Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits

Yang Liu¹, Godwin Dzidotor^{2

3}, Thinh T Le¹, Tra Vinikoor⁴, Kristin Morgan⁴, Eli J Curry⁵, Ritopa Das⁴, Aneesah McClinton², Ellen Eisenberg^{6

7}, Lorraine N Apuzzo⁸, Khanh T M Tran⁴, Pooja Prasad⁸, Tyler J Flanagan^{9

10}, Seok-Woo Lee^{9

10}, Ho-Man Kan², Meysam T Chorsi¹, Kevin W H Lo^{2

11}, Cato T Laurencin^{2

3

4

9

10

12}, Thanh D Nguyen^{1

4

10}

Affiliations

¹ Department of Mechanical Engineering, University of Connecticut, Storrs, CT 06269, USA.
² Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
³ Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁴ Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁵ Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁶ Division of Oral and Maxillofacial Diagnostic Sciences, School of Dental Medicine, University of Connecticut, Farmington, CT 06030, USA.
⁷ Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, School of Medicine, University of Connecticut, Farmington, CT 06030, USA.
⁸ Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
⁹ Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.
¹⁰ Institute of Materials Science, University of Connecticut, Storrs, CT 06269, USA.
¹¹ Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
¹² Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.

PMID: 35020409
DOI: 10.1126/scitranslmed.abi7282

Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits

Yang Liu et al. Sci Transl Med. 2022.

. 2022 Jan 12;14(627):eabi7282.

doi: 10.1126/scitranslmed.abi7282. Epub 2022 Jan 12.

Authors

Affiliations

¹ Department of Mechanical Engineering, University of Connecticut, Storrs, CT 06269, USA.
² Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA.
³ Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁴ Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.
⁵ Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁶ Division of Oral and Maxillofacial Diagnostic Sciences, School of Dental Medicine, University of Connecticut, Farmington, CT 06030, USA.
⁷ Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, School of Medicine, University of Connecticut, Farmington, CT 06030, USA.
⁸ Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
⁹ Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.
¹⁰ Institute of Materials Science, University of Connecticut, Storrs, CT 06269, USA.
¹¹ Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
¹² Department of Orthopedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.

PMID: 35020409
DOI: 10.1126/scitranslmed.abi7282

Abstract

More than 32.5 million American adults suffer from osteoarthritis, and current treatments including pain medicines and anti-inflammatory drugs only alleviate symptoms but do not cure the disease. Here, we have demonstrated that a biodegradable piezoelectric poly(L-lactic acid) (PLLA) nanofiber scaffold under applied force or joint load could act as a battery-less electrical stimulator to promote chondrogenesis and cartilage regeneration. The PLLA scaffold under applied force or joint load generated a controllable piezoelectric charge, which promoted extracellular protein adsorption, facilitated cell migration or recruitment, induced endogenous TGF-β via calcium signaling pathway, and improved chondrogenesis and cartilage regeneration both in vitro and in vivo. Rabbits with critical-sized osteochondral defects receiving the piezoelectric scaffold and exercise treatment experienced hyaline-cartilage regeneration and completely healed cartilage with abundant chondrocytes and type II collagen after 1 to 2 months of exercise (2 to 3 months after surgery including 1 month of recovery before exercise), whereas rabbits treated with nonpiezoelectric scaffold and exercise treatment had unfilled defect and limited healing. The approach of combining biodegradable piezoelectric tissue scaffolds with controlled mechanical activation (via physical exercise) may therefore be useful for the treatment of osteoarthritis and is potentially applicable to regenerating other injured tissues.

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Comment in

Electric scaffolds charge cartilage repair.
Onuora S. Onuora S. Nat Rev Rheumatol. 2022 Mar;18(3):127. doi: 10.1038/s41584-022-00752-0. Nat Rev Rheumatol. 2022. PMID: 35091703 No abstract available.

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Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits

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Exercise-induced piezoelectric stimulation for cartilage regeneration in rabbits

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