Arthroscopic cartilage cell transplantation (Spherox)
By encapsulating cartilage cells in an autologous extracellular matrix (spheroid technology), an arthroscopic applicability of cartilage cell transplantation is made possible. Current studies and our own initial experience show promising clinical results.
Articular cartilage defects are a widespread medical-therapeutic problem. It is estimated that up to 1.5 million people in Europe are affected by articular cartilage defects every year. In a retrospective study of 25,000 knee arthroscopies, cartilage lesions were found in 60% of patients. These were most frequently located retropatellar (36%) and on the medial femoral condyle (34%). Fifty-eight per cent of the cases were traumatic injuries, about half of which were related to sports. Of the sports surveyed, football and skiing were those with the greatest risk of cartilage damage. Localised grade III or IV cartilage defects in patients under 40 years of age who would potentially be candidates for cartilage surgery were found in 7% of all cases [1].
Surgical treatment options
Surgical methods available for the treatment of localised cartilage damage include bone marrow stimulation techniques (microfracturing or nanofracturing, autologous matrix-induced chondrogenesis), autologous osteochondral transplantation and autologous chondrocyte transplantation. For large cartilage defects(>2cm²) in active, young patients (<50 years), autologous chondrocyte transplantation has now established itself as the golden standard.
Generations of chondrocyte transplantation
Since its introduction, ACT has evolved over several generations. While in the 1st generation an autologous periosteal flap was used to cover the defect and the cell suspension was then applied to the defect under the periosteal flap, in the 2nd generation a membrane (e.g. made of collagen) was used instead of the periosteal flap. This reduced the invasiveness of the method, as it was no longer necessary to obtain a periosteal flap. Subsequently, the cells were already applied to a carrier material (e.g. collagen membrane, collagen gel or hyaluronic acid fleece) before transplantation. This simplified surgical handling during the operation and led to the name matrix-associated autologous chondrocyte transplantation (MACT).
Access routes
An open approach to the joint (mini-arthrotomy) is usually used for transplantation. There are approaches to perform the transplantation arthroscopically, but the insertion of the graft is technically very demanding and the cell viability of the inserted chondrocytes suffers. A study by Biant et al. found that the cell viability in arthroscopically inserted grafts was 16 times lower than in openly implanted grafts [2].
Spheroid technology
To overcome the limitations mentioned above, a spheroid technology was developed in which the autologous cells are encapsulated in their own extracellular matrix and form self-adhesive spheroids. Due to their self-adhesive property, these can be very easily inserted arthroscopically, even retropatellar. The rest of the procedure is largely the same as conventional MACT. In the first arthroscopic procedure, 2 osteochondral cylinders are first removed from the lateral side of the notch and sent to the manufacturer (Cod.on) for in vitro cultivation. After multiplication of the cells, reimplantation of the cells takes place after approx. 5-6 weeks. The second intervention is also performed arthroscopically. After thorough debridement of the cartilage defect, the arthroscopic irrigation water is drained off and the defect is drained. The spheroids are then introduced to the base of the defect via a cannula. During the first few minutes, they can be evenly distributed over the defect with the tactile hook. Due to the surface tension of the transport fluid, the spheroids can also be implanted very well retropatellar. Between 10 and 70 spheroids should be applied per cm². After 20 minutes, the spheroids adhere so well to the base of the defect that they can no longer be detached by rinsing water.
Approval studies
Spherox has an EU approval for articular cartilage defects (grade III and IV) up to 10cm² at the femoral condyle and patella and is available in Austria since the beginning of 2019. The efficacy and safety of Spherox was demonstrated in 2 large-scale phase II and III multicentre studies. The randomised phase III trial included a total of 102 patients and compared the clinical outcomes (KOOS score) of patients transplanted with Spherox against a microfracture group. After 36 months, there was a significantly better result for Spherox in the sub-scores "daily activities" and "sports and leisure" compared to microfracture. In the other subscores (pain, symptoms and quality of life), the patients with Spherox also had consistently higher score values, but without reaching statistical significance. There was no significant difference in the incidence of adverse events between the two treatment groups.
Recent publications
There are a few recently published studies in the literature on clinical outcomes of Spherox. In a second-look examination of patients with arthroscopic Spherox implantation, 91.3% of patients were found to have normal or near-normal macroscopic cartilage regeneration after an average of 3 years in a study by Siebold et al [3]. High patient satisfaction and good clinical results after 3 and 5 years, respectively, were demonstrated in two other studies [4, 5]. Retropatellar defects usually present a particular challenge in the treatment of cartilage defects and usually have clinically worse results than defects at the femoral condyle . In contrast, a high success rate was found in retropatellar defects in Spherox transplanted patients, which was comparable to results at the femoral condyle [5]. Currently, Spherox is only approved for patients 18 years of age and older. However, clinical data from adolescents (15-17 years of age) show promising results [4], so that an extension of the indication to younger patients can be considered.
Own experience
Since January 2019, we have operated on 9 patients with Spherox at the Orthopaedic Hospital Speising. The follow-up examinations (up to 6 months) showed good clinical and radiological results and high patient satisfaction. The length of stay during implantation was reduced to one night compared to conventional MACT with arthrotomy (3-5 nights). Depending on the defect localisation, the insertion of the spheroids in a "dry" arthroscopy can be tricky, so a learning curve must be expected despite ample arthroscopy experience. For osteochondral defects where autologous spongiosaplasty is necessary and the surgery has to be performed open anyway, we still use the conventional MACT.
Summary
Spherox is a method of cartilage cell transplantation that has EU-wide approval and whose effectiveness is well proven by studies. Due to its arthroscopic applicability, it brings significant advantages for patients, especially in the case of cartilage defects behind the kneecap, as a large access to the joint is no longer required, and thus the hospital stay can be shortened for the second operation and rehabilitation can be accelerated.
Literature
- Widuchowski, W., J. Widuchowski, and T. Trzaska, Articular cartilage defects: study of 25,124 knee arthroscopies. Knee, 2007. 14(3): p. 177-82.
- Biant, L.C., et al., Cell Viability in Arthroscopic Versus Open Autologous Chondrocyte Implantation. Am J Sports Med, 2017. 45(1): p. 77-81.
- Siebold, R., et al., Good clinical and MRI outcome after arthroscopic autologous chondrocyte implantation for cartilage repair in the knee. Knee Surg Sports Traumatol Arthrosc, 2018. 26(3): p. 831-839.
- Hoburg, A., et al., Matrix-Associated Autologous Chondrocyte Implantation Is an Effective Treatment at Midterm Follow-up in Adolescents and Young Adults. Orthop J Sports Med, 2019. 7(4): p. 2325967119841077.
- Niemeyer, P., et al., Clinical outcome and success rates of ACI for cartilage defects of the patella: a subgroup analysis from a controlled randomized clinical phase II trial (CODIS study). Arch Orthop Trauma Surg, 2019.
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