Peter Verdonk

Anatomy of the anterolateral ligament of the knee

In 1879, the French surgeon Segond described the existence of a ‘pearly, resistant, fibrous band’ at the anterolateral aspect of the human knee, attached to the eponymous Segond fracture. To date, the enigma surrounding this anatomical structure is reflected in confusing names such as ‘(mid‐third) lateral capsular ligament’, ‘capsulo‐osseous layer of the iliotibial band’ or ‘anterolateral ligament’, and no clear anatomical description has yet been provided. In this study, the presence and characteristics of Segonds ‘pearly band’, hereafter termed anterolateral ligament (ALL), was investigated in 41 unpaired, human cadaveric knees. The femoral and tibial attachment of the ALL, its course and its relationship with nearby anatomical structures were studied both qualitatively and quantitatively. In all but one of 41 cadaveric knees (97%), the ALL was found as a well‐defined ligamentous structure, clearly distinguishable from the anterolateral joint capsule. The origin of the ALL was situated at the prominence of the lateral femoral epicondyle, slightly anterior to the origin of the lateral collateral ligament, although connecting fibers between the two structures were observed. The ALL showed an oblique course to the anterolateral aspect of the proximal tibia, with firm attachments to the lateral meniscus, thus enveloping the inferior lateral geniculate artery and vein. Its insertion on the anterolateral tibia was grossly located midway between Gerdys tubercle and the tip of the fibular head, definitely separate from the iliotibial band (ITB). The ALL was found to be a distinct ligamentous structure at the anterolateral aspect of the human knee with consistent origin and insertion site features. By providing a detailed anatomical characterization of the ALL, this study clarifies the long‐standing enigma surrounding the existence of a ligamentous structure connecting the femur with the anterolateral tibia. Given its structure and anatomic location, the ALL is hypothesized to control internal tibial rotation and thus to affect the pivot shift phenomenon, although further studies are needed to investigate its biomechanical function.

Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis

Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic. We collected data from three families in which affected individuals had osteopoikilosis with or without manifestations of BOS or melorheostosis. A genome-wide linkage analysis in these families, followed by the identification of a microdeletion in an unrelated individual with these diseases, allowed us to map the gene that is mutated in osteopoikilosis. All the affected individuals that we investigated were heterozygous with respect to a loss-of-function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear membrane protein. A somatic mutation in the second allele of LEMD3 could not be identified in fibroblasts from affected skin of an individual with BOS and an individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and activin-TGFβ receptor–activated Smads and antagonized both signaling pathways in human cells.

Transplantation of viable meniscal allograft. Survivorship analysis and clinical outcome of one hundred cases.

BACKGROUND Few medium-term or long-term reports on meniscal allograft transplantations are available. In this study, we present the results of a survival analysis of the clinical outcomes of our first 100 procedures involving transplantation of viable medial and lateral meniscal allografts performed in ninety-six patients. METHODS Thirty-nine medial and sixty-one lateral meniscal allografts were evaluated after a mean of 7.2 years. Survival analysis was based on specific clinical end points, with failure of the allograft defined as moderate occasional or persistent pain or as poor function. An additional survival analysis was performed to assess the results of the sixty-nine procedures that involved isolated use of a viable allograft (twenty of the thirty-nine medial allograft procedures and forty-nine of the sixty-one lateral allograft procedures) and of the thirteen viable medial meniscal allografts that were implanted in combination with a high tibial osteotomy in patients with initial varus malalignment of the lower limb. RESULTS Overall, eleven (28%) of the thirty-nine medial allografts and ten (16%) of the sixty-one lateral allografts failed. The mean cumulative survival time (11.6 years) was identical for the medial and lateral allografts. The cumulative survival rates for the medial and lateral allografts at ten years were 74.2% and 69.8%, respectively. The mean cumulative survival time and the cumulative survival rate for the medial allografts used in combination with a high tibial osteotomy were 13.0 years and 83.3% at ten years, respectively. CONCLUSIONS Transplantation of a viable meniscal allograft can significantly relieve pain and improve function of the knee joint. Survival analysis showed that this beneficial effect remained in approximately 70% of the patients at ten years. This study identified the need for a prospective study comparing patients with similar symptoms and clinical findings treated with and without a meniscal allograft and followed for a longer period with use of clinical evaluation as well as more objective documentation tools regarding the actual fate of the allograft itself and the articular cartilage.

Autologous chondrocyte implantation in a novel alginate-agarose hydrogel: OUTCOME AT TWO YEARS

Autologous chondrocyte implantation is an established method of treatment for symptomatic articular defects of cartilage. CARTIPATCH is a monolayer-expanded cartilage cell product which is combined with a novel hydrogel to improve cell phenotypic stability and ease of surgical handling. Our aim in this prospective, multicentre study on 17 patients was to investigate the clinical, radiological, arthroscopic and histological outcome at a minimum follow-up of two years after the implantation of autologous chondrocytes embedded in a three-dimensional alginate-agarose hydrogel for the treatment of chondral and osteochondral defects. Clinically, all the patients improved significantly. Patients with lesions larger than 3 cm(2) improved significantly more than those with smaller lesions. There was no correlation between the clinical outcome and the body mass index, age, duration of symptoms and location of the defects. The mean arthroscopic International Cartilage Repair Society score was 10 (5 to 12) of a maximum of 12. Predominantly hyaline cartilage was seen in eight of the 13 patients (62%) who had follow-up biopsies. Our findings suggest that autologous chondrocyte implantation in combination with a novel hydrogel results in a significant clinical improvement at follow-up at two years, more so for larger and deeper lesions. The surgical procedure is uncomplicated, and predominantly hyaline cartilage-like repair tissue was observed in eight patients.

Tissue Ingrowth After Implantation of a Novel, Biodegradable Polyurethane Scaffold for Treatment of Partial Meniscal Lesions

Background: A novel, biodegradable, aliphatic polyurethane scaffold was designed to fulfill an unmet clinical need in the treatment of patients with irreparable partial meniscal lesions. Hypothesis: Treatment of irreparable partial meniscal lesions with an acellular polyurethane scaffold supports new tissue ingrowth. Study Design: Case series; Level of evidence, 4. Methods: Fifty-two patients (with 34 medial and 18 lateral lesions) were recruited into a prospective, single-arm, multicenter, proof-of-principle study and treated with the polyurethane scaffold. The scaffold was implanted after partial meniscectomy using standard surgeon-preferred techniques for suturing. Tissue ingrowth was assessed at 3 months by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and at 12 months by gross examination during second-look arthroscopy, in the course of which a biopsy sample from the inner free edge of the scaffold meniscus was taken for qualitative histologic analysis. Results: Tissue ingrowth at 3 months was demonstrated on DCE-MRI in 35 of 43 (81.4%) patients. All but one 12-month second-look (43 of 44 [97.7%]) showed integration of the scaffold with the native meniscus and all biopsy specimens (44) showed fully vital material, with no signs of cell death or necrosis. Three distinct layers were observed based on morphologic structure, vessel structure presence or absence, and extracellular matrix composition. Conclusion: The DCE-MRI demonstrated successful early tissue ingrowth into the scaffold. The biopsy findings demonstrated the biocompatibility of the scaffold and ingrowth of tissue with particular histologic characteristics suggestive of meniscus-like tissue. In conclusion, these data show for the first time consistent regeneration of tissue when using an acellular polyurethane scaffold to treat irreparable partial meniscus tissue lesions.

Matrix-Assisted Autologous Chondrocyte Transplantation for the Repair of Cartilage Defects of the Knee Systematic Clinical Data Review and Study Quality Analysis

Background The clinical application of the second-generation tissue-engineering approach for the treatment of cartilage lesions has been documented for different types of scaffolds, but systematic information on clinical efficacy and long-term results is not available. Purpose To analyze and assess the quality of clinical studies on different products in the emerging field of matrix-assisted auto-logous chondrocyte transplantation. The secondary purpose of this review was to improve the quality assessment of studies by modifying the Coleman methodology score (CMS). Study Design Systematic review. Methods For this review, a literature search was performed to identify all published and unpublished clinical studies of matrixassisted (second-generation) autologous chondrocyte transplantation using the following medical electronic databases: MED-LINE, MEDLINE preprints, EMBASE, CINAHL, Life Science Citations, and British National Library of Health, including the Cochrane Central Register of Controlled Trials (CENTRAL). The search period was January 1, 1995, to July 1, 2008. To better assess cartilage-related studies, a modification of the CMS was proposed. Results Eighteen studies were included in the analysis, reporting on 731 patients with an average follow-up of 27.3 months (6.5-60.0 months). Of the 18 studies, 2 were randomized controlled studies, 3 were prospective comparative studies, 11 were prospective cohort studies or prospective case series, and 2 were retrospective case series. Original CMSs for these studies (55.1 6 1.6) were significantly higher than those of cartilage repair studies in general (43.5 6 1.6, P <.0001) reported in 2005. The statistical analysis indicated that the modified CMS showed higher correlations and lower variability of correlations among 3 reviewers. Conclusion The quality of the currently available data on second-generation autologous chondrocyte transplantation is still limited by study designs. The modified CMS has demonstrated better sensitivity and reproducibility with respect to the original score, so it can be recommended for cartilage clinical studies evaluation.

Successful Treatment of Painful Irreparable Partial Meniscal Defects With a Polyurethane Scaffold Two-Year Safety and Clinical Outcomes

Background: A novel, biodegradable, polyurethane scaffold was designed to fulfill an unmet clinical need in the treatment of patients with painful irreparable partial meniscal defects. Hypothesis: The use of an acellular polyurethane scaffold for new tissue generation in irreparable partial meniscal defects provides both pain relief and improved functionality. Study Design: Case series; Level of evidence, 4. Methods: Fifty-two patients with irreparable partial meniscal defects (34 medial and 18 lateral, 88% with 1-3 previous surgeries on the index meniscus) were implanted with a polyurethane scaffold in a prospective, single-arm, multicenter, proof-of-principle study. Safety was assessed by the rate of scaffold-related serious adverse events (SAEs) and the International Cartilage Repair Society articular cartilage scoring system comparing magnetic resonance imaging (MRI) at 24 months to MRI at baseline (1 week). Kaplan-Meier time to treatment failure distributions were performed. Clinical outcomes were measured comparing visual analog scale, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score (KOOS), and Lysholm scores at 24 months from baseline (entry into study). Results: Clinically and statistically significant improvements (P < .0001) compared with baseline were reported in all clinical outcome scores (baseline/24 months): visual analog scale (45.7/20.3), International Knee Documentation Committee (45.4/70.1), KOOS symptoms (64.6/78.3), KOOS pain (57.5/78.6), KOOS activities of daily living (68.8/84.2), KOOS sports (30.5/59.0), KOOS quality of life (33.9/56.6), and Lysholm (60.1/80.7), demonstrating improvements in both pain and function. The incidence of treatment failure was 9 (17.3%) patients, of which 3 patients (8.8%) had medial meniscal defects and 6 patients (33.3%) had lateral meniscal defects. There were 9 SAEs requiring reoperation. Stable or improved International Cartilage Repair Society cartilage grades were observed in 92.5% of patients between baseline and 24 months. Conclusion: At 2 years after implantation, safety and clinical outcome data from this study support the use of the polyurethane scaffold for the treatment of irreparable, painful, partial meniscal defects.

Transplantation of Viable Meniscal Allograft

BACKGROUND Few medium-term or long-term reports on meniscal allograft transplantations are available. In this study, we present the results of a survival analysis of the clinical outcomes of our first 100 procedures involving transplantation of viable medial and lateral meniscal allografts performed in ninety-six patients. METHODS Thirty-nine medial and sixty-one lateral meniscal allografts were evaluated after a mean of 7.2 years. Survival analysis was based on specific clinical end points, with failure of the allograft defined as moderate occasional or persistent pain or as poor function. An additional survival analysis was performed to assess the results of the sixty-nine procedures that involved isolated use of a viable allograft (twenty of the thirty-nine medial allograft procedures and forty-nine of the sixty-one lateral allograft procedures) and of the thirteen viable medial meniscal allografts that were implanted in combination with a high tibial osteotomy in patients with initial varus malalignment of the lower limb. RESULTS Overall, eleven (28%) of the thirty-nine medial allografts and ten (16%) of the sixty-one lateral allografts failed. The mean cumulative survival time (11.6 years) was identical for the medial and lateral allografts. The cumulative survival rates for the medial and lateral allografts at ten years were 74.2% and 69.8%, respectively. The mean cumulative survival time and the cumulative survival rate for the medial allografts used in combination with a high tibial osteotomy were 13.0 years and 83.3% at ten years, respectively. CONCLUSIONS Transplantation of a viable meniscal allograft can significantly relieve pain and improve function of the knee joint. Survival analysis showed that this beneficial effect remained in approximately 70% of the patients at ten years. This study identified the need for a prospective study comparing patients with similar symptoms and clinical findings treated with and without a meniscal allograft and followed for a longer period with use of clinical evaluation as well as more objective documentation tools regarding the actual fate of the allograft itself and the articular cartilage.

Long-Term Follow-Up of 24.5 Years After Intra-Articular Anterior Cruciate Ligament Reconstruction With Lateral Extra-Articular Augmentation

Background: Many studies have reported successful outcomes 10 to 15 years after ACL reconstruction. However, few authors report results at ultra long-term follow-up (more than 20 years of follow-up). Purpose: The aim of this study was to determine how the status of the medial meniscus and the medial compartment articular cartilage observed at the time of ACL reconstruction affects results more than 24 years after surgery. This article examines long-term outcome of ACL reconstruction with extra-articular augmentation (procedure performed through a medial arthrotomy). Study Design: Case series; Level of evidence, 4. Methods: One hundred of 148 patients reviewed at 11.5 years of follow-up could be reviewed at 24.5 years. Complete clinical and radiographic evaluation (International Knee Documentation Committee scale and Knee Injury and Osteoarthritis Outcome Score) was performed. Results: The radiographic International Knee Documentation Committee rating was as follows: grade A, 39%; grade B, 7%; grade C, 27%; and grade D, 27%. Onset of osteoarthritis was correlated with medial meniscal status and femoral chondral defects at time of surgery. Conclusion: Total medial meniscectomy and articular cartilage damage were risk factors for osteoarthritis.

The “Ligamentization” Process in Anterior Cruciate Ligament Reconstruction: What Happens to the Human Graft? A Systematic Review of the Literature

Background: Surgical anterior cruciate ligament reconstruction using tendon grafts has become the standard to treat the functionally unstable anterior cruciate ligament–deficient knee. Although tendons clearly differ biologically from ligaments, multiple animal studies have shown that the implanted tendons indeed seem to remodel into a ligamentous “anterior cruciate ligament–like” structure. Purpose: The goal of this study was to systematically review the current literature on the “ligamentization” process in human anterior cruciate ligament reconstruction. Study Design: Systematic review. Methods: A computerized search using relevant search terms was performed in the PubMed, MEDLINE, EMBASE, and Cochrane Library databases, as well as a manual search of reference lists. Searches were limited to studies examining the healing of the intra-articular portion of the tendon graft based on biopsies of this graft obtained from a living human. Results: Four studies were determined to be appropriate for systematic review, none of them reaching a level of evidence higher than 3. All reports considered autografts. Biopsy specimens were evaluated by light or electron microscopy and analyzed for vascularization, cellular aspects, and appearance of extracellular matrix. All authors universally agreed that the tendon grafts survive in the intra-articular environment. Based on changes observed in the healing grafts with regard to vascularization, cellular aspects, and properties of the extracellular matrix, different chronologic stages in the ligamentization process were discerned. Conclusion: The key finding of this systematic review is that a free tendon graft replacing a ruptured human anterior cruciate ligament undergoes a series of biologic processes termed “ligamentization.” The graft seems to remain viable at any time during this course. Histologically, the mature grafts may resemble the normal human anterior cruciate ligament, but ultrastructural differences regarding collagen fibril distribution do persist. Different stages of the ligamentization process are described, but no agreement exists on their time frame. Problematic direct transmission of animal data to the human situation, the limited number of reports considering the ligamentization process in humans, and the potential biopsy sampling error attributable to superficial graft biopsies necessitate further human studies on anterior cruciate ligament graft ligamentization.