Young human plasma-derived extracellular vesicles rescue and reactivate IL-1ß and TNF-α treated chondrocytes.

Osteoarthritis (OA) is a degenerative disease that affects millions of individuals worldwide. Despite its prevalence, the exact causes and mechanisms behind OA are still not fully understood, resulting in a lack of effective treatments to slow down or halt disease progression. Recent research has discovered that extracellular vesicles (EVs) present in the circulation of young mice have a remarkable ability to activate musculoskeletal stem cells in elderly mice. Conversely, EVs derived from elderly mice do not exhibit the same potential, indicating that EVs obtained from young individuals may hold promise to activate aging cells in degenerative tissue. However, it remains unknown whether EVs derived from young individuals can also address cartilage degeneration caused by aging. In this study, we first evaluated EVs derived from young human plasma (YEVs) and EVs derived from old human plasma (OEVs) in an in vitro experiment using chondrocytes. The results revealed that YEVs effectively stimulated chondrocyte proliferation and migration, while OEVs from old plasma did not exhibit a similar effect. Given that OA represents a more complex inflammatory microenvironment, we further determine whether the benefits of YEVs on chondrocytes can be maintained in this context. Our findings indicate that YEVs have the ability to positively regulate chondrocyte function and protect them against apoptosis induced by IL-1ß and TNF-α in an in vitro OA model. Furthermore, we discovered that lyophilized EVs could be stored under mild conditions without any alterations in their physical characteristics. Considering the exceptional therapeutic effects and the wide availability of EVs from young plasma, they hold significant promise as a potential approach to activate chondrocytes and promote cartilage regeneration in early-stage OA.

Metabolic Syndrome Components and Its Impact on Acute Kidney Injury after Total Joint Arthroplasty.

BACKGROUND: Metabolic syndrome (MetS) is an independent risk factor for postoperative complications. This study aimed to evaluate the associated risk of MetS for perioperative complications, especially urinary complications, in patients who underwent primary total knee (TKA) or total hip arthroplasty (THA). METHODS: We used a publicly available all-payer administrative database to identify patients undergoing TKA and THA from 2016 to 2020. The primary exposure of interest was MetS. Multivariable adjusted models based on propensity score matching were used to evaluate the association of MetS components with acute kidney injury (AKI), urinary tract infection (UTI), and acute posthemorrhagic anemia (APHA) in patients who underwent TKA and THA. A Counterfactual-Based Mediation Analysis was conducted to investigate the mediating effect of APHA on the relationship between MetS and AKI. RESULTS: The analysis included 2,097,940 (16.4% with MetS) THA and 3,073,310 (24.0% with MetS) TKA adult hospitalizations. Multivariable adjustment analysis indicated MetS was associated with an increased risk of AKI (OR [odds ratio] 1.78, 95% CI [confidence interval]1.69 to 1.89 for THA; OR 1.88, 95% CI 1.79 to 1.96 for TKA), UTI (OR 1.13, 95% CI 1.03 to 1.23 for THA; OR 1.26, 95% CI 1.17 to 1.35 for TKA), and APHA (OR 1.17, 95% CI 1.14 to 1.20 for THA; OR 1.7, 95% CI 1.15 to 1.19 for TKA). The risk of AKI increased with the number of MetS components, with odds ratios ranging from 2.58 to 9.46 in TKA patients and from 2.22 to 5.75 in THA patients. This increase was particularly associated with diabetes and hypertension, which were the most significant associated risk factors. Furthermore, APHA mediated the association between MetS and AKI. CONCLUSION: The prevalence of MetS is increasing in TKA and THA patients. Metabolic syndrome was associated with increased risk of AKI, UTI, and APHA. The risk of AKI increased with each additional MetS component, with diabetes and hypertension contributing most. In addition, APHA may play a partial mediating role in MetS-induced AKI.

Transcription and proteome changes involved in re-innervation muscle following nerve crush in rats.

Severe peripheral nerve injury leads to the irreparable disruption of nerve fibers. This leads to disruption of synapses with the designated muscle, which consequently go through progressive atrophy and damage of muscle function. The molecular mechanism that underlies the re-innervation process has yet to be evaluated using proteomics or transcriptomics. In the present study, multi-dimensional data were therefore integrated with transcriptome and proteome profiles in order to investigate the mechanism of re-innervation in muscles. Two simulated nerve injury muscle models in the rat tibial nerve were compared: the nerve was either cut (denervated, DN group) or crushed but with the nerve sheath intact (re-innervated, RN group). The control group had a preserved and intact tibial nerve. At 4 weeks, the RN group showed better tibial nerve function and recovery of muscle atrophy compared to the DN group. As the high expression of Myh3, Postn, Col6a1 and Cfi, the RN group demonstrated superior re-innervation as well. Both differentially expressed genes (DEGs) and proteins (DEPs) were enriched in the peroxisome proliferator-activated receptors (PPARs) signaling pathway, as well as the energy metabolism. This study provides basic information regarding DEGs and DEPs during re-innervation-induced muscle atrophy. Furthermore, the crucial genes and proteins can be detected as possible treatment targets in the future.

Transtibial pull-out repair of lateral meniscus posterior root is beneficial for graft maturation after anterior cruciate ligament reconstruction: a retrospective study.

PURPOSE: To determine the repair of LMPR lesions would improve the ACL graft maturation. METHOD: A total of 49 patients underwent ACL reconstruction were included in this study. Patients were furtherly sub-grouped according to the status of LMPR: intact (17), repair (16) and resected (16). Assessments performed pre- and 2 years post-operatively included patients-reported scores and arthrometer side-to-side difference. Magnetic resonance imaging was used 2 years after the surgery to compare the lateral meniscal extrusion (LME), anterior tibial subluxation of the medial compartment (ATSMC), anterior tibial subluxation of the lateral compartment (ATSLC), the difference of ATSMC and ATSLC, and signal/noise quotient (SNQ) of ACL graft. RESULTS: In LMPR resected group, it showed greater post-operative ATSMC-ATSLC difference when compared with pre-operatively (P = 0.006) and with the other 2 groups (intact: P = 0.031; repair: P = 0.048). SNQ of ACL graft was higher in LMPR resected group than those in LMPR intact (P = 0.004) and repair group (P = 0.002). The LMPR repair group showed significant reduction in LME post-operatively (P = 0.001). Post-operative measures on ATSLC-ATSMC difference (ß = 0.304, P = 0.049) and LME (ß = 0.492, P = 0.003) showed significant association with graft SNQ. CONCLUSIONS: Transtibial repair of LMPR concomitant with ACL reconstruction restored translational stability, reduced meniscus extrusion, making it beneficial for ACL graft maturation.

The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1-5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

Comparison of hamstring and quadriceps strength after anatomical versus non-anatomical anterior cruciate ligament reconstruction: a retrospective cohort study.

BACKGROUND: Strength recovery of injured knee is an important parameter for patients who want to return to sport after anterior cruciate ligament reconstruction (ACLR). Comparison of muscle strength between anatomical and non-anatomical ACLR has not been reported. PURPOSE: To evaluate the difference between anatomical and non-anatomical single-bundle ACLR in hamstring and quadriceps strength and clinical outcomes. METHODS: Patients received unilateral primary single-bundle hamstring ACLR between January 2017 to January 2018 were recruited in this study. Patients were divided into anatomical reconstruction group (AR group) and non-anatomical reconstruction group (NAR group) according to femoral tunnel aperture position. The hamstring and quadriceps isokinetic strength including peak extension torque, peak flexion torque and H/Q ratio were measured at an angular velocity of 180°/s and 60°/s using an isokinetic dynamometer. The isometric extension and flexion torques were also measured. Hamstring and quadriceps strength were measured preoperatively and at 3, 6, and 12 months after surgery. Knee stability including Lachman test, pivot-shift test, and KT-1000 measurement and subjective knee function including International Knee Documentation Committee (IKDC) and Lysholm scores were evaluated during the follow-up. RESULTS: Seventy-two patients with an average follow-up of 30.4 months (range, 24-35 months) were included in this study. Thirty-three were in AR group and 39 in NAR group. The peak knee flexion torque was significant higher in AR group at 180°/s and 60°/s (P < 0.05 for both velocity) at 6 months postoperatively and showed no difference between the two groups at 12 months postoperatively. The isometric knee extension torque was significant higher in AR group at 6 months postoperatively (P < 0.05) and showed no difference between the two groups at 12 months postoperatively. No significant differences between AR group and NAR group were found regarding knee stability and subjective knee function evaluations at follow-up. CONCLUSIONS: Compared with non-anatomical ACLR, anatomical ACLR showed a better recovery of hamstring and quadriceps strength at 6 months postoperatively. However, the discrepancy on hamstring and quadriceps strength between the two groups vanished at 1 year postoperatively.

Combining reverse end-to-side neurorrhaphy with rapamycin treatment on chronically denervated muscle in rats.

This preliminary research determines whether a combination of reverse end-to-side neurorrhaphy and rapamycin treatment achieves a better functional outcome than a single application after prolonged peripheral nerve injury. We found that the tibial nerve function of the reverse end-to-side + rapamycin group recovered better, with a higher tibial function index value, higher amplitude recovery rate, and shorter latency delay rate (P < 0.05). The reverse end-to-side + rapamycin group better protected the gastrocnemius muscle with more forceful contractility, tetanic tension, and a higher myofibril cross-sectional area (P < 0.05). Combining reverse end-to-side neurorrhaphy with rapamycin treatment is a practical approach to promoting the recovery of chronically denervated muscle atrophy after peripheral nerve injury.

Alcohol Withdrawal Is Associated With Worse Outcomes in Patients Undergoing Primary Total Knee or Total Hip Arthroplasty.

BACKGROUND: Alcohol withdrawal (AW) syndrome is an independent risk factor for postoperative complications. This study aims to evaluate the influence of AW on perioperative outcomes in patients who underwent primary total knee (TKA) or total hip arthroplasty (THA). METHODS: We used the National Inpatient Sample database to identify patients undergoing TKA/THA from 2003 to 2014. The primary exposure of interest was AW. Multivariable adjusted models were used to evaluate the association of AW with in-hospital medical complications, surgical complications, mortality, cost, and length of stay (LOS) in patients undergoing TKA/THA. RESULTS: There were 2,971,539 adult hospitalizations for THAs and 6,367,713 hospitalizations for TKAs included in the present study, among which 0.14% of AW for THA patients and 0.10% of AW for TKA patients. Multivariable adjustment analysis suggested that AW was associated with an increased risk of medical complications (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.79-2.42, P < .0001), surgical complications (OR 1.75, 95% CI 1.51-2.03, P < .0001), and had 4.79 times increase of in-hospital mortality, 26% increase of total cost, and 53% increase of LOS in THA procedures. For TKA procedures, AW was also associated with increased risk of medical complications (OR 3.14, 95% CI 2.78-3.56, P < .0001), surgical complications (OR 2.07, 95% CI 1.82-2.34, P < .0001) and 4.24 times increase of in-hospital mortality, 29% increase of total cost, and 58% increase of LOS after multivariable adjustment. CONCLUSION: AW is associated with increased risk of in-hospital mortality, medical and surgical complications. Proactive surveillance and management of AW may be important in improving outcomes in patients who underwent THA and TKA procedure.

How to predict early clinical outcomes and evaluate the quality of primary total knee arthroplasty: a new scoring system based on lower-extremity angles of alignment.

BACKGROUND: A method that can accurately predict the outcome of surgery can give patients timely feedback. In addition, to some extent, an objective evaluation method can help the surgeon quickly summarize the patient's surgical experience and lessen dependence on the long wait for follow-up results. However, there was still no precise tool to predict clinical outcomes of total knee arthroplasty (TKA). This study aimed to develop a scoring system to predict clinical results of TKA and then grade the quality of TKA. METHODS: We retrospectively reviewed 98 primary TKAs performed between April 2013 and March 2017 to determine predictors of clinical outcomes among lower-extremity angles of alignment. Applying multivariable linear-regression analysis, we built Models (i) and (ii) to predict detailed clinical outcomes which were evaluated using the Knee Society Score (KSS). Multivariable logistic-regression analysis was used to establish Model (iii) to predict probability of getting a good clinical outcome (PGGCO) which was evaluated by Knee Injury and Osteoarthritis Outcome Score (KOOS) score. Finally, we designed a new scoring system consisting of 3 prediction models and presented a method of grading TKA quality. Thirty primary TKAs between April and December 2017 were enrolled for external validation. RESULTS: We set up a scoring system consisting of 3 models. The interpretations of Model (i) and (ii) were good (R2 = 0.756 and 0.764, respectively). Model (iii) displayed good discrimination, with an area under the curve (AUC) of 0.936, and good calibration according to the calibration curve. Quality of surgery was stratified as follows: "A" = PGGCO ≥0.8, "B" = PGGCO ≤0.6 but < 0.8, and "C" = PGGCO < 0.6. The scoring system performed well in external validation. CONCLUSIONS: This study first developed a validated, evidence-based scoring system based on lower-extremity angles of alignment to predict early clinical outcomes and to objectively evaluate the quality of TKA.

Alterations of kinematics in knees after single versus multiple radius femoral prostheses total knee arthroplasty: a retrospective study.

BACKGROUND: Design modifications in prostheses may cause alterations in gait kinematics, thus influencing functional restoration of knees after total knee arthroplasty (TKA). The aim of the study was to investigate the differences in gait kinematics and clinical outcomes after single radius (SR) versus multiple radius (MR) TKA. METHOD: The present retrospective study included 38 unilateral TKA involving 20 knees using MR design implant and 18 knees using SR design implant. Thirty-six healthy volunteers were also recruited. The mean follow-up time was 16 ± 3 months. At the end of follow-up, the 6 degrees of freedom (DOF) kinematics of knees and range of motion (ROM) were measured with a portable optical tracking system. Knee society score (KSS) and knee injury, and osteoarthritis outcome score (KOOS) were also collected. RESULTS: Patients in the SR group had significantly higher scores in activities of daily living (84.7 ± 15.9) and sports and recreation (67.5 ± 25.2) KOOS sub-score than MR group (69.9 ± 17.6, P = 0.012; 50.0 ± 20.8, P = 0.027, respectively). Significant differences were detected between MR knees and SR knees (1.82° ± 3.11° vs 4.93° ± 3.58°, P = 0.009), and MR knees and healthy knees (1.82° ± 3.11° vs 3.62° ± 3.52°, P = 0.032) in adduction/abduction ROM. The proximal/distal translation was significantly smaller in MR knees (0.58 ± 0.54 cm) compared with SR knees (1.03 ± 0.53 cm, P = 0.003) or healthy knees (0.84 ± 0.45 cm, P = 0.039). SR knees (0.24 ± 0.40 cm) had smaller translation compared with the MR group (0.54 ± 0.33 cm, P = 0.017) and control group (0.67 ± 0.36 cm, P = 0.028). No significant difference was detected in the other DOFs during the gait cycle. Significant difference was detected in extension/flexion, internal/external rotation, adduction/abduction, proximal/distal and medial/lateral among MR, SR and healthy knees. CONCLUSION: After TKA, patients have altered gait kinematics compared with the control group. MR and SR design showed varied characteristics in 6 DOF gait kinematics, which could be the cause of the difference in functional outcome.

3D uniaxial mechanical stimulation induces tenogenic differentiation of tendon-derived stem cells through a PI3K/AKT signaling pathway.

The tendon is a mechanosensitive tissue, but little is known about how mechanical stimulation selectively signals tenogenic differentiation and neo-tendon formation. In this study, we compared the impact of uniaxial and biaxial mechanical loading on tendon-derived stem cells (TDSCs). Our data show that there are variations in cell signaling and cell differentiation of mouse TDSCs in response to uniaxial and biaxial loading in monolayer culture. Whereas uniaxial loading induced TDSCs toward tenogenic and osteogenic differentiation, biaxial loading induced osteogenic, adipogenic, and chondrogenic differentiation of TDSCs. Furthermore, by applying uniaxial loading on 3-dimensional (3D) TDSC constructs, tenogenic-specific differentiation and neo-tendon formation were observed, results that were replicated in human TDSCs. We also showed that uniaxial loading induced PKB (AKT) phosphorylation (pAKT), whereas biaxial loading induced pERK. Most importantly, we found that inhibition of the PI3K/AKT signaling pathway could attenuate tenogenic differentiation and tendon formation in 3D TDSC constructs subjected to uniaxial loading. Taken together, our study highlights the importance of appropriate mechanobiological stimulation in 3D cell niches on tendon-like tissue formation and demonstrates that uniaxial mechanical loading plays an essential role in tenogenic differentiation and tendon formation by activating the PI3K/AKT signaling pathway.-Wang, T., Thien, C., Wang, C., Ni, M., Gao, J., Wang, A., Jiang, Q., Tuan, R. S., Zheng, Q., Zheng, M. H. 3D uniaxial mechanical stimulation induces tenogenic differentiation of tendon-derived stem cells through a PI3K/AKT signaling pathway.

Efficacy of the Wallis interspinous implant for primary lumbar disc herniation : a prospective randomised controlled trial.

PURPOSE: To investigate the efficacy of the Wallis implant after lumbar discectomy compared with discectomy alone for primary lumbar disc herniation. Seventy-seven patients with primary lumbar disc herniation were randomly assigned to undergo either posterior lumbar discectomy with (n=40, Wallis group) or without (n=37, control group) Wallis implantation. The primary outcomes were visual analogue scale score, Japanese Orthopedics Association score, and Oswestry Disability Index. The secondary outcomes were intervertebral disc height, range of motion of the operated segments, complications, and operating time. The primary outcomes at 1 week after treatment (P> 0.05) were not different between groups. The Wallis group had better scores at 12 months (P< 0.05) and the last follow-up visit (P< 0.05), higher disc height (P< 0.001), and significantly longer operating time (P =0.006) than the control group. Combined treatment appears beneficial for pain relief and lumbar function improvement by maintaining intervertebral disc height and limiting the range of motion of the spine compared with lumbar discectomy alone. However, its actual clinical benefit remains controversial because of the longer operating time and the relatively small difference in the visual analogue scale score and Oswestry Disability Index between the groups.

[Analysis of kinematic changes of hip joint after total hip arthroplasty].

Objective: To analyze the kinematic changes of the hip joint after total hip arthroplasty (THA) through three-dimensional gait analysis. Methods: Patients with hip joint diseases admitted between October 2022 and June 2023 were selected as the subjects. The patients who met the selective criteria were finally included in the THA group. The healthy volunteers matched with the THA group in the same age were included as the control group. Baseline data including age, gender, body mass index (BMI), and laterality were compared between the two groups. The Harris hip score (HHS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were recorded preoperatively and at last follow-up in the THA group. Three-dimensional motion capture system was utilized to collect spatiotemporal parameters and kinematic data during walking, including stride length, cadence, and maximum/minimum values, range of motion (ROM) in hip joint abduction/adduction, external/internal rotation, and flexion/extension, as well as gait scores. Differences between the two groups were analyzed. Additionally, the correlation between gait scores and postoperative HHS and WOMAC scores were analyzed in the THA group. Finally, the kinematic data of each degree of freedom (DOF) were fitted into a gait diagram, and the dynamic changes of the 3-DOF of the hip joint during the gait cycle were quantitatively analyzed. Results: There was no significant difference in gender, age, laterality, and BMI between the two groups ( n=20, P>0.05). The mean follow-up time in the THA group was 9.9 months (range, 6-12 months). The HHS and WOMAC scores at last follow-up in the THA group showed significant improvement when compared with preoperative scores ( P<0.05). Gait scores were positively correlated with postoperative HHS score ( r=0.585, P=0.007) and negatively correlated with WOMAC score ( r=-0.619, P=0.004). There was no significant difference in stride length and cadence between the THA and control groups ( P>0.05), but gait score was significantly lower in the THA group than in the control group ( P<0.05). There was no significant difference in maximum and minimum values of flexion/extension, external/internal rotation, and abduction/adduction between the two groups ( P>0.05); however, ROM in the THA group was significantly lower than that in the control group ( P<0.05). There were significant differences between the two groups of flexion/extension in multiple phases of the gait cycle ( P<0.05). Conclusion: Early post-THA hip joint kinematics exhibit relative adduction, external rotation, and flexion during the gait cycle compared to normal individuals, with incomplete recovery of kinematic parameters in three degrees of freedom. Significant differences in flexion are observed at multiple phases of the gait cycle compared to normal individuals.

Preoperative transthoracic echocardiography does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients.

PURPOSE: The present study aimed to investigate the influence of preoperative TTE on postoperative short-term mortality, surgery delay, as well as other economic and clinical outcomes in Chinese geriatric hip fracture patients. METHODS: This retrospective, matched-cohort study enrolled geriatric hip fracture patients (≥ 60 years) who underwent surgical interventions at our center between 2015 and 2020. The primary exposure was inpatient preoperative TTE. Demographic and clinical data that were reported as risk factors for postoperative mortality were retrieved from the medical data center as the covariates. The primary clinical outcomes were all-cause mortality at 30 days, 90 days, 180 days, and 1 year. Time from hospital presentation to surgery, length of stay (LOS), inpatient cost, frequency of cardiology consultation and coronary angiography (CAG) were also assessed. The propensity score matching (PSM) was performed in a ratio of 1:1. RESULTS: 447 patients were identified and 216 of them received a preoperative TTE (48.3%). After successfully matching 390 patients (87.2%), patients receiving TTE showed significantly higher 30-day mortality (6.6% vs 2.0%, P = 0.044). But no significant difference was found in 90-day, 180-day, and 365-day mortality as well as the 1-year accumulated survival rate. Receipt of TTE was also associated with significant increases in LOS (13.6 days vs 11.4 days, P = 0.017), waiting time for surgery (5.9 days vs 4.3 days, P < 0.001), and lower proportion of receiving surgery within 48 h (7.2% vs. 26.2%, P < 0.001). According to the multivariable logistic analysis, only ejection fraction (30 days, 90 days), aorta diameter (30 days, 90 days, 180 days, 365 days), left ventricular posterior wall diameter (90 days, 180 days, 365 days), aortic valve velocity (90 days) and mitral valve A-peak (90 days, 180 days) were association with postoperative mortality among the 17 parameters in the TTE reports. Besides, TTE has no influence on the frequency of preoperative cardiology consultation. CONCLUSION: Preoperative TTE does not lead to decreased postoperative mortality but with increased time to surgery and length of stay in Chinese geriatric hip fracture patients. The predictive ability of TTE parameters is limited for postoperative mortality.

Intraoperative intravenous versus periarticular injection of glucocorticoids in improving clinical outcomes after total knee arthroplasty: A prospective, randomized and controlled study.

BACKGROUND: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes. METHODS: A total of 114 patients were randomly assigned to intravenous (IV) group (n = 57) and periarticular injection (PI) group (n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA. RESULTS: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups. CONCLUSIONS: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients.

Mechanical overload-induced release of extracellular mitochondrial particles from tendon cells leads to inflammation in tendinopathy.

Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP9%) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP0%, mEP3%, and mEP6%. Partial depletion of the ExtraMito particles from mEP9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP9%. These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy.

Programmable mechanical stimulation influences tendon homeostasis in a bioreactor system.

Identification of functional programmable mechanical stimulation (PMS) on tendon not only provides the insight of the tendon homeostasis under physical/pathological condition, but also guides a better engineering strategy for tendon regeneration. The aims of the study are to design a bioreactor system with PMS to mimic the in vivo loading conditions, and to define the impact of different cyclic tensile strain on tendon. Rabbit Achilles tendons were loaded in the bioreactor with/without cyclic tensile loading (0.25 Hz for 8 h/day, 0-9% for 6 days). Tendons without loading lost its structure integrity as evidenced by disorientated collagen fiber, increased type III collagen expression, and increased cell apoptosis. Tendons with 3% of cyclic tensile loading had moderate matrix deterioration and elevated expression levels of MMP-1, 3, and 12, whilst exceeded loading regime of 9% caused massive rupture of collagen bundle. However, 6% of cyclic tensile strain was able to maintain the structural integrity and cellular function. Our data indicated that an optimal PMS is required to maintain the tendon homeostasis and there is only a narrow range of tensile strain that can induce the anabolic action. The clinical impact of this study is that optimized eccentric training program is needed to achieve maximum beneficial effects on chronic tendinopathy management.

Stem cell therapy combined with core decompression versus core decompression alone in the treatment of avascular necrosis of the femoral head: a systematic review and meta-analysis.

INTRODUCTION: Accumulated clinical trials had been focused on stem cell therapy in combination of core decompression (CD) in the treatment of avascular necrosis of the femoral head (ANFH). Nonetheless, the results were inconclusive. Here, we performed a systematic review and meta-analysis of previous randomized controlled trials (RCTs) and retrospective studies to assess whether combined stem cell augmentation with CD improved the outcomes of ANFH compared with CD alone. METHODS: The current study included 11 RCTs and 7 retrospective studies reporting the clinical outcomes of a total of 916 patients and 1257 hips. 557 and 700 hips received CD and CD plus stem cell therapy, respectively. To compare CD with CD plus stem cell therapy, we examined the clinical evaluating scores, the occurrence of the femoral head, radiologic progression and conversion to total hip arthroplasty (THA). RESULTS: Only 10 studies reported significantly greater improvement in hip functions while combining stem cell procedure with CD. The pooled results in subgroup analysis indicated that stem cell group had a lower collapse rate on a mid-term basis (P = 0.001), when combined with mechanical support (P < 0.00001), and with extracted stem cells (P = 0.0002). Likewise, stem cell group had a lower radiographic progression rate at 2- to 5-year follow-up [P = 0.003], when combined with structural grafting (P < 0.00001), and with extracted stem cells (P = 0.004). Stem cell therapy resulted in an overall lower THA conversion rate (P < 0.0001) except that at a follow-up longer than 5 years. CONCLUSION: Stem cell therapy combined with core decompression was more effective in preventing collapse, radiographic progression and conversion to THA. Trial Registration The current protocol has been registered in PROSPERO with the registration number: CRD42023417248.

In situ fabrication of an anisotropic double-layer hydrogel as a bio-scaffold for repairing articular cartilage and subchondral bone injuries.

Articular cartilage is a smooth and elastic connective tissue playing load-bearing and lubricating roles in the human body. Normal articular cartilage comprises no blood vessels, lymphatic vessels, nerves, or undifferentiated cells, so damage self-repair is very unlikely. The injuries of articular cartilage are often accompanied by damage to the subchondral bone. The subchondral bone mainly provides mechanical support for the joint, and the successful repair of articular cartilage depends on the ability of the subchondral bone to provide a suitable environment. Currently, conventional repair treatments for articular cartilage and subchondral bone defects can hardly achieve good results due to the poor self-repairing ability of the cartilage Here, we propose a bioactive injectable double-layer hydrogel to repair articular cartilage and subchondral bone. The hydrogel scaffold mimics the multilayer structure of articular cartilage and subchondral bone. Agarose was used as a common base material for the double-layer hydrogel scaffold, in which a sodium alginate (SA)/agarose layer was used for the repair of artificially produced subchondral bone defects, while a decellularized extracellular matrix (dECM)/agarose layer was used for the repair of articular cartilage defects. The double-layer hydrogel scaffold is injectable, easy to use, and can fill in the damaged area. The hydrogel scaffold is also anisotropic both chemically and structurally. Animal experiments showed that the surface of the new cartilage tissue in the double-layer hydrogel scaffold group was closest to normal articular cartilage, with a structure similar to that of hyaline cartilage and a preliminary calcified layer. Moreover, the new subchondral bone in this group exhibited many regular bone trabeculae, and the new cartilage and subchondral bone were mechanically bound without mutual intrusion and tightly integrated with the surrounding tissue. The continuous double-layer hydrogel scaffold prepared in this study mimics the multilayer structure of articular cartilage and subchondral bone and promotes the functional repair of articular cartilage and subchondral bone, favoring close integration between the newborn tissue and the original tissue.

Activating Endogenous Neurogenesis for Spinal Cord Injury Repair: Recent Advances and Future Prospects.

After spinal cord injury (SCI), endogenous neural stem cells are activated and migrate to the injury site where they differentiate into astrocytes, but they rarely differentiate into neurons. It is difficult for brain-derived information to be transmitted through the injury site after SCI because of the lack of neurons that can relay neural information through the injury site, and the functional recovery of adult mammals is difficult to achieve. The development of bioactive materials, tissue engineering, stem cell therapy, and physiotherapy has provided new strategies for the treatment of SCI and shown broad application prospects, such as promoting endogenous neurogenesis after SCI. In this review, we focus on novel approaches including tissue engineering, stem cell technology, and physiotherapy to promote endogenous neurogenesis and their therapeutic effects on SCI. Moreover, we explore the mechanisms and challenges of endogenous neurogenesis for the repair of SCI.