Biomaterials for Cardiac Tissue Engineering

Semiotics / semiolog

Chapter Biomaterials for Cardiac Tissue Engineering

Semiotics / semiolog

BDNF-Gene Transfected Schwann Cell-Assisted Axonal Extension and Sprouting on New PLA-PPy Microfiber Substrates

[EN] The work here reported analyzes the effect of increased efficiency of brainderived neurotrophic factor (BDNF) production by electroporated Schwann cells (SCs) on the axonal extension in a coculture system on a biomaterial platform that can be of interest for the treatment of injuries of the nervous system, both central and peripheral. Rat SCs are electrotransfected with a plasmid coding for the BDNF protein in order to achieve an increased expression and release of this protein into the culture medium of the cells, performing the best balance between the level of transfection and the number of living cells. Gene-transfected SCs show an about 100-fold increase in the release of BDNF into the culture medium, compared to nonelectroporated SCs. Cocultivation of electroporated SCs with rat dorsal root ganglia (DRG) is performed on highly aligned substrates of polylactic acid (PLA) microfibers coated with the electroconductive polymer polypyrrol (PPy). The coculture of DRG with electrotransfected SCs increase both the axonal extension and the axonal sprouting from DRG neurons compared to the coculture of DRG with nonelectroporated SCs. Therefore, the use of PLA¿PPy highly aligned microfiber substrates preseeded with electrotransfected SCs with an increased BDNF secretion is capable of both guiding and accelerating axonal growth.The authors acknowledge financial support from the Spanish Government's State Research Agency (AEI) through projects DPI2015-72863-EXP and RTI2018-095872-B-C22/ERDF. F.G.R. acknowledges the scholarship FPU16/01833 and the short stay mobility aid EST18/00524 of the Spanish Ministry of Universities. F.G.R. also acknowledges the hosting at the Vectorology and Anti-cancer Therapies Centre (UMR 8203 CNRS). The authors thank the Electron Microscopy Service at the UPV, where the FESEM images were obtained.Gisbert-Roca, F.; André, FM.; Más Estellés, J.; Monleón Pradas, M.; Mir, LM.; Martínez-Ramos, C. (2021). BDNF-Gene Transfected Schwann Cell-Assisted Axonal Extension and Sprouting on New PLA-PPy Microfiber Substrates. Macromolecular Bioscience (Online). 21(5):1-13. https://doi.org/10.1002/mabi.202000391S11321

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

[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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Raxworthy, G. P. Riley, and A. Saeed. A clinical, biological, and biomaterials perspective into tendon injuries and regeneration. Tissue Eng. Pt. B 23(1):44, 2017.Wei, X. L., L. Lin, Y. Hou, X. Fu, J. Y. Zhang, Z. B. Mao, and C. L. Yu. Construction of recombinant adenovirus co-expression vector carrying the human transforming growth factor-beta1 and vascular endothelial growth factor genes and its effect on anterior cruciate ligament fibroblasts. Chin. Med. J. 121(15):1426, 2008.Workman, V. L., L. B. Tezera, P. T. Elkington, and S. N. Jayasinghe. Controlled generation of microspheres incorporating extracellular matrix fibrils for three-dimensional cell culture. Adv. Funct. Mater. 24:2648, 2014.Wu, S., Y. Wang, P. N. Streubel, and B. Duan. Living nanofiber yarn-based woven biotextiles for tendon tissue engineering using cell tri-culture and mechanical stimulation. Acta Biomater. 62:102, 2005

Combined application of polyacrylate scaffold and lipoic acid treatment promotes neural tissue reparation after brain injury

[EN] Primary objective: The aim of this study was to investigate the reparative potential of a polymeric scaffold designed for brain tissue repair in combination with lipoic acid. Research design: Histological, cytological and structural analysis of a combined treatment after a brain cryo-injury model in rats. Methods and procedures: Adult Wistar rats were subjected to cryogenic brain injury. A channelled-porous scaffold of ethyl acrylate and hydroxyethylacrylate, p(EA-co-HEA) was grafted into cerebral penumbra alone or combined with intraperitoneal LA administration. Histological and cytological evaluation was performed after 15 and 60 days and structural magnetic resonance (MRI) assessment was performed at 2 and 6 months after the surgery. Main outcomes and results: The scaffold was suitable for the establishment of different cellular types. The results obtained suggest that this strategy promotes blood vessels formation, decreased microglial response and neuron migration, particularly when LA was administrated. Conclusions: These evidences demonstrated that the combination of a channelled polymer scaffold with LA administration may represent a potential treatment for neural tissue repair after brain injury.The authors report no conflicts of interest. JMSL acknowledges funding through Programa de Ayudas a la Investigación Científica Universidad CEU-Cardenal Herrera (PRCEU-UCH 34/12), PRCEU-UCH 38/10 and programa ayudas a grupos consolidados 2014-15). CMR and MMP acknowledge financing through projects MAT2011-28791-C03-02 and ERA-NET NEURON project PRI-PIMNEU-2011-1372.Rocamonde, B.; Paradells, S.; Garcia Esparza, MA.; Sanchez Vives, M.; Sauro, S.; Martínez-Ramos, C.; Monleón Pradas, M.... (2016). Combined application of polyacrylate scaffold and lipoic acid treatment promotes neural tissue reparation after brain injury. 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Electrospun adherent-antiadherent bilayered membranes based on cross-linked hyaluronic acid for advanced tissue engineering applications

[EN] A procedure to obtain electrospun mats of hyaluronic acid (HA) stable in aqueous media in one single step has been developed. It consists in combining an HA solution with a divinyl sulfone one as cross-linker in a three-way valve to immediately electroblow their mixture. Membranes obtained with this method, after sterilization and conditioning, are ready to use in cell culture without need of any additional posttreatment. HA nanofibers are deposited onto previously electrospun poly(L-lactic acid) (PLLA) mats in order to obtain stably joined bilayered membranes with an adherent face and the opposite face non-adherent, despite their different hydrophilicity and mechanical properties. These bilayered HA/PLLA membranes may be of use, for example, in applications seeking to transplant cells on a tissue surface and keep them protected from the environment: the PLLA nanofiber face is cell friendly and promotes cell attachment and spreading and can thus be used as a cell supply vehicle,. while the HA face hinders cell adhesion and thus may prevent post-surgical adherences, a major issue in many surgeries. (C) 2013 Elsevier B.V. All rights reserved.The authors acknowledge the financing through project FP7 NMP3-SL-2009-229239 "Regeneration of Cardiac Tissue Assisted by Bioactive Implants" (RECATABI).Arnal Pastor, MP.; Martínez Ramos, C.; Perez Garnes, M.; Monleón Pradas, M.; Vallés Lluch, A. (2013). Electrospun adherent-antiadherent bilayered membranes based on cross-linked hyaluronic acid for advanced tissue engineering applications. Materials Science and Engineering: C. 33(7):4086-4093. https://doi.org/10.1016/j.msec.2013.05.058S4086409333

Thermal analysis of water in reinforced plasma-polymerised poly(2-hydroxyethyl acrylate) hydrogels

Thermal analysis of water in reinforce hydrogels of plasma-polymerised poly(2-hydroxyethyl acrylate) (plPHEA) grafted onto macroporous poly(methyl methacrylate) (PMMA) are explained in a simple thermodynamic framework based on the transition diagram. Water in bulk PHEA was also analysed for comparison with plPHEA. These two hydrophilic polymers were prepared with a broad range of water mass fractions from 0.05 to 0.72. Thermal transition diagrams of water/PHEA and water/plPHEA were determined showing less undercooling of water crystallisation in plPHEA than in PHEA. Kinetics of water crystallisation for high and low water contents were studied in both hydrophilic systems following several thermal treatments. Water crystallises much faster in plPHEA than in PHEA for high water contents. For low water contents, crystallisation becomes possible holding at 30 degrees C for some time due to water segregation in both PHEA systems. However, much less water is segregated from the water/plPHEA mixture due to the influence of the hydrophobic component.This work was supported by a Marie Curie Host Fellowship and by the Spanish Science and Technology Ministry through the MAT2001-2678-C02-01 and MAT2002-04239-C03-03 projects. CIBER-BBN is 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.Serrano Aroca, Á.; Monleón Pradas, M.; Gómez Ribelles, JL.; Rault, J. (2015). Thermal analysis of water in reinforced plasma-polymerised poly(2-hydroxyethyl acrylate) hydrogels. European Polymer Journal. 72:523-534. https://doi.org/10.1016/j.eurpolymj.2015.05.032S5235347

Channeled polymeric scaffolds with polypeptide gel filling for lengthwise guidance of neural cells

CNS damages are often irreversible since neurons of the central nervous system are unable to regenerate after an injury. As a new strategy within the nervous system tissue engineering, multifunctional systems based on two different biomaterials to support axonal guidance in damaged connective tracts have been developed herein. These systems are composed of a channeled scaffold made of ethyl acrylate and hydroxyethyl acrylate copolymer, P(EA-co-HEA), with parallel tubular micropores, combined with an injectable and in situ gelable self-assembling polypeptide (RAD16-I) as pores filler. The polymer scaffold is intended to provide a three-dimensional context for axon growth; subsequently, its morphology and physicochemical parameters have been determined by scanning electron microscopy, density measurements and compression tests. Besides, the hydrogel acts as a cell-friendly nanoenvironment while it creates a gradient of bioactive molecules (nerve growth factor, NGF) along the scaffolds channels; the chemotactic effect of NGF has been evaluated by a quantitative ELISA assay. These multifunctional systems have shown ability to keep circulating NGF, as well as proper short-term in vitro biological response with glial cells and neural progenitors.The authors acknowledge funding through the Spanish Ministerio de Ciencia e Innovacion (MAT2011-28791-C03-02 and -03). Dr. J.M. Garcia Verdugo (Department of Comparative Neurobiology, Cavanilles Institute of Biodiversity and Evolutive Biology, Universitat de Valencia) is thanked for kindly providing the cells employed in this work.Conejero García, Á.; Vilarino-Feltrer, G.; Martínez Ramos, C.; Monleón Pradas, M.; Vallés Lluch, A. (2015). Channeled polymeric scaffolds with polypeptide gel filling for lengthwise guidance of neural cells. European Polymer Journal. 70:331-341. doi:10.1016/j.eurpolymj.2015.07.033S3313417

Interaction between acrylic substrates and RAD16-I peptide in its self-assembling

[EN] Self-assembling peptides (SAP) are widely used as scaffolds themselves, and recently as fillers of microporous scaffolds, where the former provides a cell-friendly nanoenvironment and the latter improves its mechanical properties. The characterization of the interaction between these short peptides and the scaffold material is crucial to assess the potential of such a combined system. In this work, the interaction between poly(ethyl acrylate) (PEA) and 90/10 ethyl acrylate-acrylic acid copolymer P(EAcoAAc) with the SAP RAD16-I has been followed using a bidimensional simplified model. By means of the techniques of choice (congo red staining, atomic force microscopy (AFM), and contact angle measurements) the interaction and self-assembly of the peptide has proven to be very sensitive to the wettability and electro-negativity of the polymeric substrate.The authors acknowledge funding through the European Commission FP7 project RECATABI (NMP3-SL-2009-229239), and from the Spanish Ministerio de Ciencia e Innovacion through projects MAT2011-28791-C03-02 and -03. This work was also supported by the Spanish Ministerio de Educacion through M. Arnal-Pastor FPU 2009-1870 grant. The authors acknowledge the assistance and advice of Electron Microscopy Service of the UPV.Arnal Pastor, MP.; González-Mora, D.; García-Torres, F.; Monleón Pradas, M.; Vallés Lluch, A. (2016). Interaction between acrylic substrates and RAD16-I peptide in its self-assembling. 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Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

[EN] Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-l-lactide acid fibers in their lumen were fabricated. Rat Schwann cells were seeded within the conduits and cultured for 10days. The conduits possessed a three-layered porous structure that impeded the leakage of the cells seeded in their interior and made them impervious to cell invasion from the exterior, while allowing free transport of nutrients and other molecules needed for cell survival. The channel's surface acted as a template for the formation of a cylindrical sheath-like tapestry of Schwann cells continuously spanning the whole length of the lumen. Schwann-cell tubes having a diameter of around 0.5mm and variable lengths can thus be generated. This structure is not found in nature and represents a truly engineered tissue, the outcome of the specific cell-material interactions. The conduits might be useful to sustain and protect cells for transplantation, and the biohybrids here described, together with neuronal precursors, might be of help in building bridges across significant distances in the central and peripheral nervous system.The authors acknowledge financing through projects MAT2011-28791-C03-02 and 03, and ERA-NET NEURON project PRI-PIMNEU-2011-1372. We thank the Cytomics Core Facility at Principe Felipe Research Center (CIPF, Valencia, Spain) for their support and advice in flow cytometry experiments, and the Electron Microscopy Service at the UPV, where the SEM images were obtained. The authors thankfully acknowledge the reviewers' comments, which have helped to improve the clarity of the paper's presentation.Vilariño Feltrer, G.; Martínez Ramos, C.; Monleon De La Fuente, A.; Vallés Lluch, A.; Moratal Pérez, D.; Barcia Albacar, JA.; Monleón Pradas, M. (2016). Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity. Acta Biomaterialia. 30:199-211. https://doi.org/10.1016/j.actbio.2015.10.040S1992113