Local delivery of strontium ranelate promotes regeneration of critical size bone defects filled with collagen sponge

Abstract

The effect of local delivery of strontium ranelate (SR) on bone regeneration of critical size bone defects filled with collagen sponge was evaluated. Bone defects of 5 mm diameter created in rat calvaria were filled with collagen sponge (C); collagen sponge with 5 mM Sr SR (C5SR) or collagen sponge with 50 mM Sr SR (C50SR). After 2, 4, and 6 weeks, bone volume (BV), bone surface (BS), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were evaluated by computed microtomography. At 6 weeks, histological analysis was performed. Intragroup comparisons were made by the Friedman test, while comparisons between groups were made by Kruskal-Wallis test (α = 5%). All groups showed increased BV, BS, Tb.Th, and Tb.N over time, but only C50SR promoted the reduction of Tb.Sp (p < 0.05). No significant differences between groups were detected at weeks 2 and 4. However, C50SR showed the highest values of BV, BS, and Tb.Th at 6 weeks (p < 0.05). Histological analysis revealed connective tissue in C and C5SR and immature bone tissue in C50SR. Local delivery of SR 50 mM Sr associated with collagen sponge increased and accelerated bone regeneration in critical bone defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 333-341, 2018.

Strontium ranelate promotes odonto-/osteogenic differentiation/mineralization of dental papillae cells in vitro and mineralized tissue formation of the dental pulp in vivo

“…SrRn has gained attention in osteoporosis therapy because it offers two mechanisms of action, i.e., induction of osteoblastogenesis and suppression of osteoclastogenesis 20 , 21 . Furthermore, local application of SrRn with a collagen sponge to artificial bone defects formed in rat calvaria promotes the regeneration of bone tissue 22 . These findings indicate the potent mineralized tissue-forming capacity of SrRn and suggest that SrRn can be used on dentin (indirect pulp capping) and dental pulp tissue (direct pulp capping) as a pulp-capping agent with a potent capacity to form mineralized tissue.…”

Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone healing

“…Several strategies have been proposed to improve the efficiency of bone regeneration by making it faster, more controlled and predictable. Among them, the association between biomaterials and molecules capable of stimulating osteoblast function or that modulate inflammation or angiogenesis . We report here a strategy to improve bone tissue healing through the implantation of porous 3D Ch scaffolds embedded with RvD1, an endogenous pro‐resolution lipid mediator.…”

“…Histological evaluation of the different experimental groups revealed that a layer of newly formed bone was observed delimiting the defect area, being thicker in the case of the animals implanted with Ch + RvD1 scaffolds. Using μCT, a widely applied technique for the 3D study of bone microstructure, we observed a statistically significant increase in trabecular thickness (Tb.Th), that is, considered a reliable indicator of bone strength, and a key factor for the success of implant‐supported rehabilitation . This result is particularly relevant when considering that this healing occurred at the bone/implant interface since conventional materials fail the integration with surrounding tissues.…”

“…Among them, the association between biomaterials and molecules capable of stimulating osteoblast function or that modulate inflammation or angiogenesis. 26 We report here a strategy to improve bone tissue healing through the implantation of porous 3D Ch scaffolds embedded with RvD1, an endogenous pro-resolution lipid mediator. Previous studies of ours have demonstrated that with the use of this mediator of the resolution of inflammation incorporated in Ch scaffolds we were able to develop an immunomodulatory strategy, that induces in vivo a shift in the macrophage phenotypic profile toward an M2 reparative phenotype during an inflammatory response to an implanted biomaterial, and thus creating an environment for prone to tissue repair.…”

“…Using lCT, a widely applied technique for the 3D study of bone microstructure, we observed a statistically significant increase in trabecular thickness (Tb.Th), that is, considered a reliable indicator of bone strength, 31 and a key factor for the success of implantsupported rehabilitation. 26 This result is particularly relevant when considering that this healing occurred at the bone/implant interface since conventional materials fail the integration with surrounding tissues. Aseptic loosening is a typical case study of the limited integration of joint prostheses, highly motivated by adverse immune responses.…”