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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.
Out of the lab and into the bathroom: Evening short-term exposure to conventional light suppresses melatonin and increases alertness perception
Life in 24-h society relies on the use of artificial light at night that might disrupt synchronization of the endogenous circadian timing system to the solar day. This could have a negative impact on sleep-wake patterns and psychiatric symptoms. The aim of the study was to investigate the influence of evening light emitted by domestic and work place lamps in a naturalistic setting on melatonin levels and alertness in humans. Healthy subjects (6 male, 3 female, 22-33 years) were exposed to constant dim light (<10 lx) for six evenings from 7:00 p.m. to midnight. On evenings 2 through 6, 1 h before habitual bedtime, they were also exposed to light emitted by 5 different conventional lamps for 30 min. Exposure to yellow light did not alter the increase of melatonin in saliva compared to dim light baseline during (38 ± 27 pg/mL vs. 39 ± 23 pg/mL) and after light exposure (39 ± 22 pg/mL vs. 44 ± 26 pg/mL). In contrast, lighting conditions including blue components reduced melatonin increase significantly both during (office daylight white: 25 ± 16 pg/mL, bathroom daylight white: 24 ± 10 pg/mL, Planon warm white: 26 ± 14 pg/mL, hall daylight white: 22 ± 14 pg/mL) and after light exposure (office daylight white: 25 ± 15 pg/mL, bathroom daylight white: 23 ± 9 pg/mL, Planon warm white: 24 ± 13 pg/mL, hall daylight white: 22 ± 26 pg/mL). Subjective alertness was significantly increased after exposure to three of the lighting conditions which included blue spectral components in their spectra. Evening exposure to conventional lamps in an everyday setting influences melatonin excretion and alertness perception within 30 min.
Heparin-based, injectable microcarriers for controlled delivery of interleukin-13 to the brain
Interleukin-13 (IL-13) drives cells of myeloid origin towards a more anti-inflammatory phenotype, but delivery to the brain remains problematic. Herein, we show that heparin-based cryogel microcarriers load high amounts of IL-13, releasing it slowly. Intra-striatal injection of loaded microcarriers caused local up-regulation of ARG1 in myeloid cells for pro-regenerative immunomodulation in the brain. © 2020 The Royal Society of Chemistry.