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Advanced injectable biomaterials for targeted gene delivery in periodontal regeneration and antimicrobial therapy

PGR-P-224

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
International (open to all nationalities, including the UK)
Funding
Non-funded
Supervisors
Dr Georg Feichtinger
Additional supervisors
Dr Robert Wynn Davies, Vanaja Krishna Naik
Schools
School of Dentistry
<h2 class="heading hide-accessible">Summary</h2>

Periodontitis is the sixth most prevalent disease in the world, mostly (but not exclusively) affecting adults in their thirties and forties with a peak incidence at around 38 years of age Periodontitis is a polymicrobial infection caused by co-operating consortia of organisms, predominantly growing as biofilms. Periodontal pockets may harbour up to 108 diverse bacteria. The same bacteria are also associated with systemic effects through gaining access to the blood, and the chronic infection/inflammation associated with periodontitis can underlie pathology at non-oral sites. <br /> <br /> P. gingivalis, a key periodontal pathogen, has been shown to invade human aortic endothelial cells and induced the production of pro-inflammatory molecules. It can occur at distant sites including atherosclerotic plaques, inflamed joints, and brain tissue. Periodontitis, is a chronic inflammatory multifactorial disease, is a significant cause of tooth loss significantly affecting the quality of life of patients with diverse chronic disease backgrounds. Current clinical treatment strategies, non-surgical, surgical, adjunctive antimicrobials, and local delivery systems lack solutions effectively offering simultaneous sustained periodontal tissue regeneration and antimicrobial action. This significant high-impact oral health challenge affecting up to one-third of the population, therefore, requires advanced multi-modal treatment strategies to combat infection effectively, inflammation whilst supporting tissue regeneration.<br /> <br /> Self-assembly peptides (SAPs) are self-assembling injectable molecules that can respond to environmental triggers forming a biomimetic hydrogel scaffold, with multiple capabilities to support enamel regeneration and mineralisation. Rational design and optimisation of these systems could potentially deliver a wide range of additional therapeutics depending on the sequence, concentration, charge, and hierarchical structures present. The properties of the hydrogel can be tailored to specific oral environments. Incorporating advanced drug payloads such as non-viral gene therapeutics into injectable SAP biomaterials could cost-effectively offer the potential to provide targeted advanced regenerative cues and antimicrobial action by delivering growth factor and antimicrobial genes directly to target cells at the defect whilst simultaneously providing a regenerative matrix. Such an approach would, therefore, minimally invasively address significant clinical challenges in dental and musculoskeletal research.

<h2 class="heading hide-accessible">Full description</h2>

<p>The present project aims at developing SAP-gene therapeutic combination treatments through peptide-chemistry, biomaterial sciences as well as molecular and cell biological approaches in vitro. The project has the potential to generate new intellectual property, preclinical research data, and facilitates interdisciplinary collaboration. SAP-gene therapeutics will be optimised and characterised regarding the physicochemical properties of the peptide sequence, and release studies will be performed via several analytical techniques (HPLC MS/ UV and FTIR spectroscopy). Biocompatibility and gene delivery efficacy testing in cell culture will be performed using clinically relevant mesenchymal dental pulp stem cells (DPSCs) extracted from teeth. Furthermore, a novel strategy incorporating functional groups for cross-linking therapeutic DNA with SAPs to improve payload delivery will be investigated.</p> <p>Successively to delivery optimisation, this project will investigate osteoinductive, angiogenic, and antimicrobial candidate genes and gene-activated matrix systems in 3D DPSC cultures to identify the most promising delivery strategies for subsequent translation-geared preclinical development.</p> <h4>Aims and Objectives</h4> <p>Development of a translation-geared advanced injectable material for the combination treatment of periodontal defects using regenerative and antimicrobial cues.</p> <ul> <li>Self-assembly peptide (SAP) matrix optimisation for gene delivery &amp; regeneration</li> <li>Preclinical characterisation and incorporation of regenerative therapeutic genes</li> <li>Preclinical characterisation and incorporation of antimicrobial therapeutic genes</li> </ul> <h4>Interdisciplinary research areas</h4> <ul> <li>Dentistry/Periodontology</li> <li>Regenerative medicine &amp; biomaterials science</li> <li>Molecular Biology</li> <li>Microbiology</li> </ul>

<h2 class="heading">How to apply</h2>

<p>Applications can be made at any time. To apply for this project applicants should complete a<a href="https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form"> Faculty Application Form</a> and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a> to inform us you would like to be considered for this project.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: &acirc;&euro;&cent; British Council IELTS - score of 6.5 overall, with no element less than 6.0 &acirc;&euro;&cent; TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

<h2 class="heading">Contact details</h2>

<p>For further information please contact the Graduate School Office<br /> e: <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>, t: +44 (0)113 343 8221.</p>