DESCRIPTION (provided by applicant): Patients with a neuropathic bladder have chronic medical problems with urinary incontinence, urinary infections, and potential renal failure. Conventional surgical management of the neuropathic bladder uses detubularized bowel as a patch (enterocystoplasty) to enlarge the bladder. However, this structural modification provides no functional improvement, and carries other complications. Alternative methods to enterocystoplasty have been explored through tissue engineering, by regrowing cells on biodegradable polymers or decellularized biological matrices. In all cases, some elements of regenerated bladder tissue structure have been obtained, but full bladder function has not been restored. Recent advances in nanotechnology provide a novel and alternative strategy for the use of tissue engineering scaffolds. Peptideamphiphile (PA) biomaterials have been developed, which self-assemble on the nanoscale to form fibrous gels, capable of retaining and releasing critical growth factors for regeneration. By non-covalently binding growth factors to the gel matrix, they are protected from degradation and can be released over time. The hypothesis of this proposal is that controlled delivery of bFGF and VEGF from a self-assembling nanofiber PA -scaffold composite will enhance the regeneration of bladder tissue. In this proposal, two well established complementary methods of binding growth factors to PAs will be characterized for their ability to effectively bind and release bFGF and VEGF (Aim 1). The in vitro effect of these PAs will then be assessed by seeding bladder cells within PA-scaffold composites and determining the effects on cell proliferation and differentiation (Aim 2). Lastly, the effects of the PAs on tissue regeneration will be studied in vivo by seeding bladder cells on PA-scaffold composites in a nude rat model. Differences in smooth muscle formation and angiogenesis in the regenerated tissue will be determined (Aim 3). This proposed research will provide the first evaluation of a novel tissue engineering nanotechnology for bladder regeneration.
|Effective start/end date||9/30/05 → 2/29/08|
- National Institute of Diabetes, Digestive and Kidney Diseases (5 R21 DK072450-02)