Surface engineering of exosomes enhances the therapeutic efficacy of rheumatoid arthritis by macrophage reprogramming.

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Rheumatoid arthritis (RA) and osteoarthritis (OA) are disabling musculoskeletal disorders that affect joints and cartilage and may lead to bone degeneration. Conventional delivery of anti-arthritic agents is limited due to short intra-articular half-life and toxicities. Innovations in polymer chemistry have led to advancements in hydrogel technology, offering a versatile drug delivery platform exhibiting tissue-like properties with tunable drug loading and high residence time properties This review discusses the advantages and drawbacks of polymeric materials along with their modifications as well as their applications for fabricating hydrogels loaded with therapeutic agents (small molecule drugs, immunotherapeutic agents, and cells). Emphasis is given to the biological potentialities of hydrogel hybrid systems/micro-and nanotechnology-integrated hydrogels as promising tools. Applications for facile tuning of therapeutic drug loading, maintaining long-term release, and consequently improving therapeutic outcome and patient compliance in arthritis are detailed. This review also suggests the advantages, challenges, and future perspectives of hydrogels loaded with anti-arthritic agents with high therapeutic potential that may alter the landscape of currently available arthritis treatment modalities.

Hyaluronic acid-based hydrogels (Hyal-Gels) have the potential to reduce wrinkles by physically volumizing the skin. However, they have limited ability to stimulate collagen generation, thus warranting repeated treatments to maintain their volumizing effect. In this study, stem cell-derived extracellular vesicle (EV)-bearing Hyal-Gels (EVHyal-Gels) were prepared as a potential dermal filler, ameliorating the dermis microenvironment. No significant differences were observed in rheological properties and injection force between Hyal-Gels and EVHyal-Gels. When locally administered to mouse skin, Hyal-Gels significantly extended the biological half-life of EVs from 1.37 d to 3.75 d. In the dermis region, EVHyal-Gels induced the overexpression of CD301b on macrophages, resulting in enhanced proliferation of fibroblasts. It was found that miRNAs, such as let-7b-5p and miR-24-3p, were significantly involved in the change of macrophages toward the CD301bhi phenotype. The area of the collagen layer in EVHyal-Gel-treated dermis was 2.4-fold higher than that in Hyal-Gel-treated dermis 4 weeks after a single treatment, and the collagen generated by EVHyal-Gels was maintained for 24 weeks in the dermis. Overall, EVHyal-Gels have the potential as an antiaging dermal filler for reprogramming the dermis microenvironment.