SBIR Phase I: A Bioactive Hernia Mesh Containing Choroid Plexus Factors For Improved Tissue Integration

SBIR 第一期：含有脉络丛因子的生物活性疝网，可改善组织整合

• 批准号: 1248710
• 负责人: Chris Thanos
• 金额: $ 15万
• 依托单位: CYTOSOLV INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1248710&HistoricalAwards=false
• 关键词: SBIR; Phase; Bioactive; Hernia; Mesh

This Small Business Innovation Research (SBIR) Phase I Project continues the development of the choroid plexus (CP) growth factor cocktail for application to biologic hernia meshes to treat the challenging hernia repair market. CP factors represent a broad spectrum of potent biologic molecules that have demonstrated a benefit in the healing of splinted open wounds in diabetic mice, are neuroprotective, and can be harvested from cultured CP epithelium for at least a year. The current project focuses on formulating these factors into coatings that can be applied to porcine derived acellular dermal matrices in an attempt to provide modulation of the inflammatory cascade and subsequent improvement of engraftment. CP factors harvested from culture will be collected, purified, and concentrated into hydrogel coatings. Three markers of potency, VEGF, TIMP-2, and TGF-â, will be assessed by ELISA to characterize the raw materials, as well release profiles of various formulations. Using the rat midline abdominal defect model, coated mesh prototypes will be compared to commercially available products with a focus on histopathological characterization, gene expression within the graft, and mechanical integrity. The experimental design and selected endpoints are expected to provide the foundation for determining potential efficacy and subsequent product development pathways. The broader impact/commercial potential of this project, if successful will address the need of, approximately 200,000-400,000 patients annually who are associated with impaired healing, poor engraftment of traditional hernia meshes, and recurrence rates as high as 65%. With very high rates of primary repair failure, as well as hernia developing from simple laparotomy, there is a significantly large unmet clinical need resulting in a market size of approximately $1.7B. A successful translation into the clinic will result in a product that improves hernia mesh engraftment by accelerating inflammation and promoting cell migration and extracellular matrix production. Such a product has the potential for an immediate impact in the clinic due to the rise in prevalence of patients with challenging hernia repairs, and lack of available efficacious therapies. The studies proposed here are preliminary steps toward commercialization, with the opportunity to capture a significant portion of the approximately $1.7B market, none of which is currently occupied by growth factor therapies. By demonstrating a therapeutic benefit, this work could be commercialized rapidly through an ongoing partnership to provide near-term benefit to patients with impaired healing.

该小型企业创新研究 (SBIR) 第一阶段项目继续开发脉络丛 (CP) 生长因子混合物，用于生物疝气网片治疗具有挑战性的疝气修复市场。 CP 因子代表了广泛的有效生物分子。在糖尿病小鼠中证实了对夹板开放性伤口愈合的益处，具有神经保护作用，并且可以从培养的 CP 上皮中收获至少一年。当前的项目重点是将这些因子配制到涂层中。可以应用于猪源性脱细胞真皮基质，以尝试调节炎症级联反应并随后改善从培养物中收集的 CP 因子，并将其浓缩成水凝胶涂层的三种效力标记物：VEGF、TIMP。 -2 和 TGF-α 将通过 ELISA 进行评估，以表征原材料以及使用大鼠中线腹部缺陷模型、涂层网原型的释放曲线。将与市售产品进行比较，重点是组织病理学特征、移植物内的基因表达和机械完整性，预计实验设计和选定的终点将为确定该产品的潜在功效和后续产品开发途径奠定基础。该项目如果成功，每年将满足大约 200,000-400,000 名患者的需求，这些患者与愈合受损、传统疝气网片植入不良以及复发率高达65%。由于初次修复失败率非常高，以及简单剖腹手术引起的疝气，因此存在大量未满足的临床需求，导致市场规模约为 $1.7B 成功转化为临床将产生一种产品。通过加速炎症、促进细胞迁移和细胞外基质产生来改善疝气网植入，由于具有挑战性的疝气修复患者的患病率上升以及缺乏可用的产品，这种产品有可能对临床产生直接影响。这里提出的研究是商业化的初步步骤，有机会占领大约 $1.7B 市场的很大一部分，目前这些市场都没有被生长因子疗法占据。通过证明治疗益处，这项工作可以商业化。通过持续的合作伙伴关系，迅速为康复受损的患者提供短期利益。