Frequently Asked Questions
How does the gelation process work?
Syringe A contains the chitosan polymer in acidic solution. The B1 and B2 syringes constitute a pH buffer system which neutralizes solution A and triggers the gelation process. The whole amount of the constituted buffer needs to be used in order to actually allow the gelation process to take place; think of it as the starter. The speed of the process is influenced by the temperature: the warmer, the faster; think of temperature as the accelerator.
What are the important aspects of the product mixing process?
Endeavor to transfer the B1+B2 syringes entirely to one side. Due to the small volumes, a few drops can have an impact on the initialization of the gelation process. For the final step, push vigorously the contents of the A syringe into the combined B syringe and continue with several vigorous back-and-forth motions (approximately 10-15 times) until mixture is completely homogeneous.
How long should it take to set?
If JointRep® is taken out straight from fridge, 3-5 min. If it is left at room temperature, 30-60 sec. It’s advisable to choose the temperature so as to leave more time for injection, as the gelation process is not reversible. If too much time elapses before administering the combined product, it will gel inside the syringe and be ejected in clumps.
Which syringe should be used with JointRep®?
We recommend an 18-16G needle or a spinal one.
What happens if we used a needle smaller than 18G in caliber?
It could make the delivery more difficult as the needle could get clogged after some seconds after the mixing took place. A needle 18 or lower minimizes this risk and allows for a better delivery of the hydrogel.
How should the lesion be prepared?
As per updated standard Bone Marrow Stimulation (BMS) procedures, the calcified layer of cartilage should be removed, etc. The lesion should be dried to a reasonable extent.
How long does JointRep® remain in the lesion after injection?
The exact amount of time is not known, but it might be around 6 weeks, which is more than enough to accomplish its intended use, namely, physically protecting the blood clot and the subsequent maturing granulation tissue during the early phases of induction and modulation of the body’s natural healing response. There is a monography for the product available; many of the possible answers to questions regarding the implant itself are addressed within this document (1).
When applying JointRep®, will the hydrogel flow along the joint surface and fit the shape of the defects automatically?
When applied into the previously prepared focal chondral lesion (not the joint surface), the viscous implant will automatically fit the shape of the defect. No further action is needed.
Do we need to smooth the surface manually? If yes, what instrument will you suggest to use?
No, there is no need to smooth the surface of the implant. The amount of implant administered, or its surface characteristics are not predictors of its final amount or shape as the implant will be replaced by maturing granulation tissue first and then by new chondral tissue, following natural biological pathways
During the application, if the hydrogel overflows the defect,
will the hydrogel stick/adhere to other tissues or the articular surface of the opposite side?
It is preferable not to overflow the defect. But if this happens, the implant is completely harmless for the rest of the synovial organ. You might have a slight increase in post op pain or effusion, but this will be transient and mild. The excess of implant will not adhere to the other tissues or the articular surface of the opposite side.
If we apply too much hydrogel over the defect and it becomes "protruded or “proud”, will the cartilage on the opposite side be painful after being pressed?
Not at all. The excess of implant will just be pressed out from the lesion; its consistency will never cause any damage to the other joint surfaces as it is an hydrogel.
During the surgery, do we need to drain out all liquids, including the normal saline and the synovial fluid, from the joint cavity? or can all the liquids be retained?
For the implantation itself, the joint must be drained from the fluids used for a standard arthroscopy and switch to a dry procedure. This is a standard arthroscopy gesture, and it does not take more than 5-7 minutes. The lesion itself must be as dry as possible. If some amount of liquid is found outside of the treated lesion itself, it is not a critical issue.
What is the nature of the cartilage generated by bone marrow?
The new cartilage obtained with Bone Marrow Stimulation (BMS) type of procedures varies in its hyaline nature, ranging from a fibrocartilage to a tissue with more of what is called “hyaline characteristics”, meaning mostly Collagen 2 content and orientation, stratification of the tissue, proper degree of hydration, GAG content and absence of Collagen 1 fibers (but for the surface where it is normal to have such fibers). With an enhanced BMS (like in the JointRep® procedure), the hyaline characteristics of the generated tissue are more consistently achieved, with less failures. This has been proved with the preclinical and clinical work on the first generation of Chitosan-based products for cartilage repair (BST-CarGel) and published in first line peer reviewed journals (2, 3, 4, 5, 6). JointRep® is the second generation of chitosan-based products for cartilage repair and its mode of action is identical to the one for BST-CarGel. Its backbone (Chitosan) is the same, and the changes are in the degree of deacetylation and in the non-active components, namely Glucosamine Chloride and Carbonate, which are the substances used to buffer the solution to make it even more biocompatible and easier to handle intraoperatively.
In the presence of more than one lesion, what will be the application steps?
In presence of more than one lesion, the advice is to prepare as usual the lesions and once ready, leave a needle aiming at the center of each lesion before the mixing of the product and then treat each lesion sequentially.
There are no reports of surgeons going out of hydrogel because of the size of the lesions. To our knowledge, up to 3 concomitant lesions have been treated in a patient and there was enough hydrogel to fill all the lesions. For the amounts mixed, and with the usual width of cartilage, lesions up to 10 cm2 or even more could be treated with the available amount of hydrogel. That does not mean that lesions which are bigger than 6-7 cm2 are advisable indications for the use of our implant.
What is the adhesion strength of the scaffold? Does it move or fall after some time?
The scaffold is kept in place by several factors, including its cationic nature. Once in place it adheres to the bottom and the sides of the lesion, which are charged negatively (anionic charge). During in vitro demonstrations (as shown with the videos), the implant adheres to the lesion and is kept in place even when attempts to dislodge the implant with water jets are carried out. During animal tests where the animals were euthanized 2-3 days after the implantation, the totality of the implant was always in place, even without any mobility or weight-bearing restriction. The same occurred with the first-generation chitosan-based product. These observations have been corroborated by the standard clinical use. There are a number of anecdotal observations when surgeons have tested intraoperatively the stability of the implant with flexion-extension cycles, and the implant has always stayed in place; this was true again for the first-generation chitosan-based product, which is less firm in the initial minutes after implantation as it relies primarily on the clotting capabilities of each patient.
What is the maximum size of a lesion that JointRep® can be used with?
Assuming a lesion with a depth of 3 mm (the average width of articular cartilage), with the amount of product you get (around 4.3 cc), you should be able to fill a lesion (or sum of lesions) of around 11 cm2. This is an area that is way beyond the average lesion size, as 75% of the lesions are around 3 cm2. Historically, there have been no reports from surgeons not having enough product to treat the lesions they wanted to fix.
What happens if the quantity injected was in surplus of the prepared lesion? Any risk on the surrounding tissue?
As the components of JointRep® are all generally regarded as safe and are very similar to molecules already present within the synovial joint, they are virtually harmless to the different tissues found within the joint. That does not mean that there can’t be a mild and transient inflammatory reaction which can last for 2-4 days and be easily treated by first line pain control medications. Even if harmless to the joint itself, the product should be implanted only within the lesions.
When can we see JointRep® results via MRI?
The amount of time needed to depict meaningful results on an MRI do not vary for JointRep® when compared to other approaches for cartilage repair (unless for auto and allografts). Usually, an MRI before 6 months is of limited utility. On most clinical settings and in some clinical studies, MRIs are performed at 1 and 2 years after the surgery. Quantitative measures like T2 are used to depict the Collagen 2 content, degree of hydration and stratification. Semi-quantitative measurements like the MOCART-2 are also currently used.
Can we move the knee after closing the incision? What is the advised time frame?
For the knee, the advice is not to move (flexion-extension) the knee for the first 24 hours and to wear a soft brace at all time after the joint (the knee in this case) is straightened. This is to allow the implant to attain its maximum gelification and strength. After that, limited passive-assisted ROM movements can be started and increased. Please refer to the document regarding the suggested physiotherapy program (7). Additionally, as stated above, occasionally we have heard from surgeons testing the stability of the implant performing several cycles of flexion-extension and there is no report of the implant being dislodged after these attempts were carried out.
When can a JointRep® patient start weight bearing and movements? Sports? Cycling?
The weight bearing will depend on the size of the lesion, localization, and other specific factors related to the patient, as stated in the Physiotherapy guidelines document (8), and by the cartilage repair standard of practice. As a rule, after the first 48 hours, a toe-touch partial weight bearing approach can be initiated and then progress according to tolerance until full weight-bearing ideally around week 6-8.
The return to sports depends also on different factors. As a rule, contact sports should be avoided for the first year, but usually patients return to recreational sports at around 9 months. Gym training can be started earlier of course, but always avoiding overstressing the involved joint. Physical activities like swimming are encouraged very early on in the process (as soon as the arthroscopy portals have healed enough to make it safe to enter a pool). Stationary biking, with no or little resistance is encouraged early in the process too (as soon as 110° of flexion are reached). This is the ideal situation, as you are moving your joint, contributing to its natural normal homeostasis including the mechanical influx to the growing tissue, without exercising full weight bearing.
Do you advise using JointRep® with patients suffering from osteoporosis?
Osteoporosis, unless too severe, is not listed amongst contraindications for cartilage repair in general or for JointRep® in particular. It is a condition which needs to be assessed by the treating surgeon and it is up to them to decide if the implant or the procedure are a good fit.
In which stage of joint osteoarthritis can we use JointRep®?
First a precision: in cartilage repair we are dealing with Secondary Osteoarthritis (OA), a different disease from Primary OA, which is probably a systemic one, not a localized condition like in the case of Secondary OA. From the Outerbridge and the ICRS classifications of cartilage lesions, JointRep is meant to be used for Grade III and IV contained lesions.
Does the patient need synovial injection(s) after applying JointRep®? Would there be a clinical benefit?
No, a patient does not need viscosupplementation with Hyaluronic Acid or similar (it is what we assume is meant by “synovial injection”). There is no proof that there can be additional meaningful benefits using such approaches after cartilage repair. However, it could be of help somehow. The benefit would be to help with the reestablishment of the homeostasis of the joint by trying to normalize the rheological properties of the synovial fluid.
What do you advise for the loss of vision right before JointRep® is applied?
If this is happening during the dry arthroscopic procedure, the surgeon should not deliver the implant blindly. The correct visualization of the lesion is crucial so that the implantation is performed in the correct way. The dry arthroscopic technique is something that a surgeon usually is familiar with. If not, our advice is to deliver the implant using what we call “arthroscopically driven mini-arthrotomy”. With this approach, a 2-3 cm incision on top of the lesion is all that is needed, to have direct access to the lesion. To perform such mini-arthrotomy, under the arthroscopic view, the center of the targeted lesion is reached from the outside with a needle, and then the 2-3 cm arthrotomy is performed exactly at this point, the joint is drained of fluids with direct visualization of the lesion. Such a small incision does not alter the recovery pace of the patients.
When can we see structural/ histological enhancement in the lesion?
The maturation period for cartilage repair lasts at least 24 months or more according to most publications and can increase its hyaline nature up to 5 years after the procedure. Nevertheless, around month 6 you can expect to depict meaningful improvements in a test like an MRI using cartilage specific sequences. This is not specific to JointRep® but for cartilage repair at large (9).
Are there any reported cases of JointRep® immune rejection? Age-related contraindications?
No, there are no reports of such cases. The components of the implant are considered safe. Nevertheless, as the Chitosan comes from the shells of crustaceans, in the warnings section there is a statement about its use on people with known allergies to crustaceans. Even if the allergenic portion of the crustaceans is in their flesh (the tropomyosin of their muscles), which is completely absent in the Chitosan powder used for the manufacturing of JointRep®. There are reports of some transient inflammatory reactions in the first 1-3 days after the procedure for less than 1% of the patients, well in line with the usual reported occurrence for arthroscopy in general. So, no regulatory authority worldwide has expressed any concerns about the safety of JointRep® so far. In any case, we advise to clean by aspiration as much as possible the remnants of product within the joint, keeping only what is already contained and jellified within the lesion.
JointRep® has been applied on patients as old as 75 years old. Nevertheless, 65 years old is an accepted upper limit. The other eventual limitations are the ones common to a cartilage repair procedure.
Can JointRep® be applied to treat meniscus illness? Or to adhere bone cracks?
No, this is not an indication for JointRep®.
Can JointRep® be used with PRP, cells, DBM and other biologics?
This is not an actual approved indication to be used with JointRep®. Nevertheless, some surgeons have used it on an “off label” situation and mixed it with blood derived products such as PRP. These substances are mixable with the hydrogel, but no data is available to support its use. When mixed, an amount of 1cc of the added substance is mixed with the B1-B2 syringe contents and then mixed with the A syringe content and applied immediately.
(1) Monographic review JointRep® device. Version 1.2-02AUG2019-Doc ID:-JR001.
(2) Hoemann CD, Hurtig M, Rossomacha E, Sun J, Chevrier A, Shive MS, Buschmann MD. Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects. The Journal of Bone and Joint Surgery 87(12):2671-2686, 2005
(3) Chevrier A, Hoemann CD, Sun J, Buschmann MD. Chitosan-glycerol phosphate/blood implants increase cell recruitment, transient vascularisation and subchondral bone remodelling in drilled cartilage defects. Osteoarthritis and Cartilage 15(3):316-327, 2007
(4) Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Restrepo A, and Shive MS. Novel scaffold-based BST-CarGel Treatment Results in Superior Cartilage Replace Compared with Microfracture in a Randomized Clinical Trial. J Bone Joint Surg Am 95:1640-50, 2013
(5) Shive MS, Stanish WD, McCormack R, Forriol F, Mohtadi N, Pelet S, Desnoyers J, Méthot S, Vehik K, Restrepo A. BST-CarGel® Treatment Maintains Cartilage Repair Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled Trial. Cartilage, 6(2): 62-72, 2015.
(6) Méthot S, Changoor A, Tran-Khanh N, Hoemann CD, Stanish WD, Restrepo A, Shive MS, Bushmann MD. Osteochondral biopsy analysis demonstrates that BST-CarGel treatment improves structural and cellular characteristics of cartilage repair tissue compared with microfracture. Cartilage,7(1):16-28, 2015
(7) Physiotherapy Guidelines-JointRep® Injectable implant. Version 1.2
(8) Ibid (7)
(9) Paatela T , Vasara A, Nurmi H, Kautiainen H, Jurvelin J.S, and Ilkka Kiviranta I. Biomechanical Changes of Repair Tissue after Autologous Chondrocyte Implantation at Long-Term Follow-Up. Cartilage Ahead of printing publication. DOI: 10.1177/1947603520921433, 2020