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Pulsed-release Dexamethasone-loaded Microspheres Mitigate Scar Contracture And Adhesions In Composite Tissue Burn Reconstruction.
Shawn Jeffrey Loder, MD1, Phoebe Lee, BS1, Wayne Vincent Nerone, BS1, Caroline Fedor, BS1, Fuat Baris Bengur, MD1, Patricia Leftwich, BS1, Lauren Kokai, PhD1, Kacey Marra, PhD1, J Peter Rubin, MD2.
1University of Pittsburgh, Pittsburgh, PA, USA, 2University of Pittsburgh, PITTSBURGH, PA, USA.

PURPOSE: Soft-tissue loss after complex burns is devastating to quality of life, ability to work, and psychosocial well-being. These are disfiguring injuries requiring surgical management and are almost universally limited by contracture, adhesion, and soft-tissue deficit. We have previously described a fat-first, delayed-skin approach to complex burn reconstruction to treat the hypodermal deficit and improve soft tissue-mobility and deficits. Here we describe the use of timed- and pulse-release dexamethasone to augment this approach and mitigate contracture during skin-graft delay.
METHODS: Yorkshire swine received 16, 4x4 cm full-thickness burns. After 48 hours, eschar was removed to fascia. Wounds were stratified across untreated pigs to receive A) No Reconstruction, B) Skin-Only, C) Fat-Only, D) Immediate-Skin, Delayed-Fat, or E) Immediate-Fat, Delayed-Skin. Treatment pigs with Group E wounds then received either 1) Empty Microspheres or Dexamethasone as follows 2) Continuous/Sustained, 3) Immediate-Pulsed, 4) Delayed-Pulsed, or 5) Bimodal-Pulsed. At 8 weeks post-engraftment animals were sacrificed and all wounds were collected for photography, ultrasound, histology and serum studies.
RESULTS: Fat-first reconstruction minimizes adhesions soft-tissue deficits, however, is limited by rapid early contracture which was mitigated by the skin-first approach. Early dexamethasone blocks contracture, however, sustained dosing limited skin graft take. Pulsed-dosing was permissive of skin grafts in the drug elution nadir. Combination fat-first with pulsed-dexamethasone resulted in significant reduction in adhesion, soft-tissue deficit, and contracture vs. skin-first approaches.
CONCLUSION: Here we demonstrate augmentation of a fat-first approach by timed-release dexamethasone to safely mitigate contracture, adhesion, and soft-tissue deficits vs. current reconstructive standards for complex burn wounds.


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