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Engineering semi-interpenetrating network biomaterials for cutaneous wound treatment and characterization of inflammatory tissue response

Posted on:2012-09-04Degree:Ph.DType:Dissertation
University:The University of Wisconsin - MadisonCandidate:Kleinbeck, Kyle RFull Text:PDF
GTID:1464390011467743Subject:Engineering
Abstract/Summary:
Wound care is a major challenge in modern medicine with respect to quality patient care, healing outcomes, and cost. In situ photopolymerizable semi-interpenetrating networks (sIPNs) provide opportunities for use in wound treatment and for studying the wound response to biomaterials. sIPN formulations can be easily modified for use as a drug delivery vehicle or adjunct therapy with other treatment modalities. The sIPN has been applied to a partial thickness wound model in swine alongside multiple clinical standards of care. This model was used to assess wound healing responses to each treatment through clinical macroscopic observation, histological analysis, and regional cytokine measurement at multiple time points throughout healing. Following characterization of efficacy and biocompatibility, modifications to sIPN formulation with loaded drugs were explored to address other challenges to patient care such as pain and infection. Drug release and efficacy were characterized in vitro followed by in vivo assessment of retained efficacy and biocompatibility in the presence of drug. Use of the sIPN as an adjunct treatment with mesenchymal stromal cell therapy was investigated with a focus on feasibility and subsequent cell tracking. Results showed that the sIPN is a biocompatible and efficacious treatment for partial thickness wounds in swine with characteristic modulation of IL-8 and keratinocyte proliferation and migration. Furthermore, sIPN can be loaded with bupivacaine and/or silver sulfadiazine and exemplifies clinically relevant release profiles. Drug loaded sIPNs do not exhibit a reduction in efficacy and biocompatibility in comparison with base sIPN formulations. sIPNs can be effectively coupled with MSC therapy with potential for future work in cell encapsulation. These results indicate the potential for sIPN translation to clinical use in humans. Product development efforts are in progress as a part of establishing standards for incorporating the development and translation pathway into student training.
Keywords/Search Tags:Wound, Sipn, Care
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