Osteoinductive Microgrooved Membranes for Alveolar Ridge Preservation

Tooth extraction is commonly followed by alveolar ridge resorption, and conventional barrier membranes act largely as passive barriers that do not actively promote early bony sealing of the socket crest. This study asked whether a barrier membrane redesigned to spatially organize early reparative cells at the socket crest preserves alveolar ridge dimensions. Gelatin methacryloyl (GelMA) membranes bearing V-shaped microgrooves were reinforced with electrospun polycaprolactone (PCL) fibers, and recombinant human bone morphogenetic protein 2 (rhBMP-2) was immobilized by stepwise photocrosslinking. Using primary macrophages and bone marrow-derived mesenchymal stem cells, as well as mouse, rat, and beagle models, we assessed macrophage localization and polarization, hypoxia signaling, lactate metabolism, histone lactylation, bone regeneration, and ridge preservation by micro-computed tomography, histology, immunofluorescence, Western blotting, and quantitative reverse transcription polymerase chain reaction. Early bone regeneration in rat calvarial defects was the primary efficacy outcome, and ridge preservation in beagles was a translational outcome. In exploratory analysis, microgrooves guided early myeloid cell enrichment across the defect and were associated with a localized hypoxic microenvironment, lactate dehydrogenase A-dependent lactate production, histone H3K18 lactylation, and a reparative macrophage phenotype that was reversed by lactate dehydrogenase A inhibition in vitro. At 7 and 14 d, microgrooved membranes showed earlier progression of defect healing and extended new bone toward the defect center. Immobilized rhBMP-2 enhanced regeneration to achieve near-complete calvarial closure within 2 wk. In beagles, central socket healing was more advanced at 2 wk in the sites treated with rhBMP-2 microgrooved membranes . At 3 mo, treated sites retained alveolar ridge width, height, and the buccal bone plate relative to natural healing. Microgrooved barrier membranes combined with localized osteoinduction increased early bone regeneration in a controlled rodent comparison and provide proof of concept for alveolar ridge preservation in a canine extraction model.