Hierarchical Hydrogels with Ordered Micro-Nano Structures for Cancer-on-a-Chip Construction

In the drug therapy of tumor, efficient and stable drug screening platforms are required since the drug efficacy varies individually. Here, inspired by the microstructures of hepatic lobules, in which hepatocytes obtain nutrients from both capillary vessel and the central vein, we present a novel hierarchical hydrogel system with ordered micro-nano structure for liver cancer-on-a-chip construction and drug screening. The hierarchical hydrogel system was fabricated by using pregel to fill and replicate self-assembled colloidal crystal arrays and microcolumn array template. Due to the synergistic effect of its interconnected micro-nano structures, the resultant system could not only precisely control the size of cell spheroids but also realize adequate nutrient supply of cell spheroids. We have demonstrated that by integrating the hierarchical hydrogel system into a multichannel concentration gradients microfluidic chip, a functional liver cancer-on-a-chip could be constructed for high-throughput drug screening with good repeatability and high accuracy. These results indicated that the hierarchical hydrogel system and its derived liver cancer-on-a-chip are ideal platforms for drug screening and have great application potential in the field of personalized medicine.

Injectable and Temperature-Sensitive Titanium Carbide-Loaded Hydrogel System for Photothermal Therapy of Breast Cancer

Recently, organic–inorganic hybrid materials have gained much attention as effective photothermal agents for cancer treatment. In this study, Pluronic F127 hydrogel-coated titanium carbide (Ti3C2) nanoparticles were utilized as an injectable photothermal agent. The advantages of these nanoparticles are their green synthesis and excellent photothermal efficiency. In this system, lasers were mainly used to irradiate Ti3C2 nanoparticles to produce a constant high temperature, which damaged cancer cells. The nanoparticles were found to be stable during storage at low temperatures for at least 2 weeks. The Ti3C2 nanoparticles exhibited a shuttle-shaped structure, and the hydrogels presented a loosely meshed structure. In addition, Ti3C2 nanoparticles did not affect the reversible temperature sensitivity of the gel, and the hydrogel did not affect the photothermal properties of Ti3C2 nanoparticles. The in vitro and in vivo results show that this hydrogel system can effectively inhibit tumor growth upon exposure to near-infrared irradiation with excellent biocompatibility and biosafety. The photothermal agent-embedded hydrogel is a promising photothermal therapeutic strategy for cancer treatment by enhancing the retention in vivo and elevating the local temperature in tumors.

Preparation, Characterization and Evaluation of the Anti-Inflammatory Activity of Epichlorohydrin-β-Cyclodextrin/Curcumin Binary Systems Embedded in a Pluronic®/Hyaluronate Hydrogel

Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-β-CD (EpiβCD) was used as polymeric CD. To characterize the binary system, solid-state and in-solution studies were performed. Afterwards, an experimental design was performed to optimize the hydrogel system. Finally, the CurEpiβCD hydrogel system was tested for anti-inflammatory activity using a HaCat psoriasis cell model. Co-grinded Cur/EpiβCD binary system showed a strong interaction and Curcumin solubility was much improved. Its combination with Pluronic® F-127/hyaluronate hydrogel demonstrated an improvement in release rate and Curcumin permeation. After testing its anti-inflammatory activity, the system showed a significant reduction in IL-6 levels. Hydrogel-containing CurEpiβCD complex is a great alternative to treat topical inflammatory diseases.

Spatiotemporal regulation of endogenous MSCs using a functional injectable hydrogel system for cartilage regeneration

Hydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.

Preparation and Characterization of Curcumin Nanoemulgel Utilizing Ultrasonication Technique for Wound Healing: In Vitro, Ex Vivo, and In Vivo Evaluation

Hydrogels being a drug delivery system has great significance particularly for topical application in cutaneous open wound. Its specific physicochemical properties such as non-adhesiveness, moisture retention, exudate absorption, and gas permeability make them ideal as a drug delivery vehicle for wound healing application. Further, curcumin (a natural bioactive) was selected as a therapeutic agent to incorporate into the hydrogel system to design and develop nanogel pharmaceutical products for wound healing. Although, curcumin possesses remarkable anti-inflammatory, antioxidant, and anti-infective activity along with hastening the healing process by acting over the different stages of the wound healing process, but its poor biopharmaceutical (low aqueous solubility and skin penetrability) attributes hamper their therapeutic efficacy for skin applications. The current investigation aimed to develop the curcumin-loaded nanogel system and evaluated to check the improvement in the therapeutic efficacy of curcumin through a nanomedicine-based approach for wound healing activity in Wistar rats. The curcumin was enclosed inside the nanoemulsion system prepared through a high-energy ultrasonic emulsification technique at a minimum concentration of surfactant required to nanoemulsify the curcumin-loaded oil system (Labrafac PG) having droplet size 56.25 ± 0.69 nm with polydispersity index 0.05 ± 0.01 and negatively surface charge with zeta potential −20.26 ± 0.65 mV. It was observed that the impact of Smix (surfactant/co-surfactant mixture) ratio on droplet size of generated nanoemulsion is more pronounced at lower Smix concentration (25%) compared to the higher Smix concentration (30%). The optimized curcumin-loaded nanoemulsion was incorporated into a 0.5% Carbopol® 940 hydrogel system for topical application. The developed curcumin nanoemulgel exhibited thixotropic rheological behavior and a significant (p < 0.05) increase in skin penetrability characteristics compared to curcumin dispersed in conventional hydrogel system. The in vivo wound healing efficacy study and histological examination of healed tissue specimen further signify the role of the nanomedicine-based approach to improve the biopharmaceutical attributes of curcumin.

An Injectable Chitosan-Based Self-Healable Hydrogel System as An Antibacterial Wound Dressing

Due to their biodegradability and biocompatibility, chitosan-based hydrogels have great potential in regenerative medicine, with applications such as bacteriostasis, hemostasis, and wound healing. However, toxicity and high cost are problems that must be solved for chitosan-based hydrogel crosslinking agents such as formaldehyde, glutaraldehyde, and genipin. Therefore, we developed a biocompatible yet cost-effective chitosan-based hydrogel system as a candidate biomaterial to prevent infection during wound healing. The hydrogel was fabricated by crosslinking chitosan with dialdehyde chitosan (CTS–CHO) via dynamic Schiff-base reactions, resulting in a self-healable and injectable system. The rheological properties, degradation profile, and self-healable properties of the chitosan-based hydrogel were evaluated. The excellent antibacterial activity of the hydrogel was validated by a spread plate experiment. The use of Live/Dead assay on HEK 293 cells showed that the hydrogel exhibited excellent biocompatibility. The results demonstrate that the newly designed chitosan-based hydrogel is an excellent antibacterial wound dressing candidate with good biocompatibility.