Etiology, Classification, Diagnostics, and Conservative Management of Osteochondral Lesions of the Talus. 2023 Recommendations of the Working Group "Clinical Tissue Regeneration" of the German Society of Orthopedics and Traumatology.

METHODS: Peer-reviewed literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLTs) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available for a particular diagnostic or therapeutic concept, including the grade of recommendation. Besides the scientific evidence, all group members rated the statements to identify possible gaps between literature and current clinical practice. CONCLUSION: In patients with minimal symptoms, OLT progression to ankle osteoarthritis is unlikely. Risk factors for progression are the depth of the lesion on MRI, subchondral cyst formation, and the extent of bone marrow edema. Conservative management is the adaptation of activities to the performance of the ankle joint. A follow-up imaging after 12 months helps not to miss any progression. It is impossible to estimate the probability of success of conservative management from initial symptoms and imaging. Cast immobilization is an option in OLTs in children, with a success rate of approximately 50%, although complete healing, estimated from imaging, is rare. In adults, improvement by conservative management ranges between 45% and 59%. Rest and restrictions for sports activities seem to be more successful than immobilization. Intra-articular injections of hyaluronic acid and platelet-rich plasma can improve pain and functional scores for more than 6 months. If 3 months of conservative management does not improve symptoms, surgery can be recommended.

Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk. / Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk.

The Working Group of the German Orthopedic and Trauma Society (DGOU) on Tissue Regeneration has published recommendations on the indication of different surgical approaches for treatment of full-thickness cartilage defects in the knee joint in 2004, 2013 and 2016. Based upon new scientific knowledge and new developments, this recommendation is an update based upon the best clinical evidence available. In addition to prospective randomised controlled clinical trials, this also includes studies with a lower level of evidence. In the absence of evidence, the decision is based on a consensus process within the members of the working group.The principle of making decision dependent on defect size has not been changed in the new recommendation either. The indication for arthroscopic microfracturing has been reduced up to a defect size of 2 cm2 maximum, while autologous chondrocyte implantation is the method of choice for larger cartilage defects. Additionally, matrix-augmented bone marrow stimulation (mBMS) has been included in the recommendation for defects ranging from 1 to 4.5 cm2. For the treatment of smaller osteochondral defects, in addition to osteochondral transplantation (OCT), mBMS is also recommended. For larger defects, matrix-augmented autologous chondrocyte implantation (mACI/mACT) in combination with augmentation of the subchondral bone is recommended.

Tibial internal rotation in combined anterior cruciate ligament and high-grade anterolateral ligament injury and its influence on ACL length.

BACKGROUND: Assessment of combined anterolateral ligament (ALL) and anterior cruciate ligament (ACL) injury remains challenging but of high importance as the ALL is a contributing stabilizer of tibial internal rotation. The effect of preoperative static tibial internal rotation on ACL -length remains unknown. The aim of the study was analyze the effect of tibial internal rotation on ACL length in single-bundle ACL reconstructions and to quantify tibial internal rotation in combined ACL and ALL injuries. METHODS: The effect of tibial internal rotation on ACL length was computed in a three-dimensional (3D) model of 10 healthy knees with 5° increments of tibial internal rotation from 0 to 30° resulting in 70 simulations. For each step ACL length was measured. ALL injury severity was graded by a blinded musculoskeletal radiologist in a retrospective analysis of 61 patients who underwent single-bundle ACL reconstruction. Preoperative tibial internal rotation was measured in magnetic resonance imaging (MRI) and its diagnostic performance was analyzed. RESULTS: ACL length linearly increased 0.7 ± 0.1 mm (2.1 ± 0.5% of initial length) per 5° of tibial internal rotation from 0 to 30° in each patient. Seventeen patients (27.9%) had an intact ALL (grade 0), 10 (16.4%) a grade 1, 21 (34.4%) a grade 2 and 13 (21.3%) a grade 3 injury of the ALL. Patients with a combined ACL and ALL injury grade 3 had a median static tibial internal rotation of 8.8° (interquartile range (IQR): 8.3) compared to 5.6° (IQR: 6.6) in patients with an ALL injury (grade 0-2) (p = 0.03). A cut-off > 13.3° of tibial internal rotation predicted a high-grade ALL injury with a specificity of 92%, a sensitivity of 30%; area under the curve (AUC) 0.70 (95% CI: 0.54-0.85) (p = 0.03) and an accuracy of 79%. CONCLUSION: ACL length linearly increases with tibial internal rotation from 0 to 30°. A combined ACL and high-grade ALL injury was associated with greater preoperative tibial internal rotation. This potentially contributes to unintentional graft laxity in ACL reconstructed patients, in particular with concomitant high-grade ALL tears. STUDY DESIGN: Cohort study; Level of evidence, 3.

Nonoperative and Operative Soft-Tissue and Cartilage Regeneration and Orthopaedic Biologics of the Knee: An Orthoregeneration Network (ON) Foundation Review.

Orthoregeneration is defined as a solution for orthopedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include: drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the knee, including symptomatic osteoarthritis and chondral injuries, as well as injuries to tendon, meniscus, and ligament, including the anterior cruciate ligament. Promising and established treatment modalities include hyaluronic acid (HA) in liquid or scaffold form; platelet-rich plasma (PRP); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs), hematopoietic stem cells, endothelial progenitor cells, and growth factors; connective tissue progenitor cells (CTPs) including adipose-derived mesenchymal stem cells (AD-MSCs) and tendon-derived stem cells (TDSCs); matrix cell-based therapy including autologous chondrocytes or allograft; vitamin D; and fibrin clot. Future investigations should standardize solution preparations, because inconsistent results reported may be due to heterogeneity of HA, PRP, BMAC, or MSC preparations and regimens, which may inhibit meaningful comparison between studies to determine the true efficacy and safety for each treatment.

Biologic Association Annual Summit: 2020 Report.

Interest and research in biologic approaches for tissue healing are exponentially growing for a variety of musculoskeletal conditions. The recent hype concerning musculoskeletal biological therapies (including viscosupplementation, platelet-rich plasma, and cellular therapies, or "stem cells") is driven by several factors, including demand by patients promising regenerative evidence supported by substantial basic and translational work, as well as commercial endeavors that complicate the scientific and lay understanding of biological therapy outcomes. While significant improvements have been made in the field, further basic and preclinical research and well-designed randomized clinical trials are needed to better elucidate the optimal indications, processing techniques, delivery, and outcome assessment. Furthermore, biologic treatments may have potential devastating complications when proper methods or techniques are ignored. For these reasons, an association comprising several scientific societies, named the Biologic Association (BA), was created to foster coordinated efforts and speak with a unified voice, advocating for the responsible use of biologics in the musculoskeletal environment in clinical practice, spearheading the development of standards for treatment and outcomes assessment, and reporting on the safety and efficacy of biologic interventions. This article will introduce the BA and its purpose, provide a summary of the 2020 first annual Biologic Association Summit, and outline the future strategic plan for the BA.

Autologous Matrix-Induced Chondrogenesis for Treatment of Focal Cartilage Defects in the Knee: A Follow-up Study.

BACKGROUND: Autologous matrix-induced chondrogenesis (AMIC) is a well-established treatment for full-thickness cartilage defects. PURPOSE: To evaluate the long-term clinical outcomes of AMIC for the treatment of chondral lesions of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A multisite prospective registry recorded demographic data and outcomes for patients who underwent repair of chondral defects. In total, 131 patients were included in the study. Lysholm, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analog scale (VAS) score for pain were used for outcome analysis. Across all patients, the mean ± SD age of patients was 36.6 ± 11.7 years. The mean body weight was 80.0 ± 16.8 kg, mean height was 176.3 ± 7.9 cm, and mean defect size was 3.3 ± 1.8 cm2. Defects were classified as Outerbridge grade III or IV. A repeated-measures analysis of variance was used to compare outcomes across all time points. RESULTS: The median follow-up time for the patients in this cohort was 4.56 ± 2.92 years. Significant improvement (P < .001) in all scores was observed at 1 to 2 years after AMIC, and improved values were noted up to 7 years postoperatively. Among all patients, the mean preoperative Lysholm score was 46.9 ± 19.6. At the 1-year follow-up, a significantly higher mean Lysholm score was noted, with maintenance of the favorable outcomes at 7-year follow-up. The KOOS also showed a significant improvement of postoperative values compared with preoperative data. The mean VAS had significantly decreased during the 7-year follow-up. Age, sex, and defect size did not have a significant effect on the outcomes. CONCLUSION: AMIC is an effective method of treating chondral defects of the knee and leads to reliably favorable results up to 7 years postoperatively.

Systematic Review and Meta-Analysis of the Clinical Evidence on the Use of Autologous Matrix-Induced Chondrogenesis in the Knee.

OBJECTIVE: A systematic review and meta-analysis of Autologous Matrix-Induced Chondrogenesis (AMIC®) outcomes for grade III/IV chondral and osteochondral lesions of the knee treated with Chondro-Gide®. DESIGN: Studies with a minimum follow-up of 1 year providing clinical results of AMIC repair in the knee were included based on PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Methodological quality was assessed by the modified Coleman Methodology Score (mCMS). The meta-analysis was comparing pain VAS (Visual Analog Scale), Lysholm score, and IKDC score (International Knee Documentation Committee) between baseline and follow-up after 1 or 2 years and after >3 years. RESULTS: Twelve studies (375 patients) were included. The mCMS demonstrated a suboptimal study design (ranking between 52 and 80). The mean age was 36.2 years (14-70 years). The mean defect size was 4.24 cm2 (0.8-22 cm2). The results from the random effects model indicated a clinically significant (P < 0.05) improvement of pain VAS from baseline to follow-up at year 1 to 2 of -4.02(confidence interval -4.37; -3.67), still significant after 3 years. Lysholm score at year 1 or 2 improved significantly and remained highly significant after 3 years. IKDC score showed highly significant improvement of 32.61 between 1 and 2 years versus baseline values maintained after 3 years. CONCLUSIONS: The AMIC procedure significantly improved the clinical status and functional scoring versus preoperative values. Evidence was obtained in a non-selected patient population, corresponding to real-life treatment of knee chondral and osteochondral defects. The evidence is sufficient to recommend AMIC in this indication.

Characterization of polydactyly chondrocytes and their use in cartilage engineering.

Treating cartilage injuries and degenerations represents an open surgical challenge. The recent advances in cell therapies have raised the need for a potent off-the-shelf cell source. Intra-articular injections of TGF-ß transduced polydactyly chondrocytes have been proposed as a chronic osteoarthritis treatment but despite promising results, the use of gene therapy still raises safety concerns. In this study, we characterized infant, polydactyly chondrocytes during in vitro expansion and chondrogenic re-differentiation. Polydactyly chondrocytes have a steady proliferative rate and re-differentiate in 3D pellet culture after up to five passages. Additionally, we demonstrated that polydactyly chondrocytes produce cartilage-like matrix in a hyaluronan-based hydrogel, namely transglutaminase cross-linked hyaluronic acid (HA-TG). We utilized the versatility of TG cross-linking to augment the hydrogels with heparin moieties. The heparin chains allowed us to load the scaffolds with TGF-ß1, which induced cartilage-like matrix deposition both in vitro and in vivo in a subcutaneous mouse model. This strategy introduces the possibility to use infant, polydactyly chondrocytes for the clinical treatment of joint diseases.

Arthroscopic and open treatment of cartilage lesions with BST-CARGEL scaffold and microfracture: A cohort study of consecutive patients.

BACKGROUND: CARGEL (Smith & Nephew Inc.), a chitosan-based polymer scaffolding biomaterial, has been used since 2012 for treating articular cartilage lesions. Limited data are available on patient outcomes following CARGEL treatment. This study aimed to describe short-term clinical and radiographic outcomes in a cohort of patients treated with CARGEL and microfracture surgery for articular cartilage defects in the knee. METHODS: A retrospective cohort study was conducted of consecutive patients with articular cartilage defects who had undergone microfracture surgery with CARGEL, or in patellar lesions microfracture and CARGEL plus Chondro-Gide (at SportsClinic Zurich). Study outcomes included reoperations, infections, allergic reactions, pain, swelling, range of motion, and tissue quality and quantity. Ethics approval was obtained from the local ethics committee on 05/09/2017 (Basec. Nr: 2017-01441). RESULTS: A total of 91 participants, with 93 treated lesions, consenting to chart review were included. No participants required reoperation due to complications on the index lesion. Fifteen participants had second-look surgery on the index knee for other reasons, allowing for visual confirmation of cartilage repair. No study participants experienced a post-surgical infection or suffered an allergic reaction. No significant changes in range of motion or T2 values were observed from pre-treatment to post-treatment follow-up. However, significant decreases were found in pain (P < 0.001) and swelling (P < 0.001), along with significant increases in MOCART II scores (P < 0.001). Similar results were found in a subgroup of patients with patellar lesions. CONCLUSIONS: Patients treated with CARGEL experienced few postoperative complications and reported promising reductions in pain and swelling after treatment. LEVEL OF EVIDENCE: IV.

Single-dose local anesthetics exhibit a type-, dose-, and time-dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature.

PURPOSE: Many studies have shown that local anesthetics may impede chondrocyte metabolism. However, the influence of a single-dose local anesthetics is controversial. The aim of this metaanalysis was to review the literature for studies investigating the cytotoxic effects of single-dose local anesthetics on chondrocytes and cartilage. METHODS: A comprehensive literature search was performed using established search engines (Medline, Embase) to identify studies, investigating the influence of single-dose local anesthetics on cartilage. The systematic analysis included the influence on histology, cell viability, morphology, and matrix production depending upon dose, exposure time, and type of local anesthetics. RESULTS: Twelve studies with four different local anesthetics were included in this metaanalysis. Bupivacaine and lidocaine were found to be more chondrotoxic than mepivacaine and ropivacaine. The amount of dead cells increased in a substance-, dose-, and time-dependent process. Osteoarthritic cartilage seems to be more vulnerable compared to intact cartilage. The toxic effects occur first in the superficial cartilage layers and include damage to membrane integrity, mitochondrial DNA, and nuclear changes. There is no study that could show a significant chondrotoxic effect with low concentrations of bupivacaine (0.0625%), ropivacaine (0.1 and 0.2%), and mepivacaine (0.5%). CONCLUSIONS: The cytotoxicity of local anesthetics on chondrocytes is dependent on dose, time, and type of local anesthetics. Single-dose intra-articular administration of local anesthetics impede chondrocyte metabolism and should be performed only with low concentrations for selected diagnostic purposes and painful joints. The use of lidocaine should be avoided. LEVEL OF EVIDENCE: II.

Anti-oxidant and immune-modulatory properties of sulfated alginate derivatives on human chondrocytes and macrophages.

Degeneration of articular cartilage represents one of the most common causes of pain and disability in our aging society. Current treatments only address the symptoms of joint disease, but not their underlying causes which include oxidative stress and inflammation in cartilage and surrounding tissues. Sulfated biopolymers that mimic aspects of the native extracellular environment of cartilage are recently gaining interest as a means to slow the inflammatory events responsible for tissue degeneration. Here we show that the natural polysaccharide alginate and particularly its sulfated derivatives have potent anti-oxidant, anti-inflammatory and anti-immunogenic properties in vitro. We found that these polymers exert a free radical scavenging activity in a sulfation-dependent manner. In particular, the sulfation degree of substitution of alginate directly correlated with its ability to scavenge superoxide radicals and to chelate metal ions. We also studied the effect of sulfated alginate on the ability of IL-1ß to stimulate inflammatory genes in human chondrocytes and found decreased expression of the pro-inflammatory markers IL-6 and CXCL8, which inversely correlated with the sulfation degree. Moreover, in studies testing the ability of the alginates to modulate macrophage polarization, we found that they decreased both the gene expression and synthesis of the proinflammatory cytokine TNF-α in human THP-1 macrophages with M1-like phenotype in a sulfation-dependent manner. To conclude, sulfated alginates effectively protect against oxidative stress and inflammation in vitro and are a promising biomaterial to be explored for treatment of osteoarthritis.

Human chondroprogenitors in alginate-collagen hybrid scaffolds produce stable cartilage in vivo.

The goal of this study was to evaluate human epiphyseal chondroprogenitor cells (ECPs) as a potential new cell source for cartilage regeneration. ECPs were compared to human bone marrow stromal cells (MSCs) and human adult articular chondrocytes (ACs) for their chondrogenic potential and phenotypic stability in vitro and in vivo. The cells were seeded in Optimaix-3D scaffolds at 5 × 104 cells/mm3 and gene expression, matrix production and mechanical properties were analysed up to 6 weeks. In vitro, ECPs synthesized consistently high collagen 2 and low collagen 10. AC-seeded constructs exhibited high donor variability in GAG/DNA values as well as in collagen 2 staining, but showed low collagen 10 production. MSCs, on the other hand, expressed high levels of collagen 2 but also of collagens 1 and 10, and were therefore not considered further. In vivo, there was considerable loss of matrix proteins in ECPs compared to in vitro cultured samples. To overcome this, a second implantation study investigated the effect of mixing cells with alginate prior to seeding in the scaffold. ECPs in alginate maintained their cartilage matrix and resisted mineralization and vessel infiltration better 6 weeks after subcutaneous implantation, whereas ACs lost their chondrogenic matrix completely. This study shows the great potential of ECPs as an off-the-shelf, highly chondrogenic cell type that produces stable cartilage in vivo. Copyright © 2016 John Wiley & Sons, Ltd.

Early osteoarthritis of the knee.

There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA.

Chondral and osteochondral operative treatment in early osteoarthritis.

In recent years treatment of early osteoarthritis came more and more into focus of orthopaedic research. In particular regenerative therapy options seem to have a high potential to fill the existing treatment gap for patients with early osteoarthritic changes. This article focuses on basic science, recent developments and available clinical data in the important field of operative regeneration procedures for treatment of chondral and osteochondral defects in early degenerative joints. It highlights current knowledge and perspectives of treatment options like microfracture, autologous or allogenous osteochondral transplantations and autologous chondrocyte transplantation. Further the role of biomaterials in a degenerative joint environment is illuminated. First clinical data of regenerative therapy in early osteoarthritis are encouraging to intensify research efforts in this important field. Future treatment perspectives for patients who suffer from early degenerative cartilage changes are discussed.

Pre-Osteoarthritis: Definition and Diagnosis of an Elusive Clinical Entity.

OBJECTIVE: An attempt to define pre-osteoarthritis (OA) versus early OA and definitive osteoarthritis. METHODS: A group of specialists in the field of cartilage science and treatment was formed to consider the nature of OA onset and its possible diagnosis. RESULTS: Late-stage OA, necessitating total joint replacement, is the end stage of a biological process, with many previous earlier stages. Early-stage OA has been defined and involves structural changes identified by arthroscopy or radiography. The group argued that before the "early-stage OA" there must exist a stage where cellular processes, due to the presence of risk factors, have kicked into action but have not yet resulted in structural changes. The group suggested that this stage could be called "pre-osteoarthritis" (pre-OA). CONCLUSIONS: The group suggests that defining points of initiation for OA in the knee could be defined, for example, by traumatic episodes or surgical meniscectomy. Such events may set in motion metabolic processes that could be diagnosed by modern MRI protocols or arthroscopy including probing techniques before structural changes of early OA have developed. Preventive measures should preferably be applied at this pre-OA stage in order to stop the projected OA "epidemic."

Practical execution of defect preparation prior to surgical cartilage intervention: results from a representative meeting survey among experts.

During a specialised orthopedic meeting held on 'the state of the art in cartilage defect repair', all previously fully-registered participants were requested to participate in an electronic survey by the use of a moderator-presented "Power Point Presentation-based" 9-item questionnaire. The aim of this survey was to assess indication, approach, and treatment execution of cartilage defect debridement prior to planned microfracture (MFX) or autologous chondrocyte implantation (ACI). All participants completed the questionnaire (n = 146) resulting in a return rate of 100 %. An uncertainty exists as to whether the removal of the calcifying layer prior to cartilage repair must be carried out or not. The same was true for the acceptability of subchondral bleeding prior to microfracturing and its handling prior to autologous chondrocyte implantation. There is a degree of unanimity among experts regarding the management of osteophytes and bone marrow edema. In a homogenous society collective of consultants that frequently deal with cartilage defective pathologies, there still remain a significant heterogeneity in selected topics of defect debridement.

Arthroscopic Treatment of Cartilage Lesions With Microfracture and BST-CarGel.

Bone marrow stimulation techniques for the treatment of articular cartilage defects such as microfracture so far have solely reproduced mechanically inferior fibrous cartilage tissue, which might result in unsatisfactory clinical results at midterm follow-up. A recent study has shown an improvement in repair tissue quality by enhancing microfracture with a chitosan-based biomaterial (BST-CarGel; Piramal, Laval, Quebec, Canada). BST-CarGel so far has only been applied by arthrotomy, which might lead to increased scar tissue formation and thus compromise recovery time and clinical outcome. We describe a surgical technique for an arthroscopic treatment of cartilage defects of the knee with microfracture in combination with BST-CarGel to benefit from improved repair tissue quality and to reduce arthrotomy-related morbidity.

Matrix-associated chondroplasty: a novel platelet-rich plasma and concentrated nucleated bone marrow cell-enhanced cartilage restoration technique.

Bone marrow stimulation techniques such as microfracture for the treatment of articular cartilage defects so far solely reproduce mechanically inferior fibrous cartilage tissue, which might result in unsatisfactory clinical results at midterm. The combination of microfracture and biomaterials-for example, autologous matrix-induced chondrogenesis technology-has not yet proved that the disadvantages of the marrow stimulation techniques can be overcome. At present, only laboratory-cultivated autologous chondrocytes are able to restore a biomechanically superior cartilage layer and might lead to superior functional results. However, the costs are high and the patient must undergo a 2-stage procedure. By selecting the appropriate cell fraction in conjunction with a controlled release of differentiating growth factors, sufficient cartilage regeneration might be achievable on the basis of bone marrow aspirate as well. We thus describe an advanced surgical technique for the treatment of articular cartilage defects based on platelet-rich plasma and bone marrow aspirate concentrate to overcome these drawbacks.

Economic evaluation of BST-CarGel as an adjunct to microfracture vs microfracture alone in knee cartilage surgery.

OBJECTIVES: Knee cartilage damage is a common cause of referral for orthopedic surgery. Treatment aims to reduce pain and symptoms by repairing cartilage. Microfracture, the current standard of care, yields good short-term clinical outcomes; however, treatment might fail after 2-3 years. A Chitosan-Beta glycerolphosphate-based medical device (BST-CarGel) is used as an adjunct to microfracture and demonstrates improvements in quantity and quality of repaired tissue, potentially reducing the risk of treatment failure. This study aimed to establish the economic value of BST-CarGel vs microfracture alone in knee cartilage repair from the societal perspective, using Germany as the reference market. METHODS: A decision tree with a 20-year time-horizon was constructed, in which undesirable clinical events were inferred following initial surgery. These events consisted of pain management, surgery, and total knee replacement. Clinical outcomes were taken from the pivotal clinical trial, supplemented by other literature. Data and assumptions were validated by a Delphi panel. All relevant resource use and costs for procedures and events were considered. RESULTS: In a group of patients with all lesion sizes, the model inferred that BST-CarGel yields a positive return on investment at year 4 (with 20-year cumulative cost savings of €6448). Reducing the incremental risk of treatment failure gap between the device and microfracture by 25-50% does not alter this conclusion. Cost savings are greatest for patients with large lesions; results for patients with small lesions are more modest. LIMITATIONS: Clinical evidence for microfracture and other interventions varies in quality. Comparative long-term data are lacking. The comparison is limited to microfracture and looks only at costs without considering quality-of-life. CONCLUSION: BST-CarGel potentially represents a cost-saving alternative for patients with knee cartilage injury by reducing the risk of clinical events through regeneration of chondral tissue with hyaline characteristics. Since the burden of this condition is high, both to the patient and society, an effective and economically viable alternative is of importance.