Homopolymer and ABC Triblock Copolymer Mixtures for Thermoresponsive Gel Formulations

Our group has recently invented a novel series of thermoresponsive ABC triblock terpolymers based on oligo(ethylene glycol) methyl ether methacrylate with average Mn 300 g mol‒1 (OEGMA300, A unit), n-butyl methacrylate (BuMA, B unit) and di(ethylene glycol) methyl ether methacrylate (DEGMA, C unit) with excellent thermogelling properties. In this study, we investigate how the addition of OEGMA300x homopolymers of varying molar mass (MM) affects the gelation characteristics of the best performing ABC triblock terpolymer. Interestingly, the gelation is not disrupted by the addition of the homopolymers, with the gelation temperature (Tgel) remaining stable at around 30 °C, depending on the MM and content in OEGMA300x homopolymer. Moreover, stronger gels are formed when higher MM OEGMA300x homopolymers are added, presumably due to the homopolymer chains acting as bridges between the micelles formed by the triblock terpolymer, thus, favouring gelation. In summary, novel formulations based on mixtures of triblock copolymer and homopolymers are presented, which can provide a cost-effective alternative for use in biomedical applications, compared to the use of the triblock copolymer only.

Construction of a liquid-liquid phase separation system from the gel-sol transition of elongated protein microgels in a crowding agent

Liquid proteinaceous materials have been frequently found in cells or tissues and are crucial for various biological processes. Unlike their solid-state counterparts, liquid-state protein compartments are challenging to engineer and control at the microscale. Conventionally, gelation (sol-gel transition) of biological molecules has been thought to be the intermediate step between liquid-liquid phase separation (LLPS) states and insoluble aggregates that are related to protein functions, malfunctions and even diseases. However, the opposite process, i.e., the gel-sol transition of materials, has not been broadly explored. Here we describe a thermoresponsive gel-sol transition of a protein in a crowded environment that results in a demixed LLPS state, contradicting the common consequence of a one-phase protein solution by the end of such transition at elevated temperature without crowding agents. We also demonstrate a simple method to monitor the gel-sol transition by showing that elongated gelatin microgels can evolve towards a spherical morphology in the crowding agents because of interfacial tension. The LLPS system was explored for the diffusion of small particles for drug-release application scenarios. Our results demonstrate a route for the rapid construction of LLPS models, where the gel-sol transition of the protein-rich phase is monitorable. The models are featured with tunable size and dimensional monodispersity of dispersed condensates. The present study can be employed in biophysics and bioengineering with practices such as 3D printing and temperature sensing.

A thermoresponsive gel photoreleasing nitric oxide for potential ocular applications

A thermoresponsive gel integrating a NO photodonor shows physico-chemical stability in simulated tear fluid, releases NO under daylight conditions, is well tolerated by corneal cells and exhibits photobactericidal action towards Staphylococcus aureus.

A Novel Thermoresponsive Gel as a Potential Delivery System for Lipoxin

The objective of this study was to evaluate a novel thermoresponsive polyisocyanopeptide (PIC)–based hydrogel as an injectable carrier for local drug delivery for periodontal applications. Three formulations of PIC gels, 0.2%, 0.5%, and 1% w/w, were prepared. As controls, commercially available poloxamer 407 (P407) gels of 20% and 26% w/w were used. Lipoxin A4 (LXA4), a proresolving drug, was suspended into the gel solutions. The systems were evaluated regarding dynamic mechanical properties, injectability and stability, release and bioactivity of LXA4, and cytocompatibility. Results showed that the gelation temperatures of PIC and P407 gels were around 13°C to 23°C. PIC gels were less viscous and mechanically weaker than P407 gels due to the low polymer concentrations. However, PIC gels kept gel integrity for at least 2 wk when incubated with phosphate-buffered saline, whereas P407 gels were disintegrated totally within 1 wk. LXA4 was chemically stable in both neutral and alkaline medium for over 1 mo. The release of LXA4 from either 1% PIC or 26% P407 gels depicted an initial burst release followed by a sustained release for around 4 d. The extent of burst release was negatively correlated to the polymer concentration. LXA4 remained bioactive after release from PIC gels. No cytotoxicity was observed for 1% PIC gel. However, 26% P407 inhibited periodontal ligament cell and gingival epithelial cell growth. In conclusion, the thermoresponsive PIC gel is a potential candidate for periodontal drug delivery.