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

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.

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.