Material-Assisted Bioengineering Strategies for Osteochondral Defect Repair
Constance Lesage, Marianne Lafont, Pierre Guihard, Pierre Weiss, Jérôme Guicheux, Vianney Delplace
*Theses authors contributed equally to this work
Key words: osteochondral defect, cartilage, subchondral bone, regenerative medicine, biomaterials, cell therapy, biologics
The osteochondral (OC) unit, composed of cartilage and subchondral bone, plays a pivotal role in joint lubrication and in the transmission of constraints to bones during movements. The OC unit can be damaged by repetitive excessive loading, trauma or diseases, leading to cartilage defects. As OC defects does not spontaneously heal, different surgical approaches have been developed (e.g. chondroplasty, arthroscopic lavages and debridement, autologous chondrocyte implantation (ACI), matrix-associated ACI) and several biomaterials have now reached the market. Although present curative care temporarily improves joint functions, it often leads to the formation of fibrocartilaginous repair tissue, the deterioration of the subchondral bone, and functional loss in the long term. OC defects are therefore considered to be one of the major risk factors for long-term degenerative joint disease development such as osteoarthritis. In this context, a plethora of tissue engineering strategies have been envisioned, combining cells, biological molecules and/or biomaterials. A comprehensive study of biomaterial-assisted bioengineering strategies that have been tested in OC defect between 2015 and 2021 was performed. The analysis of almost 300 studies provided a deeper insight into the field, with careful considerations for the therapeutic potential of the different strategies, and current OC regeneration evaluation methods. This study highlighted the multiplicity of strategies that have been envisioned, along with the unlimited number of possible combinations of biomaterials, cell types and bioactive molecules.
The careful analysis of the current state of the art has revealed the emergence of promising strategies, including injectable multilayer and gradient materials, which have shown remarkable improvement in neocartilage and subchondral bone quality, supporting the use of more biomimetic architectures. In parallel with advanced biomaterial design, the controlled release of bioactive molecules, including GFs, almost systematically improved outcomes compared to biomaterials alone. These strategies stimulate cell invasion and allow a shift to cell-free strategies, which is another promising approach to more easily meet the stringent quality and regulatory requirements for safety and efficacy needed for clinical application. Particular attention should be paid to the use of common and more comprehensive assessment methods (scoring systems, assessment methods and animal models), following clear guidelines agreed by the international community. Therefore, though our comprehensive study of biomaterial-assisted bioengineering strategies, this present work will help to build a better common knowledge and be a first step toward progressing in OC regeneration.