Biological hydroxyapatite, derived from animal bones, is the most widely used bone substitute in orthopedic and dental treatments. Fluorine is the trace element involved in bone remodeling and has been confirmed to promote osteogenesis when administered at the appropriate dose. To take advantage of this knowledge, fluorinated porcine hydroxyapatite (FPHA) incorporating increasing levels of fluoride was derived from cancellous porcine bone through straightforward chemical and thermal treatments. Physiochemical characteristics, including crystalline phases, functional groups and dissolution behavior, were investigated on this novel FPHA. Human osteoblast-like MG63 cells were cultured on the FPHA to examine cell attachment, cytoskeleton, proliferation and osteoblastic differentiation for in vitro cellular evaluation. Results suggest that fluoride ions released from the FPHA play a significant role in stimulating osteoblastic activity in vitro, and appropriate level of fluoridation (1.5 to 3.1 atomic percents of fluorine) for the FPHA could be selected with high potential for use as a bone substitute.

This present study investigated the effect of ultraviolet (UV) irradiation on bioactivity of micro-arc oxidized (MAO) titanium surface in vitro by cell culture medium immersion test and interactions with rat-derived mesenchymal stem cells (MSCs). UV-irradiated MAO surface exhibited no obvious changes in surface roughness, morphology, and phase composition when compared with MAO-only surface. However, in cell culture medium immersion test, markedly more bone-like apatite was formed on UV-modified samples than on MAO sample. Rat bone marrow- and adipose tissue-derived MSCs cultured on UV-modified samples displayed accelerated attachment, significant higher levels of alkaline phosphatase (ALP) activity, and up-regulated osteogenesis-related mRNA expression than MAO sample. XPS results provided direct evidence that the amount of basic hydroxyl groups increased with UV irradiation time, which could be one of the key mechanisms underlying their improved bioactivity.

Biogenic hydroxyapatite is known for its osteoinductive potential due to its similarity to human bone and biocompatibility, but insufficient vascularization compared to autogenous bone during early implantation limits bone integration and osteogenesis. Fluorine has been shown to improve hydroxyapatite’s mechanical properties and the coupling of osteogenic and angiogenic cells. In this study, fluorine-modified biogenic hydroxyapatite (FPHA) with varying fluorine concentrations was prepared and tested for its ability to promote vascularized osteogenesis. FPHA prepared in this study retained the natural porous structure of biological cancellous bone and released F⁻ ions when immersed in cell culture medium. The extraction solutions of FPHA0.25 and FPHA0.50 promoted the formation of capillary-like tubes by human umbilical vein endothelial cells (HUVECs), with FPHA0.25 significantly upregulating vegf mRNA and VEGF protein levels in co-cultured human bone marrow mesenchymal stem cells (HBMSCs). Additionally, FPHA0.25 and FPHA0.50 upregulated pdgf-bb mRNA and PDGF-BB protein levels in HUVECs. In vivo experiments using a rabbit cranial defect model demonstrated that FPHA0.25 promoted early bone formation and angiogenesis in the defect area, enhanced VEGF secretion, and increased PDGFR-β expression in endothelial and mesenchymal cells. These findings suggest that fluorine-modified biogenic hydroxyapatite with an optimal fluorine concentration (FPHA0.25) may offer a promising strategy to enhance the body’s innate bone-healing potential by accelerating vascularization.

Biological hydroxyapatite (BHA) has been extensively employed in alveolar socket preservation, yet its clinical application is often compromised by delayed bone healing triggered by macrophage-mediated pro-inflammatory responses. Building upon our previous work, in which we successfully incorporated fluorine into BHA to develop fluorinated biogenic hydroxyapatite (FBHA) with superior physicochemical and biological properties, this study systematically investigated the effects of fluorine doping on macrophage-mediated osteoimmunomodulation and socket bone healing. The synthesized FBHA was characterized using SEM, EDS, and fluoride ion release assays to confirm fluorine incorporation. In macrophage co-culture models, FBHA demonstrated significant advantages over BHA, effectively suppressing iNOS and TNFα gene expression, reducing NO release, and inhibiting phagocytic activity in M1 macrophages. RNAseq analysis revealed that the M1 phenotype suppression might be mediated through enhanced cellular antioxidant activity. Moreover, in macrophage-conditioned microenvironments, FBHA significantly upregulated osteogenic gene expression and ALP activity of pre-osteoblasts. In vivo experiments demonstrated FBHA’s superior performance in alveolar ridge preservation, especially in new bone formation and mineralization inside sockets. Fluorine doping significantly boosted socket bone healing via suppressing the inflammatory response of macrophages and enhancing osteogenic differentiation of pre-osteoblasts. These findings provide valuable insights into the development of next-generation biomaterials for alveolar socket preservation.