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.

这个小型企业创新研究(SBIR)第一阶段项目继续开发脉络丛(CP)生长因子鸡尾酒，应用于生物疝气网片，以治疗具有挑战性的疝气修补市场。CP因子代表了广泛的有效生物分子，已证明对糖尿病小鼠夹板开放伤口的愈合有好处，具有神经保护作用，可以从培养的CP上皮中获取至少一年。目前的项目重点是将这些因子制成涂层，应用于猪来源的脱细胞真皮基质，试图提供炎性级联的调节和随后的植入性改善。从培养中收获的CP因子将被收集、纯化并浓缩到水凝胶涂层中。三种效力的标记物，血管内皮生长因子、TIMP-2和转化生长因子-α，将通过酶联免疫吸附试验进行评估，以确定原料的特征，以及不同配方的释放情况。使用大鼠腹部中线缺陷模型，涂层网状物原型将与商业可用产品进行比较，重点关注组织病理学特征、移植物内的基因表达和机械完整性。实验设计和选定的终点有望为确定潜在疗效和后续产品开发路径提供基础。如果成功，该项目将产生更广泛的影响/商业潜力，每年将满足大约200,000-400,000名患者的需求，这些患者与愈合障碍、传统疝气网片植入不良以及高达65%的复发率有关。由于一次修补失败率非常高，以及从简单的剖腹手术发展而来的疝气，有相当大的临床需求未得到满足，导致市场规模约为17亿美元。成功地转化到临床将导致一种产品，通过加速炎症、促进细胞迁移和细胞外基质产生来改善腹股沟网片植入。这种产品有可能在临床上立即产生影响，因为具有挑战性的疝修补术的患者比例上升，而且缺乏可用的有效治疗方法。这里提出的研究是走向商业化的初步步骤，有机会在大约17亿美元的市场中占据相当大的份额，目前没有一个市场被生长因子疗法占据。通过展示治疗益处，这项工作可以通过持续的合作伙伴关系迅速商业化，为康复受损的患者提供短期好处。