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. The objectives of this study were to assess the effect of anterior cruciate ligament (ACL) resection on flexion-extension gaps, mediolateral soft tissue laxity, maximum knee extension, and limb alignment during primary total knee arthroplasty (TKA). Methods. This prospective study included 140 patients with symptomatic knee osteoarthritis undergoing primary robotic-arm assisted TKA. All operative procedures were performed by a single surgeon using a standard medial parapatellar approach. Optical motion capture technology with fixed femoral and tibial registration pins was used to assess study outcomes pre- and post-ACL resection with knee extension and 90° knee flexion. This study included 76 males (54.3%) and 64 females (45.7%) with a mean age of 64.1 years (SD 6.8) at time of surgery. Mean preoperative hip-knee-ankle deformity was 6.1° varus (SD 4.6° varus). Results. ACL resection increased the mean extension gap significantly more than the flexion gap in the medial (mean 1.2 mm (SD 1.0) versus mean 0.2 mm (SD 0.7) respectively; p < 0.001) and lateral (mean 1.1 mm (SD 0.9) versus mean 0.2 mm (SD 0.6) respectively; p < 0.001) compartments. The mean gap differences following ACL resection did not create any significant mediolateral soft tissue laxity in extension (gap difference: mean 0.1 mm (SD 2.4); p = 0.89) or flexion (gap difference: mean 0.2 mm (SD 3.1); p = 0.40). ACL resection did not significantly affect maximum knee extension (change in maximum knee extension = mean 0.2° (SD 0.7°); p = 0.23) or fixed flexion deformity (mean 4.2° (SD 3.2°) pre-ACL release versus mean 3.9° (SD 3.7°) post-ACL release; p = 0.61). ACL resection did not significantly affect overall limb alignment (change in alignment = mean 0.2° valgus (SD 1.0° valgus; p = 0.11). Conclusion. ACL resection creates flexion-extension mismatch by increasing the extension gap more than the flexion gap. However, gap differences following ACL resection do not create any mediolateral soft tissue laxity in extension or flexion. ACL resection does not affect maximum knee extension or overall limb alignment. Cite this article: Bone Joint J 2020;102-B(4):442–448

Aims. This study aims to determine the proportion of patients with end-stage knee osteoarthritis (OA) possibly suitable for partial (PKA) or combined partial knee arthroplasty (CPKA) according to patterns of full-thickness cartilage loss and anterior cruciate ligament (ACL) status. Methods. A cross-sectional analysis of 300 consecutive patients (mean age 69 years (SD 9.5, 44 to 91), mean body mass index (BMI) 30.6 (SD 5.5, 20 to 53), 178 female (59.3%)) undergoing total knee arthroplasty (TKA) for Kellgren-Lawrence grade ≥ 3 knee OA was conducted. The point of maximal tibial bone loss on preoperative lateral radiographs was determined as a percentage of the tibial diameter. At surgery, Lachman’s test and ACL status were recorded. The presence of full-thickness cartilage loss within 16 articular surface regions (two patella, eight femoral, six tibial) was recorded. Results. According to articular cartilage loss and ACL status, 195/293 (67%) were suitable for PKA or CPKA: medial unicompartmental knee arthroplasty (UKA) 97/293 (33%); lateral UKA 25 (9%); medial bicompartmental arthroplasty 31 (11%); lateral bicompartmental arthroplasty 12 (4%); bicondylar-UKA 23 (8%); and patellofemoral arthroplasty (PFA) seven (2%). The ACL was intact in 166 (55%), frayed in 82 (27%), disrupted in 12 (4%), and absent in 33 (11%). Lachman testing was specific (97%) but poorly sensitive (38%) for disrupted/absent ACLs. The point of maximal tibial bone loss showed good interclass correlation (ICC 0.797, 0.73 to 0.85 95% confidence interval (CI); p < 0.001) and was more posterior when the ACL was absent. Maximum tibial bone loss occurring at > 55% of the anterior to posterior distance predicted ACL absence with 93% sensitivity and 91% specificity (area under the curve 0.97 (0.94 to 0.99 95% CI; p < 0.001). Conclusion. ACL status can be reliably determined from a lateral radiograph using the location of maximal tibial bone loss. According to regions of cartilage loss and ACL status, two-thirds of patients with end-stage knee OA could potentially be treated with PKA or CPKA. Cite this article: Bone Joint J 2020;102-B(6):716–726

Aims. Anterior cruciate ligament (ACL) and multiligament knee (MLK) injuries increase the risk of development of knee osteoarthritis and eventual need for total knee arthroplasty (TKA). There are limited data regarding implant use and outcomes in these patients. The aim of this study was to compare the use of constrained implants and outcomes among patients undergoing TKA with a history of prior knee ligament reconstruction (PKLR) versus a matched cohort of patients undergoing TKA with no history of PKLR. Patients and Methods. Patients with a history of ACL or MLK reconstruction who underwent TKA between 2007 and 2017 were identified in a single-institution registry. There were 223 patients who met inclusion criteria (188 ACL reconstruction patients, 35 MLK reconstruction patients). A matched cohort, also of 223 patients, was identified based on patient age, body mass index (BMI), sex, and year of surgery. There were 144 male patients and 79 female patients in both cohorts. Mean age at the time of TKA was 57.2 years (31 to 88). Mean BMI was 29.7 kg/m. 2. (19.5 to 55.7). Results. There was a significantly higher use of constrained implants among patients with PKLR (76 of 223, 34.1%) compared with the control group (40 of 223, 17.9%; p < 0.001). Subgroup analysis showed a higher use of constrained implants among patients with prior MLK reconstruction (21 of 35, 60.0%) compared with ACL reconstruction (55 of 188, 29.3%; p < 0.001). Removal of hardware was performed in 69.5% of patients with PKLR. Mean operative time (p < 0.001) and tourniquet time (p < 0.001) were longer in patients with PKLR compared with controls. There were no significant differences in rates of deep vein thrombosis, pulmonary embolism, infection, transfusion, postoperative knee range of movement (ROM), or need for revision surgery. There was no significant difference in preoperative or postoperative Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) scores between groups. Conclusion. Results of this study suggest a history of PKLR results in increased use of constrained implants but no difference in postoperative knee ROM, patient-reported outcomes, or incidence of revision surgery. Cite this article: Bone Joint J 2019;101-B(7 Supple C):77–83

Aims. Different methods of anterior cruciate ligament (ACL) reconstruction have been described for skeletally immature patients before closure of the growth plates. However, the outcome and complications following this treatment remain unclear. The aim of this systematic review was to analyse the outcome and complications of different techniques which may be used for reconstruction of the ACL in these patients. Materials and Methods. We performed a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This involved a comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase and Google Scholar databases using the following combinations of keywords, “knee”, “anterior cruciate ligament”, “reconstruction”, “injury”, “children”, “adolescent”, “skeletally immature”, “open physis” and “surgery”. Results. A total of 53 studies met the inclusion criteria and were included for analysis. The overall rate of disturbance of growth after ACL reconstruction was 2.6%, with no statistical difference between transphyseal and physeal-sparing techniques. Physeal-sparing techniques had a lower rate of post-operative complications compared with transphyseal techniques (p = 0.0045). Outcomes assessed were Lysholm score, International Knee Documentation Committee (IKDC) score, the IKDC grade, the Tegner score and the KT-1000. Both techniques had similar clinical outcomes. Conclusions. This review reveals low rates of disturbance of growth after ACL reconstruction in skeletally immature patients. Although limited, the available evidence did not support any particular surgical technique when considering disturbance of growth or clinical outcome. Further randomised controlled trials are needed to investigate the efficacy of differing surgical techniques on outcomes in skeletally immature patients. Cite this article: Bone Joint J 2017;99-B:1053–60

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

Objectives. This study aimed to investigate time-dependent gene expression of injured human anterior cruciate ligament (ACL), and to evaluate the histological changes of the ACL remnant in terms of cellular characterisation. Methods. Injured human ACL tissues were harvested from 105 patients undergoing primary ACL reconstruction and divided into four phases based on the period from injury to surgery. Phase I was < three weeks, phase II was three to eight weeks, phase III was eight to 20 weeks, and phase IV was ≥ 21 weeks. Gene expressions of these tissues were analysed in each phase by quantitative real-time polymerase chain reaction using selected markers (collagen types 1 and 3, biglycan, decorin, α-smooth muscle actin, IL-6, TGF-β1, MMP-1, MMP-2 and TIMP-1). Immunohistochemical staining was also performed using primary antibodies against CD68, CD55, Stat3 and phosphorylated-Stat3 (P-Stat3). . Results. Expression of IL-6 was mainly seen in phases I, II and III, collagen type 1 in phase II, MMP-1, 2 in phase III, and decorin, TGF-β1 and α-smooth muscle actin in phase IV. Histologically, degradation and scar formation were seen in the ACL remnant after phase III. The numbers of CD55 and P-Stat3 positive cells were elevated from phase II to phase III. . Conclusions. Elevated cell numbers including P-Stat3 positive cells were not related to collagens but to MMPs’ expressions

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

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]

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

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

Aims. The aim of this prospective study was to assess the long-term clinical, radiological, functional, and quality of life (QoL)-related outcome of patients treated with the synthetic Ligament Advanced Reinforcement System (LARS) device for anterior cruciate ligament (ACL) rupture. Methods. A total of 41 patients who underwent ACL reconstruction with the LARS device (mean age 39.8 years (SD 12.1 ); 32% females (n = 13)) were prospectively included between August 2001 and March 2005. MRI scans and radiographs were performed at a median follow-up of 2.0 years (interquartile range (IQR) 1.3 to 3.0; n = 40) and 12.8 years (IQR 12.1 to 13.8; n = 22). Functional and QoL-related outcome was assessed in 29 patients at a median follow-up of 12.8 years (IQR 12.0 to 14.0) and clinically reconfirmed at latest median follow-up of 16.5 years (IQR 15.5 to 17.9). International Knee Documentation Committee (IKDC) and Tegner scores were obtained pre- and postoperatively, and Lysholm score postoperatively only. At latest follow-up, range of motion, knee stability tests, 36-Item Short Form Health Survey (SF-36), and IKDC scores were ascertained. Complications and reoperations during follow-up were documented. Results. Cumulative complication rate was 66% (n = 27), with 11 developing within one year from surgery and 16 after one year (including five patients with both early and late complications). Ten graft failures (24%) and eight cases of reactive synovitis were observed (20%). All 11 patients with early complications and ten with late complications underwent reoperation (including five with another surgical procedure for early complications), amounting to a cumulative reoperation rate of 51% (n = 21). Revision ACL reconstruction was performed in one patient (2.4%). Median IKDC at latest follow-up was 89.7 (IQR 78.2 to 93.1), being significantly worse in the event of previous complications. Lachman test was positive in 56% (n = 15) of reconstructed knees. All norm-based SF-36 items were at or above median at latest follow-up, and did not differ depending on development of complications. Conclusion. Despite good functional and QoL-related results in the long term, the cumulative complication rate of 66%, including graft failures and reactive synovitis, has to be viewed with great concern. Cite this article: Bone Joint J 2022;104-B(2):242–248

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

The anterior cruciate ligament (ACL) is frequently injured in elite athletes, with females up to eight times more likely to suffer an ACL tear than males. Biomechanical and hormonal factors have been thoroughly investigated; however, there remain unknown factors that need investigation. The mechanism of injury differs between males and females, and anatomical differences contribute significantly to the increased risk in females. Hormonal factors, both endogenous and exogenous, play a role in ACL laxity and may modify the risk of injury. However, data are still limited, and research involving oral contraceptives is potentially associated with methodological and ethical problems. Such characteristics can also influence the outcome after ACL reconstruction, with higher failure rates in females linked to a smaller diameter of the graft, especially in athletes aged < 21 years. The addition of a lateral extra-articular tenodesis can improve the outcomes after ACL reconstruction and reduce the risk of failure, and it should be routinely considered in young elite athletes. Sex-specific environmental differences can also contribute to the increased risk of injury, with more limited access to and availablility of advanced training facilities for female athletes. In addition, football kits are designed for male players, and increased attention should be focused on improving the quality of pitches, as female leagues usually play the day after male leagues. The kit, including boots, the length of studs, and the footballs themselves, should be tailored to the needs and body shapes of female athletes. Specific physiotherapy programmes and training protocols have yielded remarkable results in reducing the risk of injury, and these should be extended to school-age athletes. Finally, psychological factors should not be overlooked, with females’ greater fear of re-injury and lack of confidence in their knee compromising their return to sport after ACL injury. Both intrinsic and extrinsic factors should be recognized and addressed to optimize the training programmes which are designed to prevent injury, and improve our understanding of these injuries. Cite this article: Bone Joint J 2023;105-B(10):1033–1037

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

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

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

We sought to determine whether smoking affected the outcome of reconstruction of the anterior cruciate ligament. We analysed the results of 66 smokers (group 1 with a mean follow-up of 5.67 years (1.1 to 12.7)) and 238 non-smokers (group 2 with a mean follow-up of 6.61 years (1.2 to 11.5)), who were statistically similar in age, gender, graft type, fixation and associated meniscal and chondral pathology. The assessment was performed using the International Knee Documentation Committee form and serial cruciometer readings. Poor outcomes were reported in group 1 for the mean subjective International Knee Documentation Committee score (p < 0.001), the frequency (p = 0.005) and intensity (p = 0.005) of pain, a side-to-side difference in knee laxity (p = 0.001) and the use of a four-strand hamstring graft (p = 0.015). Patients in group 1 were also less likely to return to their original level of pre-injury sport (p = 0.003) and had an overall worse final 7 International Knee Documentation Committee grade score (p = 0.007). Despite the well-known negative effects of smoking on tissue healing, the association with an inferior outcome after reconstruction of the anterior cruciate ligament has not previously been described and should be included in the pre-operative counselling of patients undergoing the procedure