Nanomedicine has matured significantly in the past 20 years and a number of nanoformulated therapies are cleared by regulatory agencies for use across the globe. Transplant medicine is one area that has significantly benefited from the advancement of nanomedicine in recent times. However, while nanoparticle-based therapies have improved toxicological profiles of some drugs, there are still a number of aspects regarding the biocompatibility and toxicity of nanotherapies that require further research. The goal of this article is to review toxicological profiles of immunosuppressant therapies and their conversion into nanomedicine formulations as well as introduce future challenges associated with current in vitro and in vivo toxicological models.
Summary: Since the 1960s, skin has been considered to be the most allogenic tissue in humans. This tenet has remained unquestioned in the reconstructive transplant arena, which has led to skin serving as the sole monitor for early rejection in vascularized composite allotransplantation. In this article, the authors question the validity of this belief. The authors’ hypothesis is that skin is not always an accurate monitor of rejection in the deep tissues, thus questioning the positive and negative predictive value of the punch biopsy for suspected vascularized composite allotransplantation rejection. A search was carried out identifying vascularized composite allotransplantation publications where the allogenicity of transplanted skin was evaluated. Eighteen publications claimed skin was found to be the most allogenic tissue in humans, justifying its use as a superior monitor for rejection. Eight publications demonstrated skin to be a poor monitor of rejection deeper to the skin. Two vascularized composite allotransplantation animal studies reported skin rejecting simultaneously with the deeper tissues. Finally, three publications discussed a skin and kidney allograft, transplanted simultaneously, indicating skin allogenicity was equivalent to the that of the kidney allograft. Much of the literature in human vascularized composite allotransplantation claims skin to be an excellent monitor of the deep tissues. The conclusion from this study is that skin does not always function as a good monitor for what could be rejecting in the deep tissues. The authors believe continued research is necessary to focus on expanding novel monitoring techniques and technologies to accurately diagnose vascularized composite allotransplantation rejection without tissue destruction.
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