Gradient bioprinting of smart cell-instructive biomaterials for osteochondral repair

PROBLEM TO BE ADDRESSED: OSTEOCHONDRAL DEFECTS, which treatments are not fully competent represent a major concern for physicians, putting at the same time pressure on the scientific community to urgently find efficient therapeutic approaches to treat this kind of tissue injury. GOAL: The main goal of EMBODY is the development of a new-tailored therapeutic solution to meet the heterogeneous structure (from the top cartilage to the subchondral bone) of the OC tissue to restore its functionality and the overall mobility. OUR HYPOTHESIS: The hypothesis is that using Marine Coll as a main component of bioinks for 3D bioprinting of smart cell-instructive personalized templates, based on the hierarchical structure of the patient’s native tissue can significantly increase OCD regeneration accordingly to the patient needs. To fulfil the primary goal of the project, several objectives need to be achieved. AT A SCIENTIFIC AND TECHNOLOGICAL LEVEL, THE OBJECTIVES TO BE ADDRESSED ARE: DEVELOPMENT OF SCALABLE PROTOCOLS TO PRODUCE MARINE COLL: To achieve this goal, skins of blue shark resulting from the fish processing industry by-products, will be used to extract the collagen, then the collagen will be in situ mineralized following a co-precipitation approach. DEVELOPMENT OF A DRUG DELIVERY SYSTEM TO INCREASE THE THERAPEUTIC EFFICACY: for that, it will be produced PLGA microspheres to act as a sustainable method for the controlled release of GF, specifically targeting human TGF-b3 and human BMP-2 to growth the cartilage and bone regions of the OC tissue. DEVELOPMENT OF MARINE-BASED CELL FRIENDLY (BIO)INKS: Creation of collagen/doped CaPs/GFs/cells (hMSCs and hUVECs) to have three unique “smart cell-instructive bioinks”, for the OC distinctive layers (from the top cartilage to the subchondral bone). DEVELOPMENT OF A PLATFORM TO REGENERATE OC DEFECTS: This goal will be achieved by preparing tri-layered cell-laden scaffolds by 3D printing technology, based on CAD models. VALIDATION OF A NEW BIOMEDICAL PRODUCT: To reach this, the 3D printed constructs will be tested in animal models. REGARDING A SOCIETAL LEVEL, THE PROJECT AIMS: PROMOTE HEALTHY LIVES AND WELL-BEING: EMBODY goals are aligned with the mission of the Global Alliance for Musculoskeletal Health of worldwide to prevent and improve treatments for musculoskeletal diseases, while reducing the burden and costs of this conditions. The aim is not only to devise a single solution but also to establish a personalized regenerative platform for addressing various cases of OCD. In long term, the developed technology can be utilized to design and manufacture biomaterials prior to the scheduled surgeries, employing patient-specific imaging data and personalizing them with or without the patient's own cells. Patients can benefit from an enhanced quality of life, reducing pain and impaired function. VALORISATION OF MARINE RESOURCES BOTH IN ECOLOGICAL AND ECONOMICAL VECTORS: through the biotechnological exploitation of marine by-products in a more sustainable way for the development of new products for the healthcare market with businesses and economic impact. VALORIZATION OF THE GENERATED INTELLECTUAL PROPERTY: through the development of an innovative technology to fabricate OC constructs. Innovation and business development will be taken into consideration to maximize the achieved results and their recognition and visibility, contributing for the long-term success of the developed research.