Elevated Lipid Metabolites in Stored Clinical OCA Media Correlate With Chondrocyte Death.

BACKGROUND: A major limitation of osteochondral allografts (OCA) is the deterioration of cartilage health associated with cell death during prolonged storage. However, little is known about the mechanisms that contribute to chondrocyte death during storage. PURPOSE/HYPOTHESIS: This study aimed to determine whether bioactive lipid metabolites accumulate in the storage media of OCA and whether they are associated with a loss of chondrocyte viability during prolonged storage. It was hypothesized that free fatty acids (FFAs) would accumulate over time in the storage media of OCA and adversely affect cartilage health during storage. STUDY DESIGN: Controlled laboratory study. METHODS: A group of 21 (n = 6-8 OCA/treatment group) fresh human hemicondylar OCA tissues and media were analyzed after 7, 28, and 68 days of prolonged cold (4°C) storage. Targeted mass spectrometry analysis was used to quantify bioactive FFAs, as well as primary (lipid hydroperoxide [ROOH]) and secondary (malondialdehyde) lipid oxidation products. Chondrocyte viability was measured using a fluorescence-based live/dead assay and confocal microscopy. RESULTS: The concentration of all targeted fatty acid metabolites in storage media was significantly increased with increased cold storage time (P < .05). ROOH was significantly higher on day 28 of cold storage. No difference in secondary ROOH products in storage media was observed. Chondrocyte viability significantly declined in both the en face and the vertical cross-sectional analysis with increased cold storage time and inversely correlated with fatty acid metabolites (P < .05). CONCLUSION: It is well established that elevated levels of certain FFAs and lipid oxidation products can alter cell function and cause cell death via lipotoxicity and other mechanisms. This work is the first to identify elevated levels of FFA metabolites and primary oxidation lipid products in the storage media from clinical OCA. The concentrations of FFA metabolites were measured at levels (>100 µM) known to induce cell death and were directly correlated with chondrocyte viability. CLINICAL RELEVANCE: These findings provide important targets for understanding why cartilage health declines during cold storage, which can be used to optimize media formulations and improve graft health.

Difference in Correction Power between Hybrid Lateral Closed-Wedge High Tibial Osteotomy and Medial Open-Wedge High Tibial Osteotomy was Associated with Severity of Varus Deformity and Different Hinge Distance from Center of Deformity.

Hybrid lateral closed-wedge high tibial osteotomy (HBHTO) carries certain advantages over medial open-wedge high tibial osteotomy (OWHTO). We investigated the potential difference in the required correction angle between HBHTO and OWHTO to achieve an equal amount of whole lower-extremity alignment correction, retrospectively analyzing the preoperative plain radiographic images of 100 patients. The medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), mechanical lateral distal femoral angle (mLDFA), hip-knee-ankle axis (HKA), length of the tibia, width of the tibial plateau, length of the lower limb (leg length), and location of the center of deformity (CD) were measured. Differences in the required correction angle at the hinge point between the two techniques (CAD) were compared, and correlation analysis was performed to reveal the influential factors. The mean difference in CAD between HBHTO and OWHTO was 0.78 ± 0.22 (0.4~1.5)°, and mean WBL position change per correction angle was 3.9 ± 0.3 (3.0~4.6)% in HBHTO and 4.1 ± 0.3 (3.1~4.7)% in OWHTO. Correlation analysis revealed a strong positive correlation between CAD and HKA. mLDFA, JLCA, MPTA, leg length, OWCD, HBCD, and HCD were also significantly correlated with CAD. HBHTO required a 5.6% larger correction angle at the hinge point to achieve the same amount of alignment correction as OWHTO.

Clinical Outcomes and Repair Integrity After Double-Row Modified Mason-Allen Repair Technique With a Single Knot in Small to Medium Supraspinatus Tears.

Background: Various arthroscopic rotator cuff repair techniques are being used for the treatment of rotator cuff tears with the development of surgical instruments. However, retears after repair are not completely avoidable, and efforts to reduce retears remain a challenge. Purpose/Hypothesis: To introduce a new repair technique, the double-row modified Mason-Allen technique with a single knot, and to compare clinical outcomes and retear rates with the single-row modified Mason-Allen technique. It was hypothesized that this new technique would have a better clinical outcome and significantly lower retear rate than the single-row modified Mason-Allen technique. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 110 patients with small- to medium-sized (<1.5 cm) full-thickness supraspinatus tears were enrolled into 2 groups, with 65 patients receiving the single-row modified Mason-Allen technique (group A) and 45 patients receiving the double-row modified Mason-Allen technique with a single knot (group B). The clinical and functional outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score; Disabilities of the Arm, Shoulder and Hand (DASH) score; and visual analog scale (VAS) for pain and satisfaction scores. All patients enrolled in this study were monitored for a minimum of 24 months. Magnetic resonance imaging was performed to analyze the integrity of tendons and retear at 6 months after surgery. Results: No statistically significant differences between the 2 groups were found regarding the VAS for pain, ASES, and DASH scores. However, retear was found in 9 patients (13.8%) in group A and 1 patient (2.2%) in group B. The difference in the retear rate was statistically significant between the 2 groups (P = .037). Conclusion: A significantly lower retear rate and comparable clinical outcomes were seen after the double-row modified Mason-Allen repair technique with a single knot when compared with the single-row modified Mason-Allen technique. Based on these findings, the double-row modified Mason-Allen repair technique with a single knot can be considered a surgical treatment option that can provide sufficient stability in small- to medium-sized supraspinatus tears.

Effect of Meniscal Tear Patterns and Preoperative Cartilage Status on Joint Space Width After Medial Opening-Wedge High Tibial Osteotomy.

BACKGROUND: Medial opening-wedge high tibial osteotomy (MOWHTO) is performed to treat young adults with medial compartment knee osteoarthritis associated with varus deformity. However, factors influencing joint space width (JSW) vary according to the type of medial meniscal tear and have not yet been completely elucidated. PURPOSE: To examine changes in JSW according to the type of medial meniscal tear after MOWHTO and analyze the influencing factors. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study was conducted on 134 patients who underwent MOWHTO for medial osteoarthritis and were followed up for >2 years. The patients were classified into 3 groups based on medial meniscal status: intact, nonroot tear, and root tear. The authors then measured the JSW preoperatively and at 3 months, 6 months, 1 year, and >2 years postoperatively; analyzed whether the change in JSW varied according to meniscal status; and determined the association of these changes with the preoperative cartilage grade of the medial femoral condyle (MFC) and medial tibial plateau (MTP). International Knee Documentation Committee (IKDC) scores were used to evaluate clinical function. RESULTS: Of the 134 patients, the medial meniscus was intact in 29 patients, a nonroot tear was observed in 58 patients, and a root tear was observed in 47 patients. Postoperatively, JSW increased for all groups, but the timing of the increase varied between the groups (P < .001). JSW increased the most 6 months postoperatively in the intact group and 3 months postoperatively in the nonroot tear and root tear groups (P < .001). Additionally, the increase in JSW was the greatest in the root tear group. Preoperatively, MFC and MTP cartilage status differed among the groups; MTP status did not affect the JSW, but MFC status did (P < .001). The IKDC score increased from the preoperative to postoperative time point in all groups, but there was no significant difference between groups. CONCLUSION: The authors observed that the amount and timing of increase in JSW were dependent on the pattern of medial meniscal tear observed when MOWHTO was performed. In addition, the cartilage grade of MFC before surgery was associated with changes in JSW. The IKDC score was not significantly different between groups. However, a longer follow-up period is needed to analyze the correlation with the meniscal tear pattern and JSW.

In Vivo Kinematics and Cruciate Ligament Tension Are Not Restored to Normal After Bicruciate-Preserving Arthroplasty.

BACKGROUND: Whether cruciate ligament forces in cruciate-preserving designs, such as unicompartmental knee arthroplasty (UKA) or bi-cruciate-retaining total knee arthroplasty (BCR-TKA), differ from those in normal knees remains unknown. The purpose of this study was to compare the in vivo kinematics and cruciate ligament force in knees before and after UKA or BCR-TKA to those in normal knees during high-flexion activity. METHODS: Overall, twenty normal knees, 17 knees with medial UKA, and 15 knees with BCR-TKA were fluoroscopically examined while performing a squatting activity. A 2-dimensional or 3-dimensional registration technique was employed to measure tibio-femoral kinematics. Ligament strains and tensions in the anteromedial bundle of the anterior cruciate ligament and posterolateral bundle of the anterior cruciate ligament and the anterolateral bundle of the posterior cruciate ligament (aPCL) and posteromedial bundle of the posterior cruciate ligament (pPCL) during knee flexion were analyzed. RESULTS: Tension in both bundles of the anterior cruciate ligament decreased with flexion. At 60° of flexion, anteromedial bundle of the anterior cruciate ligament tension in postoperative UKA knees was greater than that in normal knees. At 30° of flexion, posterolateral bundle of the anterior cruciate ligament tension in postoperative UKA knees was greater than that in normal knees. On the other hand, aPCL and pPCL tensions increased with flexion. From 40 to 110° of flexion, the postoperative aPCL tension in UKA knees was greater than that in normal knees. At 110° of flexion, the preoperative pPCL tension in UKA knees was greater than that in normal knees. In addition, the postoperative pPCL tension in UKA knees was larger than that in normal knees beyond 20° of flexion. Furthermore, the pPCL tension of postoperative BCR-TKA knees was larger than that in normal knees from 20 to 50° and beyond 90° of flexion. CONCLUSIONS: The cruciate ligament tensions, especially posterior cruciate ligament tension in knees after UKA, were greater than those in the normal knees. Surgeons performing bi-cruciat-preserving knee arthroplasties should therefore balance cruciate ligament tension more carefully in flexion and extension.

Evolution of the throwing shoulder: why apes don't throw well and how that applies to throwing athletes.

BACKGROUND: Humans have unique characteristics making us the only primate that can throw well while most other primates throw predominately underhand with poor speed and accuracy. The purpose of this study is to illuminate the uniquely human characteristics that allow us to throw so well. When treating an injury such as a labral tear or capsule tear, this study hopes the reader can gain a better understanding of the issues that lead to the tear and those that may determine the success of treatment besides the actual repair. METHODS: In addition to a review of scientific and medical literature, information was obtained from interviews and experience with primate veterinarians, anthropologists, archeologists, and professional baseball players. These sources were used to study the connection between evolutionary throwing activities and current sports medicine issues. RESULTS: Arm acceleration requires a functional kinetic chain, rapid motor sequences, and the ability to absorb elastic energy in the shoulder. Successful treatment of the throwing shoulder requires awareness of the shoulder's position in the kinetic chain and correction of defects in the ability to execute the kinetic chain. Some problems in the shoulder could reflect regression to a more primitive anatomy or dyskinesis. Return of performance requires regaining the elasticity in the tissues of the shoulder to temporarily store kinetic energy. For example, tissue remodeling after rotator cuff repair continues for months to years; however, the newly formed tissue lacks the same elasticity of the native tendon. This suggests why throwing performance typically does not return for 7 or more months after repair even though there may be structural integrity at 3-4 months. CONCLUSION: The shoulder has developed uniquely in modern man for the act of throwing. The anatomic deficiencies in primates for throwing provide an illustration of the more subtle changes that a throwing athlete might have that are detrimental to throwing. Nonhuman primates have been unable to demonstrate the kinetic chain sequence for throwing secondary to the lack of neurologic pathways required. Humans are more sophisticated and precise in their movements but lack robusticity in their bone and muscle architecture, seen especially in the human rotator cuff. Successful treatment of a throwing injury requires familiarity with the conditions that cause the injury or affect the rehabilitation process. The return of performance following injury or surgery requires regaining the elasticity in the tissues of the shoulder to temporarily store kinetic energy from the kinetic chain.

A Network Meta-Analysis of Randomized Controlled Trials Assessing Intraoperative Anesthetic Therapies for Analgesic Efficacy and Morphine Consumption Following Total Knee Arthroplasty.

BACKGROUND: The purpose of this study was to compare intraoperative anesthetic therapies for total knee arthroplasty (TKA) regarding postoperative analgesic efficacy and morphine consumption by conducting a systematic literature search. METHODS: Randomized controlled trials of TKA using various anesthetic therapies were identified from various databases from conception through December 31, 2021. A network meta-analysis of relevant literature was performed to investigate which treatment showed better outcomes. In total, 40 trials were included in this study. RESULTS: Surface under the cumulative ranking curve showed local infiltration anesthesia (LIA) with saphenous nerve block (SNB) to produce the best pain relief on postoperative days (PODs) 1 and 2 and the best reduction of morphine consumption on PODs 1 and 3. However, femoral nerve block showed the largest effect on pain relief on POD 3, and liposomal bupivacaine showed the largest effect on reduction of morphine consumption on POD 2. CONCLUSIONS: According to this network meta-analysis, surface under the cumulative ranking curve percentage showed that LIA with SNB provided the best analgesic effect after TKA. Furthermore, patients receiving LIA with SNB had the lowest consumption of morphine. Although femoral nerve block resulted in better pain relief on POD 3, LIA with SNB could be selected first when trying to reduce morphine consumption or increase early ambulation.

Repair of medial meniscus posterior root tear is effective for root healing and cartilage regeneration in opening wedge high tibial osteotomy.

PURPOSE: This study aimed to determine whether the repair of a medial meniscus posterior root tear (MMPRT) is effective for MMPRT healing, cartilage regeneration, and clinical outcomes in opening wedge high tibial osteotomy (OWHTO). METHODS: This retrospective study included 80 patients who underwent OWHTO and subsequent second-look arthroscopy. The patients were divided into OWHTO-with-MMPRT-repair (n = 40) and OWHTO alone (n = 40) groups, and the healing rates (complete/partial/failure) were compared. Each group was further divided into over- and under-corrected subgroups to compare healing rates. The International Cartilage Repair Society (ICRS) grade, cartilage defect size, Koshino stage, ICRS cartilage repair assessment score of the medial femoral condyle (MFC), and International Knee Documentation Committee (IKDC) scores between the OWHTO-with-MMPRT-repair and OWHTO alone groups were compared according to whether microfracture was performed on the MFC. RESULTS: The overall healing rate of the MMPRT was higher in the OWHTO-with-MMPRT-repair group than that in the OWHTO alone group (P < 0.001). In addition, in the subgroup analysis, no difference in the MMPRT healing rate between the over-correction and under-correction groups when MMPRT repair was performed (n.s). In contrast, without MMPRT repair, the healing rate was lower in the under-correction group than that in the over-correction group (P = 0.03). Cartilage regeneration of the OWHTO-with-MMPRT-repair group was superior to that of the OWHTO alone group (P < 0.05). The IKDC subjective scores of the OWHTO-with-MMPRT-repair and OWHTO alone groups were 34.5 and 33.1 before surgery (n.s) and 50 and 47.2 at one year after surgery, respectively (n.s). These differences between the two groups for cartilage regeneration and IKDC subjective scores showed the same pattern regardless of microfractures. CONCLUSIONS: MMPRT repair during OWHTO might improve MMPRT healing, even with under-correction, and cartilage regeneration of MFC, regardless of microfracture. However, OWHTO with MMPRT repair might not improve short-term clinical outcomes compared to OWHTO alone. Further randomized clinical trials are necessary. LEVEL OF EVIDENCE: III, Retrospective cohort study.

Determining the Relationship between Mechanical Properties and Quantitative Magnetic Resonance Imaging of Joint Soft Tissues Using Patient-Specific Templates.

To determine whether the mechanical properties of joint soft tissues such as cartilage can be calculated from quantitative magnetic resonance imaging (MRI) data, we investigated whether the mechanical properties of articular cartilage and meniscus scheduled to be resected during arthroplasty are correlated with the T2 relaxation time on quantitative MRI at the same location. Six patients who had undergone knee arthroplasty and seven who had undergone hip arthroplasty were examined. For the knee joint, the articular cartilage and lateral meniscus of the distal lateral condyle of the femur and proximal lateral tibia were examined, while for the hip joint, the articular cartilage above the femoral head was studied. We investigated the relationship between T2 relaxation time by quantitative MRI and stiffness using a hand-made compression tester at 235 locations. The patient-individualized template technique was used to align the two measurement sites. The results showed a negative correlation (from -0.30 to -0.35) in the less severely damaged articular cartilage and meniscus. This indicates that tissue mechanical properties can be calculated from T2 relaxation time, suggesting that quantitative MRI is useful in determining when to start loading after interventional surgery on cartilage tissue and in managing the health of elderly patients.

Medial patellofemoral ligament reconstruction appears to be a better treatment than repair, proximal realignment, or conservative management for primary patellar dislocation: A network meta-analysis.

BACKGROUND: The purpose of this study was to compare the functional outcomes and re-dislocation rates of medial patellofemoral ligament (MPFL) reconstruction, MPFL repair, combined proximal realignment (CPR), and conservative management for primary patellar dislocation by conducting a systematic literature search of the available studies. The hypothesis was that MPFL repair and MPFL reconstruction would be better options for treating primary patellar dislocation. METHODS: Randomized controlled trials or prospective studies of primary patellar dislocation treated with MPFL reconstruction, MPFL repair, CPR, or conservative management were identified from the MEDLINE, EMBASE, and the Cochrane Library databases through December 31, 2021. A total of 626 patients met the prespecified inclusion criteria. The methodological quality of each study was assessed using a risk of bias table, Detsky quality index, and Newcastle-Ottawa Scale. The end-point data collected included comparisons of the mean in functional scores on knee outcomes scales and the number of patients who experienced re-dislocation. A network meta-analysis of the relevant literature was performed to investigate which treatment showed better outcomes. RESULTS: In total, 10 trials were included in this study. There was no statistically significant difference in the subgroup analysis in terms of the functional outcomes among MPFL reconstruction, MPFL repair, CPR, and conservative management. However, MPFL reconstruction showed statistically significantly better outcomes than MPFL repair, CPR, or conservative management in terms of the re-dislocation rate. Additionally, surface under the cumulative ranking curve percentage showed that MPFL reconstruction had a lower probability of re-dislocation than MPFL repair even though there was no significant difference (0.24, 95% confidence interval: 0.02-2.91). CONCLUSION: Using a network meta-analysis, this meta-analysis showed that there was no significant difference in functional outcomes in a subgroup analysis. In re-dislocation subgroup analysis, MPFL repair and MPFL reconstruction produced significantly better results than other treatments. Also, surface under the cumulative ranking curve percentage showed that MPFL reconstruction had a lower probability of re-dislocation than MPFL repair.

Bicruciate-retaining total knee arthroplasty procedure reduced tensile force in the middle and posterior components of lateral collateral ligament during deep knee flexion activities with no effect on tensile force of the medial collateral ligament.

PURPOSE: To analyse the effects of bicruciate-retaining total knee arthroplasty (BCR-TKA) on the tensile force of the collateral ligaments during two deep knee flexion activities, cross-leg sitting and squatting. METHODS: Thirteen patients (15 knees) treated using bicruciate-retaining total knee arthroplasty (BCR-TKA) for knee joint osteoarthritis were analysed. Knee joint kinematics during cross-leg sitting (open-chain flexion) and squatting (closed-chain flexion) were evaluated through fluoroscopy. The tensile force was calculated in vivo based on the change in the distance between the femoral and tibial attachment areas for the anterior, middle, and posterior components of the superficial (sMCL) and deep (dMCL) medial collateral ligament and the lateral collateral ligament (LCL). Differences in the calculated tensile forces of the collateral ligaments were evaluated using repeated measures of analysis of variance, with post hoc pairwise comparison (Bonferroni test). Statistical significance was set at P ≤ 0.05. RESULTS: The correction of the coronal alignment was related to the surgical technique, not to the implant design. No significant change in the tensile force in all three components of the sMCL from pre- to post-TKA (n.s.) was observed. For dMCL, a pre- to post-TKA change in the tensile force was observed only for the anterior dMCL component (p = 0.03). No change was observed in the tensile force of the anterior LCL with increasing flexion, with no difference in pre- to post-TKA and between activities (n.s.). In contrast, tensile force in the middle LCL slightly decreased with increasing flexion during squatting, pre- and post-TKA. After surgery, lower forces were generated at 40° of flexion (p = 0.04). Tensile force in the posterior LCL was higher in extension than flexion, which remained high in the extension post-TKA. However, after surgery, lower tensile forces were generated at 10° (p = 0.04) and 40° (p = 0.04) of flexion. CONCLUSIONS: The in vivo change in tensile forces of the collateral ligaments of the knee before and after BCR-TKA can inform the development of appropriate ligament balancing strategies to facilitate recovery of deep knee flexion activities after TKA, as well as for continued improvement of BCR-TKA designs. LEVEL OF EVIDENCE: III.

ALK-5 Inhibitors for Efficient Derivation of Mesenchymal Stem Cells from Human Embryonic Stem Cells.

Objectives: Successful tissue regeneration requires a clinically viable source of mesenchymal stem cells (MSCs). We explored activin receptor-like kinase (ALK)-5 inhibitors to rapidly derive an MSC-like phenotype with high cartilage forming capacity from a xeno-free human embryonic cell line. Methods: Embryonic stem cell (ESC) lines (H9 and HADC100) were treated with the ALK-5 inhibitor SB431542; HADC100 cells were additionally treated with ALK-5 inhibitors SB525334 or GW788388. Cells were then seeded upon human fibronectin in the presence of fibroblast growth factor 2 (FGF2) in a serum-free medium. Flow cytometry was used to assess MSC markers (positive for CD73, CD90, and CD105; negative for CD34 and CD45). Differentiation status was assessed through quantitative polymerase chain reaction. Cartilage forming capacity was determined in high-density pellet cultures, in fibrin gels containing extracellular matrix (fibrin-ECM), and after implantation in ex vivo human osteoarthritic cartilage. Gene expression, histology, and immunostaining were used to assess cartilage phenotype, tissue regeneration, and integration. Results: Exposure to all three ALK-5 inhibitors lead to expression of mesodermal gene markers and differentiation into MSC-like cells (embryonic stem cell-derived mesenchymal stem cells [ES-MSCs]) based on surface marker expression. ES-MSC in pellet cultures or in fibrin-ECM gels expressed high levels of chondrogenic genes: COL2A1, ACAN, and COMP; and low levels of COL1A1 and RUNX2. Cell pellets or fibrin constructs implanted into ex vivo human osteoarthritic cartilage defects produced GAG-rich (safranin O positive) and collagen type II-positive neocartilage tissues that integrated well with native diseased tissue. Conclusions: We developed a protocol for rapid differentiation of xeno-free ESC into MSC-like cells with high cartilage forming capacity with potential for clinical applications. Impact statement Osteoarthritis (OA) is a common disease resulting in significant disability and no approved disease modifying treatment (other than total joint replacement). Embryonic stem cell-derived cell therapy has the potential to benefit patients with cartilage lesions leading to OA and may prevent or delay the need for total joint replacement.

Senescent cell population with ZEB1 transcription factor as its main regulator promotes osteoarthritis in cartilage and meniscus.

OBJECTIVES: Single-cell level analysis of articular cartilage and meniscus tissues from human healthy and osteoarthritis (OA) knees. METHODS: Single-cell RNA sequencing (scRNA-seq) analyses were performed on articular cartilage and meniscus tissues from healthy (n=6, n=7) and OA (n=6, n=6) knees. Expression of genes of interest was validated using immunohistochemistry and RNA-seq and function was analysed by gene overexpression and depletion. RESULTS: scRNA-seq analyses of human knee articular cartilage (70 972 cells) and meniscus (78 017 cells) identified a pathogenic subset that is shared between both tissues. This cell population is expanded in OA and has strong OA and senescence gene signatures. Further, this subset has critical roles in extracellular matrix (ECM) and tenascin signalling and is the dominant sender of signals to all other cartilage and meniscus clusters and a receiver of TGFß signalling. Fibroblast activating protein (FAP) is also a dysregulated gene in this cluster and promotes ECM degradation. Regulons that are controlled by transcription factor ZEB1 are shared between the pathogenic subset in articular cartilage and meniscus. In meniscus and cartilage cells, FAP and ZEB1 promote expression of genes that contribute to OA pathogenesis, including senescence. CONCLUSIONS: These single-cell studies identified a senescent pathogenic cell cluster that is present in cartilage and meniscus and has FAP and ZEB1 as main regulators which are novel and promising therapeutic targets for OA-associated pathways in both tissues.

Subject-specific computational modeling of acromioclavicular and coracoclavicular ligaments.

BACKGROUND: Disruption of the acromioclavicular joint is a common injury. Despite the different surgical procedures described for treating this injury, complications such as loss of reduction and failure of fixation remain unacceptably high. We developed a computer model of the acromioclavicular joint to better understand the biomechanical contributions of the ligaments that are typically injured. METHODS: Six fresh frozen human cadaveric shoulders were tested on an AMTI VIVO 6-degree of freedom test platform to measure force-displacement in inferior translation, anteroposterior translation, and internal rotation before and after sequentially transecting the coracoclavicular and acromioclavicular ligaments. These data were used to construct computer models of each specimen. Three-dimensional computed tomographic scans were used to generate a rigid-body dynamics model using the AnyBody Modeling System. The scapula and clavicle were connected by the acromioclavicular joint capsule, the conoid ligament, and the trapezoid ligament. Subject-specific ligament properties were calculated by matching computer predictions to experimental force-displacement data. RESULTS: The calculated free lengths of the conoid, trapezoid, and acromioclavicular ligaments were 13.5 (±3.2), 11.8 (±2.4), and 11.0 (±2.7) mm, respectively. The calculated stiffnesses of the conoid, trapezoid, and acromioclavicular ligaments were 34.3 (±6.3), 28.4 (±3.2), and 33.8 (±8.2) N/mm, respectively. Root mean square deviation (RMSD) of predicted force-displacement curves relative to experimental force-displacement curves (during inferior and anteroposterior translation) was less than 1 mm. For validation of subject-specific models, after ligament properties were calculated, the RMSD of the predicted torque over 15° of internal rotation was 12% of maximum rotational torque (average for 6 specimens). DISCUSSION AND CONCLUSION: Acromioclavicular disruption results in multidirectional instability, which requires careful consideration of the individual contributions of the injured ligaments. In addition, variations in patient anatomy can significantly affect the biomechanical stability of the reconstruction. Subject-specific models can enhance our understanding of the individual and collective biomechanical contributions of the injured soft tissues to the multiaxial stability of the acromioclavicular joint. These models may also be useful for analyzing and assessing biomechanical stability after various types of surgical reconstruction.

Tibial sagittal and rotational alignment reduce patellofemoral stresses in posterior stabilized total knee arthroplasty.

Patellofemoral joint complications remain an important issue in total knee arthroplasty. We compared the patellofemoral contact status between cruciate-retaining and posterior-stabilized designs with varying degrees of tibial sagittal and rotational alignment using a computer simulation to ensure proper alignments in total knee arthroplasty. Knee kinematics, patellofemoral contact force and quadriceps force were computed using a musculoskeletal modeling program (LifeMOD/KneeSIM 2010; LifeModeler, Inc., San Clemente, California) during a weight-bearing deep knee bend. Two different posterior tibial slope (PTS)s (3° and 7°) and five different tibial tray rotational alignments (neutral, internal 5° and 10°, and external 5° and 10°) were simulated. Patellofemoral contact area and stresses were next computed using finite element analysis. The patellofemoral contact force for the posterior-stabilized design was substantially lower than the cruciate-retaining design after post-cam contact because of increasing femoral roll-back. Neutral rotational alignment of the tibial component resulted in smaller differences in patellofemoral contact stresses between cruciate-retaining and posterior-stabilized designs for PTSs of 3° or 7°. However, the patellar contact stresses in the cruciate-retaining design were greater than those in posterior-stabilized design at 120° of knee flexion with PTS of 3° combined with internal rotation of the tibial component. Our study provides biomechanical evidence implicating lower PTSs combined with internal malrotation of the tibial component and the resultant increase in patellofemoral stresses as a potential source of anterior knee pain in cruciate-retaining design.

Postoperative Valgus Laxity and Medial Pivot Kinematics Are Significantly Associated With Better Clinical Outcomes.

BACKGROUND: The relative impact of soft tissue balance and knee laxity on clinical outcomes after total knee arthroplasty (TKA) is not fully understood. We analyzed associations among knee laxity, kinematics, and patient-reported outcomes. METHODS: Knee Society Scores were recorded in 67 patients before and after primary TKA for osteoarthritis with varus deformity (N = 78). Varus and valgus laxity was measured in 78 knees using stress radiographs. Knee kinematics were measured fluoroscopically during stair ascent in 16 knees. RESULTS: On average, varus laxity decreased significantly, and valgus laxity increased significantly after TKA, although the net combined varus-valgus laxity did not change significantly. Postoperatively, the magnitude of valgus laxity correlated significantly with greater patient symptoms and satisfaction scores. Patients with medial pivot kinematics scored higher on patient satisfaction and standard activities. CONCLUSION: We found that postoperative valgus laxity and medial pivot kinematics were significantly associated with better clinical outcomes. These results emphasize the importance of careful preoperative planning and attention to intraoperative alignment and ligament balancing.

Pneumatospinning Biomimetic Scaffolds for Meniscus Tissue Engineering.

Nanofibrous scaffolds fabricated via electrospinning have been proposed for meniscus tissue regeneration. However, the electrospinning process is slow, and can only generate scaffolds of limited thickness with densely packed fibers, which limits cell distribution within the scaffold. In this study, we explored whether pneumatospinning could produce thicker collagen type I fibrous scaffolds with higher porosity, that can support cell infiltration and neo-fibrocartilage tissue formation for meniscus tissue engineering. We pneumatospun scaffolds with solutions of collagen type I with thicknesses of approximately 1 mm in 2 h. Scanning electron microscopy revealed a mix of fiber sizes with diameters ranging from 1 to 30 µm. The collagen scaffold porosity was approximately 48% with pores ranging from 7.4 to 100.7 µm. The elastic modulus of glutaraldehyde crosslinked collagen scaffolds was approximately 45 MPa, when dry, which reduced after hydration to 0.1 MPa. Mesenchymal stem cells obtained from the infrapatellar fat pad were seeded in the scaffold with high viability (>70%). Scaffolds seeded with adipose-derived stem cells and cultured for 3 weeks exhibited a fibrocartilage meniscus-like phenotype (expressing COL1A1, COL2A1 and COMP). Ex vivo implantation in healthy bovine and arthritic human meniscal explants resulted in the development of fibrocartilage-like neotissues that integrated with the host tissue with deposition of glycosaminoglycans and collagens type I and II. Our proof-of-concept study indicates that pneumatospinning is a promising approach to produce thicker biomimetic scaffolds more efficiently that electrospinning, and with a porosity that supports cell growth and neo-tissue formation using a clinically relevant cell source.

Collagen fibrous scaffolds for sustained delivery of growth factors for meniscal tissue engineering.

Aim: To mimic the ultrastructural morphology of the meniscus with nanofiber scaffolds coupled with controlled growth factor delivery to modulate cellular performance for tissue engineering of menisci. Methods: The authors functionalized collagen nanofibers by conjugating heparin to the following growth factors for sustained release: PDGF-BB, TGF-ß1 and CTGF. Results: Incorporating growth factors increased human meniscal and synovial cell viability, proliferation and infiltration in vitro, ex vivo and in vivo; upregulated key genes involved in meniscal extracellular matrix synthesis and enhanced generation of meniscus-like tissue. Conclusion: The authors' results indicate that functionalizing collagen nanofibers can create a cell-favorable micro- and nanoenvironment and can serve as a system for sustained release of bioactive factors.

Lay abstract Meniscal tears are a common injury to the part of the knee called the meniscus. Loss of meniscal tissue can lead to arthritis. In this study, the authors aimed to recreate the structure of the human meniscus using very thin (nanometers in diameter) fibers made of collagen. The authors also attached proteins called growth factors to the fibers. The addition of these proteins increased the growth rate of cells collected from human knee tissue. The levels of important genes involved in meniscal tissue formation were increased in these cells. These results show that adding proteins such as growth factors to collagen nanofibers can create an environment beneficial to growing meniscal tissue. Successful development of this technology could help in repairing meniscal damage in people.

Intraoperative knee kinematics measured by computer-assisted navigation and intraoperative ligament balance have the potential to predict postoperative knee kinematics.

This study was designed to analyze the effects of type of activity and cruciate ligament resection on knee kinematics and ligament balance after total knee arthroplasty (TKA), and to determine if intraoperative passive kinematics are associated with active kinematics. Fresh-frozen human cadaveric knees were examined. The knees were mounted on a quadriceps-driven simulator. Cruciate-retaining (CR-TKA) and posterior-substituting (PS-TKA) TKA was performed using a contemporary knee system. Active flexion (closed-kinetic chain [CKC] and open-kinetic-chain [OKC]) and passive flexion were analyzed by recording the knee kinematics using a specifically developed application of an imageless navigation system. An electronic ligament balancer was used to measure the tibiofemoral gap under constant distraction pressure. The femur rotated externally relative to the tibia during passive and active CKC flexion. The femur translated anteriorly from 10° to 50° of flexion after TKA. Beyond 50° of flexion, the femur translated posteriorly in all surgical conditions. The femoral location during active CKC flexion was posterior relative to that during active OKC. Femoral rotation and translation during passive knee flexion correlated significantly with that during active knee flexion. Posterior tilt of the electronic ligament balancer was greater with CR-TKA than with PS-TKA and correlated significantly with the anteroposterior position of the femur. Statement of Clinical Significance: Intraoperative knee kinematics measured by computer-assisted navigation and intraoperative ligament balance have the potential to predict postoperative knee kinematics.

Subcutaneous toxicity of a dual ionically cross-linked atelocollagen and sodium hyaluronate gel: Rat in vivo study for biological safety evaluation of the injectable hydrogel.

Hydrogels are commonly used in wound dressing, as they retain moisture, accelerate healing, and break down necrotic tissue. This process enhances patient comfort levels while simultaneously reducing pain caused by dead tissue. The purpose of this study was to investigate the in vivo toxicity of a dual hydrogel consisting of type I atelocollagen cross-linked with sodium hyaluronate hydrogel used for wound dressing. Porcine type I atelocollagen was cross-linked with sodium hyaluronate to form the hydrogel. For subcutaneous implantation, 0.5 ml of dual hydrogel was injected into two different sites of twenty rats per group. High density polyethylene rods were implanted subcutaneously to serve as a control material. Hematological assessment, blood biochemistry, histopathological, and histological evaluations were scored and graded after 4 weeks. A bioreactivity rating was used for evaluation of subacute toxicity. Differences observed in blood chemical analysis and hematological analysis between control and test groups were within normal variations and considered unrelated to the test article implantation. No significant implantation-related lesions were observed in any of the major organs of all test animals. The overall histopathological index of the test article implantation sites was evaluated as 0. The bioreactivity rating was evaluated as non-irritant after 4-week subcutaneous implantation. Overall, these results indicate that the dual hydrogel of type I atelocollagen and sodium hyaluronate is biologically and chemically safe for clinical application as a wound dressing.