SBIR-STTR Award

This Phase I SBIR proposal to develop bioelastic materials for the prevention of post-laminectomy adhesions is in response to an NICHD, National Center for Rehabilitation Research (NCMRR) solicitation (SBIR 96-2) for "the development of materials that will enhance function and quality of life of individuals with physical disabilities." The physical disability resulting from intervertebral disc herniation constitutes the third most common condition for which worker disability is granted in the U.S. To improve the outcome of intervertebral disc laminectomy would be to improve the quality of life and rehabilitate function for many millions of disabled Americans. The particular bioelastic materials, elastic protein-based polymers comprised of repeating peptide sequences, to be used to exhibit extraordinary biocompatibility; they do not elicit fibrous capsule formation when implanted; they do not support cell attachment nor the adsorption of blood proteins that do, and they can be expected to slowly degrade with breakdown products being natural amino acids. The approach to the prevention of adhesions due to post-intervertebral discectomy involve: the development of two elastic protein-based polymers, their microbial production at high molecular weights and high yields with removal of endotoxins, the sample preparation in terms of elastic sheets and viscoelastic gels, the utilization of the rabbit as the animal model for discectomy at the lumbar spine region using the sheets to cover the midline dural sac and the gel to protect the exiting nerve roots from scarring, and the evaluation of peridural scarring and the presence of inflammatory and pain markers such as interleukin-1 and substance P by means of antibody probes on the histological sections.

Thesaurus Terms:
adhesion, biomaterial development /preparation, biomaterial evaluation, elasticity, laminectomy biomaterial compatibility, gel, interleukin 1, peptide structure, polymer, protein biosynthesis, substance PEscherichia coli, fermentation, histology, laboratory rabbit, protein purification. National Institute of Child and Human Development (NICHD)

Using two biocompatible elastic protein-based polymers (in viscolelastic gel and elastic sheet forms), the Phase I study demonstrated both materials to be highly effective in preventing adhesions to the spinal dura in the rabbit laminectomy model. The specific aims of Phase II are: 1) to identify the preferred membrane and/or gel configuration(s) of two biocompatible and resorbable polymer compositions for prevention of adhesions in a large animal laminectomy model, 2) to develop sensitive double radio-label standards for purification and a quality control protocol, 3) to utilize an adult sheep lumbar spine model with laminectomies performed at two non-contiguous levels (L3-L4 and L5-L6) allowing for a randomization of the polymer placement to surgical site, 4) to develop a mechanical test method for assessing the interface between the dura mater and the tested polymer and the epidural fibrotic tissue at the control site, and 5) to complete biocompatibility testing and prepare an IDE application for the preferred polymer(s) and state(s). The physical disability resulting from intervertebral disc herniation constitutes the third most common condition for worker disability in the U.S. An improved outcome of intervertebral disc laminectomy would improve the quality of life and restore function for many millions of disabled Americans. PROPOSED COMMERCIAL APPLICATION: Low back pain, for which intervertebral disc pathology is the major cause, is second only to the common cold for work absenteeism in the United States; it is reported to result in more productivity loss than any other medical condition and in an annual health care cost of $33 billion. Over four million cases of prolapsed intervertebral discs are reported annually in the U.S. Development of materials that would improve the outcome of intervertebral disc laminectomy would clearly be of commercial significance while impacting favorably on medical care costs.