Clinical Strategies to Enhance Nerve Regeneration in Composite Tissue Allotransplantation

Abstract

Synopsis Reinnervation of a hand transplant ultimately dictates functional recovery but provides a significant regenerative challenge. The authors present a review highlighting interventions to enhance nerve regeneration through acceleration of axonal regeneration or augmentation of Schwann cell supportand discuss their relevance to composite tissue allotransplantation. Surgical techniques that may be performed at the time of transplantation to optimize intrinsic muscle recovery—including appropriate alignment of ulnar nerve motor and sensory components, transfer of the distal anterior interosseous nerve to the recurrent motor branch of the median nerve, and prophylactic release of potential nerve entrapment points—are also presented.

Scaffolds for Peripheral Nerve Regeneration, the Importance of In Vitro and In Vivo Studies for the Development of Cell-Based Therapies and Biomaterials: State of the Art

“…Nerve injury may involve variable lengths of nerve impairment, and the degree of the lesion is affected by the type of lesion [45]. Also, the prognosis is dependent on the age of the patient, location of the lesion-distal fare better than proximal lesions-and also demographics [42].…”

Advances in peripheral nerve regeneration as it relates to VCA

“…FK506 is also used as a systemic immunosuppressant to prevent nerve allograft rejection. 66,67 The immunosuppressant was found to have nerve regenerative properties when administered peripherally following injuries to peripheral nerves; subsequently several studies have demonstrated the neuroprotective and neurotrophic effects of Tacrolimus. 69 Despite the promise of this research, well-controlled clinical studies are still necessary to demonstrate the effect of FK506 in nerve regeneration.…”

“…91 Another issue more specific to VCA is the possibility that allogeneic Schwann cells in the transplanted nerve may undergo rejection. 67 Therefore, strategies to create an environment of supportive Schwann cells in the distal aspect of the regenerating nerve are of paramount research interest.…”

Alloimmune and Infectious Complications in Hand/Face Transplantation

“…tacrolimus) could enhance the regeneration of the allografts after HAT. This is based on the hypothesis that tacrolimus increases the pathway of GAP-43 protein thus enhancing axonal regeneration observed in experimental models [26]. Only very recently the clinical effect of tacrolimus on nerve regeneration has been challenged in a phase II clinical trial in five patients receiving tacrolimus after nerve primary suturing or reconstruction using autografts.…”