Thermogelling hydrogel charge and lower critical solution temperature influence cellular infiltration and tissue integration in an ex vivo cartilage explant model.

Thermogelling hydrogels based on poly(N-isopropyl acrylamide) (p[NiPAAm]) and crosslinked with a peptide-bearing macromer poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT) were fabricated to assess the role of hydrogel charge and lower critical solution temperature (LCST) over time in influencing cellular infiltration and tissue integration in an ex vivo cartilage explant model over 21 days. The p(NiPAAm)-based thermogelling polymer was synthesized to possess 0, 5, and 10 mol% dimethyl-γ-butyrolactone acrylate (DBA) to raise the LCST over time as the lactone rings hydrolyzed. Further, three peptides were designed to impart charge into the hydrogels via conjugation to the PdBT crosslinker. The positively, neutrally, and negatively charged peptides K4 (+), zwitterionic K2E2 (0), and E4 (-), respectively, were conjugated to the modular PdBT crosslinker and the hydrogels were evaluated for their thermogelation behavior in vitro before injection into the cartilage explant models. Samples were collected at days 0 and 21, and tissue integration and cellular infiltration were assessed via mechanical pushout testing and histology. Negatively charged hydrogels whose LCST changed over time (10 mol% DBA) were demonstrated to promote the greatest tissue integration when compared to the positive and neutral gels of the same thermogelling polymer formulation due to increased transport and diffusion across the hydrogel-tissue interface. Indeed, the negatively charged thermogelling polymer groups containing 5 and 10 mol% DBA demonstrated cellular infiltration and cartilage-like matrix deposition via histology. This study demonstrates the important role that material physicochemical properties play in dictating cell and tissue behavior and can inform future cartilage tissue engineering strategies.

Frequency-Dependent Light Stimulation Effects on Performance During Vigilance Tasks on a Laptop.

Students, office workers, or other computer and mobile device users can suffer from decrements in alertness or productivity, but many intervention methods on these can be too distracting or even affect daily routines. Using heart rate (HR) to determine a fast and slow target frequency at which to oscillate light brightness stimulation on a laptop, thirty-six participants joined a cognitive task where we hypothesized that fast frequency stimulation would increase alertness and decrease relaxation, while slow frequency stimulation would have the opposite effects. We found that slow frequency stimulation produces a statistically significant delay in response time, users react more slowly (3.8e2 ± 5.5e1 ms), when compared to the no stimulation (3.7e2 ± 4.1e1 ms) (p = 9.0e-3) conditions. The (Slow - No Stimulation) response time (1.7e1 ± 2.7e2 ms) produced a statistically significant delay in response time versus the (Fast - No Stimulation) response time (-0.74 ± 2.4e1 ms) (p = .016). These delays due to slow stimulation occurred without influencing accuracy or subjective sleepiness ratings. We observed that frequency-dependent light stimulation can potentially influence HRV metrics such as the mean normal-to-normal intervals and mean HR. Future work will target breathing rate to determine light stimulation oscillations as we further investigate the potential of using the slow-frequency domain to unobtrusively influence user performance and physiology.