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

这个小企业创新研究（SBIR）一期项目继续开发脉络膜丛（CP）生长因子混合物，用于生物疝补片，以应对具有挑战性的疝修补市场。CP因子代表了广泛的有效生物分子，已经证明对糖尿病小鼠的夹板开放性伤口愈合有益，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。目前的项目重点是将这些因素形成涂层，应用于猪源性脱细胞真皮基质，试图提供炎症级联的调节和随后的植入改善。从培养中收获的CP因子将被收集、纯化并浓缩成水凝胶涂层。三种效价标记，VEGF， TIMP-2和TGF- <e:2>，将通过ELISA进行评估，以表征原料，以及各种配方的释放谱。利用大鼠腹部中线缺损模型，将涂层网原型与市售产品进行比较，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。实验设计和选择的终点有望为确定潜在疗效和后续产品开发途径提供基础。如果成功，该项目的更广泛影响/商业潜力将解决每年约20 -40万患者的需求，这些患者与愈合受损、传统疝补片植入不良和复发率高达65%有关。由于一期修复失败率非常高，以及单纯剖腹手术后产生的疝气，有大量未满足的临床需求，导致市场规模约为17亿美元。如果成功转化为临床，将会产生一种产品，通过加速炎症、促进细胞迁移和细胞外基质的产生来改善疝网植入。由于疝修补患者的患病率上升，以及缺乏有效的治疗方法，这种产品有可能在临床中立即产生影响。这里提出的研究是迈向商业化的初步步骤，有机会占据约17亿美元市场的很大一部分，目前尚无生长因子疗法占据这一市场。通过展示治疗效益，这项工作可以通过持续的合作伙伴关系迅速商业化，为愈合受损的患者提供短期效益。

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.