Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases.

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

Comparison of the ability of exosomes and ectosomes derived from adipose-derived stromal cells to promote cartilage regeneration in a rat osteochondral defect model.

BACKGROUND: Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) offer promising prospects for stimulating cartilage regeneration. The different formation mechanisms suggest that exosomes and ectosomes possess different biological functions. However, little attention has been paid to the differential effects of EV subsets on cartilage regeneration. METHODS: Our study compared the effects of the two EVs isolated from adipose-derived MSCs (ASCs) on chondrocytes and bone marrow-derived MSCs (BMSCs) in vitro. Additionally, we loaded the two EVs into type I collagen hydrogels to optimize their application for the treatment of osteochondral defects in vivo. RESULTS: In vitro experiments demonstrate that ASC-derived exosomes (ASC-Exos) significantly promoted the proliferation and migration of both cells more effectively than ASC-derived ectosomes (ASC-Ectos). Furthermore, ASC-Exos facilitated a stronger differentiation of BMSCs into chondrogenic cells than ASC-Ectos, but both inhibited chondrocyte apoptosis to a similar extent. In the osteochondral defect model of rats, ASC-Exos promoted cartilage regeneration in situ better than ASC-Ectos. At 8 weeks, the hydrogel containing exosomes group (Gel + Exo group) had higher macroscopic and histological scores, a higher value of trabecular bone volume fraction (BV/TV), a lower value of trabecular thickness (Tb.Sp), and a better remodeling of extracellular matrix than the hydrogel containing ectosomes group (Gel + Ecto group). At 4 and 8 weeks, the expression of CD206 and Arginase-1 in the Gel + Exo group was significantly higher than that in the Gel + Ecto group. CONCLUSION: Our findings indicate that administering ASC-Exos may be a more effective EV strategy for cartilage regeneration than the administration of ASC-Ectos.

Short- to Midterm Clinical and Radiological Outcomes After Matrix-Associated Autologous Chondrocyte Implantation for Chondral Defects in Knees.

BACKGROUND: Matrix-associated autologous chondrocyte implantation (MACI) has been proven to provide favorable short-term results for chondral defects in knees. However, it remains unclear whether the clinical benefits of MACI persist in the longer term. PURPOSE: The purpose of this prospective study was to evaluate the clinical and radiological outcomes, at short- and midterm follow-up, for patients undergoing MACI for focal chondral defects of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 30 consecutive patients (31 knees) were treated using MACI between October 2010 and March 2018. There were 24 male patients and 6 female patients with an average age of 26 years (range, 12-48 years). The areas of the cartilage defect were consistently >2 cm2. All patients underwent MACI for a focal chondral defect of the femoral condyles or trochlea in the knee. These patients had been evaluated for up to 5 years, with an average follow-up of 44 months (range, 6-60 months) postoperatively.The International Knee Documentation Committee (IKDC) score, Lysholm score, and magnetic resonance imaging (MRI) with T2 mapping were used to assess the outcomes. RESULTS: No patients were lost to follow-up. Mean IKDC scores improved from 58.6 (range, 40.2-80.5) to 79.1 (range, 39.1-94.3) at 12 months and up to 88.4 (range, 83.9-100) at 5 years; mean Lysholm scores improved from 67.3 (range, 46-95) to 90.6 (range, 71-100) at 12 months and up to 95.9 (range, 85-100) at 5 years. The MRI with T2 mapping value of the transplanted area was evaluated for 21 knees, which revealed no differences compared with the normal area at 12 months postoperatively. CONCLUSION: From the first year onward, the clinical outcome scores and MRI with T2 mapping values showed continuous and marked improvement, suggesting that MACI is a valid option for localized cartilage defects in the knee.

Lesions of the Long Head of the Biceps Tendon Concomitant with Rotator Cuff Tears: Tenotomy or Subpectoral Mini-open Tenodesis? A Comparative Short to Mid-term Follow-up Study.

OBJECTIVE: To compare the clinical and radiological outcomes of patients who underwent rotator cuff repair (RCR) concomitant with long head of the biceps tendon (LHBT) tenotomy or subpectoral mini-open tenodesis. METHODS: Prospectively collected data was reviewed on 154 patients, who underwent a LHBT procedure (tenotomy or tenodesis) concomitant with RCR between January 2010 and January 2017. The exclusion criteria were irreparable massive rotator cuff tear, rotator cuff partial tear, subscapular tendon tear, glenohumeral arthritis, and prior shoulder surgery. The two patient groups are as follows: RCR + Tenotomy (Group A) and RCR + Subpectoral mini-open tenodesis (Group B). The visual analog scale (VAS) for pain, Constant Score scale, American Shoulder and Elbow Surgeons (ASES) scores, and the Disabilities of the Arm, Shoulder and Hand (DASH) scores preoperatively and 1 month, 3 months, 6 months, 1 year postoperatively and the latest out-patient clinic were compared between the two groups. RESULTS: Ninety-two patients in Group A and 62 patients in Group B completed the follow-up, with a median follow-up time of 27 and 42 months respectively. At the final follow-up, the VAS, Constant, ASES, and DASH scores in Group A were 0.1 ± 0.2, 87.0 ± 12.8, 96.4 ± 4.3 and 6.6 ± 4.8 respectively, and the VAS, Constant, ASES, and DASH scores in Group B were 0.1 ± 0.3, 92.5 ± 3.9, 96.3 ± 3.6 and 2.9 ± 1.3 respectively. Clinical evaluation scales showed satisfactory results in both groups, and there were no statistically significant differences between the two groups at the same follow-up time. Popeye sign was detected in one case of Group A (1.1%) and in one case of Group B (1.6%, P > 0.05). CONCLUSION: Both tenotomy and subpectoral mini-open tenodesis are effective for concomitant lesions of the LHBT in patients with reparable rotator cuff tears, and subpectoral mini-open tenodesis of the LHBT does not provide any significant clinical or functional improvement than isolated tenotomy.

How does the inclination of the tibial component matter? A three-dimensional finite element analysis of medial mobile-bearing unicompartmental arthroplasty.

BACKGROUND: Medial unicompartmental knee arthroplasty (UKA) using Oxford mobile-bearing prosthesis is performed in the treatment of medial compartmental arthritis of the knee. However, little is known about the stress distributions for mobile-bearing UKA on the medial tibial plateau. METHODS: In this study, the stresses on the coronal plane were calculated in a three-dimensional model of the proximal tibia. The features of the stress distribution were investigated when the tibial tray was placed in 15°, 10°, six degrees, and three degrees varus, neutral (0°), and in three degrees, six degrees, 10°, and 15° valgus on the coronal plane of the medial plateau. RESULTS: The peak von Mises stress was found on the cortex below the medial plateau while the stresses of cortical bone increased gradually as the inclination of the tibial tray was changed from varus to valgus. The amount of peak stress was almost the same as that in the normal knee model when the tibial tray was placed in six degrees valgus and consistently lower in varus inclination than in the normal knee model. Conversely, the peak stress of soft bone was found at the bottom of the slot. CONCLUSIONS: This study demonstrates that the inclination of the tibial component affects stress distribution in the proximal tibia after UKA. Slight varus inclination of the mobile-bearing tibial component is acceptable as it lowers the peak stress on the medial cortex. Additionally, placing the tibial tray in slight varus avoids a rise in stress between the tip of the keel and the medial tibial cortex.

Hamstring Co-Contraction in the Early Stage of Rehabilitation After Anterior Cruciate Ligament Reconstruction: A Longitudinal Study.

OBJECTIVE: Hamstring co-contraction may affect recovery from anterior cruciate ligament reconstruction. The aim of the study was to evaluate the changes in hamstring co-contraction during the early postoperative stages. DESIGN: Twenty-five patients with anterior cruciate ligament reconstruction were followed up for 1-3 mos postoperatively, during which the Lysholm and International Knee Documentation Committee questionnaires were completed and surface electromyograms were assessed during terminal knee extension maximum voluntary contraction and step-up tests. The integrated electromyogram of the tested muscles and co-contraction ratio were analyzed. RESULTS: Co-contraction ratio during terminal knee extension maximum voluntary contraction at 3 mos postoperatively was significantly less than that at 1 mo postoperatively (P < 0.0083), and it did not significantly differ from that of the uninvolved knee. In contrast, the co-contraction ratio during step-up was significantly higher at 2 and 3 mos postoperatively than that before surgery (P < 0.0167) and for the uninvolved knee (P < 0.05). Moreover, the postoperative hamstring co-contraction ratio in patients with a chronic injury was significantly higher during the step-up test than in patients with an early injury (P = 0.017). CONCLUSIONS: Hamstring co-contraction ratio during terminal knee extension maximum voluntary contraction recovers during the early postoperative stages. However, hamstring co-contraction ratio during step-up, which may be related to knee joint proprioception, remains high, particularly for patients with a chronic injury. CLINICAL TRIAL: ChiCTR-COC-17011167.