Synergistic Effects of Therapeutic Ultrasound and Biomaterials in Osteoarthritis

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation, subchondral bone remodeling, and synovial inflammation. Current treatments cannot halt or reverse OA progression, necessitating the development of novel noninvasive therapies. Therapeutic ultrasound (US), particularly low-intensity pulsed US, has demonstrated efficacy in slowing OA progression. Therapeutic US generates significant thermal and nonthermal effects through noninvasive mechanical forces, exerting biological effects and regulating cell behavior. Therapeutic US has been explored for bone and cartilage repair and shows broad potential in tissue repair when combined with biomaterials. This review summarizes the enhanced or synergistic effects of US and biomaterials in OA. This study elucidated the molecular mechanisms underlying the effects of US on synovium, cartilage, subchondral bone, and mesenchymal stem cells. Notably, the combination of US with various biomaterials can modulate cellular behavior in OA through synergistic effects, including tissue regeneration, enhanced mechanical stimulation, drug delivery, and microenvironment regulation. For each cell type, we summarize the biological mechanisms underlying the therapeutic effects of US and biomaterials, demonstrating their potential to mitigate OA progression. Furthermore, this article explores the limitations and future research prospects of combining US and biomaterials as a therapeutic strategy. Overall, the integration of US and biomaterials holds significant promise as a novel treatment for OA, with potential applications in broader musculoskeletal tissue repair and regenerative medicine. Impact Statement Osteoarthritis (OA) is a complex degenerative disorder that remains challenging to manage. This review highlights the innovative therapeutic potential of combining ultrasound (US), particularly low-intensity pulsed US, with biomaterials for OA treatment. By leveraging synergistic effects such as enhanced tissue repair, targeted drug delivery, and microenvironment regulation, this approach offers a noninvasive and effective strategy to mitigate OA progression and paves the way for advancements in musculoskeletal regenerative medicine.