Multiregulatory K@BMT@HM hydrogel nanomedicine reprograms cartilage homeostasis in osteoarthritis in vitro

Osteoarthritis (OA) is a debilitating degenerative joint disorder characterized by chronic inflammation, progressive cartilage degradation, and chondrocyte dysfunction. Current treatments primarily manage symptoms, failing to halt or reverse disease progression. The multifactorial nature of OA, involving intricate interactions among oxidative stress, inflammation, apoptosis, and extracellular matrix (ECM) degradation, presents a significant therapeutic challenge. Developing advanced intra-articular biomaterial systems that integrate multi-component bioactive agents with multifunctional carriers is crucial for achieving localized, sustained, and comprehensive therapeutic effects, addressing the complex pathology of OA.

Researchers developed a multifunctional nanomedicine, K@BMT@HM, by combining a supramolecular bioactive core with a functionalized hydrogel microsphere carrier. The K@BMT core integrated the KRFK peptide, bisdemethoxycurcumin (BDMC), and MnTBAP, designed to exert multi-dimensional regulatory effects. The HM-SCHW carrier was composed of chitosan (CS), sodium alginate (SA), hyaluronic acid (HA), and the WYRGRL peptide. The study focused on validating the integrated K@BMT@HM system through a series of in vitro chondrocyte-based assays, evaluating its capacity to enhance antioxidant defense, restore autophagic flux, modulate TGF-β-associated signaling, and support localized delivery properties.

The K@BMT core demonstrated robust multi-dimensional regulatory effects in chondrocyte-based assays. It significantly enhanced antioxidant defense, restored autophagic flux, and modulated TGF-β-associated signaling, collectively mitigating oxidative stress, inflammation, and apoptosis. This core also favored ECM anabolic balance, crucial for cartilage repair. The HM-SCHW carrier provided several critical functionalities, including thermosensitive depot formation, effective lubrication, and cartilage-associated localization and retention. Furthermore, the carrier exhibited in vitro sustained and ROS-responsive release of its bioactive components, ensuring prolonged local action. The integrated K@BMT@HM system also displayed laser-responsive thermal behavior, offering a controllable local heating modality that could support thermosensitive in situ retention. > The K@BMT@HM nanomedicine successfully coupled the multi-component regulatory capacity of its core with the multifunctional delivery advantages of its carrier, effectively reprogramming chondrocyte homeostasis in vitro.