Evaluation of a novel poly N-acetyl glucosamine (pGlcNAc) hydrogel for treatment of the degenerating intervertebral disc

Abstract

AimsThe early stages of degenerative disc disease (DDD) primarily affect the disc nucleus pulposus (NP). Tissue-engineered strategies may enhance intervertebral disc (IVD) functionality. The aim of this study was to develop and evaluate a novel deacetylated poly-N-acetyl glucosamine (pGlcNAc) hydrogel characterizing its biochemical effect on human IVD cells as well as material biomechanical properties. Main methodsA novel deacetylated derivative of a marine diatom-derived glycosaminoglycan was developed into a hydrogel formulation as a potential therapy to treat degenerating IVD NP. In vitro biochemical studies were conducted using primary human disc cell cultures to evaluate cell viability, metabolic activity, proteoglycan and extracellular matrix protein expression. The biomechanical hydration kinetics and viscoelastic behavior of the hydrogel were determined and compared with the behavior of human lumbar NP. Key findingsDisc cell viability, metabolic activity, and proteoglycan content of the treated cells were observed to be significantly greater in experimental samples when compared to untreated control groups. RT-PCR and immunohistochemical data corroborated the expression of characteristic NP disc markers, aggrecan and type II collagen in cultured cells. Rheological data demonstrated that the elastic component of the hydrogel dominated the viscous component over a frequency range of 0.1 to 15.85rad/s. Of several formulations evaluated, a sulphated, deactylated derivative of the nanofiber derived pGlcNAc hydrogel demonstrated the most robust biologic effects on cell viability, metabolic activity, and proteoglycan expression. SignificanceThis in vitro study using human disc cells demonstrates that a sulphated deacetylated glycosaminoglycan derivative hydrogel possesses promising characteristics motivating further evaluation as a potential therapy for NP degeneration.