Rapamycin Inhibits Senescence and Improves Immunomodulatory Function of Mesenchymal Stem Cells Through IL-8 and TGF-ß Signaling.

Mesenchymal stromal cells (MSCs) grown in high-density monolayers (sheets) are promising vehicles for numerous bioengineering applications. When MSC sheets are maintained in prolonged cultures, they undergo rapid senescence, limiting their downstream efficacy. Although rapamycin is a potential agent that can inhibit senescence in cell cultures, no study has investigated rapamycin's effect on MSCs grown in high-density culture and its effect on downstream target gene expression. In this study, placental-derived MSCs (PMSCs) were seeded at high density to generate PMSC sheets in 24 hours and were then treated with rapamycin or vehicle for up to 7 days. Autophagy activity, cell senescence and apoptosis, cell size and granularity, and senescence-associated cytokines (IL-6 and IL-8) were analyzed. Differential response in gene expression were assessed via microarray analysis. Rapamycin significantly increased PMSC sheet autophagy activity, inhibited cellular senescence, decreased cell size and granularity at all timepoints. Rapamycin also significantly decreased the number of cells in late apoptosis at day 7 of sheet culture, as well as caspase 3/7 activity at all timepoints. Notably, while rapamycin decreased IL-6 secretion, increased IL-8 levels were observed at all timepoints. Microarray analysis further confirmed the upregulation of IL-8 transcription, as well as provided a list of 396 genes with 2-fold differential expression, where transforming growth factor-ß (TGF-ß) signaling were identified as important upregulated pathways. Rapamycin both decreased senescence and has an immunomodulatory action of PMSCs grown in sheet culture, which will likely improve the chemotaxis of pro-healing cells to sites of tissue repair in future bioengineering applications.

Compressibility of Osteochondral Autograft Transfer Donor Grafts: A Comparison of Different Donor Regions and How Much Shortening Occurs of Plugs After Impaction.

Background: Osteochondral autograft transfer (OAT) is a useful technique for full-thickness cartilage lesions of the distal femur. Various techniques recommend harvesting a plug 2 mm longer than the recipient hole to allow for graft impaction. Grafts with limited compressibility may not sit flush when impacted. Purpose: To compare the compressibility/shortening of OAT donor plug regions from the distal femur of human cadaveric knees after impaction. Study Design: Controlled laboratory study. Methods: A total of 20 cadaveric knees (mean age, 70.3 ± 8.4 years) were divided into 4 donor regions: medial intercondylar (IC) notch, lateral IC notch, medial trochlea, and lateral trochlea. Each region was subdivided into 4 zones: far superior (FSZ), middle superior (MSZ), middle inferior (MIZ), and far inferior (FIZ). A total of 320 grafts (6-mm diameter, 15-mm depth) were extracted, and a custom-built machine was used to strike the graft 5 times using a predetermined energy of 0.11 J. The graft length was measured initially and after each impact. Statistical analysis of the compressibility for each of the 4 regions and all 16 zones was performed utilizing analysis of variance, with post hoc testing using the Fisher's least significant difference. Results: Compression in the lateral IC notch, medial IC notch, medial trochlea, and lateral trochlea was 2.4 ± 1.5, 2.1 ± 0.7, 3.1 ± 2.2, and 2.1 ± 0.6 mm, respectively, with significant differences between the 4 regions (P < .01) and the most compression in the medial trochlea (P < .01). Subgroup analysis showed that the lateral trochlea had higher compressibility for FIZ versus MIZ (P = .02) and the lateral IC notch had higher compressibility for FSZ versus FIZ and MIZ (P < .05 for both). Conclusion: Compressibility varied between OAT donor sites in the distal femur. OAT donor grafts showed the highest compressibility in the medial trochlea (3.1 mm) and lateral IC notch FSZ (3.0 mm). Clinical Relevance: The lateral trochlea, medial IC notch, and the lower zones of the lateral IC notch grafts should not be oversized more than 2 mm in length, as these grafts may not compress adequately.

Nitinol Memory Rods Versus Titanium Rods: A Biomechanical Comparison of Posterior Spinal Instrumentation in a Synthetic Corpectomy Model.

STUDY DESIGN: Biomechanical investigation. OBJECTIVE: To compare the biomechanical performance of nitinol memory metal rods and titanium rods when used as posterior spinal instrumentation in a synthetic model. METHODS: Biomechanical testing was performed using ultra-high-molecular-weight polyethylene blocks. Nineteen spinal constructs were created to allow comparison of 5.5-mm nitinol rods with 5.5-mm titanium rods. Static compression and rotational testing were performed on an Instron 8874 and Instron 4202 at 37°C to simulate body temperature. RESULTS: The average titanium construct stiffness under static compression or bending was 47.2 ± 9.1 N/mm while nitinol's stiffness averaged 48.9 ± 12.4 N/mm (P = .83). During axial rotation testing, the nitinol rod system showed no torsional stiffness difference from the titanium system: 0.95 ± 0.03 Nm/deg versus 0.96 ± 0.17 Nm/deg, respectively (P = 0.91). There was a statistically significant difference between the average torsional yield point for the titanium constructs (14.4 ± 1.6 Nm/deg) and nitinol constructs (21.3 ± 0.8 Nm/deg) (P = .004). The torsional toughness of the nitinol constructs was also statistically greater than the titanium rods: 473 GN/m3 versus 784 GN/m3 (P = .0006). There was no statistically significant difference between the nitinol group sustaining a higher number of fatigue cycles until failure and the titanium group (181 660 cycles vs 64 104 cycles, respectively, P = .22). CONCLUSIONS: This study provides biomechanical evidence that nitinol rods used in a posterior construct are comparable to titanium rods with regard to compression and have increased torsional failure load and torsional toughness. While nitinol trended toward superior fatigue resistance, there was no significant difference in nitinol versus titanium construct fatigue resistance.

Rebar Repair of Radial Meniscus Tears: A Reinforced Suture Technique.

The purpose of this paper is to describe the rebar repair as a technique for repair of radial meniscus tears and compare the rebar technique with current techniques used for meniscus repairs. This technique consists of 4 sutures placed with the inside-out technique. First, the vertical mattress reinforcement sutures are placed anteriorly and posteriorly to the tear. Then, 2 parallel horizontal sutures are placed directly in juxtaposition to the vertical sutures, ensuring the needles pass on the side of the reinforcing stitch away from the tear. This technique is less technically challenging than other meniscus repair techniques that require drilling of a transtibial tunnel. Overall, the rebar technique offers a more optimal way for stabilizing the meniscus by using 2 reinforcement sutures that run with the circumferential fibers to help restore the natural hoop stress of the meniscus. Also, the placement of the vertical mattress sutures in the rebar technique offers more direct reinforcement to the horizontal mattress sutures as compared with other techniques, which reduces the risk of pull-out tears.

Proximity of the Neurovascular Bundle During Posterior-Lateral Meniscal Repair: A Comparison of the Transpatellar, Anteromedial, and Anterolateral Portals.

PURPOSE: To compare the neurovascular proximity of the transpatellar portal with that of the medial and lateral portals and to determine the safe penetration depth for an all-inside device for use on the posterior horn lateral meniscus. METHODS: Dissection of the popliteal fossa was performed in 10 cadaveric knees to identify all structures. Arthroscopy was performed using penetration depths of 10, 12, 14, and 16 mm with the all-inside system through the anteromedial, anterolateral, and transpatellar portals. Penetrations were made 5 and 10 mm lateral to the posterior horn root at the meniscocapsular junction. Needle-tip distances were measured from the popliteal artery and vein, tibial nerve, and common peroneal nerve. RESULTS: Among 240 trials, the average distance to the popliteal neurovascular bundle using the medial, transpatellar, and lateral approaches was 6.9 mm, 6.5 mm, and 3.1 mm, respectively. The transpatellar-portal needle had a larger distance from the neurovascular bundle than the lateral portal (P = .001), with no statistical difference compared with the medial portal (P = .58). Compared with the position at a 10-mm distance from the root, the position at a 5-mm distance from the root was closer to the neurovascular bundle in all approaches (P = .001). The transpatellar approach set to 14 mm had a 5% rate of capsular underpenetration and 10% rate of gastrocnemius penetration. The transpatellar and medial portals had no neurovascular penetrations, whereas the lateral approach had a 14% rate of penetration (P < .05). CONCLUSIONS: The transpatellar portal and anteromedial portal are in less proximity to the neurovascular bundle compared with the anterolateral portal for all-inside meniscal repair of the posterior horn lateral meniscus. Low rates of neurovascular penetration, gastrocnemius muscle penetration, and capsular underpenetration occurred with a depth setting of 14 mm. CLINICAL RELEVANCE: This study shows the utility of medial and transpatellar portals when using all-inside devices to repair posterior horn lateral meniscal tears and neurovascular proximity based on penetration depth.

School Based Mental Health Promotion: Nursing Interventions for Depressive Symptoms in Rural Adolescents.

Integrating health education and health promotion into practice is routinely done by nurses. According to a national survey, the need for mental health services has increased in over two thirds of school districts.This article describes the screening of 193 adolescents in Rural Western Pennsylvania's 9th, 10th, and 11th graders for depressive symptoms. Ten percent (N=19) of students had depressive symptoms, the majority of which were female. These students were interviewed by the research team. The outcome themes and referrals are reported as well as the discussion of implications for nurses in screening for depression and health promotion.