Evolution and Current Role of Autologous Chondrocyte Implantation for Treatment of Articular Cartilage Defects in the Football (Soccer) Player

Background: Autologous chondrocyte implantation (ACI) continues to technically evolve, but how the technical innovations affect the ability to participate in high-impact sports such as football is unknown. Methods: Clinical studies describing athletes treated with first-, second-, or third-generation ACI techniques were reviewed. The technical developments of ACI were evaluated, and the results in athletes and specifically football (soccer) players were analyzed. Results: Football players reported 72% good to excellent results with significant overall improvement of knee function and activity scores. Return to football was 83% in competitive players but lower in recreational players. Eighty percent of players returned to the same competitive level after ACI, and 87% to 100% maintained their ability to play sports at 5 years postoperatively. Return to sport was better for younger, competitive players with shorter intervals between injury and ACI. New developments of the surgical technique and postoperative rehabilitation were able to reduce the limitations associated with first-generation ACI including invasiveness, graft hypertrophy, and particularly long postoperative rehabilitation. This allowed for faster return to sports like football without compromising the ability for continued competition over time. Conclusion: Articular cartilage repair in football players often allows for successful return to this high-impact sport with excellent durability. The continued evolution of this technique has improved initial shortcomings with important implications for both the professional and recreational athlete

Defining the baseline transcriptional fingerprint of rabbit hamstring autograft

Anterior cruciate ligament (ACL) injuries are common and of high relevance given their significant effects on patient function, quality of life, and posttraumatic arthritis. To date, investigators have reported on the expression of genes classically associated with tendon and ligament reconstruction, including decorin (DCN) and collagen type 1 (COL1A1 and COL1A2). However, the transcriptional fingerprint for hamstring tendons, one of the most common autografts used for ACLR, remains to be determined. The purpose of this study was to characterize the baseline transcriptional state of semitendinosus autografts in a rabbit model for ACLR and to employ such characterization to guide scientifically-driven target gene selection for future analyses. Next generation RNA sequencing was performed on whole semitendinosus autografts from four New Zealand White rabbits (mean age: 193 ± 0 days, mean weight: 2.78 kg ± 0.15 kg) and subsequently analyzed using gene enrichment and protein-protein interaction network analysis. Decorin, Secreted Protein Acidic and Cysteine Rich (SPARC), Collagen type 1, and Proline and Arginine Rich End Leucine Rich Repeat Protein (PRELP) and were determined to be the highest expressed genes with tendon-associated ontology. These results strengthen the association between genes such as DCN, COL1A1, and COL1A2 and tendon tissues as well as provide the novel addition of further high-expression, tendon characteristic genes such as SPARC and PRELP to provide guidance as to which molecules serve as high-signal candidates for future ACL research. In addition, this paper provides open-access to the expression fingerprint of hamstring autograft for ACLR in New Zealand White rabbits, thus providing a readily-accessible collaborative reference, in alignment with ethical animal research principles

Treatment of Cartilage Defects With the Matrix-Induced Autologous Chondrocyte Implantation Cookie Cutter Technique

Focal cartilage defects lead to significant pain and disability, prompting the development of various options for biologic restoration of the articular surface. Although each technique and biologic implant provides various advantages and associated limitations, matrix-induced autologous chondrocyte implantation (MACI) has gained popularity given promising long-term results. We present a technique for the facile implantation of MACI membranes using cookie cutter instrumentation to aid in defect debridement and graft preparation. The technique described allows for efficient operative workflow while ensuring the creation of vertical, stable defect edges and a form-fitting MACI membrane in a readily implemented fashion

The role of proximal tibial osteotomy in joint preservation

Introduction: Tibial osteotomy has a role in various aspects of joint preservation. Proper diagnosis and addressing all aspects of alignment both for focal cartilage lesions to support restorative repair procedures as well as in treatment of earlier phases of knee osteoarthritis in well selected patients. Malalignment of the leg axis is known to result in chronic overloading and thus contributing to the development of focal lesions as well as osteoarthritis. Objectives: To provide a comprehensive summary of the current state of utilization of tibial osteotomies in conjunction with other joint preserving procedures and to synthesize the current scientific evidence for the use of osteotomies in the setting of cartilage injuries. Methods: PubMed, Medline, Cochrane Systematic Reviews, and Clinical Keys were searched by the first author (M.H.) to validate that all papers of relevance to the area studied were included. Databases were searched comprehensively, and original research, systematic reviews, and meta-analysis were included at the authors’ discretion. References of selected articles were analyzed manually. Data from selected publications focused on tibial osteotomy were summarized. Results: Leg axis and patellofemoral alignment must be considered as important risk factors for failure of restorative cartilage procedures in the knee joint. Alignment-correcting osteotomies play a crucial role in enhancing clinical results of cartilage repair surgeries especially in the long-term. Through the redistribution of load, the biomechanical environment of the joint is optimized, and the induced or transplanted repair tissue is protected against overloading, facilitating enhanced tissue maturation. Recent evidence suggests that even small deviations from a neutral axis (<5°) should be corrected by osteotomy. Preoperative investigation of potential malalignment would therefore be beneficial in every patient who is considered for cartilage repair and joint preservation. Conclusion: Joint preservation procedures profit from addressing alignment by proximal tibial osteotomy. Unloading osteotomies are of utmost importance to facilitate a joint environment in which these procedures can be carried out successfully, reliably contributing to the long-term durability of cartilage restoration

Matrix-Applied Characterized Autologous Cultured Chondrocytes Versus Microfracture: Five-Year Follow-up of a Prospective Randomized Trial

Background: Matrix-based cell therapy improves surgical handling, increases patient comfort, and allows for expanded indications with better reliability within the knee joint. Five-year efficacy and safety of autologous cultured chondrocytes on porcine collagen membrane (MACI) versus microfracture for treating cartilage defects have not yet been reported from any randomized controlled clinical trial. Purpose: To examine the clinical efficacy and safety results at 5 years after treatment with MACI and compare these with the efficacy and safety of microfracture treatment for symptomatic cartilage defects of the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This article describes the 5-year follow-up of the SUMMIT (Superiority of MACI Implant Versus Microfracture Treatment) clinical trial conducted at 14 study sites in Europe. All 144 patients who participated in SUMMIT were eligible to enroll; analyses of the 5-year data were performed with data from patients who signed informed consent and continued in the Extension study. Results: Of the 144 patients randomized in the SUMMIT trial, 128 signed informed consent and continued observation in the Extension study: 65 MACI (90.3%) and 63 microfracture (87.5%). The improvements in Knee injury and Osteoarthritis Outcome Score (KOOS) Pain and Function domains previously described were maintained over the 5-year follow-up. Five years after treatment, the improvement in MACI over microfracture in the co-primary endpoint of KOOS pain and function was maintained and was clinically and statistically significant (P = .022). Improvements in activities of daily living remained statistically significantly better (P = .007) in MACI patients, with quality of life and other symptoms remaining numerically higher in MACI patients but losing statistical significance relative to the results of the SUMMIT 2-year analysis. Magnetic resonance imaging (MRI) evaluation of structural repair was performed in 120 patients at year 5. As in the 2-year SUMMIT (MACI00206) results, the MRI evaluation showed improvement in defect filling for both treatments; however, no statistically significant differences were noted between treatment groups. Conclusion: Symptomatic cartilage knee defects 3 cm2 or larger treated with MACI were clinically and statistically significantly improved at 5 years compared with microfracture treatment. No remarkable adverse events or safety issues were noted in this heterogeneous patient population. Keyword

Strategies for patient profiling in articular cartilage repair of the knee: A prospective cohort of patients treated by one experienced cartilage surgeon

Purpose: The purpose of this study was to report on the clinical outcome of a large heterogenic cartilage repair population treated with the profiling strategies of one experienced cartilage surgeon to provide evidence based tools for treatment selection in a clinical environment. Methods: A total of 216 patients were identified in this prospective single-surgeon study. For the primary and secondary treatment of smaller defects, microfracture (MF) was used. Hyalograft C was used for first and second line larger defects, while carbon-fiber rod and pad implantations were used as a salvage procedure. Results: Three years after the initial procedure, the clinical improvement was excellent for MF and Hyalograft C (P < 0.001) and good for carbon-fiber procedures (P < 0.05). Hyalograft C patients with prior anterior cruciate ligament reconstruction had less clinical improvement (P < 0.05), while MF patients with prior cartilage repair were more likely to fail (Odds Ratio 20.5, P < 0.05). Conclusion: This is the first study that provides an assessment of the treatment strategies used by an experienced cartilage surgeon. A treatment algorithm for cartilage repair in a heterogenic population was created that based on the findings of this study could be implemented in a clinical environment. Level of evidence: Prospective clinical case series, Level I

Regenerative Musculoskeletal Care: Ensuring Practice Implementation

The first human cartilage cell transplantation, in 1987, opened the field of regenerative musculoskeletal care. The regenerative (r)evolution has transitioned into a “technovolution” in which ingenuity and creativity enable solutions that improve quality of life. Ongoing development of regenerative strategies showcases a recognized priority in musculoskeletal care. Initial regenerative therapies are successful; treatment options remain confined to trials in specialized clinics. Thus, new cellular regenerative therapies are being introduced, but adoption in daily practice remains elusive. Regenerative therapies are integral in advancing musculoskeletal care options. Science-driven clinical trial experience has informed best practices while recognizing limitations in product development plans and regulatory frameworks impeding seamless adoption. Transnational collaborative efforts are needed to ensure standardization and expedited implementation of clinically ready therapies

Detection of early cartilage damage : feasibility and potential of gagCEST imaging at 7T

Objectives: The purpose was to implement a fast 3D glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) sequence at 7 T, test stability and reproducibility in cartilage in the knee in healthy volunteers, and evaluate clinical applicability in cartilage repair patients. Methods: Experiments were carried out on a 7-T scanner using a volume transmit coil and a 32-channel receiver wrap-around knee coil. The 3D gagCEST measurement had an acquisition time of 7 min. Signal stability and reproducibility of the GAG effect were assessed in eight healthy volunteers. Clinical applicability of the method was demonstrated in five patients before cartilage repair surgery. Results: Coefficient of variation of the gagCEST signal was 1.9%. The reproducibility of the GAG effect measurements was good in the medial condyle (ICC = 0.87) and excellent in the lateral condyle (ICC = 0.97). GAG effect measurements in healthy cartilage ranged from 2.6%-12.4% compared with 1.3%-5.1% in damaged cartilage. Difference in GAG measurement between healthy cartilage and damaged cartilage was significant (p < 0.05). Conclusions: A fast 3D gagCEST sequence was applied at 7 T for use in cartilage in the knee, acquired within a clinically feasible scan time of 7 min. We demonstrated that the method has high stability, reproducibility and clinical applicability. Key Points: • gagCEST measurements are stable and reproducible• A non-invasive GAG measurement with gagCEST can be acquired in 7 min• gagCEST is able to discriminate between healthy and damaged cartilag