ß-Lactoglobulin-based aerogels: Facile preparation and sustainable removal of organic contaminants from water.

Economically and efficiently removing organic pollutants from water is still a challenge in wastewater treatment. Utilizing environmentally friendly and readily available protein-based natural polymers to develop aerogels with effective removal performance and sustainable regeneration capability is a promising strategy for adsorbent design. Here, a robust and cost-effective method using inexpensive ß-lactoglobulin (BLG) as raw material was proposed to fabricate BLG-based aerogels. Firstly, photocurable BLG-based polymers were synthesized by grafting glycidyl methacrylate. Then, a cross-linking reaction, including photo-crosslinking and salting-out treatment, was applied to prepared BLG-based hydrogels. Finally, the BLG-based aerogels with high porosity and ultralight weight were obtained after freeze-drying. The outcomes revealed that the biocompatible BLG-based aerogels exhibited effective removal performance for a variety of organic pollutants under perfectly quiescent conditions, and could be regenerated and reused many times via a simple and rapid process of acid washing and centrifugation. Overall, this work not only demonstrates that BLG-based aerogels are promising adsorbents for water purification but also provides a potential way for the sustainable utilization of BLG.

Porous Hydrogels for Immunomodulatory Applications.

Cancer immunotherapy relies on the insight that the immune system can be used to defend against malignant cells. The aim of cancer immunotherapy is to utilize, modulate, activate, and train the immune system to amplify antitumor T-cell immunity. In parallel, the immune system response to damaged tissue is also crucial in determining the success or failure of an implant. Due to their extracellular matrix mimetics and tunable chemical or physical performance, hydrogels are promising platforms for building immunomodulatory microenvironments for realizing cancer therapy and tissue regeneration. However, submicron or nanosized pore structures within hydrogels are not favorable for modulating immune cell function, such as cell invasion, migration, and immunophenotype. In contrast, hydrogels with a porous structure not only allow for nutrient transportation and metabolite discharge but also offer more space for realizing cell function. In this review, the design strategies and influencing factors of porous hydrogels for cancer therapy and tissue regeneration are first discussed. Second, the immunomodulatory effects and therapeutic outcomes of different porous hydrogels for cancer immunotherapy and tissue regeneration are highlighted. Beyond that, this review highlights the effects of pore size on immune function and potential signal transduction. Finally, the remaining challenges and perspectives of immunomodulatory porous hydrogels are discussed.

MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogels for corneal epithelial healing.

The damage of corneal epithelium may lead to the formation of irreversible corneal opacities and even blindness. The migration rate of corneal epithelial cells directly affects corneal repair. Here, we explored ocu-microRNA 24-3p (miRNA 24-3p) that can promote rabbit corneal epithelial cells migration and cornea repair. Exosomes, an excellent transport carrier, were exacted from adipose derived mesenchymal stem cells for loading with miRNA 24-3p to prepare miRNA 24-3p-rich exosomes (Exos-miRNA 24-3p). It can accelerate corneal epithelial migration in vitro and in vivo. For application in cornea alkali burns, we further modified hyaluronic acid with di(ethylene glycol) monomethyl ether methacrylate (DEGMA) to obtain a thermosensitive hydrogel, also reported a thermosensitive DEGMA-modified hyaluronic acid hydrogel (THH) for the controlled release of Exos-miRNA 24-3p. It formed a highly uniform and clear thin layer on the ocular surface to resist clearance from blinking and extended the drug-ocular-epithelium contact time. The use of THH-3/Exos-miRNA 24-3p for 28 days after alkali burn injury accelerated corneal epithelial defect healing and epithelial maturation. It also reduced corneal stromal fibrosis and macrophage activation. MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogel as a multilevel delivery strategy has a potential use for cell-free therapy of corneal epithelial regeneration.

Engineering Hydrogels for Modulation of Dendritic Cell Function.

Dendritic cells (DCs), the most potent antigen-presenting cells, are necessary for the effective activation of naïve T cells. DCs encounter numerous microenvironments with different biophysical properties, such as stiffness and viscoelasticity. Considering the emerging importance of mechanical cues for DC function, it is essential to understand the impacts of these cues on DC function in a physiological or pathological context. Engineered hydrogels have gained interest for the exploration of the impacts of biophysical matrix cues on DC functions, owing to their extracellular-matrix-mimetic properties, such as high water content, a sponge-like pore structure, and tunable mechanical properties. In this review, the introduction of gelation mechanisms of hydrogels is first summarized. Then, recent advances in the substantial effects of developing hydrogels on DC function are highlighted, and the potential molecular mechanisms are subsequently discussed. Finally, persisting questions and future perspectives are presented.

Isoliquiritigenin Nanoemulsion Preparation by Combined Sonication and Phase-Inversion Composition Method: In Vitro Anticancer Activities.

Isoliquiritigenin (ILQ) has a number of biological activities such as antitumor and anti-inflammatory effects. However, biomedical applications of ILQ are impeded by its poor aqueous solubility. Therefore, in this research, we prepared a novel ILQ-loaded nanoemulsion, i.e., ILQ-NE, which consisted of Labrafil® M 1944 CS (oil), Cremophor® EL (surfactant), ILQ, and phosphate-buffered saline, by employing a combined sonication (high-energy) and phase-inversion composition (low-energy) method (denoted as the SPIC method). The ILQ-NE increased the ILQ solubility ~1000 times more than its intrinsic solubility. It contained spherical droplets with a mean diameter of 44.10 ± 0.28 nm and a narrow size distribution. The ILQ loading capacity was 4%. The droplet size of ILQ-NE remained unchanged during storage at 4 °C for 56 days. Nanoemulsion encapsulation effectively prevented ILQ from degradation under ultraviolet light irradiation, and enhanced the ILQ in vitro release rate. In addition, ILQ-NE showed higher cellular uptake and superior cytotoxicity to 4T1 cancer cells compared with free ILQ formulations. In conclusion, ILQ-NE may facilitate the biomedical application of ILQ, and the SPIC method presents an attractive avenue for bridging the merits and eliminating the shortcomings of traditional high-energy methods and low-energy methods.

Shape-Recoverable Macroporous Nanocomposite Hydrogels Created via Ice Templating Polymerization for Noncompressible Wound Hemorrhage.

Uncontrolled hemorrhage resulting from severe trauma or surgical operations remains a challenge. It is highly important to develop functional materials to treat noncompressible wound bleeding. In this work, a shape-recoverable macroporous nanocomposite hydrogel was facilely created through ice templating polymerization. The covalently cross-linked gelatin networks provide a robust framework, while the Laponite nanoclay disperses into the three-dimensional matrix, enabling mechanical reinforcement and hemostatic functions. The resultant macroporous nanocomposite hydrogel possesses an inherent interconnected macroporous structure and rapid deformation recovery. In vitro assessments indicate that the hydrogel displays good cytocompatibility and a low hemolysis ratio. The hydrogel shows a higher coagulation potential and more erythrocyte adhesion compared to the commercial gauze and gelatin sponge. The noncompressible liver hemorrhage models also confirm its promising hemostasis performance. This strategy of combining a nano-enabled solution with ice templating polymerization displays great potential to develop appealing absorbable macroporous biomaterials for rapid hemostasis.

Supramolecular and dynamic covalent hydrogel scaffolds: from gelation chemistry to enhanced cell retention and cartilage regeneration.

Supramolecular and dynamic covalent crosslinking (DCC) hydrogels not only display unique physicochemical properties that can mimic the dynamic extracellular matrix (ECM), but also have the capabilities of shear-thinning, self-healing and even shape memorizing. Specifically, through the breaking and reforming of the reversible linkage, cells can be readily encapsulated in the matrix and can well maintain their differentiation potentials. The dynamic shear-thinning and self-healing hydrogels can also be explored as cell-compatible bio-inks for the design of complex multicellular structures. These distinctive properties of dynamic hydrogels have attracted increasing interests in cell retention as well as cartilage tissue engineering. The biophysical and biochemical cues of hydrogel matrices have significant effects on cell fate. The studies on the relationship of cell response and the critical properties of hydrogels, such as mechanical strength, elasticity, ligand chemistry and degradation, are helpful in advancing dynamic hydrogels for cell retention and delivery. In this review, we highlight the most recent progress in the gelation strategies of biomedical supramolecular and DCC hydrogels and then focus on their applications for enhancing cell retention and cartilage/osteochondral regeneration. Furthermore, the challenges and future perspectives of supramolecular and DCC hydrogels in cell retention and cartilage regeneration are also discussed.

Quadruple hydrogen bonds and thermo-triggered hydrophobic interactions generate dynamic hydrogels to modulate transplanted cell retention.

A supramolecular hybrid hydrogel displaying a wide array of dynamic physical properties along with enhanced in vivo stem cell retention has been developed. The key strategy is facilely polymerizing bioactive gelatin methacrylate (GelMA) with 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and 2-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)ethyl methacrylate (UPyMA) to generate one hybrid branched copolymer. Rapid gelation occurs upon increasing the temperature above the lower critical solution temperature (LCST) of this supramolecular copolymer, where PMEO2MA segments dehydrate and assemble into clusters, providing a hydrophobic microenvironment facilitating UPy dimerization to connect polymer chains, thus forming quadruple hydrogen bond reinforced crosslinking networks. The biodegradable, self-healing, thermo-reversible and injectable properties of the supramolecular hydrogel are finely tunable by changing the hydrogel formulation. Mesenchymal stem cells encapsulated in the hydrogel show high viability and proliferation. The subcutaneous study shows that the stem cells delivered within the in situ formed hydrogel are well protected from mechanical damage and have significantly enhanced in vivo cell retention for three weeks. These results suggest that the dynamic supramolecular hydrogel can be utilized to regulate stem cells for tissue regeneration applications.

Weak Hydrogen Bonds Lead to Self-Healable and Bioadhesive Hybrid Polymeric Hydrogels with Mineralization-Active Functions.

Hydrogels with self-healing features that can spontaneously repair themselves upon mechanical damage are increasingly attractive for biomedical applications. Many attempts have been made to develop unique hydrogels possessing this property, as well as stimuli-responsiveness and biocompatibility; however, the hydrogel fabrication strategies often involve specific design of functional monomers that are able to optimally provide reversible physical or chemical interactions. Here, we report that weak hydrogen bonds, provided by oligo(ethylene glycol) methacrylate (OEGMA) and methacrylic acid (MAA), a monomer combination that is commonly used to prepare chemically cross-linking hydrogels, can generate self-healable hydrogels with mechanically resilient and adhesive properties through a facile one-step free radical copolymerization. The hydrogen bonds break and reform, providing an effective energy dissipation mechanism and synergic mechanical reinforcement. The physical properties can be simply tuned by OEGMA/MAA ratio control and reversible pH adjustment. Furthermore, the hydrogel can serve as a robust template for biomineralization to produce hydrogel composite that facilitate cell attachment and proliferations. This work is synthetically simple and dramatically increases the choice of amendable and adhesive hydrogels for industrial and biomedical applications.

Antimicrobial colloidal hydrogels assembled by graphene oxide and thermo-sensitive nanogels for cell encapsulation.

Hydrogels are promising 3D materials that have demonstrated increasing applications in the encapsulation and delivery of drugs and cells. Herein we report an injectable colloidal hydrogel that directly assembled by graphene oxide (GO) and thermo-sensitive nanogels (tNG). The pH dependent hydrogen bonding interactions between the carboxyl and oxethyl groups induce the reversible assembly of GO and nanogels. The hydrogel is mouldable and can be shaped into different macroscopic objects, and the mechanical strengths are tunable with pH and temperature adjustment. The hybrid hydrogel by its own possesses high antibacterial activity, and demonstrates responsive drug release behaviour and high viability of 3D encapsulated cells. We expect this hybrid colloidal hydrogel can serve as an interesting scaffold for active cargo delivery and cell culture.

The Antibacterial Applications of Graphene and Its Derivatives.

Graphene materials have unique structures and outstanding thermal, optical, mechanical and electronic properties. In the last decade, these materials have attracted substantial interest in the field of nanomaterials, with applications ranging from biosensors to biomedicine. Among these applications, great advances have been made in the field of antibacterial agents. Here, recent advancements in the use of graphene and its derivatives as antibacterial agents are reviewed. Graphene is used in three forms: the pristine form; mixed with other antibacterial agents, such as Ag and chitosan; or with a base material, such as poly (N-vinylcarbazole) (PVK) and poly (lactic acid) (PLA). The main mechanisms proposed to explain the antibacterial behaviors of graphene and its derivatives are the membrane stress hypothesis, the oxidative stress hypothesis, the entrapment hypothesis, the electron transfer hypothesis and the photothermal hypothesis. This review describes contributions to improving these promising materials for antibacterial applications.