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Alginate/gelatin (Alg-Gel) hydrogels have been used experimentally, associated with mesenchymal stromal/stem cells (MSCs), to guide bone tissue formation. One of the main challenges for clinical application is optimizing Alg-Gel stiffness to guide osteogenesis. In this study, we investigated how Alg-Gel stiffness could modulate the dental pulp stem cell (DPSC) attachment, morphology, proliferation, and osteogenic differentiation, identifying the optimal conditions to uncouple osteogenesis from the other cell behaviors. An array of Alg-Gel hydrogels was prepared by casting different percentages of alginate and gelatin cross-linked with 2% CaCl2. We have selected two hydrogels: one with a stiffness of 11 ± 1 kPa, referred to as “low-stiffness hydrogel”, formed by 2% alginate and 8% gelatin, and the other with a stiffness of 55 ± 3 kPa, referred to as “high-stiffness hydrogel”, formed by 8% alginate and 12% gelatin. Hydrogel analyses showed that the average swelling rates were 20 ± 3% for the low-stiffness hydrogels and 35 ± 2% for the high-stiffness hydrogels. The degradation percentage was 47 ± 5% and 18 ± 2% for the low- and high-stiffness hydrogels, respectively. Both hydrogel types showed homogeneous surface shape and protein (Alg-Gel) interaction with CaCl2 as assessed by physicochemical characterization. Cell culture showed good adhesion of the DPSCs to the hydrogels and proliferation. Furthermore, better osteogenic activity, determined by ALP activity and ARS staining, was obtained with high-stiffness hydrogels (8% alginate and 12% gelatin). In summary, this study confirms the possibility of characterizing and optimizing the stiffness of Alg-Gel gel to guide osteogenesis in vitro without altering the other cellular properties of DPSCs.

The release of drugs from core/shell nanoparticles (NPs) is a crucial factor in ensuring high reproducibility, stability, and quality control. It serves as the scientific basis for the development of nanocarriers. Several factors, such as composition, composition ratio, ingredient interactions, and preparation methods, influence the drug release from these carrier systems. The objective of our study was to investigate and discuss the relationship between modifications of core/shell NPs as multifunctional drug delivery systems and the properties and kinetics of drug release using an in vitro drug release model. In this paper, we prepared four core/shell NPs consisting of a superparamagnetic iron oxide NPs (Fe3−δO4) core encapsulated by a biocompatible thermo-responsive copolymer, poly(2-(2-methoxy) ethyl methacrylate-oligo (ethylene glycol) methacrylate) or P(MEO2MAx-OEGMA100−x) (where x and 100 − x represented the molar fractions of MEO2MA and OEGMA, respectively), and loaded with doxorubicin (DOX). Colloidal behavior measurements in water and PBS as a function of temperature showed an optimization of the lower critical solution temperature (LCST) depending on the molar fractions of MEO2MA and OEGMA used to form each NPs. In vitro studies of doxorubicin release as a function of temperature demonstrated a high control of release based on the LCST. A temperature of approximately 45 °C for 60 h was sufficient to release 100% of the DOX loaded in the NPs for each sample. In conclusion, external stimuli can be used to modulate the drug release behavior. Core/shell NPs hold great promise as a technique for multifunctional drug delivery systems.

Abstract Here, a versatile strategy to engineer smart theranostic nanocarriers is reported. The core/shell nanosystem is composed of a superparamagnetic iron oxide (Fe3−δO4) nanoparticle (NP) core bearing the biocompatible thermo‐responsive poly(2‐(2‐methoxy)ethyl methacrylate‐oligo(ethylene glycol methacrylate), P(MEO2MAx‐OEGMA100−x) copolymer (where x and 100‐x represent the molar fractions of MEO2MA and OEGMA, respectively). Folic acid (FA) is end‐conjugated to the P(MEO2MAx‐OEGMA100−x) copolymer, leading to Fe3−δO4@P(MEO2MAx‐OEGMA100−x)‐FA, to facilitate active targeting of NPs to cancer cells. A highly potent hydrophobic anticancer agent doxorubicin (DOX) is incorporated in the thermo‐responsive P(MEO2MAx‐OEGMAy) brushes via supramolecular interactions to increase its solubility and the assessment of therapeutic potentials. These experiments confirm the magnetic hyperthermia properties of nanocarrier and reveal that only a small amount (10% ± 4%) of DOX is diffused at room temperature, while almost full drug (100%) is released after 52 h at 41 °C. Interestingly, it is found that P(MEO2MA60‐OEGMA40) polymers offer to NPs a promising stealth behavior against Human Serum Albumin and Fibrinogen model proteins.