Photobiomodulation and extracellular vesicles-loaded alginate from adipose mesenchymal stem cells for cartilage repair in a rat model of osteoarthritis.

Osteoarthritis (OA) presents complex pain mechanisms and progressive cartilage degradation, presenting ongoing challenges in clinical management. Extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) have garnered attention as cell-free therapeutic agents with potential application in regenerative medicine. To improve local retention, ADSC-EVs were delivered using a viscosity-enhanced alginate matrix (ADSC-EVs/Alg) as an injectable carrier. Photobiomodulation (PBM), a noninvasive and drug-free therapeutic approach known to modulate inflammation and promote tissue regeneration, was investigated alone and in combination with ADSC-EV delivery via cell proliferation in vitro and cartilage repair of KOA in rats in this study. In vitro, PBM significantly promoted cell proliferation, while the optimized ADSC-EVs/Alg matrix (10% alginate, 1: 9 Alg:EV ratio) served as a stable delivery vehicle without further enhancing PBM-induced proliferation. In a rat model of knee OA, the treatments of ADSC-EVs/Alg, PBM, and their simultaneous administration all demonstrated comparable cartilage preservation. Collectively, these findings indicate that both PBM and ADSC-EVs/Alg promote cartilage repair; however, their combined therapy offers no marked additional benefit under the evaluated conditions.