Mineralised Tissue Group
Our research is focused into three broad areas associated with repair, regeneration and maintenance of mineralised tissues and the underlying pathophysiology of these tissues.
The mineralised tissues of the oral cavity are important for both overall function and facial aesthetics. The microbial burden within the oral cavity lends dentine / pulp and bone supporting the teeth susceptible to pathological destruction. These microbial infection results in loss of general health but, haemolytic spread of bacteria have been linked with abscess formation in body organs, strokes and myocardial infarction. A key focus of our research is in the development of novel targeted delivery technology for the elimination of such bacterial infections.
Central to the repair process are mesenchymal stem cells (MSCs), which differentiate into either osteoblasts or odontoblast-like cells to synthesise bone or reparative dentine respectively. MSCs of dental pulp show great promise as a cell source not only for bone and dentine repair, but other tissues including nerves, muscle, cartilage, heart and liver.
Our research has advanced understanding regarding the heterogeneity of MSCs populations, which vary in terms of their proficiency to synthesise bone, dentine and other tissue types, informing on their utilisation in clinical therapy.
Moreover, repair is orchestrated by a variety of bioactive growth factors, which may be produced by MSCs. Additional matrix proteins within dentine have also been established as potent stimulators of bone and dentine repair. These bioactive factor sources could be utilised to restore inefficient signalling where repair is compromised as associated with conditions such as diabetes, osteoporosis and as a general consequence of aging.
A significant feature of our research has been to harness these valuable bioactive sources in stimulating bone and dentine repair for dental, craniofacial and orthopaedic applications.
The group's research is focused into three broad areas associated with repair, regeneration and maintenance of mineralised tissues and the underlying pathophysiology of these tissues
Dentine Regeneration and Dental Pulp Stem cells
We have interests in understanding the in situ repair processes of the dentine-pulp complex and how the tissue matrix influences progenitor cell recruitment, proliferation and differentiation. In particular we are interested in understanding the biological function of the dental pulp stem cells both in 2D and 3D environments, their lineage commitment and their inherent heterogeneity. Such information is vital for the banking of such cells for wider therapeutic use.
We have developed novel 3D tissue culture models in support of these studies and development of novel non-animal alternatives remain a focus of the research.
Bone Repair and Regeneration
Rapid bone healing is often the goal for bone healing in craniofacial tissues. However, clinicians are facing an additional challenge for achieving efficient bone repair in compromised patients associated with type 2 diabetes, osteoporosis and as a consequence of aging.
Our research focusses on the role of the extracellular matrix proteins in providing an effective signalling environment for mesenchymal stem cells in promoting bone repair. We have identified signalling roles for "cocktails" of growth factors but our research is demonstrating how this can be further enhanced by novel direct or indirect signalling roles provided by extracellular matrix proteins previously only considered to provide roles in matrix assembly. Our interdisciplinary approach is leading to the development of novel bioactive scaffolds for enhanced tissue repair. This understanding is intended to be of value in restoring the lost signalling power in compromised patients
Novel Antimicrobial Delivery Vehicles for Dental/Orthopaedic Clinical Translation
Research is focussed on the development of novel, nanoscale delivery vehicles for treatment of pulpitis, endodontic failure and orthopaedic infections surrounding prostheses. In line with increasing problems around antibiotic resistance, we are investigating the development of the use non-antibiotic antimicrobials and more specific targeted delivery mechanisms to control infection in these clinical situations.
We are also striving to understand the interaction between bacterial species associated with these infections and the tissue matrix to better understand the process of infection and we have developed several 3D co-culture systems to model infection.
- Colombo, J. S. et al. 2011. Delayed osteoblast differentiation and altered inflammatory response around implants placed in incisor sockets of type 2 diabetic rats. Clinical Oral Implants Research 22 (6), pp.578-586. (10.1111/j.1600-0501.2010.01992.x)
- Lynch, C. D. et al. 2011. Hunter-Schreger Band patterns and their implications for clinical dentistry. Journal of Oral Rehabilitation 38 (5), pp.359-365. (10.1111/j.1365-2842.2010.02162.x)
- Smith, E. et al. 2010. An ex vivo rodent mandible culture model for bone repair. Tissue Engineering Part C: Methods 16 (6), pp.1287-1296. (10.1089/ten.tec.2009.0698)
Current PhD projects
- Abeer Al Mouallad - Endogenous Growth Factor Release for Maxillofacial Tissue Repair. Taibah University, Saudi Arabia
- Ahmed Al Qarakhli - Altered bone cell biology associated with type 2 diabetes Mellitus – consequences for periodontal disease. Iraqi Ministry of Higher Education and Scientific Research
- Steven Avery - Elucidating novel roles for extracellular matrix components in directing stem cell biology
- Paul Battersby - The Role of Biglycan in Regulating Mesenchymal Stem Cell and Growth Factor Activity
- Elen Everett - Novel Antimicrobial Restorative Materials to Manage Dental Disease
- Jabur Khan - Developing Ex Vitro Models for Understanding Microbial Infection Associated with Hip Implants
- Madhan Natarajan - Characterisation of Pulpal Responses to Bacterial Challenge and Novel Antimicrobials for Management of Bacterial Contamination of Infected Pulps and Root Canals
- Leili Sadaghiani - The Effect of Adhesive Restorative Agents on Solubilisation of Bioactive Dentine Matrix Components and Dentine Regeneration
Current and recent grants
- MRC Regenerative Medicine Hub Liposomal delivery of bioactive matrices and antimicrobials for dental tissue repair. AJ Sloan, RJ Waddington 6/15 – 12/15. £50,000.
- Renishaw plc. Evaluation of Renishaw Cobalt Chromium LaserAbutment effects on peri-implant health. RJ Waddington and AJ Sloan. 8/13 – 4/14. £48,425.
- Renishaw plc. Bacterial adhesion and anti-microbial activation of metal surfaces for dental prostheses. AJ Sloan, RJ Waddington, Q Jones, W Ayre. 10/15 – 9/18. £50,000
- Philips Research. Bleaching, tooth colour and Dentine-pulp complex responses. AJ Sloan, RJ Waddington. 12/13-11/14. £207,000.
- Phillips Research. Cytotoxicity of an oral hygiene mouthwash combined with ultrasound. RJ Waddington, AJ Sloan 12/14-2/15 £62,000.
- NISCHR. Novel Antimicrobial Restorative Materials to Manage Dental Disease. AJ Sloan, A Paul, RJ Waddington, S Denyer. 1/10/14 – 30/09/17. £66,000
- Rosetrees Trust. Elucidating the bioactive properties of dentine matrix for translation into novel bone repair and regeneration therapies. RJ Waddington and SJ Avery. 7/13-6/15. £15,500.
- Ser Cymru / Welsh Government. Local delivery of osteogenic molecules to encourage regenerative bone repair around cemented joint replacements. W Ayre, A J Sloan, RJ Waddington, S Evans, D Mason, J Birchall, B Evans. 2/15 -1/16. £49,500.
- MRC Confidence in Concept Scheme. Liposomal Delivery of Antimicrobials from dental cements for Dental Tissue Repair AJ Sloan, J-Y Maillard, C Lynch. £50,000.
- SARTRE Health Technology Challenge Scheme. Liposomal antimicrobial delivery system for PMMA bone cement. WN Ayre, R Morgan-Jones, SL Evans SL and SP Denyer SP. 6/14 ––8/14 £19,635.
- SARTRE Health Technology Challenge Scheme. Phosphonate-tethered lysophosphatidic acid-functionalised titanium: a novel surface finish for bone regenerative applications. WN Ayre, JP Mansell, SP Denyer, T Scott and A Blom. 9/14 – 11/14. £31,512.
- The Pet Plan Charitable Trust. Development of a novel in vitro model to investigate the role of pathogens in the aetiology of feline chronic gingiovostomatitis and to test therapeutic interventions. MP Riggio, AJ Sloan D Bennett, DF Lappin, C Nile, SP Denyer. 2015-2018; £89942
Cyfarwyddwr Cyswllt Ymgysylltu a Menter, Professor in Oral Biochemistry, Director of Postgraduate Research Studies
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