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.
The proposed NSF work was geared around the idea that the "protein cocktail" formulated by CytoSOlv may provide a benefit in the engraftment of hernia meshes in the population of patients with co-morbidities or other compounding factors associated with hernia recurrence and graft failure. Through a collaboration with Davol, the division of CR Bard responsible for supplying the majority of hernia meshes worldwide, Cytosolv has formulated a biological hernia mesh with a hydrogel coating containing CP factors. Several rodent models were used to evaluate the effectiveness of a protein cocktail in the acceleration and improvement of engraftment of porcine accellular dermal matrix on to the fascia. Improvements were noted in the peak and average peel strength of meshes on injured tissue . Improvements of 82% and 47% respectively at 6weeks. Additionally we studied the ability of the protein cocktail to strengthen the tissue following incisional injury to the linea alba. Likewise the linea alba responded with a 74% increase in break strength associated with CP factor treatment. The broader impact of these studies is the potential for a BioActive Hernia Mesh that could lower the recurrence of hernia. Furthermore the increase in strength could yeild longer term replacement and improved healing.
