Therapeutic factors and biomaterial-based delivery tools for degenerative intervertebral disc repair

Song, Haoyang; Guo, Chuan; Wu, Ye; Liu, Yuheng; Kong, Qingquan; Wang, Yu

doi:10.3389/fcell.2024.1286222

Cited by 2 publications

(1 citation statement)

References 78 publications

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“…It could avoid the impairment of AF integrity and NP depressurization by multiple intradiscal injections. However, to date, most delivery strategies for a consecutive and controlled drug release are not compatible with single injection approaches [ 65 ]. Therefore, a single intradiscal injection is often not practical for IDD treatment.…”

Section: Discussionmentioning

confidence: 99%

Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration

Jiang,

Qin,

Yang

et al. 2024

J Nanobiotechnol

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Background The use of gene therapy to deliver microRNAs (miRNAs) has gradually translated to preclinical application for the treatment of intervertebral disc degeneration (IDD). However, the effects of miRNAs are hindered by the short half-life time and the poor cellular uptake, owing to the lack of efficient delivery systems. Here, we investigated nucleus pulposus cell (NPC) specific aptamer-decorated polymeric nanoparticles that can load miR-150-5p for IDD treatment. Methods The role of miR-150-5p during disc development and degeneration was examined by miR-150-5p knockout (KO) mice. Histological analysis was undertaken in disc specimens. The functional mechanism of miR-150-5p in IDD development was investigated by qRT-PCR assay, Western blot, coimmunoprecipitation and immunofluorescence. NPC specific aptamer-decorated nanoparticles was designed, and its penetration, stability and safety were evaluated. IDD progression was assessed by radiological analysis including X-ray and MRI, after the annulus fibrosus needle puncture surgery with miR-150-5p manipulation by intradiscal injection of nanoparticles. The investigations into the interaction between aptamer and receptor were conducted using mass spectrometry, molecular docking and molecular dynamics simulations. Results We investigated NPC-specific aptamer-decorated polymeric nanoparticles that can bind to miR-150-5p for IDD treatment. Furthermore, we detected that nanoparticle-loaded miR-150-5p inhibitors alleviated NPC senescence in vitro, and the effects of the nanoparticles were sustained for more than 3 months in vivo. The microenvironment of NPCs improves the endo/lysosomal escape of miRNAs, greatly inhibiting the secretion of senescence-associated factors and the subsequent degeneration of NPCs. Importantly, nanoparticles delivering miR-150-5p inhibitors attenuated needle puncture-induced IDD in mouse models by targeting FBXW11 and inhibiting TAK1 ubiquitination, resulting in the downregulation of NF-kB signaling pathway activity. Conclusions NPC-targeting nanoparticles delivering miR-150-5p show favorable therapeutic efficacy and safety and may constitute a promising treatment for IDD. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration

Jiang,

Qin,

Yang

et al. 2024

J Nanobiotechnol

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Cutting-Edge Biomaterials in Intervertebral Disc Degeneration Tissue Engineering

Wang,

Zhang,

Cheng

et al. 2024

Pharmaceutics

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Intervertebral disc degeneration (IVDD) stands as the foremost contributor to low back pain (LBP), imposing a substantial weight on the world economy. Traditional treatment modalities encompass both conservative approaches and surgical interventions; however, the former falls short in halting IVDD progression, while the latter carries inherent risks. Hence, the quest for an efficacious method to reverse IVDD onset is paramount. Biomaterial delivery systems, exemplified by hydrogels, microspheres, and microneedles, renowned for their exceptional biocompatibility, biodegradability, biological efficacy, and mechanical attributes, have found widespread application in bone, cartilage, and various tissue engineering endeavors. Consequently, IVD tissue engineering has emerged as a burgeoning field of interest. This paper succinctly introduces the intervertebral disc (IVD) structure and the pathophysiology of IVDD, meticulously classifies biomaterials for IVD repair, and reviews recent advances in the field. Particularly, the strengths and weaknesses of biomaterials in IVD tissue engineering are emphasized, and potential avenues for future research are suggested.

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Therapeutic factors and biomaterial-based delivery tools for degenerative intervertebral disc repair

Cited by 2 publications

References 78 publications

Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration

Effective delivery of miR-150-5p with nucleus pulposus cell-specific nanoparticles attenuates intervertebral disc degeneration

Cutting-Edge Biomaterials in Intervertebral Disc Degeneration Tissue Engineering

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