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.
Highlights
The management of fractures and bone defects remains a significant challenge, and there is the need for improved therapeutic strategies[1]
In the current study we aim to evaluate the in vivo response to the designed Sr-rich hybrid system and its influence on new bone formation using a rat metaphyseal femoral critical-sized defect model, compared to a similar Sr-free material
In hybrid-filled defects (Fig. 2A to D), microspheres are located inside the created bone defect, where the higher radiopacity of the HAp microspheres allowed for the easy monitoring using X-ray
Summary
The management of fractures and bone defects remains a significant challenge, and there is the need for improved therapeutic strategies[1]. Some pre-clinical studies performed in both normal and osteopenic/osteoporotic animal models confirmed these in vitro results, showing the beneficial effects of Sr ranelate on bone formation and remodeling[28,29,30,31,32]. Despite these important effects, cardiovascular safety of orally administered Sr ranelate has been questioned due to a small but significant increase in non-fatal myocardial infarctions[12, 33, 34]. These cations bind homoguluronic blocks in adjacent alginate chains in a cooperative manner (egg-box model) producing a crosslinked hydrogel network[51, 52]
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