A Suturable Multilayered Fibrous Scaffold Loaded with α-Ketoglutarate for Enhanced Bone Regeneration

Abstract

The successful application of guided bone regeneration (GBR) membranes requires overcoming the limitations of traditional materials in terms of active biological regulation and clinical operability. To address this, following a systematic rationale that progresses from "functional component optimization" to "structural gradient integration," this study designed and fabricated a multifunctional, suturable triple-layer nanofibrous membrane (MPGCA). The membrane features a functionally graded design: a top aligned fibrous layer serves as a barrier to prevent soft tissue invasion; a middle layer provides mechanical support and suturability; and a bottom layer loaded with calcium phosphate oligomers (CPO) and α-ketoglutarate (αKG) enables dual modulation of osteogenesis and immunometabolism. The scaffold sustainably releases active ingredients, effectively scavenges free radicals, promotes macrophage M2 polarization, and enhances osteogenic differentiation and mineralization of stem cells in vitro. In a rat calvarial defect model, the membrane significantly accelerated bone regeneration through the synergistic effects of osteogenesis, immunomodulation, and angiogenesis. This work provides a novel structure-function cooperative design strategy and offers a guiding framework for future development of personalized, temporally controlled smart bone regeneration materials.