Awaiting Public Project Summary

The global market for surgical meshes is over $1 billion and increasing due to increasing obesity and aging populations. Despite being a well-established market there remain unmet needs and attractive opportunities for advanced mesh materials which promote rapid endogenous healing and reduce risk of rejection and infection. In this proposal two SMEs, The Electrospinning Company Ltd. and Collagen Solutions plc., will combine their expertise in synthetic and biological materials to develop a ‘bio-synthetic’ hybrid material that combines the advantages of synthetic polymers, such as flexibility, strength and consistency, with the bio-performance advantages of collagen, such as providing cell recognition sites for cell adhesion, proliferation and ultimately improved tissue regeneration at wound sites. Electrospinning technology will be used to create a non-woven mesh with dual properties.

For many of us, there is hardly any more life-changing disability imaginable than loss of sight. Whether through trauma or disease, the inability to rely on visual cues impacts on all matters of daily life; doing your job or bringing your kids to school are no longer straightforward activities. Blindness or reduced sight is often caused by a damaged conjunctiva, a super-thin layer of cells covering the white of your eye and inside of your eye-lids. Fortunately for many in the western world, repair of this damaged tissue is possible through established surgical procedures, many of them using a tissue graft sourced during birth called the amniotic membrane (AM). Microscopically, the AM closely resembles the damaged ocular tissue and can be used as a patch (Amniotic Membrane Transplantation, AMT) to help the body regenerate the damaged tissue. There is however a caveat, our population is ageing and AMT is expected to rise. As it can only be sourced during birth (usually during C-section), AM supply is not available in (virtually) unlimited supply, increasing its price and healthcare costs. Furthermore, AM is often stored in expensive facilities with a significant administrative burden (donor tissue traceability), further adding to the costs. Last but not least, donor tissue regulation, unlike medical device regulation, is complicated for international deployment. In developing countries such as India and China, loss of sight is closely correlated with occupational hazards (i.e. chemical burns of the eye) and is estimated that over 2M people in India alone would benefit from AMT procedures. However, high costs and non-existent national tissue donation regulation literally leave these people in the dark. The aim of the proposed project is to assess the technical and commercial feasibility of developing a fully resorbable synthetic AM alternative. The use of nano-fibre technology, called electrospinning, to fabricate such a device will closely mimic the native AM and ocular tissue. Successful adoption of such a device would directly address the global shortage in AM, easing the pressure on tissue banking and simplifying regulation for swift market deployment (medical device). Furthermore, the manufacturing process can be scaled to meet global demand, allowing cost-effective production for low-income countries and making a truly impact on a global level, made in Great Britain.

This project will progress the development of the Symatix medical device for corneal repair and evaluate the device’s efficacy in vivo. The Symatix device is an innovative, synthetic biomaterial designed to support healing in cornea repair and recalcitrant wounds. It can replace the use of Human Amniotic Membrane (HAM) which has been successfully used for several decades despite having up to 40% failure rate due to its variable nature as a tissue-derived material. HAM is expensive and its availability limited by the complicated supply chain from tissue donation through to implantation. This is a particular problem in developing countries with low tissue donation rates and poor regulatory infrastructure where the clinical need is greatest due to high levels of corneal trauma in manual labour. As a synthetic product, the Symatix device will provide the surgical benefits of HAM but with a step change in availability, affordability and product reliability. If successful, the Symatix device can offer more predictable outcomes to patients, reduce the number of patients that need repeated treatment and extend the opportunity for such treatment to a much greater pool of potential patients. To date, Symatix membrane has been tested in a range of laboratory studies. Product design and development has been guided by surgeons including Dr Sangwan, Director at Dr Shroff's eye hospital in new Delhi and the LVPrasad eye institute in Hyderabad and Harminder Dua, Professor of Ophthalmology at University of Nottingham (UoN) and Consultant ophthalmologist at QMC Nottingham, partner in this application. Both are interested in clinical evaluation of the product. In this project TECL will conduct pre-clinical efficacy tests on the Symatix device and prepare the device for pre-clinical biocompatibility testing. It will improve the manufacturing process to ensure reproducibility and scalability. The University of Nottingham will conduct in vitro cell tests and laboratory evaluations on samples to compare the performance of the Symatix device with HAM and lead on clinical trial design and patient involvement. The output of the activities will be: • Data on the performance of Symatix, also in comparison to HAM • Negotiations with licensing partners to take the device development forward and fund subsequent biocompatibility tests

The project will develop 96 well microplates with fixed electrospun nanofibre scaffolds for use in 3D cell-based assays. There is strong demand in the pharmaceutical industry for more predictive efficacy and toxicology in vitro assays to reduce both the number of costly drug failures in clinical trials and the number of animals used in pre-clinical testing. Despite significant interest in the use of 3D cell-based assays, 3D techniques have not yet been adopted into mainstream research programmes because current formats do not meet industry requirements for highly consistent, off-the-shelf, easy to use products that are compatible with standard automated handling and imaging equipment. The Electrospinning Company (TECL) has developed an innovative microplate into which is laser welded a fibre scaffold, and which has been shown to support the growth of a model breast cancer cell line in 3D. This project will improve this prototype to meet pharmaceutical industry specifications. Cell loading efficiency will be increased to over 90% by testing scaffolds of different fibre specifications, by coating with proteins that increase cell-scaffold anchorage and by pre-loading with denser medium. The optical properties of the plate will be optimised for use on confocal high content analysers by incorporating a glass base plate of appropriate refractive index, and we will reengineer the fabrication process to deliver this cost-effectively. A protocol to sterilise coated scaffolds without damaging the proteins will be developed. The results of these investigations will be used to design a 96 well microplate which will be validated with cell-based assays to prove the concept that it can support the growth of cells in 3D with high reproducibility batch to batch and well-to-well and with the benefits of 3D cell culture. TECL will work with UK SMEs Avanticell, Orla Protein Technologies and 4titude to access expertise in cell-based assays, protein coating and design and manufacture.