Osteoarthritis comprises several joint disorders characterized by articular cartilage degeneration and persistent pain, causing disability and economic burden. The incidence of osteoarthritis is rapidly increasing worldwide due to aging and obesity trends. Basic and clinical research on osteoarthritis has been carried out for decades, but many questions remain unanswered. The exact role of subchondral bone during the initiation and progression osteoarthritis remains unclear. Accumulating evidence shows that subchondral bone lesions, including bone marrow edema and angiogenesis, develop earlier than cartilage degeneration. Clinical interventions targeting subchondral bone have shown therapeutic potential, while others targeting cartilage have yielded disappointing results. Abnormal subchondral bone remodeling, angiogenesis and sensory nerve innervation contribute directly or indirectly to cartilage destruction and pain. This review is about bone-cartilage crosstalk, the subchondral microenvironment and the critical role of both in osteoarthritis progression. It also provides an update on the pathogenesis of and interventions for osteoarthritis and future research targeting subchondral bone.

Bone tissue engineering has emerged as a significant research area that provides promising novel tools for the preparation of biomimetic hydrogels applied in bone-related diseases (e.g., bone defects, cartilage damage, osteoarthritis, etc.). Herein, thermal sensitive polymers (e.g., PNIPAAm, Soluplus, etc.) were introduced into main chains to fabricate biomimetic hydrogels with injectability and compatibility for those bone defect need minimally invasive surgery. Mineral ions (e.g., calcium, copper, zinc, and magnesium), as an indispensable role in maintaining the balance of the organism, were linked with polymer chains to form functional hydrogels for accelerating bone regeneration. In the chemically triggered hydrogel section, advanced hydrogels crosslinked by different molecular agents (e.g., genipin, dopamine, caffeic acid, and tannic acid) possess many advantages, including extensive selectivity, rapid gel-forming capacity and tunable mechanical property. Additionally, photo crosslinking hydrogel with rapid response and mild condition can be triggered by different photoinitiators (e.g., I2959, LAP, eosin Y, riboflavin, etc.) under specific wavelength of light. Moreover, enzyme triggered hydrogels were also utilized in the tissue regeneration due to its rapid gel-forming capacity and excellent biocompatibility. Particularly, some key factors that can determine the therapy effect for bone tissue engineering were also mentioned. Finally, brief summaries and remaining issues on how to properly design clinical-oriented hydrogels were provided in this review.

Yolk-shell nanomaterials with a rattle-like structure have been considered ideal carriers and nanoreactors. Traditional methods to constructing yolk-shell nanostructures mainly rely on multistep sacrificial template strategy. In this study, a facile and effective plasmolysis-inspired nanoengineering strategy is developed to controllably fabricate yolk-shell magnetic mesoporous silica microspheres via the swelling-shrinkage of resorcinol-formaldehyde (RF) upon soaking in or removal of n-hexane. Using FeO@RF microspheres as seeds, surfactant-silica mesostructured composite is deposited on the swelled seeds through the multicomponent interface coassembly, followed by solvent extraction to remove surfactant and simultaneously induce shrinkage of RF shell. The obtained yolk-shell microspheres (FeO@RF@void@mSiO) possess a high magnetization of 40.3 emu/g, high surface area (439 m/g), radially aligned mesopores (5.4 nm) in the outer shell, tunable middle hollow space (472-638 nm in diameter), and a superparamagnetic core. This simple method allows a simultaneous encapsulation of Au nanoparticles into the hollow space during synthesis, and it leads to spherical FeO@RF@void-Au@mSiO magnetic nanocatalysts, which show excellent catalysis efficiency for hydrogenation of 4-nitrophenol by NaBH with a high conversion rate (98%) and magnetic recycling stability.