract manufacturing organization, and perform GMP/GLP preclinical and toxicity studies, which will be the focus of the Phase II proposal.
Public Health Relevance: Hypertrophic scars commonly form during healing of deep dermal wounds including second and third degree burns, and are characterized as bulky, inelastic scars, which can restrict mobility, constrict orifices, and severely compromise physical appearance. Internal scarring can detrimentally affect healing following surgical procedures. The proposed work aims to evaluate a new potential therapeutic to inhibit scar formation and restore normal healing.
Thesaurus Terms: "21+ Years Old; Address; Adult; Affect; Animal Sources; Animals; Appearance; Architecture; Assay; Behavior; Bgn Protein; Binding; Binding (Molecular Function); Bioassay; Biochemical; Biologic Assays; Biological Assay; Body Tissues; Burn Injury; Burns; Cdc; Caliber; Cell-Extracellular Matrix; Cell/Tissue, Immunohistochemistry; Cells; Centers For Disease Control; Centers For Disease Control (U.S.); Centers For Disease Control And Prevention; Centers For Disease Control And Prevention (U.S.); Chondroitin Sulfates; Chondroitin, Hydrogen Sulfate; Cicatrix; Cicatrix, Hypertrophic; Clinical Evaluation; Clinical Testing; Collagen; Collagen Fibril; Collagen Type I; Common Rat Strains; Contracting Opportunities; Contracts; Dermal; Development; Diameter; Drug Formulations; Ecm; Elastin; Elements; Employee Strikes; Engineering / Architecture; Extracellular Matrix; Family Suidae; Fibroblasts; Formulation; Formulations, Drug; Foundations; Gel; Glycosaminoglycans; Healed; Healing Abnormal; Healing Delayed; Human, Adult; Hyaluronic Acid; Hydrogen Oxide; Hypertrophic Cicatrix; Ihc; Immunohistochemistry; Immunohistochemistry Staining Method; Impaired Healing; Impaired Tissue Repair; Impaired Wound Healing; In Vitro; Keloid; Knockout Mice; Leiomyocyte; Mammals, Rats; Measurement; Mechanics; Methods And Techniques; Methods, Other; Mice, Knock-Out; Mice, Knockout; Modeling; Molecular Interaction; Mucopolysaccharides; Murein; Myocytes, Smooth Muscle; Nih; National Institutes Of Health; National Institutes Of Health (U.S.); Null Mouse; Operation; Operative Procedures; Operative Surgical Procedures; Outcome; Pg-S1; Parents; Peptides; Peptidoglycan; Phase; Pigs; Prevention; Process; Production; Property; Property, Loinc Axis 2; Proteoglycan; Rat; Rattus; Relative; Relative (Related Person); Rheology; Sbir; Sbirs (R43/44); Scars; Scars, Hypertrophic; Skin; Small Business Innovation Research; Small Business Innovation Research Grant; Smooth Muscle Cells; Smooth Muscle Myocytes; Smooth Muscle Tissue Cell; Staining Method; Stainings; Stains; Strikes; Strikes, Employee; Suidae; Surgical; Surgical Interventions; Surgical Procedure; Swine; Techniques; Technology; Tensile Strength; Therapeutic; Thick; Thickness; Time; Tissues; Translations; Type 1 Collagen; United States Centers For Disease Control; United States Centers For Disease Control And Prevention; United States National Institutes Of Health; Water; Work; Wound Healing; Wound Repair; Abnormal Tissue Repair; Adult Human (21+); Biglycan; Biocompatibility; Biomaterial Compatibility; Bone Proteoglycan I; Clinical Test; Commercialization; Cost; Decorin; Delayed Wound Healing; Design; Designing; Efficacy Testing; Feeding; Fibrillogenesis; Healing; His-Pg; Improved; In Vivo; Insight; Keloid Skin Disorder; Novel; Porcine; Pre-Clinical; Preclinical; Preclinical Toxicity; Prevent; Preventing; Progesterone 11-Hemisuccinate-(2-Iodohistamine); Proteoglycan I; Proteoglycan S1; Public Health Relevance; Research Clinical Testing; Scale Up; Suid; Surgery; Therapeutic Development; Tissue Repair; Versican; Wound"
