Immunomodulatory biomaterials and regenerative immunology

Organ damage and loss remain important clinical problems, where the current gold standard is transplantation. One of the main problems with transplants, even when they are successful, is the need to use immuno suppressants (IS) for preventing acute rejection. The use of IS entails several side effects such as increased risk of tumor formation, higher susceptibility to infections and IS-related toxicity. Even though in certain cases, such as liver transplants, weaning off the IS has been achieved [1], in many transplant scenarios the use of IS is indispensable. This aspect was one of the initial promises of tissue engineering as the use of autologous cells and bio compatible biomaterials would render the use of IS unnecessary. In order to prevent rejection, a strict donor–recipient match is necessary and although a high level of efficacy has been achieved with transplant recipients (>95% 1-year survival rate), the increasing number of patients on the donor waiting lists without a corresponding increase in the number of donated organs demonstrates the need for an alternative source of replacement organs. Moreover, beyond the donor–recipient matching, the level of long-term success will be dependent on the demographic data pertaining to donor and the donor’s medical history together with the reason of death. For example, donors for whom the reason of death was cerebro vascular disease have been shown to be more prone to induce rejection [2]. Furthermore, even though the survival rates are high, the deterioration of the transplant is not completely evitable. T-cell mediated scarring of the allograft or antibody-mediated processes will still be active. Immunomodulation methods beyond systemic immunosuppression have been under development. Such technologies include donor regulatory T-cell therapy for promoting tolerance, antibody-based approaches for suppression of alloreactive T cells, allogenic antigen presentation methods during autologous cell debris scavenging to induce tolerance or low-dose IL-2 application for increasing host-regulatory T-cell numbers [3,4]. The use of biomaterials as immunomodulatory agents started with the encapsulation of allogenic Langerhans islets for treatment of diabetes using materials with low immunogenicity such as alginate. This provides an active barrier between the immune cells and antibodies of the host, and the metabolically active implanted allogenic cells. In a similar vein, biomaterial-based controlled delivery systems can achieve local control of immune response, hence circumventing most of the side effects of systemic immunomodulation [5]. Immunomodulatory biomaterials and regenerative immunology