Biointerface Membranes Orchestrating Site‐Specific Osteoimmunomodulatory and Antibacterial Effects for Enhanced Osseous Regeneration in Periodontal Therapy

ABSTRACT In periodontal therapy, successful regeneration of osseous defects necessitates biomaterials capable of overcoming challenges such as infection, inflammation, and impaired intrinsic osteogenic capacity within the complex oral environment. Herein, we introduce a biointerface membrane engineered to precisely manipulate cellular activities and coordinate healing events at the soft–hard tissue interface. The membrane fabricated through mixed and co‐axial electrospinning techniques comprises two distinct layers: an antibacterial (Ab) layer (near gingival) laden with controlled‐release chlorhexidine‐conjugated nanogels (nGel‐CHX), and an osteoinductive (OI) layer (near defect) incorporating nanoneedle‐shaped magnesium (Mg) oxychloride ceramic colloids (MOC NN). Upon implantation, ingrowth barrier to pathogenic bacteria and rapidly growing soft tissues is retained at the gingival–Ab layer interface. Concurrently, a pro‐healing osteoimmune niche is established at the OI layer–defect interface, promoting in situ osteogenesis and new bone ingrowth. In a rat periodontal defect model, the biointerface membrane presents remarkably optimized regenerative performance compared to the clinically utilized Bio‐Gide membrane. Histological, immunohistochemical, immunofluorescence, and micro‐CT analysis reveal the enhanced macrophage M2 polarization, notably elevated osteogenic activity, and accelerated formation of new bone with functional periodontal ligament structure. Collectively, these findings render this biointerface membrane as a promising candidate for effective periodontal defect repair in clinical applications.