The mechanistic study of injectable hydrogel loaded with BMSC-exosomes in regulating the TGF-β/MMP axis to inhibit...

Pathological myopia involves reduced collagen deposition and scleral thinning, leading to axial elongation-a process exacerbated by chronic inflammation that disrupts scleral extracellular matrix homeostasis. To address this, we developed an injectable microgel system based on methacrylated alginate (AlgMA) loaded with BMSC-derived exosomes for preventing myopia progression. The photocrosslinkable AlgMA hydrogel exhibited a compressive modulus of ∼10 kPa, providing mechanical support for scleral reinforcement, while its porous network facilitated sustained exosome release. Processing into microgels (AlgMA-MGs) via repeated extrusion through a 25-gauge needle significantly improved injectability of AlgMA hydrogel. Exosome-loaded AlgMA-MGs (Exos-AlgMA-MGs) enhanced fibroblast proliferation and migration, downregulated MMP-2, and upregulated collagen I synthesis via modulation of the TGF-β/MMP axis. In a guinea pig form-deprivation model, both AlgMA-MGs and Exos-AlgMA-MGs attenuated axial elongation in myopic eyes, with the Exos-AlgMA-MGs showing optimal efficacy over four weeks, attributable to the combined biomechanical and bioactive effects. Histological analysis further confirmed that Exos-AlgMA-MGs increased scleral thickness and downregulated the expression of inflammatory factors in myopic eyes, thereby achieving effective anti-scleral remodeling. These findings suggest that Exos-AlgMA-MGs represents a promising strategy for controlling myopia progression.