A Multi-Functional Hybrid System Comprised of Polydopamine Nanobottles and Biological Effectors for Cartilage Repair

Serving as the connective tissue between bones, articular cartilage plays an essential role in shock absorption and load-bearing. An injury to cartilage is expected to trigger degenerative changes, ultimately leading to osteoarthritis. Among the numerous methods for treating articular cartilage injuries, stem cell therapy stands out as a viable approach owing to the self-renewal and multi-directional differentiation capacities of stem cells. Despite recent progress, it remains a challenge to recruit stem cells to the injured site while ensuring subsequent cell survival and directing their differentiation into chondrocytes. Herein, we report a hybrid system consisting of polydopamine (PDA) nanobottles embedded in a hydrogel matrix to stepwise release biological effectors for the recruitment and protection of stem cells while promoting their chondrogenic differentiation. Specifically, we load a homing effector in the hydrogel matrix, together with the encapsulation of a cartilage effector in PDA nanobottles filled with a phase-change material. In action, the homing effector is quickly released from the hydrogel in the initial step to recruit stem cells from the surroundings. Owing to the antioxidation effect of PDA, the recruited cells are shielded from reactive oxygen species. The cartilage effector is then slowly released from the nanobottles to promote chondrogenic differentiation, facilitating cartilage repair. Altogether, this strategy encompassing recruitment, protection, and differentiation of stem cells offers a viable route to tissue repair or regeneration through stem cell therapy.