Pre-clinical validation of a Braided Electrospun Cord designed for ACL reconstruction

Anterior Cruciate Ligament (ACL) tears affect an estimated 20,000 people per year in the UK, the majority of which are teenagers and young adults (16% under 19yo, 40% between 20-29yo). These injuries can cause a profound reduction in quality of life and decrease physical activity. Furthermore, they increase the risk of osteoarthritis in an otherwise young and fit patient population. Around 80% of cases require surgery and these are typically done through reconstruction. ACL reconstruction (ACLR) often utilises autografts such as hamstring grafts. Although ACLR with autografts aims to restore knee stability, it suffers from limited donor-site availability (particularly in young patients), consequent harvest-site morbidity and re-rupture in 15% of cases. Furthermore, contralateral ACL rupture and removal of native tissue contribute to higher rates of knee osteoarthritis. Postoperative pain management using injections of anaestethics and various drug combinations, is common.

To replace the need for autografts and improve outcomes, we have developed BioLig, a unique synthetic braided cord made of polycaprolactone (PCL) that can be implanted with existing fixation devices and methods used in ACLR. BioLig can stabilise the knee mechanically and is designed to encourage tissue repair. The soft cord is made by electrospinning to mimic the structure of the extracellular matrix of ACL and provide physical cues that stimulate tissue infiltration from the torn tissue ends. This was demonstrated both with human ACL tissue explants and in a pilot in vivo study in sheep. Unlike other electrospun competitors, BioLig is sufficiently strong for its application in humans. Furthermore, PCL is a well-known polymer that has proven track record of safety and that degrades completely over time (<4y) to leave newly formed tissue.

The main goal of this translational project is to collect robust in vivo data that will support a future safety clinical trial application. This will be achieved through performing:

(1) documentation and cleanroom production activities,

(2) key Good Laboratory Practice (GLP) in vitro assays,

(3) a 12-month in vivo ovine preclinical study with a mechanical primary outcome and GLP evidence of safety (local tissue response and systemic toxicity).

If proven successful in the ovine in vivo study, we will be in a position to prepare a compelling dossier to obtain approval from the MHRA for performing a first-in-man study. BioLig will also represent the first significant step forward for synthetic ligaments in decades and it will give the UK the lead in the development of a solution for ACL treatment that could overtake the gold standard of reconstruction with autografts.