Articular cartilage regeneration with a microgel as a support biomaterial. A rabbit knee model.

Articular cartilage has limited regenerative capacity, so focal lesions generate mechanical stress in the joint that induces an aggravation of the damage, which ultimately leads to osteoarthritis. We recently suggested the use of microgels at the site of the cartilage defect, as a support material, to generate a biomechanical environment where pluripotent cells differentiate towards the hyaline cartilage phenotype. Here we propose a chondral regeneration strategy based on subchondral bone injury, and filling the defect site with an agglomerate of two types of microspheres, some rigid made of a biodegradable polyester (40 μm mean diameter), and others with a gel consistency made of platelet-rich plasma obtained from circulating blood (70-110 μm diameter).

Mesenchymal Stem Cells Cultured in a 3D Microgel Environment Containing Platelet-Rich Plasma Significantly Modify Their Chondrogenesis-Related miRNA Expression.

The aim of this work is to study the effect of platelet factors on the differentiation of mesenchymal stem cells (MSCs) to hyaline cartilage chondrocytes in a three-dimensional environment. MSCs were cultured in a microgel environment with a chondrogenic medium. The microgel consisted of microspheres that combine gelatin and platelet-rich plasma (PRP).

Viscoelastic Properties of Acellular Matrices of Porcine Esophageal Mucosa and Comparison with Acellular Matrices of Porcine Small Intestine Submucosa and Bovine Pericardium.

The aim of this study was to compare the viscoelastic properties of a decellularized mesh from the porcine esophagus, prepared by our group, with two commercial acellular tissues derived from porcine small intestine submucosa and bovine pericardium for use in medical devices. The tissues' viscoelastic properties were characterized by creep tests in tension, applying the load in the direction of the fibers or the transverse direction, and also by dynamic-shear mechanical tests between parallel plates or in tension at frequencies between 0.1 and 35 Hz.

Primary human hepatocytes-laden scaffolds for the treatment of acute liver failure.

Cell-based liver therapies based on retrieving and steadying failed metabolic function(s) for acute and chronic diseases could be a valuable substitute for liver transplants, even though they are limited by the low engraftment capability and reduced functional quality of primary human hepatocytes (PHH). In this paper we propose the use of gelatin-hyaluronic acid (Gel-HA) scaffolds seeded with PHH for the treatment of liver failure. We first optimized the composition using Gel-HA hydrogels, looking for the mechanical properties closer to the human liver and determining HepG2 cells functionality.

Influence of the Inclusion of Propylene Carbonate Electrolyte Solvent on the Microstructure and Thermal and Mechanical Stability of Poly(l-lactic acid) and Poly(vinylidene fluoride--hexafluoropropylene) Battery Separator Membranes.

The influence of the inclusion of the organic solvent propylene carbonate (PC) in microporous membranes based on poly(l-lactic acid) (PLLA) and poly(vinylidene fluoride--hexafluoropropylene) P(VDF-HFP) has been studied based on its relevance for the application of those separator membranes in lithium-ion batteries. The membranes have been produced through solvent casting and characterized with respect to the swelling ratio originated by the uptake of the organic solvent. The organic solvent uptake affects the porous microstructure and crystalline phase of both membrane types.

Microfluidic Processing of Piezoelectric and Magnetic Responsive Electroactive Microspheres.

Poly(vinylidene fluoride) (PVDF) combined with cobalt ferrite (CFO) particles is one of the most common and effective polymeric magnetoelectric composites. Processing PVDF into its electroactive phase is a mandatory condition for featuring electroactive behavior and specific (post)processing may be needed to achieve this state, although electroactive phase crystallization is favored at processing temperatures below 60 °C. Different techniques are used to process PVDF-CFO nanocomposite structures into microspheres with high CFO dispersion, with microfluidics adding the advantages of high reproducibility, size tunability, and time and resource efficiency.

Covalently Grafted Peptides to Decellularized Pericardium: Modulation of Surface Density.

The covalent functionalization of synthetic peptides allows the modification of different biomaterials (metallic, polymeric, and ceramic), which are enriched with biologically active sequences to guide cell behavior. Recently, this strategy has also been applied to decellularized biological matrices. In this study, the covalent anchorage of a synthetic peptide (REDV) to a pericardial matrix decellularized via Schiff base is realized starting from concentrated peptide solutions (10 M and 10 M).

Protein-Functionalized Microgel for Multiple Myeloma Cells' 3D Culture.

Multiple myeloma is a hematologic neoplasm caused by an uncontrolled clonal proliferation of neoplastic plasma cells (nPCs) in the bone marrow. The development and survival of this disease is tightly related to the bone marrow environment. Proliferation and viability of nPCs depend on their interaction with the stromal cells and the extracellular matrix components, which also influences the appearance of drug resistance.

Stability of Biomimetically Functionalised Alginate Microspheres as 3D Support in Cell Cultures.

Alginate hydrogels can be used to develop a three-dimensional environment in which various cell types can be grown. Cross-linking the alginate chains using reversible ionic bonds opens up great possibilities for the encapsulation and subsequent release of cells or drugs. However, alginate also has a drawback in that its structure is not very stable in a culture medium with cellular activity.

Magnetically Activated Piezoelectric 3D Platform Based on Poly(Vinylidene) Fluoride Microspheres for Osteogenic Differentiation of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) osteogenic commitment before injection enhances bone regeneration therapy results. Piezoelectric stimulation may be an effective cue to promote MSCs pre-differentiation, and poly(vinylidene) fluoride (PVDF) cell culture supports, when combined with CoFeO (CFO), offer a wireless in vitro stimulation strategy. Under an external magnetic field, CFO shift and magnetostriction deform the polymer matrix varying the polymer surface charge due to the piezoelectric effect.

Novel microgel culture system as semi-solid three-dimensional in vitro model for the study of multiple myeloma proliferation and drug resistance.

Multiple myeloma (MM) is a hematological malignancy in which the patient's drug resistance is one of the main clinical problems. As 2D cultures do not recapitulate the cellular microenvironment, which has a key role in drug resistance, there is an urgent need for better biomimetic models. Here, a novel 3D platform is used to model MM.

Adipose tissue derived stromal cells in a gelatin-based 3D matrix with exclusive ascorbic acid signalling emerged as a novel neural tissue engineering construct: an innovative prototype for soft tissue.

The current study investigated a triad, which comprises of adipose tissue derived stem cells isolated from infrapatellar fat pad and gelatin/polyvinyl alcohol (PVA)-based matrix with exclusive ascorbic acid signalling. Though, the bio-mechanical properties of the gelatin-PVA blended scaffolds in wet condition are equivalent to the ECM of soft tissues in general, in this study, the triad was tested as a model for neural tissue engineering. Apart from being cytocompatible and biocompatible, the porosity of the scaffold has been designed in such a manner that it facilitates the cell signalling and enables the exchange of nutrients and gases.

Biomimetic 3D Environment Based on Microgels as a Model for the Generation of Drug Resistance in Multiple Myeloma.

The development of three-dimensional environments to mimic the in vivo cellular response is a problem in the building of disease models. This study aimed to synthesize and validate three-dimensional support for culturing monoclonal plasma cells (mPCs) as a disease model for multiple myeloma. The three-dimensional environment is a biomimetic microgel formed by alginate microspheres and produced on a microfluidic device whose surface has been functionalized by a layer-by-layer process with components of the bone marrow's extracellular matrix, which will interact with mPC.

Covalent functionalization of decellularized tissues accelerates endothelialization.

In the field of tissue regeneration, the lack of a stable endothelial lining may affect the hemocompatibility of both synthetic and biological replacements. These drawbacks might be prevented by specific biomaterial functionalization to induce selective endothelial cell (EC) adhesion. Decellularized bovine pericardia and porcine aortas were selectively functionalized with a REDV tetrapeptide at 10 M and 10 M working concentrations.

Non-Markovian Methods in Glass Transition.

A model for the heterogeneity of local dynamics in polymer and other glass-forming materials is provided here. The fundamental characteristics of the glass transition phenomenology emerge when simulating a condensed matter open cluster that has a strong interaction with its heterogeneous environment. General glass transition features, such as non-exponential structural relaxations, the slowing down of relaxation times with temperature and specific off-equilibrium glassy dynamics can be reproduced by non-Markovian dynamics simulations with the minimum computer resources.

Design and characterization of microspheres for a 3D mesenchymal stem cell culture.

Recent studies have shown the relevance of growing mesenchymal stem cells (MSCs) in three-dimensional environments with respect to the monolayer cell culture on an adherent substrate. In this sense, macroporous scaffolds and hydrogels have been used as three-dimensional (3D) supports. In this work, we explored the culture of MSCs in a 3D environment created by microspheres, prepared with a fumarate-vinyl acetate copolymer and chitosan.

In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

In hematological malignancies, leukemias or myelomas, malignant cells present bone marrow (BM) homing, in which the niche contributes to tumor development and drug resistance. BM architecture, cellular and molecular composition and interactions define differential microenvironments that govern cell fate under physiological and pathological conditions and serve as a reference for the native biological landscape to be replicated in engineered platforms attempting to reproduce blood cancer behavior. This review summarizes the different models used to efficiently reproduce certain aspects of BM in vitro; however, they still lack the complexity of this tissue, which is relevant for fundamental aspects such as drug resistance development in multiple myeloma.

Effect of electrical stimulation on chondrogenic differentiation of mesenchymal stem cells cultured in hyaluronic acid - Gelatin injectable hydrogels.

Electrical stimulation (ES) has provided enhanced chondrogenesis of mesenchymal stem cells (MSCs) cultured in micro-mass without the addition of exogenous growth factors. In this study, we demonstrate for the first time that ES of MSCs encapsulated in an injectable hyaluronic acid (HA) - gelatin (GEL) mixture enhances the chondrogenic potential of the hydrogel. Samples were stimulated for 21 days with 10 mV/cm at 60 kHz, applied for 30 min every 6 h a day.

A new waterborne chitosan-based polyurethane hydrogel as a vehicle to transplant bone marrow mesenchymal cells improved wound healing of ulcers in a diabetic rat model.

Foot ulcers, a common complication of diabetes, can cause physical incapacity and are derived from several factors, including poor wound healing. New therapeutic strategies are needed to minimize this complication for the sake of patients' health. We therefore developed a new chitosan- polyurethane hydrogel membrane (HPUC) and the test results confirmed that HPUC present low cytotoxicity and improved wound healing when used with mononuclear bone marrow fraction cells in the diabetic rat model.

An innovative bioresorbable gelatin based 3D scaffold that maintains the stemness of adipose tissue derived stem cells and the plasticity of differentiated neurons.

Neural tissue engineering aims at producing a simulated environment using a matrix that is suitable to grow specialized neurons/glial cells pertaining to CNS/PNS which replace damaged or lost tissues. The primary goal of this study is to design a compatible scaffold that supports the development of neural-lineage cells which aids in neural regeneration. The fabricated, freeze-dried scaffolds consisted of biocompatible, natural and synthetic polymers: gelatin and polyvinyl pyrrolidone.

Biomimetic microspheres for 3D mesenchymal stem cell culture and characterization.

Stem cells reside in niches, specialized microenvironments that sustain and regulate their fate. Extracellular matrix (ECM), paracrine factors or other cells are key niche regulating elements. As the conventional 2D cell culture lacks these elements, it can alter the properties of naïve stem cells.

Maintenance of chondrocyte phenotype during expansion on PLLA microtopographies.

Articular chondrocytes are difficult to grow, as they lose their characteristic phenotype following expansion on standard tissue culture plates. Here, we show that culturing them on surfaces of poly(L-lactic acid) of well-defined microtopography allows expansion and maintenance of characteristic chondrogenic markers. We investigated the dynamics of human chondrocyte dedifferentiation on the different poly(L-lactic acid) microtopographies by the expression of collagen type I, collagen type II and aggrecan at different culture times.

Electrospun PVA/Bentonite Nanocomposites Mats for Drug Delivery.

Electrospun mats and films of polyvinyl alcohol (PVA) hydrogel are produced for drug delivery. To provide mechanical consistency to the gel a reinforcement by nanoclays is introduced in the polymer matrix. Four different suspensions of nanoparticles in the polymer solution are prepared in an adequate solvent.