Electrostatic attachment of exosome onto a 3D-fabricated calcium silicate/polycaprolactone for enhanced bone regeneration.

Exosomes have garnered attention for use in bone regeneration, but their low activity, rapid degradation, and inaccurate delivery have been obstacles to their use in clinical applications. As such, there exists a need for an exosome-integrated delivery platform. Calcium silicate (Ca-Si) is considered one of the most promising bioceramics for bone regeneration because of its remarkable ability to promote hydroxyapatite formation, osteoblast proliferation, and differentiation. However, Ca-Si has limitations, such as a high degradation rate leading to high pH values. Here, we propose a bone regeneration platform: three-dimensional-fabricated Ca-Si scaffolds immersed in polycaprolactone (PCL) coated with exosomes. This setup enhanced porosity, mechanical strength, and natural hydroxyapatite formation. Ca-Si incorporation increased the quantity of attached exosomes on the scaffold and enabled more sustainable control of their release compared to bare PCL. The exosome-coated scaffold exhibited excellent cell attachment and osteogenic differentiation, significantly increasing biocompatibility and the in situ recruitment of stem cells when transplanted into the subcutaneous tissue of mice. The bone regenerating efficacy of the exosome-attached scaffold was confirmed using a mouse calvarial bone defect animal model. These findings suggest a potential application of exosome-coated Ca-Si/PCL scaffolds as an osteogenic platform for critical bone defects.

Bursal Tissue Harvested During Rotator Cuff Repair Contains Viable Mesenchymal Stem Cells.

Purpose: To evaluate the effect of intraoperative ablation on the viability, distribution, phenotype, and potential for culture expansion of bursal cells harvested during arthroscopic rotator cuff surgery. Methods: Tissue was collected during primary arthroscopic rotator cuff repair on 6 healthy, randomly selected patients from a fellowship-trained surgeon's practice between September 2020 and January 2021. There were 3 women (aged 60 ± 8 years) and 3 men (aged 61 ± 10 years). At the time of surgery, subacromial bursal tissue was subjected to no ablation, 1 second of ablation, or 3 seconds of ablation. Tissues were collected by an autograft harvesting system connected to an arthroscopic shaver and a pituitary grasper. Tissue fragments from each condition were sampled for viability testing or cell isolation. A viability kit with confocal microscopy was used to assess live and dead cells. Cell isolation consisted of collagenase digestion or placing tissue fragments onto tissue culture-treated plates that induced migration of cells out of the tissue. Cell proliferation rates were monitored and surface markers for mesenchymal stem cells (MSC) and pericytes were analyzed via multicolor flow cytometry. Results: Increased ablation time significantly reduced cell viability. The mean percentage of live cells was 55.2% ± 27.2% (range, 26%-90% live) in the control group, 46.8% ± 23.8% (range, 9.6%-69.6%, P = .045) in the short-ablation group, and 35.5% ± 19% (range, 11%-54%, P = .03) in the long-ablation group. No significant differences in population doubling level (1.6 ± 0.5 days) and population doubling time (6.7 ± 2.4 days) were observed in cells from any treatment. The surface marker profile indicated an MSC phenotype with absence of a pericyte population. Ablation or cell isolation procedure had no significant effect on the surface marker profile of isolated cells. Conclusions: Radiofrequency ablation significantly reduced the overall tissue viability but had no significant effect on cell proliferation or expression of surface markers on isolated subacromial bursal cells harvested arthroscopically. Clinical Relevance: Analysis of the viability and performance of cells harvested after the use of ablation devices using mechanical surgical collection during rotator cuff repair surgery could further our understanding of subacromial bursal tissue and its potential role in augmenting rotator cuff repair healing.

Biocompatibility Study of Purified and Low-Temperature-Sterilized Injectable Collagen for Soft Tissue Repair: Intramuscular Implantation in Rats.

The clinical application of collagen-based biomaterials is expanding rapidly, especially in tissue engineering and cosmetics. While oral supplements and injectable skin boosters are popular for enhancing skin health, clinical evidence supporting their effectiveness remains limited. Injectable products show potential in revitalizing skin, but safety concerns persist due to challenges in sterilization and the risk of biological contamination. Traditional methods of sterilization (heat and irradiation) can denature collagen. This study addresses these issues by introducing a novel technique: the double filtration and low-temperature steam sterilization of a collagen gel. In vitro tests documented the sterility and confirmed that the collagen did not show cytotoxicity, degradation, integrity, and viscosity characteristics changes after the processing and sterilization. The collagen gel induced new collagen expression and the proliferation of human dermal fibroblasts when the cells were cultured with the collagen gel. An in vivo study found no adverse effects in rats or significant lesions at the implantation site over 13 weeks. These results suggest that this novel method to process collagen gels is a safe and effective skin booster. Advanced processing methods are likely to mitigate the safety risks associated with injectable collagen products, though further research is needed to validate their biological effectiveness and clinical benefits.

Does the femoral component design modified in consideration of Asian anatomical characteristics fit better than the conventional design for Korean femora in reality?

INTRODUCTION: We aimed to investigate the anatomical and clinical advantages of an Asian-specific femoral component design with a high femoral aspect ratio, compared with the conventional femoral component design. MATERIALS AND METHODS: A retrospective analysis of the operation and outpatient clinic records of 239 knees operated on using an anatomically modified femoral component design (MFCD, Group A) and 153 knees operated on using a conventional femoral component design (CFCD, Group B) in Korean patients was performed. Three subgroups were created based on the mediolateral size of the two different femoral component designs. The geometric accommodation of each femoral component was assessed using intraoperatively measured femoral posterior condylar resection and posterior condylar trimming amounts. Clinical outcomes were assessed using a range of motion (ROM) and patient-reported outcome measurements. RESULTS: In the comparison between Groups A and B, the mean combined bilateral posterior condylar trimming (XPCT) was 2.91 [2SD: - 4.12-9.94] and 1.45 [2SD: - 5.89-8.80], and the median XPCT was 3 and 1.5. In the largest subgroup (subgroup 2), Groups A and B included 100 and 112 patients, all six posterior condylar resection and trimming parameters were significantly larger in Group A. Preoperative and postoperative ROM and Hospital for Special Surgery scores were similar between the two groups. Preoperative Western Ontario and McMaster Universities Arthritis Index (WOMAC) was higher in Group A. However, postoperative WOMAC was similar between the groups. Perioperative improvement in WOMAC index was significantly greater in Group B. CONCLUSIONS: The Asian-specific femoral component design resulted in more resection and trimming of the femoral posterior condyle than the conventional design despite it was not associated with different clinical outcomes. Surgeons should be aware of unexpected excessive posterior condylar resection and formation of large flexion gap when using femoral component design with high femoral aspect ratio.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.