Electrical Stimulation-Mediated Tissue Healing in Porcine Intervertebral Disc Under Mechanically Dynamic Organ Culture Conditions

Kanan, Mohamad; Eby, Oliver; Kelkar, Amey; Serhan, Hassan; Zodak, Yehuda; Aldoohan, Sulaiman; Elsamaloty, Haitham; Goel, Vijay K.; Yildirim-Ayan, Eda

doi:10.1097/brs.0000000000004331

Cited by 7 publications

(5 citation statements)

References 52 publications

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“…As such, PPy-3% exhibited the best electrical conductivity of 23.60 × 10 –4 S/m, as demonstrated in Figure d. It has been reported that electrical stimulation can speed cartilage healing, , and the recreation of electro-osmotic gradients within the IVD can promote tissue regeneration and reduce the inflammatory response . Therefore, the incorporation of PPy would endow the NPR-structured PCL scaffold with more functionality, thus increasing its biomedical application effect.…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that electrical stimulation can speed cartilage healing, 34,35 and the recreation of electro-osmotic gradients within the IVD can promote tissue regeneration and reduce the inflammatory response. 36 Therefore, the incorporation of PPy would endow the NPR-structured PCL scaffold with more functionality, thus increasing its biomedical application effect. PPy preferentially deposited on the surface of the hydrophobic substrate, 24,25 and the prepared −vPCL scaffold was immersed in a pyrrole reaction mixture to obtain −vPCL-PPy.…”

Section: Resultsmentioning

confidence: 99%

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Bioinspired Construction of Annulus Fibrosus Implants with a Negative Poisson’s Ratio for Intervertebral Disc Repair and Restraining Disc Herniation

Jiang

Wang

et al. 2023

Bioconjugate Chem.

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Inspired by the negative Poisson’s ratio (NPR) effects of the annulus fibrosus (AF) in intervertebral discs (IVDs), we designed a re-entrant honeycomb model and then 3D printed it into a poly(ε-caprolactone) (PCL) scaffold with NPR effects, which was followed by in situ polymerization of polypyrrole (PPy), thus constructing a PPy-coated NPR-structured PCL scaffold (−vPCL-PPy) to be used as the AF implant for the treatment of lumbar herniated discs. Mechanical testing and finite element (FE) simulation indicated that the NPR composite implant could sustain axial spine loading and resist nucleus pulposus (NP) swelling while displaying uniform stress diffusion under NP swelling and contraction. More interestingly, the NPR-structured composite scaffold could also apply a reacting force to restrain NP herniation owing to the NPR effect. In addition, the in vitro biological assessment and in vivo implantation demonstrated that the NPR composite scaffold exhibited good biocompatibility and exerted the ability to restore the physiological function of the disc segments.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Bioinspired Construction of Annulus Fibrosus Implants with a Negative Poisson’s Ratio for Intervertebral Disc Repair and Restraining Disc Herniation

Jiang

Wang

et al. 2023

Bioconjugate Chem.

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“…Initial pre-clinical evidence using a porcine model demonstrated downregulation of pain markers and proinflammatory factors within damaged discs and exhibited distinct morphological changes histologically and on MRI of extensive annular and nucleus pulposus regeneration. 62…”

Section: Future Directionsmentioning

confidence: 99%

Perspective on Intradiscal Therapies for Lumbar Discogenic Pain: State of the Science, Knowledge Gaps, and Imperatives for Clinical Adoption

Lorio,

Tate,

Myers

et al. 2024

JPR

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Specific clinical diagnostic criteria have established a consensus for defining patients with lumbar discogenic pain. However, if conservative medical management fails, these patients have few treatment options short of surgery involving discectomy often coupled with fusion or arthroplasty. There is a rapidly-emerging research effort to fill this treatment gap with intradiscal therapies that can be delivered minimally-invasively via fluoroscopically guided injection without altering the normal anatomy of the affected vertebral motion segment. Viable candidate products to date have included mesenchymal stromal cells, platelet-rich plasma, nucleus pulposus structural allograft, and other cell-based compositions. The objective of these products is to repair, supplement, and restore the damaged intervertebral disc as well as retard further degeneration. In doing so, the intervention is meant to eliminate the source of discogenic pain and avoid surgery. Methodologically rigorous studies are rare, however, and based on the best clinical evidence, the safety as well as the magnitude and duration of clinical efficacy remain difficult to estimate. Further, we summarize the US Food and Drug Administration's (FDA) guidance regarding the interpretation of the minimal manipulation and homologous use criteria, which is central to designating these products as a tissue or as a drug/device/biologic. We also provide perspectives on the core evidence and knowledge gaps associated with intradiscal therapies, propose imperatives for evaluating effectiveness of these treatments and highlight several new technologies on the horizon.

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“…Similarly electrically stimulated isolated porcine IVD were able to exhibit extensive annular regeneration and prevented NP protrusion. Gene expression showed an increase in ECM markers and the anti-inflammatory cytokine interleukin-4 (IL-4) and a decrease in pro-inflammatory markers and pain markers in electrically stimulated IVD ( Kanan et al, 2022 ). On the other hand, IL-1β-mediated positive effects in terms of morphological phenotypes and kinetic properties after the resultant electrical stimulation of human NP cells ( Kim et al, 2021 ).…”

Section: Piezoelectric Tissue Engineering For Regenerative Ivd Repairmentioning

confidence: 99%

“…And similarly load-induced potentials are observed within the normal IVD, which mainly include flow and diffusion potentials ( Lai et al, 2000 ). This electrical stimulation promotes the emergence of extensive annular regeneration in the isolated IVD of pigs and upregulates the production of intervertebral disc matrix macromolecules glycans, collagen II and sulphated glycosaminoglycans (sGAGs) through a mechanism associated with BMPs ( Kim et al, 2009 ; Kanan et al, 2022 ). This piezoelectric effect, which converts mechanical stimuli into electrical stimuli, is widespread in living organisms, ranging from very basic building blocks (amino acids, peptides, proteins, etc.…”

Section: Introductionmentioning

confidence: 99%

Can self-powered piezoelectric materials be used to treat disc degeneration by means of electrical stimulation?

Huang,

Wang,

Liu

et al. 2024

Front. Bioeng. Biotechnol.

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Intervertebral disc degeneration (IDD) due to multiple causes is one of the major causes of low back pain (LBP). A variety of traditional treatments and biologic therapies are currently used to delay or even reverse IDD; however, these treatments still have some limitations. Finding safer and more effective treatments is urgent for LBP patients. With increasing reports it has been found that the intervertebral disc (IVD) can convert pressure loads from the spine into electrical stimulation in a variety of ways, and that this electrical stimulation is of great importance in modulating cell behavior, the immune microenvironment and promoting tissue repair. However, when intervertebral disc degeneration occurs, the normal structures within the IVD are destroyed. This eventually leads to a weakening or loss of self-powered. Currently various piezoelectric materials with unique crystal structures can mimic the piezoelectric effect of normal tissues. Based on this, tissue-engineered scaffolds prepared using piezoelectric materials have been widely used for regenerative repair of various types of tissues, however, there are no reports of their use for the treatment of IDD. For this reason, we propose to utilize tissue-engineered scaffolds prepared from piezoelectric biomaterials with excellent biocompatibility and self-powered properties to be implanted into degenerated IVD to help restore cell type and number, restore extracellular matrix, and modulate immune responses. It provides a feasible and novel therapeutic approach for the clinical treatment of IDD.

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Electrical Stimulation-Mediated Tissue Healing in Porcine Intervertebral Disc Under Mechanically Dynamic Organ Culture Conditions

Cited by 7 publications

References 52 publications

Bioinspired Construction of Annulus Fibrosus Implants with a Negative Poisson’s Ratio for Intervertebral Disc Repair and Restraining Disc Herniation

Bioinspired Construction of Annulus Fibrosus Implants with a Negative Poisson’s Ratio for Intervertebral Disc Repair and Restraining Disc Herniation

Perspective on Intradiscal Therapies for Lumbar Discogenic Pain: State of the Science, Knowledge Gaps, and Imperatives for Clinical Adoption

Can self-powered piezoelectric materials be used to treat disc degeneration by means of electrical stimulation?

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