The regenerative medicine company’s CelGro® platform forms the basis of a specialised collagen ‘rope’ that could help reconstruct the anterior cruciate ligament (ACL), a strong band of tissue linking the thigh and shin bones that can rupture during athletic activity.
Essentially, the pre-clinical study found that using the collagen rope is a viable alternative to the current gold standard for ACL reconstruction, which involves transplanting a patient’s own tissue to repair the ligament tear.
If it enters development, the treatment candidate could be the first off-the-shelf biological device used in ACL reconstruction.
A potential first
Commenting on the study’s findings, Orthocell managing director Paul Anderson said the company was “extremely excited” by the potential of this new application for its CelGro® platform.
“There are currently no biological off-the-shelf solutions that mimic native ligament to enable the optimal repair of ACL injuries and synthetic alternatives have proven to be disastrous for patients.
“… Orthocell is ideally placed to deliver the CelGro® collagen rope in this rapidly growing and lucrative market.”
With the early findings in tow, the company intends to replicate the study in a larger animal model like sheep, because this mammal has knee joint structures and dynamics that are closer to a human’s biology.
After that, Orthocell hopes to move into first in-human trials using the collagen device.
The results are in
In order to test the collagen rope against mainstream surgical solutions, Orthocell set out to conduct a pre-clinical study using rabbits.
Essentially, the program was designed to determine whether the device was equal to or better than the gold-standard autograft for ACL reconstruction.
During the study, 30 rabbits received the CelGro® collagen rope, while another 30 underwent hamstring tendon autografts.
Scientists compared the performance of both treatments at the six, 12, 18 and 26-week mark after surgery was complete.
Ultimately, the pre-clinical evidence indicates that the collagen rope is a potentially superior off-the-shelf alternative to the current gold standard tendon autograft.
Specifically, at the 26-week mark, the study indicated that the collagen rope:
- Promoted ligamentisation of the collagen rope into ligamentlike tissue;
- Exhibited comparable tissue architecture to hamstring tendon autograft and, importantly, closely mimicked that of native ACL;
- Promoted integration of the ligament into bone in the same fashion as normal ACL; and
- Exhibited comparable biomechanical properties to human hamstring tendon grafts.
Data from the pre-clinical study that compares the CelGro® collagen rope’s performance to the gold standard autograft treatment against the native ACL’s metrics.
Orthocell chief scientific officer Professor Ming-Hao Zheng led the study in conjunction with the University of Western Australia.
His team will present on the key findings at the 26th Australian and New Zealand Orthopaedic Research Society Annual Conference on October 6.
Growing health economic burden
The ACL is one of the key ligaments that provides stability and mechanical support to the knee joint, but if this tissue sprains or ruptures, it can mean a long road to recovery for patients.
That’s because an ACL injury usually requires surgical intervention, with a long period of rehabilitation required before a patient can get back to their pre-injury activities.
Around 15,000 ACL knee reconstructions take place every year in Australia, while in the US, the numbers are as high as 200,000.
Economically speaking, the lifetime burden of ACL tears in the US alone is estimated to be more than $7.5 billion every year when treated with an ACL reconstruction, while that figure balloons to $17.5 billion when treated with rehabilitation.
ACL injuries can be associated with sports, especially those which involve pivoting such as netball and gymnastics. Source: CHUTTERSNAP/Unsplash.
Treating ACL injuries: the current problems
Currently, ACL repair involves one of two conventional treatment options.
The first, which involves transplanting the patient’s own tissue — typically from a hamstring — to the repair site in a process known as an autograft.
This procedure is currently the gold standard for this kind of tendon repair.
However, the procedure is time-heavy and can involve significant pain, and there’s also risk of nerve damage to the patient.
Alternatively, surgeons can use a synthetic LARS ligament, but this option isn’t viable in the long term because of the implant’s poor durability.
In fact, a 2020 journal article indicated that as many as one in three patients recorded LARS ligament failures.
This outcome not only causes further injury and requires more surgery to remedy, but distributes small plastic fragments throughout the body as the ligament shreds.
As a result, Anderson said: “An off-the-shelf biological device that augments ACL reconstruction and is biologically compatible is highly desired by the orthopaedic industry.”
Enter the collagen rope solution
To combat the problems associated with conventional ACL grafts, Orthocell has developed a rope structure that’s made up of braided collagen fibres.
Once implanted during surgery, the rope can help reconstruct the ligament without the need for an autograft or synthetic implant.
The collagen rope that could be used to repair ACL injuries is built using Orthocell’s flagship medical device: the CelGro® platform.
Essentially, CelGro® is being developed as an assistant for tissue repair that could one day be used across nerve and tendon repair surgeries.
Once the medical device is placed over an injury, a ‘smooth’ layer of collagen fibre bundles help deliver all-important nutrients to the repair site while keeping external tissue at bay, giving the tissue the best shot at regeneration.
Then, a ‘rough’ layer of collagen bundles create a scaffold, providing support for new cell growth as the tissue starts to heal.
From here, cells from the regenerating tissue mingle with the collagen fibres, paving the way for further tissue regeneration.
Once CelGro® has done its job, it’s absorbed into the patient’s own bloodstream — meaning there’s no further work required to remove the surgical device.
Owing to its protective and nurturing properties, CelGro® can be used by itself or with other cell therapies.
Already, it’s being used in dental offices around the world, but further clinical studies could see the device branch into other applications.