Injectable hydrogels for IVD regeneration
Hydrogels are crosslinked polymers that contain large amounts of water. We have developed a novel pNIPAM-DMAc-Laponite® hydrogel loaded with Mesenchymal Stem Cells (MSCs), which can be maintained as a liquid ex vivo and be injected into the affected tissue site where body temperature triggers in situ gelation.
There is an urgent need for new therapeutic options for low back pain, which targeted degeneration of the intervertebral disc (IVD). Here, we provide a proof of concept for our hydrogel system, where following injection into the IVD, body temperature triggers gelation. The combined effects of hypoxia (5% O2) and the structural environment of the hydrogel delivery system on the differentiation of human mesenchymal stem cells (hMSCs), towards an NP cell phenotype was investigated.
hMSCs were incorporated into the liquid hydrogel, the mixture solidified and cultured for up to 6 weeks under 5% O2 where viability was maintained. Immunohistochemistry revealed significant increases in NP matrix components: aggrecan; collagen type II and chondroitin sulphate after culture, accompanied by increased matrix staining for proteoglycans and collagen, observed histologically.
MSCs cultured under hypoxic conditions, which mimic the native disc microenvironment, accelerate differentiation of hMSCs within the hydrogel system, towards the NP phenotype without the need for additional growth factors, thus simplifying the treatment strategy for the repair of IVD degeneration.
Thermally Triggered Injectable Hydrogel, which Induces Mesenchymal Stem Cell Differentiation to nucleuspulposus cells: potential for regeneration of the Intervertebral Disc. A A Thorpe, C Sammon and C L Le Maitre, Acta Biomaterialia (in press).