Oxford Biomaterials Limited Public Funding

The project will deliver preclinical data for a novel silk-based haemodialysis graft, ultimate validation which will bring the graft to the first human trials. There are 3.2 million patients treated for End Stage Renal Disease worldwide, a number increasing by 6% each year. Those treated by dialysis require blood filtering 3 times a week to replace kidney functions. The most effective approach is to create a fistula connecting an artery directly to a vein in the patient’s arm. Where the veins are unsuitable or exhausted following long standing dialysis, a synthetic graft is implanted to connect an artery to a vein. However, current commercial grafts on the market are inefficient, as a consequence of their material composition. Most grafts require 2 post-operative interventions a year to remain functional and over 75% are replaced within 2 years. By comparison, over 70% of fistulas are functioning after 18 months. This project will deliver a novel, more biomimetic haemodialysis graft based on natural silk proteins, material very different to those used so far in dialysis grafting applications. The graft leverages silk’s natural properties and OBM’s proprietary silk processing technologies to combine the advantages of existing biological and synthetic grafts. In vitro evaluations performed against competitor’s products have produced very promising results, showing a significantly improved performance over existing grafts. We therefore aim to offer the first efficient alternative to the gold standard fistula by simultaneously addressing the multiple factors contributing to current graft failure. The prototype has been optimised in previous development phases and will be ready for ultimate validation in-vivo to be carried out in this project. By reducing multiple post-operative interventions, our silk graft promises to improve the quality of life of this large, growing and currently underserved patient population and significantly reduce the overall dialysis costs

Awaiting Public Project Summary

This 12 months project aims at developing a new economically viable process to produce nonmulberry silk solutions and to offer scaffolds with increased tissue regenerative potential. Silk solutions extracted from the domesticated Bombyx mori can be assembled into a wide range of materials, from hydrogels, films to sponges and composites, all particularly suited to biomedical applications due to their protein composition. Several varieties of wildtype (or nonmulberry) silkworms have a range of mechanical properties closer to native tissues as well as cellular adhesion motives naturally occuring in their protein sequence, both significantly enhancing the potential to repair or replace damaged tissue. However the exploitation of their protein solutions has been limited so far, as extracting the proteins from their highly crosslinked fibres requires extensive and hazardous chemicals treatments, preventing future manufacture. Under this proof of concept project, OBM will develop a new, ecological process to produce non-mulberry silk solutions, with potential for upscale and commercialisation.

Low-energy, high-quality wet processing of sustainable polymeric materials is a key societal and economic challenge facing today’s polymer industry. Our answer is to exploit a source of natural polymer feedstocks, silk, to provide a sustainable solution to the production of engineering plastics.

Oxford Biomaterials is a company developing novel medical implants made from silk protein materials. The company is seeking external expertise in computational modelling to reduce the need for iterative prototyping of its novel silk-based hemodialysis graft.

The project will produce an optimised novel non-degradable silk-based graft for dialysis to demonstrate the graft’s suitability for haemodialysis applications and will deliver prototypes for a first implantation in-vivo. There are 2 million patients treated for End Stage Renal Disease worldwide, a number increasing by 6-7% each year. Those treated by dialysis require blood filtering 3 times a week to replace kidneys function. The most effective approach is to create an arteriovenous fistula connecting an artery directly to a nearby vein in the patient’s forearm. Where the veins are unsuitable, a synthetic graft is implanted to connect the artery to the vein. However, current synthetic grafts on the market are inefficient, as a consequence of their material composition. Most grafts require 2 post-operative interventions a year to remain functional and over 75% are replaced within 2 years. By comparison, over 70% of fistulas are functioning after 18 months. This project will deliver a novel graft prototype using natural, commercially available silk proteins formed into a bio-mimetic tubular scaffold and with properties tailored to the specific requirements of haemodialysis. The optimised prototype will be tested to demonstrate its superior mechanical and biological characteristics and prepared for in-vivo evaluations. The biomimetic and inherently biocompatible graft will offer the first real alternative to the gold standard fistula. As it will be better integrated and lasts longer than current products, multiple post-operative interventions will be eliminated, significantly improving quality of life and reducing overall dialysis costs to the NHS and other healthcare providers worldwide.

Awaiting Public Summary