2017 – 2021 EPSRC Programme Grant – Engineering growth factor microenvironments – a new therapeutic paradigm for regenerative medicine.
Our team at CeMi joins efforts with labs at Imperial College London (Prof Molly Stevens), Nottingham University (Dr Felicity Rose) and other labs in Glasgow (Prof Jon Cooper – University of Glasgow, Prof Godfrey Smith – University of Glasgow, and Dr Jo Mountford – SNBTS). We receive annual external advice from five selected top international experts in the field.
Our vision is to develop a toolbox of novel functional materials to modify the local stem cell niche in a flexible and dynamic manner in order to deliver new bioengineering-driven therapies in musculoskeletal, cardiovascular and haematological diseases. We are (in order of increasing risk and ambition): (1) developing innovative acellular bone scaffolds to engineer living bone graft with speed, efficiency and safety; (2) engineering systems to promote the maturation of cardiomyocytes in vitro (a major translational hurdle), so that large population of mature cells are available for either transplantation or for cardiotoxicity testing; 3) engineering bone marrow niches comprising mesenchymal (MSC) and haematopoietic (HSC) stem cells to allow better maintenance of clinically important HSCs (e.g. leukaemia therapies) to enable gene editing or even allow expansion of these cells in vitro – a stem cell ‘holy grail’.
We work with translation-ready approaches to achieve these grand challenges. Rather than take a traditional, biological approach of adding abundant growth factors (GFs) associated with numerous off-target effects in vivo, we focus on producing unique bioengineered environments that self-organise the ECM to present adhesion sites and enable GF delivery topically and at physiological levels; efficiently and safely.
Dr Oana Dobre, Research Associate:
‘I am currently developing new hybrid protein/synthetic hydrogels with controlled mechanical properties, MMP–degradability with the ability to present growth factors (GFs) in an efficient way for tissue regeneration (i.e., bone, vascular, CNS and cardiovascular). The hydrogels incorporate laminin protein with application including 3D cell culture and bioprinting’.
Dr Hannah Donnelly, Research Associate:
‘My research focuses on developing novel systems that recapitulate aspects of the bone marrow microenvironment. The bone marrow is home to two clinically relevant sources of stem cells, haematopoietic stems cells (HSCs) and mesenchymal stromal cells (MSCs), both of which lose their stemness upon removal from the specialised bone marrow microenvironment. Using ECM protein and growth factor based technologies alongside hydrogels we are interested in engineering bone marrow mimetic systems that will ultimately allow investigation into fundamental stem cell properties’.
Dr Virginia Llopiz-Hernandez, Research Associate:
‘I am in charge of the stem cell and bone regeneration package of the project. I have been using different materials from the project (thermoresponsible scaffolds, liposomes, and hydrogels) to deliver growth factors in an efficient way to the stem cells, as well as I am helping to supervise a Ph.D. student to develop a bone and vascularised model using nanokicking. My role is to study and optimise the potential of mesenchymal stem cells to induce osteogenesis using these materials. On the other hand, I have been using epidermal growth factors (e.g. PDGF-BB) in an efficient way employing different systems to improve wound healing’.
Dr Sara Trujillo-Munoz, Research Associate:
‘My work in the EPSRC Programme Grant includes development of new biomaterials for better control of therapeutic growth factor delivery and also, the preclinical evaluation of bone regeneration from these new biomaterials.
In particular my research involves the design and fabrication of synthetic hydrogels that incorporate full-length fibronectin. By using a synthetic polymer we are able to control important biophysical properties of the material such as stiffness. The incorporation of fibronectin – a key protein of the extracellular matrix – allows us to have several biological signals such as adhesive cues (so the cells can attach) and growth factor binding cues (so growth factors can bind). Fibronectin is a special protein as it improves the cooperation between growth factors and cells to activate cell differentiation pathways (for more information about this work please refer to https://www.biorxiv.org/content/10.1101/687244v1).
To evaluate these biomaterials in vivo we use murine models of non-healing bone defects (these are gaps of bone that cannot regenerate) so we can test how the new implants perform. To do so we use techniques such as X-ray micro-computed tomography to quantify the new bone formed and histology to assess the quality of the new bone’.