What is ChondroFiller®?

ChondroFiller is a product line for treatment of defects in the hyaline joint cartilage. It is a biological, acellular cartilage implant on a collagen basis for autoregenerative treatment of joint cartilage defects. The first generation of ChondroFiller – the ChondroFillerGel – was licensed in 2012. This is a pressure-resistant gel plug on a collagen basis. In 2013 the next generation was then already launched with the patented ChondroFiller® liquid. On this product the collagen is liquid and is delivered arthroscopically with a two-chamber syringe into the affected joint. The liquid collagen then forms a gel directly in the cartilage defect and thus adapts perfectly to its shape.

What is the difference between ChondroFiller® liquid and ChondroFillerGel?

ChondroFillerGel was the first collagen implant in the ChondroFiller® product range. It was a gel plug that was available in various sizes (height, diameter). This implant needed to be trimmed to size to match the individual requirements, which represented an additional step for the orthopaedic surgeon. ChondroFiller® liquid is the patented and worldwide unique successor product to this implant. The liquid components of the product are supplied in a two-chamber syringe. By placing a mixing adapter on the syringe and pressing out the components, they are mixed and the pH-dependent gelation of the collagen starts immediately once the collagen has been implanted in the cartilage defect.

What is the classification of ChondroFiller® liquid?

ChondroFiller® liquid is a Class 3 medical device.

For which types of damage to joint cartilage can ChondroFiller® liquid be used?

ChondroFiller® liquid can be used to treat clearly localised cartilage damage in joints such as the knee, ankle or shoulder joints both gently and effectively.

A prerequisite for treatment is grade III or grade IV joint cartilage damage based on the Outerbridge classification, as well as deep and/or subchondral defects and osteochondral defects in the case of partial injuries to the joint cartilage.

ChondroFiller® is available in different volumes for treatment of defects of different sizes:

  • up to 3 cm2: ChondroFiller® liquid, HCFL-23
  • up to 2 cm2: ChondroFiller® liquid, HCFL-15
  • up to 1.5 cm2: ChondroFiller® liquid, HCFL-10

The use of ChondroFiller® liquid in other parts of the body, for example in the outer ear or in breast tissue, is not permitted.

For which indications is ChondroFiller® liquid used?

  • Preserved cartilage shoulder
  • Intact surrounding cartilage
  • Intact corresponding
  • Articular surface (damage to the corresponding articular surface up to a maximum Outerbridge classification of grade II is permitted)
  • Intact meniscus (a partial resection of up to a maximum of 1/3 of the total volume is permitted)
  • Intact ligament guidance, physiological leg axis
  • Free joint mobility
  • Patient’s age: 18 or older
  • Outerbridge defect classification: grade III and IV
  • Defect size < 3 cm2

Are there any contraindications for ChondroFiller® liquid?

  • Hypersensitivity and/or allergy to collagen or rat protein
  • Multi-compartmental arthrosis
  • Hematopoietic diseases
  • Malignant disorders
  • Neurological diseases
  • Increased risk of bleeding
  • Pregnant and breastfeeding women
  • Incapacitated and compulsory treatment patients
  • Patients with a cartilage defect ≥ 2.5 cm in diameter
  • Joint stiffness
  • Arthrofibrosis
  • Joint infections
  • Metabolic disorders
  • Leg malalignment > 5°
  • If surgical procedures are necessary in connection e.g. with

    • Ligament injuries,
    • Meniscus injuries,
    • Leg malalignment of > 5°,
    • Patellar malalignment or
    • Other orthopaedic/accident surgery injuries in which cartilage defects are discovered in the surrounding tissue during the procedure that meet the above criteria; ChondroFiller® liquid can also be used in these cases in accordance with the application rules set out above.

How many surgical procedures are required for ChondroFiller® liquid?

Only one arthroscopic procedure is required for treatment with ChondroFiller® liquid.

Do cells need to be cultivated for the ChondroFiller® technique?

No, ChondroFiller® liquid is an acellular, liquid collagen implant.

How does the matrix conversion from collagen type 1 to collagen type 2 take place?

The migrated chondrocytes synthesise collagen type 2 and convert the collagen type 1 matrix.

How do the cells get into the ChondroFiller® liquid?

Cell bonding to the collagen matrix takes place via beta-1 integrins. Generally speaking, a tissue injury (given as a result of debridement) causes a cell migration. In addition, collagen type 1 has a chemotactic effect on a wide number of cells.

Which cells migrate into the ChondroFiller® liquid?

In animal studies the migration of chondrocytes (morphology, collagen type 2 expression via immunohistochemistry) and, in some cases, mesenchymal stem cells was demonstrated. However, no specific proof was performed.

Can it be demonstrated what quality of cartilage is produced by ChondroFiller® liquid?

Yes, in a preclinical study on the Göttingen minipig the collagen type 2 synthesis (immunohistochemistry), chondrocytary cell morphology and characteristic cell distribution (H&E staining) indicated that, after treatment with ChondroFiller® liquid, hyaline-like regenerated cartilage is generated. In an ongoing, retrospective clinical study on humans this is also indicated by the MRT-T2 mapping.

How was a qualitative analysis of the regenerated cartilage performed?

The regenerated cartilage was investigated in a preclinical study on the Göttingen minipig: collagen type 2 synthesis (immunohistochemistry), assessment of cell morphology and cell distribution (H&E staining), and in a retrospective study on humans: MRT images (T2 mapping).

Does ChondroFiller® liquid contain cytokines or growth factors?

No cytokines or growth factors are added to ChondroFiller

What does ChondroFiller® liquid consist of?

ChondroFiller® liquid consists of collagen type 1 and a neutralisation solution. The high-quality collagen type 1 that meidrix biomedicals uses for ChondroFiller is extracted from rat tail tendons. These animals are SPF rats (specific pathogen free animals) with health certificates. The gel neutralisation solution consists of water, HEPES and salt.

Is there a risk that patients could infect themselves via the ChondroFiller® collagen implant with hantavirus or other pathogens that are transmitted from rats to humans?

No, as the animals are bred to be specific pathogen free and are regularly examined by a veterinary.

What advantage does collagen from rat tail tendons have over collagen produced from tissue from pigs, horses or cattle?

In skin tests, around 3% of the population displays allergic reactions to collagen of bovine or porcine origin. Allergic reactions to ChondroFiller products (collagen from rats) are not known to date.

Are any side effects known?

In rare cases, hypersensitivity reactions (e.g. allergic reactions, inflammatory conditions) can occur in response to collagen or to one of the other ingredients.

What is the mechanism by which gelation of the liquid component into a pressure-resistant gel takes place?

With the aid of the mixing adapter, the two liquid components are mixed with each other when they are pressed out of the two-chamber syringe. Here, the pH value of the previously acidic collagen is neutralised. As a result, the mass starts to form a gel and a pressure-resistant collagen gel is produced.

How can I obtain ChondroFiller® liquid?

ChondroFiller® liquid is sold worldwide in more than 20 countries and can be obtained via our sales partners or from the manufacturer.

Which joints has ChondroFiller® liquid been used on so far?

ChondroFiller® liquid has been used in the following joints to date: knee, hip, upper ankle joint, shoulder, metatarsophalangeal joint, thumb basal joint, wrist.

How is ChondroFiller® liquid stored?

ChondroFiller® liquid is stored in a freezer at between -35 and -15°C. Standard commercially available freezers are normally set to -18°C.

How long can ChondroFiller® liquid be kept for?

ChondroFiller® can be kept for a period of 24 months after manufacture provided it is stored at between -35 and -15°C. The expiry date can be found on the packaging.

Can ChondroFiller® liquid be kept in the refrigerator?

After thawing, ChondroFiller® liquid may be stored for up to four weeks in a refrigerator at 2 to 8°C. If the product has been allowed to reach a temperature of more than 8°C, then storage for more than 24 hours at 2 to 8°C is no longer permitted.

Can ChondroFiller® liquid be refrozen after thawing?


How quickly does ChondroFiller® liquid thaw?

ChondroFiller® liquid can either be thawed for 24 hours at 2 to 8°C, or it is also possible to thaw the product directly before use for approx. 30 minutes at a temperature of approx. 25 to 30°C, e.g. in a heat cabinet.

Which accessories are required for treatment with ChondroFiller® liquid?

For storage: a freezer and/or refrigerator, plus an injection cannula.

In which sizes is ChondroFiller® liquid available?

ChondroFiller® liquid is available in three volumes: 1.0, 1.5 and 2.3 ml

How long does the ChondroFiller® liquid remain in the body? Does the procedure need to be repeated in similar fashion to the technique with hyaluronic acid?

No, only a single procedure is required with the ChondroFiller® technique. The high-quality collagen implant is converted into endogenous, hyaline-like collagen type 1 tissue.

Does microfracture surgery (MFx) need to be performed prior to treatment with ChondroFiller® liquid?


How is the high-quality collagen type 1 implanted in the joint in the ChondroFiller® liquid technique?

As the first step, an arthroscopy of the joint is performed using the standard technique. Here, the indication for application of the ChondroFiller® liquid technique must be checked. Only if all indication criteria are met should this technique be used. Concurrent joint pathologies such as meniscus damage, ligament insufficiencies, joint malalignment etc. should be treated first as part of the procedure.

How does the patient need to be positioned?

Prior to injection of the ChondroFiller® liquid, the affected limb should be positioned in such a way that run-off of the initially liquid collagen implant to the side is prevented. Consequently the positioning depends very much on the localisation of the defect. On femoral defects it is generally sufficient to fix the leg with hip and knee flexion of around 90°. Defects in the area of the tochlea and tibia generally do not require special positioning. Defects on the back of the patella (retropatellar defects) can normally be treated with the patient in the prone position.

Does the defect zone need to be dried prior to implantation, and how is this drying performed?

Yes, prior to application of the ChondroFiller® liquid the cartilage defect zone should be as dry as possible. When using rinsing fluid for the arthroscopy, this should be completely drained. In addition, the cartilage bed should be dried separately. This can be done with the aid of a compress inserted through a working channel. Alternatively, the filling of the defect can also be performed under gas arthroscopy.

How is wound cleaning (debridement) performed?

Debridement of the cartilage damage is performed purely arthroscopically either with a shaver (avoid major build-up of heat) or also with appropriately sized curettes. It is important here that all diseased parts with chondromalacia are removed and that a stable cartilage shoulder remains on all sides. During the preparation of the defect, it is important to ensured that the subchondral plate is not broken. It has proved successful to undermine the cartilage edges lightly with a sharp spoon so that good anchoring of the implant in the defect can be achieved. For good documentation the debrided defect should be measured.

How is ChondroFiller® liquid prepared for implantation?

After confirmation of the indication for carrying out the ChondroFiller® liquid technique, it first needs to be thawed. This can be done either over 24 hours at a temperature of 2 to 8°C, or directly before use for approx. 30 minutes at a temperature of approx. 25 to 30°C, e.g. in a heat cabinet. Immediately prior to application of the ChondroFiller® liquid the two-chamber syringe needs to be briefly (<15 minutes) heated in the two-chamber syringe to 30 to 33°C (either in a heat cabinet or using your hands). The Luerlock mixing adapter can only be attached in one position (“lug-on-lug” clicking sound). Once an injection cannula has been attached (e.g. G 20 x 2 ¾ single-use injection cannula Sterican®, article no. 4665791, B. Braun Melsungen AG, Germany), the first few μl of the primarily liquid matrix are discarded immediately prior to injection.

How is the defect zone filled?

Filling of the defect should be performed quickly, in less than 20 seconds, and should be completed without interruptions, as the reaction between the two solutions starts immediately. The quicker they are pressed through the mixing adapter of the two-chamber syringe, the more stably the implant matrix solidifies. In the process, the cartilage defect is filled completely with the collagen matrix, with a minimal amount above the surrounding cartilage. Hardening of the matrix takes 2 – 5 minutes under an optimum processing temperature of 30 to 33°C. This process is visible, as the initially clear gel changes to a milky, opaque appearance.

How quickly does ChondroFiller® liquid form a solid collagen gel?

For treatment with ChondroFiller® liquid it is necessary that the implant is at a temperature of 30 to 35°C. If this temperature is maintained then gelation will take place within 2 to 5 minutes.

How can the height of the implant be matched to the surrounding cartilage?

Once it has solidified, the implant height can either be shaped by hand or it can automatically be adapted to the height of the surrounding cartilage by the pressure of the corresponding articular surface.

Further treatment of the patient after filling of the defect?

The patient’s limb is carefully moved into the extended position. The surgical access routes can now be closed. It is not normally necessary to use drainage. The filling of the defect should preferably not be checked at this stage since the bleeding taking place into the joint prevents a free view of the implant. Repeated inflation of the joint potentially risks detachment of the implant. With the aid of detailed core spin tomography imaging on all patients treated with this method, in all cases to date it has been possible to demonstrate that the implanted matrix remained safely in place. Once the wound has been dressed the treated joint should be immobilised with a brace for 48 hours in a neutral position.

What rehabilitation measures should take place after treatment with ChondroFiller® liquid?

The follow-up treatment is mainly determined by the anatomic location of the defect in the joint. There are two fundamental options:

defects located in the main load area of the joint, which are therefore subjected to an axial load, and

  1. defects on the knee joint located on the patella or on its corresponding articular surfaces, i.e. on the femoral trochlea, which are loaded only during flexion of the joint.

In both cases, the follow-up treatment is based on the relevant recommendations of the professional societies for trauma surgery DGU and orthopaedics DGOOC (Pietschmann 2012):

Main loading zone of the femoral condyles/talus:

  • Mobilisation on day 2 post-surgery
  • 20 kg partial weight bearing on the operated limb for 6 weeks
  • Exercise bar (CPM) 2x daily for 1 hour
  • From week 7: increase load by 30 kg every 2 weeks to full weight bearing
  • After reaching full weight bearing capability: cycling and swimming permitted, careful build-up of muscle through isometric training
  • Jumping, running and contact sports permitted after 1 year

Patellar and retropatellar bearings:

  • Mobilisation on day 2 post-surgery
  • Flexion of the knee joint is limited with an IROM rail for 3 weeks to 0-30°.
  • 20 kg partial weight bearing on the operated limb for 1 week
  • Full weight bearing permitted from week 2
  • From week 3: increase in flexion by 30° every 2 weeks, when flexion reaches 90° the IROM rail can be removed.
  • Once 90° flexion is attained: cycling and swimming permitted, careful build-up of muscle through isometric training
  • Sports with a high risk of falls are not permitted until after 1 year.

Detailed information about rehabilitation measures can be found in the PDF file Follow-up treatment/Rehabilitation