Electrical stimulation of piezoelectric BaTiO3 coated Ti6Al4V scaffolds promotes anti-inflammatory polarization of macrophages and bone repair via MAPK/JNK inhibition and OXPHOS activation

Wu, Hao; Dong, Hongyan; Tang, Zhi; Chen, Yu; Liu, Yichao; Wang, Mo; Wei, Xiao-Gang; Wang, Ning; Bao, Shusen; Yu, Dongmei; Wu, Zhigang; Yang, Zeyu; Li, Xiaokang; Guo, Zheng; Shi, Lei

doi:10.1016/j.biomaterials.2022.121990

Cited by 97 publications

(49 citation statements)

References 45 publications

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“…Besides, the activation of MAPK signaling pathways was required for proinflammatory M1 macrophage polarization . Wu et al reported that piezoelectric BaTiO3/Ti6Al4V scaffolds inhibited the MAPK/JNK signaling pathway by bioelectrical stimulation and thus significantly promoted the M2 macrophage polarization . In line with that study, our present data showed that treating macrophages with magneto-mechanical stimulation obviously inhibited the phosphorylation of JNK, with no alteration in that of ERK1/2 and p38.…”

Section: Discussionmentioning

confidence: 99%

“…43 Wu et al reported that piezoelectric BaTiO3/ Ti6Al4V scaffolds inhibited the MAPK/JNK signaling pathway by bioelectrical stimulation and thus significantly promoted the M2 macrophage polarization. 44 In line with that study, our present data showed that treating macrophages with magneto- mechanical stimulation obviously inhibited the phosphorylation of JNK, with no alteration in that of ERK1/2 and p38. Thus, a possible explanation was that magneto-mechanical stimulation ameliorated inflammation by suppressing the phosphorylation of JNK and activated macrophage polarization toward M2.…”

Section: Discussionmentioning

confidence: 99%

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Remote Activation of M2 Macrophage Polarization via Magneto-Mechanical Stimulation To Promote Osteointegration

Shao

Weng

et al. 2023

ACS Biomater. Sci. Eng.

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Osteoimmunomodulation has been considered to play a key role in osteointegration of orthopedic biomaterials. However, regulation of the macrophage phenotype in vivo with a spatiotemporal controllable way still remains a challenge. In this study, we designed a novel magnetic-responsive mineralized collagen coating to exert remotely controlled magneto-mechanical stimulation on macrophages using an external magnetic field. The magneto-mechanical stimulation exhibited immunomodulatory capability to activate M2 macrophage polarization via triggering the integrin-related cascade pathway and suppressing the phosphorylation of JNK in the MAPK pathway. The optimized inflammatory microenvironment subsequently promoted the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and the osteointegration in vivo. This work, therefore, provides a remote spatiotemporal controllable strategy to promote the osteointegration of orthopedic biomaterials via regulation of the osteoimmune microenvironment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Remote Activation of M2 Macrophage Polarization via Magneto-Mechanical Stimulation To Promote Osteointegration

Shao

Weng

et al. 2023

ACS Biomater. Sci. Eng.

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“…[48] The results (Figure S20, Supporting Information) showed that the expression of iNOS was inhibited and that of Arg-1 enhanced in macrophages under the effect of ES, which confirmed that ES may be involved in immunomodulation by regulating the antiinflammatory polarization of macrophages. [49] To further explore the mechanism of ES in our system, we monitored the intracellular Ca 2+ dynamics in response to ES, as shown in Figure S21 (Supporting Information), the Ca 2+ fluorescence intensity increased rapidly during ES. According to our results, ES was able to activate significant calcium signal change (ΔF/F 0 > 60%) to regulate intracellular calcium signaling, which may play an important role in the induction of macrophage polarization.…”

Section: Cellular and Molecular Level Analysismentioning

confidence: 99%

Wearable, Self‐powered, Drug‐Loaded Electronic Microneedles for Accelerated Tissue Repair of Inflammatory Skin Disorders

Qian

Jin

Wei

et al. 2023

Adv Funct Materials

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Electrical stimulation (ES) is widely used in physiological and medical sciences, while its application to treat inflammatory skin diseases (ISDs) remains a challenge owing to their natural pathological cuticle barrier and lack of an effective combination with chemotherapy to achieve specific immunomodulation. Here, a wearable, battery-free, multi-component drugloaded electronic microneedle (mD-eMN) system is developed by integrating remodeled metal microneedles loaded with multi-component chemical drugs and flexible triboelectric nanogenerators (TENGs). The system can rapidly release drugs into the site of ISDs and then realize an efficient penetration into cell body and specific immunomodulation under the synergism of pulsed electrons originating from the TENG. Also, the pulsed electrons can promote skin tissue homeostasis reconstruction to alleviate the inflammatory process of ISDs. Sufficient evidence shows that a significant skin inflammation regression of psoriasis (a typical ISDs model) is achieved using the mD-eMN system compared to traditional ES or chemotherapy alone. This innovative wearable mD-eMN system provides an effective flexible electronic and chemical drug joint technological platform for the treatment of ISDs, which is not only suitable for the treatment of psoriasis in this study but also maybe for other ISDs such as diabetic ulcers and skin tumors.

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“…[157] Bone is a dynamic tissue and the electromechanical performance induced by the sonopiezoelectric effect has a profound impact on the feedback mechanism of constant adaptation and the bone remodeling. [158,159] In addition, it was found that the bone defect led to the electrical potential reduction relative to the normal bone, while the attenuated potential recovered to normal after bone repair. [160] Sonopiezoelectric biomaterials can form a built-in electric field with precise spatial control and durability under the US stimulation.…”

Section: Bone Regenerationmentioning

confidence: 99%

Sonopiezoelectric Nanomedicine and Materdicine

Wang

Dai

Chen

2023

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Endogenous electric field is ubiquitous in a multitude of important living activities such as bone repair, cell signal transduction, and nerve regeneration, signifying that regulating the electric field in organisms is highly beneficial to maintain organism health. As an emerging and promising research direction, piezoelectric nanomedicine and materdicine precisely activated by ultrasound with synergetic advantages of deep tissue penetration, remote spatiotemporal selectivity, and mechanical‐electrical energy interconversion, have been progressively utilized for disease treatment and tissue repair by participating in the modulation of endogenous electric field. This specific nanomedicine utilizing piezoelectric effect activated by ultrasound is typically regarded as “sonopiezoelectric nanomedicine”. This comprehensive review summarizes and discusses the substantially employed sonopiezoelectric nanomaterials and nanotherapies to provide an insight into the internal mechanism of the corresponding biological behavior/effect of sonopiezoelectric biomaterials in versatile disease treatments. This review primarily focuses on the sonopiezoelectric biomaterials for biosensing, drug delivery, tumor therapy, tissue regeneration, antimicrobia, and further illuminates the underlying sonopiezoelectric mechanism. In addition, the challenges and developments/prospects of sonopiezoelectric nanomedicine are analyzed for promoting the further clinical translation. It is earnestly expected that this kind of nanomedicine/biomaterials‐enabled sonopiezoelectric technology will provoke the comprehensive investigation and promote the clinical development of the next‐generation multifunctional materdicine.

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Electrical stimulation of piezoelectric BaTiO3 coated Ti6Al4V scaffolds promotes anti-inflammatory polarization of macrophages and bone repair via MAPK/JNK inhibition and OXPHOS activation

Cited by 97 publications

References 45 publications

Remote Activation of M2 Macrophage Polarization via Magneto-Mechanical Stimulation To Promote Osteointegration

Remote Activation of M2 Macrophage Polarization via Magneto-Mechanical Stimulation To Promote Osteointegration

Wearable, Self‐powered, Drug‐Loaded Electronic Microneedles for Accelerated Tissue Repair of Inflammatory Skin Disorders

Sonopiezoelectric Nanomedicine and Materdicine

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