Abstract
Hydrogels, such as fibrin, offer a promising delivery vehicle to introduce cells into the intervertebral disc (IVD) to regenerate damaged disc tissue as a potential treatment for low back pain. However, fibrin lacks key extracellular matrix (ECM) components, such as collagen (Col) and hyaluronan (HA), normally found in native nucleus pulposus (NP) tissue. The overall aim of this work was to create a fibrin-based hydrogel, by incorporating Col and HA into the matrix to enhance NP-like matrix accumulation using articular chondrocytes (CC). Firstly, we assessed the effect of fibrin concentrations on hydrogel stability, and the viability and proliferation kinetics of articular chondrocytes. Secondly, we investigated the effect of incorporating Col and HA to enhance NP-like matrix accumulation, and finally, examined the influence of various HA concentrations. Results showed that increasing fibrin concentration enhanced cell viability and proliferation. Interestingly, incorporation of HA promoted sGAG accumulation and tended to suppress collagen formation at higher concentrations. Taken together, these results suggest that incorporation of ECM components can enhance the bioactivity of fibrin-based hydrogels, which may help advance the clinical potential of commercial cell and biomaterial ventures in the treatment of IVD regeneration.
Highlights
Low back pain (LBP) is one of the most prevalent pathologies worldwide [1], placing a substantial burden on healthcare resources
We investigated fibrin hydrogels of different compositions in an attempt to identify a suitable composition to promote nucleus pulposus (NP)-like extracellular matrix accumulation that may be compatible with commercial ventures
Whether the beneficial effect of the highest concentration of HA is due to the binding of HA or due to the initiated condensation of the construct remains unclear, and warrants further investigation. These findings suggest, despite increased contraction, a concentration of 5 mg/mL HA to be suitable for disc repair, due to the enhanced NP-like matrix accumulation of articular chondrocytes within this network
Summary
Low back pain (LBP) is one of the most prevalent pathologies worldwide [1], placing a substantial burden on healthcare resources It occurs naturally with age, and is considered to be associated with degeneration of the intervertebral disc (IVD), which is characterised by increased cell death [2] and decreased accumulation of extracellular matrix (ECM) components, such as collagen and proteoglycans. These are the main constituents of nucleus pulposus (NP) tissue, providing its unique biomechanical properties. There are associated limitations with ADCT, including cell leakage following injection into the disc [4], diminished matrix-forming capacity of culture-expanded NP cells derived from degenerated tissue [5], and the paucity of nucleus pulposus (NP) cells that can be isolated
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