Research progress of electroactivity graphene-based materials in bone repair_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

KANG Ruohan ,  YUAN Wei ,  ZHU Yue

Department of Orthopedics, the First Hospital of China Medical University, Shenyang Liaoning, 110001, P. R. China;

Corresponding?author：

YUAN Wei, Email: wyuan@cmu.edu.cn; ZHU Yue, Email: zhuyuedr@163.com

Keywords：

Graphene; electroactivity; bone repair; conductive scaffold

DOI：

10.7507/1002-1892.202512052

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the application and research progress of the electroactivity graphene-based materials (GBMs) in the field of bone defect repair. Methods The recent domestic and international literature was extensively reviewed to systematically summarize the electroactive performance of GBMs in bone repair composite materials. The unique advantages of GBMs in material preparation, multi-functionalization, and application were discussed, along with their contributions and clinical translation challenges in bone tissue engineering. Results Bone defect repair remains a major global clinical challenge. Utilizing electroactive biomaterials to mimic the endogenous bioelectric microenvironment is a frontier strategy to accelerate bone regeneration. With outstanding electrical conductivity and physicochemical properties, GBMs exhibit great potential in constructing electroactive bone repair materials. The introduction of GBMs into conductive scaffolds or self-powered piezoelectric systems not only builds a continuous conductive network to promote electrical signal transduction and osteogenic differentiation, but also exerts broad-spectrum antibacterial effects via physical cutting and induced oxidative stress. Furthermore, GBMs promote the M2 polarization of macrophages, achieving a multi-effect synergy of antimicrobial and immunomodulatory functions within a single material system. Extensive animal experiments have verified that GBMs can significantly accelerate new bone formation and interfacial integration in complex or even infected microenvironments. Moreover, the biocompatibility and degradation performance of GBMs are highly dependent on their concentration, size, and oxidation degree. The cytotoxicity induced by high concentrations, the batch-to-batch heterogeneity of materials, and the long-term retention of large-sized residues in vivo remain the primary challenges at present. Conclusion Electroactivity GBMs materials provide an innovative, efficient, and multifunctional synergistic solution for bone repair. Future research should focus on the standardization of electrical stimulation parameters, overcoming the physicochemical heterogeneity of the materials, and systematically evaluating their long-term in vivo biosafety and degradation kinetics to accelerate their clinical translation.

Citation： KANG Ruohan, YUAN Wei, ZHU Yue. Research progress of electroactivity graphene-based materials in bone repair. Chinese Journal of Reparative and Reconstructive Surgery, 2026, 40(6): 1001-1012. doi: 10.7507/1002-1892.202512052 Copy

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1. Findeisen S, Gr?fe N, Schwilk M, et al. Use of autologous bone graft with bioactive glass as a bone substitute in the treatment of large-sized bone defects of the femur and tibia. J Pers Med, 2023, 13(12): 1644. doi: 10.3390/jpm13121644.
2. Martonosi AN. Animal electricity, Ca²⁺ and muscle contraction. A brief history of muscle research. Acta Biochim Pol, 2000, 47(3): 493-516.
3. Chen Y, Zheng Z, Zhou R, et al. Developing a strontium-releasing graphene oxide-/collagen-based organic-inorganic nanobiocomposite for large bone defect regeneration via MAPK signaling pathway. ACS Appl Mater Interfaces, 2019, 11(17): 15986-15997.
4. He Y, Li Y, Chen G, et al. Concentration-dependent cellular behavior and osteogenic differentiation effect induced in bone marrow mesenchymal stem cells treated with magnetic graphene oxide. J Biomed Mater Res, 2020, 108A: 50-60.
5. Bordoni V, Reina G, Orecchioni M, et al. Stimulation of bone formation by monocyte-activator functionalized graphene oxide in vivo. Nanoscale, 2019, 11(41): 19408-19421.
6. Heng BC, Bai Y, Li X, et al. Electroactive biomaterials for facilitating bone defect repair under pathological conditions. Adv Sci (Weinh), 2023, 10(2): 2204502. doi: 10.1002/advs.202204502.
7. Li J, Wang G, Geng H, et al. CVD growth of graphene on NiTi alloy for enhanced biological activity. ACS Appl Mater Interfaces, 2015, 7(36): 19876-19881.
8. Cheng J, Liu J, Wu B, et al. Graphene and its derivatives for bone tissue engineering: in vitro and in vivo evaluation of graphene-based scaffolds, membranes and coatings. Front Bioeng Biotechnol, 2021, 9: 734688. doi: 10.3389/fbioe.2021.734688.
9. Sarker B, Hum J, Nazhat SN, et al. Combining collagen and bioactive glasses for bone tissue engineering: a review. Adv Healthcare Mater, 2015, 4(2): 176-194.
10. Ribeiro C, Correia DM, Rodrigues I, et al. In vivo demonstration of the suitability of piezoelectric stimuli for bone reparation. Materials Letters, 2017, 209: 118-121.
11. Xue W, Du J, Li Q, et al. Preparation, properties, and application of graphene-based materials in tissue engineering scaffolds. Tissue Eng Part B Rev, 2022, 28(5): 1121-1136.
12. Geim AK. Graphene: status and prospects. Science, 2009, 324(5934): 1530-1534.
13. Li J, Liu X, Crook JM, et al. A 3D printed graphene electrode device for enhanced and scalable stem cell culture, osteoinduction and tissue building. Materials & Design, 2021, 201: 109473. doi: 10.1016/j.matdes.2021.109473.
14. Huang Y, Zhang L, Ji Y, et al. A non-invasive smart scaffold for bone repair and monitoring. Bioactive Materials, 2023, 19: 499-510.
15. Shuai C, Zeng Z, Yang Y, et al. Graphene oxide assists polyvinylidene fluoride scaffold to reconstruct electrical microenvironment of bone tissue. Materials & Design, 2020, 190: 108564. doi: 10.1016/j.matdes.2020.108564.
16. Lee C, Wei X, Kysar JW, et al. Measurement of the elastic properties and intrinsic strength of monolayer graphene. Science, 2008, 321(5887): 385-388.
17. Lee WC, Lim CH, Shi H, et al. Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide. ACS Nano, 2011, 5(9): 7334-7341.
18. Sasidharan A, Swaroop S, Chandran P, et al. Cellular and molecular mechanistic insight into the DNA-damaging potential of few-layer graphene in human primary endothelial cells. Nanomedicine, 2016, 12(5): 1347-1355.
19. Xi M, Wan R, Luo W, et al. Graphene oxide-based biomaterials in sports medicine. BIO Integration, 2026, 7: 1-20.
20. Daneshmandi L, Barajaa M, Tahmasbi Rad A, et al. Graphene-based biomaterials for bone regenerative engineering: a comprehensive review of the field and considerations regarding biocompatibility and biodegradation. Adv Healthc Mater, 2021, 10(1): e2001414. doi: 10.1002/adhm.202001414.
21. Raslan A, Saenz Del Burgo L, Ciriza J, et al. Graphene oxide and reduced graphene oxide-based scaffolds in regenerative medicine. International Journal of Pharmaceutics, 2020, 580: 119226. doi: 10.1016/j.ijpharm.2020.119226.
22. Li X, Liu YM, Li WG, et al. Effects of graphene oxide agglomerates on workability, hydration, microstructure and compressive strength of cement paste. Construction and Building Materials, 2017, 145: 402-410.
23. Hosseini FS, Kan HM, Whitfield T, et al. Graphene oxide in bone regenerative engineering: current challenges and future perspectives. ACS Bio & Med Chem Au, 2025, 5(3): 350-364.
24. Yuan B, Chen H, Zhao R, et al. Construction of a magnesium hydroxide/graphene oxide/hydroxyapatite composite coating on Mg-Ca-Zn-Ag alloy to inhibit bacterial infection and promote bone regeneration. Bioactive Materials, 2022, 18: 354-367.
25. Mahanta AK, Patel DK, Maiti P. Nanohybrid scaffold of chitosan and functionalized graphene oxide for controlled drug delivery and bone regeneration. ACS Biomater Sci Eng, 2019, 5(10): 5139-5149.
26. Liao C, Li Y, Tjong SC. Graphene nanomaterials: synthesis, biocompatibility, and cytotoxicity. Int J Mol Sci, 2018, 19(11): 3564. doi: 10.3390/ijms19113564.
27. Tavakol M, Montazeri A, Aboutalebi SH, et al. Mechanical properties of graphene oxide: the impact of functional groups. Applied Surface Science, 2020, 525: 146554. doi: 10.1016/j.apsusc.2020.146554.
28. Chen D, Feng H, Li J. Graphene oxide: preparation, functionalization, and electrochemical applications. Chem Rev, 2012, 112(11): 6027-6053.
29. Bahrami S, Baheiraei N, Shahrezaee M. Biomimetic reduced graphene oxide coated collagen scaffold for in situ bone regeneration. Sci Rep, 2021, 11(1): 16783. doi: 10.1038/s41598-021-96271-1.
30. Seonwoo H, Choung HW, Park S, et al. Reduced graphene oxide-incorporated calcium phosphate cements with pulsed electromagnetic fields for bone regeneration. RSC Adv, 2022, 12(9): 5557-5570.
31. Shin YC, Bae JH, Lee JH, et al. Enhanced osseointegration of dental implants with reduced graphene oxide coating. Biomater Res, 2022, 26(1): 11. doi: 10.1186/s40824-022-00257-7.
32. ?wi?tek M, Bro? A, Tarasiuk J, et al. Carbon nanotube/iron oxide hybrid particles and their PCL-based 3D composites for potential bone regeneration. Materials Science and Engineering C, 2019, 104: 109913. doi: 10.1016/j.msec.2019.109913.
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