Plastic Surgery Research Council
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ADIPOSE DERIVED-MESENCHYMAL STEM CELL SEEDED HYDROGELS ACCELERATE CLOSURE OF MURINE WOUNDS
Presenter: Ravi Garg, MD
Co-Authors: Rennert RC; Sorkin M; Auerbach LJ; Lennon J; Longaker MT; Gurtner GC
Stanford University and University of Wisconsin

In the search for novel strategies towards tissue regeneration, our group has developed a biomimetic hydrogel, and demonstrated that seeding with bone marrow derived mesenchymal stem cells augments wound healing. However, the clinical adoption of a stem cell seeded scaffold requires a more readily accessible source of progenitor cells. This study explores the potential of adipose derived mesenchymal stem cell (ASC) seeded hydrogels for the enhancement of wound healing in a murine excisional wound model.In sequential experiments, murine and human ASCs were isolated and delivered to hydrogels by capillary force. ASC viability, migration and proliferation capacity within the hydrogel were assessed in vitro using live/dead, transwell migration and MTT proliferation assays. In vivo ASC viability was determined following injection or hydrogel application in excisional wounds using bioluminescent imaging. The effect of ASC seeded hydrogels on wound healing was determined by comparing the wound closure rates, neovascularization response and inflammatory cytokine profiles of wounds receiving no treatment, unseeded hydrogels or ASC seeded hydrogels. ASCs remained viable for up to 14 days following hydrogel seeding in vitro, with a retained ability to migrate through the hydrogel and a low basal metabolism. Delivery of ASCs within the hydrogel significantly increased their in vivo survival compared to direct injection. Excisional wounds treated with ASC seeded hydrogels closed significantly faster and demonstrated increased neovascularization compared to wounds receiving no treatment or unseeded hydrogels. Transcriptional analyses revealed significantly decreased inflammatory cytokines in wounds treated with ASC seeded hydrogels compared to unseeded hydrogels. A 5% collagen-pullulan biomimetic hydrogel provides a stem cell niche for sustained ASC delivery to excisional wounds. The capacity of ASC seeded hydrogels to accelerate wound closure, increase neovascularization rates and modulate the inflammatory environment of wounds confirms the utility of this platform for tissue regeneration.


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