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The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events, including pathogen clearance, immunological modulation, and osteogenesis. In this study, we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PCL/PVDF with multiple antibacterial, immunomodulatory, and osteogenic effects using electrospinning technology. This scaffold’s piezoelectric signal output under ultrasound (US) control can be similar to the physiological electrical signals of healthy bone tissue, creating a truly biomimetic electrical microenvironment in the bone defect. In vitro studies have shown that ZnO@PCL/PVDF scaffold significantly enhances the proliferation, migration, and osteogenic differentiation of MC3T3-E1 cells under piezoelectric drive provided by ultrasound. Furthermore, the scaffold exhibits inhibitory effects on the growth of E. coli and S. aureus, as well as the ability to induce M2 macrophage polarization, indicating potent antibacterial and immunomodulatory properties. In vivo experiments demonstrated that the ZnO@PCL/PVDF scaffold can accelerate the repair of mandibular defects in rats, effectively inhibit bacterial colonization, and reduce inflammatory responses. Altogether, this study confirms that the newly developed ZnO@PCL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing, thus providing a simple and effective solution for bone defects.
Jian, G. Y.; Li, D. Z.; Ying, Q. W.; Chen, X.; Zhai, Q. M.; Wang, S.; Mei, L.; Cannon, R. D.; Ji, P.; Liu, W. Z. et al. Dual photo-enhanced interpenetrating network hydrogel with biophysical and biochemical signals for infected bone defect healing. Adv. Healthc. Mater. 2023, 12, 2300469.
Zhang, M.; Matinlinna, J. P.; Tsoi, J. K. H.; Liu, W. L.; Cui, X.; Lu, W. W.; Pan, H. B. Recent developments in biomaterials for long-bone segmental defect reconstruction: A narrative overview. J. Orthop. Translat. 2020, 22, 26–33.
Zhu, Y.; Goh, C.; Shrestha, A. Biomaterial properties modulating bone regeneration. Macromol. Biosci. 2021, 21, 2000365.
Sun, M. L.; Wang, J. M.; Huang, X. B.; Hang, R. Q.; Han, P. D.; Guo, J. Q.; Yao, X. H.; Chu, P. K.; Zhang, X. Y. Ultrasound-driven radical chain reaction and immunoregulation of piezoelectric-based hybrid coating for treating implant infection. Biomaterials 2024, 307, 122532.
Wu, H.; Dong, H.; Tang, Z.; Chen, Y.; Liu, Y. C.; Wang, M.; Wei, X. H.; Wang, N.; Bao, S. S.; Yu, D. M. et al. Electrical stimulation of piezoelectric BaTiO3 coated Ti6Al4V scaffolds promotes anti-inflammatory polarization of macrophages and bone repair via MAPK/JNK inhibition and OXPHOS activation. Biomaterials 2023, 293, 121990.
Wang, L. Y.; Pang, Y. Y.; Tang, Y. J.; Wang, X. Y.; Zhang, D. X.; Zhang, X.; Yu, Y. J.; Yang, X. P.; Cai, Q. A biomimetic piezoelectric scaffold with sustained Mg2+ release promotes neurogenic and angiogenic differentiation for enhanced bone regeneration. Bioact. Mater. 2023, 25, 399–414.
Liu, Z. R.; Wan, X. Y.; Wang, Z. L.; Li, L. L. Electroactive biomaterials and systems for cell fate determination and tissue regeneration: Design and applications. Adv. Mater. 2021, 33, 2007429.
Rajabi, A. H.; Jaffe, M.; Arinzeh, T. L. Piezoelectric materials for tissue regeneration: A review. Acta Biomater. 2015, 24, 12–23.
Zhang, Y.; An, Q.; Zhang, S. T.; Ma, Z. Q.; Hu, X. T.; Feng, M. C.; Zhang, Y. H.; Zhao, Y. T. A healing promoting wound dressing with tailor-made antibacterial potency employing piezocatalytic processes in multi-functional nanocomposites. Nanoscale 2022, 14, 2649–2659.
Liu, X.; Wan, X. Y.; Sui, B. Y.; Hu, Q. H.; Liu, Z. R.; Ding, T. T.; Zhao, J.; Chen, Y. X.; Wang, Z. L.; Li, L. L. Piezoelectric hydrogel for treatment of periodontitis through bioenergetic activation. Bioact. Mater. 2024, 35, 346–361.
Robinson, A. J.; Pérez-Nava, A.; Ali, S. C.; González-Campos, J. B.; Holloway, J. L.; Cosgriff-Hernandez, E. M. Comparative analysis of fiber alignment methods in electrospinning. Matter 2021, 4, 821–844.
Li, T.; Qu, M. H.; Carlos, C.; Gu, L.; Jin, F.; Yuan, T.; Wu, X. W.; Xiao, J. J.; Wang, T.; Dong, W. et al. High-performance poly(vinylidene difluoride)/dopamine core/shell piezoelectric nanofiber and its application for biomedical sensors. Adv. Mater. 2021, 33, 2006093.
Azimi, B.; Milazzo, M.; Lazzeri, A.; Berrettini, S.; Uddin, M. J.; Qin, Z.; Buehler, M. J.; Danti, S. Electrospinning piezoelectric fibers for biocompatible devices. Adv. Healthc. Mater. 2020, 9, 1901287.
Hoop, M.; Chen, X. Z.; Ferrari, A.; Mushtaq, F.; Ghazaryan, G.; Tervoort, T.; Poulikakos, D.; Nelson, B.; Pané, S. Ultrasound-mediated piezoelectric differentiation of neuron-like PC12 cells on PVDF membranes. Sci. Rep. 2017, 7, 4028.
Zhao, F. J.; Zhang, C. G.; Liu, J.; Liu, L.; Cao, X. D.; Chen, X. F.; Lei, B.; Shao, L. Q. Periosteum structure/function-mimicking bioactive scaffolds with piezoelectric/chem/nano signals for critical-sized bone regeneration. Chem. Eng. J. 2020, 402, 126203.
Felice, B.; Sánchez, M. A.; Socci, M. C.; Sappia, L. D.; Gómez, M. I.; Cruz, M. K.; Felice, C. J.; Martí, M.; Pividori, M. I.; Simonelli, G. et al. Controlled degradability of PCL-ZnO nanofibrous scaffolds for bone tissue engineering and their antibacterial activity. Mater. Sci. Eng. C Mater. Biol. Appl. 2018, 93, 724–738.
Sarkar, L.; Sushma, M. V.; Yalagala, B. P.; Rengan, A. K.; Singh, S. G.; Vanjari, S. R. K. ZnO nanoparticles embedded silk fibroin-a piezoelectric composite for nanogenerator applications. Nanotechnology 2022, 33, 265403.
Hossain, S. I.; Kukushkina, E. A.; Izzi, M.; Sportelli, M. C.; Picca, R. A.; Ditaranto, N.; Cioffi, N. A review on montmorillonite-based nanoantimicrobials: State of the art. Nanomaterials 2023, 13, 848.
Xia, Y.; Fan, X.; Yang, H.; Li, L.; He, C.; Cheng, C.; Haag, R. ZnO/nanocarbons-modified fibrous scaffolds for stem cell-based osteogenic differentiation. Small 2020, 16, 2003010.
Wen, Z.; Shi, X. Y.; Li, X. J.; Liu, W. C.; Liu, Y. K.; Zhang, R. Y.; Yu, Y. Q.; Su, J. S. Mesoporous TiO2 coatings regulate ZnO nanoparticle loading and Zn2+ release on titanium dental implants for sustained osteogenic and antibacterial activity. ACS Appl. Mater. Interfaces 2023, 15, 15235–15249.
Fan, W.; Zhang, C.; Liu, Y.; Wang, S. J.; Dong, K.; Li, Y.; Wu, F.; Liang, J. H.; Wang, C. L.; Zhang, Y. Y. An ultra-thin piezoelectric nanogenerator with breathable, superhydrophobic, and antibacterial properties for human motion monitoring. Nano Res. 2023, 16, 11612–11620.
Sun, H. S.; Zheng, K.; Zhou, T.; Boccaccini, A. R. Incorporation of zinc into binary SiO2-CaO mesoporous bioactive glass nanoparticles enhances anti-inflammatory and osteogenic activities. Pharmaceutics 2021, 13, 2124.
Szewczyk, P. K.; Gradys, A.; Kim, S. K.; Persano, L.; Marzec, M.; Kryshtal, A.; Busolo, T.; Toncelli, A.; Pisignano, D.; Bernasik, A., et al. Enhanced piezoelectricity of electrospun polyvinylidene fluoride fibers for energy harvesting. ACS Appl. Mater. Interfaces. 2020, 12, 13575–13583.
Zhang, W. T.; Sun, T. Z.; Zhang, J.; Hu, X. T.; Yang, M.; Han, L. W.; Xu, G.; Zhao, Y. T.; Li, Z. H. Construction of artificial periosteum with methacrylamide gelatin hydrogel-wharton's jelly based on stem cell recruitment and its application in bone tissue engineering. Mater. Today Bio. 2023, 18, 100528.
Cai, K. Z.; Jiao, Y. L.; Quan, Q.; Hao, Y. L.; Liu, J.; Wu, L. Improved activity of MC3T3-E1 cells by the exciting piezoelectric BaTiO3/TC4 using low-intensity pulsed ultrasound. Bioact. Mater. 2021, 6, 4073–4082.
Alahzm, A. M.; Alejli, M. O.; Ponnamma, D.; Elgawady, Y.; Al-Maadeed, M. A. A. Piezoelectric properties of zinc oxide/iron oxide filled polyvinylidene fluoride nanocomposite fibers. J. Mater. Sci. Mater. Electron. 2021, 32, 14610–14622.
Kim, M.; Wu, Y. S.; Kan, E. C.; Fan, J. T. Breathable and flexible piezoelectric ZnO@PVDF fibrous nanogenerator for wearable applications. Polymers 2018, 10, 745.
Singh, B. K.; Tripathi, S. p-n homojunction based on Bi doped p-type ZnO and undoped n-type ZnO for optoelectronic application in yellow-red region of visible spectrum. J. Lumin. 2018, 198, 427–432.
Liang, D.; Yang, M. W.; Guo, B. L.; Cao, J. J.; Yang, L.; Guo, X. D. Zinc upregulates the expression of osteoprotegerin in mouse osteoblasts MC3T3-E1 through PKC/MAPK pathways. Biol. Trace Elem. Res. 2012, 146, 340–348.
Li, C. X.; Sun, F. B.; Tian, J. J.; Li, J. H.; Sun, H. D.; Zhang, Y.; Guo, S. G.; Lin, Y. H.; Sun, X. D.; Zhao, Y. Continuously released Zn2+ in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties. Bioact. Mater. 2023, 24, 361–375.
Zhao, Y. T.; Li, J. T.; Liu, L. L.; Wang, Y.; Ju, Y.; Zeng, C.; Lu, Z. H.; Xie, D. H.; Guo, J. S. Zinc-based tannin-modified composite microparticulate scaffolds with balanced antimicrobial activity and osteogenesis for Infected bone defect repair. Adv. Healthc. Mater. 2023, 12, e2300303.
Zheng, T. Y.; Huang, Y. Q.; Zhang, X. H.; Cai, Q.; Deng, X. L.; Yang, X. P. Mimicking the electrophysiological microenvironment of bone tissue using electroactive materials to promote its regeneration. J. Mater. Chem. B 2020, 8, 10221–10256.
Aydemir Sezer, U.; Ozturk, K.; Aru, B.; Yanıkkaya Demirel, G.; Sezer, S.; Bozkurt, M. R. Zero valent zinc nanoparticles promote neuroglial cell proliferation: A biodegradable and conductive filler candidate for nerve regeneration. J. Mater. Sci. Mater. Med. 2017, 28, 19.
Sun, T. W.; Yu, W. L.; Zhu, Y. J.; Chen, F.; Zhang, Y. G.; Jiang, Y. Y.; He, Y. H. Porous nanocomposite comprising ultralong hydroxyapatite nanowires decorated with zinc-containing nanoparticles and chitosan: Synthesis and application in bone defect repair. Chem. -Eur. J. 2018, 24, 8809–8821.
Miri, A.; Mahdinejad, N.; Ebrahimy, O.; Khatami, M.; Sarani, M. Zinc oxide nanoparticles: Biosynthesis, characterization, antifungal and cytotoxic activity. Mater. Sci. Eng. C Mater. Biol. Appl. 2019, 104, 109981.
Fotouhiardakani, F.; Mohammadi, M.; Mashayekhan, S. ZnO-incorporated polyvinylidene fluoride/poly (ε-caprolactone) nanocomposite scaffold with controlled release of dexamethasone for bone tissue engineering. Appl. Phys. A 2022, 128, 654.
Ribeiro, C.; Moreira, S.; Correia, V.; Sencadas, V.; Rocha, J. G.; Gama, F. M.; Ribelles, J. G.; Lanceros-Méndez, S. Enhanced proliferation of pre-osteoblastic cells by dynamic piezoelectric stimulation. RSC Adv. 2012, 2, 11504–11509.
Bhang, S. H.; Jang, W. S.; Han, J.; Yoon, J. K.; La, W. G.; Lee, E.; Kim, Y. S.; Shin, J. Y.; Lee, T. J.; Baik, H. K. et al. Zinc oxide nanorod-based piezoelectric dermal patch for wound healing. Adv. Funct. Mater. 2017, 27, 1603497.
Parangusan, H.; Ponnamma, D.; Al-Maadeed, M. A. A. Stretchable electrospun PVDF-HFP/Co-ZnO nanofibers as piezoelectric nanogenerators. Sci. Rep. 2018, 8, 754.
Khare, D.; Basu, B.; Dubey, A. K. Electrical stimulation and piezoelectric biomaterials for bone tissue engineering applications. Biomaterials 2020, 258, 120280.
Huang, X. B.; Das, R.; Patel, A.; Duc Nguyen, T. Physical stimulations for bone and cartilage regeneration. Regen. Eng. Transl. Med. 2018, 4, 216–237.
Fan, B.; Guo, Z.; Li, X. K.; Li, S. K.; Gao, P.; Xiao, X.; Wu, J.; Shen, C.; Jiao, Y. L.; Hou, W. T. Electroactive barium titanate coated titanium scaffold improves osteogenesis and osseointegration with low-intensity pulsed ultrasound for large segmental bone defects. Bioact. Mater. 2020, 5, 1087–1101.
Chen, J.; Li, S. J.; Jiao, Y. L.; Li, J. D.; Li, Y. B.; Hao, Y. L.; Zuo, Y. In vitro study on the piezodynamic therapy with a BaTiO3-coating titanium scaffold under low-intensity pulsed ultrasound stimulation. ACS Appl. Mater. Interfaces 2021, 13, 49542–49555.
Liu, Y.; Dzidotor, G.; Le, T. T.; Vinikoor, T.; Morgan, K.; Curry, E. J.; Das, R.; Mcclinton, A.; Eisenberg, E.; Apuzzo, L. N. et al. Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits. Sci. Transl. Med. 2022, 14, eabi7282.
Rath, G.; Hussain, T.; Chauhan, G.; Garg, T.; Goyal, A. K. Development and characterization of cefazolin loaded zinc oxide nanoparticles composite gelatin nanofiber mats for postoperative surgical wounds. Mater. Sci. Eng. C Mater. Biol. Appl. 2016, 58, 242–253.
Münchow, E. A.; Albuquerque, M. T. P.; Zero, B.; Kamocki, K.; Piva, E.; Gregory, R. L.; Bottino, M. C. Development and characterization of novel ZnO-loaded electrospun membranes for periodontal regeneration. Dent. Mater. 2015, 31, 1038–1051.
Ye, J.; Li, B.; Li, M.; Zheng, Y. F.; Wu, S. L.; Han, Y. Formation of a ZnO nanorods-patterned coating with strong bactericidal capability and quantitative evaluation of the contribution of nanorods-derived puncture and ROS-derived killing. Bioact. Mater. 2022, 11, 181–191.
Stefanowski, J.; Lang, A.; Rauch, A.; Aulich, L.; Köhler, M.; Fiedler, A. F.; Buttgereit, F.; Schmidt-Bleek, K.; Duda, G. N.; Gaber, T. et al. Spatial distribution of macrophages during callus formation and maturation reveals close crosstalk between macrophages and newly forming Vessels. Front. Immunol. 2019, 10, 2588.
Leppik, L.; Oliveira, K. M. C.; Bhavsar, M. B.; Barker, J. H. Electrical stimulation in bone tissue engineering treatments. Eur. J. Trauma. Emerg. Surg. 2020, 46, 231–244.
Chen, Y. N.; Hu, M. R.; Wang, L.; Chen, W. D. Macrophage M1/M2 polarization. Eur. J. Pharmacol. 2020, 877, 173090.
Wu, P.; Shen, L.; Liu, H. F.; Zou, X. H.; Zhao, J.; Huang, Y.; Zhu, Y. F.; Li, Z. Y.; Xu, C.; Luo, L. H. et al. The marriage of immunomodulatory, angiogenic, and osteogenic capabilities in a piezoelectric hydrogel tissue engineering scaffold for military medicine. Mil. Med. Res. 2023, 10, 35.