創傷性腦損傷（Traumatic Brain Injury，TBI）是受外部大力撞擊形成，發生當下會引起大量細胞死亡，並使患者在生理以及心理上產生改變，並造成生活上的困難。導致受傷部位惡化通常是繼發性損傷引起的，其中包括星形膠質細胞的積累，導致形成嚴重的疤痕，阻礙細胞浸潤並阻礙組織修復；以及引發的免疫反應和產生的活性氧(Reactive Oxygen Species，ROS)使傷口癒合不易，並影響損傷部位腦神經的信號傳輸。
本實驗利用明膠、有機金屬框架(Metal-Organic Framework, MOF,本篇為MoCx-Cu)，以及過氧化氫酶(CAT)三種材料，並結合微流道系統製作微球(MP)，開發出封裝CAT並包覆MoCx-Cu的可注射微球水凝膠系統(命名為MoCx-Cu@CAT-GelMA MPs)，用於治療TBI。
在組織工程中，水凝膠通常用於填充大腦受損區域，模仿細胞外基質以促進組織修復。然而傳統的水凝膠缺乏必要的孔隙率來促進細胞滲透到受損區域，導致組織修復的效果有限。在這項研究中，明膠先利用甲基丙烯酸酐(Methacrylic anhydride, MA)改質獲得光交聯的特性，使其在紫外光照射下立即交聯，產生具有優異熱穩定性的GelMA水凝膠。在利用微流道製作直徑約為150 μm微球的過程中，將CAT封裝在MPs內，CAT有助於抑制創傷處的ROS，並降低免疫反應的發生。CAT-GelMA MPs可用來填補腦損傷產生的空洞並促進組織修復，高生物相容性的GelMA不會對腦部造成傷害，並且可降解性能夠緩慢釋放封裝的CAT。當此水凝膠系統在高頻磁場(High Frequency Magnetic Field)環境下，MP外面包覆的MoCx-Cu因其導電特性，可以產生渦電流，電場改變可促進神經突向外生長，導致腦神經的生長和修復。
細胞實驗中,本研究證明了MoCx-Cu 對於 NIH-3T3 細胞在適當濃度下具有低毒性,也藉由胚胎神經幹細胞(Neural Stem Cells. NSCs) 來展示此材料對於神經的刺激以及影響。在動物實驗當中,治療後14天的組織切片結果來看，阻擋新生細胞進入的星狀膠質细胞的量和未治療的組別相比降低了約2%的表現量,免疫反應亦減少了2%的表現量,而受傷區的神經細胞也比未治療組多了約5%的表現量,血管細胞則是多了約4%的表現量,證明除了能減少創傷處免疫反應的發生，還能促進神經細胞細胞的分化和血管的再生。動物行為實驗也展現治療組老鼠四肢的運用能力及靈活度都比未治療組的高。由此可知,本文所製作的可注射微球水凝膠系統,因為微流道的可調整性,可製造不同大小微球,且能包覆及釋放不同的藥物,另外在藉由外部磁場能使结合的 MoCx-Cu造成電場改變以及CAT的輔助,進而促進神經細胞的分化及生長,提供了腦創傷一種非常有效的治療方式。

Traumatic brain injury (TBI) can cause physical and psychological changes in patients, leading to difficulties in daily life. Wound deterioration is often caused by secondary injury, including the accumulation of astrocytes, which form severe scarring and impede cellular infiltration and tissue repair. In addition, it triggers an immune response and generates reactive oxygen species (ROS), making it harder for wounds to heal and affecting signaling to neurons in damaged areas of the brain.
In this experiment, three materials, gelatin, metal-organic frameworks (MOFs) (specifically MoCx-Cu), and catalase (CAT) were combined with a microfluidic system to create microspheres (MPs). An injectable hydrogel system encapsulating CAT and coated with MoCx-Cu, termed MoCx-Cu@CAT-GelMA MP, was developed for TBI treatment. In tissue engineering, hydrogels are often used to fill in damaged areas of the brain, mimicking the extracellular matrix to facilitate tissue repair. However, conventional hydrogels lack the necessary porosity to facilitate cell penetration into injured areas, leading to limited effectiveness in tissue repair. In this study, gelatin was modified with methacrylic anhydride (MA) to achieve photocrosslinking properties, allowing immediate crosslinking under UV irradiation and yielding GelMA hydrogels with excellent thermal stability. During the fabrication of microspheres with a diameter of ~150 μm using microfluidics, CAT was encapsulated within MPs. CAT helps inhibit ROS at the site of injury and reduces the occurrence of immune responses. CAT-GelMA MP can be used to fill cavities created by brain injury and promote tissue repair. GelMA is highly biocompatible, does not harm the brain, and its biodegradability allows slow release of encapsulated CAT. When this hydrogel system was exposed to a high-frequency magnetic field, the MoCx-Cu coated on the outside of the MP generated eddy currents due to its electrical conductivity. Changes in the electric field can promote the outgrowth of neuronal protrusions, leading to neuronal growth and repair.
In cell experiments, this study demonstrates that MoCx-Cu has low toxicity to NIH-3T3 cells at an appropriate concentration and shows its stimulation and effects on neural stem cells (NSCs). In animal experiments, tissue sections taken 14 days after treatment showed about 2 percent less accumulation of astrocytes, which block the entry of new cells, compared with untreated groups. The immune response also fell by about 2%. Neuronal cell expression increased by about 5% and blood vessel cell expression increased by about 4% in the injured area compared to the untreated group. This suggests that this system can promote neuronal cell differentiation and angiogenesis in addition to reducing the occurrence of immune responses at the site of injury. Animal behavior experiments also showed that the treated mice showed higher limb use and agility compared to the untreated mice. Therefore, the injectable microsphere hydrogel system developed in this study, combined with the electric field change induced by the presence of MoCx-Cu and the assistance of CAT, provides a highly effective treatment for traumatic brain injury.

中文摘要 I
Abstract III
致謝 VI
Table of Contents VII
List of Figure X
Chapter 1 Introduction 1
Chapter 2 Literature review and theory 4
2.1 Traumatic brain injury (TBI) 4
2.1.1 Cerebral ischemia after TBI 6
2.1.2 Astrocytes in TBI 8
2.1.3 Microglia in TBI 10
2.1.4 ROS release after TBI 12
2.2 Gas therapy for tissue 15
2.2.1 Application of oxygen (O2) in biomedicine 17
2.2.2 The role of oxygen (O2) in angiogenesis 19
2.3 Catalase (CAT) 21
2.3 Hydrogel for tissue engineering 23
2.3.1 Application of injectable hydrogel in TBI 25
2.3.2 Injectable microsphere hydrogel 27
2.4 Metal-organic frameworks (MOF) 29
2.4.1 MOFs for biomedical engineering 31
2.4.2 Electrical stimulation and neuron modulation 33
Chapter 3 Experimental section 36
3.1 Materials 36
3.2 Apparatus 38
3.3 Methods 40
3.3.1 Fabrication of microfluidic chip 40
3.3.2 Synthesis of GelMA 40
3.3.3 Fabrication of GelMA microspheres 41
3.3.4 Synthesis of metal-organic frameworks 42
3.3.5 Coating metal-organic frameworks on MPs 43
3.3.6 Degradation of microspheres 44
3.3.7 In vitro cell culture 45
3.3.7.1 Cell viability assay 45
3.3.7.2 Co-culture of cells with MPs 48
3.3.7.3 Inhibition of ROS level 48
3.3.7.4 Embryonic NSCs extraction experiment 49
3.3.7.5 Differentiation of NSCs experiment 49
3.3.8 In vivo experiment 51
3.3.8.1 Brain collection and immunofluorescence staining 52
3.3.8.2 Animal behavior experiment 53
Chapter 4 Results and discussions 55
4.1 Characterization of material 55
4.1.1 Characterization of microspheres 55
4.1.2 Characterization of MOF 59
4.1.3 MOF coating on MPs 67
4.2 In vitro experiment 68
4.2.1 Cytotoxicity of materials 68
4.2.2 Co-culture of materials and cells 70
4.2.3 Stimulate neuron differentiation 72
4.3 In vivo experiment 74
4.3.1 Animal behavior 74
4.3.2 In vivo degradation of microspheres 77
4.3.3 Immunofluorescence staining and analysis 79
4.3.4 H&E stain 92
Chapter 5 Conclusion 93
Reference 95

1. Werner, C. &Engelhard, K. Pathophysiology of traumatic brain injury. BJA Br. J. Anaesth. 99, 4–9 (2007).
2. Doğanyiğit, Z. et al. The Role of Neuroinflammatory Mediators in the Pathogenesis of Traumatic Brain Injury: A Narrative Review. ACS Chem. Neurosci. 13, 1835–1848 (2022).
3. Jarrahi, A. et al. Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions. Biomedicines vol. 8 (2020).
4. Maas, A. I. R. et al. Traumatic brain injury: progress and challenges in prevention, clinical care, and research. Lancet Neurol. 21, 1004–1060 (2022).
5. Cornelius, C. et al. Traumatic brain injury: oxidative stress and neuroprotection. Antioxid. Redox Signal. 19, 836–853 (2013).
6. Lutton, E. M. et al. Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury. Sci. Rep. 7, 1–15 (2017).
7. Sweeney, M. D., Kisler, K., Montagne, A., Toga, A. W. &Zlokovic, B.V. The role of brain vasculature in neurodegenerative disorders. Nat. Neurosci. 21, 1318–1331 (2018).
8. Shlosberg, D., Benifla, M., Kaufer, D. &Friedman, A. Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat. Rev. Neurol. 6, 393–403 (2010).
9. Hay, J. R., Johnson, V. E., Young, A. M. H., Smith, D. H. &Stewart, W. Blood-brain barrier disruption is an early event that may persist for many years after traumatic brain injury in humans. J. Neuropathol. Exp. Neurol. 74, 1147–1157 (2015).
10. Sweeney, M. D. et al. Vascular dysfunction—the disregarded partner of Alzheimer’s disease. Alzheimer’s Dement. 15, 158–167 (2019).
11. Sandsmark, D. K., Bashir, A., Wellington, C. L. &Diaz-Arrastia, R. Cerebral Microvascular Injury: A Potentially Treatable Endophenotype of Traumatic Brain Injury-Induced Neurodegeneration. Neuron 103, 367–379 (2019).
12. Cheng, X. et al. Morphological and functional alterations of astrocytes responding to traumatic brain injury. JIN 18, 203–215 (2019).
13. Li, B., Zhang, D. &Verkhratsky, A. Astrocytes in Post-traumatic Stress Disorder. Neurosci. Bull. 38, 953–965 (2022).
14. Frik, J. et al. Cross-talk between monocyte invasion and astrocyte proliferation regulates scarring in brain injury. EMBO Rep. 19, e45294 (2018).
15. Verkhratsky, A., Illes, P., Tang, Y. &Semyanov, A. The anti-inflammatory astrocyte revealed: the role of the microbiome in shaping brain defences. Signal Transduct. Target. Ther. 6, 150 (2021).
16. Zhou, Y. et al. Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury. Cell Commun. Signal. 18, 62 (2020).
17. Sofroniew, M.V. Astrocyte Reactivity: Subtypes, States, and Functions in CNS Innate Immunity. Trends Immunol. 41, 758–770 (2020).
18. Shao, F., Wang, X., Wu, H., Wu, Q. &Zhang, J. Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration. Front. Aging Neurosci. 14, 1–16 (2022).
19. Salter, M. W. &Stevens, B. Microglia emerge as central players in brain disease. Nat. Med. 23, 1018–1027 (2017).
20. Grovola, M. R. et al. Diverse changes in microglia morphology and axonal pathology during the course of 1 year after mild traumatic brain injury in pigs. Brain Pathol. 31, e12953 (2021).
21. Stratoulias, V., Venero, J. L., Tremblay, M.-È. &Joseph, B. Microglial subtypes: diversity within the microglial community. EMBO J. 38, e101997 (2019).
22. Kumar, A., Alvarez-Croda, D. M., Stoica, B. A., Faden, A. I. &Loane, D. J. Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury. J. Neurotrauma 33, 1732–1750 (2016).
23. Long, X. et al. Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury. J. Neuroinflammation 17, 89 (2020).
24. Yao, X. et al. TLR4 signal ablation attenuated neurological deficits by regulating microglial M1/M2 phenotype after traumatic brain injury in mice. J. Neuroimmunol. 310, 38–45 (2017).
25. Debels, H. et al. Macrophages Play a Key Role in Angiogenesis and Adipogenesis in a Mouse Tissue Engineering Model. Tissue Eng. Part A 19, 2615–2625 (2013).
26. Angeloni, C., Prata, C., Vieceli Dalla Sega, F., Piperno, R. &Hrelia, S. Traumatic Brain Injury and NADPH Oxidase: A Deep Relationship. Oxid. Med. Cell. Longev. 2015, 370312 (2015).
27. Russo, M.V &McGavern, D. B. Inflammatory neuroprotection following traumatic brain injury. Science (80-. ). 353, 783–785 (2016).
28. Han, Z. et al. A Novel Targeted Nanoparticle for Traumatic Brain Injury Treatment: Combined Effect of ROS Depletion and Calcium Overload Inhibition. Adv. Healthc. Mater. 11, 1–15 (2022).
29. Eastman, C. L., D’Ambrosio, R. &Ganesh, T. Modulating neuroinflammation and oxidative stress to prevent epilepsy and improve outcomes after traumatic brain injury. Neuropharmacology 172, 107907 (2020).
30. Ismail, H. et al. Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone. Antioxidants vol. 9 (2020).
31. Ganguly, U. et al. Oxidative Stress, Neuroinflammation, and NADPH Oxidase: Implications in the Pathogenesis and Treatment of Alzheimer’s Disease. Oxid. Med. Cell. Longev. 2021, 7086512 (2021).
32. Shin, M. H. et al. Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, and mitochondrial electron transport system mediate heat shock-induced MMP-1 and MMP-9 expression. Free Radic. Biol. Med. 44, 635–645 (2008).
33. Dohi, K. et al. Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury. J. Neuroinflammation 7, 41 (2010).
34. Cooney, S. J., Bermudez-Sabogal, S. L. &Byrnes, K. R. Cellular and temporal expression of NADPH oxidase (NOX) isotypes after brain injury. J. Neuroinflammation 10, 917 (2013).
35. Schröder, K. et al. Nox4 Is a Protective Reactive Oxygen Species Generating Vascular NADPH Oxidase. Circ. Res. 110, 1217–1225 (2012).
36. Brouwer, R. J., Lalieu, R. C., Hoencamp, R., vanHulst, R. A. &Ubbink, D. T. A systematic review and meta-analysis of hyperbaric oxygen therapy for diabetic foot ulcers with arterial insufficiency. J. Vasc. Surg. 71, 682-692.e1 (2020).
37. Huang, X. et al. Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. Life Sci. 259, 118246 (2020).
38. Guan, Y. et al. Sustained oxygenation accelerates diabetic wound healing by promoting epithelialization and angiogenesis and decreasing inflammation. Sci. Adv. 7, eabj0153 (2023).
39. Wang, S.-B. et al. A Versatile Carbon Monoxide Nanogenerator for Enhanced Tumor Therapy and Anti-Inflammation. ACS Nano 13, 5523–5532 (2019).
40. Romão, C. C., Blättler, W. A., Seixas, J. D. &Bernardes, G. J. L. Developing drug molecules for therapy with carbon monoxide. Chem. Soc. Rev. 41, 3571–3583 (2012).
41. Liu, C. et al. Carbon Monoxide Controllable Targeted Gas Therapy for Synergistic Anti-inflammation. iScience 23, 101483 (2020).
42. Malone-Povolny, M. J., Maloney, S. E. &Schoenfisch, M. H. Nitric Oxide Therapy for Diabetic Wound Healing. Adv. Healthc. Mater. 8, 1801210 (2019).
43. Shekhter, A. B., Serezhenkov, V. A., Rudenko, T. G., Pekshev, A.V &Vanin, A. F. Beneficial effect of gaseous nitric oxide on the healing of skin wounds. Nitric Oxide 12, 210–219 (2005).
44. Wu, Y., Yuan, M., Song, J., Chen, X. &Yang, H. Hydrogen Gas from Inflammation Treatment to Cancer Therapy. ACS Nano 13, 8505–8511 (2019).
45. Yu, S. et al. NIR-Laser-Controlled Hydrogen-Releasing PdH Nanohydride for Synergistic Hydrogen-Photothermal Antibacterial and Wound-Healing Therapies. Adv. Funct. Mater. 29, 1905697 (2019).
46. Jin, Q., Deng, Y., Jia, F., Tang, Z. &Ji, J. Gas Therapy: An Emerging “Green” Strategy for Anticancer Therapeutics. Adv. Ther. 1, 1800084 (2018).
47. Skylar-Scott, M. A. et al. Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels. Sci. Adv. 5, eaaw2459 (2023).
48. Ashammakhi, N. et al. Advances in Controlled Oxygen Generating Biomaterials for Tissue Engineering and Regenerative Therapy. Biomacromolecules 21, 56–72 (2020).
49. Suvarnapathaki, S., Wu, X., Lantigua, D., Nguyen, M. A. &Camci-Unal, G. Breathing life into engineered tissues using oxygen-releasing biomaterials. NPG Asia Mater. 11, 65 (2019).
50. Agarwal, T. et al. Oxygen releasing materials: Towards addressing the hypoxia-related issues in tissue engineering. Mater. Sci. Eng. C 122, 111896 (2021).
51. Augustine, R., Gezek, M., Bostanci, N. S., Nguyen, A. &Camci-Unal, G. Oxygen-generating scaffolds: One step closer to the clinical translation of tissue engineered products. Chem. Eng. J. 455, 140783 (2023).
52. Veith, A. P., Henderson, K., Spencer, A., Sligar, A. D. &Baker, A. B. Therapeutic strategies for enhancing angiogenesis in wound healing. Adv. Drug Deliv. Rev. 146, 97–125 (2019).
53. Nandi, A., Yan, L.-J., Jana, C. K. &Das, N. Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases. Oxid. Med. Cell. Longev. 2019, 9613090 (2019).
54. Willemen, N. G. A. et al. Enzyme-Mediated Alleviation of Peroxide Toxicity in Self-Oxygenating Biomaterials. Adv. Healthc. Mater. 11, 2102697 (2022).
55. Li, Y. et al. A Microneedle Patch with Self-Oxygenation and Glutathione Depletion for Repeatable Photodynamic Therapy. ACS Nano 16, 17298–17312 (2022).
56. Galasso, M., Gambino, S., Romanelli, M. G., Donadelli, M. &Scupoli, M. T. Browsing the oldest antioxidant enzyme: catalase and its multiple regulation in cancer. Free Radic. Biol. Med. 172, 264–272 (2021).
57. Lutton, E. M. et al. Acute administration of catalase targeted to ICAM-1 attenuates neuropathology in experimental traumatic brain injury. Sci. Rep. 7, 3846 (2017).
58. Zhao, Y. et al. Supramolecular Adhesive Hydrogels for Tissue Engineering Applications. Chem. Rev. 122, 5604–5640 (2022).
59. Khuu, N., Kheiri, S. &Kumacheva, E. Structurally anisotropic hydrogels for tissue engineering. Trends Chem. 3, 1002–1026 (2021).
60. Serafin, A., Culebras, M. &Collins, M. N. Synthesis and evaluation of alginate, gelatin, and hyaluronic acid hybrid hydrogels for tissue engineering applications. Int. J. Biol. Macromol. 233, 123438 (2023).
61. Sakr, M. A. et al. Recent trends in gelatin methacryloyl nanocomposite hydrogels for tissue engineering. J. Biomed. Mater. Res. Part A 110, 708–724 (2022).
62. Cao, H., Duan, L., Zhang, Y., Cao, J. &Zhang, K. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal Transduct. Target. Ther. 6, 426 (2021).
63. Li, Y., Yang, H. Y. &Lee, D. S. Advances in biodegradable and injectable hydrogels for biomedical applications. J. Control. Release 330, 151–160 (2021).
64. Kornev, V. A., Grebenik, E. A., Solovieva, A. B., Dmitriev, R. I. &Timashev, P. S. Hydrogel-assisted neuroregeneration approaches towards brain injury therapy: A state-of-the-art review. Comput. Struct. Biotechnol. J. 16, 488–502 (2018).
65. Wang, L. et al. Injectable hyaluronic acid hydrogel loaded with BMSC and NGF for traumatic brain injury treatment. Mater. Today Bio 13, 100201 (2022).
66. Li, Q. et al. Recent trends in the development of hydrogel therapeutics for the treatment of central nervous system disorders. NPG Asia Mater. 14, 14 (2022).
67. Huang, X. et al. Reactive Oxygen Species Scavenging Functional Hydrogel Delivers Procyanidins for the Treatment of Traumatic Brain Injury in Mice. ACS Appl. Mater. Interfaces (2022) doi:10.1021/acsami.2c04930.
68. Li, J. et al. Dual-enzymatically cross-linked gelatin hydrogel promotes neural differentiation and neurotrophin secretion of bone marrow-derived mesenchymal stem cells for treatment of moderate traumatic brain injury. Int. J. Biol. Macromol. 187, 200–213 (2021).
69. Zhao, Z. et al. Injectable Microfluidic Hydrogel Microspheres for Cell and Drug Delivery. Adv. Funct. Mater. 31, 2103339 (2021).
70. Zhao, Z. et al. Capturing Magnesium Ions via Microfluidic Hydrogel Microspheres for Promoting Cancellous Bone Regeneration. ACS Nano 15, 13041–13054 (2021).
71. Koh, C. S. L. et al. Plasmonic Nanoparticle-Metal–Organic Framework (NP–MOF) Nanohybrid Platforms for Emerging Plasmonic Applications. ACS Mater. Lett. 3, 557–573 (2021).
72. Zong, Z. et al. Recent Advances in Metal–Organic-Framework-Based Nanocarriers for Controllable Drug Delivery and Release. Pharmaceutics vol. 14 (2022).
73. Cedrún-Morales, M., Ceballos, M., Polo, E., delPino, P. &Pelaz, B. Nanosized metal–organic frameworks as unique platforms for bioapplications. Chem. Commun. 59, 2869–2887 (2023).
74. Tian, H., Zhang, M., Jin, G., Jiang, Y. &Luan, Y. Cu-MOF chemodynamic nanoplatform via modulating glutathione and H2O2 in tumor microenvironment for amplified cancer therapy. J. Colloid Interface Sci. 587, 358–366 (2021).
75. Xu, X.-Y. et al. Light-responsive UiO-66-NH2/Ag3PO4 MOF-nanoparticle composites for the capture and release of sulfamethoxazole. Chem. Eng. J. 350, 436–444 (2018).
76. Wang, C., Tian, G., Yu, X. &Zhang, X. Recent Advances in Functional Nanomaterials for Catalytic Generation of Nitric Oxide: A Mini Review. Small 19, 2207261 (2023).
77. Zhou, Y., Yang, T., Liang, K. &Chandrawati, R. Metal-organic frameworks for therapeutic gas delivery. Adv. Drug Deliv. Rev. 171, 199–214 (2021).
78. Bazi Alahri, M. et al. Theranostic applications of metal–organic frameworks (MOFs)-based materials in brain disorders: Recent advances and challenges. Inorg. Chem. Commun. 134, 108997 (2021).
79. Niu, H., Bu, H., Zhao, J. &Zhu, Y. Metal–Organic Frameworks-Based Nanoplatforms for the Theranostic Applications of Neurological Diseases. Small n/a, 2206575 (2023).
80. Shyngys, M. et al. Metal-Organic Framework (MOF)-Based Biomaterials for Tissue Engineering and Regenerative Medicine . Frontiers in Bioengineering and Biotechnology vol. 9 (2021).
81. Kopyl, S., Surmenev, R., Surmeneva, M., Fetisov, Y. &Kholkin, A. Magnetoelectric effect: principles and applications in biology and medicine– a review. Mater. Today Bio 12, 100149 (2021).
82. Zheng, B. &Tuszynski, M. H. Regulation of axonal regeneration after mammalian spinal cord injury. Nat. Rev. Mol. Cell Biol. 24, 396–413 (2023).
83. Jara, J. S., Agger, S. &Hollis, E. R. Functional Electrical Stimulation and the Modulation of the Axon Regeneration Program . Frontiers in Cell and Developmental Biology vol. 8 (2020).
84. Hogan, M. K., Hamilton, G. F. &Horner, P. J. Neural Stimulation and Molecular Mechanisms of Plasticity and Regeneration: A Review . Frontiers in Cellular Neuroscience vol. 14 (2020).
85. Juckett, L., Saffari, T. M., Ormseth, B., Senger, J.-L. &Moore, A. M. The Effect of Electrical Stimulation on Nerve Regeneration Following Peripheral Nerve Injury. Biomolecules vol. 12 (2022).
86. Wu, H.Bin, Xia, B. Y., Yu, L., Yu, X.-Y. &Lou, X. W. (David). Porous molybdenum carbide nano-octahedrons synthesized via confined carburization in metal-organic frameworks for efficient hydrogen production. Nat. Commun. 6, 6512 (2015).
87. Shen, H. et al. MoC@Cu@C composites with structural advantages exhibit excellent electrochemical performance and stability in LIBs. J. Energy Storage 64, 107207 (2023).