Regenerative Biology Group

Understanding the cellular and molecular mechanisms regulating the repair and regeneration of oral, dental, dermal and neural tissues.

Our research aims to enhance understanding of the cellular and molecular mechanisms regulating the repair and regeneration of oral, dental, dermal and neural tissues, during health and disease.

By understanding these mechanisms, our objectives are to develop stem cell, pharmaceutical, biomaterial, bioelectrical and other therapeutic strategies to promote repair in these and other tissues throughout the body.

Despite significant medical advancements in recent years, clinical conditions associated with impaired or dysfunctional healing remain a major healthcare challenge; especially with the rising incidence of these conditions due to ever-increasing ageing populations, diabetes, antimicrobial resistance and the acknowledged inadequacies in current treatment options.

Research within the Regenerative Biology Group is particularly focussed on the basic cellular biology of tissue-derived mesenchymal stromal cells (isolated from dental pulp, bone marrow, oral mucosa) in driving tissue repair processes.

A further focus of our research is the development of novel targeted delivery technology for the elimination of bacterial infections that can hamper repair processes. As part of achieving impact on patient health and well-being, our research is focussed on developing stem cell, pharmaceutical, biomaterial, bioelectrical and other therapeutic approaches for the treatment of diseases and conditions in clinical areas, such as dentistry, maxillofacial surgery and orthopaedics; impaired dermal wound healing and fibrosis; spinal cord repair and chronic kidney disease.

Through academic, clinical and industrial collaborations, our objectives are to facilitate the advancement of novel and more effective regenerative therapies to drive improvements in patient quality of life.

Research

Research areas

Within the Regenerative Biology Group, we have a number of inter-related research projects that support our research mission for delivering strong translational knowledge for patient benefit.

Stem cell Biology

Our research is advancing understanding of the biological function of dental pulp stem cells, their lineage commitment and their inherent heterogeneity. This information is vital for the banking of such cells for wider therapeutic use. We have additionally developed novel 3D tissue culture models in support of these studies and development of novel non-animal alternatives remain a focus of our research.

The preferential healing capabilities of the oral mucosa suggest that oral mucosal cells are more foetal or stem cell-like in nature. Our recent work is investigating the potential of these cells and their extracellular vesicles to help down-regulate the immune system in patients during transplantation, auto-immune diseases or chronic infections.

Dermal wound healing

Wounds in the mouth heal extremely well compared to normal skin wounds, as oral mucosal wounds demonstrate minimal inflammation and more rapid healing with reduced scarring. We are interested in understanding the mechanisms responsible for these preferential healing responses in oral mucosal fibroblasts, to identify novel pathways to be targeted by newly-developed therapies to help repair/regenerate damaged or diseased tissues.

Non-healing, chronic skin wounds (such as venous and diabetic ulcers), are an important source of morbidity in ageing societies and a significant financial burden to healthcare providers. Our research is focused on elucidating the mechanisms responsible for impaired cellular wound healing responses in chronic wounds, with the aim to utilize this information to develop novel therapies to restore healing potential in these wounds.

Bone and dentine repair

Our research focusses on the role of the extracellular matrix proteins and extracellular vesicles in providing an effective signalling environment for mesenchymal stem cells in promoting bone and dentine repair. We have identified signalling roles for 'cocktails' of growth factors, and our research is demonstrating how this can be further enhanced by novel direct or indirect signalling roles by matrix proteins previously only considered to provide roles in matrix assembly.

Clinicians are facing additional challenges for achieving efficient bone and dentine repair, due to conditions such as type 2 diabetes, osteoporosis, caries, acid erosion and as a consequence of aging. Our research looks to understand the pathological mechanisms behind the impaired healing processes underlying these conditions.

We are also investigating the interaction between bacterial species associated with bone and dentine infections and the tissue matrix, to better understand the process of infection and we have developed several 3D co-culture systems to model infection ex vivo.

Spinal cord repair

Spinal cord injury (SCI) frequently provokes serious detrimental outcomes, as neuronal regeneration is limited in the central nervous system. Our research is currently evaluating the role of the immuno-inflammatory responses in the pathogenesis of SCI, in addition to assessing the potential of biomaterial, electrical signal regulation, microfluidics, growth factor and stem/progenitor cell (e.g. neural, oligodendrocyte and dental pulp) strategies, for the replacement of lost neuronal cells, promotion of repair and functional plasticity.

Novel antimicrobial and repair therapies

Existing therapies aimed at treating impaired healing wounds or excessive scarring situations are established to offer limited benefit to healing outcomes or scar prevention. We are currently evaluating the potential of a number of novel pharmaceuticals, in terms of their abilities to restore or enhance normal healing functions and/or reduced scarring in these patients.

Our interdisciplinary approach is leading to the development of novel bioactive scaffolds for enhanced tissue repair. This research is focused on the development of novel, nanoscale delivery vehicles for encouraging bone formation, treatment of pulpitis, endodontic failure and orthopaedic infections surrounding prostheses.

Additionally, in line with increasing problems around antibiotic resistance, we are investigating the development of novel antimicrobial scaffolds for a more specific targeted delivery mechanisms to control infection in these clinical situations.

Projects

Grant Awards

2019

Industrial Pilot Research Grant, Cultech Ltd., UK. “Evaluation of the dermal wound healing properties of Lactobacillus-based, probiotics.” PI: Ryan Moseley.
EPSRC ECR Institutional Equipment. "Contact angle goniometer and quartz crystal microbalance." PI: Wayne Ayre.
Dunhill Medical Trust “Oral progenitor-derived vesicles as a novel treatment for chronic skin wounds in the aged population.” PI: Phil Stephens.
Dunhill Medical Trust. “Identifying a utility for dentally derived extracellular vesicles to restore impaired bone healing associated with age-related systemic conditions.” PI: Rachel Waddington.

2018

Collaborative Award, Royal Botanic Gardens Kew, Richmond. “Evaluation of the modulatory effects of plant-derived saps on inflammatory cell, fibroblast and keratinocyte responses associated with impaired healing, tropical ulcers.” PI: Ryan Moseley.
Industrial Postdoctoral Research Associate, QBiotics Group, Australia. “Evaluation of novel epoxy-tigliane pharmaceuticals as modulators of impaired wound healing responses in chronic wound fibroblasts.” PI: R Moseley.
Colgate-Palmolive Company. “Modelling of periodontal connective tissue regeneration.” PI: Alastiar Sloan.
Wellcome Trust ISSF3 – “Novel antimicrobial and osteogenic laser-sintered implant surfaces using ultra short-pulsed laser ablated micro/nano-topographies.” PI: Wayne Ayre.
British Skin Foundation “The development of oral exosomes as a novel treatment for chronic skin wound infections.” PI: Phil Stephens.
Phillips Research. “Cytotoxicity of an oral products.” PI AJ Sloan.

2017

ISSF Translational Kickstart Award, Wellcome Trust. “Repurposing ingenol mebutate as a novel pharmaceutical therapy for dermal fibrosis.” PI: Ryan Moseley. 2017-18.
MRC Confidence in Concept. “Evaluation of novel epoxy-tigliane pharmaceuticals as modulators of impaired wound healing responses in chronic wound fibroblasts.” PI: Ryan Moseley.
MRC Confidence in Concept. “Robust and facile lipid coating to enhance lubrication and reduce biofilm formation on urinary catheters.” PI: Wayne Ayre.
Innovate UK KTP award / Renishaw plc. “To transfer and embed new knowledge to develop world-leading innovative manufacturing processes for medical and dental prostheses, using robust assays that identify the behaviour of implant surfaces.” PI: Rachel Waddington.
MRC-Proximity to Discovery “Radiolabelling of exosomes for in vivo tracking in murine glioma.” PI: Phil Stephens.

Student prize awards

2018

Cardiff University, Postgraduate Research Day Poster Prize (Nadia Alaidaroos).
BSODR OMIG Poster Prize (Clotilde Haury).

2017

CITER Oral Presentation Prize (Glyn Morris).
ETRS Poster Prize (Glyn Morris).

2016

British Orthopaedic Research Society, International Travelling Fellowship (Wayne Nishio Ayre).

2015

CITER Young Investigator Award (Wayne Nishio Ayre).
Sêr Cymru (Life Sciences Research Network Wales) PhD Student Oral Presentation Prize (Jordanna Dally).
Cardiff University, Postgraduate Research Day Poster Prize (Jordanna Dally).
CITER Oral Presentation Prize (Lorena Hidalgo San Jose).

External academic collaborators

Mr Elijah Ablorsu, Mr Rhidian Morgan-Jones & Mr Stephen Jones, Cardiff and Vale University Health Board, UK.
Dr Ernest Azzopardi, Swansea University, UK.
Dr Mark Bass & Dr Simon Whawell, University of Sheffield, UK.
Dr Glen Boyle, QIMR Berghofer Medical Research Institute, Australia.
Dr John Colombo, University of Nevada, USA.
Prof Kamal Mustafa & Dr Salwa Suliman, University of Bergen, Norway.
Prof Joji Okazaki, Osaka Dental University, Japan.
Dr Steven Ogbourne & Dr Fraser Russell, University of the Sunshine Coast, Australia.
Dr Tom Prescott, Royal Botanical Gardens Kew, UK.

External industrial collaborators

Colgate, UK.
Cultech, UK.
IK4-Tekniker, Spain.
Philips Research, Netherlands.
QBiotics, Australia.
ReNeuron, UK.
Renishaw, UK.

Patents

Moseley R, Stephens, P, Systagenic Wound Management Ltd. EP1889069, GB2426335, US2009299161, WO2006123091: total antioxidant capacity as a prognostic/diagnostic biomarker of chronic wound infection and healing.
Moseley R, Stephens, P, Systagenic Wound Management Ltd. GB2447865, US2010166694, US2012010099, WO2008119974: quantification of various cytokines and growth factors as prognostic/diagnostic biomarkers of diabetic foot ulcer wound infection and healing.
Moseley R, Peplin Inc. (LEO Pharma A/S). AU20050906601, AU2006317523, AU20100213362, BRPI0618926, CA2629899, CA2752389, CN101360506, CN102316866, DK2395993, EP1965818, EP2395993, ES2633755, IL214133, JP2009517345, JP2012517450, JP5638008, KR20080077625, NZ568168, NZ594184, PT2395993, RU2011137530, RU2491050, US2009215884, US2012041064, US2016317486, WO2007059584, WO2010091472: application of ingenol mebutate and related compounds in the promotion of dermal wound healing.
Stephens P. AU2009259053, CN200980122121, E09761964, JP501125275; and US12/997,363: isolation and use of a novel progenitor cell population from the oral mucosal lamina propria for clinical applications.
Moseley R, QBiotics Group. AU20140253608, BR112015026388, CA2909653, CN105308052, EA201591996, EP2986615, HK1214256, JP2016522801, KR20160023651, MX2015014607, PH12015502405, SG11201508588X, US2016068499, US2017144981,WO2014169356, application of epoxy-tiglianes in the promotion of dermal wound healing and reduced scarring.
Denyer S, Evans S, Ayre W. WO2015004450 A1. Liposomal drug delivery system for bone cements.