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Implantable electrical stimulation bioreactor with liquid crystal polymer-based electrodes for enhanced bone regeneration at mandibular large defects in rabbit

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Abstract

The osseous regeneration of large bone defects is still a major clinical challenge in maxillofacial and orthopedic surgery. Previous studies demonstrated that biphasic electrical stimulation (ES) stimulates bone formation; however, polyimide electrode should be removed after regeneration. This study presents an implantable electrical stimulation bioreactor with electrodes based on liquid crystal polymer (LCP), which can be permanently implanted due to excellent biocompatibility to bone tissue. The bioreactor was implanted into a critical-sized bone defect and subjected to ES for one week, where bone regeneration was evaluated four weeks after surgery using micro-CT. The effect of ES via the bioreactor was compared with a sham control group and a positive control group that received recombinant human bone morphogenetic protein (rhBMP)-2 (20 μg). New bone volume per tissue volume (BV/TV) in the ES and rhBMP-2 groups increased to 132% (p < 0.05) and 174% (p < 0.01), respectively, compared to that in the sham control group. In the histological evaluation, there was no inflammation within the bone defects and adjacent to LCP in all the groups. This study showed that the ES bioreactor with LCP electrodes could enhance bone regeneration at large bone defects, where LCP can act as a mechanically resistant outer box without inflammation.

To enhance bone regeneration, a bioreactor comprising collagen sponge and liquid crystal polymer-based electrode was implanted in the bone defect. Within the defect, electrical current pulses having biphasic waveform were applied from the implanted bioreactor.

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Glossary of terms

ESElectrical stimulation; LCPLiquid crystal polymer; rhBMPRecombinant human bone morphogenetic protein; ACSAbsorbable collagen sponge; CTComputed tomography; ROIRegion of interest; BV/TVBone volume per tissue volume; Tb.ThTrabecular thickness; Tb.SpTrabecular separation; Tb.NTrabecular number; BMDBone mineral density; CaHACalcium hydroxyapatite; WDWhole defect; SBSuperior-buccal; IBInferior-buccal; CCentral; SLSuperior-lingual; ILInferior-lingual; MTMasson’s trichrome; hMSCHuman mesenchymal stromal cell; VEGFVascular endothelial growth factor; ILInterleukin; CAMKCalcium/calmodulin-dependent protein kinase; CnCalcineurin; NOSNitric oxide synthase; cAMPCyclic adenosine monophosphate; CREBcAMP response element-binding protein; CDKCyclin-dependent kinase; NFATNuclear factor of activated T cells; IGFInsulin-like growth factor; MAPKMitogen-activated protein kinase.

Funding

This work was supported in part by the Dentistry–Engineering Interdisciplinary Research Grant jointly funded by the School of Dentistry and College of Engineering, Seoul National University, and in part by a grant to the CABMC project funded by the Defense Acquisition Program Administration (UD170030ID).

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  1. Chaebin Kim and Hoon Joo Yang contributed equally to this work.

Authors and Affiliations

  1. Department of Electrical and Computer Engineering, Seoul National University, Seoul, Republic of Korea

    Chaebin Kim, Tae Mok Gwon, Soowon Shin & Sung June Kim

  2. Inter-University Semiconductor Research Center, Seoul National University, Seoul, Republic of Korea

    Chaebin Kim, Tae Mok Gwon, Soowon Shin & Sung June Kim

  3. Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul, Republic of Korea

    Hoon Joo Yang & Soon Jung Hwang

  4. Orthognathic Surgery Center, Seoul National University Dental Hospital, Seoul, Republic of Korea

    Hoon Joo Yang & Soon Jung Hwang

  5. Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea

    Tae Hyung Cho, Beom Seok Lee, In Sook Kim & Soon Jung Hwang

  6. Institute on Aging, Seoul National University, Seoul, Republic of Korea

    Sung June Kim

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Kim, C., Yang, H.J., Cho, T.H. et al. Implantable electrical stimulation bioreactor with liquid crystal polymer-based electrodes for enhanced bone regeneration at mandibular large defects in rabbit. Med Biol Eng Comput 58, 383–399 (2020). https://doi.org/10.1007/s11517-019-02046-2

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