Title: A novel electrospun patch to augment rotator cuff tendon repair
Funder: Department of Health and Social Care

Abstract: Rotator cuff tendon tears are a common cause of pain and disability and their management represents a substantial and growing social and economic burden. Evidence from cohort studies and a large multicentre NIHR funded randomised controlled trial of open versus arthroscopic rotator cuff repair in 273 patients recruited from 19 centres in the UK revealed that overall 40% of repairs fail within 12 months. A failed repair adversely affects patient outcomes. The innovation we will further develop is a novel material (Biopatch) that is designed to stimulate the endogenous repair of tendon using biophysical cues when in contact with the torn tissue. Biopatch is constructed of biodegradable electrospun polydioxanone (PDO) nanofibres and is designed and manufactured to mimic the hierarchical architecture of normal tendons. It is laminated with a woven PDO layer that provides mechanical support to the repair and which allows the patch to be secured in place during surgery. Thermoplastic bonding of the two layers is achieved with a thin layer of polycaprolactone (PCL) that melts at a lower temperature than PDO. Laboratory and pre-clinical studies (in vitro and in vivo) have demonstrated that the material stimulates cell growth and new tissue formation, and has a good safety profile. We aim to significantly reduce the current failure rate of surgery and to improve patient outcomes. Accordingly we propose four workpackages each with deliverables and milestones. Workpackage 1 Objective Manufacturing the Biopatch in a cleanroom under good manufacturing practice (GMP) conditions. The design of Biopatch has been frozen. We are currently finalising the manufacturing and up-scaling process which would enable us to manufacture Biopatch in large volumes in a cleanroom environment and according to the regulatory requirements for clinical trials and commercialisation. In addition, we are working together with ISO 17025 accredited laboratories to further test and validate the biocompatibility of our product in compliance with regulatory and industry standards (ISO 10993). The arrangements for packaging and sterilisation of Biopatch are in place and a quality control and quality and risk management system are currently being developed with input from external regulatory consultants. 6 months GO signal: Manufacturing of 150 scaffolds to GMP standards Workpackage 2 Objective Obtaining regulatory and ethical approval for a clinical trial. We will complete our device dossier and clinical investigation plan for MHRA regulatory approval (the content of the dossier will be put together with the clinical evidence from the trial when approaching notified bodies for CE marking and commercialisation). 150 patches are required to complete the trial and preclinical testing. 9 months GO signal: MHRA and ethical approval Workpackage 3 Objective Undertaking a first-in-human clinical trial assessing safety and feasibility. We will conduct a first-in-human clinical trial of the Biopatch using a single arm design where patients requiring a rotator cuff repair receive the Biopatch implant during surgery. The first 3 patients (recruited in Oxford) will have their 1 month outcome sequentially assessed prior to recruiting the next participant to ensure patient safety at the very early stage. An ultrasound guided biopsy will be performed to ensure no adverse tissue response. Given positive findings, twelve further patients will be recruited in Oxford, Southampton, Leicester, Cardiff and Plymouth. 30 months GO signal: Successful use of Biopatch and completion of the clinical trial Workpackage 4 Objective Exploring commercialisation of Biopatch. Although partnering and licensing are possible, the current strategy is the creation of a spinout company focused in the field of medical implants for soft tissue repair. It may be preferable to undertake an investigator led randomised trial in order to demonstrate clinical efficacy. 36 months GO signal: Successful commercial development of Biopatch

Lay abstract: Shoulder muscles and tendons allow us to move our arms, carry out daily activities, work and play sport. Pain arising from tears of these tendons can cause significant long term disability. Currently 10,000 patients annually in England have torn shoulder tendons, called the rotator cuff", that require surgical repair and this number is increasing. Unfortunately around 40% of these surgical repairs fail which can result in long term disability. Various approaches have been used to protect and strengthen the surgical repair. Unfortunately none of these attempts to reduce the number of surgical failures have so far proved successful. We have developed a new type of synthetic degradable patch which is made of very fine fibres that mimic a normal tendon and a woven material that gives it strength (Biopatch). We believe this new material will promote much better healing when used to bind the torn tendon to the bone. The synthetic polymers used in Biopatch are already in common use in surgery as sutures and have an excellent safety record. We propose undertaking a research study (called a clinical trial) in patients to determine if the Biopatch can be used safely, and if surgeons can easily use it to treat a rotator cuff tear. If successful we then hope to involve commercial partners to allow scale up and more widespread use of Biopatch. Patients have been involved in this project from its outset and will continue to be involved throughout the clinical trial and during dissemination of the findings. We aim to reduce significantly the current failure rate of surgery and to improve patient outcomes. If successful this technology could be used in a much wider range of surgical applications where improved soft tissue repair would benefit patients."

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL