Shock wave treatment in composite tissue allotransplantation.

Composite tissue allotransplantation (CTA) is an emerging field of transplantation that offers a potential treatment for complex tissue defects after traumatic loss or tumor resection and for the repair of congenital abnormalities. Since CTA of hand, face, and other tissues is a clinical reality, CTA has gained importance as an alternative reconstruction procedure. However, all these procedures are not routinely performed because most CTAs compared to solid organ transplantation are non—life saving operations. Consequently, there has been a wide debate about whether the benefit of CTA justifies the risks of lifelong immunosuppressive therapies, as they remain nonspecific to the type of donor and still bear significant risks of serious side effects. These side effects include an increased incidence of neoplasms, organ toxicity, and opportunistic infections. The most appealing solution to this problem would be the induction of immunologic tolerance, defined as lifelong, donor-specific unresponsiveness without the need for immunosuppressive drugs. In the past 10 years, it has been shown that it is possible to achieve prolonged hand allograft survival with a good functional outcome, superior to that obtained by prostheses, with mainly the same triple drug immunosuppressive regime used routinely in kidney transplants to control rejection of transplanted hands.1-8 These intermediate long-term results have far exceeded expectations both from an immunological and a functional point of view. Improvement of immunotherapy with the eventual aim of tolerance induction therefore continues to be a highly desirable goal in both organ and CTA. Until now, the effect of extracorporeal shock waves (ESW) has not been investigated in a CTA. There is very limited published information as to the safety and complications of ESW treatment in conjunction with CTA. Shock waves are high-energy acoustic waves, generated through an electrohydraulic method in this case, that result from high voltage explosion and vaporization.9,10 Since its successful introduction in 1980 for fragmentation of kidneys stone, ESW has been adapted for many other clinical indications such as musculoskeletal disorders (nonunion of long bone fractures, calcifying tendonitis).11-14 Previous animal and clinical studies found that during shock wave treatment various angiogenic factors are being released.15-26 Aicher et al27 demonstrated that low-energy ESW treatment improves recruitment of circulating endothelial progenitor cells via enhanced expression of chemoattractant factors in hindlimb ischemia in a rat model. Recently published studies showed that early proangiogenic and anti-inflammatory effects of ESW promote tissue revascularization and wound healing by augmenting angiogenesis and suppressing proinflammatory immune response.28,29 The potential of ESW to augment angiogenesis and suppress proinflammatory immune response has aroused interest about its use in other procedures. The aim of this study was to investigate the effect of ESW in a rodent in vivo model of CTA (hindlimb transplantation).