Nowadays, the treatment of osteoarthritis (OA), a highly prevalent joint disorder, remains a medical challenge because of the lack of understanding of its pathogenesis. In this work, we developed an alternative strategy of OA treatment using magnesium-based materials as potential therapeutic agent towards subchondral bone remodeling. We selected deer antlers as the animal model where calcification behaviors could provide interesting references for the rapid and reproducible endochondral bone growth. Extremely high content of Mg was detected in the antler, which was able to affect the evolutions of biological apatite. Herein, octacalcium phosphate (OCP) and amorphous calcium phosphate (ACP), which are critically involved in the calcification process, were respectively synthesized under the Mg-containing conditions to understand the role of Mg in the evolution of biological apatite. Results showed that the substitution of Mg 2+ at lower contents stabilized OCP and ACP, while higher contents of Mg inhibited the formation of both phases. The size of both calcium phosphates was also altered significantly by the addition of Mg. The results of cell culture indicated that excess Mg notably accelerated the secretion of extracellular matrix and inhibited the mineralization of chondrocyte matrix. Hence, utilization of Mg-based materials in subchondral bone was supposed to provide a potential therapeutic approach to treat the OA by inhibiting subchondral of ossification process.
Targeted and sustained delivery of drugs to diseased tissues/organs, where body fluid exchange and catabolic activity are substantial, is challenging due to the fast cleansing and degradation of the drugs by these harsh environmental factors. Herein, a multifunctional and bioadhesive polycaprolactone-β-cyclodextrin (PCL-CD) polymersome is developed for localized and sustained co-delivery of hydrophilic and hydrophobic drug molecules. This PCL-CD polymersome affords multivalent crosslinking action via surface CD-mediated host–guest interactions to generate a supramolecular hydrogel that exhibits evident shear thinning and efficient self-healing behavior. The co-delivery of small molecule and proteinaceous agents by the encapsulated PCL-CD polymersomes enhances the differentiation of stem cells seeded in the hydrogel. Furthermore, the PCL-CD polymersomes are capable of in situ grafting to biological tissues via host–guest complexation between surface CD and native guest groups in the tissue matrix both in vitro and in vivo, thereby effectively extending the retention of loaded cargo in the grafted tissue. It is further demonstrated that the co-delivery of small molecule and proteinaceous drugs via PCL-CD polymersomes averts cartilage degeneration in animal osteoarthritic (OA) knee joints, which are known for their biochemically harsh and fluidically dynamic environment.
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