Schiff-Base Cross-Linked Hydrogels Based on Properly Synthesized Poly(ether urethane)s as Potential Drug Delivery Vehicles in the Biomedical Field: Design and Characterization.

-forming hydrogels based on the Schiff-base chemistry are promising for drug delivery applications, thanks to their stability under physiological conditions, injectability, self-healing properties, and pH-responsiveness. In this work, two water-soluble poly(ethylene glycol)-based poly(ether urethane)s (PEUs) were engineered. A high-molecular-weight PEU (SHE3350, 24 kDa, 1.

Three-Dimensional Microfibrous Scaffold with Aligned Topography Produced via a Combination of Melt-Extrusion Additive Manufacturing and Porogen Leaching for In Vitro Skeletal Muscle Modeling.

Skeletal muscle tissue (SMT) has a highly hierarchical and anisotropic morphology, featuring aligned and parallel structures at multiple levels. Various factors, including trauma and disease conditions, can compromise the functionality of skeletal muscle. The in vitro modeling of SMT represents a useful tool for testing novel drugs and therapies.

In Vitro Mechanical Stimulation to Reproduce the Pathological Hallmarks of Human Cardiac Fibrosis on a Beating Chip and Predict The Efficacy of Drugs and Advanced Therapies.

Cardiac fibrosis is one of the main causes of heart failure, significantly contributing to mortality. The discovery and development of effective therapies able to heal fibrotic pathological symptoms thus remain of paramount importance. Micro-physiological systems (MPS) are recently introduced as promising platforms able to accelerate this finding.

Biomimetic Electrospun Scaffold-Based In Vitro Model Resembling the Hallmarks of Human Myocardial Fibrotic Tissue.

Adverse remodeling post-myocardial infarction is hallmarked by the phenotypic change of cardiac fibroblasts (CFs) into myofibroblasts (MyoFs) and over-deposition of the fibrotic extracellular matrix (ECM) mainly composed by fibronectin and collagens, with the loss of tissue anisotropy and tissue stiffening. Reversing cardiac fibrosis represents a key challenge in cardiac regenerative medicine. Reliable models of human cardiac fibrotic tissue could be useful for preclinical testing of new advanced therapies, addressing the limited predictivity of traditional 2D cell cultures and animal models.

Thiol-Ene Photo-Click Hydrogels with Tunable Mechanical Properties Resulting from the Exposure of Different -Ene Moieties through a Green Chemistry.

Temperature and light responsiveness are widely exploited stimuli to tune the physico-chemical properties of double network hydrogels. In this work, new amphiphilic poly(ether urethane)s bearing photo-sensitive moieties (i.e.

Biomaterials-Enhanced Intranasal Delivery of Drugs as a Direct Route for Brain Targeting.

Intranasal (IN) drug delivery is a non-invasive and effective route for the administration of drugs to the brain at pharmacologically relevant concentrations, bypassing the blood-brain barrier (BBB) and minimizing adverse side effects. IN drug delivery can be particularly promising for the treatment of neurodegenerative diseases. The drug delivery mechanism involves the initial drug penetration through the nasal epithelial barrier, followed by drug diffusion in the perivascular or perineural spaces along the olfactory or trigeminal nerves, and final extracellular diffusion throughout the brain.

Design of Injectable Bioartificial Hydrogels by Green Chemistry for Mini-Invasive Applications in the Biomedical or Aesthetic Medicine Fields.

Bioartificial hydrogels are hydrophilic systems extensively studied for regenerative medicine due to the synergic combination of features of synthetic and natural polymers. Injectability is another crucial property for hydrogel mini-invasive administration. This work aimed at engineering injectable bioartificial in situ cross-linkable hydrogels by implementing green and eco-friendly approaches.

Biomimetic design of bioartificial scaffolds for the modelling of human cardiac fibrosis.

models of pathological cardiac tissue have attracted interest as predictive platforms for preclinical validation of therapies. However, models reproducing specific pathological features, such as cardiac fibrosis size (i.e.

Tissue-Engineered Models of the Human Brain: State-of-the-Art Analysis and Challenges.

Neurological disorders affect billions of people across the world, making the discovery of effective treatments an important challenge. The evaluation of drug efficacy is further complicated because of the lack of in vitro models able to reproduce the complexity of the human brain structure and functions. Some limitations of 2D preclinical models of the human brain have been overcome by the use of 3D cultures such as cell spheroids, organoids and organs-on-chip.

Development of an Innovative Soft Piezoresistive Biomaterial Based on the Interconnection of Elastomeric PDMS Networks and Electrically-Conductive PEDOT:PSS Sponges.

A deeply interconnected flexible transducer of polydimethylsiloxane (PDMS) and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) was obtained as a material for the application of soft robotics. Firstly, transducers were developed by crosslinking PEDOT:PSS with 3-glycidyloxypropryl-trimethoxysilane (GPTMS) (1, 2 and 3% /) and using freeze-drying to obtain porous sponges. The PEDOT:PSS sponges were morphologically characterized, showing porosities mainly between 200 and 600 µm; such surface area dimensions tend to decrease with increasing degrees of crosslinking.

Direct Reprogramming of Adult Human Cardiac Fibroblasts into Induced Cardiomyocytes Using miRcombo.

Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) through microRNAs (miRNAs) is a new emerging strategy for myocardial regeneration after ischemic heart disease. Previous studies have reported that murine fibroblasts can be directly reprogrammed into iCMs by transient transfection with four miRNAs (miRs-1, 133, 208 and 499 - termed "miRcombo"). While advancement in the knowledge of direct cell reprogramming molecular mechanism is in progress, it is important to investigate if this strategy may be translated to humans.

Lipoplexes for effective in vitro delivery of microRNAs to adult human cardiac fibroblasts for perspective direct cardiac cell reprogramming.

Design of nanocarriers for efficient miRNA delivery can significantly improve miRNA-based therapies. Lipoplexes based on helper lipid, dioleoyl phosphatidylethanolamine (DOPE) and cationic lipid [2-(2,3-didodecyloxypropyl)-hydroxyethyl] ammonium bromide (DE) were formulated to efficiently deliver miR-1 or a combination of four microRNAs (miRcombo) to adult human cardiac fibroblasts (AHCFs). Lipoplexes with amino-to-phosphate groups ratio of 3 (N/P 3) showed nanometric hydrodynamic size (372 nm), positive Z-potential (40 mV) and high stability under storage conditions.

Electroconductive Photo-Curable PEGDA-Gelatin/PEDOT:PSS Hydrogels for Prospective Cardiac Tissue Engineering Application.

Electroconductive hydrogels (ECHs) have attracted interest for tissue engineering applications due to their ability to promote the regeneration of electroactive tissues. Hence, ECHs with tunable electrical and mechanical properties, bioactivity, biocompatibility and biodegradability are demanded. In this work, ECHs based on photo-crosslinked blends of polyethylene glycol diacrylate (PEGDA) and gelatin with different PEGDA:gelatin ratios (1:1, 1.

Cardiac Tissue-like 3D Microenvironment Enhances Route towards Human Fibroblast Direct Reprogramming into Induced Cardiomyocytes by microRNAs.

The restoration of cardiac functionality after myocardial infarction represents a major clinical challenge. Recently, we found that transient transfection with microRNA combination (miRcombo: miR-1, miR-133, miR-208 and 499) is able to trigger direct reprogramming of adult human cardiac fibroblasts (AHCFs) into induced cardiomyocytes (iCMs) in vitro. However, achieving efficient direct reprogramming still remains a challenge.

Forming Hyperbranched PEG-Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties.

The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds.

Bioengineering Methods in MicroRNA-Mediated Direct Reprogramming of Fibroblasts Into Cardiomyocytes.

Ischemic heart disease is the major cause of mortality worldwide. Despite the most recent pharmacological progresses, cardiac regeneration is yet not possible, and heart transplantation is the only therapeutic option for end-stage heart failure. Traditional cardiac regenerative medicine approaches, such as cell therapies and tissue engineering, have failed in the obtainment of human functional cardiac tissue, mainly due to unavailability of high quantities of autologous functional cardiomyocytes (CMs), low grafting efficiency, and/or arrhythmic events.

Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds.

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds. In this work, a thermo- and pH-responsive hydrogel (P-CHP407) was prepared from an synthesized amphiphilic poly(ether urethane) (CHP407) exposing a significant amount of -COOH groups (8.8 ± 0.

Mussel-inspired antimicrobial coating on PTFE barrier membranes for guided tissue regeneration.

Guided tissue regeneration procedures to treat periodontitis lesions making use of polytetrafluoroethylene (PTFE) membranes exhibit large variability in their surgical outcomes, due to bacterial infection following implantation. This work reports on a facile method to obtain antimicrobial coatings for such PTFE membranes, by exploiting a mussel-inspired approach andformation of silver nanoparticles (AgNPs). PTFE films were initially coated with self-polymerized 3,4-dihydroxy-DL-phenylalanine (DOPA) (PTFE-DOPA), then incubated with AgNOsolution.