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

描述(由申请人提供)：本提案涉及PHS 2009-02综合征集NIH、CDC、FDA和ACF的小型企业创新研究资助申请(家长SBIR[R43/R44])。增生性瘢痕通常在深部皮肤创面愈合过程中形成，其特征是巨大的、无弹性的疤痕，可限制活动、狭窄开口，并严重损害身体外观。根据Aetna的说法，10%-15%的皮肤伤口会导致肥厚性或瘢痕疙瘩疤痕。导致增生性瘢痕的异常愈合机制尚不完全清楚，但对健康组织和增生性组织之间的生化差异，如细胞外基质成分及其如何影响成纤维细胞行为的了解的进展，为开发促进愈合和减少或消除瘢痕的治疗方法提供了见解。Glytrix在核心蛋白的启发下设计了一种新型的胶原结合肽聚糖，它可以调节胶原纤维的形成，并像核心蛋白一样增加胶原凝胶的硬度。在成人原代平滑肌细胞中，与单独使用胶原凝胶相比，在含有肽聚糖的I型胶原凝胶中发现了更高的弹性蛋白产量，从而证明了肽聚糖对成人细胞愈合的积极影响。最近，Glytrix已经证明，一次将肽聚糖引入大鼠的全层皮肤伤口可以改善愈合，这是通过减少可见的疤痕和提高伤口抗张强度来确定的。Glytrix假设，在Red Duroc猪模型的深层真皮伤口中引入胶原结合肽聚糖将抑制增生性瘢痕的形成，减少整体疤痕并促进伤口愈合。此外，还将开发一种用于确定肽聚糖合成标准的功能性分析方法。在6个月的项目完成后，Glytrix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：增生性瘢痕通常在深度皮肤创面(包括二度和三度烧伤)愈合过程中形成，其特征是巨大的、无弹性的疤痕，可限制活动、狭窄孔道，并严重影响身体外观。内部疤痕可能会对手术后的愈合造成不利影响。这项拟议的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。

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.