Grant: Collaborative Health Research Projects (NSERC partnered)

"OBJECTIVES: The objective of this proposal is to combine two complementary research fields of advanced biomaterials and nanotechnology (Frank Ko) and burn and wound healing (Aziz Ghahary) to design, develop and validate a nanofibre system for the controlled release of antifibrogenic factors that may be used to reduce scarring in those who may suffer from fibrotic conditions. RATIONALE: Deleterious fibrotic conditions such as keloid and post-burn hypertrophic scarring are disfiguring and devastating for patients, thus placing a significant financial burden on the Canadian Health Care system. We hypothesized that there must be a set of Keratinocyte Derived Anti-fibrogenic Factors (KDAF) that gradually slow down and/or terminate the dynamic process of wound healing. A systematic study to identify and characterize these factors was conducted and the KDAF was identified to be a keratinocyte releasable form of stratifin. A subsequent study showed that KDAF stimulates a number of matrix metalloproteinases in fibroblasts. Finally, topical application of KDAF in rabbit ear fibrotic wounds significantly improved the healing quality and reduced the formation of hypertrophic scarring. Although this study proved successful, the need for an improved delivery system is underscored by an observed burst release and thus, premature degradation of the factor and that topical formulations would not be practical for closed wounds. HYPOTHESIS: We hypothesize that by developing an application of sheets, strips and linear assemblies of nanofibres whose shell are prepared from PLGA or other suitable polymers and core comprise a KDAF- or any other anti-fibrogenic factors such as IFN-alpha-2b complex we will be able to mitigate scarring in patients who are prone to fibrosis. RESEARCH PLAN: Briefly, our research plan encompasses the design, development and validation of three products both in vitro and in vivo: 1. Wound dressing: Sheet of nanofibres carrying KDAF that will in addition to serving as coverage, also provide a slow release of anti-fibrogenic factors to improve or even prevent the development of devastating hypertrophic scarring. 2. Anti-fibrogenic strips for closed wounds: Implantable strips that will slowly release KDAF into the incisional area to mitigate fibrosis within the wound. 3. Anti-fibrogenic sutures: Sutures comprising KDAF within a nanofibre core that will be slowly released to mitigate surgical wound related scarring and fibrosis.