Tissue engineering strategies for the clinical treatment of cartilage defects are mainly based on the transplantation of expanded autologous chondrocytes in vitro into the patient's damaged tissue. However, the differentiation of chondrocytes during in vitro expansion often leads to suboptimal results in the therapeutic intervention. Three-dimensional (3D) culture systems can restore this de-differentiated state and re-establish the chondrogenic phenotype. In this scenario, 3D bioprinting is a suitable technology for creating patient-shaped grafts from cell-laden bio-ink by layer-by-layer fabrication. This allows for a more physiological environment for transplanted cells, promoting tissue regeneration and repair.
Human joint chondrocytes (hACs) were isolated from patient tissue biopsies and expanded in vitro in a monolayer (2D culture). 3D bioprinting was performed by incorporating expanded hACs in mixed bioinks of platelet-rich plasma (PRP) alginate or alginate. Cell morphology, viability, growth, and chondrogenic differentiation were studied in vitro in both types of printed constructs.
3D culture in both inks significantly increased the expression of chondrogenic markers compared to the 2D condition. Furthermore, the addition of PRP to the alginate upregulated the expression of these markers. Functionalization of PRP ink also increased the vitality, growth, and metabolic activity of hACs compared to alginate alone.
3D bioprinting of hAC allowed them to preserve the chondrogenic phenotype, furthermore, the use of bioink integrated with PRP supported the maintenance of metabolically active articular cartilage collagen type II positive. In view of future clinical translation, the choice of cell source for the 3D bioprinting of patient-specific grafts will have to be oriented towards cell types with a higher potential, such as chondro-progenitors, than mature hACs in order to ensure a more efficient regeneration and repair of cartilage.