Pre-Clinical Evaluation of Novel Peptidoglycan for Prevention of Hypertrophic Sca

新型肽聚糖预防肥厚性疤痕的临床前评价

• 批准号: 8001371
• 负责人: John Paderi
• 金额: $ 19.5万
• 依托单位: GLYTRIX, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8001371
• 关键词: Address; Adult; Affect; Animal Sources; Animals; Appearance; Architecture; Behavior; Binding; Biochemical; Biological Assay; Burn injury; Caliber; Cells; Centers for Disease Control and Prevention (U.S.); Chondroitin Sulfates; Cicatrix; Collagen; Collagen Fibril; Collagen Type I; Contracts; Dermal; Development; Drug Formulations; Elastin; Elements; Employee Strikes; Extracellular Matrix; Family suidae; Fibroblasts; Foundations; Gel; Glycosaminoglycans; Healed; Hyaluronic Acid; Hypertrophic Cicatrix; Immunohistochemistry; Impaired wound healing; In Vitro; Keloid; Knockout Mice; Measurement; Mechanics; Modeling; Operative Surgical Procedures; Outcome; Parents; Peptides; Peptidoglycan; Phase; Prevention; Process; Production; Property; Proteoglycan; Rattus; Relative (related person); Rheology; Skin; Small Business Innovation Research Grant; Smooth Muscle Myocytes; Staining method; Stains; Techniques; Technology; Tensile Strength; Therapeutic; Thick; Time; Tissues; Translations; United States National Institutes of Health; Water; Work; Wound Healing; biglycan; biomaterial compatibility; commercialization; cost; decorin; design; efficacy testing; feeding; fibrillogenesis; healing; improved; in vivo; insight; novel; pre-clinical; preclinical toxicity; prevent; progesterone 11-hemisuccinate-(2-iodohistamine); public health relevance; research clinical testing; scale up; therapeutic development; versican; wound

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：本提案涉及NIH、CDC、FDA和ACF的PHS 2009-02小企业创新研究资助申请综合征集（母公司SBIR [R43/R44]）。增生性瘢痕通常在深层皮肤伤口愈合期间形成，并且其特征为体积大、无弹性的瘢痕，其可限制活动性、收缩孔口并严重损害身体外观。根据Aetna的说法，10-15%的皮肤伤口会导致增生性或瘢痕疙瘩。引起增生性瘢痕的异常愈合机制尚未完全了解，然而，在了解健康和增生组织之间的生化差异方面的进展，例如细胞外基质成分以及它们如何影响成纤维细胞行为，为开发用于改善愈合和减少或消除瘢痕的治疗方法提供了见解。Glycoprotein设计了一种新的胶原结合肽聚糖，灵感来自核心蛋白聚糖，它调节胶原原纤维的形成，并增加胶原凝胶硬度作为核心蛋白聚糖。使用成人原代平滑肌细胞，在肽聚糖存在下，相对于单独的胶原蛋白凝胶，在I型胶原蛋白凝胶中发现更高的弹性蛋白产生，从而证明肽聚糖对成人细胞愈合的积极影响。最近，Glycoprotein已经表明，将肽聚糖一次性引入大鼠的全层皮肤伤口中导致改善的愈合，如通过可见疤痕的减少和改善的伤口拉伸强度所确定的。Glycine假设，在红杜洛克猪模型中将胶原结合肽聚糖引入深层真皮伤口将抑制增生性瘢痕形成，减少总体瘢痕形成并改善伤口愈合。此外，还将开发用于确定肽聚糖合成标准的功能测定法。在6个月的项目完成后，Glycoprotein将准备与合同制造组织扩大生产，并进行GMP/GLP临床前和毒性研究，这将是第二阶段提案的重点。 公共卫生相关性：增生性瘢痕通常在包括二度和三度烧伤的深层皮肤伤口的愈合期间形成，并且其特征在于体积大、无弹性的瘢痕，其可限制活动性、收缩孔口并严重损害身体外观。内部疤痕会在心理上影响外科手术后的愈合。这项工作旨在评估一种新的潜在治疗方法，以抑制瘢痕形成并恢复正常愈合。