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. STATEMENT OF SIGNIFICANCE: This review presents a critical analysis of the role of the interactions between the immune system and biomaterials in determining the therapeutic success of biomaterial-based approaches. No such review addressing the lack of understanding of biomaterial-immune system interactions during the developmental and pre-clinical stages of biomaterials, including the impact of the endotoxin levels of biomaterials on the immune response, is published. As there is a lack of in vitro regulations to evaluate the immune response to biomaterials, a standardised in vitro pathway to evaluate the immune response to biomaterials (hydrogels) and their immunomodulatory and regenerative potential for use in tissue engineering/regenerative medicine applications is presented. The aim of the proposed pathway of biomaterial evaluation is to ensure safety and consistency in the biomaterials research community, while reducing costs and animal use (through the concept of the 3R's - reduction, refinement, and replacement of animals).

Lysozyme hydrolyses β-(1,4) linkages between d-glucosamine and N-acetyl-d-glucosamine units in chitosan, and degrades one of the bifunctional crosslinks in chitosan–genipin hydrogels. Degraded particles have potential to be renally excreted in vivo.

Molecularly Imprinted Polymers (MIPs) were synthesised for the selective detection of amoxicillin in aqueous samples. Different functional monomers were tested to determine the optimal composition via batch rebinding experiments. Two different sensor platforms were tested using the same MIP solution; one being bulk synthesized and surface modified Screen Printed Electrodes (SPEs) via drop casting the microparticles onto the electrode surface and the other being UV polymerized directly onto the SPE surface in the form of a thin film. The sensors were used to measure amoxicillin in conjunction with the Heat-Transfer Method (HTM), a low-cost and simple thermal detection method that is based on differences in the thermal resistance at the solid–liquid interface. It was demonstrated that both sensor platforms could detect amoxicillin in the relevant concentration range with Limits of Detection (LOD) of 1.89 ± 1.03 nM and 0.54 ± 0.10 nM for the drop cast and direct polymerisation methods respectively. The sensor platform utilising direct UV polymerisation exhibited an enhanced response for amoxicillin detection, a reduced sensor preparation time and the selectivity of the platform was proven through the addition of nafcillin, a pharmacophore of similar shape and size. The use of MIP-modified SPEs combined with thermal detection provides sensors that can be used for fast and low-cost detection of analytes on-site, which holds great potential for contaminants in environmental aqueous samples. The platform and synthesis methods are generic and by adapting the MIP layer it is possible to expand this sensor platform to a variety of relevant targets.

This Feature Article evaluates ongoing efforts to adapt adhesives toward the goal of zero-waste living and suggests the most promising future directions. Adhesives are not always considered in zero-waste manufacturing because they represent only a small fraction of a product and offer no additional functionality. However, their presence restricts the reintegration of constituent parts into a circular economy, so a new generation of adhesives is required. Furthermore, their production often leads to harmful pollutants. Here, two main approaches toward addressing these problems are considered: first, the use of natural materials that replace petroleum-based polymers from which conventional adhesives are made and second, the production of dismantlable adhesives capable of debonding on demand with the application of an external stimulus. These approaches, either individually or combined, offer a new paradigm in zero-waste industrial production and consumer applications.