GRAPH-OCD

Osteochondral defects can significantly impact an individual's quality of life. As the global population ages, there is a growing need for effective solutions for joint restoration and repair. Osteochondral repair involves the restoration of both the articular cartilage (the smooth, protective covering of the joint) and the underlying subchondral bone. Osteochondral repair through cell-free scaffolds has emerged as a promising method to address this clinical challenge. The proposed GRAPH-OCD approach combines a three-dimensional scaffold that could slowly release key signaling/differentiation factors, in particular factors that can contribute to recruiting and stimulating endogenous progenitor cells that will contribute to the regeneration of the osteochondral unit. This project aims to develop and refine strategies for osteochondral tissue engineering, specifically focusing on injectable shear-thinning sodium alginate (SA)-graphene oxide (GO) hydrogels that can be administered in a minimally invasive manner. These hydrogels possess the ability to conform to irregular defects and meet most of the requirements for successful osteochondral repair. Tissue engineering approaches in osteochondral repair have demonstrated significant potential. However, the design of an injectable scaffold that can effectively integrate repaired and native tissues is a complex task due to disparities in mechanical properties, composition, and cellularity. Consequently, this remains a major challenge in the field. The GRAPH-OCD project seeks to address this challenge by developing a viscoelastic hydrogel utilizing a combination of SA and GO. Graphene oxide and its bioinspired derivatives will be incorporated into the hydrogel to enhance its mechanical properties, enabling it to closely resemble the extracellular matrix (ECM) and facilitate effective cell integration. Moreover, bioorthogonal chemistry will be employed to introduce non-covalent and covalent crosslinks for the preparation of the injectable scaffold. The biocompatibility of the hydrogel will be carefully ensured throughout this process. To the best of our knowledge, GO-based injectable hydrogels have not been tested in osteochondral repair. In summary, this innovative approach represents a significant advancement in the repair of both cartilage and subchondral bone, holding great promise for future developments in the field. To meet the fundamental requirements for successful osteochondral repair, the hydrogel composition will be carefully modulated within the GRAPH-OCD project. This modulation will address key aspects such as chondrogenesis promotion, bone formation, and biodegradation without toxic by-products. By optimizing these properties, the proposed GRAPH-OCD platform aims to provide an effective solution for osteochondral repair. The performance and efficacy of the developed hydrogel will be evaluated in a sheep model, serving as a representative animal model for osteochondral defect repair. These innovative strategies and materials are expected to pave the way for future advancements in cell-free scaffold constructs, bringing shear-thinning hydrogels one step closer to clinical application in the field of joint regenerative medicine.