A protective growth factor delivery strategy based on polyphenol-protein self-assembly to promote inflammatory bone regeneration

Abstract

The efficacy of growth factor delivery-based therapies for bone tissue regeneration is frequently undermined by oxidative stress, especially under inflammatory conditions, which results in structure damage and function inactivation of growth factors. Herein, a straightforward and universal protective delivery strategy is proposed by employing the multiple physical interactions between epigallocatechin-3-gallate (EGCG) and growth factors (e.g., neuregulin-1/NRG-1) to efficiently form self-assembled particles (NE APs). NE APs provide sustained release of NRG-1 while protecting it from oxidative damage, preserving its biological functions of cell recruitment, migration, and angiogenesis. Additionally, NE APs leverage EGCG's ability to scavenge reactive oxygen species and maintain mitochondrial homeostasis, while synergistically enhancing TNF/NF-κB/JAK-STAT signaling pathways to support immune responses and osteogenic differentiation. In vivo experiments demonstrated that NE APs create a favorable microenvironment for bone regeneration through stem cell recruitment, angiogenesis, and immune modulation, effectively promoting the repair of inflammatory bone defects. This versatile protective delivery strategy, based on polyphenol and growth factor self-assembly, offers the potential to advance the application of growth factors in regenerative medicine.