Fluorine-Incorporated Biogenic Hydroxyapatite Enhances Socket Bone Healing via Addressing Macrophage-Mediated Inflammatory Response
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...
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2025-04-01
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| author | Chengwu Liu Leyao Xu Junming Feng Bo Yang Kaidi Chen Yuanxiang Liu Xiayi Wu Shiyu Wu Zhipeng Li Shoucheng Chen Zhuofan Chen |
| author_facet | Chengwu Liu Leyao Xu Junming Feng Bo Yang Kaidi Chen Yuanxiang Liu Xiayi Wu Shiyu Wu Zhipeng Li Shoucheng Chen Zhuofan Chen |
| author_sort | Chengwu Liu |
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| description | 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 <i>iNOS</i> and <i>TNFα</i> 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. |
| format | Article |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-755105892c38448dbb7bc56f69dd1bfe2025-08-20T02:28:18ZengMDPI AGBioengineering2306-53542025-04-0112439610.3390/bioengineering12040396Fluorine-Incorporated Biogenic Hydroxyapatite Enhances Socket Bone Healing via Addressing Macrophage-Mediated Inflammatory ResponseChengwu Liu0Leyao Xu1Junming Feng2Bo Yang3Kaidi Chen4Yuanxiang Liu5Xiayi Wu6Shiyu Wu7Zhipeng Li8Shoucheng Chen9Zhuofan Chen10Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaHospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangdong Research Center for Dental and Cranial Rehabilitation and Material Engineering, Guangzhou 510055, ChinaBiological 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 <i>iNOS</i> and <i>TNFα</i> 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.https://www.mdpi.com/2306-5354/12/4/396alveolar socket preservationbiogenic hydroxyapatitefluorinemacrophage polarizationbone healing |
| spellingShingle | Chengwu Liu Leyao Xu Junming Feng Bo Yang Kaidi Chen Yuanxiang Liu Xiayi Wu Shiyu Wu Zhipeng Li Shoucheng Chen Zhuofan Chen Fluorine-Incorporated Biogenic Hydroxyapatite Enhances Socket Bone Healing via Addressing Macrophage-Mediated Inflammatory Response Bioengineering alveolar socket preservation biogenic hydroxyapatite fluorine macrophage polarization bone healing |
| title | Fluorine-Incorporated Biogenic Hydroxyapatite Enhances Socket Bone Healing via Addressing Macrophage-Mediated Inflammatory Response |
| title_full | Fluorine-Incorporated Biogenic Hydroxyapatite Enhances Socket Bone Healing via Addressing Macrophage-Mediated Inflammatory Response |
| title_fullStr | Fluorine-Incorporated Biogenic Hydroxyapatite Enhances Socket Bone Healing via Addressing Macrophage-Mediated Inflammatory Response |
| title_full_unstemmed | Fluorine-Incorporated Biogenic Hydroxyapatite Enhances Socket Bone Healing via Addressing Macrophage-Mediated Inflammatory Response |
| title_short | Fluorine-Incorporated Biogenic Hydroxyapatite Enhances Socket Bone Healing via Addressing Macrophage-Mediated Inflammatory Response |
| title_sort | fluorine incorporated biogenic hydroxyapatite enhances socket bone healing via addressing macrophage mediated inflammatory response |
| topic | alveolar socket preservation biogenic hydroxyapatite fluorine macrophage polarization bone healing |
| url | https://www.mdpi.com/2306-5354/12/4/396 |
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