Mimicking microenvironment for controlling stem cell behaviour to enhance tissue engineering efficacy

Project description

Project Summary

It has been generally accepted that tissue engineering requires three basic elements: cells, growth factors and biomaterial scaffolds. However, only these three basic elements may be not sufficient enough for functional tissue engineering. Therefore, there are increasing research efforts looking at how the biological, chemical and/or mechanical microenvironments influence stem cell/progenitor behaviour.

In natural conditions, bone is formed by two processes – intramembranous and endochondral ossification. Intramembranous ossification is that osteoblast directly lays down type I collagen extra cellular matrix (ECM) into the primitive connective tissue (mesenchyme). These ECMs can then become mineralised to form bone. While endochondral ossification involves cartilage as a precursor and osteoblast lay done bone matrix to replace the cartilage precursor. But in both processes, osteoblasts will be trapped within the newly formed bone matrix and either change to osteocytes or undergo apoptosis. During this cascade event of bone formation, the microenvironments surrounding the stem cells, osteoprogenitor, osteoblast and osteocytes are dynamically changed. Therefore, how to mimic the microenvironmental surroundings may play a key role in controlling cell function, which in turn controls tissue regeneration strategy.

We have recently shown the possibility of fabricating hydroxyapatite nanocrystal composites on the surface of individual stem cells (Saha et al, Chemistry Letters, 2015). The overall aim of this project is to use similar approaches and/or develop novel approaches to mimic the microenvironment of targeting cells for controlling cell behaviour and function to enhance tissue engineering efficacy.

This is a collaborative project between Dr Xuebin Yang (Clinician and bioengineer with expertise in clinical orthopaedics and tissue engineering), Dr Lin-Hua Jiang (Biologist with expertise in ionic signalling) and Dr Michiya Matsusaki (Material scientist with expertise in functional polymers and biomaterials for biomedical applications) at Osaka University (Japan).

Aims and Objectives

The objectives include but are not limited to:

1. Isolation of stem cells from human tissues (such as bone marrow or dental pulp tissue);
2. In vitro expansion and characterisation of these stem cells;
3. Using layer-by layer coating methods or 3D printing methods to create nano-films on individual cells or 3D in vitro models;
4. Using alternate soaking method to fabricate Hap nanocrystals on the individual cell or cell pelleted to create a hard shell on individual cell or pellet;
5. Assessment of the effect of this microenvironment change on the cell cycle, signalling pathway and functionality;
6. Assessment of stem cell surface marker expression before and after the change of the microenvironment;
7. assessment of the cell functionality after removing the shell;
8. Use elected/optimised approaches to test their potential for enhancing bone tissue engineering strategy in vitro and/or 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