Loss of extracellular matrix from articular cartilage is mediated by the synovium and ligament after anterior cruciate ligament injury.

OBJECTIVE: Post-traumatic osteoarthritis (PTOA) occurs after anterior cruciate ligament (ACL) injury. PTOA may be initiated by early expression of proteolytic enzymes capable of causing degradation of the articular cartilage at time of injury. This study investigated the production of three of these key proteases in multiple joint tissues after ACL injury and subsequent markers of cartilage turnover. METHODS: ACL transection was performed in adolescent minipigs. Collagenase (MMP-1 and MMP-13) and aggrecanase (ADAMTS-4) gene expression changes were quantified in the articular cartilage, synovium, injured ligament, and the provisional scaffold at days 1, 5, 9, and 14 post-injury. Markers of collagen degradation (C2C), synthesis (CPII) and aggrecan synthesis (CS 846) were quantified in the serum and synovial fluid. Histologic assessment of the cartilage integrity (OARSI scoring) was also performed. RESULTS: MMP-1 gene expression was upregulated in the articular cartilage, synovium and ligament after ACL injury. MMP-13 expression was suppressed in the articular cartilage, but upregulated 100-fold in the synovium and ligament. ADAMTS-4 was upregulated in the synovium and ligament but not in the articular cartilage. The concentration of collagen degradation fragments (C2C) in the synovial joint fluid nearly doubled in the first five days after injury. CONCLUSION: We conclude that upregulation of genes coding for proteins capable of degrading cartilage ECM is seen within the first few days after ACL injury, and this response is seen not only in chondrocytes, but also in cells in the synovium, ligament and provisional scaffold.

Mesenchymal stem cells from the retropatellar fat pad and peripheral blood stimulate ACL fibroblast migration, proliferation, and collagen gene expression.

Mesenchymal stem cells (MSCs) have been of recent interest as adjuncts for ligament repair. However, the effect of these cells on the resident ligament fibroblasts has not yet been defined. In this study, we hypothesized that co-culture of MSCs and ligament fibroblasts would result in increases in the proliferative rate of the ligament fibroblasts and their expression of collagen-related genes, as well as differentiation of the MSCs down a fibroblastic pathway. In addition, we hypothesized that these effects would be dependent on the source of the MSCs. Porcine MSCs were isolated from both the retro-patellar fat pad (ADSCs) and the peripheral blood (PBMCs) and co-cultured with porcine anterior cruciate ligament (ACL) fibroblasts. Fibroblast migration, proliferation, and collagen gene expression were evaluated at time points up to 14 days. ADSCs had a greater effect on stimulating ACL-fibroblast proliferation and procollagen production, while PBMCs were more effective in stimulating ligament fibroblast migration. In addition, co-culture with the ACL fibroblasts led to significant increases in collagen gene expression for ADSCs, suggesting a differentiation of these cells down a fibroblastic pathway during the co-culture period. This was not seen for the PBMCs. Thus, the effects of MSCs on in situ ACL fibroblasts were found to be source dependent, and the choice of MSC source should take into account the different performance characteristic of each type of MSC.

Focused ion beam characterization of bicomponent polymer fibers.

Previous work has shown that focused ion beam (FIB) nanomachining can be effectively utilized for the cross-sectional analysis of polymers such as core-shell solid microspheres and hollow latex nanospheres. While these studies have clearly demonstrated the precise location selection and nanomachining control provided by the FIB technique, the samples studied consisted of only a single polymer. In this work, FIB is used to investigate bicomponent polymeric fiber systems by taking advantage of the component's differing sputter rates that result from their differing physical properties. An approach for cross sectioning and thus revealing the cross-sectional morphology of the polymeric components in a bicomponent polymeric fiber with the island-in-the-sea (I/S) structure is presented. The two I/S fibers investigated were fabricated using the melt spinning process and are composed of bicomponent combinations of linear low density polyethylene (LLDPE) and nylon 6 (PA6) or polylactic acid (PLA) and an EastONE proprietary polymer. Topographical contrast as a result of differential sputtering and the high surface specificity and high signal-to-noise obtained using FIB-induced secondary electron imaging is shown to provide a useful approach for the rapid characterization of the cross-sectional morphology of bicomponent polymeric fibers without the necessity of staining or other sample preparation.

A clinical prediction rule for delirium after elective noncardiac surgery.

OBJECTIVE: To develop and validate a clinical prediction rule for postoperative delirium using data available to clinicians preoperatively. DESIGN: Prospective cohort study. SETTING: General surgery, orthopedic surgery, and gynecology services at Brigham and Women's Hospital, Boston, Mass. PATIENTS: Consenting patients older than 50 years admitted for major elective noncardiac surgery between November 1, 1990, and March 15, 1992 (N = 1341). MEASUREMENTS: All patients underwent preoperative evaluations, including a medical history, physical examination, laboratory tests, and assessments of physical and cognitive function using the Specific Activity Scale and the Telephone Interview for Cognitive Status. Postoperative delirium was diagnosed using the Confusion Assessment Method or using data from the medical record and the hospital's nursing intensity index. Patients were followed up for the duration of hospitalization to determine major complication rates, length of stay, and discharge disposition. RESULTS: Postoperative delirium occurred in 117 (9%) of the 1341 patients studied. Independent correlates included age 70 years or older; self-reported alcohol abuse; poor cognitive status; poor functional status; markedly abnormal preoperative serum sodium, potassium, or glucose level; noncardiac thoracic surgery; and aortic aneurysm surgery. Using these seven preoperative factors, a simple predictive rule was developed. In an independent population, the rule stratified patients into groups with low (2%), medium (8%, 13%), and high (50%) rates of postoperative delirium. Patients who developed delirium had higher rates of major complications, longer lengths of stay, and higher rates of discharge to long-term care or rehabilitative facilities. CONCLUSIONS: Using data available preoperatively, clinicians can stratify patients into risk groups for the development of delirium. Since delirium is associated with a variety of adverse outcomes, patients with substantial risk for this complication could be candidates for interventions to reduce the incidence of postoperative delirium and potentially improve overall surgical outcomes.