Enhanced Bone Regeneration in Alveolar Ridge Preservation with Novel DCPD-based Grafts Functionalized with Resolvin E1

Abstract

Bone regeneration remains a significant challenge in orthopedic and dental medicine, particularly in cases involving complex defects, persistent inflammation, or underlying pathology. Traditional bone graft materials, while widely used, are limited by factors such as donor site morbidity, immune rejection, and insufficient integration. To address these limitations, bioactive materials with osteoinductive and osteoconductive properties have emerged as promising alternatives. In parallel, specialized pro-resolving mediators (SPMs) have gained attention for their ability to modulate inflammation and promote tissue repair. Among them, resolvin E1 (RvE1)—a lipid mediator biosynthesized from eicosapentaenoic acid (EPA)—has demonstrated strong potential in accelerating inflammation resolution and supporting bone regeneration. This study evaluated the regenerative effects of a novel bone graft system composed of highly porous dicalcium phosphate dihydrate (DCPD) granules functionalized with RvE1 in a preclinical model of alveolar ridge preservation. Thirty male Sprague–Dawley rats underwent maxillary first molar extraction with standardized socket preparation and were randomly assigned to one of three treatment groups: negative control (unfilled socket), DCPD granules alone, or DCPD granules coated with RvE1. Specimens were collected at 3- and 6 weeks post-extraction for comprehensive analysis. Bone regeneration was quantified using micro-computed tomography (µCT) to assess bone volume/total volume (BV/TV) and bone mineral density (BMD). Soft tissue healing was evaluated using a composite scoring system based on occlusal photographs, and histological staining provided tissue-level validation. At 3 weeks, the DCPD+RvE1 group demonstrated significantly higher BV/TV compared to both the control and DCPD-only groups (p 0.01). Improved soft tissue healing was also observed in the RvE1-treated group (p 0.05), characterized by reduced erythema and smoother mucosal surfaces. These early enhancements were attributed to the localized burst release of RvE1 during the acute inflammatory phase, promoting a pro-resolving microenvironment conducive to regeneration. By 6 weeks, all groups showed progressive bone fill and soft tissue maturation, and differences in BV/TV, BMD, and healing scores were no longer statistically significant. Histological analysis corroborated the imaging results, showing more organized connective tissue and early woven bone in RvE1-treated sockets at 3 weeks. The DCPD granules provided a biocompatible and resorbable scaffold capable of one-time local drug delivery, aligning with clinical needs for minimally invasive and scalable treatments. In conclusion, RvE1-functionalized DCPD granules significantly enhance early bone and soft tissue healing following tooth extraction. This single-step, bioactive bone graft system presents a promising strategy for socket preservation and regenerative therapies by coupling osteoconductive support with targeted immunomodulation.