Extracellular matrix-mimetic enhanced porous bioscaffolds for accelerating bone defect repair

• An ECM-mimetic functionalized bioscaffold were prepared by conjugating OGP onto a PDA-modified PCL scaffold. • The OGP component precisely regulated OME (induction, modulation, protection, and support) and accelerated bone regeneration by activating PI3K/AKT/mTOR signaling pathway. • MCS/PCL@PDA@OGP bioscaffold achieved critical-sized bone defect repair that integrates both architectural matching and bioactive regulation. The repair of critical-sized bone defects remains a great challenge in orthopaedics, as present bioscaffolds exhibit insufficient capability in replicating the osteogenic microenvironment (OME). Thus, we developed an extracellular matrix (ECM)-mimetic functionalized bioscaffold (MCS/PCL@PDA@OGP) to address this challenge. The matrix simulates the three-dimensional porous topology of the ECM to provide mechanical strength for structural support during bone regeneration, while stably anchoring osteogenic growth peptide (OGP) through polydopamine (PDA) surface modification to replicate critical ECM biochemical characteristics. The PDA@OGP coating significantly enhanced surface hydrophilicity, stimulated MC3T3-E1 cell proliferation and triggered pseudopodia formation and upregulated four expression osteogenic markers (Runx2, ALP, OPN, BMP-2), indicating both enhanced cellular adhesion and osteogenic activity. Transcriptomic profiling identified potential signalling pathways, through which the bioscaffold modulates the OME. Further findings demonstrated that OGP promoted osteogenesis by activating PI3K/AKT/mTOR signalling pathway. In vivo implantation into rat bone-defect models confirmed the scaffold’s robust bone regenerative capacity. By integrating hierarchical structure optimization, multi-component chemical modification, and ECM-mimetic microenvironment induction, MCS/PCL@PDA@OGP bioscaffold has promise for clinical use in bone defect regeneration.