Staff member

Oscar Castaño Linares

Senior Researcher
Biomaterials for Regenerative Therapies
+34 934 020 211
Staff member publications

Sachot, N., Roguska, A., Planell, J. P., Lewandowska, M., Engel, E., Castaño, O., (2017). Fast-degrading PLA/ORMOGLASS fibrous composite scaffold leads to a calcium-rich angiogenic environment International Journal of Nanomedicine 12, 4901-4919

The success of scaffold implantation in acellular tissue engineering approaches relies on the ability of the material to interact properly with the biological environment. This behavior mainly depends on the design of the graft surface and, more precisely, on its capacity to biodegrade in a well-defined manner (nature of ions released, surface-to-volume ratio, dissolution profile of this release, rate of material resorption, and preservation of mechanical properties). The assessment of the biological behavior of temporary templates is therefore very important in tissue engineering, especially for composites, which usually exhibit complicated degradation behavior. Here, blended polylactic acid (PLA) calcium phosphate ORMOGLASS (organically modified glass) nanofibrous mats have been incubated up to 4 weeks in physiological simulated conditions, and their morphological, topographical, and chemical changes have been investigated. The results showed that a significant loss of inorganic phase occurred at the beginning of the immersion and the ORMOGLASS maintained a stable composition afterward throughout the degradation period. As a whole, the nanostructured scaffolds underwent fast and heterogeneous degradation. This study reveals that an angiogenic calcium-rich environment can be achieved through fast-degrading ORMOGLASS/PLA blended fibers, which seems to be an excellent alternative for guided bone regeneration.

Keywords: Angiogenesis, Calcium release, Electrospinning, Fast degradation, Nanofibers, ORMOGLASSES

Echalier, C., Levato, R., Mateos-Timoneda, M. A., Castaño, O., Déjean, S., Garric, X., Pinese, C., Noël, D., Engel, E., Martinez, J., Mehdi, A., Subra, G., (2017). Modular bioink for 3D printing of biocompatible hydrogels: sol-gel polymerization of hybrid peptides and polymers RSC Advances 7, (20), 12231-12235

An unprecedented generic system allowing the 3D printing of peptide-functionalized hydrogels by soft sol-gel inorganic polymerization is presented. Hybrid silylated inorganic/bioorganic blocks are mixed in biological buffer in an appropriate ratio, to yield a multicomponent bioink that can be printed as a hydrogel without using any photochemical or organic reagent. Hydrolysis and condensation of the silylated precursors occur during the printing process and result in a covalent network in which molecules are linked through siloxane bonds. The viscosity of the colloidal solution used as bioink was monitored in order to set up the optimal conditions for extrusion printing. Grid-patterned hydrogel scaffolds containing a hybrid integrin ligand were printed using a pressure-driven rapid prototyping machine. Finally, they were seeded with mesenchymal stem cells, demonstrating their suitability for cell culture. The versatility of the sol-gel process and its biocompatibility makes this approach highly promising for the preparation of tailor-made cell-laden scaffolds.

Castaño, O., Pérez, S., Mateos-Timoneda, M. A., Engel, E., (2017). Cell Interactions with Calcium Phosphate Glasses RSC Smart Materials (ed. Boccaccini, Aldo R., Brauer, Delia S., Hupa, L.), Royal Society of Chemistry (London, UK) Bioactive Glasses: Fundamentals, Technology and Applications, 303-315

This chapter will review the interactions between calcium phosphate (CaP) glasses and different cell types. These glasses are less established in the biomaterials field than silicate-based glasses, but phosphate glasses generate interest owing to their higher solubility. CaP glasses have been less studied than silicate-based glasses, possibly due to the commercialization of Hench's Bioglass that allowed many laboratory groups to use them for different studies, including cell culture studies, without having to prepare them in-house. Studies on CaP glasses focused on compositional modification in order to elicit different properties to enhance biodegradability and bioactivity, two main properties for the application of these glasses. These properties have opened the application of these glasses and have enhanced the effect on cells allowing exploration of the bioactivity of ions released by these exceptionally interesting biomaterials.

Sachot, N., Castaño, O., Oliveira, H., Martí-Muñoz, J., Roguska, A., Amedee, J., Lewandowska, M., Planell, J. A., Engel, E., (2016). A novel hybrid nanofibrous strategy to target progenitor cells for cost-effective: In situ angiogenesis Journal of Materials Chemistry B 4, (43), 6967-6978

Although the impact of composites based on Ti-doped calcium phosphate glasses is low compared with that of bioglass, they have been already shown to possess great potential for bone tissue engineering. Composites made of polylactic acid (PLA) and a microparticle glass of 5TiO2-44.5CaO-44.5P2O5-6Na2O (G5) molar ratio have already demonstrated in situ osteo- and angiogenesis-triggering abilities. As many of the hybrid materials currently developed usually promote osteogenesis but still lack the ability to induce vascularization, a G5/PLA combination is a cost-effective option for obtaining new instructive scaffolds. In this study, nanostructured PLA-ORMOGLASS (organically modified glass) fibers were produced by electrospinning, in order to fabricate extra-cellular matrix (ECM)-like substrates that simultaneously promote bone formation and vascularization. Physical-chemical and surface characterization and tensile tests demonstrated that the obtained scaffolds exhibited homogeneous morphology, higher hydrophilicity and enhanced mechanical properties than pure PLA. In vitro assays with rat mesenchymal stem cells (rMSCs) and rat endothelial progenitor cells (rEPCs) also showed that rMSCs attached and proliferated on the materials influenced by the calcium content in the environment. In vivo assays showed that hybrid composite PLA-ORMOGLASS fibers were able to promote the formation of blood vessels. Thus, these novel fibers are a valid option for the design of functional materials for tissue engineering applications.

Sachot, N., Mateos-Timoneda, M. A., Planell, J. A., Velders, A. H., Lewandowska, M., Engel, E., Castaño, O., (2015). Towards 4th generation biomaterials: A covalent hybrid polymer-ormoglass architecture Nanoscale 7, (37), 15349-15361

Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials.

Won, J. E., Mateos-Timoneda, M. A., Castaño, O., Planell, J. A., Seo, S. J., Lee, E. J., Han, C. M., Kim, H. W., (2015). Fibronectin immobilization on to robotic-dispensed nanobioactive glass/polycaprolactone scaffolds for bone tissue engineering Biotechnology Letters 37, (4), 935-342

Bioactive nanocomposite scaffolds with cell-adhesive surface have excellent bone regeneration capacities. Fibronectin (FN)-immobilized nanobioactive glass (nBG)/polycaprolactone (PCL) (FN-nBG/PCL) scaffolds with an open pore architecture were generated by a robotic-dispensing technique. The surface immobilization level of FN was significantly higher on the nBG/PCL scaffolds than on the PCL scaffolds, mainly due to the incorporated nBG that provided hydrophilic chemical-linking sites. FN-nBG/PCL scaffolds significantly improved cell responses, including initial anchorage and subsequent cell proliferation. Although further in-depth studies on cell differentiation and the in vivo animal responses are required, bioactive nanocomposite scaffolds with cell-favoring surface are considered to provide promising three-dimensional substrate for bone regeneration.

Keywords: Bone scaffolds, Cell response, Fibronectin, Nanobioactive glass, Nanocomposites, Polycaprolactone, Bone, Cell proliferation, Cells, Cytology, Glass, Nanocomposites, Polycaprolactone, Robotics, Bone scaffolds, Bone tissue engineering, Cell response, Fibronectin, Fibronectin immobilizations, Nano bioactive glass, Nanocomposite scaffolds, Three-dimensional substrates, Scaffolds (biology)

Engel, E., Planell, J. A., Castaño, O., Navarro, M., (2014). Glass nanoparticles Universitat Politècnica de Catalunya; Fundació Institut de Bioenginyeria de Catalunya , (PCT/IB2014/000522)

Álvarez, Z., Castaño, O., Castells, A. A., Mateos-Timoneda, M. A., Planell, J. A., Engel, E., Alcántara, S., (2014). Neurogenesis and vascularization of the damaged brain using a lactate-releasing biomimetic scaffold Biomaterials 35, (17), 4769-4781

Regenerative medicine strategies to promote recovery following traumatic brain injuries are currently focused on the use of biomaterials as delivery systems for cells or bioactive molecules. This study shows that cell-free biomimetic scaffolds consisting of radially aligned electrospun poly-l/dl lactic acid (PLA70/30) nanofibers release l-lactate and reproduce the 3D organization and supportive function of radial glia embryonic neural stem cells. The topology of PLA nanofibers supports neuronal migration while l-lactate released during PLA degradation acts as an alternative fuel for neurons and is required for progenitor maintenance. Radial scaffolds implanted into cavities made in the postnatal mouse brain fostered complete implant vascularization, sustained neurogenesis, and allowed the long-term survival and integration of the newly generated neurons. Our results suggest that the endogenous central nervous system is capable of regeneration through the invivo dedifferentiation induced by biophysical and metabolic cues, with no need for exogenous cells, growth factors, or genetic manipulation.

Keywords: Lactate, Nanofibers, Neural stem cells, Neurogenesis, Regeneration, Vascularization

Castaño, O., Sachot, N., Xuriguera, E., Engel, E., Planell, J. A., Park, J. H., Jin, G. Z., Kim, T. H., Kim, J. H., Kim, H. W., (2014). Angiogenesis in bone regeneration: Tailored calcium release in hybrid fibrous scaffolds ACS Applied Materials and Interfaces 6, (10), 7512-7522

In bone regeneration, silicon-based calcium phosphate glasses (Bioglasses) have been widely used since the 1970s. However, they dissolve very slowly because of their high amount of Si (SiO2 > 45%). Recently, our group has found that calcium ions released by the degradation of glasses in which the job of silicon is done by just 5% of TiO2 are effective angiogenic promoters, because of their stimulation of a cell-membrane calcium sensing receptor (CaSR). Based on this, other focused tests on angiogenesis have found that Bioglasses also have the potential to be angiogenic promoters even with high contents of silicon (80%); however, their slow degradation is still a problem, as the levels of silicon cannot be decreased any lower than 45%. In this work, we propose a new generation of hybrid organically modified glasses, ormoglasses, that enable the levels of silicon to be reduced, therefore speeding up the degradation process. Using electrospinning as a faithful way to mimic the extracellular matrix (ECM), we successfully produced hybrid fibrous mats with three different contents of Si (40, 52, and 70%), and thus three different calcium ion release rates, using an ormoglass–polycaprolactone blend approach. These mats offered a good platform to evaluate different calcium release rates as osteogenic promoters in an in vivo subcutaneous environment. Complementary data were collected to complement Ca2+ release analysis, such as stiffness evaluation by AFM,

Keywords: Biological materials, Blood vessels, Calcium, Electrospinning, Glass, Hybrid materials, Silicon oxides, Sol-gel process, Sol-gels, Angiogenesis, Biological characterization, Calcium phosphate glass, Calcium-sensing receptors, Degradation process, Extracellular matrices, Organic/inorganic hybrid materials, ormoglasses, Silicon

Rajzer, I., Menaszek, E., Kwiatkowski, R., Planell, J. A., Castaño, O., (2014). Electrospun gelatin/poly( Materials Science and Engineering: C 44, 183-190

In this study gelatin (Gel) modified with calcium phosphate nanoparticles (SG5) and polycaprolactone (PCL) were used to prepare a 3D bi-layer scaffold by collecting electrospun PCL and gelatin/SG5 fibers separately in the same collector. The objective of this study was to combine the desired properties of PCL and Gel/SG5 in the same scaffold in order to enhance mineralization, thus improving the ability of the scaffold to bond to the bone tissue. The scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and the wide angle X-ray diffraction (WAXD) measurements confirmed that SG5 nanoparticles were successfully incorporated into the fibrous gelatin matrix. The composite Gel/SG5/PCL scaffold exhibited more enhanced mechanical properties than individual Gel and Gel/SG5 scaffolds. The presence of SG5 nanoparticles accelerated the nucleation and growth of apatite crystals on the surface of the composite Gel/SG5/PCL scaffold in simulated body fluid (SBF). The osteoblast response in vitro to developed electrospun scaffolds (PCL and Gel/SG5/PCL) was investigated by using normal human primary NHOst cell lines. NHOst cell culture studies showed that higher alkaline phosphatase (ALP) activity and better mineralization were obtained in the case of composite materials than in pure PCL scaffolds. The mechanically strong PCL scaffold served as a skeleton, while the Gel/SG5 fibers facilitated cell spreading and mineralization of the scaffold.

Keywords: Bilayer fibrous scaffold, Ceramic nanoparticles, Electrospinning, Gelatin, Polycaprolactone, Biomechanics, Bone, Calcium phosphate, Cell culture, Electrospinning, Fourier transform infrared spectroscopy, Mechanical properties, Mineralogy, Nanoparticles, Phosphatases, Polycaprolactone, Scanning electron microscopy, X ray diffraction, Polycaprolactone, Alkaline phosphatase activity, Bone tissue engineering, Calcium phosphate nanoparticles, Ceramic nanoparticles, Fibrous scaffolds, Gelatin, Simulated body fluids, Wide-angle x-ray diffraction, Electrospuns, Scaffolds (biology), Electrospinning

Mateos-Timoneda, M. A., Castaño, O., Planell, J. A., Engel, E., (2014). Effect of structure, topography and chemistry on fibroblast adhesion and morphology Journal of Materials Science: Materials in Medicine 25, (7), 1781-1787

Surface biofunctionalisation of many biodegradable polymers is one of the used strategies to improve the biological activity of such materials. In this work, the introduction of collagen type I over the surface of a biodegradable polymer (poly lactic acid) processed in the forms of films and fibers leads to an enhancing of the cellular adhesion of human dermal fibroblast when compared to unmodified polymer and biomolecule-physisorbed polymer surface. The change of topography of the material does not affect the cellular adhesion but results in a higher proliferation of the fibroblast cultured over the fibers. Moreover, the difference of topography governs the cellular morphology, i.e. cells adopt a more stretched conformation where cultured over the films while a more elongated with lower area morphology are obtained for the cells grown over the fibers. This study is relevant for designing and modifying different biodegradable polymers for their use as scaffolds for different applications in the field of Tissue Engineering and Regenerative Medicine.

Sachot, N., Engel, E., Castaño, O., (2014). Hybrid organic-inorganic scaffolding biomaterials for regenerative therapies Current Organic Chemistry 18, (18), 2299-2314

The introduction of hybrid materials in regenerative medicine has solved some problems related to the mechanical and bioactive properties of biomaterials. Calcium phosphates and their derivatives have provided the basis for inorganic components, thanks to their good bioactivity, especially in bone regeneration. When mixed with biodegradable polymers, the result is a synergic association that mimics the composition of many tissues of the human body and, additionally, exhibits suitable mechanical properties. Together with the development of nanotechnology and new synthesis methods, hybrids offer a promising option for the development of a third or fourth generation of smart biomaterials and scaffolds to guide the regeneration of natural tissues, with an optimum efficiency/cost ratio. Their potential bioactivity, as well as other valuable features of hybrids, open promising new pathways for their use in bone regeneration and other tissue repair therapies. This review provides a comprehensive overview of the different hybrid organic-inorganic scaffolding biomaterials developed so far for regenerative therapies, especially in bone. It also looks at the potential for research into hybrid materials for other, softer tissues, which is still at an initial stage, but with very promising results.

Keywords: Biodegradable polymer, Hybrid materials, Nanoparticles, Ormoglass

Castaño, Oscar, Planell, Josep A., (2014). Cements Bio-Ceramics with Clinical Applications (ed. Vallet-Regí, M.), John Wiley & Sons, Ltd (Chichester, UK) , 193-247

Calcium phosphate cements (CPCs) were meant to produce hydroxyapatite (HA), which is the calcium phosphate that usually results when the cements are mixed with or immersed in aqueous media. The golden age of CPCs was in the late 1990s and the beginning of the 21st century, when they were presented as promising bone substitutes and drug delivery systems. The different reactions that take part in the cement self-setting process depend on many experimental factors – the composition of the cement, the stability of the different components, pH, liquid-to-powder ratio (LPR), and temperature, among others. CPCs have demonstrated fair efficiency for bone regeneration. Cements have gradually been embraced in the wider field of composites by hybridizing their compositions in order that they may adapt to the new trends.

Keywords: Calcium phosphate cements (CPCs), Cements, Hydroxyapatite (HA), Liquid-to-powder ratio (LPR)

Álvarez, Zaida, Mateos-Timoneda, Miguel A., Hyrossová, Petra, Castaño, Oscar, Planell, Josep A., Perales, José C., Engel, Elisabeth, Alcántara, Soledad, (2013). The effect of the composition of PLA films and lactate release on glial and neuronal maturation and the maintenance of the neuronal progenitor niche Biomaterials 34, (9), 2221-2233

To develop tissue engineering strategies useful for repairing damage in the central nervous system (CNS) it is essential to design scaffolds that emulate the NSC niche and its tight control of neural cell genesis, growth, and differentiation. In this study we tested two types of poly l/dl lactic acid (PLA95/5 and PLA70/30), a biodegradable material permissive for neural cell adhesion and growth, as materials for nerve regeneration. Both PLA were slightly hydrophobic and negatively charged but differed in crystallinity, stiffness and degradation rate. PLA95/5 films were highly crystalline, stiff (GPa), and did not degrade significantly in the one-month period analyzed in culture. In contrast, PLA70/30 films were more amorphous, softer (MPa) and degraded faster, releasing significant amounts of lactate into the culture medium. PLA70/30 performs better than PLA95/5 for primary cortical neural cell adhesion, proliferation and differentiation, maintaining the pools of neuronal and glial progenitor cells in vitro. l-lactate in the medium recapitulated PLA70/30's maintenance of neuronal restricted progenitors but did not sustain bipotential or glial restricted progenitors in the cultures, as occurred when neural cells were grown on PLA70/30. Our results suggest that PLA70/30 may mimic some of the physical and biochemical characteristics of the NSC niche. Its mechanical and surface properties may act synergistically in the modulation of bipotential and glial restricted progenitor phenotypes, while it is l-lactate, either added to the medium or released by the film that drives the maintenance of neuronal restricted progenitor cell phenotypes.

Keywords: Polylactic acid, Degradation, Neurons, Progenitors, Lactate, Glial cells, NSC niche

Sachot, N., Castaño, Oscar, Mateos-Timoneda, Miguel A., Engel, Elisabeth, Planell, Josep A., (2013). Hierarchically engineered fibrous scaffolds for bone regeneration Journal of The Royal Society Interface Journal of the Royal Society Interface , 10, (88), 20130684

Surface properties of biomaterials play a major role in the governing of cell functionalities. It is well known that mechanical, chemical and nanotopographic cues, for example, influence cell proliferation and differentiation. Here, we present a novel coating protocol to produce hierarchically engineered fibrous scaffolds with tailorable surface characteristics, which mimic bone extracellular matrix. Based on the sol–gel method and a succession of surface treatments, hollow electrospun polylactic acid fibres were coated with a silicon–calcium–phosphate bioactive organic–inorganic glass. Compared with pure polymeric fibres that showed a completely smooth surface, the coated fibres exhibited a nanostructured topography and greater roughness. They also showed improved hydrophilic properties and a Young's modulus sixfold higher than non-coated ones, while remaining fully flexible and easy to handle. Rat mesenchymal stem cells cultured on these fibres showed great cellular spreading and interactions with the material. This protocol can be transferred to other structures and glasses, allowing the fabrication of various materials with well-defined features. This novel approach represents therefore a valuable improvement in the production of artificial matrices able to direct stem cell fate through physical and chemical interactions.

Castaño, O., Eltohamy, M., Kim, H. W., (2012). Electrospinning technology in tissue regeneration Nanotechnology in Regenerative Medicine - Methods and Protocols (Methods in Molecular Biology) (ed. Navarro, M., Planell, J. A.), Springer (New York, USA) 811, 127-140

Electrospinning is one of the most versatile and effective tools to produce nanostructured fibers in the biomedical science fields. The nanofibrous structure with diameters from tens to hundreds of nanometers largely mimics the native extracellular matrix (ECM) of many tissues. Thus far, a range of compositions including polymers and ceramics and their composites/hybrids have been successfully applied for generating electrospun nanofibers. Different processing tools in electrospinning set-ups and assemblies are currently developed to tune the morphology and properties of nanofibers. Herein, we demonstrate the electrospinning process and the electrospun biomaterials for specific use in tissue regeneration with some examples, involving different material combinations and fiber morphologies.

Keywords: Ceramic, Composites, Electrospinning, Nanofi bers, Nanostructured fi bers, Polymer, Tissue regeneration

Frontera, C., García-Muñoz, J. L., Castaño, O., Ritter, C., Brunelli, M., (2010). Structural properties, magnetic and oxygen-vacancies order in Y(Ba 1-xSrx)Co2O5.5 layered cobaltites Journal of Physics: Conference Series International Conference on Magnetism (ICM 2009) , IOP Publishing (Karlsruhe, Germany) 200, (Section 1), 012039 (4)

We present a study of the family Y(Ba1-xSrx)Co 2O5.5 (x = 0, 1/8, 1/4, 1/3, 3/8, 1/2). The complex magnetic behavior characterizing the parent (x = 0) compound and other RBaCo2O5.5 compounds can still be guessed in M(T) curves of x = 1/8 compound, but it disappears under substitution of Ba by Sr for all the studies cases (x ≥ 1/8). This is linked to the fact that the order of oxygen vacancies is lost, as found by neutron and synchrotron X-ray powder diffraction.

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