The sustained PGE₂ release matrix improves neovascularization and skeletal muscle regeneration in a hindlimb ischemia...

The promising therapeutic strategy for the treatment of peripheral artery disease (PAD) is to restore blood supply and promote regeneration of skeletal muscle regeneration. Increasing evidence revealed that prostaglandin E₂ (PGE₂), a lipid signaling molecule, has significant therapeutic potential for tissue repair and regeneration. Though PGE₂ has been well reported in tissue regeneration, the application of PGE₂ is hampered by its short half-life in vivo and the lack of a viable system for sustained release of PGE₂.

In this study, we designed and synthesized a new PGE₂ release matrix by chemically bonding PGE₂ to collagen. Our results revealed that the PGE₂ matrix effectively extends the half-life of PGE₂ in vitro and in vivo. Moreover, the PGE₂ matrix markedly improved neovascularization by increasing angiogenesis, as confirmed by bioluminescence imaging (BLI). Furthermore, the PGE₂ matrix exhibits superior therapeutic efficacy in the hindlimb ischemia model through the activation of MyoD1-mediated muscle stem cells, which is consistent with accelerated structural recovery of skeletal muscle, as evidenced by histological analysis.

Our findings highlight the chemical bonding strategy of chemical bonding PGE₂ to collagen for sustained release and may facilitate the development of PGE₂-based therapies to significantly improve tissue regeneration.