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

Abstract

Abstract Background 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. Results 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. Conclusions 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. Graphical Abstract

Keywords

• Prostaglandin E2 (PGE2)
• Sustained release
• Hindlimb ischemia (HI)
• Angiogenesis
• Muscle regeneration
• MyoD1