Electrical stimulation waveform-dependent osteogenesis on PVDF/BaTiO3 composite using a customized and programmable cell stimulator

Panda, AK and Sitaramgupta, V and Pandya, HJ and Basu, B (2022) Electrical stimulation waveform-dependent osteogenesis on PVDF/BaTiO3 composite using a customized and programmable cell stimulator. In: Biotechnology and Bioengineering .

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Abstract

Directing cellular functionalities using biomaterial-based bioelectronic stimulation remains a significant constraint in translating research outcomes to address specific clinical needs. Electrical stimulation is now being clinically used as a therapeutic treatment option to promote bone tissue regeneration and to improve neuromuscular functionalities. However, the nature of the electrical waveforms during the stimulation and underlying biophysical rationale are still not scientifically well explored. Furthermore, bone-mimicking implant-based bioelectrical regulation of osteoinductivity has not been translated to clinics. The present study demonstrates the role of the electrical stimulation waveform to direct differentiation of stem cells on an electroactive polymeric substrate, using monophasic direct current (DC), square waveform, and biphasic waveform. In this regard, an in-house electrical stimulation device has been fabricated for the uninterrupted delivery of programmed electrical signals to stem cells in culture. To provide a functional platform for stem cells to differentiate, barium titanate (BaTiO3, BT) reinforced poly(vinylidene difluoride) (PVDF) has been developed with mechanical properties similar to bone. The electrical stimulation of human mesenchymal stem cells (hMSCs) on PVDF/BT composite inhibited proliferation rate at day 7, indicating early commitment for differentiation. The phenotypical characteristics of DC stimulated hMSCs provided signatures of differentiation towards osteogenic lineage, which was subsequently confirmed using alkaline phosphatase assay, collagen deposition, matrix mineralization, and genetic expression. Our findings suggest that DC stimulation induced early osteogenesis in hMSCs with a higher level of intracellular reactive oxygen species (ROS), whereas the stimulation with square wave directed late osteogenesis with a lower ROS regeneration. In summary, the present study critically analyzes the role of electrical stimulation waveforms in regulating osteogenesis, without external biochemical differentiation inducers, on a bone-mimicking functional biomaterial substrate. Such a strategy can potentially be adopted to develop orthopedic implant-based bioelectronic medicine for bone regeneration. © 2022 Wiley Periodicals LLC.

Item Type:	Journal Article
Publication:	Biotechnology and Bioengineering
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to John Wiley and Sons Inc
Keywords:	Alkalinity; Barium titanate; Biomechanics; Bone; Cell culture; Clinical research; Phosphatases; Tissue regeneration, (BaTiO3, BT) reinforced poly(vinylidene difluoride)/BaTiO3 composite; BaTiO 3; Bioelectronic medicine; Direct-current; Electrical stimulations; Human mesenchymal stem cells; Osteogenesis; Polyvinylidene difluoride; Stem-cell; Stimulation waveforms, Stem cells
Department/Centre:	Division of Chemical Sciences > Materials Research Centre Division of Electrical Sciences > Electronic Systems Engineering (Formerly Centre for Electronic Design & Technology) Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Mechanical Sciences > Centre for Product Design & Manufacturing
Date Deposited:	18 May 2022 10:39
Last Modified:	18 May 2022 10:39
URI:	https://eprints.iisc.ac.in/id/eprint/71854

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