Platelet-rich plasma (PRP) as therapy for cartilage, tendon and muscle damage - German working group position statement.

PURPOSE: Platelet rich plasma (PRP) is widely used in orthopaedics, but is still heavily debated. Therefore, a survey among the German "Working Group for Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology was conducted to achieve a consensus about the current therapeutical potential of PRP. METHODS: A first survey (n = 65 experts, all orthopaedic/trauma surgeons) was conducted (n = 13 questions). Following, a second round (n = 40 experts) was conducted with 31 questions to achieve consensus in 5 categories: three most common indications, PRP application, future research areas. RESULTS: Therapeutic PRP application was regarded as useful (89%), possibly even more important in the future (90%). Most common indications were tendon pathologies (77%), osteoarthritis (OA) (68%), muscle injuries (57%) and cartilage damage (51%). Consensus was reached in 16/31 statements. The application of PRP for early knee OA (Kellgren-Lawrence grade II) was regarded as potentially useful, as well as for acute and chronic tendinopathies. For chronic lesions (cartilage, tendons), multiple injections (2-4) were seen preferable to singular injections. However, no sufficient data exists on the time interval between the injections. Standardization of PRP preparation, application, frequency, as well as determining the range of indication is strongly recommended. CONCLUSIONS: There is a need of further standardization of the PRP preparation methods, indication and application protocols for knee OA and other indications, which must be further evaluated in basic science studies and randomized controlled clinical trials. LEVEL OF EVIDENCE: Consensus of expert opinion, Level V.

Clinical outcome is significantly better with spheroid-based autologous chondrocyte implantation manufactured with more stringent cell culture criteria.

Objective: Spherox (CO.DON AG) is an autologous chondrocyte implantation (ACI) product, consisting of spheroids of human autologous matrix-associated chondrocytes. The tendency of primary chondrocytes to dedifferentiate during cultivation and the high biologic variability caused by the autologous nature of the starting material makes it challenging to design a manufacturing process that performs consistently and delivers products that meet their intended function and the high quality criteria for cell-based ATMPs. The current study was submitted during the European authorization procedure, and addresses the requirement to justify the operational ranges of the manufacturing process using clinical data. Methods: In order to define the operational ranges, statistical correlation analyses were conducted between process parameters and clinical improvement data of 120 patients from Phase II and III treated with ACI (KOOS score, 1 year follow-up). Results: This approach identified cell culture time as a critical process parameter that negatively correlates with the product's efficacy. Subsequent analyses of the Phase III patients that were treated with chondrocyte spheroids that have been manufactured with shorter monolayer and spheroid cultivation times showed a higher average clinical improvement as well as a higher responder rate compared to the total group. In addition, retrospective analyses demonstrated superiority for the treatment with short-cultivated chondrocyte spheroids over micro-fracture treatment. Conclusion: These findings underscore the need to use clinical data to optimize the manufacturing process for autologous cell-based therapies. We expect that restricting the cultivation times during manufacturing minimizes the production of suboptimal batches, thus ensuring an efficacious product.

Degenerative isolated cartilage defects of the patellofemoral joint are associated with more severe symptoms compared to trauma-related defects: results of the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: The purpose of this study was to utilize data from the German Cartilage Registry (KnorpelRegister DGOU) to examine the hypothesis that degenerative cartilage defects of the patellofemoral joint are associated with more severe clinical symptoms compared to trauma-related defects. METHODS: All patients with isolated focal cartilage defects of the patellofemoral joint registered in the German Cartilage Registry until May 2017 were included in the study. Patients with previous surgery of the ipsilateral knee were excluded. Baseline data including etiology (traumatic, degenerative), size, location and ICRS grade of the cartilage defects as well as the duration of symptoms were analyzed. Clinical symptoms were evaluated by means of the numeric analog scale (NAS) for pain and the Knee injury and Osteoarthritis Outcome Score (KOOS). Group comparisons were performed using the Mann-Whitney-U test along with the Chi-squared test and Fisher's exact test. A bivariate correlation analysis and a multivariable linear regression analysis were performed to investigate the association between the defect characteristics and the clinical scores. RESULTS: A total of 423 patients (203 traumatic and 220 degenerative defects) were included. Isolated degenerative cartilage defects were found to have significantly more trochlear locations (28% vs. 18%; p = 0.006), significantly less ICRS grade 4 lesions (50% vs. 73%; p = 0.002) and a significantly smaller defect size [median 300 (IQR 105-400) vs. 300 (200-400) mm2] when compared to those from traumatic etiology. Traumatic defects showed significantly better KOOS-ADL [77 (60-90) vs. 69 (56-82); p = 0.005], KOOS-pain [69 (56-81) vs. 61 (47-75); p = 0.001] and NAS [2 (1-5) vs. 4 (1-6); p = 0.005] scores compared to degenerative defects. The correlation analysis revealed only weak correlations between the quantitative defect characteristics and clinical scores. CONCLUSIONS: Degenerative isolated cartilage defects in the patellofemoral joint are associated with more severe clinical symptoms in comparison to trauma-related defects. Additionally, they show a larger variance regarding their location with more trochlear defects. LEVEL OF EVIDENCE: III.

Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: A guideline by the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU).

BACKGROUND: Autologous chondrocyte implantation (ACI) is an established and well-accepted procedure for the treatment of localised full-thickness cartilage defects of the knee. METHODS: The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning therapeutic consequences of primary cartilage lesions and the suitable indication for ACI. RESULTS: Based on best available scientific evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than three to four square centimetres; in the case of young and active sports patients at 2.5cm(2), while advanced degenerative joint disease needs to be considered as the most important contraindication. CONCLUSION: The present review gives a concise overview on important scientific background and the results of clinical studies and discusses the advantages and disadvantages of ACI. LEVEL OF EVIDENCE: Non-systematic Review.

[The German Cartilage Registry (KnorpelRegister DGOU) for evaluation of surgical treatment for cartilage defects: experience after six months including first demographic data]. / Das KnorpelRegister DGOU zur Erfassung von Behandlungsergebnissen nach Knorpeloperationen: Erfahrungen nach 6 Monaten und erste epidemiologische Daten.

The German Cartilage Registry (KnorpelRegister DGOU) has been introduced in October 2013 and aims on the evaluation of patients who underwent cartilage repair for symptomatic cartilage defects. It represents a nation-wide cohort study which has been introduced by the working group "Tissue Regeneration" of the Germany Society of Orthopaedic Surgery and Traumatology and is technically based upon a web-based remote data entry (RDE) system. The present article describes first experiences with the registry including patient and treatment characteristics. Between October 2013 and April 2014, a total of 230 patients who had undergone surgical cartilage repair for symptomatic full-thickness cartilage defects of the knee has been included in the German Cartilage Registry from 23 cartilage repair centres. Mean age was 37.11 years (SD 13.61) and mean defect size was 3.68 cm(2) (SD 0.23). Since the introduction of the KnorpelRegister DGOU the total number of registered patients has increased steadily up to the most recent figure of 72 patients within one month. Patients were treated mainly according to the recommended therapies. The highest percentage in therapy is represented by the bone marrow stimulation techniques (55.02 %) as well as by the autologous chondrocyte transplantation (34.92 %). Unlike the patient collective in the majority of prospective randomised controlled trials, the patient population within the registry shows a high proportion of patients with accompanying pathologies, with an age of more than 50 years at the time of treatment and with unfavourably assessed accompanying pathologies such as an affection of the opposite cartilage surface or a previously resected meniscus. In summary, the technical platform and forms of documentation of the KnorpelRegister DGOU have proved to be very promising within the first six months. Unlike data from other clinical trials, the previous analysis of the patients' data and therapies reflects successfully the actual medical care situation of patients with cartilage defects of the knee joint. This analysis also provides new information on subgroups of patients that have not yet been recorded in the scientific literature. This will be part of the first analysis of clinical treatment data. An expansion of the KnorpelRegister DGOU to patients with cartilage defects of the ankle and hip joints is already decided upon and initialised.

[Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU)]. / Stellenwert der autologen Chondrozytentransplantation (ACT) in der Behandlung von Knorpelschäden des Kniegelenks - Empfehlungen der AG Klinische Geweberegeneration der DGOU.

Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI.

[Reconstruction of osteochondral defects with a collagen I hydrogel. Results of a prospective multicenter study]. / Rekonstruktion von Gelenkknorpeldefekten mit einem Kollagen-I-Hydrogel. Ergebnisse einer prospektiven Multicenterstudie.

STUDY GOALS: The aim of the study was to evaluate the therapeutic benefit of CaReS®, a type I collagen hydrogel-based autologous chondrocyte implantation technique, for the treatment of osteochondral defects of the knee (Outerbridge grades III and IV) within a prospective multicenter study. MATERIAL AND METHODS: A total of 116 patients in 9 clinical centers were treated with CaReS between 2003 and 2008. The Cartilage Injury Evaluation Package 2000 of the International Cartilage Repair Society (ICRS) was employed for data acquisition and included the subjective International Knee Documentation Committee score (IKDC score), the pain level (visual analog scale, VAS), the physical and mental SF-36 score, the overall treatment satisfaction and the functional IKDC status of the indexed knee. Follow-up evaluation was performed 3, 6 and 12 months after surgery and annually thereafter. RESULTS: The mean defect size treated was 5.4 ± 2.7 cm(2) with 30% of the cartilage defects being ≤4 cm(2) and 70% ≥4 cm(2). The mean follow-up period was 30.2 ± 17.4 months (minimum 12 months and maximum 60 months). The mean IKDC score significantly improved from 42.4 ± 13.8 preoperatively to 70.5 ± 18.7 (p < 0.01) in the mean follow-up period. Global pain level significantly decreased (p < 0.001) from 6.7 ± 2.2 preoperatively to 3.2 ± 3.1 at the latest follow-up. Both the physical and mental components of the SF-36 score significantly increased. At the latest follow-up 80% of the patients rated the overall treatment satisfaction as either good or very good. The functional IKDC knee status clearly improved from preoperative to the latest follow-up when 23.4% of the patients reported having no restriction of knee function (I), 56.3% had mild restriction (II), 17,2% had moderate restriction (III) and 3.1% revealed severe restriction (IV). CONCLUSIONS: The CaReS technique is a clinically effective and safe method for the reconstruction of isolated osteochondral defects of the knee joint and reveals promising clinical outcome up to 5 years after surgery. A longer follow-up period and larger patient cohorts are needed to evaluate the sustainability of CaReS treatment.