Contribution of the in situ release of endogenous cations from xenograft bone driven by fluoride incorporation toward enhanced bone regeneration

Abstract

Xenograft, namely bone-derived biological apatite (BAp), is widely recognized as a favorable biomaterial in bone tissue engineering owing to its biodegradability, biocompatibility, and osteoconductive properties. Substitutions of endogenous trace ions are thought to improve the osteogenic capacity of xenograft compared with synthetic hydroxyapatite (HAp). In order to modify the physicochemical and biological properties of apatite, different approaches to induce trace ion incorporation have been widely considered. In this study, we demonstrated that the incorporation of fluoride ions into porcine bone-derived biological apatite (pBAp) contributes to altered crystal morphology of the apatite, the sustained release of fluoride, and the in situ release of endogenous trace ions (e.g., magnesium and calcium) into the peripheral tissue microenvironment. This ionic balanced perimaterial microenvironment not only led to superior proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs), but also accelerated new bone formation of the calvarial defect on a rat model via the activation of Wnt/β-catenin signaling. These promising observations may be attributed to the controlled release of endogenous trace ions from the xenograft to the peripheral tissue microenvironment driven by fluoride ion incorporation. Lastly, this study may provide a new insight to strengthen the osteogenicity of xenografts for clinical applications in the future.

Concentration‐dependent cellular behavior and osteogenic differentiation effect induced in bone marrow mesenchymal stem cells treated with magnetic graphene oxide

“…OCN is a marker of bone formation and mineralization in late stages of osteogenic differentiation (Liu et al, ). Wnt/β‐catenin has been reported to be an important signaling pathway, which affects cell proliferation and osteogenic differentiation (Clevers, ; Qiao et al, ). Runx2 is recognized as a major regulatory gene for the osteoblastic differentiation process in bone‐forming cells and has been identified as the direct transcriptional target of the WNT/β‐catenin signaling pathway (Cai et al, ; Long et al, ).…”

Bioinorganic supplementation of calcium phosphate-based bone substitutes to improvein vivoperformance: a systematic review and meta-analysis of animal studies

“…One paper was not analyzed in the further steps of the review because it was in Japanese and there were no resources that allowed proper translation, 122 one paper was retracted 123 and three papers were excluded because they used non-synthetic CaPs. [124][125][126] In the meta-analysis, 45 papers with 133 quantitative bone formation comparisons and 20 studies with 57 quantitative remaining material comparisons could be included.…”

Current Stage of Marine Ceramic Grafts for 3D Bone Tissue Regeneration

“…The resulting bone xenograft showed an apparent increase in bone ingrowth when compared to non-treated deproteinized bovine and porcine grafts [49]. In a similar way, fluoride ions were added to porcine bone xenografts leading to an increase in mesenchymal stem cell proliferation and osteogenic differentiation together with an accelerated “in vivo” bone ingrowth [50]. Additionally, different authors added polymers and proteins as collagen to bioceramic xenografts to increase their hydrophilicity and improve mechanical properties [51].…”