Osteochondral tissue engineering using novel epigenetic approaches and multi-layered cell sheet technology

Project description

Project Summary

Osteochondral tissue damage or loss is one of the most common diseases due to traumatic injuries, natural degradation of cartilaginous tissue with aging, arthritis or surgery. These clinical situations encompass serious damage to not only articular cartilage but also the underlying calcified subchondral bone. The conventional therapeutic approaches include autografts, allografts, stimulation of bone marrow and debridement. Autografts have limited stock and allografts are associated with the risk of immune rejection or disease transmission, while bone marrow stimulation treatments are only palliative and not completely curative. Therefore, the ability to treat osteochondral defects is a major clinical need. Over the last decades, tissue engineering approaches have been utilised for regenerating articular cartilage. However the output of these is still not satisfactory. In this project, a multidisciplinary approach will be utilised to combine material science and mechanical engineering with stem cell biology for engineering functional osteochondral tissue for clinical translation.

Previously we have showed the potential of using epigenetic approaches to control stem cell function without change the genome. A novel histone deacetylase inhibitors (HDACi), MI192 pre-treatment enhanced the osteogenic differentiation of human adipose derived stem cells. In close collaboration with Tokyo Women’s Medical University, we have established the multi-layered cell sheet (MLCS) technology platform at Leeds, which allows us to harvest intact cell sheet with minimum damage to the cells and maximum retention of cell-cell junctions, extracellular matrix and growth factors embedded in the matrix.

Aims and Objectives

The aim of this project is to combine epigenetic approaches with multi-layered cell sheet technology for osteochondral tissue engineering in vitro and in vivo.

The objectives include but not limited to:

1. Establishment of an epigenetic modified stem cell bank.

2. Fabricate cartilage phase in vitro using epigenetic modified stem cell, MLCS technology and novel collagen scaffolds.

3. Fabricate bone phase in vitro using epigenetic modified stem cell, MLCS technology and 3D printed porous polymer scaffold.

4. Osteochondral tissue engineering in vitro and in vivo.

Entry requirements

Please contact our staff for further details about entry requirements.

How to apply (email)

fmhgrad@leeds.ac.uk

How to apply (phone)

+44 (0)113 343 7497