15 research outputs found

    Regenerative and resorbable PLA/HA hybrid construct for tendon/ligament tissue engineering

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    [EN] Tendon and ligament shows extremely limited endogenous regenerative capacity. Current treatments are based on the replacement and or augmentation of the injured tissue but the repaired tissue rarely achieve functionality equal to that of the preinjured tissue. To address this challenge, tissue engineering has emerged as a promising strategy. This study develops a regenerative and resorbable hybrid construct for tendon and ligament engineering. The construct is made up by a hollow poly-lactic acid braid with embedded microspheres carrying cells and an anti-adherent coating, with all the parts being made of biodegradable materials. This assembly intends to regenerate the tissue starting from the interior of the construct towards outside while it degrades. Fibroblasts cultured on poly lactic acid and hyaluronic acid microspheres for 6 h were injected into the hollow braid and the construct was cultured for 14 days. The cells thus transported into the lumen of the construct were able to migrate and adhere to the braid fibers naturally, leading to a homogeneous proliferation inside the braid. Moreover, no cells were found on the outer surface of the coating. Altogether, this study demonstrated that PLA/HA hybrid construct could be a promising material for tendon and ligament repair.This work was supported by AITEX (Textil Research Institute, Alcoi, Alicante, Spain) through the researching contract "Development of braided biomaterials for biomedical applications'' and also funded by AEI "RTI2018-095872-B-C21 and C22/ERDF''.Araque-Monrós, MC.; García-Cruz, DM.; Escobar-Ivirico, JL.; Gil-Santos, L.; Monleón Pradas, M.; Más Estellés, J. (2020). Regenerative and resorbable PLA/HA hybrid construct for tendon/ligament tissue engineering. Annals of Biomedical Engineering. 48(2):757-767. https://doi.org/10.1007/s10439-019-02403-0S757767482Aktas, E., C. S. Chamberlain, E. E. Saether, S. E. Duenwald-Kuehl, J. Kondratko-Mittnacht, M. Stitgen, J. S. Lee, A. E. Clements, W. L. Murphy, and R. Vanderby. Immune modulation with primed mesenchymal stem cells delivered via biodegradable scaffold to repair an Achilles tendon segmental defect. J. Orthop. Res. 35(2):269, 2017. https://doi.org/10.1002/jor.23258 .Araque Monrós, M. C., J. Más Estellés, M. Monleón Pradas, L. Gil Santos, S. Gironés Bernabé. Process for obtaining a biodegradable prosthesis. Patent ES2392857, 2013.Araque-Monrós, M. C., T. C. Gamboa-Martínez, L. Gil Santos, S. Gironés-Bernabé, M. Monleón-Pradas, and J. Más-Estellés. New concept for a regenerative and resorbable prosthesis for tendon and ligament: physicochemical and biological characterization of PLA-braided biomaterial. J. Biomed. Mater. Res. A 101A:3228, 2013.Araque-Monrós, M. C., A. Vidaurre, L. Gil Santos, S. Gironés-Bernabé, M. Monleón-Pradas, and J. Más-Estellés. 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Biomaterials 30(35):6724, 2009.Dominkus, M., M. Sabeti, C. Toma, F. Abdolvahab, K. Trieb, and R. I. Kotz. Reconstructing the extensor apparatus with a new polyester ligament. Clin. Orthop. Relat. Res. 453:328, 2006.Freeman, J. W., M. D. Woods, and C. T. Laurencin. Tissue engineering of the anterior cruciate ligament using a braid-twist scaffold design. J. Biomech. 40(9):2029, 2007.García Cruz, D. M., J. L. Escobar Ivirico, M. Gomes, J. L. Gómez Ribelles, M. Salmerón Sánchez, R. L. Reis, and J. F. Mano. Chitosan microparticles as injectable scaffolds for tissue engineering. J. Tissue Eng. Regen. Med. 2(6):378, 2008.Gaspar, D., K. Spanoudes, C. Holladay, A. Pandit, and D. Zeugolis. Progress in cell-based therapies for tendon repair. Adv. Drug Deliv. Rev. 84:240, 2015.Iannace, S., A. Maffezzoli, G. Leo, and L. Nicolais. Influence of crystal and amorphous phase morphology on hydrolytic degradation of PLLA subjected to different processing conditions. Polymer 42(8):3799, 2001.Iwuagwu, F. C., and D. A. McGrouther. Early cellular response in tendon injury: the effect of loading. Plast. Reconstr. Surg. 102(6):2064, 1998.Jayasinghe, S. N., A. N. Qureshi, and P. A. M. Eagles. Electrohydrodynamic jet processing: an advanced electric-field-driven jetting phenomenon for processing living cells. Small 2:216, 2006.Kimura, Y., A. Hokugo, T. Takamoto, Y. Tabata, and H. Kurosawa. Regeneration of anterior cruciate ligament by biodegradable scaffold combined with local controlled release of basic fibroblast growth factor and collagen wrapping. Tissue Eng. Pt. C-Meth. 14(1):47, 2006.Krampera, M., G. Pizzolo, G. Aprili, and M. Franchini. Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone 39(4):678, 2006.Kuo, C., J. Marturano, and R. Tuan. Novel strategies in tendon and ligament tissue engineering: advanced biomaterials and regeneration motifs. Sports Med. Arthrosc. Rehabil. Ther. Technol. 2(1):20, 2010.Lao, L., H. Tan, Y. Wang, and C. Gao. Chitosan modified poly(l-lactide) microspheres as cell microcarriers for cartilage tissue engineering. Colloids Surf. B Biointerfaces 66(2):218, 2008.Lu, H. H., J. A. Cooper, S. Manuel, J. W. Freeman, M. A. Attawia, F. K. Ko, and C. T. Laurencin. Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies. Biomaterials 26(23):4805, 2005.Mengstreab, P. Y., L. S. Nair, and C. T. Laurencin. The past, present and future of ligament regenerative engineering. Regen. Med. 11(8):871, 2016.Molloy, T., Y. Wang, and G. A. C. Murrell. The roles of growth factors in tendon and ligament healing. Sports Med. 33(5):381, 2003.Murray, A. W., and M. F. Macnicol. 10–16 year results of Leeds–Keio anterior cruciate ligament reconstruction. Knee 11(1):9, 2004.Nelson, C. M., and C. S. Chen. Cell–cell signaling by direct contact increases cell proliferation via a PI3K-dependent signal. FEBS Lett. 514(2–3):238, 2002.Nixon, A. J., A. E. Watts, and L. V. Schnabel. Cell- and gene-based approaches to tendon regeneration. J. Shoulder Elbow Surg. 21:278, 2012.Nurettin Sahiner, X. J. One-step synthesis of hyaluronic acid-based (sub)micron hydrogel particles: process optimization and preliminary characterization. Turk. J. Chem. 32:397, 2008.Ortuño-Lizarán, I., G. Vilariño-Feltrer, C. Martínez-Ramos, M. Monleón Pradas, and A. Vallés-Lluch. Influence of synthesis parameters on hyaluronic acid hydrogels intended as nerve conduits. Biofabrication 8(4):1–12, 2016. https://doi.org/10.1088/1758-5090/8/4/045011 .Pen-hsiu, G. C., H. Hsiang-Yi, and T. Hsiao-Yun. Electrospun microcrimped fibers with nonlinear mechanical properties enhance ligament fibroblast phenotype. Biofabrication 6(3):035008, 2014. https://doi.org/10.1088/1758-5082/6/3/035008 .Porzionato, A., E. Stocco, S. Barbon, F. Grandi, V. Macchi, and R. De Caro. Tissue-engineered grafts from human decellularized extracelular matrices: a systematic review and future perspectives. Int. J. Mol. 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    A standardised approach to the biomechanical evaluation of tracheal grafts

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    [EN] The ideal tracheal substitute must have biomechanical properties comparable to the native trachea, but currently there is no standardised approach to evaluating these properties. Here we propose a novel method for evaluating and comparing the properties of tracheal substitutes, thus systematising both measurement and data curation. This system was tested by comparing native rabbit tracheas to frozen and decellularised specimens and determining the histological characteristics of those specimens. We performed radial compression tests on the anteroposterior tracheal axis and longitudinal axial tensile tests with the specimens anastomosed to the jaw connected to a measuring system. All calculations and results were adjusted according to tracheal size, always using variables relative to the tracheal dimensions, thus permitting comparison of different sized organs. The biomechanical properties of the decellularised specimens were only slightly reduced compared to controls and significant in regard to the maximum stress withstood in the longitudinal axis (-0.246 MPa CI [-0.248, -0.145] MPa) and the energy stored per volume unit (-0.124 mJ & BULL;mm(-3) CI [-0.195, -0.055] mJ & BULL;mm(-3)). The proposed method is suitable for the systematic characterisation of the biomechanical properties of different tracheal substitutes, regardless of the size or nature of the substitute, thus allowing for direct comparisons.This research was funded by the 2018 Spanish Society of Thoracic Surgery grant to National Multicentric Study [Number 180101 to N.J.M.-H.] and [PI16-01315 to M.M.-R.] from the Instituto de Salud Carlos III. CIBERER is funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and the Instituto de Salud Carlos III, with assistance from the European Regional Development Fund.Martínez-Hernández, NJ.; Más Estellés, J.; Milián-Medina, L.; Martínez-Ramos, C.; Cerón-Navarro, J.; Galbis-Caravajal, J.; Roig-Bataller, A.... (2021). A standardised approach to the biomechanical evaluation of tracheal grafts. Biomolecules. 11(10):1-12. https://doi.org/10.3390/biom11101461S112111

    Optimization of a decellularized protocol of porcine tracheas. Long-term effects of cryopreservation. A histological study

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    [EN] Objective: The aim of this study was to optimize a decellularization protocol in the trachea of Sus scrofa domestica (pig) as well as to study the effects of long-term cryopreservation on the extracellular matrix of decellularized tracheas. Methods: Porcine tracheas were decellularized using Triton X-100, SDC, and SDS alone or in combination. The effect of these detergents on the extracellular matrix characteristics of decellularized porcine tracheas was evaluated at the histological, biomechanical, and biocompatibility level. Morphometric approaches were used to estimate the effect of detergents on the collagen and elastic fibers content as well as on the removal of chondrocytes from decellularized organs. Moreover, the long-term structural, ultrastructural, and biomechanical effect of cryopreservation of decellularized tracheas were also estimated. Results: Two percent SDS was the most effective detergent tested concerning cell removal and preservation of the histological and biomechanical properties of the tracheal wall. However, long-term cryopreservation had no an appreciable effect on the structure, ultrastructure, and biomechanics of decellularized tracheal rings. Conclusion: The results presented here reinforce the use of SDS as a valuable decellularizing agent for porcine tracheas. Furthermore, a cryogenic preservation protocol is described, which has minimal impact on the histological and biomechanical properties of decellularized porcine tracheas.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants MAT2016-76039-C4-2-R (MST) and PID2019-106099RB-C42 (MM) from the Ministry of Economy and Competitiveness of the Spanish Government, by grant PI16-01315 from the ISCIII (Ministerio de Ciencia, Innovacion y Universidades, Spain), and by grant PROMETEO/2020/069 (CC) from the local government of the Comunitat Valenciana (Spain), CIBER-BBN and CIBERER are funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III, with assistance from the European Regional Development Fund.Milián, L.; Sancho-Tello, M.; Roig-Soriano, J.; Foschini, G.; Martínez-Hernández, NJ.; Más Estellés, J.; Ruiz-Sauri, A.... (2021). Optimization of a decellularized protocol of porcine tracheas. Long-term effects of cryopreservation. A histological study. The International Journal of Artificial Organs. 44(12):998-1012. https://doi.org/10.1177/03913988211008912S9981012441

    Hydrolytic and enzymatic degradation of a poly(å-caprolactone) network

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    “NOTICE: this is the author’s version of a work that was accepted for publication in Polymer Degradation and Stability. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Polymer Degradation and Stability, [Volume 97, Issue 8, August 2012, Pages 1241–1248] DOI 10.1016/j.polymdegradstab.2012.05.038Long-term hydrolytic and enzymatic degradation profiles of poly(å-caprolactone) (PCL) networks were obtained. The hydrolytic degradation studies were performed in water and phosphate buffer solution (PBS) for 65 weeks. In this case, the degradation rate of PCL networks was faster than previous results in the literature on linear PCL, reaching a weight loss of around 20% in 60 weeks after immersing the samples either in water or in PBS conditions. The enzymatic degradation rate in Pseudomonas Lipase for 14 weeks was also studied, with the conclusion that the degradation profile of PCL networks is lower than for linear PCL, also reaching a 20% weight loss. The weight lost, degree of swelling, and calorimetric and mechanical properties were obtained as a function of degradation time. Furthermore, the morphological changes in the samples were studied carefully through electron microscopy and crystal size through X-ray diffraction. The changes in some properties over the degradation period such as crystallinity, crystal size and Young¿s modulus were smaller in the case of enzymatic studies, highlighting differences in the degradation mechanism in the two studies, hydrolytic and enzymatic.The authors would like to acknowledge the support of the Spanish Ministry of Science and Education through the DPI2010-20399-004-03 project. JM Meseguer-Duenas and A Vidaurre also would like to acknowledge the support of the CIBER-BBN, an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The translation of this paper was funded by the Universidad Politecnica de Valencia, SpainCastilla Cortázar, MIC.; Más Estellés, J.; Meseguer Dueñas, JM.; Escobar Ivirico, JL.; Marí Soucase, B.; Vidaurre, A. (2012). Hydrolytic and enzymatic degradation of a poly(å-caprolactone) network. Polymer Degradation and Stability. 97(8):1241-1248. https://doi.org/10.1016/j.polymdegradstab.2012.05.038S1241124897

    Análisis del rendimiento académico en los estudios de informática de la Universidad Politécnica de Valencia aplicando técnicas de minería de datos

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    En este trabajo presentamos un análisis del rendimiento académico de los alumnos de nuevo ingreso en la titulación de Ingeniería Técnica en Informática de Sistemas de la Universidad Politécnica de Valencia (UPV) a lo largo de tres cursos, aunque también se ha trabajado con las titulaciones de Ingeniería Técnica en Informática de Gestión y de Ingeniería Informática. Este análisis relaciona el rendimiento con las características socioeconómicas y académicas de los alumnos, que se obtienen en el momento de su matrícula, y que se recogen en la base de datos de la universidad. Hemos definido un indicador del rendimiento para cada alumno, teniendo en cuenta las calificaciones obtenidas y las convocatorias utilizadas. Para el estudio utilizamos técnicas de minería de datos, que pretenden determinar qué nivel de condicionamiento existe entre dicho rendimiento y características como el nivel de conocimientos de entrada del alumno, su contexto geográfico y sociocultural, etc… Esto proporciona una herramienta importante para la acción tutorial, que puede apoyarse en las predicciones de los modelos que se obtienen para encauzar sus recomendaciones y encuadrar las expectativas y el esfuerzo necesario para cada alumno, lógicamente dentro de la cautela habitual a la hora de tratar modelos inferidos a partir de datos.Universidad Politécnica de Valencia, a través del programa PACE

    Polymer scaffolds with interconnected spherical pores and controlled architecture for tissue engineering: fabrication, mechanical properties, and finite element modeling

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    A method is proposed in which the geometric properties of 3D scaffolds with application in tissue engineering can be tailored: porosity, pore size, and interconnection throat size. The architecture of the fabricated scaffolds is analyzed by scanning electron microscopy. The mechanical properties of these structures are discussed on the basis of compression stress–strain measurements. Moreover, the mechanical properties of the scaffolds are estimated by means of finite element modeling (FEM) in which the compression stress–strain test is simulated on an ideal structure based on the crystalline face centered cubic system. The elastic properties of the constructs are explained on the basis of the FEM model that supports the main mechanical conclusion of the experimental results: the compressive modulus in the first linear region does not depend on the geometric characteristics of the pore (pore size, interconnection throat size) but only on the total porosity of the scaffold

    Microcomputed tomography and microfinite element modeling for evaluating polymer scaffolds architecture and their mechanical properties

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    Detailed knowledge of the porous architecture of synthetic scaffolds for tissue engineering, their mechanical properties, and their interrelationship was obtained in a nondestructive manner. Image analysis of microcomputed tomography (μCT) sections of different scaffolds was done. The three-dimensional (3D) reconstruction of the scaffold allows one to quantify scaffold porosity, including pore size, pore distribution, and struts' thickness. The porous morphology and porosity as calculated from μCT by image analysis agrees with that obtained experimentally by scanning electron microscopy and physically measured porosity, respectively. Furthermore, the mechanical properties of the scaffold were evaluated by making use of finite element modeling (FEM) in which the compression stress–strain test is simulated on the 3D structure reconstructed from the μCT sections. Elastic modulus as calculated from FEM is in agreement with those obtained from the stress–strain experimental test. The method was applied on qualitatively different porous structures (interconnected channels and spheres) with different chemical compositions (that lead to different elastic modulus of the base material) suitable for tissue regeneration. The elastic properties of the constructs are explained on the basis of the FEM model that supports the main mechanical conclusion of the experimental results: the elastic modulus does not depend on the geometric characteristics of the pore (pore size, interconnection throat size) but only on the total porosity of the scaffold

    Digital design of scaffold for mandibular defect repair based on tissue engineering*

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    Mandibular defect occurs more frequently in recent years, and clinical repair operations via bone transplantation are difficult to be further improved due to some intrinsic flaws. Tissue engineering, which is a hot research field of biomedical engineering, provides a new direction for mandibular defect repair. As the basis and key part of tissue engineering, scaffolds have been widely and deeply studied in regards to the basic theory, as well as the principle of biomaterial, structure, design, and fabrication method. However, little research is targeted at tissue regeneration for clinic repair operations. Since mandibular bone has a special structure, rather than uniform and regular structure in existing studies, a methodology based on tissue engineering is proposed for mandibular defect repair in this paper. Key steps regarding scaffold digital design, such as external shape design and internal microstructure design directly based on triangular meshes are discussed in detail. By analyzing the theoretical model and the measured data from the test parts fabricated by rapid prototyping, the feasibility and effectiveness of the proposed methodology are properly verified. More works about mechanical and biological improvements need to be done to promote its clinical application in future
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