Regenerative rehabilitation with conductive biomaterials for spinal cord injury

Kiyotake, Emi A.; Martin, Michael D.; Detamore, Michael S.

doi:10.1016/j.actbio.2020.12.021

Cited by 61 publications

(53 citation statements)

References 226 publications

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“…StemPro Accutase Cell Dissociation Reagent was used to dissociate cells for passaging (at 80% confluency). For the in vitro study, cells were seeded at 50,000 cells/cm 2 (passage 2, 16,000 cells/gel) and cultured for 7 days with medium changes every other day.…”

Section: Methodsmentioning

confidence: 99%

“…There are two main approaches to promote functional recovery after SCI: (1) rehabilitation approaches (e.g., motor training, electrical stimulation [ES]) and (2) regenerative medicine approaches (e.g., cells, drugs, biologics, scaffolds). For SCI, rehabilitative and regenerative medicine approaches individually have not yet resulted in full functional recovery in humans, and each has limitations 2 . The combination of regenerative medicine and rehabilitation, known as regenerative rehabilitation , 3 may be needed for full functional recovery.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the focus of the studies here was to develop a conductive biomaterial that, in the future, would be able to synergize and enhance rehabilitation approaches, and specifically the use of ES 2 . Conductive biomaterials (and biomaterials in general) have the potential to replace/reduce the inhibitory environment that prevents axon regeneration, which rehabilitative approaches typically cannot accomplish.…”

Section: Introductionmentioning

confidence: 99%

“…There are three major challenges in developing conductive biomaterials: (1) low conductivity of conductive composites, (2) most conductive components are cytotoxic, and (3) most conductive biomaterials are pre‐formed scaffolds, which may have limited surgical translation. First, given that most biomaterials are insulators, conductive composites (in the semi‐conductor range) have typically been created by combining biomaterials with added conductive components (e.g., carbon‐based structures, conductive polymers, metallic‐based particles 2 ). Gold nanoparticle‐based composites have been widely investigated for tissue engineering purposes, particularly in cardiac, muscle, and peripheral nerve applications.…”

Section: Introductionmentioning

confidence: 99%

“…For SCI, rehabilitative and regenerative medicine approaches individually have not yet resulted in full functional recovery in humans, and each has limitations. 2 The combination of regenerative medicine and rehabilitation, known as regenerative rehabilitation, 3 may be needed for full functional recovery. First, regenerative medicine may be needed to regenerate the axonal pathways, and second, rehabilitation approaches may be needed to promote functionality of the axons.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Conductive and injectable hyaluronic acid/gelatin/gold nanorod hydrogels for enhanced surgical translation and bioprinting

Kiyotake

Thomas

Homburg

et al. 2021

J Biomedical Materials Res

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There is growing evidence indicating the need to combine the rehabilitation and regenerative medicine fields to maximize functional recovery after spinal cord injury (SCI), but there are limited methods to synergistically combine the fields. Conductive biomaterials may enable synergistic combination of biomaterials with electric stimulation (ES), which may enable direct ES of neurons to enhance axon regeneration and reorganization for better functional recovery; however, there are three major challenges in developing conductive biomaterials: (1) low conductivity of conductive composites, (2) many conductive components are cytotoxic, and (3) many conductive biomaterials are pre‐formed scaffolds and are not injectable. Pre‐formed, noninjectable scaffolds may hinder clinical translation in a surgical context for the most common contusion‐type of SCI. Alternatively, an injectable biomaterial, inspired by lessons from bioinks in the bioprinting field, may be more translational for contusion SCIs. Therefore, in the current study, a conductive hydrogel was developed by incorporating high aspect ratio citrate‐gold nanorods (GNRs) into a hyaluronic acid and gelatin hydrogel. To fabricate nontoxic citrate‐GNRs, a robust synthesis for high aspect ratio GNRs was combined with an indirect ligand exchange to exchange a cytotoxic surfactant for nontoxic citrate. For enhanced surgical placement, the hydrogel precursor solution (i.e., before crosslinking) was paste‐like, injectable/bioprintable, and fast‐crosslinking (i.e., 4 min). Finally, the crosslinked hydrogel supported the adhesion/viability of seeded rat neural stem cells in vitro. The current study developed and characterized a GNR conductive hydrogel/bioink that provided a refinable and translational platform for future synergistic combination with ES to improve functional recovery after SCI.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Conductive and injectable hyaluronic acid/gelatin/gold nanorod hydrogels for enhanced surgical translation and bioprinting

Kiyotake

Thomas

Homburg

et al. 2021

J Biomedical Materials Res

Self Cite

View full text Add to dashboard Cite

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Microenvironments‐Modulated Biomaterials Enhance Spinal Cord Injury Therapy

Li,

Zhang,

Liu

et al. 2024

Adv Funct Materials

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Spinal cord injury (SCI) results from various causes, including sports‐related incidents, degenerative cervical myelopathy, traffic accidents, and falls. SCI typically leads to sensory and motor dysfunction and even paralysis. Current treatments for SCI include systemic administration of high‐dose steroids and surgical decompression and stabilization. However, excessive use of glucocorticoids may increase susceptibility to infections and systemic bleeding. The long‐term effect of surgery intervention remains unclear, with ongoing debates regarding its timing, efficacy, and safety. Therefore, innovative approaches are urgently needed to alleviate secondary injuries and promote spinal recovery. One emerging therapeutic approach for SCI is modulating the microenvironments to achieve neuroprotection and neurogenesis during recovery. Several biomaterials with favorable physicochemical properties have been developed to enhance therapeutic effects by regulating microenvironments. This Review first discusses the pathology of SCI microenvironments and then introduces biomaterials‐based regulatory strategies targeting various microenvironmental components, including anti‐inflammation, anti‐oxidation, reduction of excitotoxicity, revascularization, neurogenesis, and scar density reduction. Additionally, the research and clinical application prospects for microenvironment regulation are presented.

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Injectable, Electroconductive, Free Radical Scavenging Silk Fibroin/Black Phosphorus/Glycyrrhizic Acid Nanocomposite Hydrogel for Enhancing Spinal Cord Repair

Zhang,

Wang,

Gao

et al. 2024

Adv Healthcare Materials

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Spinal cord injury (SCI) often leads to a severe permanent disability. A poor inflammatory microenvironment and nerve electric signal conduction block are the main reasons for difficulty in spinal cord nerve regeneration. In this study, black phosphorus (BP) and glycyrrhizic acid (GA) are integrated into methacrylate‐modified silk fibroin (SF) to construct a bifunctional injectable hydrogel (SF/BP/GA) with appropriate conductivity and the ability to inhibit inflammation to promote neuronal regeneration after SCI. This work discovers that the SF/BP/GA hydrogel can reduce the oxidative damage mediated by oxygen free radicals, promote the polarization of macrophages toward the anti‐inflammatory M2 phenotype, reduce the expression of inflammatory factors, and improve the inflammatory microenvironment. Moreover, it induces neural stem cell (NSC) differentiation and neurosphere formation, restores signal conduction at the SCI site in vivo, and ameliorates motor function in mice with spinal cord hemisection, revealing a significant neural repair effect. An injectable, electroconductive, free‐radical‐scavenging hydrogel is a promising therapeutic strategy for SCI repair.

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Regenerative rehabilitation with conductive biomaterials for spinal cord injury

Cited by 61 publications

References 226 publications

Conductive and injectable hyaluronic acid/gelatin/gold nanorod hydrogels for enhanced surgical translation and bioprinting

Conductive and injectable hyaluronic acid/gelatin/gold nanorod hydrogels for enhanced surgical translation and bioprinting

Microenvironments‐Modulated Biomaterials Enhance Spinal Cord Injury Therapy

Injectable, Electroconductive, Free Radical Scavenging Silk Fibroin/Black Phosphorus/Glycyrrhizic Acid Nanocomposite Hydrogel for Enhancing Spinal Cord Repair

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