Intradiscal injection of simvastatin retards progression of intervertebral disc degeneration induced by stab injury

Abstract

IntroductionEarlier work indicates that the cholesterol-lowering drug, simvastatin, is anabolic to chondrogenic expression of rat intervertebral disc (IVD) cells, which suggests a potential role for simvastatin in IVD regeneration. In this study, we expand on our earlier work to test the effectiveness of simvastatin on disc degeneration utilizing a rat tail disc degeneration model.Methods30 rats that underwent 21 G needle-puncture at rat tail discs were injected with simvastatin-loaded poly(ethylene glycol)-poly(lactic acid-co-glycolic acid)-poly(ethylene glycol) (PEG-PLGA-PEG) gel (5 mg/ml) or vehicle control at 4 weeks after needle injury. All animals were sacrificed 2 weeks after simvastatin injection. Bone morphogenetic protein-2 (BMP-2), aggrecan, collagen type II, and collagen type I messenger ribonucleic acid (mRNA) expression in the rat nucleus pulposus (NP) were measured by real-time polymerase chain reaction (PCR). In vivo magnetic resonance imaging (MRI) was performed to monitor changes in disc degeneration. Rat discs were also assessed by histology using hematoxylin and eosin (H&E) and safranin O staining. In addition, the NP weight, glycosaminoglycan (sGAG) and DNA content were also measured.ResultsA single dose of simvastatin loaded in thermo-sensitive PEG-PLGA-PEG gel injected into the NP had the trend to increase aggrecan expression and sGAG content, and significantly increased mRNA levels of BMP-2, collagen type II, and the differentiation index (the ratio of collagen type II to collagen type I). The decreased NP weight, T2 intensity, as well as MRI index in the rat tail discs induced by needle puncture were significantly reversed after 2 weeks of simvastatin treatment. In addition, simvastatin treatment also improved histological changes induced by needle puncture.ConclusionsA single injection of simvastatin loaded in PEG-PLGA-PEG gel into rat tail discs had the potential to retard or regenerate the degenerative disc.

Migration of fragments into the spinal canal after intervertebral polyethylene glycol implantation: an extremely rare adverse effect

“…Furthermore, established clinical therapeutic agents that aim to regenerate the degenerated nucleus pulposus in humans are not yet available. 4,6 In recent years, procedures to restore the dehydrated nucleus pulposus and save the elasticity of the disc space, if not cellular nucleus pulposus regeneration, are being practiced. An example of this procedure is the implantation of intervertebral hydrogel (polyethylene glycol) using minimally invasive procedures.…”

“…Regeneration of a degenerated disc is not possible with current treatment modalities, and degeneration of the disc tissue is an important factor in the etiology of disc herniation. 6 Currently, there are practices to restore the hydration of the degenerated disc, if not ensuring cellular nucleus pulposus regeneration. One such approach is known as percutaneous intervertebral hydrogel (polyethylene glycol) implantation.…”

Osteogenic effect of fluvastatin combined with biodegradable gelatin-hydrogel

“…When administered by injection their effect has been reported to be lost within 5 days 7) , making this modality impractical for clinical application in bone healing. Therefore, various methods of local administration, or drug delivery system (DDS), have been explored, and include the use of collagen gel, polyethylene glycol, and polylactide-co-glycolide [8][9][10] . One such carrier, gelatin-hydrogel, is biodegradable and already in use in various types of food and drug.…”

142 Intradiscal Injection of Simvastatin Results in Radiologic, Histologic, and Genetic Evidence of Disc Regeneration in a Rat Model of Degenerative Disc Disease

“…Previous work on a smaller number of animals at one time point showed 5 mg/mL simvastatin to be a beneficial dose [48]; we used this dose as well as higher doses of 10 mg/mL and 15 mg/mL to determine whether greater benefit would be attained with more drug, which was not the case. One question that presents itself, then, is: Why did lower doses of simvastatin demonstrate greater benefit than higher doses?…”