Multilayer hydrogels with spatially controllable mechanical and functional properties are increasingly valuable, yet their utility is often constrained by fabrication challenges such as weak interfacial adhesion as well as reliance on cytotoxic photoinitiators and UV exposure. This study presents a simple, robust, and photoinitiator-free method to engineer multilayer poly(ethylene glycol) (PEG) hydrogels using off-stoichiometry thiol–ene (OSTE) Michael addition chemistry. By deliberately utilizing an alternating thiol-rich and vinyl sulfone-rich PEG formulation, residual functional groups are preserved at the layer interfaces and subsequently form covalent bonds between the adjacent layers, enabling strong interfacial adhesion without UV irradiation, photoinitiators, or adhesives. The resulting hydrogels exhibited rapid and tunable gelation (1–5 min), with mechanical properties spanning ∼0.5–6 kPa through varying polymer concentration (5–10 wt %) and thiol–ene ratio (0.6–1.6). Ellman’s assay confirmed the presence of stoichiometry-dependent unreacted thiol groups, validating the proposed interfacial bonding mechanism. Peel tests revealed strong interfacial adhesion, with failure occurring within the bulk material rather than at the interface. Nanoindentation further revealed spatially defined stiffness profiles across the multilayer construct, confirming precise mechanical compartmentalization. The hydrogels displayed tunable swelling behavior and degradation profiles depending on the formulations. Additionally, all single- and multilayer hydrogels maintained high cytocompatibility (>90% NIH/3T3 mice fibroblast viability) independent of polymer concentration, thiol–ene ratios, or layering. Incorporation of alginate microparticles provided an additional strategy for modulating hydrogel properties, significantly reducing swelling and enhancing stiffness while preserving structural integrity. Overall, the findings established a platform for engineering heterogeneous hydrogel constructs with spatially controlled properties, biofunctionality, and compatibility features that make them relevant for biomedical applications.
Conductive hydrogels with simultaneous high stretchability, robust mechanical toughness, and reliable strain-sensing sensitivity remain challenging to fabricate, particularly without toxic chemical initiators or cross-linkers. To address this, a multifunctional poly(acrylic acid)/gallium-bacterial cellulose (PAA/Ga-BC) hydrogel was developed through an initiator-free approach. BC serves simultaneously as an emulsifier to stabilize liquid metal nanoparticles (LMNPs) in aqueous suspension and as a rigid reinforcing scaffold within the PAA matrix, yielding a physically cross-linked dual-network structure governed by hydrogen bonds, Ga3+ ionic coordination, and polymer chain entanglement. The optimized PAA/Ga1.0-BC0.5 hydrogel achieves a tensile strength of 155 kPa, an elongation at break of 1869%, and a toughness of 1.28 MJ·m–3. As a strain sensor, it exhibits a gauge factor (GF) of 4.8 over the 500–800% strain range, detects strains as low as 1%, and retains stable cyclic performance over 300 stretching cycles at 75% strain. The hydrogel also demonstrates rapid electrical self-reconnection (200 ms), mechanical recovery exceeding 90% after 6 h, broad substrate adhesion (up to 6.4 kPa on wood), and measurable antibacterial inhibition against both S. aureus and E. coli. Furthermore, the hydrogel undergoes water-triggered disintegration within 21 days. This work establishes a platform for high-performance flexible strain sensors applicable to wearable human motion detection and emerging soft robotics.
Qianqian Wang, Lin Zhong, He-li Cheng et al.· ACS Applied Polymer Material...· 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
Conductive hydrogels have risen as a promising material for flexible wearable sensors. However, achieving a hydrogel that simultaneously possesses high mechanical properties, conductivity, self-healing ability, and adhesion remains a challenge. Herein, we developed a dual-network ionic conductive hydrogel (P-P(C-A)-PA) by incorporating poly(vinyl alcohol) and a copolymer of catechol-modified ionic liquid and acrylamide. The optimized hydrogel exhibited outstanding mechanical performance (stress: 883 kPa, strain: 1120%), self-healing efficiency (stress recovery of 58.6% ± 4.6% and toughness recovery of 57.7% ± 5.5%), ionic conductivity (3.91 S/m), and adhesion strength (50 kPa on Ecoflex). The hydrogel-based flexible sensor reliably monitored human motion with rapid and accurate signal response even after self-healing. The hydrogel-based triboelectric nanogenerator showed excellent output performance (180 V, 7.9 μA, and 65 nC), further identifying grasped objects and monitoring finger rehabilitation before and after self-healing. These results highlighted the considerable potential of our hydrogel for applications in advanced electronics.
Jingjing Du, Xi-Xi Zhu, Zengsheng Wang et al.· Biomacromolecules· 0 citations
Developing hydrogels that simultaneously combine high mechanical robustness, antifreezing capability, and stable conductivity remains a substantial challenge for flexible sensing materials. Herein, we report a multifunctional conductive rotaxane-crosslinked hydrogel constructed from a γ-cyclodextrin/poly(ethylene glycol) diacrylate (γ-CD/PEGDA) slide-ring crosslinker embedded in a poly(vinyl alcohol) (PVA)/acrylamide (AM)/xanthan gum (XG)/Zn2+ network. The threaded crosslinker introduces movable junctions into the network, allowing stress redistribution through a pulley effect and thereby improving the mechanical performance of the hydrogel. Together with hydrogen bonding, Zn2+ coordination, and the physically crosslinked PVA network, this design generates a robust multicomponent architecture. The optimized hydrogel exhibited a tensile stress of 3.2 MPa, an elongation at break of 254%, and a toughness of 40 MJ m−3, together with high puncture resistance and cyclic stability. The hydrogel also showed a freezing point of −20.59 °C and a low equilibrium swelling ratio in water, indicating favorable antifreezing and antiswelling performance. Owing to interconnected ionic conduction pathways, the material further displayed stable ionic conductivity and reliable strain-sensing behavior over a broad strain range, with rapid response/recovery and effective monitoring of human motion and subtle physiological activities. This work provides a practical strategy for constructing mechanically robust, antifreezing, and conductive hydrogels for wearable sensing and related bioelectronic applications.
Jie Ren, Ziqiong Zhou, Wenjing Zhang et al.· Macromolecules· 0 citations
Background/Objectives: Tissue bio-adhesives have gained significant attention as efficient alternatives to conventional wound closures, which are often hindered by insufficient adhesion and poor biocompatibility. Methods: Inspired by nature’s robust wet-adhesion strategies that use dynamic covalent interactions, we have reported a facilely fabricated hydrogel bio-adhesive based on lactobionic acid-conjugated polyethylenimine (LA-PEI) and oxidized dextran (ODex) via Schiff base linkages. Results: The prepared hydrogels exhibited three-dimensional interconnected porous networks, regulated swelling ratios, typical viscoelasticity, shear-thinning behavior, and self-healing ability. Notably, the swelling ratios of the hydrogels depended on composition, and OLP11 displayed the highest swelling ratio of over 1500%. The hydrogel bio-adhesives exhibited strong adhesion to various surfaces, including glass, metal, plastic, rubber, and wood, as well as to different chicken organs, including the heart, liver, spleen, and stomach. Furthermore, the hydrogels exhibited excellent ABTS radical-scavenging activity, effective intracellular reactive oxygen species (ROS) scavenging, and good hemocompatibility, with hemolysis ratios of all hydrogels close to 0%, below the threshold of 5%. After culturing with NIH 3T3 fibroblasts, the hydrogels demonstrated good cytocompatibility and promoted cell proliferation, with cell viabilities on day 3 reaching over 90%. Conclusions: This design yields multifunctional hydrogel bio-adhesives, showing strong promise for wound care and tissue repair applications.
Lei Nie, Xiao-Ran Hu, Shichang Cheng et al.· Pharmaceutics· 1 citation
Thiol-ene gelatin-based hydrogels, particularly gelatin-norbornene (GelNB)-based hydrogels, are promising for extrusion-based three-dimensional (3D) bioprinting owing to their rapid oxygen-insensitive crosslinking and excellent biocompatibility. Dithiothreitol (DTT) is commonly used as a thiol crosslinker because of its efficient and well-characterized reaction kinetics and ability to fine-tune the mechanical properties of the resulting hydrogel with minimal changes to its composition. However, application of DTT in cell-laden constructs is limited by cytotoxicity arising from direct cellular exposure to its strong reducing activity. To address this limitation, we introduced an indirect DTT delivery approach, in which DTT was incorporated into a starch-based support material alternately deposited with a GelNB bioink, enabling interfacial diffusion-mediated thiol-ene crosslinking upon light irradiation while minimizing direct cellular exposure to free DTT. Incorporation of 64.8 mM DTT into a 16.7 w/w% starch-based support material produced constructs (10 w/v% GelNB) with mechanical properties, shape fidelity, and stability comparable to those fabricated using direct DTT premixing (6.5 mM). Fibroblasts encapsulated within the constructs prepared via indirect DTT supply exhibited enhanced cytocompatibility (up to a 47% increase in the cell viability), a significantly higher mitochondrial activity, and reduced reactive oxygen species generation compared with those in the constructs prepared via direct DTT premixing in the bioink. These improvements were consistently observed across multiple cell types. The proposed extrusion-based 3D bioprinting strategy offers a practical and cell-friendly approach for expanding the application scope of a DTT-mediated thiol-ene reaction for GelNB-based bioprinting and may be adapted to other bioink systems relying on cytotoxic crosslinkers.
P. W. Prasetyaningrum, Shinji Sakai· ACS Biomaterials Science & E...· 0 citations