This proposal will establish the feasibility of an innovative Synthetic Fascia(tm) for improved repair of abdominal wall hernias. The manufacture of Synthetic Fascia(tm) from engineered structural proteins will lead to greater control over degradation and purity than processed biologic tissues and is less expensive. The objective of this proposal is to modify Synthetic Fascia(tm) to promote tissue repair without accelerating degradation or undermining mechanical strength.
The specific aims are:
Aim I : Determine the optimal micro tunnel pore network that can be introduced while maintaining mechanical property targets. Fabrication methods will be developed to produce Synthetic Fascia(tm) with defined pore size, spacing, and orientation to enhance host cell infiltration. Pore microstructure will be systematically analyzed to establish repeatable fabrication processes. Two cross linking methods will be investigated. The capacity to scale up sheet size will be verified. Mechanics of porous Synthetic Fascia(tm) will be measured in uniaxial tension and suture retention tests to meet strength and flexibility endpoints.
AIM II : Enhance cell infiltration with the addition of a cell-inductive biopolymer. The Synthetic Fascia(tm) formulation will be augmented with a cell-supportive biomaterial. Co focal laser scanning microscopy will be used to assess the uniformity, repeatability, and efficacy of these modifications. Subcutaneous implants in the rat will be used to characterize host cell infiltration and degradation rates of three biomaterial variants. The optimal Synthetic Fascia(tm) variant will be implanted in a rat abdominal repair model and hernia recurrence, tissue repair rate, adhesion formation, and other functional endpoints will be assessed. Successful completion of Phase I will result in Synthetic Fascia(tm) optimized to provide host immune cell access through the generation of native repair tissue. Of equal importance, the novel material will degrade slowly and without sacrificing mechanical integrity. The Synthetic Fascia(tm) developed in this Phase I SBIR proposal provides the critical foundation for a Phase II SBIR that will include small animal testing of infected defect repair, ISO 10993 biocompatibility testing, sterilization verification, final product characterization, and large animal testing. In summary, the biomaterials developed in this proposal will enhance abdominal wall repair in the presence of infection or contamination. Obese, immunocompromised, diabetic, or battlefield wounded patient populations are especially susceptible to prosthetic infection, and are uniquely positioned to benefit from this innovative bioengineering technology.
With over one million operations per year, the repair of abdominal wall hernias is the most common major general surgery operation in the US. Degradable biologic meshes are increasingly used to repair previously infected or grossly contaminated fields, but infection rapidly accelerates mesh degradation, leading to hernia recurrence. The novel biomaterial constructs developed in this proposal will provide an infection resistant repair with enhanced long-term stability.
