Amorphous calcium zinc phosphate promotes macrophage-driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasis
The repair of alveolar bone defects continues to pose a significant challenge within the field of stomatology. As the primary implant material utilized in clinical treatment, the mechanisms by which calcium phosphate-based materials promote bone formation necessitate further in-depth exploration. Si...
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KeAi Communications Co., Ltd.
2025-10-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25002890 |
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| author | Shuze Wang Lei Cao Caihao Huang Junyi Wang Jialin Liu Yeyuan Wang Qiang Wang Qing Zhou Xing Zhang Dan Zhang |
| author_facet | Shuze Wang Lei Cao Caihao Huang Junyi Wang Jialin Liu Yeyuan Wang Qiang Wang Qing Zhou Xing Zhang Dan Zhang |
| author_sort | Shuze Wang |
| collection | DOAJ |
| description | The repair of alveolar bone defects continues to pose a significant challenge within the field of stomatology. As the primary implant material utilized in clinical treatment, the mechanisms by which calcium phosphate-based materials promote bone formation necessitate further in-depth exploration. Single-cell RNA sequencing was employed to characterize the immune microenvironment surrounding hydroxyapatite (HA)-mediated alveolar bone regeneration, confirming the macrophage-dependent enhancement of regenerative outcomes. Based on this finding, amorphous calcium zinc phosphate (ACZP) nanoparticles were developed as immunomodulatory nanomaterials. ACZP can accelerate bone regeneration via anti-inflammatory phenotype polarization, specifically by inhibiting endoplasmic reticulum-mitochondria coupling, reducing pathological Ca2+ transfer, and shifting macrophage metabolism from glycolysis to oxidative phosphorylation (OXPHOS), thereby enhancing bioenergetics. Our results demonstrated that ACZP can inhibit the IP3R/MCU pathway in macrophages, restoring their anti-inflammatory capabilities and ultimately achieving significant effects in the alveolar bone defects of New Zealand white rabbits. Twelve weeks post-surgery, the defects in the ACZP group were filled with nearly 70 % newly formed bone tissue. This study elucidated the immunomodulatory role of ACZP materials in the dynamic process of alveolar bone healing, providing novel insights and methodologies for the design of materials in the fields of tissue engineering and regenerative medicine. |
| format | Article |
| id | doaj-art-8b5962b720004d8b83cbe76d4710aedd |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-10-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-8b5962b720004d8b83cbe76d4710aedd2025-08-24T05:13:50ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-10-015282984410.1016/j.bioactmat.2025.06.053Amorphous calcium zinc phosphate promotes macrophage-driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasisShuze Wang0Lei Cao1Caihao Huang2Junyi Wang3Jialin Liu4Yeyuan Wang5Qiang Wang6Qing Zhou7Xing Zhang8Dan Zhang9School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China; Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, 110001, ChinaInstitute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China; School of Materials Science and Engineering, University of Science and Technology of China, Shenyang, Liaoning, 110016, ChinaInstitute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China; School of Materials Science and Engineering, University of Science and Technology of China, Shenyang, Liaoning, 110016, ChinaSchool and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China; Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, 110001, ChinaSchool and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China; Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, 110001, ChinaSchool and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China; Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, 110001, ChinaSchool and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China; Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, 110001, China; Corresponding author. School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China.School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China; Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, 110001, ChinaInstitute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China; School of Materials Science and Engineering, University of Science and Technology of China, Shenyang, Liaoning, 110016, China; Corresponding author. Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning, 110016, China.School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China; Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, Liaoning, 110001, China; Corresponding author. School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, 110001, China.The repair of alveolar bone defects continues to pose a significant challenge within the field of stomatology. As the primary implant material utilized in clinical treatment, the mechanisms by which calcium phosphate-based materials promote bone formation necessitate further in-depth exploration. Single-cell RNA sequencing was employed to characterize the immune microenvironment surrounding hydroxyapatite (HA)-mediated alveolar bone regeneration, confirming the macrophage-dependent enhancement of regenerative outcomes. Based on this finding, amorphous calcium zinc phosphate (ACZP) nanoparticles were developed as immunomodulatory nanomaterials. ACZP can accelerate bone regeneration via anti-inflammatory phenotype polarization, specifically by inhibiting endoplasmic reticulum-mitochondria coupling, reducing pathological Ca2+ transfer, and shifting macrophage metabolism from glycolysis to oxidative phosphorylation (OXPHOS), thereby enhancing bioenergetics. Our results demonstrated that ACZP can inhibit the IP3R/MCU pathway in macrophages, restoring their anti-inflammatory capabilities and ultimately achieving significant effects in the alveolar bone defects of New Zealand white rabbits. Twelve weeks post-surgery, the defects in the ACZP group were filled with nearly 70 % newly formed bone tissue. This study elucidated the immunomodulatory role of ACZP materials in the dynamic process of alveolar bone healing, providing novel insights and methodologies for the design of materials in the fields of tissue engineering and regenerative medicine.http://www.sciencedirect.com/science/article/pii/S2452199X25002890Alveolar bone healingAmorphous calcium zinc phosphateSingle-cell RNA sequencingMacrophageMitochondria |
| spellingShingle | Shuze Wang Lei Cao Caihao Huang Junyi Wang Jialin Liu Yeyuan Wang Qiang Wang Qing Zhou Xing Zhang Dan Zhang Amorphous calcium zinc phosphate promotes macrophage-driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasis Bioactive Materials Alveolar bone healing Amorphous calcium zinc phosphate Single-cell RNA sequencing Macrophage Mitochondria |
| title | Amorphous calcium zinc phosphate promotes macrophage-driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasis |
| title_full | Amorphous calcium zinc phosphate promotes macrophage-driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasis |
| title_fullStr | Amorphous calcium zinc phosphate promotes macrophage-driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasis |
| title_full_unstemmed | Amorphous calcium zinc phosphate promotes macrophage-driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasis |
| title_short | Amorphous calcium zinc phosphate promotes macrophage-driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasis |
| title_sort | amorphous calcium zinc phosphate promotes macrophage driven alveolar bone regeneration via modulation of energy metabolism and mitochondrial homeostasis |
| topic | Alveolar bone healing Amorphous calcium zinc phosphate Single-cell RNA sequencing Macrophage Mitochondria |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25002890 |
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