Type of Document Dissertation Author Hafeman, Andrea Elise URN etd-03292010-181953 Title Polyurethane scaffold with delivery of biologically active small molecules for tissue regeneration Degree PhD Department Chemical Engineering Advisory Committee
Advisor Name Title Scott A. Guelcher Committee Chair G. Kane Jennings Committee Member Jeffrey M. Davidson Committee Member M. Douglas LeVan Committee Member Paul E. Laibinis Committee Member Keywords
- skin wound healing
- bone fracture repair
- tissue engineering
- mechanical properties
- controlled release
Date of Defense 2010-03-25 Availability unrestricted AbstractLimited availability of autograft tissue for bone and skin wound healing has established the demand for improved synthetic biomaterials. Biodegradable polyurethane (PUR) scaffolds exhibit favorable properties for wound healing applications, as they support cellular proliferation and new tissue formation both in vitro and in vivo. This work describes the design and development of PUR scaffolds with polyester triols and aliphatic triisocyanates. The scaffolds, with up to 93% porosity, were evaluated based on physical, thermal, mechanical, and biological properties; these properties could be adjusted by variations in PUR scaffold composition. Furthermore, the scaffolds were formulated for injectable application, which allows for customizable and minimally invasive procedures.
PUR scaffolds degrade by hydrolysis in vitro, but faster degradation in vivo implicates cell-mediated degradation, specifically by macrophages along the material surfaces. Indeed, PUR degradation was accelerated in vitro when the scaffolds were incubated in enzymatic or oxidative media. In particular, reactive oxygen intermediates had a significant effect on degradation, presumably causing chain scission in both the hard and soft segments of the PUR.
Biologically active molecules, such as antibiotics, small molecule drugs, and growth factors, were incorporated into the foams during synthesis for local, controlled release to enhance wound repair. Local antibiotic delivery could help in healing infected wounds, especially bone fractures, as the scaffold and antibiotic delivery system could be administered in one procedure. This would preclude the need to first implant antibiotic-loaded cement beads, followed by additional surgeries to remove the beads and implant a bone graft. Lovastatin is known to stimulate osteogenesis, and so it was also examined as a potential additive for local release. Scaffolds containing lovastatin enhanced new bone formation both in vitro and in vivo within the defect area. Due to their injectability, biocompatibility, tunable degradation, and potential for release of biologically active small molecules, these PUR scaffolds are potentially promising therapies for tissue engineering.
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