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

基本信息

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
项目类别：
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

项目摘要

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.

说明（由申请人提供）：本提案针对 NIH、CDC、FDA 和 ACF 的 PHS 2009-02 小型企业创新研究补助金申请综合征集（母公司 SBIR [R43/R44]）。肥厚性疤痕通常在深层真皮伤口愈合过程中形成，其特点是体积大、无弹性疤痕，它会限制活动性、收缩孔口并严重损害外观。据 Aetna 称，10-15% 的皮肤伤口会导致肥厚性疤痕或疤痕疙瘩。引起肥厚性疤痕的异常愈合机制尚不完全清楚，然而，对健康组织和肥厚组织之间生化差异（例如细胞外基质成分及其如何影响成纤维细胞行为）的理解的进展，为开发改善愈合的治疗方法提供了见解并减少或消除疤痕。 Glytrix 受核心蛋白聚糖的启发，设计了一种新型胶原蛋白结合肽聚糖，它可以像核心蛋白聚糖一样调节胶原纤维的形成并增加胶原蛋白凝胶的硬度。使用成体原代平滑肌细胞，发现在肽聚糖存在的情况下，相对于单独的胶原凝胶，I型胶原凝胶产生更高的弹性蛋白，从而证明肽聚糖对成体细胞愈合具有积极影响。最近，Glytrix 表明，将肽聚糖一次性引入大鼠全层真皮伤口可改善愈合效果，具体表现为可见疤痕的减少和伤口拉伸强度的改善。 Glytrix 假设，将胶原蛋白结合肽聚糖引入红杜洛克猪模型的深层真皮伤口中将抑制肥厚性疤痕形成，减少整体疤痕并改善伤口愈合。此外，还将开发一种确定肽聚糖合成标准的功能测定法。为期 6 个月的项目完成后，Glytrix 将准备与合同制造组织扩大生产规模，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。公众健康相关性：肥厚性疤痕通常在深部真皮伤口（包括二度和三度烧伤）愈合过程中形成，其特点是体积大、无弹性疤痕，会限制活动性、收缩孔口并严重损害外观。内部疤痕会对手术后的愈合产生不利影响。拟议的工作旨在评估一种新的潜在疗法，以抑制疤痕形成并恢复正常愈合。