Research projects

Inflammation and Repair - Regenerative Medicine - IVD regeneration - current projects (projects)

Development of Mechanically Robust Functionalised Chitosan-Based Hydrogels for Tissue Engineering Applications in Cartilaginous Tissues

Duration of the project

May 2011 - April 2013

Funding body

Biotechnology and Biological Sciences Research Council (BBSRC)

Members of the project

Professor Judith HoylandPrincipal investigator
Dr Stephen RichardsonCo-investigator
Dr Hamish GilbertResearch associate

The ultimate aim of this project will be to develop a novel functionalised, mechanically-robust, thermosensitive chitosan-based hydrogel for mesenchymal stem cell (MSC)-based tissue engineering strategies to treat age-related diseases of cartilaginous tissues, such as intervertebral disc (IVD) degeneration. Low back pain (LBP), caused predominantly by IVD degeneration, poses a huge socioeconomic problem to economies and healthcare systems around the globe, costing the UK government alone over £12 billion per annum, and causes pain and suffering to over 1 million people in the UK. While there are currently no successful long-term treatments for age-related cartilaginous tissue disorders, cell-based tissue engineering offers great potential to revolutionise future treatment options. The Manchester team have previously demonstrated that MSCs seeded in thermosensitive chitosan/glycerophosphate hydrogels differentiate to cells of the nucleus pulposus (NP) of the IVD. However, these gels are not ideal and specifically   do not have the mechanical properties required withstand the loaded environment of the human spine. Thus our aim is to use state-of-the-art chemistries, combined with expertise in MSC biology and tissue engineering to develop novel chitosan-based hydrogels, which are thermosensitive, mechanically robust and functionalised to enhance cell survival within the spine and prevent future disease reoccurrence.

 To achieve this vision a number of objectives must be realised within this project. We shall:

  1.  Develop, through highly efficient cross-linking chemistry, chitosan-based hydrogels with improved mechanical properties; 
  2. Assess whether such hydrogels can support MSC survival and differentiation to an NP phenotype and that appropriate matrix can be synthesized; ,
  3. By means of  Diels-Alder chemistry, convert the mechanically robust chitosan based hydrogels  into thermosensitive  hydrogels suitable for injection;  
  4. Using a unique “bioreactor” and novel ex-vivo whole disc explant model   assess the ability of these mechanically robust, thermosensitive gels to be injected within the IVD,  support MSCs and function appropriately  within the loaded environment of the degenerate IVD;
  5. Introduce appropriate functionality to mechanically robust thermosensitive chitosan based hydrogels to ensure  enhanced cell survival or to prevent further tissue damage within the “regenerate niche”

These objectives can be divided into three main research themes: A) Development of mechanically robust chitosan-based hydrogels to support MSC survival and differentiation (objectives 1 & 2 above); B) conversion of mechanically-robust chitosan-based hydrogels into thermosensitive hydrogels suitable for injection (objectives 3 & 4); and C) introduction of appropriate functionality into mechanically robust, thermosensitive chitosan-based hydrogels (objective 5).