ENSURING REPRODUCIBILITY IN GEL-MA-BASED BIOINKS FOR CARTILAGE REGENERATION

Osteoarthritis, which impacts more than 500 million individuals globally and results in annual healthcare expenditures exceeding 7.2 billion euros, poses a substantial clinical challenge due to cartilage damage which, when left untreated, can develop into osteochondral defects. The current medical procedures are often inadequate, underscoring the necessity of providing long-term approaches. Biofabrication is a promising approach to addressing e.g. cartilage defects, with Gelatin Methacryloyl (Gel-MA) becoming a material that is extensively researched in tissue engineering. Nevertheless, Gel-MA is frequently criticized for its perceived lack of reproducibility. This issue originates from a variety of reasons including inconsistent selection of raw materials, variations in modification strategies, varying degrees of substitution, and differences in solvent and photoinitiator concentrations employed in various studies. To overcome these issues, a new bioink is presented based on porcine gelatin where these issues are tackled through a combination of batch control, significant QMS protocols and a purification step to remove endotoxins from the gelatin, and significant Quality control in the following bio ink production, resulting in a true medical grade bioink. From the production of gelatin to the final formulation of ink, quality assurance protocols are implemented at each stage of material development. The printability of the ink was optimized to provide high reproducibility in 3D bioprinting. Primary human chondrocytes were mixed with the bioink and UV-crosslinked for biological validation. Biological assays for cartilage regeneration were conducted on the resulting constructs, which included metabolic activity assays, live/dead cell viability tests, and histological analysis. The bioink's compatibility with human chondrocytes was suggested by high cell viability and metabolic activity of the constructs, as indicated by preliminary results. This study introduces a GelMA-based bioink that is reproducible and ready-to-use by implementing rigorous quality assurance protocols and tackling the reproducibility issues at the earliest phases of bioink development. In the future, the primary objective will be to enhance biofabrication techniques for patient-specific constructs, with the ultimate objective of clinical translation for cartilage repair.