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1. Finding the sweet spot: a library of hydrogels with tunable degradation for tissue model development

   https://doi.org/10.1039/d1tb02436a  

   Pandala, Narendra; LaScola, Michael A.; Hinton, Zachary; Korley, La Shanda; Lavik, Erin (March 2022, Journal of Materials Chemistry B)

   In vitro models are valuable tools for applications including understanding cellular mechanisms and drug screening. Hydrogel biomaterials facilitate in vitro models by mimicking the extracellular matrix and in vivo microenvironment. However, it can be challenging for cells to form tissues in hydrogels that do not degrade. In contrast, if hydrogels degrade too much or too quickly, tissue models may be difficult to assess in a high throughput manner. In this paper, we present a poly(allylamine) (PAA) based synthetic hydrogel system which can be tuned to control the mechanical and chemical cues provided by the hydrogel scaffold. PAA is a polycation with several biomedical applications, including the delivery of small molecules, nucleic acids, and proteins. Based on PAA and poly(ethylene glycol) (PEG), we developed a synthetic non-degradable system with potential applications for long-term cultures. We then created a second set of gels that combined PAA with poly- l -lysine (PLL) to generate a library of semi-degradable gels with unique degradation kinetics. In this work, we present the hydrogel systems’ synthesis, characterization, and degradation profiles along with cellular data demonstrating that a subset of gels supports the formation of endothelial cell cord-like structures. 

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2. Two-Dimensional and Three-Dimensional Ultrathin Multilayer Hydrogels through Layer-by-Layer Assembly

   https://doi.org/10.1021/acs.langmuir.2c00630  

   Kozlovskaya, Veronika; Dolmat, Maksim; Kharlampieva, Eugenia (January 2022, Langmuir)

   Stimuli-responsive multilayer hydrogels have opened new opportunities to design hierarchically organized networks with properties controlled at the nanoscale. These multilayer materials integrate structural, morphological, and compositional versatility provided by alternating layer-bylayer polymer deposition with the capability for dramatic and reversible changes in volumes upon environmental triggers, a characteristic of chemically crosslinked responsive networks. Despite their intriguing potential, there has been limited knowledge about the structure−property relationships of multilayer hydrogels, partly because of the challenges in regulating network structural organization and the limited set of the instrumental pool to resolve structure and properties at nanometer spatial resolution. This Feature Article highlights our recent studies on advancing assembly technologies, fundamentals, and applications of multilayer hydrogels. The fundamental relationships among synthetic strategies, chemical compositions, and hydrogel architectures are discussed, and their impacts on stimuli-induced volume changes, morphology, and mechanical responses are presented. We present an overview of our studies on thin multilayer hydrogel coatings, focusing on controlling and quantifying the degree of layer intermixing, which are crucial issues in the design of hydrogels with predictable properties. We also uncover the behavior of stratified “multicompartment” hydrogels in response to changes in pH and temperature. We summarize the mechanical responses of free-standing multilayer hydrogels, including planar thin coatings and films with closed geometries such as hollow microcapsules and nonhollow hydrogel microparticles with spherical and nonspherical shapes. Finally, we will showcase potential applications of pH- and temperature-sensitive multilayer hydrogels in sensing and drug delivery. The knowledge about multilayer hydrogels can advance the rational design of polymer networks with predictable and well-tunable properties, contributing to modern polymer science and broadening hydrogel applications. 

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3. Fracture tolerance induced by dynamic bonds in hydrogels

   https://doi.org/10.1016/j.jmps.2022.105083  

   Yang, Hang; Chen, Xi; Sun, Bonan; Tang, Jingda; Vlassak, Joost J. (December 2022, Journal of the Mechanics and Physics of Solids)

   Among soft materials, hydrogels with dynamic bonds that can be activated by a range of stimuli including temperature, pH, and infrared or ultraviolet light, constitute a special class of materials with unusual properties such as self-healing, actuation, and controlled degradation. Here, we take a hydrogel with reconfigurable disulfide crosslinks as an example and investigate its mechanical behavior. We demonstrate that this material has excellent fracture and fatigue resistance when the disulfide crosslinks are activated by ultraviolet illumination. We propose a simple constitutive model that describes the mechanical behavior of the material under a broad range of conditions. 

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4. Biocompatible Polyglycidol-based hydrogels for load-bearing tissue engineering

   Beezer, Dain; Harth, Eva (March 2024, SciMeetings, A product from ACS Publications)

   The post-polymerization modification of polyglycidol is of great interest for the synthesis of functional polyether-based polymeric biomaterials. We present a degradable polyglycidol-based hydrogel system using oxime click chemistry by employing a ketone-functionalized and an amino-oxy functionalized branched polyglycidol. Ratio-controlled amino-oxy functionalized species were obtained by controlling the ratio of N-hydroxy phthalimide to the hydroxyl groups attached to the polyether backbone. A similar strategy was utilized to obtain ratio-controlled keto functionalized branched polyglycidols. This unique feature will allow for the tailoring of this branched PEG-like structural motif for the synthesis of novel biomaterials with tailored biochemical and biomechanical properties. The bio-orthogonal nature of this crosslinking reaction makes these hydrogels an attractive option for load-bearing tissue engineering. Our hydrogel synthesis methodology allows for control over the properties of the resulting polymeric network, based upon the ratio between the keto and the amino-oxy functionalities. The potential of these polyether-based networks to serve as a successful delivery platform was assessed by studying their swelling and degradation profiles. Biocompatibility and cytotoxicity of the gels were studied using NIH 3T3 cells. Our preliminary results highlighting the potential of our hydrogels platform will be discussed. 

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5. Transient Competitors to Modulate Dynamic Covalent Cross-Linking of Recombinant Hydrogels

   https://doi.org/10.1021/acs.chemmater.3c01575  

   Gilchrist, Aidan E.; Liu, Yueming; Klett, Katarina; Liu, Yu-Chung; Ceva, Sofía; Heilshorn, Sarah C. (November 2023, Chemistry of Materials)

   Hydrogels cross-linked by dynamic covalent chemistry (DCC) are stiff and remodelable, making them ideal biomimetics for tissue engineering applications. Due to the reversibility of DCC cross-links, the opportunity exists to transiently control hydrogel network formation through the use of small molecule competitors. Specifically, we incorporate low molecular weight competitors that reversibly disrupt the formation of hydrazone cross-links as they diffuse through a recombinant hydrogel. Using complementary experimental, computational, and theoretical polymer physics approaches, we present a family of competitors that predictably alter hydrogel gelation time and mechanics. By changing the competitor chemistry, we connect key reaction parameters (forward and reverse reactions rates and thermodynamic equilibrium constants) to the delayed onset of a percolated network, increased hydrogel gelation time, and transient control of hydrogel stiffness. Using human intestinal organoids as a model system, we demonstrate the ability to tune gelation kinetics of a recombinant hydrogel for uniform encapsulation of individual, patient-derived stem cells and their proliferation into three-dimensional structures. Taken together, our data establish a validated framework to relate molecular-level parameters of transient competitors to predicted macromolecular-network properties. As interest in biomimetic, DCC-cross-linked hydrogels continues to grow, these results will enable the rationale design of bespoke, dynamic biomaterials for tissue engineering. 

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