Hydrogel-Based Platforms for Advanced Therapy and Theranostics

Personalised controlled drug delivery systems (CDDSs) can adjust drug concentration levels according to patient needs, which has enormous research prospects in precision medicine. In this study, the topological optimisation method was utilised in the structural design of a hydrogel CDDS to achieve a parameter-based adjustment of the drug average concentration in the hydrogel. A polyacrylamide/sodium alginate dual-network hydrogel was selected as a drug carrier, and tetracycline hydrochloride was used as a model drug. The topological optimisation model of the hydrogel CDDS was developed. The effects of the mesh size, target concentration, and volume factor on the optimised results were investigated. Hydrogel flow channel structures were obtained, which satisfied the different target concentrations. To verify the rationality of the optimisation model, in vitro drug release experiments were carried out. The results show that the hydrogel CDDS can control drug release within 7 days, and the drug release tends to follow zero-order release behaviour. The adjustable average concentration of tetracycline hydrochloride in hydrogel CDDS is recommended in the range of 20.79 to 31.04 mol/m³. This novel method provides a reference for personalised structure design of CDDS in the context of precision medicine. Full article

As advanced radiotherapy techniques progress to deliver a high absorbed dose to the target volume while minimizing the dose to normal tissues using intensity-modulated beams, arcs or stereotactic radiosurgery, new challenges occur to assure that the high treatment dose is delivered homogeneously to the tumor. Small irradiation field sizes (≤1 cm²) that tightly conform to precise target regions and allow for the deliverance of doses with a high therapeutic ratio, are of particular interest. However, the small field dosimetry using conventional dosimeters is limited by the relative large size of the detector. Radiation-sensitive polymer gels have the potential to meet this dosimetry challenge due to their almost unlimited ability in resolving three-dimensional dose distributions of any shape and makes them unique and suitable for the evaluation of dose profiles and the verification of complex doses. In this work, dose distributions in nMAG gels that have been irradiated to different doses by applying a 6 MV FFF photon beam collimated to 1 cm², were analyzed and the dose profiles were evaluated by applying a gamma passing rate criteria of 3%/3 mm and considering different post-irradiation time intervals between the irradiation and the gels read out process. X-ray CT and NMR imaging procedures were used for the dose evaluation. It was found that the shape and uniformity of the dose profiles were changing due to post-irradiation polymerization and gelation processes, indicating time dependent growing uniformity which was better expressed for the higher delivered doses. It was estimated that in order to obtain acceptably symmetric small field dose profiles, a longer post-irradiation time is needed for getting the full scope of the polymerization as compared with the recently recommended 24 h period between irradiation and the read out processes of the dose gels. An estimated overall uncertainty (double standard deviation, 95% confidence level) of 3.66% was achieved by applying R2 measurements (NMR read out), and a 3.81–applying X-ray CT read out for 12 Gy irradiated gels 56 h post-irradiation. An increasing tendency for the uncertainty was observed with a decreasing post-irradiation time. A gamma passing rate of 90.3% was estimated for the 12 Gy irradiated gels and, 56 h post-irradiation, the X-ray CT evaluated gels as well as a gamma passing rate of 92.7% was obtained for the NMR evaluated gels applying a 3%/3 mm passing criteria. Full article

Hydrogels are basic materials widely used in various fields, especially in biological engineering and medical imaging. Hydrogels consist of a hydrophilic three-dimensional polymer network that rapidly expands in water and can hold a large volume of water in its swelling state without dissolving. These characteristics have rendered hydrogels the material of choice in drug delivery applications. In particular, carboxymethyl cellulose (CMC) hydrogels have attracted considerable research attention for the development of safe drug delivery carriers because of their non-toxicity, good biodegradability, good biocompatibility and low immunogenicity. Aiming to inspire future research in this field, this review focuses on the current preparation methods and applications of CMC gels and highlights future lines of research for the further development of diverse applications. Full article

Background: In vitro three-dimensional (3D) hepatic spheroid culture has shown great promise in toxicity testing because it better mimics the cell–cell and cell–matrix interactions found in in vivo conditions than that of the traditional two-dimensional (2D) culture. Despite embedding HepaRG spheroids with collagen type I (collagen I) extracellular matrix (ECM) revealed a much better differentiation capability, almost all the collagen utilized in in vitro hepatocytes cultures is animal-derived collagen that may limit its use in human toxicity testing. Method: Here, a preliminary investigation of HepaRG cells cultured in different dimensionalities and with the addition of ECM was performed. Comparisons of conventional 2D culture with 3D spheroid culture were performed based on their functional or structural differences over 7 days. Rat tail collagen (rtCollagen) I and recombinant human collagen (rhCollagen) I were investigated for their ability in promoting HepaRG spheroid differentiation. Results: An immunofluorescence analysis of the hepatocyte-specific functional protein albumin suggested that HepaRG spheroids demonstrated better hepatic function than spheroids from 2D culture, and the function of HepaRG spheroids improved in a time-dependent manner. The fluorescence intensities per unit area of spheroids formed by 1000 cells on days 7 and 10 were 25.41 and 45.38, respectively, whereas almost undetectable fluorescence was obtained with 2D cells. In addition, the embedding of HepaRG spheroids into rtCollagen and rhCollagen I showed that HepaRG differentiation can be accelerated relative to the differentiation of spheroids grown in suspension, demonstrating the great promise of HepaRG spheroids. Conclusions: The culture conditions established in this study provide a potentially novel alternative for promoting the differentiation of HepaRG spheroids into mature hepatocytes through a collagen-embedded in vitro liver spheroid model. This culture method is envisioned to provide insights for future drug toxicology. Full article