The effect of resolvin D1 on bone regeneration in a rat calvarial defect model

Abstract

Resolvin D1 (RvD1) is a pro‐resolving lipid mediator of inflammation, endogenously synthesized from omega‐3 docosahexaenoic acid. The purpose of this study was to investigate the effect of RvD1 on bone regeneration using a rat calvarial defect model. Collagen 3D nanopore scaffold (COL) and Pluronic F127 hydrogel (F127) incorporated with RvD1 (RvD1‐COL‐F127 group) or COL and F127 (COL‐F127 group) were implanted in symmetrical calvarial defects. After implantation, RvD1 was administrated subcutaneously every 7 days for 4 weeks. The rats were sacrificed at weeks 1 and 8 post‐implantation. Tissue samples were analyzed by real‐time reverse transcriptase‐polymerase chain reaction and histology at week 1. Radiographical and histological analyses were done at week 8. At week 1, calvarial defects treated with RvD1 exhibited decreased numbers of inflammatory cells and tartrate‐resistant acid phosphatase (TRAP) positive cells, greater numbers of newly formed blood vessels, upregulated gene expression of vascular endothelial growth factor and alkaline phosphatase, and downregulated gene expression of receptor activator of nuclear factor‐κB ligand, interleukin‐1β and tumor necrosis factor‐α. At week 8, the radiographical results showed that osteoid area fraction of the RvD1‐COL‐F127 group was higher than that of the COL‐F127 group, and histological examination exhibited enhanced osteoid formation and newly formed blood vessels in the RvD1‐COL‐F127 group. In conclusion, this study showed that RvD1 enhanced bone formation and vascularization in rat calvarial defects.

Resolvin D1 improves allograft osteointegration and directly enhances osteoblasts differentiation

“…Xiaofeng et al demonstrated improved bone healing in rat-calvaria model. Rats were treated with collagen scaffolds, in addition to weekly subcutaneous (SC) injections of RvD1 (39). Subcutaneous tissue enables slow release of molecules due to its special tissue architecture and its combination with collagen scaffolds, thereby reducing the need for frequent injections and their related side effects.…”

Immune homeostasis modulation by hydrogel-guided delivery systems: a tool for accelerated bone regeneration

“…126 It has been demonstrated that collagen/Pluronic F127 hydrogel loaded with resolvin D1 (RvD1), derived from omega-3 docosahexaenoic acid, effectively reduced inflammation and promoted calvarial defect repair in rats. 127 Hydrogels have also been employed as delivery carriers for sustained release of anti-inflammatory drugs in bone tissue regeneration. For instance, Chauhan et al loaded dexamethasone (Dex) into an oxidized pullulan (OP)/PEG hydrazine hydrogel, providing pH-sensitive sustained release and improved chronic inflammatory conditions.…”

The impact of Resolvin E1 on bone regeneration in critical‐sized calvarial defects of rat model—A gene expression and micro‐CT analysis

“…In rat calvarial defects, a recent work by Jiang et al 3 showed that RvD1 had enhanced bone regeneration and vascularization potential. Similarly, Pinto et al 9 have shown that RvD1 may be a viable therapeutic bioagent for osseous regeneration following the placement of allografts.…”

“…4 Previous studies have reported better bone regeneration with adjunctive use of platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), bone morphogenic proteins (BMP), specialized pro-resolving mediators (SPMs) and platelet-derived growth factor (PDGF). 3,[5][6][7][8][9] An essential element of inflammatory responses is the resolution of inflammation. 10 Previously, it was understood that after the initiating stimulus had been eliminated, there would be a passive, progressive reduction in inflammatory processes.…”

“…Recently, Jiang et al3 demonstrated that a D variant of resolvins (RvD1) incorporated into nanopore scaffold and Pluronic F127 hydrogel group had enhanced bone formation and vascularization in rat calvarial defects compared to combined collagen 3D nanopore scaffold and pluronic F127 hydrogel group. Similarly, Pinto et al9 who also evaluated RvD1, demonstrated that RvD1 enhanced bone regeneration by increasing osteoblast differentiation and decreasing osteoclastogenesis and the RANKL/OPG ratio.…”