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Title page for ETD etd-03292010-181953

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
  • skin wound healing
  • bone fracture repair
  • tissue engineering
  • mechanical properties
  • controlled release
  • elastomeric
  • biodegradable
  • porous
  • injectable
  • lovastatin
  • antibiotic
Date of Defense 2010-03-25
Availability unrestricted
Limited 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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