Establishing a through-puncture model for assessing post-injection leakage in the intervertebral disc

Varden, Lara; Turner, Evan J; Coon, Allison T; Michalek, Arthur J.

doi:10.1007/s00586-022-07140-y

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…We next assessed the toxicity of SP@NNPm to other tissues, given the risk of leakage after intradiscal injection. [ 39 ] Hemolysis assays revealed that nanoparticles at different concentrations were biocompatible with red blood cells (hemolysis rate < 5%) (Figure 4C ). Moreover, hematoxylin and eosin (HE) staining suggested that major organs, such as the heart, liver, spleen, lung, and kidney, were not markedly damaged after intravenous administration injection of SP@NPm or SP@NNPm (Figure 4D ).…”

Section: Resultsmentioning

confidence: 99%

PGC1α‐Inducing Senomorphic Nanotherapeutics Functionalized with NKG2D‐Overexpressing Cell Membranes for Intervertebral Disc Degeneration

Liu,

Li,

et al. 2024

Advanced Science

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Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting senescence markers and the senescence‐associated secretory phenotype (SASP), remains limited due to challenges in precise delivery. Given that the natural killer group 2D (NKG2D) ligands are increased on the surface of senescent nucleus pulposus (NP) cells, the NKG2D‐overexpressing NP cell membranes (NNPm) are constructed, which is expected to achieve a dual targeting effect toward senescent NP cells based on homologous membrane fusion and the NKG2D‐mediated immunosurveillance mechanism. Then, mesoporous silica nanoparticles carrying a peroxisome proliferator‐activated receptor‐ɣ coactivator 1α (PGC1α)inducer (SP) are coated with NNPm (SP@NNPm) and it is found that SP@NNPm selectively targets senescent NP cells, and the SP cores exhibit pH‐responsive drug release. Moreover, SP@NNPm effectively induces PGC1α‐mediated mitochondrial biogenesis and mitigates senescence‐associated markers induced by oxidative stress and the SASP, thereby alleviating puncture‐induced senescence and disc degeneration. This dual‐targeting nanotherapeutic system represents a novel approach to delivery senomorphics for disc degeneration treatment.

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Section: Resultsmentioning

confidence: 99%

PGC1α‐Inducing Senomorphic Nanotherapeutics Functionalized with NKG2D‐Overexpressing Cell Membranes for Intervertebral Disc Degeneration

Liu,

Li,

et al. 2024

Advanced Science

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“…In the current study, the volumes injected were limited, as was needle size. A recent study showed that this risk of leakage could be minimized to zero by using small injection volume, small needle diameters [ 35 ]. Hence direct leakage through the injection tract is less likely, and extradiscal bone formation is probably due to diffusion.…”

Section: Discussionmentioning

confidence: 99%

Intradiscal injection of human recombinant BMP-4 does not reverse intervertebral disc degeneration induced by nuclectomy in sheep

Garcia

Bach

et al. 2022

Journal of Orthopaedic Translation

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Enzymatic Digestion of the Intervertebral Disc Alters Intradiscal Injection and Leakage Mechanics

Appel,

Michalek

2024

Journal of Biomechanical Engineering

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Intradiscal injection is required to deliver therapeutic agents to the intervertebral disc (IVD) nucleus pulposus (NP). However, injectate leakage following needle retraction may result in decreased treatment efficacy and adverse side effects. While enzymatic digestion is a common research approach for simulating degeneration in healthy animal IVDs, contributions to the leakage phenomenon are unknown. In this study, bovine caudal discs were treated with injection into the NP of either a tris buffer control, collagenase (to primarily target collagen), or trypsin (to primarily target proteoglycans), then injected with fluorescent saline using a through-puncture defect protocol. Pressure-volume records during injection were used to determine volume and pressure at leakage. Discs were then frozen, transected, and photographed to visualize injectate dispersion. Collagenase treatment resulted in a large increase in injectate dispersion, along with a decrease in injection pressure relative to control. Trypsin treatment resulted in a moderate increase in dispersion, with no associated effect on pressure. This study concludes that care should be taken when employing enzymatic digestion to simulate IVD degeneration, as NP tissue disruption may affect both retention and dispersion of subsequent therapeutic injections.

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Establishing a through-puncture model for assessing post-injection leakage in the intervertebral disc

Cited by 4 publications

References 34 publications

PGC1α‐Inducing Senomorphic Nanotherapeutics Functionalized with NKG2D‐Overexpressing Cell Membranes for Intervertebral Disc Degeneration

PGC1α‐Inducing Senomorphic Nanotherapeutics Functionalized with NKG2D‐Overexpressing Cell Membranes for Intervertebral Disc Degeneration

Intradiscal injection of human recombinant BMP-4 does not reverse intervertebral disc degeneration induced by nuclectomy in sheep

Enzymatic Digestion of the Intervertebral Disc Alters Intradiscal Injection and Leakage Mechanics

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