An Injectable Hydrogel Bioimplant Loaded with Engineered Exosomes and Triple Anti-Tuberculosis Drugs with Potential for Treating Bone and Joint Tuberculosis

Purpose: Treatment for bone and joint tuberculosis (BJTB) is challenging due to its refractory and recurrent nature. This study aimed to develop a bioimplantable scaffold with osteoinductive and antituberculosis characteristics to treat BJTB. Methods: This scaffold is built on oxidized hyaluronic acid and carboxymethyl chitosan hydrogel mixed with hydroxyapatite as a bone tissue engineered material. In order to make the scaffold have the biological activity of promoting tissue repair, the engineered exosomes (Exo eng ) were added innovatively. In addition, drug-loaded liposomes equipped with an aldehyde group on the surface are cross-linked with the amine group of the hydrogel skeleton to participate in the Schiff base reaction. Results: The designed scaffold has characteristics of self-healing and injectability exhibit excellent anti-tuberculosis and promoting bone repair activities. Exo eng strongly stimulates cellular angiogenesis and osteogenic differentiation. The liposomes coated in hydrogel can release three kinds of anti-tuberculosis drugs smoothly and slowly, achieving a long term anti-tuberculosis. Conclusion: The composite bio-scaffold shows good tissue repair and long-term anti-tuberculosis abilities, which expected to provide a viable treatment plan for bone-related BJTB. Keywords: hydrogel scaffolds, engineered exosomes, triple anti-tuberculosis drugs loaded, bone and joint tuberculosis, therapy