- Participants will learn specific activities in cartilage treatment emphasized on German institutions and clinics.
0.1 - Introduction: 21st Century Cartilage Regeneration in Germany
For 30 years several regenerative cartilage treatment procedures are in clinical use in Germany. Not all of them are available in other countries inside and outside Europe.
According to guidelines from the working group “Clinical Tissue Regeneration” of the German Society of Orthopaedics and Trauma (DGOU) the selection of a distinct regenerative cartilage treatment procedure is dependent on cartilage defect size, the involvement of the subchondral plate and the underlying subchondral bone. Of course, further patient-specific parameters, like BMI, sport / work activities and patient expectations will further help to choose the most suitable regenerative cartilage treatment procedure for an individual patient. Also the necessity of treating the comorbidities (Leg axis deviation, instability, meniscus tear) has to be included in the treatment plan of the patients.
Microfracture is still the most frequently used technique for cartilage repair, also in Germany. In order to be successful with microfracture, one should use it only in small defects (<2cm2) or combine it with cell free biomaterials.
The indication of Osteochondral transplantation (OCT) has narrowed over the years. It is indicated for small, mainly osteochondral defects, which allow sufficient treatment with one or two osteochondral plugs. For larger defects, the donor-side morbidity is of concern.
Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. This technique is available and widely used in Germany. Due to regulatory burdens in terms of harvest and culture of chondrocytes, the organizational effort of this technique is high. Therefore, this technique is mainly performed in center with specialization to cartilage treatment. In Germany, 3 different chondrocyte-based transplantation techniques are available (Novocart 3D (Aesculap, TETEC), Novocart inject (Aesculap, TETEC), Spherox (Codon). According to the German cartilage registry, which include over 10.000 patients, treated with regenerative cartilage procedures, the outcome of the 3 techniques is significant but comparable with each other. Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects, not only for traumatic but also for early-OA cartilage defects, starting from defect sizes of more than 2 cm2, while advanced degenerative joint disease needs to be considered as the most important contraindication.
Due to the limited access to osteochondral allografts, special sandwich techniques were developed in Germany to address bone and cartilage defects in huge osteochondral defects. The talk will describe recent developed techniques and show outcome results.
Unfortunately, recent advances in stem cell technology could not be translated in the clinic due to regulatory burdens in Germany. The use of these techniques in clinical trials would be of interest.
A newly developed cartilage repair procedure, minced cartilage technique, is used in Germany. The advantage is an one-step cartilage repair procedure without the regulatory burdens of the ACI technique. First results are promising, however, prospective outcome results are not available.
The rehabilitation after regenerative cartilage repair procedures is long. After ACI a return to sport is possible approximately after 1 year. Return to sport tests are used in Germany in order to analyze the neuromuscular ability for pivoting sports after 1year. The talk will show the need for these return to sport tests to avoid further reinjuries after rehabilitation.
0.2 - Matrix-Induced Autologous Cartilage Repair (MACR) – An Update
Articular cartilage lesions are a common pathology of the knee joint even in young patients resulting in pain and function loss. ith time). Given the limitations of MFx, efforts have focused on modifications and augmentation techniques for improving the quality of the repair tissue. Autologous, matrix-induced chondrogenesis (AMIC) is an enhanced MFx technique by covering the microfractured lesion site with a collagen I/III membrane in the knee (ChondroGide®, Geistlich Pharma AG).
In basic science, Kramer et al. showed in an in-vitro work that a membrane consisting of collagen can retain cartilage building cells, like, e.g., mesenchymal stem cells from bone marrow after microfracturing . Dickhut et al.  demonstrated in another in-vitro study that a biphasic carrier made of collagen type I/III supports chondrogenesis of MSCs and further that in comparison to collagen-free-membrane the form stability of the repair tissue was enhanced.
In vivo, 1 long-term study in sheep showed that AMIC significantly enhanced the cartilaginous repair tissue volume (eg, defect fill) compared with microfracture alone .
Intial clincal studies that have investigated short-term and medium-term follow-up cohorts suggest that AMIC in cartilage repair is a safe and effective treatment option that improves patient outcome measures and pain [4, 5]. To assess extended effectiveness and reliability of the AMIC procedure as well as the durability of the repaired cartilage, long-term follow up is essential. Two studies provide longer term data following an AMIC procedure, in which significant clinical and functional improvement was maintained over the 7-year follow-up [6, 7]. The AMIC procedure can be either performed with an open surgical approach or arthroscopically .
Steinwachs et al. summarize the results of 12 studies including 375 patients in a recent meta-analysis. The authors conclude that the AMIC procedure significantly improved the clinical status and functional scoring versus preoperative values .
 Kramer J, Böhrnsen F, Lindner U, Behrens P, Schlenke P, Rohwedel J. In vivo matrix-guided human mesenchymal stem cells. Cell Mol Life Sci 2006; 63: 616-626 [PMID: 16482398 DOI: 10.1007/s00018-005-5527-z]
 Dickhut A, Gottwald E, Steck E, Heisel C, Richter W. Chondrogenesis of mesenchymal stem cells in gel-like biomaterials in vitro and in vivo. Front Biosci 2008; 13: 4517-4528 [PMID: 18508526 DOI: 10.2741/3020]
 Gille J, Kunow J, Boisch L, Behrens P, Bos I, Hoffmann C, Köller W, Russlies M, Kurz B. Cell-Laden and Cell-Free Matrix-Induced Chondrogenesis versus Microfracture for the Treatment of Articular Cartilage Defects: A Histological and Biomechanical Study in Sheep. Cartilage 2010; 1: 29-42 [DOI: 10.1177/1947603509358721]
 Gille J, Behrens P, Volpi P, et al. Outcome of Autologous Matrix Induced Chondrogenesis (AMIC) in cartilage knee surgery: data of the AMIC Registry. Arch Orthop Trauma Surg. 2013;133(1):87-93.
 Gille J, Schuseil E, Wimmer J, et al. Mid-term results of Autologous Matrix-Induced Chondrogenesis for treatment of focal cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc. 2010;18(11):1456-1464.
 Schiavone Panni A, Del Regno C, Mazzitelli G, et al. Good clinical results with autologous matrix-induced chondrogenesis (AMIC) technique in large knee chondral defects. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2018;26(4):1130-1136.
 Gille J, Reiss E, Freitag M et al. AMIC for treatment of focal cartilage defects in the knee. Orthopaedic Journal of Sports Medicine. 2021; 66, 9(2) 2325967120981872
 Schagemann J, Behrens P, Paech A, et al. Mid-term outcome of arthroscopic AMIC for the treatment of articular cartilage defects in the knee joint is equivalent to mini-open procedures. Arch Orthop Trauma Surg. 2018;138(6):819-825.
 Steinwachs MR, Gille J, Volz M, et al. Systematic Review and Meta-Analysis of the Clinical Evidence on the Use of Autologous Matrix-Induced Chondrogenesis in the Knee. Cartilage. 2019:1947603519870846.
0.3 - Is it About Time to Abandon Microfracture?
Hyaline articular cartilage is critical for the normal functioning of the knee joint. Untreated focal cartilage defects have the potential to rapidly progress to diffuse osteoarthritis. Over the last several decades, a variety of interventions aiming at preserving articular cartilage and preventing osteoarthritis have been investigated. There have been numerous clinical studies that support the use of marrow-stimulation techniques.
Reparative cartilage procedures, such as microfracture, penetrate the subchondral bone plate in effort to fill focal cartilage defects with marrow elements and stimulate fibrocartilaginous repair.
Although microfracture is still a popular iteration of marrow stimulation, many leaders in the field question the technique’s sustainability (1,2). Unquestionably, the early clinical outcomes of microfracture have been proven positive; however, a loss of benefit has been described after ~2 years raising concerns of the technique’s validity (3). Complications are not uncommon, such as early OA reported in 40–50% of cases (4,5) and bone overgrowth which is visualized on MRI in 63% of cases at 2 years. Whilst over- growth is rarely symptomatic, with no significant difference in KOOS scores between those radiographically diagnosed with or without overgrowth, it does predict a significantly higher failure rate (25% vs. 3%) (6). Risk factors for poorer outcomes include long-standing symptoms, poor baseline Lysholm score, concurrent mild degenerative changes or partial meniscectomy (7). Long-term outcomes have been negatively correlated with increased age, larger defects ( > 2.5 cm2), and increased BMI (BMI > 30 kg/m2) (8). Furthermore, several authors have reported suboptimal outcomes in highly active and athletic patients (9). Microfracture when applied in young patients with smaller lesions can offer good clinical results at short- and long-term follow-up; lesion size is more important prognostic factor of outcome than age. Deterioration of the clinical outcome should be expected after 2 and 5 years post-treatment and degenerative changes are present at long-term follow-up corroborated by several authors.
Conclusion: Isolated microfracture is a non anatomical treatment compromising intact anatomical structures leading to avoidable complications and therefore should be abandoned instead of superior alternative therapies which furthermore have proven to be more cost effective in the long run.
1)Case JM, Scopp JM. Treatment of articular cartilage defects of the knee with microfracture and enhanced microfracture techniques. Sports Med Arthrosc Rev. 2016;24:63–68.
2) Steinwachs MR, Guggi T, Kreuz PC. Marrow stimulation techniques. Injury. 2008;39(suppl 1):S26–S31.
3)Gudas R, Gudaite A, Pocius A, et al. Ten-year follow-up of a prospective, randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint of athletes. Am J Sports Med. 2012;40:2499–2508.
4)Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Ludvigsen TC, Loken S, et al. A randomized multicenter trial comparing au- tologous chondrocyte implantation with microfracture: long-term follow-up at 14 to 15 years. J Bone Joint Surg Am. 2016;98: 1332–9.
5)Ulstein S, Aroen A, Rotterud JH, Loken S, Engebretsen L, Heir S. Microfracture technique versus osteochondral autologous trans- plantation mosaicplasty in patients with articular chondral lesions of the knee: a prospective randomized trial with long-term follow- up. Knee Surg Sports Traumatol Arthrosc. 2014;22:1207–15.
6)Mithoefer K, Venugopal V, Manaqibwala M. Incidence, degree, and clinical effect of subchondral bone overgrowth after microfracture in the knee. Am J Sports Med. 2016;44:2057–63.
7)Solheim E, Hegna J, Inderhaug E, Oyen J, Harlem T, Strand T. Results at 10–14 years after microfracture treatment of articular cartilage defects in the knee. Knee Surg Sports Traumatol Arthrosc. 2016;24:1587–93.
8)Mithoefer K, McAdams T, Williams RJ, et al. Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med. 2009;37:2053–2063.
9)Harris JD, Walton DM, Erickson BJ, et al. Return to sport and performance after microfracture in the knees of National Basketball Association Players. Orthop J Sports Med. 2013;1: 2325967113512759.
0.4 - Arthroscopic Matrix-Assisted Chondrocyte Transplantation (MACT) – State of the Art?
0.5 - Minced Cartilage – A Promising New Technique
0.6 - Rehabilitation After Cartilage Procedures – Do We Need Special Concepts?
The rehabilitation of cartilage-regenerative interventions, especially after autologous chondrocyte transplantation, is a scientifically well-studied field. There are several randomized, controlled studies with a follow-up of up to 10 years that surveyed various follow-up treatment schemes [2–5, 15].
The extent of postoperative weightbearing of the treated leg plays an important role in early rehabilitation after cartilage intervention. Especially in that point the rehabilitation differs significantly from other sport-orthopedic interventions such as anterior cruciate ligament reconstructions (ACLR) or meniscus surgery. Already in a review from 2006 it became apparent that the point in time at which full weight-bearing was permitted varied greatly between the different centers; for patellofemoral interventions between 6 hours and 12 weeks . Because the patella does not articulate with the trochlea in full extension up to about 20° flexion, or only to an extent, in 2003 the "Oscell protocol" stipulated direct postoperative full weight bearing with a permitted range of motion (ROM) of 0/0/30 recommended . This recommendation was also made in a consensus of US orthopedists in 2020 . A scientific investigation in the sense of a controlled study or a specific clinical and/or radiological trials of this early full weight-bearing has not yet taken place. Wondrasch and Ebert examined the radiological and functional outcome of earlier full weightbearing (after up to 6 weeks) in multiple studies with a follow-up of up to 10 years and showed that a scheme with increasing weight-bearing with return to full weight-bearing after 6 weeks is safe. In all those randomized controlled trials, patients were prescribed a range of motion (ROM) controlled orthosis as well as CPM (Continuous Passive Motion). The flexion for the CPM was limited to 30°-40° and the use was recommended for 1-3 hours a day [1, 3, 8, 12, 15]. The use of passive motor movement can be found in many study protocols and aftercare recommendations from various societies and centers after cartilage regenerative interventions even though there are no randomized controlled studies on their use after cartilage regenerative therapies. Individual studies have demonstrated an advantage both subjectively and histologically .
One subject which is implemented in many rehabilitation protocols, but was never studied individually is the need and duration of postoperative immobilization or bed rest.
Throughout the whole rehabilitation process the integrity and safety of the “new” cartilage plays the most important role and influence not only early rehabilitation. That is also the reason why it is reasonable to refer cartilage patient to physiotherapeutic facilities that are familiar with the aftercare, so that the right amount of training is applied. In comparison to ACLR return to low- and high-impact sports are recommended at later timepoints for patients who underwent cartilage repair. Study protocols and recommendations from different cartilage societies show similar timeframes for return to different sport intensities: very-low-impact (ergometer, walking, exercises in closed-chain) after 7 weeks, rowing ergometer, cross-trainer, and open-chain exercises after 12 weeks, jogging (starting on a treadmill) after 6 months and return to high-impact-sports after 1 year [2, 6, 7, 10, 14]. Whereas the late rehabilitation is not as well studied scientifically as the early rehabilitation, such that there are no controlled trials on that topic. One study of Niethammer at al. from 2014 showed within a group of 44 patients, that the ones returning to high-impact sports after 12 months or more, showed significantly better results after two years .
In summary: we definitely need special concepts for patients undergoing cartilage repair. Many aspects of the rehabilitation are scientifically well studied, but many open questions remain, such as postoperative bed rest, very early full weight-bearing after cartilage repair in the patellofemoral compartment, and timepoints in return to low- and high-impact sports as well as patient-and therapeutic-individual cofounders.
1. Bailey A, Goodstone N, Roberts S et al (2003) Rehabilitation after oswestry autologous-chondrocyte implantation: The Oscell protocol. Journal of Sport Rehabilitation 12:104–118. https://doi.org/10.1123/jsr.12.2.104
2. Ebert JR, Edwards PK, Fallon M et al (2017) Two-Year Outcomes of a Randomized Trial Investigating a 6-Week Return to Full Weightbearing after Matrix-Induced Autologous Chondrocyte Implantation. American Journal of Sports Medicine 45:838–848. https://doi.org/10.1177/0363546516673837
3. Ebert JR, Fallon M, Ackland TR et al (2020) Minimum 10-Year Clinical and Radiological Outcomes of a Randomized Controlled Trial Evaluating 2 Different Approaches to Full Weightbearing After Matrix-Induced Autologous Chondrocyte Implantation. American Journal of Sports Medicine 48:133–142. https://doi.org/10.1177/0363546519886548
4. Ebert JR, Fallon M, Wood DJ, Janes GC (2021) An accelerated 6-week return to full weight bearing after matrix-induced autologous chondrocyte implantation results in good clinical outcomes to 5 years post-surgery. Knee Surgery, Sports Traumatology, Arthroscopy. https://doi.org/10.1007/s00167-020-06422-6
5. Ebert JR, Fallon M, Zheng MH et al (2012) A randomized trial comparing accelerated and traditional approaches to postoperative weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation: Findings at 5 years. American Journal of Sports Medicine 40:1527–1537. https://doi.org/10.1177/0363546512445167
6. Edwards PK, Ackland T, Ebert JR (2014) Clinical rehabilitation guidelines for matrix-induced autologous chondrocyte implantation on the tibiofemoral joint. Journal of Orthopaedic and Sports Physical Therapy 44:102–119. https://doi.org/10.2519/jospt.2014.5055
7. Edwards PK, Ackland TR, Ebert JR (2013) Accelerated weightbearing rehabilitation after matrix-induced autologous chondrocyte implantation in the tibiofemoral joint: Early clinical and radiological outcomes. American Journal of Sports Medicine 41:2314–2324. https://doi.org/10.1177/0363546513495637
8. Flanigan DC, Sherman SL, Chilelli B et al (2020) Consensus on Rehabilitation Guidelines among Orthopedic Surgeons in the United States following Use of Third-Generation Articular Cartilage Repair (MACI) for Treatment of Knee Cartilage Lesions. Cartilage. https://doi.org/10.1177/1947603520968876
9. Hambly K, Bobic V, Wondrasch B et al (2006) Autologous chondrocyte implantation postoperative care and rehabilitation: Science and practice. American Journal of Sports Medicine 34:1020–1038. https://doi.org/10.1177/0363546505281918
10. Hirschmüller A, Baur H, Braun S et al (2011) Rehabilitation after autologous chondrocyte implantation for isolated cartilage defects of the knee. American Journal of Sports Medicine 39:2686–2696. https://doi.org/10.1177/0363546511404204
11. Niethammer TR, Müller PE, Safi E et al (2014) Early resumption of physical activities leads to inferior clinical outcomes after matrix-based autologous chondrocyte implantation in the knee. Knee Surgery, Sports Traumatology, Arthroscopy 22:1345–1352. https://doi.org/10.1007/s00167-013-2583-z
12. Pietschmann MF, Horng A, Glaser C et al (2014) Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the clinical tissue regeneration study group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic. Unfallchirurg 117:235–241. https://doi.org/10.1007/s00113-012-2293-x
13. Rogan S, Taeymans J, Hirschmüller A et al (2013) Wirkung von passiven Motorbewegungsschienen nach knorpelregenerativen Eingriffen - eine systematische Literaturübersicht. Zeitschrift fur Orthopadie und Unfallchirurgie 151:468–474. https://doi.org/10.1055/s-0033-1350707
14. Villa S della, Kon E, Filardo G et al (2010) Does intensive rehabilitation permit early return to sport without compromising the clinical outcome after arthroscopic autologous chondrocyte implantation in highly competitive athletes? American Journal of Sports Medicine 38:68–77. https://doi.org/10.1177/0363546509348490
15. Wondrasch B, Zak L, Welsch GH, Marlovits S (2009) Effect of Accelerated Weightbearing after Matrix-Associated Autologous Chondrocyte Implantation on the Femoral Condyle on Radiographic and Clinical Outcome after 2 Years: A Prospective, Randomized Controlled Pilot Study. American Journal of Sports Medicine 37:88S-96S. https://doi.org/10.1177/0363546509351272