Aims

MRI has been suggested as an objective method of assessing anterior crucate ligament (ACL) graft “ligamentization” after reconstruction. It has been proposed that the MRI appearances could be used as an indicator of graft maturity and used as part of a return-to-sport assessment. The aim of this study was to evaluate the correlation between MRI graft signal and postoperative functional scores, anterior knee laxity, and patient age at operation.

Aims. The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction. Methods. The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and tenogenic genes (scleraxis (SCX), tenascin C (TNC), and tenomodulin (TNMD)) of the hamstring tendons were compared between the co-culture medium (ACL remnant cells (ACLRCs) and BMSCs co-culture) and control medium (BMSCs-only culture). We also evaluated the apoptosis, cell proliferation, migration, and gene expression of hamstring tenocytes with exposure to co-culture and control media. Results. Compared to BMSCs-only culture medium, the co-culture medium showed substantially decreased early and late apoptosis rates, attenuation of intrinsic and extrinsic apoptotic pathways, and enhanced proliferation of the hamstring tendons and tenocytes. In addition, the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes in the hamstring tendons and tenocytes significantly increased in the co-culture medium compared to that in the control medium. Conclusion. In the presence of ACLRCs and BMSCs, the hamstring tendons and tenocytes significantly attenuated apoptosis and enhanced the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes. This in vitro study suggests that the ACLRCs mixed with BMSCs could aid regeneration of the hamstring tendon graft during ACL reconstruction. Cite this article: Bone Joint Res 2023;12(1):9–21

Aims. The aim of this study was to estimate the incremental use of resources, costs, and quality of life outcomes associated with surgical reconstruction compared to rehabilitation for long-standing anterior cruciate ligament (ACL) injury in the NHS, and to estimate its cost-effectiveness. Methods. A total of 316 patients were recruited and randomly assigned to either surgical reconstruction or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment). Healthcare resource use and health-related quality of life data (EuroQol five-dimension five-level health questionnaire) were collected in the trial at six, 12, and 18 months using self-reported questionnaires and medical records. Using intention-to-treat analysis, differences in costs, and quality-adjusted life years (QALYs) between treatment arms were estimated adjusting for baseline differences and following multiple imputation of missing data. The incremental cost-effectiveness ratio (ICER) was estimated as the difference in costs divided by the difference in QALYs between reconstruction and rehabilitation. Results. At 18 months, patients in the surgical reconstruction arm reported higher QALYs (0.052 (95% confidence interval (CI) -0.012 to 0.117); p = 0.177) and higher NHS costs (£1,017 (95% CI 557 to 1,476); p < 0.001) compared to rehabilitation. This resulted in an ICER of £19,346 per QALY with the probability of surgical reconstruction being cost-effective of 51% and 72% at a willingness-to-pay threshold of £20,000 and £30,000 per QALY, respectively. Conclusion. Surgical reconstruction as a management strategy for patients with long-standing ACL injury is more effective, but more expensive, at 18 months compared to rehabilitation management. In the UK setting, surgical reconstruction is cost-effective. Cite this article: Bone Joint J 2024;106-B(1):38–45

Aims. The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily. Plasmin has been identified as a major component in the synovial fluid that varies among patients. The aim of this study was to test whether plasmin, a component of synovial fluid, could be a main factor responsible for the poor wound healing capacity of the ACL. Methods. The effects of increasing concentrations of plasmin (0, 0.1, 1, 10, and 50 µg/ml) onto the wound closing speed (WCS) of primary ACL-derived ligamentocytes (ACL-LCs) were tested using wound scratch assay and time-lapse phase-contrast microscopy. Additionally, relative expression changes (quantitative PCR (qPCR)) of major LC-relevant genes and catabolic genes were investigated. The positive controls were 10% fetal calf serum (FCS) and platelet-derived growth factor (PDGF). Results. WCS did not differ significantly among no plasmin versus each of the tested concentrations (six donors). The positive controls with PDGF and with FCS differed significantly from the negative controls. However, we found a trend demonstrating that higher plasmin concentrations up-regulate the expression of matrix metalloproteinase 13 (MMP13), 3 (MMP3), and tenomodulin (TNMD). Conclusion. The clinical relevance of this study is the possibility that it is not solely the plasmin, but also additional factors in the synovial fluid of the knee, that may be responsible for the poor healing capacity of the ACL. Cite this article: Bone Joint Res 2020;9(9):543–553

Aims. Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive. Methods. A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed. Results. Eight-week treadmill-walking was effective at maintaining the integrity of cartilage-subchondral bone unit and reducing the elevated systematic inflammation factors and microbiome-derived metabolites. Furthermore, 16S ribosomal ribonucleic acid (rRNA) sequencing showed disease-relevant microbial shifts in PTOA animals, characterized by the decreased abundance of phylum TM7 and the increase of phylum Fusobacteria. At the genus level, the abundance of Lactobacillus, Turicibacter, Adlercreutzia, and Cetobacterium were increased in the PTOA animals, while the increase of Adlercreutzia and Cetobacterium was weakened as a response to exercise. The correlation analysis showed that genus Lactobacillus and Adlercreutzia were correlated to the structural OA phenotypes, while phylum Fusobacteria and genus Cetobacterium may contribute to the effects of exercise on the diminishment of serological inflammatory factors. Conclusion. Exercise is effective at maintaining the integrity of cartilage-subchondral bone unit, and the exercise-induced modification of disease-relevant microbial shifts is potentially involved in the mechanisms of exercise-induced amelioration of PTOA. Cite this article: Bone Joint Res 2022;11(4):214–225

The Anterior Cruciate Ligament (ACL) plays a vital role in maintaining function and stability in the knee. Over the last several decades, much research has been focused on elucidating the anatomy, structural properties, biomechanics, pathology, and optimal treatments for the ACL. Through careful and objective study, the ACL can be understood to be a dynamic structure, rich in neurovascular supply. Although it is referred to as one ligament, it is comprised of two dis-tinct bundles which function synergistically to facilitate normal knee kinematics. The bony morphology of the knee defines normal knee kinematics, as well as the nature of the soft-tissue structures about the knee. Characterized by individual uniqueness, bony morphology varies from patient to patient. The ACL, which is a reflection of each patient's unique bony morphol-ogy, is inherently subject to both anatomic and morphologic variation as well. Furthermore, the ACL is subject to physiologic aging, which can affect the anatomic and structural properties of the ligament over time. A successful anatomic ACL Reconstruction, which may be considered the functional restoration of the ACL to its native dimensions, collagen orientation, and inser-tion sites according to individual anatomy, considers all these principles. It is vital to respect the nature we observe, rather than to “create” nature to fit a one-size-fits-all surgery. Double bundle ACL Reconstruction may therefore be thought of more as a concept rather than a specific technique, one that respects the individual unique anatomy of each patient to provide a truly indi-vidualized, anatomic, and value-based ACL Reconstruction

The anterior cruciate ligament (ACL) is the connective tissue located at the end of long bones providing stability to the knee joint. After tear or rupture clinical reconstruction of the tissue remains a challenge due to the particular mechanical properties required for proper functioning of the tissue. The outstanding mechanical properties of the ACL are characterized by a viscoelastic behavior responsible of the dissipation of the loads that are transmitted to the bone. These mechanical properties are the result of a very specialized graded extracellular matrix that transitions smoothly between the heterotypic cells, stiffness and composition of the ACL and the adjacent bone. Thus, mimicking the zonal biochemical composition, cellular phenotype and organization are key to reset the proper functioning of the ACL. We have previously shown how the biochemical composition presented to cells in electrospun scaffolds results in haptokinesis, reverting contact-guidance effects. [1]. Here, we demonstrate that contact guidance can also be disrupted by structural parameters in aligned wavy scaffolds. The presentation of a wavy fiber arrangement affected the cell organization and the deposition of a specific ECM characteristic of fibrocartilage. Cells cultured in wavy scaffolds grew in aggregates, deposited an abundant ECM rich in fibronectin and collagen II, and expressed higher amounts of collagen II, X and tenomodulin as compared to aligned scaffolds. In-vivo implantation in rabbits of triphasic scaffolds accounting for aligned-wavy-aligned zones showed a high cellular infiltration and the formation of an oriented ECM, as compared to traditional aligned scaffolds. [2]

Aims. The aim of this study was to screen the entire genome for genetic markers associated with risk for anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) injury. Methods. Genome-wide association (GWA) analyses were performed using data from the Kaiser Permanente Research Board (KPRB) and the UK Biobank. ACL and PCL injury cases were identified based on electronic health records from KPRB and the UK Biobank. GWA analyses from both cohorts were tested for ACL and PCL injury using a logistic regression model adjusting for sex, height, weight, age at enrolment, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNPs). The data from the two GWA studies were combined in a meta-analysis. Candidate genes previously reported to show an association with ACL injury in athletes were also tested for association from the meta-analysis data from the KPRB and the UK Biobank GWA studies. Results. There was a total of 2,214 cases of ACL and PCL injury and 519,869 controls within the two cohorts, with three loci demonstrating a genome-wide significant association in the meta-analysis: INHBA, AEBP2, and LOC101927869. Of the eight candidate genes previously studied in the literature, six were present in the current dataset, and only COL3A1 (rs1800255) showed a significant association (p = 0.006). Conclusion. Genetic markers in three novel loci in this study and one previously-studied candidate gene were identified as potential risk factors for ACL and PCL injury and deserve further validation and investigation of molecular mechanisms. Cite this article: Bone Jt Open 2021;2(6):414–421

External validation of machine learning predictive models is achieved through evaluation of model performance on different groups of patients than were used for algorithm development. This important step is uncommonly performed, inhibiting clinical translation of newly developed models. Recently, machine learning was used to develop a tool that can quantify revision risk for a patient undergoing primary anterior cruciate ligament (ACL) reconstruction (https://swastvedt.shinyapps.io/calculator_rev/). The source of data included nearly 25,000 patients with primary ACL reconstruction recorded in the Norwegian Knee Ligament Register (NKLR). The result was a well-calibrated tool capable of predicting revision risk one, two, and five years after primary ACL reconstruction with moderate accuracy. The purpose of this study was to determine the external validity of the NKLR model by assessing algorithm performance when applied to patients from the Danish Knee Ligament Registry (DKLR). The primary outcome measure of the NKLR model was probability of revision ACL reconstruction within 1, 2, and/or 5 years. For the index study, 24 total predictor variables in the NKLR were included and the models eliminated variables which did not significantly improve prediction ability - without sacrificing accuracy. The result was a well calibrated algorithm developed using the Cox Lasso model that only required five variables (out of the original 24) for outcome prediction. For this external validation study, all DKLR patients with complete data for the five variables required for NKLR prediction were included. The five variables were: graft choice, femur fixation device, Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life subscale score at surgery, years from injury to surgery, and age at surgery. Predicted revision probabilities were calculated for all DKLR patients. The model performance was assessed using the same metrics as the NKLR study: concordance and calibration. In total, 10,922 DKLR patients were included for analysis. Average follow-up time or time-to-revision was 8.4 (±4.3) years and overall revision rate was 6.9%. Surgical technique trends (i.e., graft choice and fixation devices) and injury characteristics (i.e., concomitant meniscus and cartilage pathology) were dissimilar between registries. The model produced similar concordance when applied to the DKLR population compared to the original NKLR test data (DKLR: 0.68; NKLR: 0.68-0.69). Calibration was poorer for the DKLR population at one and five years post primary surgery but similar to the NKLR at two years. The NKLR machine learning algorithm demonstrated similar performance when applied to patients from the DKLR, suggesting that it is valid for application outside of the initial patient population. This represents the first machine learning model for predicting revision ACL reconstruction that has been externally validated. Clinicians can use this in-clinic calculator to estimate revision risk at a patient specific level when discussing outcome expectations pre-operatively. While encouraging, it should be noted that the performance of the model on patients undergoing ACL reconstruction outside of Scandinavia remains unknown

Successful anterior cruciate ligament (ACL) reconstructions strive a firm ligament-bone integration. Therefore, the aim of this study was to address in more detail the enthesis as the thriphasic bone attachment of the ACL using a tissue engineering approach. To establish a tissue-engineered enthesis-like construct, triphasic scaffolds embroidered from poly(L-lactide-co-caprolactone) and polylactic acid functionalized with collagen foam were colonized with osteogenically differentiated human mesenchymal stromal cells (hMSCs) and lapine (L) ACL fibroblasts. These triphasic scaffolds with a bone-, a fibrocartilage transition- and a ligament phase were seeded directly after spheroid assembly or with 14 days precultured LACL fibroblast spheroids and 14 days osteogenically differentiated hMSCs spheroids (=longer preculture) and cultured for further 14 days. Cell survival was tested. Collagen type I and vimentin were immunolabeled and the content of DNA and sulfated glycosaminoglycan (sGAG) was quantified. The relative gene expression of tenascin C, type I and X collagens, Mohawk and Runx2 was analyzed. Compared to the LACL spheroids the hMSC spheroids adhered better to the scaffold surface with faster cell outgrowth on the fibers. Collagen type I and vimentin were mainly detected in the hMSCs colonizing the bone zone. The DNA content was generally higher in the bone (hMSCs) than in the ligament zones and after short spheroid preculture higher than after longer preculture whereas the sGAG content was greater after longer preculture for both cell types. The longer precultivated hMSCs expressed more type I collagen in comparison to those only shortly precultured before scaffold seeding. Type I collagen and tenascin C were higher expressed in scaffolds directly colonized with LACL compared to those seeded after longer spheroid preculture. The gene expression of ECM components and transcription factors depended on cell type and preculturing condition. Zonal colonization of triphasic scaffolds using the spheroid method is possible offering a novel approach for enthesis tissue engineering

Aim. Quadrupled hamstring anterior cruciate ligament plasties (4xHp) have been described as having a higher risk of infection than bone patellar tendon bone plasties (BPTBp). There are 2 theories that might explain this phenomenon. One is the presence of sutures in a 4xHp that could act as a foreign body, The other is the more complex preparation of a 4xHp that might lead to higher contamination rates during the process. The objective of the present study was to evaluate the formation of biofilm in these plasties and to compare it between a 4xHp and a BPTBp. The hypothesis was that the presence of sutures in 4xHp would increase the amount of biofilm present in them in comparison to BPTBp. Method. A descriptive in vitro study was conducted. One 4xHp and one BPTBp were prepared. They were subsequently divided into 8 fragments. Three of them were reserved for negative control, and the rest were contaminated with a strain of S. Epidermidis (ATCC 35984) 10–5. Finally, a quantitative analysis was carried out by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was carried out by means of electron microscopy. Results. In isothermal microcalorimetry, both contaminated plasties showed the same growth dynamics with a population peak (200uW) at 8h. No significant differences were found between the bacterial growth profiles of 4xHp and BPTBp. The product of sonication was plated and the number of colony forming units per milliliter (CFU/ml) was counted at 24 hours. No significant differences were detected between the 4×Hp (mean +/− sem = 3,5×107 +/− 3450000) and the BPTBp (4,6 ×107 +/− 1,455e+7). With a p value of 0.6667, there were no differences of significance (Mann-Whitney test). In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing BPTBp with 4xHp. Conclusions. There were no significant differences at either the quantitative or qualitative level when comparing bacterial growth in BPTBp and 4xHp. Therefore, the presence of sutures in 4xHp cannot be established as a predisposing factor to higher infection rates. These findings may be justified in the sense that the plasties themselves already behave like foreign bodies. Therefore, the presence of sutures does not increase the possibility of biofilm forming on their surface

Objectives. In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models. Methods. OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score. Results. Both models showed an increase in joint pain as indicated by a significant (p < 0.05) decrease in the values of %HLWD at one week post-surgery. In the osteochondral injury model, the %HLWD returned to normal within three weeks, while in the ACLT model, a significant decrease in the %HLWD was persistent over an eight-week period. In addition, OA progression was more advanced in the ACLT model than in the osteochondral injury model. Furthermore, the ACLT model exhibited a higher mean OA score than that of the osteochondral injury model at 12 weeks. Conclusion. The development of pain patterns in the ACLT and osteochondral injury models is different in that the OA progression was significant in the ACLT model. Although both can be used as models for a post-traumatic injury of the knee, the selection of appropriate models for OA in preclinical studies should be specified and relevant to the clinical scenario. Cite this article: T. Tawonsawatruk, O. Sriwatananukulkit, W. Himakhun, W. Hemstapat. Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models. Bone Joint Res 2018;7:244–251. DOI: 10.1302/2046-3758.73.BJR-2017-0121.R2

Increasing expectations from arthroscopic anterior cruciate ligament (ACL) reconstructions require precise knowledge of technical details such as minimum intra-femoral tunnel graft lengths. A common belief of having ≥20mm of grafts within the femoral tunnel is backed mostly by hearsay rather than scientific proof. We examined clinico-radiological outcomes in patients with intra-femoral tunnel graft lengths <20 and ≥20mm. Primary outcomes were knee scores at 1-year. Secondarily, graft revascularization was compared using magnetic resonance imaging (MRI). We hypothesized that outcomes would be independent of intra-femoral tunnel graft lengths. This prospective, single-surgeon, cohort study was conducted at a tertiary care teaching centre between 2015–2018 after obtaining ethical clearances and consents. Eligible arthroscopic ACL reconstruction patients were sequentially divided into 2 groups based on the intra-femoral tunnel graft lengths (A: < 20 mm, n = 27; and B: ≥ 20 mm, n = 25). Exclusions were made for those > 45 years of age, with chondral and/or multi-ligamentous injuries and with systemic pathologies. All patients were postoperatively examined and scored (Lysholm and modified Cincinnati scores) at 3, 6 and 12 months. Graft vascularity was assessed by signal-to-noise quotient ratio (SNQR) using MRI. Statistical significance was set at p<0.05. Age and sex-matched patients of both groups were followed to 1 year (1 dropout in each). Mean femoral and tibial tunnel diameters (P =0.225 and 0.595) were comparable. Groups A (<20mm) and B (≥20mm) had 27 and 25 patients respectively. At 3 months, 2 group A patients and 1 group B patient had grade 1 Lachman (increased at 12 months to 4 and 3 patients respectively). Pivot shift was negative in all patients. Lysholm scores at 3 and 6 months were comparable (P3= 0.195 and P6= 0.133). At 1 year both groups showed comparable Cincinnati scores. Mean ROM was satisfactory (≥130 degrees) in all but 2 patients of each group (125–130 degrees). MRI scans at 3 months and 1 year observed anatomical tunnels in all without any complications. Femoral tunnel signals in both groups showed a fall from 3–12 months indicating onset of maturation of graft at femoral tunnel. Our hypothesis, clinical and radiological outcomes would be independent of intra-tunnel graft lengths on the femoral aspect, did therefore prove correct. Intra-femoral tunnel graft lengths of <20 mm did not compromise early clinical and functional outcomes of ACL reconstructions. There seems to be no minimum length of graft within the tunnel below which suboptimal results should be expected

Reconstruction of the anterior cruciate ligament (ACL) allows to restore stability of the knee, in order to facilitate the return to activity (RTA). Although it is understood that the tendon autograft undergoes a ligamentous transformation postoperatively, knowledge about longitudinal microstructural differences in tissue integrity between types of tendon autografts (ie, hamstring vs. patella) remains limited. Diffusion tensor imaging (DTI) has emerged as an objective biomarker to characterize the ligamentization process of the tendon autograft following surgical reconstruction. One major limitation to its use is the need for a pre-injury baseline MRI to compare recovery of the graft, and inform RTA. Here, we explore the relationship for DTI biomarkers (fractional anisotropy, FA) between knees bilaterally, in healthy participants, with the hypothesis that agreement within a patient's knees may support the use of the contralateral knee as a reference to monitor recovery of the tendon autograft, and inform RTA. Fifteen participants with no previous history of knee injuries were enrolled in this study (age, 26.7 +/− 4.4 years; M/F, 7/8). All images were acquired on a 3T Prisma Siemens scanner using a secured flexible 18-channel coil wrapped around the knee. Both knees were scanned. A 3D anatomical Double Echo Steady State (DESS) sequence was acquired on which regions of interest (ROI) were placed consistent with the footprints of the ACL (femur, posteromedial corner on medial aspect of lateral condyle; tibia, anteromedial to intercondylar eminence). Diffusion images were acquired using fat saturation based on optimized parameters in-house. All diffusion images were pre-processed using the FMRIB FSL toolbox. The footprint ROIs of the ACL were then used to reconstruct the ligament in each patient with fiber-based probabilistic tractography (FBPT), providing a semi-automated approach for segmentation. Average FA was computed for each subject, in both knees, and then correlated against one another using a Pearson correlation to assess the degree of similarity between the ACLs. A total of 30 datasets were collected for this study (1/knee/participant; N=15). The group averaged FA (+/− standard deviation) for the FBPT segmented ACLs were found to equal 0.1683 +/− 0.0235 (dominant leg) and 0.1666 +/− 0.0225 (non-dominant leg). When comparing both knees within subjects, reliable agreement was found for the FBPT-derived ACL with a linear correlation coefficient (rho) equal to 0.87 (P < 0 .001). We sought to assess the degree of concordance in FA between the knees of healthy participants with hopes to provide a method for using the contralateral “healthy” knee in the comparison of autograft-dependent longitudinal changes in microstructural integrity, following ACL reconstruction. Our results suggest that good agreement in anisotropy can be achieved between the non-dominant and dominant knees using DTI and the FBPT segmentation method. Contralateral anisotropy of the ACL, assuming no previous injuries, may be used as a quantitative reference biomarker for monitoring the recovery of the tendon autograft following surgical reconstruction, and gather further insight as to potential differences between chosen autografts. Clinically, this may also serve as an index to supplement decision-making with respect to RTA, and reduce rates of re-injuries

Due to unsatisfactory results and reported drawbacks of anterior cruciate ligament (ACL) reconstruction new regenerative approaches based on tissue-engineering strategies are currently under investigation. It was the purpose of this study to determine if a novel silk fiber-based ACL scaffold is able to initiate osteointegration in the femoral and tibial bone tunnels under in vivo conditions. Furthermore we tested if the osteointegration process will be improved by intraoperatively seeding the scaffolds with the autologous stromal vascular fraction, an adipose-derived, stem cell-rich isolate from knee fat pads. In this controlled laboratory study, 33 sheep underwent ACL resection and were then randomly assigned to 2 experimental groups: ACL reconstruction with a scaffold alone and ACL reconstruction with a cell-seeded scaffold. Half of the sheep in each group were randomly chosen and euthanized 6 months after surgery and the other half at 12 months. To analyze the integration of the silk-based scaffold in the femoral and tibial bone tunnels, hard tissue histology and micro-computed tomography measurements were performed. The histological workup showed that in all treatment groups, with or without the application of the autologous stromal vascular fraction, an interzone of collagen fibers had formed between bone and silk-based graft. This collagen-fiber continuity partly consisted of Sharpey fibers, comparable with tendon-bone healing known for autografts and allografts. Insertion sites were more broad based at 6 months and more concentrated on the slightly protruding, bony knoblike structures at 12 months. Histologically, no differences between the treatment groups were detectable. Analysis of micro-computed tomography measurements revealed a significantly higher tissue density for the cell-seeded scaffold group as compared with the scaffold-alone group in the tibial but not femoral bone tunnel after 12 months of implantation. The novel silk fiber-based scaffold for ACL regeneration demonstrated integration into the bone tunnels via the formation of a fibrous interzone similar to allografts and autografts. Histologically, additional cell seeding did not enhance osteointegration. No significant differences between 6 and 12 months could be detected. After 12 months, there was still a considerable amount of silk present, and a longer observation period is necessary to see if a true ligament-bone enthesis will be formed

Aims. Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells. Methods. Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm. 2. , 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system. Results. ESW-treated ACL remnant cells presented higher cell viability, proliferation, migration, and increased expression of COL-I A1, TGF-β, and VEGF. BMSC proliferation and migration rate significantly increased after coculture with ACL remnant cells with and without ESW stimulation compared to the BMSCs alone group. Furthermore, ESW significantly enhanced ACL remnant cells’ capability to upregulate the collagen gene expression and tenogenic differentiation of BMSCs, without affecting cell viability, TGF-β, and VEGF expression. Conclusion. ACL remnant cells modulated activity and differentiation of surrounding cells. The results indicated that ESW enhanced ACL remnant cells viability, proliferation, migration, and expression of collagen, TGF-β, VEGF, and paracrine regulation of BMSC proliferation, migration, collagen expression, and tenogenesis. Cite this article: Bone Joint Res 2020;9(8):457–467

The aim of the this study was to determine the effect of the knee flexion angle (KFA) during tibial anterior cruciate ligament (ACL) graft fixation on patient reported outcomes, graft stability, extension loss and re-operation following anatomic single-bundle ACL reconstruction. All 169 included patients (mean age 28.5 years, 65% male) were treated with anatomic single bundle ACL reconstruction using patellar tendon autograft and randomized to tibial fixation of the ACL graft at either 0o (n=85) or 30o (n=84). The primary outcome was the Knee Injury and Osteoarthritis Outcome Score (KOOS) two years following surgery. Secondary outcomes were the Marx Activity Scale (MAS), the rate of re-operation, and physical exam findings at one year including KT-1000 and side to side differences in knee extension. The follow-up rate was 82% (n=139) for the primary outcome. Graft failure rate at two years was 1% (n=2, 1 per group). ACL tibial graft fixation at 0o or 30o did not have a significant effect on KOOS scores at two years following ACLR. Patients whose graft was fixed at a knee flexion angle of 0o had greater scores on the Marx Activity Scale (mean 9.6 [95%CI 8.5-10.6] versus 8.0 [95%CI 6.9-9.1, p=0.04) and a greater proportion of patients who achieved the minimal clinical important difference (MCID) for the KOOS pain subscale (94% vs 81%, p=0.04). There was no significant difference in knee extension loss, KT-1000 measurements or re-operation between the two groups. In the setting of anatomic single-bundle ACLR using patellar tendon autograft and anteromedial portal femoral drilling, there was no difference in KOOS scores among patients fixed at 0o and 30o. Patient fixed in full extension did demonstrate higher activity scores at 2 years following surgery and a greater likelihood of achieving the MCID for KOOS pain

Recent findings have identified the importance of previously undiagnosed or neglected meniscus lesions in association with anterior cruciate ligament (ACL) injuries (e.g. medial meniscus ramp lesions and posterior root tears of the lateral meniscus). There is increasing biomechanical evidence that they bear the potential to alter both anteroposterior and rotational laxity patterns in ACL injured knees. Few data exist with respect to the presence of these specific tear entities in large series of ACL injured patients. The purpose of the study was to analyze the meniscus tear pattern in a series of ACL injured knees with a special focus on ramp lesions of the medial meniscus and posterior root lesions of the lateral meniscus. The hypothesis was that a significant number of ACL injured patients would display these types of lesions. Data from 358 patients undergoing an ACL reconstruction (227 males /131 females, age: 28±10) were extracted from a center-based registry. The type of ACL tear (partial versus complete) as well as the presence of associated meniscus lesions were documented. Meniscus lesions were classified into the following categories: medial ramp lesions, lateral root lesions, medial ramp and lateral root lesion, other medial meniscus injuries, other lateral meniscus injuries, other bimeniscal injuries. Chi-square tests were used to determine whether the percentage of meniscal lesions differed between types of ACL tear, gender and age (below 21, 21–35, above 35). Significance was set at p < 0.05. Isolated ACL tears were present in 107 (30%) of the operated knees (31 partial; 327 complete). Complete ACL lesions were more likely to present an associated meniscus injury (321 out of 327, 71%) than partial tears (13 out of 31, 42%). The incidence of meniscus injuries which are associated with ACL tears is very high (70%). Previously undiagnosed or neglected meniscus injuries like medial ramp or lateral root tears could be identified in 35% of patients. As such, the hypothesis was confirmed that an important amount of ACL injured knees display this specific intraarticular soft tissue damage. A systematic evaluation of these lesions under arthroscopy should thus be performed and specific repair needs to be evaluated

Anterior cruciate ligament (ACL)-retaining total knee arthroplasty (TKA) has been associated with more physiologic motion patterns, more normal knee kinematics, and higher patient preference than ACL-sacrificing implant designs. However, it remains unclear how many osteoarthritic patients can be expected to have an intact ACL at the time of surgery in order to undergo ACL-retaining TKA. A systematic literature review was performed in November 2018 using the PubMed and EMBASE databases. Papers written in English, with more than 10 adult patients relevant to the research question were included, whereas cadaveric, revision, animal and simulation studies and conference abstracts were excluded. Data on ACL retention during intraoperative assessment or MRI scans were extracted and analysed using proportional meta-analyses. Twenty-six eligible publications (4167 knees) were included: 20 using intraoperative assessment, 4 using MRI, and 2 using both. Intraoperative assessment of the ACL during TKA showed that the ligament was present in 78% (95% confidence interval [CI]: 72–84%) and intact in 55% (95% CI: 45–65%) of the patients examined. MRI scans revealed higher percentages of ACL presence and intactness than intraoperative assessment, with 91% (95% CI: 79–96%) of the ACL being present and 68% (95% CI: 28–92%) intact. Fewer studies reported on MRI results compared to studies reporting on the intraoperative status of the ACL. In conclusion, intraoperative assessment suggests that over half of the osteoarthritic patients have an intact ACL at the time of TKA surgery, some of whom may qualify for bicruciate-retaining arthroplasty. For any figures or tables, please contact authors directly

The concept of decellularised xenografts as a basis for anterior cruciate ligament (ACL) reconstruction was introduced to overcome limitations in alternative graft sources such as substantial remodelling delaying recovery and donor site morbidity. This study aimed to measure the biomechanical properties of decellularised porcine super flexor tendon (pSFT) processed to create ACL grafts of varying diameters, with a view to facilitating production of stratified ‘off the shelf’ products with specified functional properties for use in ACL reconstructive surgery. Decellularisation was carried out using a previously established procedure, including antibiotic washes, low concentration detergent (0.1% sodium dodecyl sulphate) washes and nuclease treatments. Decellularised pSFTs were prepared to create double-bundle grafts of 7, 8 and 9mm diameter (n=6 in each group). Femoral and tibial fixations were simulated utilising Arthrex suspension devices (Tightrope®) and interference screws in bovine bone respectively. Dynamic stiffness and creep were measured under cyclic loading between 50–250N for 1000 cycles at 1Hz. This was followed by ramp to failure at 200mm/min from which linear stiffness and load at failure were measured. Data were analysed using either 1- or 2-way ANOVA as appropriate with Tukey post-hoc analysis (p<0.05). Significant differences were found between all groups for dynamic stiffness and between 7 & 9mm and 8 & 9mm groups for dynamic creep. Significant differences were also found between 7, 8 & 9mm groups for linear stiffness (167.8±4.9, 186.9±16.6 & 216.3±12.4N/mm respectively), but no significant differences were found between groups for load at failure (531.5±58.9, 604.1±183.3 & 627.9±72.4N respectively). This study demonstrated that decellularised pSFTs possess comparable biomechanical properties to other ACL graft options (autografts and allografts). Furthermore, grafts can be stratified by their diameter to provide varying biomechanical profiles depending on the anatomy and individual needs of the recipient