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  • A bioactive elastin-like recombinamer reduces unspecific protein adsorption and enhances cell response on titanium surfaces.

     Salvagni, Emiliano; Berguig, Geoffrey Yehuda; Engel Lopez, Elisabet; Rodriguez Cabello, Jose Carlos; Coullerez, Geraldine; Textor, Marcus; Planell Estany, Josep Antón; Gil Mur, Francisco Javier; Aparicio, Conrado
    Colloids and Surfaces B. Biointerfaces
    Vol. 17, p. 225-233
    DOI: 10.1016/j.colsurfb.2013.10.008
    Date of publication: 2014-02-01
    Journal article

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    We present the immobilization on synthetic substrates of elastin-like recombinamers (ELR) that combine a bioactive motif for cell adhesion with protein antifouling properties. Physical adsorption of the recombinamers and covalent-grafting through organosilane chemistry were investigated. The biochemically-modified surfaces were thoroughly characterized and tested for protein absorption in serum by fluorescence-labelling, XPS, Ellipsometry, and OWLS. The ELR were successfully grafted and stable, even upon mechanical stresses; being the covalent bonding favourable over physical adsorption. The coated metal surfaces exhibited excellent reduction of serum protein adsorption (9 ng/cm2) compared to the bare metal surface (310 ng/cm2). Non-specific protein adsorption may mask the introduced bioactive motifs; therefore, the bioactivated surfaces should display serum-protein antifouling properties. Finally, improved hMSCs response was assessed on the bioactivated substrates. In summary, the coatings simultaneously displayed anti-fouling and bioactive properties. These studies investigated key factors to enhance tissue material interactions fundamental for the design of bioactive devices and future biomedical applications

    We present the immobilization on synthetic substrates of elastin-like recombinamers (ELR) that combine a bioactive motif for cell adhesion with protein antifouling properties. Physical adsorption of the recombinamers and covalent-grafting through organosilane chemistry were investigated. The biochemically-modified surfaces were thoroughly characterized and tested for protein absorption in serum by fluorescence-labelling, XPS, Ellipsometry, and OWLS. The ELR were successfully grafted and stable, even upon mechanical stresses; being the covalent bonding favourable over physical adsorption. The coated metal surfaces exhibited excellent reduction of serum protein adsorption (9 ng/cm2) compared to the bare metal surface (310 ng/cm2). Non-specific protein adsorption may mask the introduced bioactive motifs; therefore, the bioactivated surfaces should display serum-protein antifouling properties. Finally, improved hMSCs response was assessed on the bioactivated substrates. In summary, the coatings simultaneously displayed anti-fouling and bioactive properties. These studies investigated key factors to enhance tissue material interactions fundamental for the design of bioactive devices and future biomedical applications.

  • Bioactivation of calcium deficient hydroxyapatite with foamed gelatin gel. A new injectable self-setting bone analogue

     Dessi, Mariagemiliana; Alvarez Perez, Marco Antonio; De Santis, Roberto; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Ambrosio, Luigi
    Journal of materials science. Materials in medicine
    Vol. 25, num. 2, p. 283-295
    DOI: 10.1007/s10856-013-5071-6
    Date of publication: 2014-02
    Journal article

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    An alternative approach to bone repair for less invasive surgical techniques, involves the development of biomaterials directly injectable into the injury sites and able to replicate a spatially organized platform with features of bone tissue. Here, the preparation and characterization of an innovative injectable bone analogue made of calcium deficient hydroxyapatite and foamed gelatin is presented. The biopolymer features and the cement self-setting reaction were investigated by rheological analysis. The porous architecture, the evolution of surface morphology and the grains dimension were analyzed with electron microscopy (SEM/ESEM/TEM). The physico-chemical properties were characterized by X-ray diffraction and FTIR analysis. Moreover, an injection test was carried out to prove the positive effect of gelatin on the flow ensuing that cement is fully injectable. The cement mechanical properties are adequate to function as temporary substrate for bone tissue regeneration. Furthermore, MG63 cells and bone marrow-derived human mesenchymal stem cells (hMSCs) were able to migrate and proliferate inside the pores, and hMSCs differentiated to the osteoblastic phenotype. The results are paving the way for an injectable bone substitute with properties that mimic natural bone tissue allowing the successful use as bone filler for craniofacial and orthopedic reconstructions in regenerative medicine.

  • Effect of structure, topography and chemistry on fibroblast adhesion and morphology

     Mateos Timoneda, Miguel Angel; Castaño Linares, Oscar; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    Journal of materials science. Materials in medicine
    Vol. 25, num. 7, p. 1781-1787
    DOI: 10.1007/s10856-014-5199-z
    Date of publication: 2014-07
    Journal article

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    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.

  • Relevance of PEG in PLA-based blends for tissue engineering 3D-printed scaffolds

     Serra, Tiziano; Ortiz Hernandez, Monica; Engel Lopez, Elisabet; Planell Estany, Josep Antón; Navarro Toro, Melba Eugenia
    Materials science and engineering C. Biomimetic and supramolecular systems
    Vol. 38, p. 55-62
    DOI: 10.1016/j.msec.2014.01.003
    Date of publication: 2014-05-01
    Journal article

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    Achieving high quality 3D-printed structures requires establishing the right printing conditions. Finding processing conditions that satisfy both the fabrication process and the final required scaffold properties is crucial. This work stresses the importance of studying the outcome of the plasticizing effect of PEG on PLA-based blends used for the fabrication of 3D-direct-printed scaffolds for tissue engineering applications. For this, PLA/PEG blends with 5, 10 and 20% (w/w) of PEG and PLA/PEG/bioactive CaP glass composites were processed in the form of 3D rapid prototyping scaffolds. Surface analysis and differential scanning calorimetry revealed a rearrangement of polymer chains and a topography, wettability and elastic modulus increase of the studied surfaces as PEG was incorporated. Moreover, addition of 10 and 20% PEG led to non-uniform 3D structures with lower mechanical properties. In vitro degradation studies showed that the inclusion of PEG significantly accelerated the degradation rate of the material. Results indicated that the presence of PEG not only improves PLA processing but also leads to relevant surface, geometrical and structural changes including modulation of the degradation rate of PLA-based 3D printed scaffolds. (C) 2014 Elsevier B.V. All rights reserved.

  • Neurogenesis and vascularization of the damaged brain using a lactate-releasing biomimetic scaffold

     Álvarez Pinto, Zaída; Castaño Linares, Oscar; Castells, Alba; Mateos Timoneda, Miguel Angel; Planell Estany, Josep Antón; Engel Lopez, Elisabet; Alcantara, Soledad
    Biomaterials
    Vol. 35, num. 17, p. 4769-4781
    DOI: 10.1016/j.biomaterials.2014.02.051
    Date of publication: 2014-06-01
    Journal article

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    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 in vivo dedifferentiation induced by biophysical and metabolic cues, with no need for exogenous cells, growth factors, or genetic manipulation. (C) 2014 Elsevier Ltd. All rights reserved.

    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.

  • Angiogenesis in bone regeneration: tailored calcium release in hybrid fibrous scaffolds

     Castaño Linares, Oscar; Sachot, Nadège; Xuriguera Martin, Elena; Engel Lopez, Elisabet; Planell Estany, Josep Antón; Park, Jaegyun; Jin, Guang-Zhen; Kim, Tae-Hyun; Kim, Joong-Hyun; Kim, Hae-Won
    ACS applied materials and interfaces
    Vol. 6, num. 10, p. 7512-7522
    DOI: 10.1021/am500885v
    Date of publication: 2014-05-28
    Journal article

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    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, zeta-potential, morphology evaluation by FESEM, proliferation and differentiation analysis, as well as in vivo subcutaneous implantations. Material and biological characterization suggested that compositions of organic/inorganic hybrid materials with a Si content equivalent to 40%, which were also those that released more calcium, were osteogenic. They also showed a greater ability to form blood vessels. These results suggest that Si-based ormoglasses can be considered an efficient tool for calcium release modulation, which could play a key role in the angiogenic promoting process.

  • Extracellular calcium and CaSR drive osteoinduction in mesenchymal stromal cells

     Gonzalez Vazquez, Arlyng; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    Acta biomaterialia
    Vol. 10, num. 6, p. 2824-2833
    DOI: 10.1016/j.actbio.2014.02.004
    Date of publication: 2014-06-01
    Journal article

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    Bone is the main store of calcium and progenitor cells in the body. During the resorption process, the local calcium concentration reaches 8-40 mM, and the surrounding cells are exposed to these fluctuations in calcium. This stimulus is a signal that is detected through the calcium sensing receptor (CaSR), which modulates chemotactic and proliferative G protein-dependent signaling pathways. The objective of the present work is to evaluate the roles of extracellular calcium ([Ca2+](o)) and the CaSR in osteoinduction. Rat bone marrow mesenchymal stromal cells (rBMSCs) were stimulated with 10 mM of Ca2+. Several experiments were conducted to demonstrate the effect of [Ca2+](o) on chemotaxis, proliferation and differentiation on the osteoblastic lineage. It was found that [Ca2+](o) induces rBMSCs to migrate and proliferate in a concentration-dependent manner. Real-time polymerase chain reaction and immunofluorescence also revealed that 10 mM Ca2+ stimulates overexpression of osteogenic markers in rBMSCs, including alkaline phosphatase (ALP), bone sialoprotein, collagen Ia1 and osteocalcin. Functional assays determining ALP activity and mineralization tests both corroborate the increased expression of these markers in rBMSCs stimulated with Ca2+. Moreover, CaSR blockage inhibited the cellular response to stimulation with high concentrations of [Ca2+](o), revealing that the CaSR is a key modulator of these cellular responses. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • Role of porosity and pore architecture in the in vivo bone regeneration capacity of biodegradable glass scaffolds

     Sanzana, Edgardo; Navarro Toro, Melba Eugenia; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Ojeda, Alvaro; Montecinos, Hernan
    Journal of biomedical materials research. Part A
    Vol. 102, num. 6, p. 1767-1773
    DOI: 10.1002/jbm.a.34845
    Date of publication: 2014-06-01
    Journal article

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    The aim of this work is to shed light on the role of porosity and pore architecture in the in vivo bone regeneration capacity of biodegradable glass scaffolds. A calcium phosphate glass in the system P2O5-CaO-Na2O-TiO2 was foamed using two different porogens, namely albumen and hydrogen peroxide (H2O2); the resulting three-dimensional porous structures were characterized and implanted in New Zealand rabbits to study their in vivo behavior. Scaffolds foamed with albumen displayed a monomodal pore size distribution centered around 150 m and a porosity of 82%, whereas scaffolds foamed with H2O2 showed lower porosity (37%), with larger elongated pores, and multimodal size distribution. After 12 weeks of implantation, histology results revealed a good osteointegration for both types of scaffolds. The quantitative morphometric analysis showed the substitution of the biomaterial by new bone in the case of glasses foamed with albumen. In contrast, bone neoformation and material resorption were significantly lower in the defects filled with the scaffolds foamed with H2O2. The results obtained in this study showed that both calcium phosphate glass scaffolds were osteoconductive, biocompatible, and biodegradable materials. However, differences in porosity, pore architecture, and microstructure led to substantially different in vivo response. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1767-1773, 2014.

  • Enhanced cell-material interactions through the biofunctionalization of polymeric surfaces with engineered peptides

     Punet, Xavier; Mauchauffé, Rodolphe; Giannotti, Marina I.; Rodriguez Cabello, Jose Carlos; Sanz Carrasco, Fausto; Engel Lopez, Elisabet; Mateos Timoneda, Miguel Angel; Planell Estany, Josep Antón
    Biomacromolecules
    Vol. 14, num. 8, p. 2690-2702
    DOI: 10.1021/bm4005436
    Date of publication: 2013-08
    Journal article

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    Research on surface modification of polymeric materials to guide the cellular activity in biomaterials designed for tissue engineering applications has mostly focused on the use of natural extracellular matrix (ECM) proteins and short peptides, such as RGD. However, the use of engineered proteins can gather the advantages of these strategies and avoid the main drawbacks. In this study, recombinant engineered proteins called elastin-like recombinamers (ELRs) have been used to functionalize poly(lactic) acid (PLA) model surfaces. The structure of the ELRs has been designed to include the integrin ligand RGDS and the cross-linking module VPGKG. Surface functionalization has been characterized and optimized by means of ELISA and atomic force microscopy (AFM). The results suggest that ELR functionalization creates a nonfouling canvas able to restrict unspecific adsorption of proteins. Moreover, AFM analysis reveals the conformation and disposition of ELRs on the surface. Biological performance of PLA surfaces functionalized with ELRs has been studied and compared with the use of short peptides. Cell response has been assessed for different functionalization conditions in the presence and absence of the bovine serum albumin (BSA) protein, which could interfere with the surface-cell interaction by adsorbing on the interface. Studies have shown that ELRs are able to elicit higher rates of cell attachment, stronger cell anchorages and faster levels of proliferation than peptides. This work has demonstrated that the use of engineered proteins is a more efficient strategy to guide the cellular activity than the use of short peptides, because they not only allow for better cell attachment and proliferation, but also can provide more complex properties such as the creation of nonfouling surfaces.

    Research on surface modi fi cation of polymeric materials to guide the cellular activity in biomaterials designed for tissue engineering applications has mostly focused on the use of natural extracellular matrix (ECM) proteins and short peptides, such as RGD. However, the use of engineered proteins can gather the advantages of these strategies and avoid the main drawbacks. In this study, recombinant engineered proteins called elastin- like recombinamers (ELRs) have been used to functionalize poly(lactic) acid (PLA) model surfaces. The structure of the ELRs has been designed to include the integrin ligand RGDS and the cross-linking module VPGKG. Surface functionalization has been characterized and optimized by means of ELISA and atomic force microscopy (AFM). The results suggest that ELR functionalization creates a nonfouling canvas able to restrict unspeci fi c adsorption of proteins. Moreover, AFM analysis reveals the conformation and disposition of ELRs on the surface. Biological performance of PLA surfaces functionalized with ELRs has been studied and compared with the use of short peptides. Cell response has been assessed for di ff erent functionalization conditions in the presence and absence of the bovine serum albumin (BSA) protein, which could interfere with the surface − cell interaction by adsorbing on the interface. Studies have shown that ELRs are able to elicit higher rates of cell attachment, stronger cell anchorages and faster levels of proliferation than peptides. This work has demonstrated that the use of engineered proteins is a more e ffi cient strategy to guide the cellular activity than the use of short peptides, because they not only allow for better cell attachment and proliferation, but also can provide more complex properties such as the creation of nonfouling surfaces

  • High-resolution PLA-based composite scaffolds via 3-D printing technology

     Serra, Tiziano; Planell Estany, Josep Antón; Navarro Toro, Melba Eugenia
    Acta biomaterialia
    Vol. 9, num. 3, p. 5521-5530
    DOI: 10.1016/j.actbio.2012.10.041
    Date of publication: 2013-03
    Journal article

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    Fabrication of new biodegradable scaffolds that guide and stimulate tissue regeneration is still a major issue in tissue engineering approaches. Scaffolds that possess adequate biodegradability, pore size, interconnectivity, bioactivity and mechanical properties in accordance with the injured tissue are required. This work aimed to develop and characterize three-dimensional (3-D) scaffolds that fulfill the aforementioned requirements. For this, a nozzle-based rapid prototyping system was used to combine polylactic acid and a bioactive CaP glass to fabricate 3-D biodegradable scaffolds with two patterns (orthogonal and displaced double layer). Scanning electron microscopy and micro-computer tomography showed that 3-D scaffolds had completely interconnected porosity, uniform distribution of the glass particles, and a controlled and repetitive architecture. Surface properties were also assessed, showing that the incorporation of glass particles increased both the roughness and the hydrophilicity of the scaffolds. Mechanical tests indicated that compression strength is dependent on the scaffold geometry and the presence of glass. Preliminary cell response was studied with primary mesenchymal stem cells (MSC) and revealed that CaP glass improved cell adhesion. Overall, the results showed the suitability of the technique/materials combination to develop 3-D porous scaffolds and their initial biocompatibility, both being valuable characteristics for tissue engineering applications.

  • The effect of the composition of PLA films and lactate release on glial and neuronal maturation and the maintenance of the neuronal progenitor niche

     Álvarez Pinto, Zaída; Mateos Timoneda, Miguel Angel; Hýro¿¿ová, Petra; Castaño Linares, Oscar; Planell Estany, Josep Antón; Perales Losa, José Carlos; Engel Lopez, Elisabet; Alcántara Horrillo, Soledad
    Biomaterials
    Vol. 34, num. 9, p. 2221-2233
    DOI: 10.1016/j.biomaterials.2012.12.001
    Date of publication: 2013-03-06
    Journal article

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    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.

    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.

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    Hierarchically engineered fibrous scaffolds for bone regeneration  Open access

     Sachot, Nadège; Castaño Linares, Oscar; Mateos Timoneda, Miguel Angel; Engel Lopez, Elisabet; Planell Estany, Josep Antón
    Journal of the Royal Society Interface
    Vol. 10, num. 88, p. 1-5
    DOI: 10.1098/rsif.2013.0684
    Date of publication: 2013-08-28
    Journal article

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    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. © 2013 The Author(s).

    Surface properties of biomaterials play a major role in the governing of cell functionalities. It is well known that mechanical, chemical and nanotopo- graphic cues, for example, influence cell proliferation and differentiation. Here, we present a novel coating protocol to produce hierarchicallyengineered 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 var- ious 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

  • Ion-selective electrodes to monitor osteoblast-like cellular influence on the extracellular concentration of calcium

     Gustavsson, Johan; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    Journal of tissue engineering and regenerative medicine
    Vol. 7, num. 8, p. 609-620
    DOI: 10.1002/term.550
    Date of publication: 2013-04-27
    Journal article

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    In bone tissue engineering, the composition of the ionic extracellular environment (IEE) can determine both cellular fate and a biomaterial ’ s development and performance. Therefore, precise control of the IEE and a perfect understanding of the dynamic changes that it can be subject to due to cellular activity ishighlydesired.Toachievethis,weinitiallymonito redhowtwostandardosteoblast-likecellmodelsthat expressedeitherhighorlowalkalinephosphataseactivity-SAOS-2andMG63cells,respectively-affected the extracellular concentrations of calcium and phosphate during long-term cultures. It was observed that cellular in fl uence onthe IEE varied greatly between the two models and could be linked to the capac- ity of cells to deposit calcium in the extracellular matri x. Miniaturized ion-selective electrodes that could allow for real-time monitoring ofcalcium in aminimally invasive waywere then constructed.The electro- des were characterized in standard in vitro cell culture environments, prior to being successfully applied for periods of 24h, to record the dynamics of cell-induced deposition of calcium in the extracellular matrix, while using osteogenic media of either high or low concentrations of phosphate. As a result, this study provides the background and technological means for the non-destructive evaluation of the IEE in vitro and allows for the optimization and development of better models of bone tissue construction

  • Adsorption of fibronectin, fibrinogen and albumin on TiO2: A kinetics, structural changes, and competition study

     Pegueroles Neyra, Marta; Tonda Turo, Chiara; Planell Estany, Josep Antón; Gil Mur, Francisco Javier; Aparicio, Conrado
    Journal of the Royal Society Interface
    Vol. 7, num. 1-4, p. 1-13
    DOI: 10.1007/s13758-012-0048-4
    Date of publication: 2012-12
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  • Inducing functional radial glia-like progenitors from cortical astrocyte cultures using micropatterned PMMA.

     Mattotti, Marta; Álvarez Pinto, Zaída; Ortega, Juan A.; Planell Estany, Josep Antón; Engel Lopez, Elisabet; Alcántara Horrillo, Soledad
    Biomaterials
    Vol. 33, num. 6, p. 1759-1770
    DOI: 10.1016/j.biomaterials.2011.10.086
    Date of publication: 2012-02-01
    Journal article

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    Radial glia cells (RGC) are multipotent progenitors that generate neurons and glia during CNS development, and which also served as substrate for neuronal migration. After a lesion, reactive glia are the main contributor to CNS regenerative blockage, although some reactive astrocytes are also able to dedifferentiate in situ into radial glia-like cells (RGLC), providing beneficial effects in terms of CNS recovery. Thus, the identification of substrate properties that potentiate the ability of astrocytes to transform into RGLC in response to a lesion might help in the development of implantable devices that improve endogenous CNS regeneration. Here we demonstrate that functional RGLC can be induced from in vitro matured astrocytes by using a precisely-sized micropatterned PMMA grooved scaffold, without added soluble or substrate adsorbed biochemical factors. RGLC were extremely organized and aligned on 2 mm line patterned PMMA and, like their embryonic counterparts, express nestin, the neuron-glial progenitor marker Pax6, and also proliferate, generate different intermediate progenitors and support and direct axonal growth and neuronal migration. Our results suggest that the introduction of line patterns in the size range of the RGC processes in implantable scaffolds might mimic the topography of the embryonic neural stem cell niche, driving endogenous astrocytes into an RGLC phenotype, and thus favoring the regenerative response in situ.

  • Modular polylactic acid microparticle-based scaffolds prepared via microfluidic emulsion/solvent displacement process: Fabrication, characterization, and in vitro mesenchymal stem cells interaction study

     Salerno, Aurelio; Levato, R.; Mateos Timoneda, Miguel Angel; Engel Lopez, Elisabet; Netti, Paolo Antonio; Planell Estany, Josep Antón
    Journal of biomedical materials research. Part A
    Vol. 101, num. 3, p. 720-732
    DOI: 10.1002/jbm.a.34374
    Date of publication: 2012-08-31
    Journal article

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    The present study reports a novel approach for the design and fabrication of polylactic acid (PLA) microparticle- based scaffolds with microstructural properties suitable for bone and cartilage regeneration. Macroporous PLA scaffolds with controlled shape were fabricated by means of a semicon- tinuous process involving (1) microfluidic emulsification of a PLA/ethyl lactate solution (5% w/v) in a span 80/paraffin oil so- lution (3% v/v) followed by (2) particles coagulation/assembly in an acetone/water solution for the development of a continu- ous matrix. Porous scaffolds prepared from particles with monomodal or bimodal size distribution, overall porosity ranges from 93 to 96%, interparticles porosity from 41 to 54%, and static compression moduli from 0.3 to 1.4 MPa were man- ufactured by means of flow rate modulation of of the continu- ous phase during emulsion. The biological response of the scaffolds was assessed in vitro by using bone marrow-derived rat mesenchymal stem cells (MSCs). The results demonstrated the ability of the scaffolds to support the extensive and uni- form three-dimensional adhesion, colonization, and prolifera- tion of MSCs within the entire construct

  • In silico evaluation of a new composite disc substitute with a L3-L5 lumbar spine finite element model

     Noailly, Jerome; Ambrosio, Luigi; K. Elizabeth, Tanner; Planell Estany, Josep Antón; Lacroix, Damien
    European spine journal
    Vol. Supl5, p. S675-S687
    DOI: 10.1007/s00586-011-1716-7
    Date of publication: 2012-06-21
    Journal article

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    When the intervertebral disc is removed to relieve chronic pain, subsequent segment stabilization should restore the functional mechanics of the native disc. Because of partially constrained motions and the lack of intrinsic rotational stiffness ball-on-socket implants present many disadvantages. Composite disc substitutes mimicking healthy disc structures should be able to assume the role expected for a disc substitute with fewer restrictions than ball-on-socket implants. A biomimetic composite disc prototype including artificial nucleus fibre-reinforced annulus and endplates was modelled as an L4–L5 disc substitute within a L3–L5 lumbar spine finite element model. Different device updates, i.e. changes of material properties fibre distributions and volume fractions and nucleus placements were proposed. Load- and displace- ment-controlled rotations were simulated with and without body weight applied. The original prototype reduced greatly the flexibility of the treated segment with signifi- cant adjacent level effects under displacement-controlled or hybrid rotations. Device updates allowed restoring large part of the global axial and sagittal rotational flexibility predicted with the intact model. Material properties played a major role, but some other updates were identified to potentially tune the device behaviour against specific motions. All device versions altered the coupled interseg- mental shear deformations affecting facet joint contact through contact area displacements. Loads in the bony endplates adjacent to the implants increased as the implant stiffness decreased but did not appear to be a strong limi- tation for the implant biomechanical and mechanobiolog- ical functionality. In conclusion, numerical results given by biomimetic composite disc substitutes were encouraging with greater potential than that offered by ball-on-socket implants

  • Injectable calcium-phosphate-based composites for skeletal bone treatments

     Ambrosio, Luigi; Guarino, V.; Torricelli, P.; Fini, M.; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Giardino, R.
    Biomedical materials
    Vol. 7, num. 2, p. 1-10
    DOI: 10.1088/1748-6041/7/2/024113
    Date of publication: 2012
    Journal article

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  • Access to the full text
    Control of microenvironmental cues with a smart biomaterial composite promotes endothelial progenitor cell angiogenesis  Open access

     Aguirre, Adrián; Gonzalez, Arlyng; Navarro, Melba; Castaño Linares, Oscar; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    European cells and materials
    Vol. 24, p. 90-106
    Date of publication: 2012-09
    Journal article

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    Smart biomaterials play a key role when aiming at successful tissue repair by means of regenerative medicine approaches, and are expected to contain chemical as well as mechanical cues that will guide the regenerative process. Recent advances in the understanding of stem cell biology and mechanosensing have shed new light onto the importance of the local microenvironment in determining cell fate. Herein we report the biological properties of a bioactive, biodegradable calcium phosphate glass/polylactic acid composite biomaterial that promotes bone marrowderived endothelial progenitor cell (EPC) mobilisation, differentiation and angiogenesis through the creation of a controlled bone healing-like microenvironment. The angiogenic response is triggered by biochemical and mechanical cues provided by the composite, which activate two synergistic cell signalling pathways: a biochemical one mediated by the calcium-sensing receptor and a mechanosensitive one regulated by non-muscle myosin II contraction. Together, these signals promote a synergistic response by activating EPCs-mediated VEGF and VEGFR-2 synthesis, which in turn promote progenitor cell homing, differentiation and tubulogenesis. These findings highlight the importance of controlling microenvironmental cues for stem/progenitor cell tissue engineering and offer exciting new therapeutical opportunities for biomaterialbased vascularisation approaches and clinical applications

  • Angiogenic nanostructured materials for non-consolidating bone fractures

     Planell Estany, Josep Antón; Engel Lopez, Elisabet; Navarro Toro, Melba; Castaño Linares, Oscar; Mateos Timoneda, Miguel Angel
    Competitive project

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  • Osteoblast-like cellular response to dynamic changes in the ionic extracellular environment produced by calcium-deficient hydroxyapatite

     Gustavsson, Johan; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    Journal of materials science. Materials in medicine
    Vol. 23, num. 10, p. 2509-2520
    DOI: 10.1007/s10856-012-4705-4
    Date of publication: 2012-10
    Journal article

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  • Preparation of biodegradable polylactide microparticles via a biocompatible procedure

     Levato, R.; Mateos Timoneda, Miguel Angel; Planell Estany, Josep Antón
    Macromolecular bioscience
    Vol. 12, num. 4, p. 557-566
    DOI: 10.1002/mabi.201100383
    Date of publication: 2012-04
    Journal article

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    PLA MPs are prepared via a novel and toxic-chemical-free fabrication route using ethyl lactate, a green solvent and FDA-approved aroma. MPs are obtained by a solution jet break-up and solvent displacement method. Adjusting flow parameters allows the tuning of MPs size between 60 and 180 mm, with reduced polydispersity. Morphological analysis shows microporous particles with Janus-like surface. A fluorophore is successfully loaded into the MPs during their formation step. This versatile green solvent-based procedure is proven to be suitable for drug encapsulation and delivery applications. The method may be extended to different droplet generation techniques.

  • 3D electrospun PLA nanofibers favours neurovascular niche regeneration in vivo

     Álvarez Pinto, Zaída; Castaño Linares, Oscar; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    TERMIS World Congress
    p. 278
    Presentation's date: 2012
    Presentation of work at congresses

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  • Biofunctionalization of rapid prototyping PLA scaffolds for tissue engineering

     Serra Devesa, Teresa; Navarro, M; Mateos Timoneda, Miguel Angel; Rodriguez Cabello, Jose Carlos; Planell Estany, Josep Antón
    TERMIS World Congress
    p. 373
    Presentation's date: 2012
    Presentation of work at congresses

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  • Biopolímeros Biodegradabes Funcionalizados con colágeno que comprenden células de epitelio del limbo esclerocorneal para la reconstrucción de la superficie ocular

     Planell Estany, Josep Antón; Mateos Timoneda, Miguel Angel; Engel Lopez, Elisabet; Calonge Cano, Margarita; de la Mata Sampedro, Ana; Lopez Paniagua, Marina; Galindo de la Rosa, Sara; Nieto Miguel, Teresa
    Date of request: 2012-06-28
    Invention patent

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  • Electrochemical microelectrodes for improved spatial and temporal characterization of aqueous environments around calcium phosphate cements.

     Gustavsson, Johan; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    Acta biomaterialia
    Vol. 8, num. 1, p. 386-393
    DOI: 10.1016/j.actbio.2011.10.002
    Date of publication: 2011-10-07
    Journal article

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    Calcium phosphate compounds can potentially influence cellular fate through ionic substitutions. However, to be able to turn such solution-mediated processes into successful directors of cellular response, a perfect understanding of the material-induced chemical reactions in situ is required. We therefore report on the application of home-made electrochemical microelectrodes, tested as pH and chloride sensors, for precise spatial and temporal characterization of different aqueous environments around calcium phosphate- based biomaterials prepared from a-tricalcium phosphate using clinically relevant liquid to powder ratios. The small size of the electrodes allowed for online measurements in traditionally inaccessible in vitro environments, such as the immediate material–liquid interface and the interior of curing bone cement. The kinetic data obtained has been compared to theoretical sorption models, confirming that the proposed setup can provide key information for improved understanding of the biochemical environment imposed by chemically reactive biomaterials.

  • On the collagen criss-cross angles in the annuli fibrosi of lumbar spine finite element models

     Planell Estany, Josep Antón; Lacroix, Damien Jerome; Noailly, Jerome
    Biomechanics and modeling in mechanobiology
    Vol. 10, num. 2, p. 203-219
    DOI: 10.1007/s10237-010-0227-5
    Date of publication: 2011-04
    Journal article

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    In the human lumbar spine, annulus fibrosus fibres largely contribute to intervertebral disc stability. Detailed annulus models are therefore necessary to obtain reliable predictions of lumbar spine mechanics by finite element modelling. However, different definitions of collagen orientations coexist in the literature for healthy human lumbar annuli. Therefore, four annulus fibre-induced anisotropy models were built from reported anatomical descriptions, and inserted in a L3–L5 lumbar bi-segment finite element model. Annulus models were, respectively, characterized by radial, tangential, radial and tangential, and no fibre orientation gradients. The effect of rotational and axial compressive loadings was simulated and first, predictions were compared to experimental data. Then, intervertebral disc local biomechanics was studied under axial rotation and axial compression. A new parameter, i.e. the fibre contribution quality parameter, was computed in the anterior, lateral, postero-lateral, and posterior annuli of each model, in function of fibre stresses, radial load distributions, and matrix shear strains. Locally, each annulus model behaved differently, affecting intervertebral disc biomechanics and segmentalmotions. The fibre contribution quality parameter allowed establishing direct links between local annulus fibre organization and local annulus loadings, while other kinematical and biomechanical data did not. It was concluded that functional relations should exist between local annulus fibre orientations and overall segment morphology. The proposed fibre contribution quality parameter could be used to examine such relations and calibrate lumbar spine finite element models by locally adjusting the annulus bundle criss-cross angles. Conclusions of this study are particularly relevant to patient-specific models or artificial disc designs.

  • Ion reactivity of calcium-deficient hydroxyapatite in standard cell culture media

     Gustavsson, Johan; Ginebra Molins, Maria Pau; Engel Lopez, Elisabet; Planell Estany, Josep Antón
    Acta biomaterialia
    Vol. 7, num. 12, p. 4242-4252
    DOI: 10.1016/j.actbio.2011.07.016
    Date of publication: 2011-12
    Journal article

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  • Effect of blasting treatment and Fn coating on MG63 adhesion and differentiation on titanium: a gene expression study using real-time RT-PCR.

     Pegueroles Neyra, Marta; Aguirre Cano, Aitor; Engel Lopez, Elisabet; Pavon-Djavid, Graciela; Gil Mur, Francisco Javier; Planell Estany, Josep Antón; Migonney, Veronique; Aparicio, C
    Journal of materials science. Materials in medicine
    Vol. 22, num. 3, p. 617-627
    DOI: 10.1007/s10856-011-4229-3
    Date of publication: 2011-03-02
    Journal article

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    Biomaterial surface properties, via alterations in the adsorbed protein layer, and the presence of specific functional groups can influence integrin binding specificity, thereby modulating cell adhesion and differentiation processes. The adsorption of fibronectin, a protein directly involved in osteoblast adhesion to the extracellular matrix, has been related to different physical and chemical properties of biomaterial surfaces. This study used blasting particles of different sizes and chemical compositions to evaluate the response of MG63 osteoblast-like cells on smooth and blasted titanium surfaces, with and without fibronectin coatings, by means of real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays. This response included (a) expression of the a5, av and a3 integrin subunits, which can bind to fibronectin through the RGD binding site, and (b) expression of alkaline phosphatase (ALP) and osteocalcin (OC) as cell-differentiation markers. ALP activity and synthesis of OC were also tested. Cells on SiC-blasted Ti surfaces expressed higher amounts of the a5 mRNA gene than cells on Al2O3-blasted Ti surfaces. This may be related to the fact that SiC-blasted surfaces adsorbed higher amounts of fibronectin due to their higher surface free energy and therefore provided a higher number of specific cell-binding sites. Fn-coated Tisurfaces decreased a5 mRNA gene expression, by favoring the formation of other integrins involved in adhesion over a5b1. The changes in a5 mRNA expression induced by the presence of fibronectin coatings may moreover influence the osteoblast differentiation pathway, as fibronectin coatings on Ti surfaces also decreased both ALP mRNA expression and ALP activity after 14 and 21 days of cell culture.

  • Comparison of a low molecular weight and a macromolecular surfactant as foaming agents for injectable self setting hydroxyapatite foams: Polysorbate 80 versus gelatine

     Montufar Jimenez, Edgar Benjamin; Traykova, Tania; Planell Estany, Josep Antón; Ginebra Molins, Maria Pau
    Materials science and engineering C. Biomimetic and supramolecular systems
    Vol. 31, num. 7, p. 1498-1504
    DOI: 10.1016/j.msec.2011.06.008
    Date of publication: 2011-10-10
    Journal article

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    Hydroxyapatite foams are potential synthetic bone grafting materials or scaffolds for bone tissue engineering. A novel method to obtain injectable hydroxyapatite foams consists in foaming the liquid phase of a calcium phosphate cement. In this process, the cement powder is incorporated into a liquid foam, which acts as a template for macroporosity. After setting, the cement hardens maintaining the macroporous structure of the foam. In this study a low molecular weight surfactant, Polysorbate 80, and a protein, gelatine, were compared as foaming agents of a calcium phosphate cement. The foamability of Polysorbate 80 was greater than that of gelatine, resulting in higher macroporosity in the set hydroxyapatite foam and higher macropore interconnectivity. Gelatine produced less interconnected foams, especially at high concentrations, due to a higher liquid foam stability. However it increased the injectability and cohesion of the foamed paste, and enhanced osteoblastic-like cell adhesion, all of them important properties for bone grafting materials.

  • Desarrollo y Caracterización de Andamios Biodegradables para Sustitución Ósea mediante Ingeniería Tisular

     Márquez Pérez, Lucia
    Department of Automatic Control, Universitat Politècnica de Catalunya
    Theses

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  • Modifying biomaterial surfaces for the repair and regeneration of nerve cells

     Planell Estany, Josep Antón; Engel Lopez, Elisabet; Mateos Timoneda, Miguel Angel
    Date of publication: 2011-09-01
    Book chapter

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  • Tailoring the bio/non-bio interface: from atomic modification to cell scale organization

     Pegueroles Neyra, Marta; García, José Luís; Fernández, Marc; Engel Lopez, Elisabet; Palacio, Inés; Mascaraque, Aranzazu; de la Fuente, Oscar; Planell Estany, Josep Antón; Castaño Linares, Oscar
    International Symposium on Ceramics in Medicine
    Presentation's date: 2011-11
    Presentation of work at congresses

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  • Adsorption of proteins on TiO2-surfaces. A conformational and competitive study using QCM-D

     Pegueroles Neyra, Marta; Tondo, Chiara; Gil Mur, Francisco Javier; Planell Estany, Josep Antón; Aparicio, Conrado
    European Conference on Biomaterials
    Presentation's date: 2011-09
    Presentation of work at congresses

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  • Fabrication and characterization of biodegradable composite scaffolds for tissue engineering

     Serra, Tiziano; Navarro, Melba; Planell Estany, Josep Antón
    International Conference on Advanced Research in Virtual and Rapid Prototyping
    p. 67-72
    DOI: 10.1201/b11341-12
    Presentation's date: 2011-09
    Presentation of work at congresses

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  • 8è premi de valorització de la recerca, modalitat 2

     Ginebra Molins, Maria Pau; Gil Mur, Francisco Javier; Planell Estany, Josep Antón
    Award or recognition

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  • Simulation of bone tissue formation within a porous scaffold under dynamic compression

     Milan, Jean-Louis; Planell Estany, Josep Antón; Lacroix, Damien Jerome
    Biomechanics and modeling in mechanobiology
    Vol. 9, num. 5, p. 583-596
    DOI: 10.1007/s10237-010-0199-5
    Date of publication: 2010-10
    Journal article

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  • Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis

     Aguirre Cano, Aitor; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    Biochemical and biophysical research communications
    Vol. 400, num. 2, p. 284-291
    DOI: 10.1016/j.bbrc.2010.08.073
    Date of publication: 2010-09-17
    Journal article

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  • Different assembly of type IV collagen on hydrophilic and hydrophobic substrata alters endothelial cells interaction

     Coelho, Nuno Miranda Guerra; Gonzalez Garcia, C.; Planell Estany, Josep Antón; Salmeron Sánchez, M; Altankov, George Petrov
    European cells and materials
    Vol. 19, p. 262-272
    Date of publication: 2010-06
    Journal article

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    Considering the structural role of type IV collagen (Col IV) in the assembly of the basement membrane (BM) and the perspective of mimicking its organization for vascular tissue engineering purposes, we studied the adsorption pattern of this protein on model hydrophilic (clean glass) and hydrophobic trichloro(octadecyl)silane (ODS) surfaces known to strongly affect the behavior of other matrix proteins. The amount of fluorescently labeled Col IV was quantified showing saturation of the surface for concentration of the adsorbing solution of about 50μg/ml, but with approximately twice more adsorbed protein on ODS. AFM studies revealed a fine – nearly single molecular size – network arrangement of Col IV on hydrophilic glass, which turns into a prominent and growing polygonal network consisting of molecular aggregates on hydrophobic ODS. The protein layer forms within minutes in a concentration-dependent manner. We further found that human umbilical vein endothelial cells (HUVEC) attach less efficiently to the aggregated Col IV (on ODS), as judged by the significantly altered cell spreading, focal adhesions formation and the development of actin cytoskeleton. Conversely, the immunofluorescence studies for integrins revealed that the fine Col IV network formed on hydrophilic substrata is better recognized by the cells via both α1 and α2 heterodimers which support cellular interaction, apart from these on hydrophobic ODS where almost no clustering of integrins was observed.

  • Self-hardening calcium deficient hydroxyapatite/gelatine foams for bone regeneration

     Montufar Jimenez, Edgar Benjamin; Traykova, Tania; Schacht, Etienne; Ambrosio, Luigi; Santin, Matteo Alfredo Giovanni; Planell Estany, Josep Antón; Ginebra Molins, Maria Pau
    Journal of materials science. Materials in medicine
    Vol. 21, num. 3, p. 863-869
    DOI: 10.1007/s10856-009-3918-7
    Date of publication: 2010-03
    Journal article

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    In this work gelatine was used as multifunctional additive to obtain injectable self-setting hydroxyapatite/ gelatine composite foams for bone regeneration. The foaming and colloidal stabilization properties of gelatine are well known in food and pharmaceutical applications. Solid foams were obtained by foaming liquid gelatine solutions at 50 C, followed by mixing them with a cement powder consisting of alpha tricalcium phosphate. Gelatine addition improved the cohesion and injectability of the cement paste. After setting the foamed paste transformed into a calcium deficient hydroxyapatite. The final porosity, pore interconnectivity and pore size were modulated by modifying the gelatine content in the liquid phase.

  • Novel soybean/gelatine-based bioactive and injectable hydroxyapatite foam: material properties and cell response

     Perut, Francesca; Montufar Jimenez, Edgar Benjamin; Ciapetti, Gabriela; Santin, Matteo Alfredo Giovanni; Salvage, J; Traykova, Tania; Planell Estany, Josep Antón; Ginebra Molins, Maria Pau; Baldini, Nicola
    Acta biomaterialia
    DOI: 10.1016/j.actbio.2010.12.012
    Date of publication: 2010-12-10
    Journal article

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    Despite their known osteoconductivity, clinical use of calcium phosphate cements is limited both by their relatively slow rate of resorption and by rheological properties incompatible with injectability. Bone in-growth and material resorption have been improved by the development of porous calcium phosphate cements. However, injectable formulations have so far only been obtained through the addition of relatively toxic surfactants. The present work describes the response of osteoblasts to a novel injectable foamed bone cement based on a composite formulation including the bioactive foaming agents soybean and gelatine. The foaming properties of both defatted soybean and gelatine gels were exploited to develop a self-hardening soy/gelatine/hydroxyapatite composite foam able to retain porosity upon injection. After setting, the foamed paste produced a calcium-deficient hydroxyapatite scaffold, showing good injectability and cohesion as well as interconnected porosity after injection. The intrinsic bioactivity of soybean and gelatine was shown to favour osteoblast adhesion and growth. These findings suggest that injectable, porous and bioactive calcium phosphate cements can be produced for bone regeneration through minimally invasive surgery.

  • Extracellular calcium modulates in vitro bone marrow-derived Flk-1282B29 CD34282B29 progenitor cell chemotaxis and differentiation through a calcium-sensing receptor

     Aguirre Cano, Aitor; Planell Estany, Josep Antón; Gonzalez Colas, Antonio Maria; Engel Lopez, Elisabet
    Biochemical and biophysical research communications
    Vol. 393, num. 1, p. 156-161
    DOI: 10.1016/j.bbrc.2010.01.109
    Date of publication: 2010-02-26
    Journal article

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  • Foamed surfactant solution as a template for self-setting injectable hydroxyapatite scaffolds for bone regeneration

     Montufar Jimenez, Edgar Benjamin; Traykova, Tania Valentinova; Gil, C.; Harr, I.; Almirall Gonzalo, Arturo; Aguirre Cano, Aitor; Engel Lopez, Elisabet; Planell Estany, Josep Antón; Ginebra Molins, Maria Pau
    Acta biomaterialia
    Vol. 6, num. 3, p. 876-885
    DOI: 10.1016/j.actbio.2009.10.018
    Date of publication: 2010-03
    Journal article

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  • Spatial organization of osteoblast fibronectin matrix on titanium surfaces: Effects of roughness, chemical heterogeneity and surface energy

     Pegueroles Neyra, Marta; Aparicio Bádenas, Conrado José; Bosio, Mattia; Engel Lopez, Elisabet; Gil Mur, Francisco Javier; Planell Estany, Josep Antón; Altankov, George Petrov
    Acta biomaterialia
    Vol. 6, num. 1, p. 291-301
    DOI: 10.1016/j.actbio.2009.07.030
    Date of publication: 2010-01
    Journal article

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  • Injectable and fast resorbable calcium phosphate cement for body-setting bone grafts

     Rajzer, I.; Castaño Linares, Oscar; Engel Lopez, Elisabet; Planell Estany, Josep Antón
    Journal of materials science. Materials in medicine
    Vol. 21, num. 7, p. 2049-2056
    DOI: 10.1007/s10856-010-4078-5
    Date of publication: 2010
    Journal article

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  • Materials Surface Effects on Biological Interactions

     Planell Estany, Josep Antón; Navarro, M; Altankov, George Petrov; Aparicio, Conrado; Engel Lopez, Elisabet; Gil Mur, Francisco Javier; Ginebra Molins, Maria Pau; Lacroix, Damien Jerome
    NATO Science for Peace and Security Series A. Chemistry and Biology
    p. 233-252
    DOI: 10.1007/978-90-481-8790-4_12
    Date of publication: 2010
    Journal article

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  • Perfusion cell seeding on large porous PLA/calcium phosphate composite scaffolds in a perfusion bioreactor system under varying perfusion parameters

     Koch, Martin Andreas; Vrij, E. J; Engel Lopez, Elisabet; Planell Estany, Josep Antón; Lacroix, Damien Jerome
    Journal of biomedical materials research. Part A
    Vol. 95A, num. 4, p. 1011-1018
    DOI: 10.1002/jbm.a.32927
    Date of publication: 2010-12-15
    Journal article

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    A promising approach to bone tissue engineering lies in the use of perfusion bioreactors where cells are seeded and cultured on scaffolds under conditions of enhanced nutrient supply and removal of metabolic products. Fluid flow alterations can stimulate cell activity, making the engineering of tissue more efficient. Most bioreactor systems are used to culture cells on thin scaffold discs. In clinical use, however, bone substitutes of large dimensions are needed. In this study, MG63 osteoblast-like cells were seeded on large porous PLA/glass scaffolds with a custom developed perfusion bioreactor system. Cells were seeded by oscillating perfusion of cell suspension through the scaffolds. Applicable perfusion parameters for successful cell seeding were determined by varying fluid flow velocity and perfusion cycle number. After perfusion, cell seeding, the cell distribution, and cell seeding efficiency were determined. A fluid flow velocity of 5 mm/s had to be exceeded to achieve a uniform cell distribution throughout the scaffold interior. Cell seeding efficiencies of up to 50% were achieved. Results suggested that perfusion cycle number influenced cell seeding efficiency rather than fluid flow velocities. The cell seeding conducted is a promising basis for further long term cell culture studies in large porous scaffolds.

  • Materials surface effects on biological interactions

     Planell Estany, Josep Antón; MELBA, NAVARRO TORO; Altankov, George Petrov; Aparicio, Conrado; Engel Lopez, Elisabet; Gil Mur, Francisco Javier; Ginebra Molins, Maria Pau; Lacroix, D.
    DOI: 10.1007/978-90-481-8790-4_2
    Date of publication: 2010-08-20
    Book chapter

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  • Development of provisional extracellular matrix on biomaterials interface: lessons from in vitro cell culture

     Altankov, George Petrov; Groth, Thomas; Gustavsson, Johan; Engel Lopez, Elisabet; Pegueroles Neyra, Marta; Aparicio, Conrado; Gil Mur, Francisco Javier; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón
    DOI: 10.1007/978-90-481-8790-4_2
    Date of publication: 2010-08-20
    Book chapter

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  • Gene expression of integrins alpha 5, alpha V, alpha 3, beta 1 and beta 3 by osteoblasts adhered on plane and fibronectin coated cp Ti. Effect of physical, chemical and topographical surface properties

     Gil Mur, Francisco Javier; Pegueroles Neyra, Marta; Aparicio, Conrado; Aguirre Cano, Aitor; Engel Lopez, Elisabet; Planell Estany, Josep Antón
    European Conference on Biomaterials
    Presentation's date: 2010-09
    Presentation of work at congresses

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