José Luis Gomez Ribelles

• Polytechnic University of Valencia

Physical cues have been shown to be effective in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Here, we propose piezoelectric stimulation as a potential osteogenic cue mimicking the electroactive properties of bone’s extracellular matrix. When combined with a magnetostrictive component, piezoelectric polymers can be used for...

Adequate simulation mimicking a tissue’s native environment is one of the elemental premises in tissue engineering. Although various attempts have been made to induce human mesenchymal stem cells (hMSC) into an osteogenic pathway, they are still far from widespread clinical application. Most strategies focus primarily on providing a specific type o...

This study investigates the effect of electroactivity and electrical charge distribution on the biological response of human bone marrow stem cells (hBMSCs) cultured in monolayer on flat poly(vinylidene fluoride), PVDF, substrates. Differences in cell behaviour, including proliferation, expression of multipotency markers CD90, CD105 and CD73, and e...

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 (P...

In order to tailor dielectric response and electrical conductivity, novel polymer blends based on poly(vinylidene fluoride (PVDF) and different fillers composed by poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), and PEDOT:PSS/ionic liquids (ILs): PEDOT:PSS/ N-ethyl-N-methylpyrrolidinium bis(fluorosulfonyl)imide ([C2mpyr][FSI])...

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...

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-h...

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-co-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 produce...

Bone marrow mechanical conditions play a key role in multiple myeloma cancer. The complex mechanical and chemical conditions, as well as the interactions with other resident cells, hinder the development of effective treatments. Agent-based computational models, capable of defining the specific conditions for every single cell, can be a useful tool...

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 synth...

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 m...

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 CoFe2O4 (CFO), offer a wireless in vitro stimulation strategy. Under an...

In the present work the surface of Ti6Al4V alloy, widely used for the fabrication of implants, was modified by incorporating a novel biocompatible and antibacterial coating composed of multiple layers of hydroxyapatite (HA) and Ag deposited on a TiO2/TiN/Ti trilayer. During the characterization of the coatings, their chemical and phase compositions...

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...

Background and objective The mechanical signals received from the multiple myeloma microenvironment play a key role in bone marrow cancer development. However, the complexity of the cues received hinders the development of a novel and effective treatment. As such, agent-based computational models that consider coupled fluid and mechanical dynamics...

Ti alloys are widely used in the biomedical field because they have an adequate balance between mechanical properties, corrosion resistance and biocompatibility. However, when this material is incorporated in the human body, unfavorable reactions can be obtained which do not allow a good osseointegration due to the formation of a fibrous and non-ad...

In the present work the surface of Ti6Al4V alloy, widely used for the fabrication of implants, was modified by incorporating a novel biocompatible and antibacterial coating composed of multiple layers of hydroxyapatite (HA) and Ag deposited on a TiO2/TiN/Ti trilayer. During the characterization of the coatings, their chemical and phase compositions...

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 electroacti...

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 tissu...

Mesenchymal stem cells (MSCs) play a major role in bone tissue engineering (BTE) thanks to their capacity for osteogenic differentiation and being easily available. In vivo, MSCs are exposed to an electroactive microenvironment in the bone niche, which has piezoelectric properties. The correlation between the electrically active milieu and bone's a...

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. The semi-soli...

Glass transition processes have often been explained in terms of wide distributions of relaxation times. By means of a simple stochastic model we here show how dynamic heterogeneity is the key to the emergence of the glass transition. A non-Markovian model representing a small open region of the amorphous material was previously shown to reproduce...

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 microge...

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 selecti...

In order to advance towards more sustainable electronics generation, natural polymers with tailored dielectric response are essential. In this search, the combination of bio-based materials with active fillers in composite form, suppose one of the most viable alternatives. To achieve it, this work has explored the ability to control dielectric resp...

Bone’s inherent piezoelectricity is a key factor in regulating bone growth and mesenchymal stem cells (MSCs) fate towards the osteogenic lineage. The piezoelectric polymer poly(vinylidene) fluoride (PVDF) was thus used to manufacture electroactive membranes by means of non-solvent induced phase separation (NIPS), producing porous membranes with app...

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-e...

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 conditio...

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 environmen...

Biocompatible and antibacterial multi-layer coatings of hydroxyapatite (HA)-Ag/SiO2/TiN/Ti were obtained on the Ti-6Al-4V alloy, by means of the magnetron sputtering technique. During characterization of the coatings, the chemical composition was evaluated by energy dispersive X-ray spectroscopy and the phase analysis was carried out by X-ray diffr...

Polymer-ceramic composites based on poly(vinylidene fluoride) and ceramic particles of the inorganic piezoelectric material Pb(Zr0.53Ti0.47)O3 were prepared with different particle concentrations and size by solution casting in the non-polar (α−) and polar (β-) phases of the polymer. The influence of amount and particle size on the overall dielectr...

The use of piezoelectric materials in tissue engineering has grown considerably since inherent bone piezoelectricity was discovered. Combinations of piezoelectric polymers with magnetostrictive nanoparticles (MNP) can be used to magnetoelectrically stimulate cells by applying an external magnetic field which deforms the magnetostrictive nanoparticl...

The crystallization kinetics of poly(vinylidene fluoride), PVDF, in blends with the ionic liquid 1-ethyl-3-methylimidazolium chloride [Emim][Cl] has been studied as a function of [Emim][Cl] content up to 40 wt%. Blends were produced by solvent casting technique from diluted solutions and solvent evaporation at a temperature higher than the melting...

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...

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 conf...

Films based on poly (vinylidene fluoride) (PVDF) blended with ionic liquids (ILs) comprising different cations and anions were developed in order to investigate the IL influence on the resulting PVDF crystalline phase. Blends with 25 wt.% of IL content were produced by solvent-casting followed by solvent evaporation at 210 °C in an air oven. Five d...

The objective of this study was to test a regenerative medicine strategy for the regeneration of articular cartilage. This approach combines microfracture of the subchondral bone with the implant at the site of the cartilage defect of a supporting biomaterial in the form of microspheres aimed at creating an adequate biomechanical environment for th...

Esta comunicación resume parte de los resultados del proyecto Erasmus+ “CRİTİCAL THİNKİNG AS A STEP FORWARD İN VET EDUCATİON: VET students immersed in high technology teams” en el que han participado empresas de base tecnológica, centros superiores de investigación y centros de formación profesional europeos. Durante dos años se han diseñado estrat...

Poly(vinylidene fluoride) (PVDF) is a semicrystalline polymer with four crystalline phases, of which the all trans conformation (β-phase) is the one with the largest piezoelectric response and best electroactive properties. This smart material is able to reproduce physiological events such as inherent bone piezoelectricity, making it a perfect cand...

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 regenera...

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. In this work we designed a novel biomimetic microe...

Blends of poly(vinylidene fluoride) (PVDF) and ionic liquids (ILs) with different cations and anions have been prepared by solvent casting. The IL content was the same in all blends of the series. Molecular relaxation and ionic conductivity have been systematically studied by broadband dielectric relaxation spectroscopy (BDS) in wide frequency (0.1...

The increasing use of electronic portable systems and the consequent energy demand, leads to the need to improve energy storage systems. According to that and due to safety issues, high-performance non-flammable electrolytes and solid polymer electrolytes (SPE) are needed. SPE containing different amounts of lithium bis(trifluoromethanesulfonyl)imi...

Mesoporous silica nanoparticles (MSNs) are one of the most promising nanocarriers in biomedicine. Nonetheless, surface modification has been pointed out as a condition necessary for drug delivery applications, where stability and biocompatibility are extremely important for the vehicle performance. Likewise, zwitterionic polymers are outstanding ca...

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...

The heterogeneity of local dynamics in disordered systems is behind some key features of glass transition. In order to improve our understanding of the molecular dynamics in disordered systems in the vicinity of the glass transition, different parameters have been proposed to quantitatively describe dynamical heterogeneity. In the case of polymers,...

Dynamics of multilayer adsorption of macromolecules with different degree of polymerization is studied by coarse‐grained Monte Carlo simulations, focusing on both the interface macromolecule‐surface and chain–chain interaction in and out of equilibrium conditions. The interfacial interaction between the solid flat surface and the macromolecules is...

The glass transition dynamics and the charge transport for blends composed of poly(vinylidene fluoride) (PVDF) and the ionic liquid (IL) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide, [Emim][TFSI] have been investigated as a function of different IL content (0, 10, 25 and 40 % wt) by differential scanning calorimetry (DSC), dynamic...

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. These suspensions are subjected to an e...

Polymer blends based on poly(vinylidene fluoride) (PVDF) and poly(ethylene oxide) (PEO) have been prepared to analyze the crystallization kinetics of poly(ethylene oxide) confined in semicrystalline PVDF with different ratios of both polymers. Both blend components were dissolved in a common solvent, dimethyl formamide. Blend films were obtained by...

All variables affecting the morphology of mesoporous silica nanoparticles (MSN) should be carefully analyzed in order to truly tailored design their mesoporous structure according to their final use. Although complete control on MCM-41 synthesis has been already claimed, reproducibility and repeatability of results remain a big issue due to the lac...

The aim of this work was to determine the influence of the biomaterial environment on human mesenchymal stem cell (hMSC) fate when cultured in supports with varying topography. Poly(vinylidene fluoride) (PVDF) culture supports were prepared with structures ranging between 2D and 3D, based on PVDF films on which PVDF microspheres were deposited with...

Titanium and its alloys are widely used in medical implants because of their excellent properties. However, bacterial infection is a frequent cause of titanium-based implant failure and also compromises its osseointegration. In this study, we report a new simple method of providing titanium surfaces with antibacterial properties by alternating anti...

The aim of this study was to develop micro- or macro-porous substrates of poly(L-lactic acid) (PLLA) for the sustained release of water-soluble proteins. A model protein, bovine serum albumin (BSA), was incorporated into the hydrophobous PLLA matrix by emulsifying an aqueous BSA solution into an organic PLLA solution. The work focused on the effect...

TaN(Ag) composited coatings are being investigated to improve biocompatibility of different biomedical devices due to the mechanical and chemical stability of TaN and bactericidal effect of silver nanoparticles. However, controlling the size, density, shape and especially the release of silver ions (Ag) into the surrounding medium becomes a challen...

Highly swellable hydrogels were produced by crosslinking of high molecular weight carboxymethylated chitosan (CmCHT) with poly(ethylene glycol) (PEG) oligomers. The hydrogel swelling capacity could be controlled via the crosslinking density and ranged from 900 to 5600 %. The hydrogels showed good homogeneity with a high interconnected porosity in t...

Purpose: To study the influence of scaffold properties on the organization of in vivo cartilage regeneration. Our hypothesis was that stress transmission to the cells seeded inside the pores of the scaffold or surrounding it, which is highly dependent on the scaffold properties, determines the differentiation of both mesenchymal cells and dediffer...

The clinical management of large-size cartilage lesions is difficult due to the limited regenerative ability of the cartilage. Different biomaterials have been used to develop tissue engineering substitutes for cartilage repair, including chitosan alone or in combination with growth factors to improve its chondrogenic properties. The main objective...

Thermal degradation of chitosan with varying deacetylation degree (DD) ranging between 50 and 85% was analyzed by dynamic thermogravimetric analysis at different heating rates. The present study focused on the temperature range between 500 and 800 K, above water evaporation. Thermal degradation showed a main degradation stage in this temperature in...

Chitosan/PCL block-copolymer networks were synthesized using different amounts of aldehyde end-capped polycaprolactone as crosslinking agent. The crosslinking reaction was performed by dissolving both components in the common solvent hexafluoroisopropanol (HFIP). The formation of the network was confirmed by solubility tests in good solvents of bot...

Chondrogenesis of Mesenchymal stem cells (MSCs) is known to be regulated by a number of environmental factors, including local oxygen levels. The hypothesis of this study is that the response of MSCs to hypoxia is dependent on the physical and chemical characteristics of the substrate used. The objective of this study was to explore how different m...

In this work macroporous membrane for mesenchymal stem cells, MSCs, transplant has been developed. The membranes support cell seeding and proliferation and completely degrade in less than one week in “in vitro” culture. The biodegradable material is a polymer network based on carboxymethyl chitosan (a water soluble modification of chitosan) crossli...

Poly(ethyl acrylate) (PEA) induces the formation of biomimetic fibronectin (FN) (nano)networks upon simple adsorption from solutions, a process referred to as material-driven FN fibrillogenesis. The ability of PEA to organize FN has been demonstrated in 2D and 2.5D environments, but not as yet in 3D scaffolds, which incorporate three-dimensionality...

The polymer α relaxation process for net-PEA gels swollen with non-polar p-xylene is studied by employing Dielectric Relaxation Spectroscopy (DRS). The results present the in situ monitoring of the dielectric behavior of α relaxation process under p-xylene cold crystallization, isothermal crystallization as well as crystallization from quenching. F...

Novel Cellulose (Cel) reinforced polyvinyl alcohol (PVA)-Silica (Si) composite which has good stability and in vitro degradation was prepared by lyophilization technique and implanted using N 3+ ions of energy 24 keV in the fluences of 1×10 15 , 5×10 15 and 1×10 16 ions/cm 2 . SEM analysis revealed the formation of microstructures, and improved...

The aim of this study is to prove the feasibility of a system able to apply local mechanical loading on cells seeded in a hydrogel for tissue engineering applications. This experimental study is based on a previously developed artificial cartilage model with different concentrations of poly(vinyl alcohol) (PVA) that simulates the cartilage extracel...

Dental implantology is still an expanding field of scientific study because of the number of people that receive dental therapies throughout their lives worldwide. Recovery times associated to dental surgery are still long and demand strategies to improve integration of metallic devices with hard tissues. In this work, an in vitro ceramic coating i...

The aim of this study is to show that introducing a small fraction of hydrophilic groups into a hydrophobic polyester favor the macrophage activity by accelerating the degradation action in aqueous media. It is also seen that differentiation of MSCs cultured in monolayer towards bone in specific differentiation media is favored in these materials w...

Mechanical cues such as hydrostatic pressure (HP) are known to regulate mesenchymal stem cell (MSC) differentiation. The fate of such cells is also strongly influenced by their substrate. The objective of this study was to test how different modifications of polycaprolactone (PCL) scaffolds would influence the response of MSCs to HP. Porcine bone m...

In the sensors field, titanium based coatings are being used for the acquisition/application of electrical signals from/to piezoelectric materials. In this particular case, sensors are used to detect dynamic mechanical loads at early stages after intervention of problems associated with prostheses implantation. The aim of this work is to select an...

Statement of significance: It is well known the importance of biomechanical cues in chondrogenesis. This paper reviews the existing literature on the effect of mechanical stimulation on chondrogenic differentiation of mesenchymal stem cells in order to regenerate hyaline cartilage. Contradictory results found with respect to the effect of differen...

Purpose: Articular cartilage has limited repair capacity. Two different implant devices for articular cartilage regeneration were tested in vivo in a sheep model to evaluate the effect of subchondral bone anchoring for tissue repair. Methods: The implants were placed with press-fit technique in a cartilage defect after microfracture surgery in t...