Interplay between biomaterials and the immune system: Challenges and opportunities in regenerative medicine

The use of biomaterials for tissue engineering and regenerative medicine applications has increased dramatically over recent years. However, the clinical uptake of a wide variety of biomaterials remains limited due to adverse effects commonly exhibited by patients, which are caused by the host immune response. Despite this, current in vitro evaluation standards (ISO-10993) for assessing the host response to biomaterials have limitations in predicting the likelihood of in vivo biomaterial acceptance. Furthermore, endotoxin contamination of biomaterials is rarely considered, despite its ability to significantly affect the performance of biomaterials and engineered tissues. This review highlights the importance of the immune response to biomaterials and discusses existing challenges and opportunities in the development and standardised assessment of the immune response to biomaterials, including the importance of endotoxin levels. In addition, the properties of biomaterials that impact the host immune response and the exploitation of immunomodulatory biomaterials in regenerative medicine are explored. Finally, a standardised in vitro pathway of evaluating the immune response to biomaterials (hydrogels) and their regenerative potential is proposed, aiming to ensure safety and consistency, while reducing costs and the use of animals in the biomaterials research for tissue engineering and regenerative medicine.