Kevin Wu1, Renford Cindass2, Lin Wang2, Sharon Lawson3, Jeffrey Karp4, Nitin Joshi4, Praveen Vemula5, Vijay Gorantla6, Michael Davis7. 1RESTOR™ Program, 59th Medical Wing, JBSA Lackland AFB, TX, 2San Antonio Military Medical Center, JBSA Fort Sam Houston, TX, 3University of Texas Health Sciences Center at San Antonio, 4Brigham & Women’s Hospital, Harvard Medical School, 5Institute for Stem Cell Biology and Regenerative Medicine, 6University of Pittsburgh Medical Center, 759th Medical Wing, JBSA Lackland AFB
Objectives: Sophisticated body armor and advanced combat casualty care have improved survival after catastrophic extremity and maxillofacial trauma. Vascularized composite allotransplantation (VCA) is a superior restorative option compared to traditional reconstruction in these complex injuries. We used a robust porcine preclinical VCA model to evaluate the efficacy of graft-implanted immunosuppression in preventing acute rejection (AR) and prolonging graft survival without systemic therapy.
Methods: Heterotopic gracilis myocutaneous flap VCA was performed between swine donor-recipient pairs with a single swine leukocyte antigen (SLA) mismatch. Group 1 (controls, n=8) received no drug intervention. In Group 2 (experimental, n=10), a tacrolimus-eluting hydrogel (7 mg/cc, 28mg total) was injected subcutaneously into the donor flap at surgery. Serum and serial biopsies were collected for tacrolimus levels and grafts were clinicopathologically assessed for acute rejection. The study end point was Banff grade 4 rejection.
Results: All control animals developed Banff Grade 1 AR by POD 7 and Grade 4 AR by POD 10.5±2.6. Three technical failures occurred. The remaining six treated with the locally applied tacrolimus-eluting hydrogel had prolonged graft survival to POD 21.2±10.1.
Conclusion: Donor graft tissue-specific immunomodulation with drug-eluting compounds is evolving and holds promise in VCA as a strategy to obviate need for systemic immunosuppression. The improved benefit-to-risk and utility justification could dramatically potentiate the field of reconstructive transplantation in the management of unreconstructable extremity, facial or genitourinary injuries suffered by our service members. Reapplication of this therapy is possible for extended therapeutic effect.
Presented at the SAGES 2017 Annual Meeting in Houston, TX.
Abstract ID: 79749
Program Number: MSS10
Presentation Session: Full-Day Military Surgical Symposium – Basic Science Presentations
Presentation Type: MSSPodium