Coating typologies and constrained swelling of hyaluronic acid gels within scaffold pores

[EN] A set of elastomeric scaffolds with a well defined porous structure was prepared with a template leaching procedure and coated with hyaluronic acid solutions. Depending on the coating process parameters the hyaluronic acid deposited on the pores had configurations ranging from thin disconnected aggregates to a thick continuous layer on the pore surface. The development of the coating layer was studied by scanning electron microscopy and the materials were subjected to dynamical and equilibrium swelling experiments in a water vapor ambient of fixed activity. The porosity change due to coating and to swelling of the coating layer were determined. The hyaluronic acid coating the pores has a different swelling capacity depending on the type of layer formed, as a consequence of the scaffold constraint and of the layer typology. These factors were investigated analytically by modifying the standard theory of gel swelling. An experimental quantity is introduced which reflects the constrainment build-up on gel swelling. © 2011 Elsevier Inc.The authors acknowledge the support of the FP7 NMP3-SL-2009-229239 project "Regeneration of cardiac tissue assisted by bioactive implants (RECATABI)". MMP further acknowledges the support of the Spanish Science & Innovation Ministry through project MAT2008-06434. Roberto Garcia Gomez is thanked for his help in preparing the bare scaffolds.Arnal Pastor, MP.; Vallés Lluch, A.; Keicher, M.; Monleón Pradas, M. (2011). Coating typologies and constrained swelling of hyaluronic acid gels within scaffold pores. Journal of Colloid and Interface Science. 361(1):361-369. https://doi.org/10.1016/j.jcis.2011.05.013S361369361

Topologically controlled hyaluronan-based gel coatings of hydrophobic grid-like scaffolds to modulate drug delivery

[EN] Scaffolds based on poly(ethyl acrylate) having interwoven channels were coated with a hyaluronan (HA) hydrogel to be used in tissue engineering applications. Controlled typologies of coatings evolving from isolated aggregates to continuous layers, which eventually clog the channels, were obtained by using hyaluronan solutions of different concentrations. The efficiency of the HA loading was determined using gravimetric and thermogravimetric methods, and the hydrogel loss during the subsequent crosslinking process was quantified, seeming to depend on the mass fraction of hyaluronan initially incorporated to the pores. The effect of the topologically different coatings on the scaffolds, in terms of mechanical properties and swelling at equilibrium under different conditions was evaluated and correlated with the hyaluronan mass fraction. The potential of these hydrogel coatings as vehicle for controlled drug release from the scaffolds was validated using a protein model.The authors acknowledge the financing through projects FP7 NMP3-SL-2009-229239 (RECATABI) and MAT2011-28791-C03-02 and -03. This work was also supported by the Spanish Ministry of Education through M. Arnal-Pastor FPU2009-1870 and M. Perez-Garnes BES-2009-015314 grants.Arnal Pastor, MP.; Perez Garnes, M.; Monleón Pradas, M.; Vallés Lluch, A. (2016). Topologically controlled hyaluronan-based gel coatings of hydrophobic grid-like scaffolds to modulate drug delivery. Colloids and Surfaces B Biointerfaces. 140:412-420. https://doi.org/10.1016/j.colsurfb.2016.01.004S41242014

Hydrophilic surface modification of acrylate-based biomaterials

[EN] Acrylic polymers have proved to be excellent with regard to cell adhesion, colonization and survival, in vitro and in vivo. Highly ordered and regular pore structures thereof can be produced with the help of polyamide templates, which are removed with nitric acid. This treatment converts a fraction of the ethyl acrylate side groups into acrylic acid, turning poly(ethyl acrylate) scaffolds into a more hydrophilic and pH-sensitive substrate, while its good biological performance remains intact. To quantify the extent of such a modification, and be able to characterize the degree of hydrophilicity of poly(ethyl acrylate), poly(ethyl acrylate) was treated with acid for different times (four, nine and 17 days), and compared with poly(acrylic acid) and a 90/10%wt. EA/AAc copolymer (P(EA-co-AAc)). The biological performance was also assessed for samples immersed in acid up to four days and the copolymer, and it was found that the incorporation of acidic units on the material surface was not prejudicial for cells. This surface modification of 3D porous hydrophobic scaffolds makes easier the wetting with culture medium and aqueous solutions in general, and thus represents an advantage in the manageability of the scaffolds.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors acknowledge financing through project FP7 NMP3-SL-2009-229239 'Regeneration of cardiac tissue assisted by bioactive implants' (RECATABI) and projects MAT2011-28791-C03-02 and -03 from the Spanish Ministerio de Ciencia e Innovacion. This work was also supported by the Spanish Ministry of Education through M. Arnal-Pastor FPU AP2009-1870 grant.Arnal Pastor, MP.; Comín-Cebrián, S.; Martínez-Ramos, C.; Monleón Pradas, M.; Vallés Lluch, A. (2016). Hydrophilic surface modification of acrylate-based biomaterials. Journal of Biomaterials Applications. 30(9):1429-1441. doi:10.1177/0885328215627414S1429144130

Scaffolds based on hyaluronan and carbon nanotubes gels

[EN] Physico-chemical and mechanical properties of hyaluronic acid/carbon nanotubes nanohybrids have been correlated with the proportion of inorganic nanophase and the preparation procedure. The mass fraction of -COOH functionalized carbon nanotubes was varied from 0 to 0.05. Hyaluronic acid was crosslinked with divinyl sulfone to improve its stability in aqueous media and allow its handling as a hydrogel. A series of samples was dried by lyophilization to obtain porous scaffolds whereas another was room-dried allowing the collapse of the hybrid structures. The porosity of the former, together with the tighter packing of hyaluronic acid chains, results in a lower water absorption and lower mechanical properties in the swollen state, because of the easier water diffusion. The presence of even a small amount of carbon nanotubes (mass fraction of 0.05) limits even more the swelling of the matrix, owing probably to hybrid interactions. These nanohybrids do not seem to degrade significantly during 14 days in water or enzymatic medium.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Contract grant sponsor: Spanish Ministerio de Economia y Competitividad; contract grant numbers: MAT2011-28791-C03-02 and -03.Arnal Pastor, MP.; Tallà-Ferrer, C.; Herrero-Herrero, M.; Martínez-Gómez Aldaraví, A.; Monleón Pradas, M.; Vallés Lluch, A. (2016). Scaffolds based on hyaluronan and carbon nanotubes gels. Journal of Biomaterials Applications. 31(4):534-543. https://doi.org/10.1177/0885328216644535S53454331

Grid polymeric scaffolds with polypeptide gel filling as patches for infarcted tissue regeneration

© 2013 IEEE. Personal use of this material is permitted. Permissíon from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertisíng or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.[EN] Scaffolds of poly(ethyl acrylate) (PEA) with interconnected cylindrical orthogonal pores filled with a self-assembling peptide (SAP) gel are here proposed as patches for infarcted tissue regeneration. These combined systems aim to support cell therapy and meet further requirements posed by the application: the three-dimensional architecture of the elastomeric scaffold is expected to lodge the cells of interest in the damaged zone avoiding their death or migration, and at the same time conduct cell behavior and give mechanical support if necessary; the ECM-like polypeptide gel provides a cell-friendly aqueous microenvironment, facilitates diffusion of nutrients and cell wastes and is expected to improve the distribution and viability of the seeded cells within the pores and stimulate angiogenesis.Research supported by the European Comission through the RECATABI FP7 NMP3-SL-2009-229239 project and the spanish Ministerio de Ciencia e Innovación through the MAT2011-28791-C03-02 and -03 projects.Vallés Lluch, A.; Arnal Pastor, MP.; Martínez-Ramos, C.; Vilariño, G.; Vikingsson, L.; Monleón Pradas, M. (2013). Grid polymeric scaffolds with polypeptide gel filling as patches for infarcted tissue regeneration. Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society. 6961-6964. https://doi.org/10.1109/EMBC.2013.6611159S6961696

Development of Bioactive Patch for Maintenance of Implanted Cells at the Myocardial Infarcted Site

[EN] Ischemia produced as a result of myocardial infarction might cause moderate or severe tissue death. Studies under development propose grafting stem cells into the affected area and we hypothesize that this mechanism could be enhanced by the application of a "bioactive implant." The implant herein proposed consists of a thin porous elastomeric membrane, filled with self-assembling nanofibers and human subcutaneous adipose tissue derived progenitor cells. We describe the development and characterization of two elastomeric membranes: poly(ethyl acrylate) (PEA) and poly(caprolactone 2-(methacryloyloxy) ethyl ester) (PCLMA). Both are a good material support to deliver cells within a soft self-assembling peptide and are elastic enough to withstand the stresses arising from the heartbeat. Both developed composites (PEA and PCLMA, combined with self-assembling peptide) equally facilitate the propagation of electrical pulses and maintain their genetic profile of the seeded cells. Preliminary studies with small animal models suggest that, at short times, the bioimplant shows good adhesion with the myocardium. After three days cells loaded in the patch remain alive at the implanted site. We propose that the bioactive patch (elastomeric membranes with self-assembling peptide and cells) could increase the efficacy of future cardiac cell therapy by improving cell immobilization and survival at the affected site.The authors wish to thank the Department of Cardiac Surgery (Hospital Germans Trias i Pujol, Badalona) for their collaboration in obtaining human samples, Dr. Bago for his kind contribution in the cell transduction process and BLI analysis, and Joan Gilabert from Biomaterials Laboratory (GEMAT, IQS-School of Engineering) who kindly helped them with wettability measurements. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant agreement no. 229239. This work was also supported by Grants from Ministerio de Educacion y Ciencia (SAF2011-30067-C02-01 and M. Arnal-Pastor FPU 2009-1870 grant), Red de Terapia Celular-TerCel (RD12/0019/0029), Red Cardio-vascular (RD12/0042/0047), and Fundacio La Marato de TV3 (122232).Castells-Sala, C.; Vallés Lluch, A.; Soler-Botija, C.; Arnal Pastor, MP.; Martínez Ramos, C.; Fernandez-Muinos, T.; Mari-Buye, N.... (2015). Development of Bioactive Patch for Maintenance of Implanted Cells at the Myocardial Infarcted Site. Journal of Nanomaterials. (804017). https://doi.org/10.1155/2015/804017S80401

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

New scaffolding materials for the regeneration of infarcted myocardium

There is growing interest in the development of biomimetic matrices that are simultaneously cell-friendly, allow rapid vascularization, exhibit enough mechanical integrity to be comfortably handled and resist mechanical stresses when implanted in the site of interest. Meeting all these requirements with a single component material has proved to be very challenging. The hypothesis underlying this work was that hybrid materials obtained by combining scaffolds with bioactive hydrogels would result in a synergy of their best properties: a construct with good mechanical properties, easily handled and stable thanks to the scaffold; but also, because of the gel, cell-friendly and with enhanced oxygen and nutrients diffusion, and promoter of cell colonization. Moreover, such a composite material would also be useful as a controlled release system because of the gel’s incorporation. Poly (ethyl acrylate) (PEA) scaffolds prepared with two different morphologies were envisaged to provide the mechanical integrity to the system. Both types of scaffolds were physicochemically characterized and the effect of the scaffolds production process on the PEA properties was examined. The scaffolds preparation methods affected the PEA properties; nevertheless, the modifications induced were not detrimental for the PEA biological performance. Two different bioactive gels were studied as fillers of the scaffolds’ pores: hyaluronan (HA), which is a natural polysaccharide, and a synthetic self-assembling peptide, RAD16-I. HA is ubiquitously present in the body and its degradation products have been reported to be angiogenic. RAD16-I is a synthetic polypeptide that mimics the extracellular matrix providing a favourable substrate for cell growth and proliferation. Given the hydrophobic nature of poly(ethyl acrylate), the combination of PEA scaffolds with aqueous gels raised a number of problems regarding the methods to combine such different elements, the ways to gel them inside the pores, and the procedures to seed cells in the new composite materials. Different alternatives to solve these questions were thoroughly studied and yielded protocols to reliably obtain these complex structures and their biohybrids. An extensive physico-chemical characterization of the components’ interaction and the combined systems was undertaken. As these materials were intended for cardiac tissue engineering applications, the mechanical properties and the effect of the fatigue on them were studied. The different composite systems here developed were homogeneously filled or coated with the hydrogels, were easy to manipulate, and displayed appropriate mechanical properties. Interestingly, these materials exhibited a very good performance under fatigue. The use of the composite systems as a controlled release device was based on the possibility of incorporating active soluble molecules in the hydrogel within the pores. A release study of bovine serum albumin (BSA), intended as a model protein, was performed, which served as a proof of concept. The biological performance of the hybrid scaffolds was first evaluated with fibroblasts to discard the materials cytotoxicity and to optimize the cell seeding procedure. Subsequently, human umbilical vein endothelial cells (HUVECs) cultures were performed for their interest in angiogenic and vascularization processes. Finally, co-cultures of HUVECs with adipose-tissue derived mesenchymal cells (MSCs) were carried out. These last cells are believed to play an important role for clinical regenerative medicine, and their cross-talk with the endothelial cells enhances the viability and phenotypic development of HUVECs. Through the different experiments undertaken, hybrid scaffolds exceeded the outcome achieved by bare PEA scaffolds.Arnal Pastor, MP. (2014). New scaffolding materials for the regeneration of infarcted myocardium [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/46129TESISPremios Extraordinarios de tesis doctorale

Évolution de la taille des régions de réarrangements cooperatifs dans du plla amorphe et semi-cristallin : influence du vieillissement

Consulta en la Biblioteca ETSI Industriales (8063)Arnal Pastor, MP. (2009). Évolution de la taille des régions de réarrangements cooperatifs dans du plla amorphe et semi-cristallin : influence du vieillissement. http://hdl.handle.net/10251/33999.Archivo delegad

Influence of scaffold morphology on co-cultures of human endothelial and adipose tissue-derived stem cells

[EN] The interior of tissue engineering scaffolds must be vascularizable and allow adequate nutrients perfusion in order to ensure the viability of the cells colonizing them. The promotion of rapid vascularization of scaffolds is critical for thick artificial constructs. In the present study co-cultures of human endothelial and adipose tissue-derived stem cells have been performed in poly(ethyl acrylate) scaffolds with two different pore structures: grid-like (PEA-o) or sponge-like (PEA-s), in combination with a self-assembling peptide gel filling the pores, which aims to mimic the physiological niche. After 2 and 7 culture days, cell adhesion, proliferation and migration, the expression of cell surface markers like CD31 and CD90 and the release of VEGF were assessed by means of immunocytochemistry, scanning electronic microscopy, flow cytometry and ELISA analyses. The study demonstrated that PEA-s scaffolds promoted greater cell organization into tubular-like structures than PEA-o scaffolds, and this was enhanced by the presence of the peptide gel. Paracrine signaling from adipose cells significantly improved endothelial cell viability, proving the advantageous combination of this system for obtaining easily vascularizable tissue engineered grafts.Contract grant sponsor: Spanish Ministry of Education; contract grant number: FPU 2009-1870Arnal Pastor, MP.; Martínez-Ramos, C.; Vallés Lluch, A.; Monleón Pradas, M. (2016). Influence of scaffold morphology on co-cultures of human endothelial and adipose tissue-derived stem cells. Journal of Biomedical Materials Research Part A. 104(6):1523-1533. https://doi.org/10.1002/jbm.a.35682S15231533104