Microenvironmental dysregulation and advances in functional biomaterial-based interventions for diabetic bone defect repair_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

YANG Kun ^1,2 , SUN Yuanlin ^1,3 , BAI Rui ⁴ ,  YANG Yunkang ¹

1. Department of Orthopedics and Joint Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P. R. China;
2. Department of Bone and Joint Surgery, Luzhou People’s Hospital, Luzhou Sichuan, 646000, P. R. China;
3. Department of Orthopedics, the First People’s Hospital of Yibin, Yibin Sichuan, 644000, P. R. China;
4. Department of Orthodontics, Hospital of Stomatology, Southwest Medical University, Luzhou Sichuan, 646000, P. R. China;

Corresponding?author：

YANG Yunkang, Email: Droyyk@126.com

Keywords：

Diabetes mellitus; bone defect; microenvironmental dysregulation; osteoimmunity; angiogenic-osteogenic coupling; functional biomaterials

DOI：

10.7507/1002-1892.202603109

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the research progress on the major microenvironmental abnormalities in diabetic bone defect repair and functional biomaterial-based intervention strategies. Methods Relevant literature on diabetic bone defect repair and functional biomaterial-based interventions was reviewed and synthesized, with emphasis on the core pathological features of the diabetic bone defect repair microenvironment, principal regulatory strategies, representative material platforms, and the current status of clinical translation. Results Persistent hyperglycemia promotes the accumulation of advanced glycation end products and excessive generation of reactive oxygen species (ROS), together with osteoimmune dysregulation, unresolved chronic inflammation, and microvascular dysfunction. These abnormalities collectively impair cell recruitment, vascular regeneration, and new bone formation. Functional biomaterials are designed to modulate macrophage polarization and inflammatory responses, restore angiogenic-osteogenic coupling, and enable on-demand therapeutic release in response to pathological cues such as glucose and ROS, thereby improving the local regenerative microenvironment. Hydrogels, bioactive inorganic or composite materials, and multifunctional delivery systems constitute the principal material platforms. However, their broader application remains limited by inadequate mechanical suitability, insufficient manufacturing reproducibility, and a lack of robust clinical evidence. Conclusion Sustained dysregulation of the local microenvironment is a central determinant of impaired diabetic bone defect repair. Future biomaterial design should prioritize the precise recognition and active remodeling of the diabetes-specific pathological microenvironment to enhance bone regeneration and osseointegration.

Citation： YANG Kun, SUN Yuanlin, BAI Rui, YANG Yunkang. Microenvironmental dysregulation and advances in functional biomaterial-based interventions for diabetic bone defect repair. Chinese Journal of Reparative and Reconstructive Surgery, 2026, 40(9): 1458-1465. doi: 10.7507/1002-1892.202603109 Copy

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2.	Deng J, Van Duyn C, Cohen DJ, et al. Strategies for improving impaired osseointegration in compromised animal models[J]. J Dent Res, 2024, 103(5): 467-476.
3.	Li Z, Yue M, Zhou Y. Advances in material-based strategies for diabetic bone regeneration[J]. Stem Cells Transl Med, 2024, 13(3): 243-254.
4.	Yang Y, He X, Zhao Z, et al. Macrophage-centric biomaterials for bone regeneration in diabetes mellitus: contemporary advancements, challenges, and future trajectories[J/OL]. Cureus, 2024, 16(8): e66621. doi: 10.7759/cureus.66621.
5.	Zhou X, Chen S, Pich A, et al. Advanced bioresponsive drug delivery systems for promoting diabetic vascularized bone regeneration[J]. ACS Biomater Sci Eng, 2025, 11(1): 182-207.
6.	Cavati G, Pirrotta F, Merlotti D, et al. Role of advanced glycation end-products and oxidative stress in type-2-diabetes-induced bone fragility and implications on fracture risk stratification[J/OL]. Antioxidants (Basel), 2023, 12(4): 928. doi: 10.3390/antiox12040928.
7.	Tian K, Xiong T, Zeng D, et al. Impact of reactive oxygen species on bone regeneration in diabetes: Mechanisms and therapeutic strategies[J/OL]. Redox Biol, 2025, 88: 103941. doi: 10.1016/j.redox.2025.103941.
8.	Sheng N, Xing F, Wang J, et al. Recent progress in bone-repair strategies in diabetic conditions[J/OL]. Mater Today Bio, 2023, 23: 100835. doi: 10.1016/j.mtbio.2023.100835.
9.	Luo M, Zhao Z, Yi J. Osteogenesis of bone marrow mesenchymal stem cell in hyperglycemia[J/OL]. Front Endocrinol (Lausanne), 2023, 14: 1150068. doi: 10.3389/fendo.2023.1150068.
10.	Shen Y, Zhang Y, Zhou Z, et al. Dysfunction of macrophages leads to diabetic bone regeneration deficiency[J/OL]. Front Immunol, 2022, 13: 990457. doi: 10.3389/fimmu.2022.990457.
11.	Zhang D, Dang Y, Deng R, et al. Research progress of macrophages in bone regeneration[J/OL]. J Tissue Eng Regen Med, 2023, 2023: 1512966. doi: 10.1155/2023/1512966.
12.	Cai F, Liu Y, Liu K, et al. Diabetes mellitus impairs bone regeneration and biomechanics[J/OL]. J Orthop Surg Res, 2023, 18(1): 169. doi: 10.1186/s13018-023-03644-5.
13.	Song S, Zhang G, Chen X, et al. HIF-1α increases the osteogenic capacity of ADSCs by coupling angiogenesis and osteogenesis via the HIF-1α/VEGF/AKT/mTOR signaling pathway[J/OL]. J Nanobiotechnology, 2023, 21(1): 257. doi: 10.1186/s12951-023-02020-z.
14.	Li P, Alenazi KKK, Dally J, et al. Role of oxidative stress in impaired type II diabetic bone repair: scope for antioxidant therapy intervention?[J/OL]. Front Dent Med, 2024, 5: 1464009. doi: 10.3389/fdmed.2024.1464009.
15.	Wang Y, Wang B, Liu D, et al. Osteoimmunology uncovered: How macrophages and biomaterials revolutionize bone healing [J/OL]. Mater Today Bio, 2026, 36: 102647. doi: 10.1016/j.mtbio.2025.102647.
16.	Bixel MG, Sivaraj KK, Timmen M, et al. Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration [J/OL]. Nat Commun, 2024, 15(1): 4575. doi: 10.1038/s41467-024-48579-5.
17.	Xu Z, Wang B, Huang R, et al. Efforts to promote osteogenesis-angiogenesis coupling for bone tissue engineering[J]. Biomater Sci, 2024, 12(11): 2801-2830.
18.	邢飛, 吳岐佑, 者漫, 等. 無機生物材料在骨修復中的骨免疫調節作用[J]. 中國修復重建外科雜志, 2022, 36(4): 517-522.
19.	Wang C, Li T, Zeng X, et al. Sustained delivery of IL-10 by self-assembling peptide hydrogel to reprogram macrophages and promote diabetic alveolar bone defect healing[J]. Dent Mater, 2023, 39(4): 418-429.
20.	Yang P, Chen X, Qin Y, et al. Regulation of osteoimmune microenvironment via functional dynamic hydrogel for diabetic bone regeneration[J/OL]. Biomaterials, 2025, 320: 123273. doi: 10.1016/j.biomaterials.2025.123273.
21.	Wang L, Wu Z, Chen X, et al. A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair[J/OL]. Mater Today Bio, 2025, 34: 102162. doi: 10.1016/j.mtbio.2025.102162.
22.	Zhuang Y, Wu D, Zhou L, et al. Electrospun biomimetic periosteum promotes diabetic bone defect regeneration through regulating macrophage polarization and sequential drug release[J]. ACS Biomater Sci Eng, 2025, 11(3): 1690-1704.
23.	Chen T, Wu Z, Hou Q, et al. The dual angiogenesis effects via Nrf2/HO-1 signaling pathway of melatonin nanocomposite scaffold on promoting diabetic bone defect repair[J]. Int J Nanomedicine, 2024, 19: 2709-2732.
24.	Xu Z, Qi X, Bao M, et al. Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu[J]. Bioact Mater, 2023, 25: 239-255.
25.	Wang L, Yang H, Zhang C, et al. A blood glucose fluctuation-responsive delivery system promotes bone regeneration and the repair function of Smpd3-reprogrammed BMSC-derived exosomes[J/OL]. Int J Oral Sci, 2024, 16(1): 65. doi: 10.1038/s41368-024-00328-6.
26.	Jiang Y, Li W, Bao C. A novel glucose-sensitive scaffold accelerates osteogenesis in diabetic conditions[J/OL]. Biomed Res Int, 2022, 2022: 4133562. doi: 10.1155/2022/4133562.
27.	Zhang Q, Chen W, Li G, et al. A factor-free hydrogel with ROS scavenging and responsive degradation for enhanced diabetic bone healing[J/OL]. Small, 2024, 20(24): e2306389. doi: 10.1002/smll.202306389.
28.	Li D, Chen K, Tang H, et al. A logic-based diagnostic and therapeutic hydrogel with multistimuli responsiveness to orchestrate diabetic bone regeneration[J/OL]. Adv Mater, 2022, 34(11): e2108430. doi: 10.1002/adma.202108430.
29.	Fu X, Luo Z, Guo Y, et al. Microenvironment-responsive multifunctional enzyme-linked hydrogel for diabetic bone defect regeneration[J/OL]. Nat Commun, 2025, 16(1): 10275. doi: 10.1038/s41467-025-65165-5.
30.	Liu S, Lu M, Zhang M, et al. Multifaceted catalytic glucose depletion and reactive oxygen species-scavenging nanoenzyme composite hydrogel for facilitating diabetic bone regeneration[J]. ACS Nano, 2025, 19(2): 2677-2694.
31.	Hui Y, Mao J, Rui M, et al. Hydrogel microsphere-encapsulated bimetallic nanozyme for promoting diabetic bone regeneration via glucose consumption and ROS scavenging[J/OL]. Adv Healthc Mater, 2024, 13(32): e2402596. doi: 10.1002/adhm.202402596.
32.	付正, 李潤澤, 羅皓天, 等. 自修復水凝膠在骨組織工程中的應用[J]. 中國組織工程研究, 2022, 26(16): 2590-2595.
33.	Li Z, Ren K, Chen J, et al. Bioactive hydrogel formulations for regeneration of pathological bone defects[J]. J Control Release, 2025, 380: 686-714.
34.	Peng G, Li W, Peng L, et al. Multifunctional DNA-based hydrogel promotes diabetic alveolar bone defect reconstruction [J/OL]. Small, 2024, 20(10): e2305594. doi: 10.1002/smll.202305594.
35.	Pei M, Li P, Guo X, et al. Sustained release of hydrogen and magnesium ions mediated by a foamed gelatin-methacryloyl hydrogel for the repair of bone defects in diabetes[J]. ACS Biomater Sci Eng, 2024, 10(7): 4411-4424.
36.	Chen Z, Yang D, Wang S, et al. The role of magnesium hydrogels in bone regeneration: a systematic review and meta-analysis[J/OL]. J Mater Sci Mater Med, 2025, 36(1): 66. doi: 10.1007/s10856-025-06881-8.
37.	Zhu Y, Su J, Qi T, et al. Research progress on the role and mechanism of magnesium-containing materials in bone repair[J]. Biomater Transl, 2025, 6(2): 114-126.
38.	黃勇華, 李理, 石展英, 等. 生物活性玻璃在骨修復中的應用和研究現狀[J]. 中國修復重建外科雜志, 2020, 34(5): 660-666.
39.	Zhu T, Ni Q, Wang W, et al. Cu-MOF-decorated 3D-printed scaffolds for infection control and bone regeneration[J/OL]. J Funct Biomater, 2025, 16(3): 83. doi: 10.3390/jfb16030083.
40.	Li D, Ai Z, Tian Y, et al. Bioactive prosthetic interface constructed with cascading multi-nanozyme hydrogel to induce M2 macrophage polarization and heal diabetic bone defects [J/OL]. Biomaterials, 2026, 325: 123624. doi: 10.1016/j.biomaterials.2025.123624.
41.	Zhang H, Wang Y, Qiao W, et al. An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages[J/OL]. J Nanobiotechnology, 2025, 23(1): 283. doi: 10.1186/s12951-025-03358-2.
42.	Song Q, Zhang Y, Hu H, et al. Multifunctional hydrogel with synergistic reactive oxygen species scavenging and macrophage polarization-induced osteo-immunomodulation for enhanced bone regeneration[J]. ACS Appl Mater Interfaces, 2025, 17(27): 38985-9001.
43.	Norazman SI, Zaffarin ASM, Shuid AN, et al. A review of animal models for studying bone health in type-2 diabetes mellitus (T2DM) and obesity[J/OL]. Int J Mol Sci, 2024, 25(17): 9399. doi: 10.3390/ijms25179399.
44.	Hoveidaei AH, Sadat-Shojai M, Nabavizadeh SS, et al. Clinical challenges in bone tissue engineering—A narrative review [J/OL]. Bone, 2025, 192: 117363. doi: 10.1016/j.bone.2024.117363.
45.	Jagadale S, Damle M, Joshi MG. Bone tissue engineering: from biomaterials to clinical trials[J]. Adv Exp Med Biol, 2025, 1479: 73-115.
46.	Sillmann YM, Eber P, Orbeta E, et al. Milestones in mandibular bone tissue engineering: a systematic review of large animal models and critical-sized defects[J]. J Clin Med, 2025, 14(8): 2717. doi: 10.3390/jcm14082717.
47.	Laubach M, Whyte S, Chan HF, et al. Lost in translation: the lack of agreement between surgeons and scientists regarding biomaterials research and innovation for treating bone defects [J/OL]. BMC Med, 2024, 22(1): 517. doi: 10.1186/s12916-024-03734-z.
48.	Zhao X, Li N, Zhang Z, et al. Beyond hype: unveiling the real challenges in clinical translation of 3D printed bone scaffolds and the fresh prospects of bioprinted organoids[J/OL]. J Nanobiotechnology, 2024, 22(1): 500. doi: 10.1186/s12951-024-02759-z.
49.	Oliveira LM, Zanatta FB, Antoniazzi RP, et al. Does diabetes mellitus affect guided bone regeneration outcomes in individuals undergoing dental implants? A systematic review and meta-analysis[J/OL]. Front Dent Med, 2024, 5: 1352763. doi: 10.3389/fdmed.2024.1352763.
50.	Lindfors SC, Arts JJC, Lindfors NC. Clinical use of S53P4 bioactive glass in the treatment of bone defects and infected bone: a systematic review of the quality of clinical outcomes and a grade assessment[J/OL]. Adv Healthc Mater, 2026, 15(5): e03013. doi: 10.1002/adhm.202503013.
51.	Cim?es R, Santiago LM, Caldas AD Jr, et al. Treatment of intrabony periodontal defects in controlled diabetic patients with an enamel matrix derivative: a split-mouth randomized clinical trial[J]. Clin Oral Investig, 2022, 26(3): 2479-2489.
52.	Song PR, Zhou DY, Wang FX, et al. Programmable biomaterials for bone regeneration[J/OL]. Mater Today Bio, 2024, 29: 101296. doi: 10.1016/j.mtbio.2024.101296.
53.	Yang K, Wu Z, Zhang K, et al. Unlocking the potential of stimuli-responsive biomaterials for bone regeneration[J/OL]. Front Pharmacol, 2024, 15: 1437457. doi: 10.3389/fphar.2024.1437457.

1. 趙鵬飛, 王琪. 伴糖尿病患者種植骨缺損的病因及治療的研究進展[J]. 國際口腔醫學雜志, 2019, 46(2): 244-248.
2. Deng J, Van Duyn C, Cohen DJ, et al. Strategies for improving impaired osseointegration in compromised animal models[J]. J Dent Res, 2024, 103(5): 467-476.
3. Li Z, Yue M, Zhou Y. Advances in material-based strategies for diabetic bone regeneration[J]. Stem Cells Transl Med, 2024, 13(3): 243-254.
4. Yang Y, He X, Zhao Z, et al. Macrophage-centric biomaterials for bone regeneration in diabetes mellitus: contemporary advancements, challenges, and future trajectories[J/OL]. Cureus, 2024, 16(8): e66621. doi: 10.7759/cureus.66621.
5. Zhou X, Chen S, Pich A, et al. Advanced bioresponsive drug delivery systems for promoting diabetic vascularized bone regeneration[J]. ACS Biomater Sci Eng, 2025, 11(1): 182-207.
6. Cavati G, Pirrotta F, Merlotti D, et al. Role of advanced glycation end-products and oxidative stress in type-2-diabetes-induced bone fragility and implications on fracture risk stratification[J/OL]. Antioxidants (Basel), 2023, 12(4): 928. doi: 10.3390/antiox12040928.
7. Tian K, Xiong T, Zeng D, et al. Impact of reactive oxygen species on bone regeneration in diabetes: Mechanisms and therapeutic strategies[J/OL]. Redox Biol, 2025, 88: 103941. doi: 10.1016/j.redox.2025.103941.
8. Sheng N, Xing F, Wang J, et al. Recent progress in bone-repair strategies in diabetic conditions[J/OL]. Mater Today Bio, 2023, 23: 100835. doi: 10.1016/j.mtbio.2023.100835.
9. Luo M, Zhao Z, Yi J. Osteogenesis of bone marrow mesenchymal stem cell in hyperglycemia[J/OL]. Front Endocrinol (Lausanne), 2023, 14: 1150068. doi: 10.3389/fendo.2023.1150068.
10. Shen Y, Zhang Y, Zhou Z, et al. Dysfunction of macrophages leads to diabetic bone regeneration deficiency[J/OL]. Front Immunol, 2022, 13: 990457. doi: 10.3389/fimmu.2022.990457.
11. Zhang D, Dang Y, Deng R, et al. Research progress of macrophages in bone regeneration[J/OL]. J Tissue Eng Regen Med, 2023, 2023: 1512966. doi: 10.1155/2023/1512966.
12. Cai F, Liu Y, Liu K, et al. Diabetes mellitus impairs bone regeneration and biomechanics[J/OL]. J Orthop Surg Res, 2023, 18(1): 169. doi: 10.1186/s13018-023-03644-5.
13. Song S, Zhang G, Chen X, et al. HIF-1α increases the osteogenic capacity of ADSCs by coupling angiogenesis and osteogenesis via the HIF-1α/VEGF/AKT/mTOR signaling pathway[J/OL]. J Nanobiotechnology, 2023, 21(1): 257. doi: 10.1186/s12951-023-02020-z.
14. Li P, Alenazi KKK, Dally J, et al. Role of oxidative stress in impaired type II diabetic bone repair: scope for antioxidant therapy intervention?[J/OL]. Front Dent Med, 2024, 5: 1464009. doi: 10.3389/fdmed.2024.1464009.
15. Wang Y, Wang B, Liu D, et al. Osteoimmunology uncovered: How macrophages and biomaterials revolutionize bone healing [J/OL]. Mater Today Bio, 2026, 36: 102647. doi: 10.1016/j.mtbio.2025.102647.
16. Bixel MG, Sivaraj KK, Timmen M, et al. Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration [J/OL]. Nat Commun, 2024, 15(1): 4575. doi: 10.1038/s41467-024-48579-5.
17. Xu Z, Wang B, Huang R, et al. Efforts to promote osteogenesis-angiogenesis coupling for bone tissue engineering[J]. Biomater Sci, 2024, 12(11): 2801-2830.
18. 邢飛, 吳岐佑, 者漫, 等. 無機生物材料在骨修復中的骨免疫調節作用[J]. 中國修復重建外科雜志, 2022, 36(4): 517-522.
19. Wang C, Li T, Zeng X, et al. Sustained delivery of IL-10 by self-assembling peptide hydrogel to reprogram macrophages and promote diabetic alveolar bone defect healing[J]. Dent Mater, 2023, 39(4): 418-429.
20. Yang P, Chen X, Qin Y, et al. Regulation of osteoimmune microenvironment via functional dynamic hydrogel for diabetic bone regeneration[J/OL]. Biomaterials, 2025, 320: 123273. doi: 10.1016/j.biomaterials.2025.123273.
21. Wang L, Wu Z, Chen X, et al. A multifunctional self-assembled hydrogel with bactericidal activity and macrophage metabolic reprogramming for diabetic bone defect repair[J/OL]. Mater Today Bio, 2025, 34: 102162. doi: 10.1016/j.mtbio.2025.102162.
22. Zhuang Y, Wu D, Zhou L, et al. Electrospun biomimetic periosteum promotes diabetic bone defect regeneration through regulating macrophage polarization and sequential drug release[J]. ACS Biomater Sci Eng, 2025, 11(3): 1690-1704.
23. Chen T, Wu Z, Hou Q, et al. The dual angiogenesis effects via Nrf2/HO-1 signaling pathway of melatonin nanocomposite scaffold on promoting diabetic bone defect repair[J]. Int J Nanomedicine, 2024, 19: 2709-2732.
24. Xu Z, Qi X, Bao M, et al. Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu[J]. Bioact Mater, 2023, 25: 239-255.
25. Wang L, Yang H, Zhang C, et al. A blood glucose fluctuation-responsive delivery system promotes bone regeneration and the repair function of Smpd3-reprogrammed BMSC-derived exosomes[J/OL]. Int J Oral Sci, 2024, 16(1): 65. doi: 10.1038/s41368-024-00328-6.
26. Jiang Y, Li W, Bao C. A novel glucose-sensitive scaffold accelerates osteogenesis in diabetic conditions[J/OL]. Biomed Res Int, 2022, 2022: 4133562. doi: 10.1155/2022/4133562.
27. Zhang Q, Chen W, Li G, et al. A factor-free hydrogel with ROS scavenging and responsive degradation for enhanced diabetic bone healing[J/OL]. Small, 2024, 20(24): e2306389. doi: 10.1002/smll.202306389.
28. Li D, Chen K, Tang H, et al. A logic-based diagnostic and therapeutic hydrogel with multistimuli responsiveness to orchestrate diabetic bone regeneration[J/OL]. Adv Mater, 2022, 34(11): e2108430. doi: 10.1002/adma.202108430.
29. Fu X, Luo Z, Guo Y, et al. Microenvironment-responsive multifunctional enzyme-linked hydrogel for diabetic bone defect regeneration[J/OL]. Nat Commun, 2025, 16(1): 10275. doi: 10.1038/s41467-025-65165-5.
30. Liu S, Lu M, Zhang M, et al. Multifaceted catalytic glucose depletion and reactive oxygen species-scavenging nanoenzyme composite hydrogel for facilitating diabetic bone regeneration[J]. ACS Nano, 2025, 19(2): 2677-2694.
31. Hui Y, Mao J, Rui M, et al. Hydrogel microsphere-encapsulated bimetallic nanozyme for promoting diabetic bone regeneration via glucose consumption and ROS scavenging[J/OL]. Adv Healthc Mater, 2024, 13(32): e2402596. doi: 10.1002/adhm.202402596.
32. 付正, 李潤澤, 羅皓天, 等. 自修復水凝膠在骨組織工程中的應用[J]. 中國組織工程研究, 2022, 26(16): 2590-2595.
33. Li Z, Ren K, Chen J, et al. Bioactive hydrogel formulations for regeneration of pathological bone defects[J]. J Control Release, 2025, 380: 686-714.
34. Peng G, Li W, Peng L, et al. Multifunctional DNA-based hydrogel promotes diabetic alveolar bone defect reconstruction [J/OL]. Small, 2024, 20(10): e2305594. doi: 10.1002/smll.202305594.
35. Pei M, Li P, Guo X, et al. Sustained release of hydrogen and magnesium ions mediated by a foamed gelatin-methacryloyl hydrogel for the repair of bone defects in diabetes[J]. ACS Biomater Sci Eng, 2024, 10(7): 4411-4424.
36. Chen Z, Yang D, Wang S, et al. The role of magnesium hydrogels in bone regeneration: a systematic review and meta-analysis[J/OL]. J Mater Sci Mater Med, 2025, 36(1): 66. doi: 10.1007/s10856-025-06881-8.
37. Zhu Y, Su J, Qi T, et al. Research progress on the role and mechanism of magnesium-containing materials in bone repair[J]. Biomater Transl, 2025, 6(2): 114-126.
38. 黃勇華, 李理, 石展英, 等. 生物活性玻璃在骨修復中的應用和研究現狀[J]. 中國修復重建外科雜志, 2020, 34(5): 660-666.
39. Zhu T, Ni Q, Wang W, et al. Cu-MOF-decorated 3D-printed scaffolds for infection control and bone regeneration[J/OL]. J Funct Biomater, 2025, 16(3): 83. doi: 10.3390/jfb16030083.
40. Li D, Ai Z, Tian Y, et al. Bioactive prosthetic interface constructed with cascading multi-nanozyme hydrogel to induce M2 macrophage polarization and heal diabetic bone defects [J/OL]. Biomaterials, 2026, 325: 123624. doi: 10.1016/j.biomaterials.2025.123624.
41. Zhang H, Wang Y, Qiao W, et al. An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages[J/OL]. J Nanobiotechnology, 2025, 23(1): 283. doi: 10.1186/s12951-025-03358-2.
42. Song Q, Zhang Y, Hu H, et al. Multifunctional hydrogel with synergistic reactive oxygen species scavenging and macrophage polarization-induced osteo-immunomodulation for enhanced bone regeneration[J]. ACS Appl Mater Interfaces, 2025, 17(27): 38985-9001.
43. Norazman SI, Zaffarin ASM, Shuid AN, et al. A review of animal models for studying bone health in type-2 diabetes mellitus (T2DM) and obesity[J/OL]. Int J Mol Sci, 2024, 25(17): 9399. doi: 10.3390/ijms25179399.
44. Hoveidaei AH, Sadat-Shojai M, Nabavizadeh SS, et al. Clinical challenges in bone tissue engineering—A narrative review [J/OL]. Bone, 2025, 192: 117363. doi: 10.1016/j.bone.2024.117363.
45. Jagadale S, Damle M, Joshi MG. Bone tissue engineering: from biomaterials to clinical trials[J]. Adv Exp Med Biol, 2025, 1479: 73-115.
46. Sillmann YM, Eber P, Orbeta E, et al. Milestones in mandibular bone tissue engineering: a systematic review of large animal models and critical-sized defects[J]. J Clin Med, 2025, 14(8): 2717. doi: 10.3390/jcm14082717.
47. Laubach M, Whyte S, Chan HF, et al. Lost in translation: the lack of agreement between surgeons and scientists regarding biomaterials research and innovation for treating bone defects [J/OL]. BMC Med, 2024, 22(1): 517. doi: 10.1186/s12916-024-03734-z.
48. Zhao X, Li N, Zhang Z, et al. Beyond hype: unveiling the real challenges in clinical translation of 3D printed bone scaffolds and the fresh prospects of bioprinted organoids[J/OL]. J Nanobiotechnology, 2024, 22(1): 500. doi: 10.1186/s12951-024-02759-z.
49. Oliveira LM, Zanatta FB, Antoniazzi RP, et al. Does diabetes mellitus affect guided bone regeneration outcomes in individuals undergoing dental implants? A systematic review and meta-analysis[J/OL]. Front Dent Med, 2024, 5: 1352763. doi: 10.3389/fdmed.2024.1352763.
50. Lindfors SC, Arts JJC, Lindfors NC. Clinical use of S53P4 bioactive glass in the treatment of bone defects and infected bone: a systematic review of the quality of clinical outcomes and a grade assessment[J/OL]. Adv Healthc Mater, 2026, 15(5): e03013. doi: 10.1002/adhm.202503013.
51. Cim?es R, Santiago LM, Caldas AD Jr, et al. Treatment of intrabony periodontal defects in controlled diabetic patients with an enamel matrix derivative: a split-mouth randomized clinical trial[J]. Clin Oral Investig, 2022, 26(3): 2479-2489.
52. Song PR, Zhou DY, Wang FX, et al. Programmable biomaterials for bone regeneration[J/OL]. Mater Today Bio, 2024, 29: 101296. doi: 10.1016/j.mtbio.2024.101296.
53. Yang K, Wu Z, Zhang K, et al. Unlocking the potential of stimuli-responsive biomaterials for bone regeneration[J/OL]. Front Pharmacol, 2024, 15: 1437457. doi: 10.3389/fphar.2024.1437457.

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