Background
The shift to damage control resuscitation practice in forward combat hospitals and the many major advances over the years in combat gear has helped military troops to survive catastrophic extremity and maxillofacial trauma. Vascularized composite allotransplantation (VCA) is a superior restorative option compared to conventional reconstructive methods, however these patients require systemic multi-drug immunosuppression. 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. Group 2 (experimental, n = 3) and Group 3 (experimental, n = 3), a tacrolimus-eluting hydrogel injected subcutaneously into the donor flap at surgery with 28 mg/4cc and 49 mg/4cc, respectively. Serum and VCA tissues were collected for tacrolimus levels and grafts were clinically and histologically assessed for AR until the end point (23 days).
Results
All control animals developed Banff Grade 1 AR by post-operative day (POD) 7 and Grade 4 AR by POD 10. The tacrolimus-eluting hydrogel prolonged graft survival in both groups with an average of reaching Grade 4 AR by POD 20 and POD 28, respectively. Tissue and systemic tacrolimus levels showed no residual amount of the drug at time of euthanasia.
Conclusion
The use of injected tacrolimus-eluting hydrogel in VCA showed delaying of acute rejection and increasing graft survivability that is dose dependent. Donor graft tissue-specific immunomodulation with drug-eluting compounds holds promise in VCA as a strategy to obviate need for systemic immunosuppression. Ultimately, propelling the field of reconstructive transplantation in the management of nonreconstructable injuries.