Bioresorbable 2D and 3D ordered mesoporous phosphate glasses for bone tissue regeneration and drug delivery

Lead Research Organisation: University of Surrey
Department Name: Chemistry

Abstract

Regeneration or repair of hard and soft tissues represents a major challenge of the modern society. The number of patients that require an implant in order to replace damaged tissue is growing due to the increase of life expectancy. Therefore, the development of new and more efficient biomaterials is a great scientific and human challenge as it has an effect on the everyday life of millions of people worldwide. It has been forecasted that the global market for biomaterials will reach about $130B by 2020.

The function of biomaterials has evolved with time. The first generation of biomaterials had a pure mechanical role with no interaction with the physiological environment (e.g. metals). More recently, a second generation of biomaterials, defined as bioactive, based on calcium silicate glasses has been developed. Their key feature is the capability of their surface to spontaneously with physiological fluids in the human body generating a bone-like layer of hydroxyapatite Ca10(PO4)6(OH)2. Human cells grow and proliferate on this layer promoting a tight bond between the implant and the living tissue. As silicate based glasses are non-soluble in physiological fluids, a subsequent surgery is needed to remove the implant with increased risk for the patient and a lengthening of the total recovery time.

This proposal refers to the latest generation of biomaterials also called "third generation". In addition to the bioactivity, they also show bioresorbability as they react and dissolve over time in the physiological fluid and they are replaced by regenerated hard or soft tissue. The use of soluble bioresorbable materials avoids the necessity of a second surgery. Phosphate-based glasses, differently from the commercially used polymers, are ideal bioresorbable materials being totally biocompatible as any of the degradation products can cause inflammation.

The aim of this proposal is to design, for the first time, phosphate-based glasses with highly ordered structure of mesopores (2-50 nm) and high textural properties (large surface area, pore size and volume, narrow pore size distribution) using a combination of supramolecular chemistry and sol-gel. Phosphate based glasses with ordered 2D channels of mesopores aligned in one direction and 3D ordered cubic network of interconnected pores are excellent candidates for multifunctional biomaterials, being able to combining simultaneously anti-bacterial/anti-cancer activity with cell stimulation and vascularisation.

This makes them ideal materials to be used in two major clinical applications: orthopedics (bone pins and anchors, bone platelets, joint replacements, tissue fixation screws) and drug delivery (e.g. anticancer drugs, antimicrobial agents, growth factors, DNA).

I will demonstrate this potentiality through synthesis and textural/structural characterisation of phosphate glasses with composition close to the bone (P2O5-CaO-Na2O) with and without addition of antimicrobial ions (Ag+/Cu2+/Zn2+) followed by dissolution and biocompatibility tests.

Planned Impact

This proposal comprises leading edge physical and materials chemistry/science and aims to manufacture bioresorbable implants with synergic biocompatibility and controlled drug delivery to benefit society and improve the quality of life within the UK.

A direct output of the proposed project in short term (1-2 years window) will be highly skilled researchers (a postdoctoral researcher, a PhD student, MRes students and undergraduates interns) who will have developed multidisciplinary skills and will have experienced a broad range of technological fields that are important to the development of functional biomaterials, from the synthesis to the in-vitro testing for biocompatibility and antimicrobial activity.
Moreover, the research programme will introduce several new collaborations with UK and overseas Universities (UCL, Kent, Warwick, Queen Mary in the UK and Cagliari in Italy). In particular, the collaboration with Eastman Dental Institute, UCL will give me the opportunity to directly translate the novel materials into development of novel treatments and therapies for treating oral disorders. The UK and international partners are committed to supporting aspects of this project within their own research capacity. Further collaborations with leading groups and the development of multidisciplinarity research projects will be fostered during this project.

Commercial beneficiaries of the research (wealth generation in 5-25 years) will be companies in the UK and worldwide in, or part of the supply chain for, bioresorbable implants. In particular, healthcare companies through the design of new materials with antimicrobial properties and localised drug delivery and medical device manufacturers through the design of implants for orthopaedics and dentistry, devices to assist with brain injuries (dissolvable sensors to monitor patients with traumatic brain injuries), neurodegenerative diseases (nerve conduits) and wound repair (resorbable sutures).

Research on new materials and recipes that could facilitate advanced bioresorbable implants could impact these industries in the long term by incorporating these concepts within their product technologies. There is a significant gap in the research relating to bioresorbable materials alternative to polymers. The strategy of this proposal bears significant impact for the bioresorbable materials industry, as I foresee the reshaping of the existing market of polymeric materials, with the potential to facilitate novel applications that in turn could provoke further R&D investments for auxiliary exploitation in emerging products and services. Besides, the spin-off consulting company SPINODE, world leader in taking bioactive glass technology to market is actively supporting this proposal (see letter of support), being particularly interested in the potential of ordered mesoporous phosphate glasses technology, offering expert advice and opportunities for translation. The SPINODE support demonstrates a clear commitment for realising industrial research impact, but also attracting additional investments to capitalize on this technology.

On successful commercialisation, society will ultimately benefit (25-50 year longer term) as breakthroughs in the proposed technology sector will have a huge impact on quality of life of people suffering traumatic injuries preventing bacterial infections and promoting natural healing process.

This proposal aims to realise research impact through academic excellence and a willingness to work in an interdisciplinary environment. Although this proposal is aimed at addressing bioresorbable phosphate glasses synthesis challenges, the culminating impact stems from all research activities planned throughout the project, concurrently providing insights into science's fundamentals.

Publications

10 25 50
 
Description Mesoporous phosphate-based glasses in the system P2O5-CaO-Na2O undoped and doped with copper and zinc ions have been prepared for the first time. Hexagonal channels of mesopores hcan be clearly identified. All samples show antibacterial activity.
Exploitation Route Mesoporous phosphate-based glasses can find use as biomedical materials but also but also in catalysis, electronics (fast ions conductors) and energy (glass to metal seals for solid oxide fuel cells).
Sectors Chemicals,Energy,Environment,Healthcare

 
Description We are currently running an Impact acceleration account project with NPL which started from the outcomes of this EPSRC award on the use of phopshate-based glasses nanosphere as ultrasound contrast agents.
First Year Of Impact 2017
Sector Healthcare
Impact Types Societal

 
Description Chemistry Degree MChem course. Final year Advanced Topics inPhysical Chemistry module
Geographic Reach Europe 
Policy Influence Type Influenced training of practitioners or researchers
Impact Result of reserch have been included in the final year module Advanced topics in Physical chemistry, taught at the University of Surrey
 
Description Capital Award Competition
Amount £153,000 (GBP)
Funding ID EP/S017771/1 to University of Surrey 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2018 
End 03/2020
 
Description Impact Acceleration Account
Amount £60,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 11/2018 
End 07/2019
 
Title A novel technique for production of mesoporous phosphate-based glasses 
Description A protocol for the synthesis of mesoporous antibacterial phosphate-based glasses containing silver, copper and zinc ions has been established. A short-term publication embargo in line with the standard University Technology Transfer procedures was in place until the GB Priority application number was filed on the 25/1/2019 (GB1901044.6). 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? No  
Impact Increased bioactivity of the glasses proved by acceleration of hydrozyapatite formation and fibroblast cell growth 
 
Description Characterisation of mesoporous phosphate glasses 
Organisation Queen Mary University of London
Department School of Biological and Chemical Science QMUL
Country United Kingdom 
Sector Academic/University 
PI Contribution We have performed interdisciplinary characterisation of samples prepared at the host institution
Collaborator Contribution University of Kent: low angle XRD and density measurements Queen Mary and Warwick: siolid state NMR University of cagliari: Surface area and microscopy Spinode: consultancy on IP Eastman Dental Institute: ICP measurements Aston University, Birmingham: antibacterial studies
Impact As a result of the collaborations, all characterisation performed have proven that the new materials are mesoporous and never been prepared before. As an outcome, UK patent has been filed on 25/1/2019
Start Year 2017
 
Description Characterisation of mesoporous phosphate glasses 
Organisation University College London
Department Eastman Dental Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We have performed interdisciplinary characterisation of samples prepared at the host institution
Collaborator Contribution University of Kent: low angle XRD and density measurements Queen Mary and Warwick: siolid state NMR University of cagliari: Surface area and microscopy Spinode: consultancy on IP Eastman Dental Institute: ICP measurements Aston University, Birmingham: antibacterial studies
Impact As a result of the collaborations, all characterisation performed have proven that the new materials are mesoporous and never been prepared before. As an outcome, UK patent has been filed on 25/1/2019
Start Year 2017
 
Description Characterisation of mesoporous phosphate glasses 
Organisation University of Kent
Department School of Physical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution We have performed interdisciplinary characterisation of samples prepared at the host institution
Collaborator Contribution University of Kent: low angle XRD and density measurements Queen Mary and Warwick: siolid state NMR University of cagliari: Surface area and microscopy Spinode: consultancy on IP Eastman Dental Institute: ICP measurements Aston University, Birmingham: antibacterial studies
Impact As a result of the collaborations, all characterisation performed have proven that the new materials are mesoporous and never been prepared before. As an outcome, UK patent has been filed on 25/1/2019
Start Year 2017
 
Description Characterisation of mesoporous phosphate glasses 
Organisation University of Warwick
Department Department of Physics
Country United Kingdom 
Sector Academic/University 
PI Contribution We have performed interdisciplinary characterisation of samples prepared at the host institution
Collaborator Contribution University of Kent: low angle XRD and density measurements Queen Mary and Warwick: siolid state NMR University of cagliari: Surface area and microscopy Spinode: consultancy on IP Eastman Dental Institute: ICP measurements Aston University, Birmingham: antibacterial studies
Impact As a result of the collaborations, all characterisation performed have proven that the new materials are mesoporous and never been prepared before. As an outcome, UK patent has been filed on 25/1/2019
Start Year 2017
 
Description Presentation of the research at Queen Mary University, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact Several undergraduates attended the talk entitled: "Antibacterial phosphate-based glasses for biomedical applications" and a discussion has arisen on the topic
Year(s) Of Engagement Activity 2018