Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model.

Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (µCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate.

Respiratory acidosis during bronchoscopy-guided percutaneous dilatational tracheostomy: impact of ventilator settings and endotracheal tube size.

BACKGROUND: The current study investigates the effect of bronchoscopy-guided percutaneous dilatational tracheostomy (PDT) on the evolution of respiratory acidosis depending on endotracheal tube (ET) sizes. In addition, the impact of increasing tidal volumes during the intervention was investigated. METHODS: Two groups of ICU-patients undergoing bronchoscopy-guided PDT with varying tidal volumes and tube sizes were consecutively investigated: 6 ml/kg (N = 29, mean age 57.4 ± 14.5 years) and 12 ml/kg predicted body weight (N = 34, mean age 59.5 ± 12.8 years). RESULTS: The mean intervention time during all procedures was 10 ± 3 min. The combination of low tidal volumes and ETs of 7.5 mm internal diameter resulted in the most profound increase in PaCO2 (32.2 ± 11.6 mmHg) and decrease in pH-value (- 0.18 ± 0.05). In contrast, the combination of high tidal volumes and ETs of 8.5 mm internal diameter resulted in the least profound increase in PaCO2 (8.8 ± 9.0 mmHg) and decrease of pH (- 0.05 ± 0.04). The intervention-related increase in PaCO2 was significantly lower when using higher tidal volumes for larger ET: internal diameter 7.5, 8.0 and 8.5: P > 0.05, =0.006 and = 0.002, respectively. Transcutaneous PCO2 monitoring revealed steadily worsening hypercapnia during the intervention with a high correlation of 0.87 and a low bias of 0.7 ± 9.4 mmHg according to the Bland-Altman analysis when compared to PaCO2 measurements. CONCLUSIONS: Profound respiratory acidosis following bronchoscopy-guided PDT evolves in a rapid and dynamic process. Increasing the tidal volume from 6 to 12 ml/kg PBW was capable of attenuating the evolution of respiratory acidosis, but this effect was only evident when using larger ETs. TRIAL REGISTRATION: DRKS00011004 . Registered 20th September 2016.

Impact of sweep gas flow on extracorporeal CO2 removal (ECCO2R).

BACKGROUND: Veno-venous extracorporeal carbon dioxide (CO2) removal (vv-ECCO2R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates range in clinical practice from 200 mL/min to more than 1500 mL/min, and sweep gas flow rates range from less than 1 to more than 10 L/min. The present porcine model study was aimed at determining the impact of varying sweep gas flow rates on CO2 removal under different blood flow conditions and membrane lung surface areas. METHODS: Two different membrane lungs, with surface areas of 0.4 and 0.8m2, were used in nine pigs with experimentally-induced hypercapnia. During each experiment, the blood flow was increased stepwise from 300 to 900 mL/min, with further increases up to 1800 mL/min with the larger membrane lung in steps of 300 mL/min. Sweep gas was titrated under each condition from 2 to 8 L/min in steps of 2 L/min. Extracorporeal CO2 elimination was normalized to a PaCO2 of 45 mmHg before the membrane lung. RESULTS: Reversal of hypercapnia was only feasible when blood flow rates above 900 mL/min were used with a membrane lung surface area of at least 0.8m2. The membrane lung with a surface of 0.4m2 allowed a maximum normalized CO2 elimination rate of 41 ± 6 mL/min with 8 L/min sweep gas flow and 900 mL blood flow/min. The increase in sweep gas flow from 2 to 8 L/min increased normalized CO2 elimination from 35 ± 5 to 41 ± 6 with 900 mL blood flow/min, whereas with lower blood flow rates, any increase was less effective, levelling out at 4 L sweep gas flow/min. The membrane lung with a surface area of 0.8m2 allowed a maximum normalized CO2 elimination rate of 101 ± 12 mL/min with increasing influence of sweep gas flow. The delta of normalized CO2 elimination increased from 4 ± 2 to 26 ± 7 mL/min with blood flow rates being increased from 300 to 1800 mL/min, respectively. CONCLUSIONS: The influence of sweep gas flow on the CO2 removal capacity of ECCO2R systems depends predominantly on blood flow rate and membrane lung surface area. In this model, considerable CO2 removal occurred only with the larger membrane lung surface of 0.8m2 and when blood flow rates of ≥ 900 mL/min were used.