Emerging strategies to bypass transplant rejection via biomaterial-assisted immunoengineering: Insights from islets and beyond.

Novel transplantation techniques are currently under development to preserve the function of impaired tissues or organs. While current technologies can enhance the survival of recipients, they have remained elusive to date due to graft rejection by undesired in vivo immune responses despite systemic prescription of immunosuppressants. The need for life-long immunomodulation and serious adverse effects of current medicines, the development of novel biomaterial-based immunoengineering strategies has attracted much attention lately. Immunomodulatory 3D platforms can alter immune responses locally and/or prevent transplant rejection through the protection of the graft from the attack of immune system. These new approaches aim to overcome the complexity of the long-term administration of systemic immunosuppressants, including the risks of infection, cancer incidence, and systemic toxicity. In addition, they can decrease the effective dose of the delivered drugs via direct delivery at the transplantation site. In this review, we comprehensively address the immune rejection mechanisms, followed by recent developments in biomaterial-based immunoengineering strategies to prolong transplant survival. We also compare the efficacy and safety of these new platforms with conventional agents. Finally, challenges and barriers for the clinical translation of the biomaterial-based immunoengineering transplants and prospects are discussed.