Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.

Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines.

During the last few years, metal–organic frameworks (MOFs) are being considered as ideal candidates to find more efficient systems for the production and storage of energy

Alterations in neurogenesis result in the inevitable loss of brain nervous tissue and cause neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease (HD). In this regard, hydrogels based on natural biopolymers have attractive properties, such as excellent biocompatibility, a low immune response, and a significant similarity to the extracellular matrix (ECM) of tissues, thus supporting cell proliferation and migration. Human ECM is composed by relatively small amounts of fibrous, proteins, and polysaccharides. For example, scaffolds composed of gelatin and hyaluronic acid are highly abundant components in human ECM. The methacrylation of hyaluronic acid (HAMA) and gelatin (GelMA) through carboxyl and hydroxyl groups under UV light radiation at 365 nm produce polymeric scaffolds with elastic moduli similar to tissues, and, therefore, potential candidates to adhere, host, and facilitate cell proliferation and differentiation, which are dependent on their mechanical properties. In this work, the mechanical, thermal, and morphological properties of HAMA and GelMA hydrogel mixtures were studied and characterized via linear rheological measurements, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM).

Hybrid nanocomposites offer promising alternatives for the treatment of various diseases by enabling multifunctional therapeutic strategies. In this work, a hybrid nanocomposite based on hollow bimetallic nanoparticles (HBNPs) coated with poly(N-isopropylacrylamide) (PNIPAM) was designed as a stimuli-responsive platform for controlled drug delivery and photothermal therapy. This system exploits the strong near-infrared absorption of HBNPs and the thermoresponsive behavior of PNIPAM, which undergoes reversible swelling-contraction transitions that regulate drug release. The successful synthesis of the nanocomposite with combined chemotherapeutic and photothermal functionality was demonstrated. The nanocomposite exhibited stable and reproducible photothermal performance, generating sufficient temperature increases to induce cell death via hyperthermia. In addition, the platform showed low intrinsic cytotoxicity and favorable properties as a drug carrier for doxorubicin. Drug release displayed clear pH dependence reaching cumulative values of 84% of its load at pH 5.5 and 76% at physiological pH (7.4) after 24 h. Furthermore, NIR laser irradiation enhanced drug release up to 90% within the same period. In all cases, doxorubicin encapsulation improved therapeutic efficacy, which was further amplified when combined with laser irradiation. Overall, these results demonstrate the potential of the nanocomposite as an effective dual-modality platform for controlled, stimuli-responsive chemo-photothermal therapy.