Abstract
Intervertebral disc (IVD) degeneration is a leading cause of low back pain worldwide, incurring a significant burden on the healthcare system and society. IVD degeneration is characterized by an abnormal cell-mediated response leading to the stimulation of different catabolic biomarkers and activation of signalling pathways. In the last few decades, hyaluronic acid (HA), which has been broadly used in tissue-engineering, has popularised due to its anti-inflammatory, analgesic and extracellular matrix enhancing properties. Hence, there is expressed interest in treating the IVD using different HA compositions. An ideal HA-based biomaterial needs to be compatible and supportive of the disc microenvironment in general and inhibit inflammation and downstream cascades leading to the innervation, vascularisation and pain sensation in particular. High molecular weight hyaluronic acid (HMW HA) and HA-based biomaterials used as therapeutic delivery platforms have been trialled in preclinical models and clinical trials. In this paper, we reviewed a series of studies focused on assessing the effect of different compositions of HA as a therapeutic, targeting IVD degeneration. Overall, tremendous advances have been made towards an optimal form of a HA biomaterial to target specific biomarkers associated with IVD degeneration, but further optimization is necessary to address regeneration.
Highlights
A total of 80% of the world population suffer from low back pain (LBP) which is considered the most significant cause of disability, resulting in a negative socioeconomic impact [1,2]
We found sialylation, which is an indicator of inflammation was down-regulated on days 7, 28 and 56 when the injured discs were treated with high molecular weight (HMW) hyaluronic acid (HA)
LBP generation is initiated by low numbers of native intervertebral disc (IVD) cells, which leads to extracellular matrix disintegration, and vascularisation promoting inflammation and low back pain sensation
Summary
A total of 80% of the world population suffer from low back pain (LBP) which is considered the most significant cause of disability, resulting in a negative socioeconomic impact [1,2]. LBP is more common in patients above 65 years old [5,6], it can start as early as in the late teenage years [7]. It is classified as the most expensive healthcare treatment, ranging between 12 to 90 billion dollars in the United States alone [8] and above 500 million pounds in the United Kingdom according to the nice guideline [9]. In terms of biochemical changes, the deficiency in nutrient diffusion into the disc due to the calcified cartilaginous endplate (CEP) is a fundamental cause of IVD
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