Regeneration of intervertebral disc by the intradiscal application of cross-linked hyaluronate hydrogel and cross-linked chondroitin sulfate hydrogel in a rabbit model of intervertebral disc injury

Abstract

The degeneration of intervertebral disc (IVD) is a major cause of low back pain. However, there is no satisfactory preventive treatment for degenerative disc disease (DDD). In this study, we examined the effects of a novel cross-linked hyaluronate hydrogel and cross-linked chondroitin sulfate (CS) hydrogel on a rabbit model of IVD injury. We injected 300 µl of phosphate buffer saline, 1% sodium hyaluronate, cross-linked hyaluronate hydrogel, or cross-linked CS hydrogel into the injured IVDs.One, three or six months after treatment, the whole spinal columns were dissected and magnetic resonance (MR) images of the IVDs were examined. It was noted that the IVD, which was injected with cross-linked hyaluronate hydrogel or cross-linked CS hydrogel mostly retained the normal signal intensity of the MR images. These IVDs exhibited a higher degree of staining with safranin-O than the control discs or 1% sodium hyaluronate-injected discs, suggesting that the intradiscal application of cross-linked hyaluronate hydrogel or cross-linked CS hydrogel probably inhibits the degenerative cascade of the DDD. The intradiscal administration of these drugs is safe, easy and costs less. In the near future, these intradiscal injections may become the standard therapy for the treatment of DDD instead of the spine surgeries.

Intradiscal Therapeutics for Degenerative Disc Disease

“…Hyaluronic acid alone reduced degeneration on imaging following nucleotomy procedures in nonhuman primate lumbar spines (Pfeiffer et al 2003). Within a rabbit annular puncture model of IVD degeneration, crosslinked HH and cross-linked chondroitin sulphate hydrogel retained MRI T2 intensity for 3 months, and histologically had increased proteoglycan staining (Nakashima et al 2009). Within a sheep nucleotomy model, after 6 months HH completely regenerated sheep IVD histologically, biochemically, and radiologically (Benz et al 2012).…”

New possibilities of treatment of low back pain

“…Учитывая роль ОА в формировании синдрома ПБ, значительный интерес представляет возможность применения препаратов SYSADOA, в частности ХС (особенно инъекционных форм -например инъектран), для лечения таких больных. Результаты экспериментального исследования [41] продемонстрировали возможность уменьшения выраженности дегенеративного поражения межпозвонковых дисков при локальном введении ХС в комбинации с другими лечебными мероприятиями. По мнению авторов исследования, по мере совершенствования методов доставки ХС в пораженные ткани, такие препараты смогут занять важное место в лечении пациентов с ПБ.…”

The Role of Hyaluronic Acid in Intervertebral Disc Regeneration

“…Different materials were incorporated with HA to form composites with biocompatible properties including biological performance, stiffness, and degradation both in vitro and in vivo. Such composites, including collagen, Fibrin and chondroitin sulphate [142,143,146,156], have been investigated in order to tackle extracellular matrix degradation by enhancing the synthesis of key matrix modulating proteins, GAGs and increasing cellular viability. Pre-clinical models of IVD degeneration to test the efficacy of HA-based materials have been developed in mice [155], rats [60], rabbit [143], sheep [153], goats [154], pigs [156], cows [142], and primates [144].…”

“…Such composites, including collagen, Fibrin and chondroitin sulphate [142,143,146,156], have been investigated in order to tackle extracellular matrix degradation by enhancing the synthesis of key matrix modulating proteins, GAGs and increasing cellular viability. Pre-clinical models of IVD degeneration to test the efficacy of HA-based materials have been developed in mice [155], rats [60], rabbit [143], sheep [153], goats [154], pigs [156], cows [142], and primates [144]. HA formulations have been cross-linked using many methods including UV cross-linking [142], divinyl sulfone [144], polyethyleneglycol (PEG)-amine with EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), NHS (N-hydroxysuccinimide) cross-linking [59], fibrin [150], batroxobin [152], butanediol diglycidyl ether [157] and enzymatic cross-linking using transglutaminase in a fibrin/HA material [154].…”