Efficacy of intradiscal hepatocyte growth factor injection for the treatment of intervertebral disc degeneration

Abstract

Abstract.A poor nutritional supply to the cells of the avascular intervertebral discs, caused by dehydration of the extracellular matrix, is a major cause of intervertebral disc degeneration (IDD). Since hepatocyte growth factor (HGF) has been shown to exert antifibrotic effects, we hypothesized that HGF treatment may be capable of retarding IDD. The present study aimed to evaluate the efficacy of HGF treatment in retarding IDD in a rat tail model of disc degeneration. The disc degeneration models were induced by needle puncture of the rat tail discs. Four weeks following needle puncture, a triblock poly(lactide-co-glycolide)-poly(ethyleneglycol)-poly(lactide-co-glycolide; PLGA-PEG-PLGA) polymer gel loaded with HGF or the gel alone was injected into rat tail discs. The efficacy of HGF in retarding IDD was assessed by magnetic resonance imaging (MRI), histological and immunohistochemical evaluation of the type I collagen, type II collagen and bone morphogenetic protein-2 (BMP-2) expression levels. Following injection of the HGF-loaded gel into the nucleus pulposus (NP), a significant trend towards an increase in T2 signal intensity (P=0.028), type II collagen staining in the NP and the number of BMP-2-positive cells in the annulus fibrosus was observed. In addition, the results demonstrated a significant trend towards a decrease in the histological score (P=0.025) and type I collagen staining in the NP compared with segments treated with the gel alone, following the induction of disc degeneration by stab injury. Following treatment with HGF, a tendency for the level of disc height to be maintained was also observed (no statistical significance). By MRI, histological and immunohistochemical evaluation, the present study demonstrated that HGF-loaded PLGA-PEG-PLGA gel was able to retard disc degeneration when injected into the degenerative discs of rat tail models.

Overexpressed IGFBP5 promotes cell proliferation and inhibits apoptosis of nucleus pulposus derived from rats with disc degeneration through inactivating the ERK/MAPK axis

“…With back pain as the main clinical symptom, patients with conservative treatment failure might face intraoperative morbidity . The main reason leading to DD is that extracellular matrix dehydration may result in an undersupplied nutrition for the cells in the avascular intervertebral discs (IVD) . It still remains a clinically significant situation for the expensive and correlatively ineffective therapy .…”

Controlled release of simvastatin‐loaded thermo‐sensitive PLGA‐PEG‐PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics

“…In particular, thermo‐sensitive hydrogels are safe and convenient for phase transitions and can change between a liquid state and a solid state based on the ambient temperature . Thermo‐sensitive hydrogels are capable of being injected directly into the defect cavity in the impaired tissue at a low temperature and solidify at body temperature, avoiding any use of physical or chemical initiators …”

“…Among the currently reported thermo‐sensitive systems, poly( d,l ‐lactide‐ co ‐glycolide)‐poly(ethylene glycol)‐poly( d,l ‐lactide‐ co ‐glycolide) triblock copolymers (PLGA‐PEG‐PLGA) have attracted significant attention for their significant potential in clinical applications due to their excellent biocompatibility and biodegradability; they also overcome many of the drawbacks of using the copolymers PEG or PLGA . In addition, to take full advantage of the characteristics of the hydrogels, drugs are loaded into the hydrogels to create controlled‐release systems.…”

Annular Repair Using High-Density Collagen Gel

“…16,17 In such models, degeneration is initiated by extrusion of nucleus pulposus (NP) tissue through the puncture defect. Although the needle puncture model has been frequently used to test biological materials for IVD regeneration, 18–21 no study yet has used this model to investigate repair of induced defects to prevent disc degeneration.…”