Injectable hybrid system for strontium local delivery promotes bone regeneration in a rat critical-sized defect model

Abstract

Strontium (Sr) has been described as having beneficial influence in bone strength and architecture. However, negative systemic effects have been reported on oral administration of Sr ranelate, leading to strict restrictions in clinical application. We hypothesized that local delivery of Sr improves osteogenesis without eliciting detrimental side effects. Therefore, the in vivo response to an injectable Sr-hybrid system composed of RGD-alginate hydrogel cross-linked in situ with Sr and reinforced with Sr-doped hydroxyapatite microspheres, was investigated. The system was injected in a critical-sized bone defect model and compared to a similar Sr-free material. Micro-CT results show a trend towards higher new bone formed in Sr-hybrid group and major histological differences were observed between groups. Higher cell invasion was detected at the center of the defect of Sr-hybrid group after 15 days with earlier bone formation. Higher material degradation with increase of collagen fibers and bone formation in the center of the defect after 60 days was observed as opposed to bone formation restricted to the periphery of the defect in the control. These histological findings support the evidence of an improved response with the Sr enriched material. Importantly, no alterations were observed in the Sr levels in systemic organs or serum.

Enhancement of the Biological and Mechanical Performances of Sintered Hydroxyapatite by Multiple Ions Doping

“…Statistical significance values were p < 0.05 for all samples related to TCP and S-HA (data not shown); the statistical significance between each sample is also indicated as: *p < 0.05, **p < 0.01 and ***p < 0.001. Huang et al, 2016;Khan et al, 2016;Henriques Lourenço et al, 2017;Montesi et al, 2017), whereas no studies reported on the effect of strontium on MMP expression. However, these previous results were obtained with nanostructured and nanocrystalline materials, synthesized at near body temperature and characterized by high surface activity and greater ability of releasing Ca 2+ , PO 4 3− , and Sr 2+ ions, in comparison with sintered ceramics.…”

Elastin-derived scaffolding associated or not with bone morphogenetic protein (BMP) or hydroxyapatite (HA) in the repair process of metaphyseal bone defects

“…Descriptive analysis of collagen fibers under polarized light showed a predominance of redorange birefringence in newly regenerated bone referring to thicker and more organized fibers, similar to the original lamellar bone of the defect edge [39]. In the E24/50/HA and E96/ 37/HA groups, the hydroxyapatite microparticles were in darkfield surrounded by red-orange birefringence collagen fibers arranged neatly [32].…”

A thermoresponsive, citrate‐based macromolecule for bone regenerative engineering

“…This underscores the local release and clearance of strontium from the site and encourages the case for PPCN‐Sr as a safe macromolecule clinically. Of the in vivo Sr‐biomaterial literature, only two studies used injectable systems and none of the materials were inherently antioxidant—the first was the study by Lourenco et al which employed 100 mM Sr‐doped HA‐alginate microspheres and the second incorporated 9 mol % SrO in borate bioactive glass . The majority of the other materials used were calcium phosphate‐based, doped with HA, or variants of bioactive glass .…”