Designing Inherently Photodegradable Cell‐Adhesive Hydrogels for 3D Cell Culture

Light-based microfabrication techniques constitute an indispensable approach to fabricate tissue assemblies, benefiting from noncontact spatially and temporarily controlled manipulation of soft matter. Light-triggered degradation of soft materials, such as hydrogels, is important in tissue engineering, bioprinting, and related fields. The photoresponsiveness of hydrogels is generally not intrinsic and requires complex synthetic procedures wherein photoresponsive crosslinking groups are incorporated into the hydrogel. This paper demonstrates a novel biocompatible and inherently photodegradable poly(ethylene glycol) methacrylate (PEGMA)-based gelatin-methacryloyl (GelMA)-containing hydrogel that can be used to culture cells in 3D for at least 14 d. These gels are conveniently and quickly degraded via UV irradiation for 10 min to produce structured hydrogels of various geometries, sizes, and free-standing cell-laden hydrogel particles. These structures can be flexibly produced on demand. In particular, photodegradation can be temporarily delayed from photopolymerization, offering an alternative to hydrogel array production via photopolymerization with a photomask. The paper investigates the influences of hydrogel composition and swelling liquid on both its photodegradability and biocompatibility

Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening

International audienceDrug development often relies on high-throughput cell-based screening oflarge compound libraries. However, the lack of miniaturized andparallelized methodologies in chemistry as well as strict separation andincompatibility of the synthesis of bioactive compounds from theirbiological screenings makes this process expensive and inefficient.Here, we demonstrate an on-chip platform that combines solution-basedsynthesis of compound libraries with high-throughput biologicalscreenings (chemBIOS). The chemBIOS platform is compatible with bothorganic solvents required for the synthesis and aqueous solutionsnecessary for biological screenings. We use the chemBIOS platform toperform 75 parallel, three-component reactions to synthesize a libraryof lipidoids, followed by characterization via MALDI-MS, on-chipformation of lipoplexes, and on-chip cell screening. The entire processfrom the library synthesis to cell screening takes only 3 days and about1 mL of total solutions, demonstrating the potential of the chemBIOStechnology to increase efficiency and accelerate screenings and drugdevelopment

Designing Inherently Photodegradable Cell‐Adhesive Hydrogels for 3D Cell Culture

Light-based microfabrication techniques constitute an indispensable approach to fabricate tissue assemblies, benefiting from noncontact spatially and temporarily controlled manipulation of soft matter. Light-triggered degradation of soft materials, such as hydrogels, is important in tissue engineering, bioprinting, and related fields. The photoresponsiveness of hydrogels is generally not intrinsic and requires complex synthetic procedures wherein photoresponsive crosslinking groups are incorporated into the hydrogel. This paper demonstrates a novel biocompatible and inherently photodegradable poly(ethylene glycol) methacrylate (PEGMA)-based gelatin-methacryloyl (GelMA)-containing hydrogel that can be used to culture cells in 3D for at least 14 d. These gels are conveniently and quickly degraded via UV irradiation for 10 min to produce structured hydrogels of various geometries, sizes, and free-standing cell-laden hydrogel particles. These structures can be flexibly produced on demand. In particular, photodegradation can be temporarily delayed from photopolymerization, offering an alternative to hydrogel array production via photopolymerization with a photomask. The paper investigates the influences of hydrogel composition and swelling liquid on both its photodegradability and biocompatibility

Effect of Early Sustained Prophylactic Hypothermia on Neurologic Outcomes Among Patients With Severe Traumatic Brain Injury: The POLAR Randomized Clinical Trial.

Importance After severe traumatic brain injury, induction of prophylactic hypothermia has been suggested to be neuroprotective and improve long-term neurologic outcomes. Objective To determine the effectiveness of early prophylactic hypothermia compared with normothermic management of patients after severe traumatic brain injury. Design, Setting, and Participants The Prophylactic Hypothermia Trial to Lessen Traumatic Brain Injury-Randomized Clinical Trial (POLAR-RCT) was a multicenter randomized trial in 6 countries that recruited 511 patients both out-of-hospital and in emergency departments after severe traumatic brain injury. The first patient was enrolled on December 5, 2010, and the last on November 10, 2017. The final date of follow-up was May 15, 2018. Interventions There were 266 patients randomized to the prophylactic hypothermia group and 245 to normothermic management. Prophylactic hypothermia targeted the early induction of hypothermia (33°C-35°C) for at least 72 hours and up to 7 days if intracranial pressures were elevated, followed by gradual rewarming. Normothermia targeted 37°C, using surface-cooling wraps when required. Temperature was managed in both groups for 7 days. All other care was at the discretion of the treating physician. Main Outcomes and Measures The primary outcome was favorable neurologic outcomes or independent living (Glasgow Outcome Scale-Extended score, 5-8 [scale range, 1-8]) obtained by blinded assessors 6 months after injury. Results Among 511 patients who were randomized, 500 provided ongoing consent (mean age, 34.5 years [SD, 13.4]; 402 men [80.2%]) and 466 completed the primary outcome evaluation. Hypothermia was initiated rapidly after injury (median, 1.8 hours [IQR, 1.0-2.7 hours]) and rewarming occurred slowly (median, 22.5 hours [IQR, 16-27 hours]). Favorable outcomes (Glasgow Outcome Scale-Extended score, 5-8) at 6 months occurred in 117 patients (48.8%) in the hypothermia group and 111 (49.1%) in the normothermia group (risk difference, 0.4% [95% CI, -9.4% to 8.7%]; relative risk with hypothermia, 0.99 [95% CI, 0.82-1.19]; P = .94). In the hypothermia and normothermia groups, the rates of pneumonia were 55.0% vs 51.3%, respectively, and rates of increased intracranial bleeding were 18.1% vs 15.4%, respectively. Conclusions and Relevance Among patients with severe traumatic brain injury, early prophylactic hypothermia compared with normothermia did not improve neurologic outcomes at 6 months. These findings do not support the use of early prophylactic hypothermia for patients with severe traumatic brain injury. Trial Registration clinicaltrials.gov Identifier: NCT00987688; Anzctr.org.au Identifier: ACTRN12609000764235