Hydrogels are cross-linked polymeric networks with wide applications in drug delivery, tissue engineering, biosensing, and environmental remediation. These hydrogels additionally host living cells, small molecules, and biological propagules, which further expand the applications of these materials. However, most, if not all, fabrication methods require covalent modifications. In this work, by deliberately selecting polymers with a known propensity to phase separate and formulating compositions far from the binodal boundary, we demonstrate the propensity of the system to transition directly into viscoelastic liquids or gels. This behavior is demonstrated using a model system of poly(ethylene glycol) (PEG) and dextran (DEX). We carried out rheological studies to provide insights into the viscoelastic behavior of these gels. We systematically characterized the gels through colorimetric assays, FTIR, MALDI-TOF, and thermogravimetric analysis (TGA) to discern the molecular compositions and solvent content of the gels. These experimental findings are supplemented with coarse-grained (CG) simulation insights to investigate the mechanistic origins of phase separation propensity with varying molecular weights of DEX. We utilized coexisting densities in the two phases using CG simulations to predict the role of DEX molecular weight in the partitioning of PEG and DEX in the two phases. Finally, we exploit the fabricated gel's ability to encapsulate live cells, antibiotics, and plant seeds. We anticipate that this ATPS-based fabrication technique will provide a scalable, cross-linker-free route to multifunctional gels, enabling advanced applications in drug delivery and responsive materials.
An integrated analysis of gelation kinetics, micellization thermodynamics, and viscoelastic properties (G′, G″) of Pluronic F127-based hydrogels is provided to support the rational design of thermoresponsive hydrogels and identify critical knowledge gaps to guide future research in advanced therapeutic biomaterials.
Sharifah Nafisah Syed Ismail, H. Holilah, Lisman Suryanegara et al.· Polymer Bulletin· 0 citations
Both natural and synthetic polymers offer distinct advantages in regenerative medicine, yet their properties are often orthogonal, requiring trade-offs when used individually. Gelatin, the gold standard, exhibits cell adhesivity and is biodegradable but suffers from low mechanical tunability, a UCST around physiological conditions, and inferior porosity following hydrogel production. In contrast, poly(l-lactic acid) (PLA) and poly(trimethylene carbonate) (PTMC) often display mechanical tunability and low batch-to-batch variability, but lack bioactivity. Herein, PLA and PTMC were grafted onto gelatin through thiol-ene coupling, producing hybrid grafted constructs with either semicrystalline or amorphous grafts. These constructs can form physical gels through hydrophobic interactions, which can be covalently cross-linked into porous hydrogels. Graft lengths between 2000 and 10000 g mol were studied, combined with a successful translation to continuous flow ring-opening polymerization. Mass Determination Diffusion Ordered Spectroscopy (MaDDOSY) using a benchtop NMR was employed to measure molar masses, in which good agreements (Δ = 0.02 ± 0.09) were found with conventional techniques. After thiolation (>93%), no influence of graft length on thiol-ene coupling yields was observed. By varying graft length and graft type (PLA vs PTMC), a high tunability of physical hydrogels’ mechanical properties (4–50 kPa), transparency (25–97%), swelling capacity (500–2500%), and pore areas (10–100 000 μm2) upon cross-linking was achieved. These hybrid systems highlight the strong synergy between natural and synthetic polymers for regenerative materials design.
Nicolas Deroose, D. Haddleton, William Pointer et al.· Chemistry of Materials· 0 citations
SUMMARY Hydrogels are promising for biomedical applications due to their tunable properties and extracellular matrix (ECM)-mimicking capabilities, but available chemistries limit customization potential. We present a modular bioconjugation system using polyphenol radical crosslinking, where gallic acid (GA)-modified glycosaminoglycans rapidly crosslink with diverse biomolecules under blue light and riboflavin. This method enables the creation of customizable, cell-compatible matrices. We validate conjugation chemistry using 1 H NMR, size-exclusion chromatography, and gel electrophoresis. As proof-of-concept, we have created injectable hydrogels from GA-modified hyaluronic acid (HA-GA) crosslinked with various proteins. Mechanical properties are tunable via riboflavin concentration and light exposure. HCT116 colon cancer cells form spheroids in HA-GA-BSA, while other protein-containing hydrogels support dispersed growth, indicating enhanced cell adhesion. HA-GA hydrogels upregulate stemness markers compared to 2D culture, while protein incorporation reduces this effect. Matrix-activated Wnt signaling confirms functional biomolecule integration using HA-GA-Wnt3A matrices. This strategy enables tailored ECM design for tissue engineering and 3D cell culture.
Austin D. Evans, R. P. Parvathaneni, Rolle Rahikainen et al.· Cell Reports Physical Scienc...· 0 citations
Hydrogels are three‐dimensional elastic networks that have applications in wide array of biomedical fields. Hydrogels can be crosslinked via dynamic covalent bonds (DCB) in order to done them with the ability to be injected, to self‐heal, and to respond to stimuli. In our previous work, reversible thiol‐conjugate crosslinks were used in the preparation of dynamic poly(ethylene glycol) (PEG) hydrogels. Because the equilibrium state of these reversible thiol‐conjugate bonds can be shifted by temperature, both thermal and photothermal stimuli were used to induce the gel‐to‐sol transition of these materials to develop an on‐demand pulsatile cargo release. However, the dynamic nature of the crosslinks resulted in rapid gel dissolution that prevented their use for long‐term drug delivery. In this work, the hydrogels were complemented with stable thiol‐maleimide crosslinks to decrease their dissolution rate and prolong their functional lifetime. Data shows that even a small addition of thiol‐maleimide crosslinks significantly stabilizes the hydrogels, providing improved control of cargo release initiated by photothermal stimuli but does not cause a notable difference in cargo release at physiological temperature when compared to the hydrogels lacking the stable thiol‐maleimide crosslinks.
K. Thapa, Amelia Scott, Mackenzie U. Otakpor et al.· Macromolecular Bioscience· 0 citations
Recombinant spider silk proteins (spidroins) are emerging as a promising feedstock for biomaterial production due to their inherent ability to form hydrogels at 37 °C. However, their broader application as a robust cell culture platform has been hindered by slow gelation kinetics, CO2-induced turbidity, unknown long-term stability, and the use of Tris-HCl buffers that are suboptimal for most mammalian cells. In this study, we aimed to accelerate gelation kinetics of mini-spidroin-based hydrogels, reduce their turbidity, and improve gel stability under physiological conditions. Systematic evaluation of protein pre-treatments and buffer compositions identified parameters governing conformational behavior, gelation dynamics, and structural stability. Multimodal characterization, including turbidity measurements, circular dichroism spectroscopy, Fourier-transform infrared spectroscopy, mechanical assessment, transmission electron microscopy, Thioflavin T assays, and in vitro studies, enabled the formulation of a cytocompatible buffer system optimized for mini-spidroin hydrogels. The formulation improves transparency and accelerates gelation, while maintaining experimental simplicity, thereby advancing the utility of mini-spidroin hydrogels as cell culture platforms. This study accelerates gelation kinetics of mini-spidroin-based hydrogels. By identifying parameters that govern conformational behavior, gelation dynamics, and structural stability, a cytocompatible buffer system is optimized, improving optical transparency.
S. Stadlmayr, Tove Kivijärvi, B. Gross et al.· Communications Materials· 1 citation