Injectable hydrogels for bone regeneration
Hydrogels are crosslinked polymers that contain large amounts of water. We have developed a novel pNIPAM-DMAc-Laponite® hydrogel loaded with hydroxyapatite nanoparticles (HAPna), which can be maintained as a liquid ex vivo and be injected into the affected bone tissue site where body temperature triggers in situ gelation.
There is an urgent need for new therapeutic options for low back pain, which target 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.
The ability of the hydrogel to induce osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro, without the use of additional osteogenic inducing factors and the ability to promote bone density in vivo has been proven. SEM analysis shows that when the hydrogel is placed in cell culture media for 6 weeks, the porous structure remains intact (acellular). However in the presence of MSCs, from 48h onwards, the open pores are filled via matrix deposition (hMSC), there is histological evidence of bone differentiation markers and collagen deposition, this is accompanied by an increase in storage modulus (G’). These are all strong indicators of new bone formation.
1. Osteogenic Differentiation of Human Mesenchymal Stem Cells in Hydroxyapatite Nanoparticle Injectable Hydrogel Scaffold. A A Thorpe, S Creasey, C Sammon and C L Le Maitre, European Cells and Materials (in press).