Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel–drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
Bioinspired polydopamine (PDA) has served as a universal coating to nanoparticles (NPs) for various biomedical applications. However, one remaining critical question is whether the PDA shell on NPs is stable in vivo. In this study, we modified gold nanoparticles (GNPs) with finely controlled PDA nanolayers to form uniform core/shell nanostructures (GNP@PDA). In vitro study showed that the PDA-coated GNPs had low cytotoxicity and could smoothly translocate to cancer cells. Transmission electron microscopy (TEM) analysis demonstrated that the PDA nanoshells were intact within cells after 24 h incubation. Notably, we found the GNP@PDA could partially escape from the endosomes/lysosomes to cytosol and locate close to the nucleus. Furthermore, we observed that the PDA-coated NPs have very different uptake behavior in two important organs of the liver and spleen: GNP@PDA in the liver were mainly uptaken by the Kupffer cells, while the GNP@PDA in the spleen were uptaken by a variety of cells. Importantly, we proved the PDA nanoshells were stable within cells of the liver and spleen for at least six weeks, and GNP@PDA did not show notable histological toxicity to main organs of mice in a long time. These results provided the direct evidence to support that the PDA surface modification can serve as an effective strategy to form ultrastable coatings on NPs in vivo, which can improve the intracellular delivery capacity and biocompatibility of NPs for biomedical application.
The development of hydrogels for cartilage replacement and soft robotics has highlighted a challenge: load-bearing hydrogels need to be both stiff and tough. Several approaches have been reported to improve the toughness of hydrogels, but simultaneously achieving high stiffness and toughness remains difficult. Here we report that alginate-polyacrylamide hydrogels can simultaneously achieve high stiffness and toughness. We combine short-and long-chain alginates to reduce the viscosity of pregel solutions and synthesize homogeneous hydrogels of high ionic cross-link density. The resulting hydrogels can have elastic moduli of ∼1 MPa and fracture energies of ∼4 kJ m −2 . Furthermore, this approach breaks the inverse relation between stiffness and toughness: while maintaining constant elastic moduli, these hydrogels can achieve fracture energies up to ∼16 kJ m −2 . These stiff and tough hydrogels hold promise for further development as load-bearing materials.
Most hydrogels have poor mechanical properties, severely limiting their scope of applications.Here we report on a hybrid hydrogel that combines extremely high stiffness, strength, and toughness, while maintaining physical integrity in electrolyte solutions. The hydrogel consists of a hydrophilic polymer network that is covalently cross-linked and a second polymer network that can crystallize. We show that the crystallites serve as physical cross-links for the second network.The crystallites contribute to the high stiffness and strength of the hydrogel; they unzip and dissipate energy under deformation, and reform due to the incompatibility of the two polymers in the hydrogel. The crystallite-toughened hydrogel can achieve an elastic modulus of 5 MPa, a strength of 2.5 MPa, and a fracture energy of 14,000 Jm -2 . Unlike alginate-based hybrid hydrogels, this hydrogel preserves its mechanical properties in electrolyte solutions and could be considered for further development in a variety of engineering applications. 20 Unfortunately, hydrogels synthesized using this method are compliant and brittle. 22 It is possible to achieve higher stiffness and toughness using a dry-anneal method, but only at the expense of a much lower water content ( Supplementary Fig. S1). 23 Muratoglu and coworkers polymerized acrylamide monomers in the pores of a PVA hydrogel to form uncross-linked chains, and showed that the equilibrium water content of the resulting gels increased with acrylamide content, while the coefficient of friction, tear strength and creep resistance decreased. 21Here we propose that a hybrid network of a crystalline polymer and a covalently crosslinked hydrophilic polymer may form a hydrogel with robust mechanical properties and good chemical stability: the crystalline polymer can generate a large number of crystallites to serve as physical cross-links that are both stable and reversible; the covalently cross-linked hydrophilic polymer maintain the elasticity of the network during deformation and controls the swelling of the hydrogel. We describe one such hybrid hydrogel that combines extremely high stiffness, strength, and toughness. The hydrogel consists of a hydrophilic polyacrylamide (PAAm) polymer network that is covalently cross-linked and a PVA network that forms crystallites. We show that the PVA crystallites result in a high cross-link density, thus producing a gel of remarkable stiffness and strength. The crystallites unzip under deformation, dissipating energy in the process and yielding a hydrogel with exceptional toughness. After deformation, unzipped crystallites recover at room temperature due to the incompatibility of the two polymers in the gel. The 4 crystallite-toughened hydrogel can achieve an elastic modulus of 5 MPa, a strength of 2.5 MPa, and a fracture energy of 14,000 Jm -2 . Moreover, these properties are stable, even in concentrated electrolyte solutions. ResultsWe prepared the hybrid hydrogels in a simple three-step protocol. First, we form a cross- Supplementary Fig. S2); e...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019 has spread throughout the world and caused many thousands of deaths. The previous study reported a higher severe status rate and mortality rate in male patients in China. However, the reason underlying this difference has not been reported. The convalescent plasma containing a high level of
High-Ni layered oxides are promising next-generation cathodes for lithium-ion batteries owing to their high capacity and lower cost. However, as the Ni content increases over 70 %, they have a high dynamic affinity towards moisture and CO in ambient air, primarily reacting to form LiOH, Li CO , and LiHCO on the surface, which is commonly termed "residual lithium". Air exposure occurs after synthesis as it is common practice to handle and store them under ambient conditions. The air exposure leads to significant performance losses, and hampers the electrode fabrication, impeding their practical viability. Herein, we show that substituting a small amount of Al for Ni in the crystal lattice notably improves the chemical stability against air by limiting the formation of LiOH, Li CO , LiHCO , and NiO in the near-surface region. The Al-doped high-Ni oxides display a high capacity retention with excellent rate capability and cycling stability after being exposed to air for 30 days.
Graphical Abstract Injectable gelatin hydrogels formed with bio-orthogonal click chemistry (ClickGel) are cell-responsive ECM mimics for in vitro and in vivo biomaterials applications. Gelatin polymers with pendant norbornene (GelN) or tetrazine (GelT) groups can quickly and spontaneously crosslink upon mixing, allowing for high viability of encapsulated cells, establishment of 3D elongated cell morphologies, and biodegradation when injected in vivo.
organic carbonate electrolytes used.  Specifically, the parasitic electrolyte decomposition occurs on the charged cathode surface, resulting in the formation of cathode-electrolyte interphase (CEI) with complicated surface chemistry.  Moreover, the surface degradation on cathode usually involves active mass dissolution, which is a common phenomenon in various cathodes.  Subsequently, the dissolved transition-metal ions reach the anode side through chemical crossover and poison the anode-electrolyte interphase (AEI) on graphite surface. [13,14] Thus, understanding the chemical and electrochemical reaction between the electrode and electrolyte, which influences the composition, microstructure, and chemical properties of the formed electrolyteelectrolyte interphases (EEIs), is crucial to establishing high-energy-density Li-ion batteries with long, stable service life.Conventionally, inert materials coating (e.g., Al 2 O 3 ,  AlPO 4 ,  AlF 3 ,  etc.) has been applied to modify the cathode surface chemistry and mitigate the interphase degradation on the cathode. Nevertheless, the cathode bulk particle could gradually lose contact with the coating layer due to the anisotropic volume change during lithiation and delithiation. [18,19] On the other hand, electrolyte additive, which is able to regulate the EEI chemistry through an in situ modification strategy, has been widely studied and proved to ensure high Coulombic efficiency and voltage efficiencies with long cycle life.  However, due to the complexity and air-sensitivity of the EEI chemistry, there is a limited understanding of the EEI configuration and architecture, and how different components influence the EEI layer properties and battery performance is yet to be fully understood.  Herein, with an ultrahigh-Ni layered oxide (LiNi 0.94 Co 0.06 O 2 ) as a model cathode and lithium bis(oxalate) borate (LiBOB) as a model electrolyte additive, the EEI chemical and physical property changes on both the cathode and anode are elucidated. Moreover, the layered architecture of the CEI and AEI at the nanometer scale is revealed by time-of-flight secondary ion mass spectrometry (TOF-SIMS) and the correlation between CEI and AEI properties is illustrated. On a chemical perspective, the tuned EEIs are configured with B x O y species and less ethylene carbonate/LiPF 6 decomposition products, which endows the CEI with extreme robustness against As a high-energy-density cathode for Li-ion batteries, high-Ni layered oxides, especially with ultrahigh Ni-content, suffer from short lifespans, due in part to their unstable electrode-electrolyte interphase (EEI). Herein, the cycle life of LiNi 0.94 Co 0.06 O 2 is greatly extended by manipulating the EEI with a lithium bis(oxalate) (LiBOB) additive even when operated at a moderately high voltage (4.4 V vs Li/Li + ). Impressively, the capacity retention can be increased from 61 to 80% after 500 cycles in a full cell paired with a graphite anode. Additionally, the...
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