A guide to preclinical evaluation of hydrogel-based devices for treatment of cartilage lesions

The drive to develop cartilage implants for the treatment of major defects in the musculoskeletal sys-tem has resulted in a major research thrust towards developing biomaterial devices for cartilage repair. Investigational devices for the restoration of articular cartilage are considered as significant risk mate-rials by regulatory bodies and therefore proof of efficacy and safety prior to clinical testing represents a critical phase of the multidisciplinary effort to bridge the gap between bench and bedside. To date, review articles have thoroughly covered different scientific facets of cartilage engineering paradigm, but surprisingly, little attention has been given to the preclinical considerations revolving around the valida-tion of a biomaterial implant. Considering hydrogel-based cartilage products as an example, the present review endeavors to provide a summary of the critical prerequisites that such devices should meet for cartilage repair, for successful implantation and subsequent preclinical validation prior to clinical trials. Considerations pertaining to the choice of appropriate animal model, characterization techniques for the quantitative and qualitative outcome measures, as well as concerns with respect to GLP practices are also extensively discussed. This article is not meant to provide a systematic review, but rather to intro-duce a device validation-based roadmap to the academic investigator, in anticipation of future healthcare commercialization.Statement of significance There are significant challenges around translation of in vitro cartilage repair strategies to approved ther-apies. New biomaterial-based devices must undergo exhaustive investigations to ensure their safety and efficacy prior to clinical trials. These considerations are required to be applied from early developmental stages. Although there are numerous research works on cartilage devices and their in vivo evaluations, little attention has been given into the preclinical pathway and the corresponding approval processes. With a focus on hydrogel devices to concretely illustrate the preclinical path, this review paper intends to highlight the various considerations regarding the preclinical validation of hydrogel devices for car-tilage repair, from regulatory considerations, to implantation strategies, device performance aspects and characterizations.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )