{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:21:54Z","timestamp":1787638914025,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Element doping has emerged as a promising strategy to enhance the osteogenic capacity of bone substitutes. Among various dopants, fluoride has attracted considerable attention because of its modulatory effects on bone regeneration; however, a critical gap remains regarding the long-term systemic safety of fluoride-doped materials before clinical translation. A fluoride-specific, biosafety-oriented translational pathway was therefore applied to complement conventional biomaterial assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fluorinated porcine-derived hydroxyapatite (FPHA) was prepared through a chemical and thermal process and characterized to confirm the stable incorporation of fluoride into the hydroxyapatite lattice. A dual-validation dissolution assay was developed to estimate the total fluoride content of FPHA. Multiple in vitro models simulating physiological and artificial extreme environments were established to evaluate material degradation, associated fluoride release, and changes in the surrounding medium pH. A 26-week beagle dog study was conducted to evaluate serum fluoride concentrations, blood biochemical parameters, ridge contour maintenance, and bone formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Characterization confirmed stable fluoride incorporation into FPHA, which exhibited a lower degradation rate than deproteinized bovine bone mineral (DBBM) and controlled fluoride release under simulated physiological conditions. In the 26-week beagle dog study, serum fluoride concentrations remained comparable to baseline levels, with no clinically relevant adverse changes in blood biochemical parameters. FPHA also showed effective long-term ridge contour maintenance and enhanced bone formation compared to DBBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings provide preclinical evidence supporting the preliminary long-term biosafety profile and osteogenic performance of FPHA, illustrating a fluoride-specific, biosafety-oriented evaluation strategy for ion-functionalized biomaterials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbioe.2026.1889739","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:35:09Z","timestamp":1787636109000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating biosafety and osteogenic efficacy: a translational pathway of fluorinated porcine-derived hydroxyapatite for bone 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