Fin whales as bioindicators of multi-decadal change in carbon and oxygen stable isotope shifts in the North Atlantic

Global changes, and particularly the massive release of CO2 to the atmosphere and subsequent global warming, have altered the baselines of carbon and oxygen stable isotopic ratios. Temporal shifts in these baselines can be advantageously monitored through cetacean skin samples because these animals are highly mobile and therefore integrate in their tissues the heterogeneity of local environmental signals. In this study, we examine variation of delta C-13 and delta O-18 values in the skin of fin whales sampled over three decades in two different North Atlantic feeding grounds: west Iceland and northwest Spain. These locations are situated about 2700 km apart and thus represent a wide latitudinal range within the North Atlantic Ocean. The delta C-13 decrease in both areas is attributed to the burning of fossil fuels and increased deforestation worldwide, the so-called Suess effect. The dissimilarity in the magnitude of the shift between the two areas is coincidental with previous information on local shifts and lies within the ranges of variation observed. delta O-18 values experienced a minimal, yet significant change in fin whales from W Iceland (a decline of - 0.44 parts per thousand between 1986 and 2013) but not in those from NW Spain. This is in concordance with a higher rise in temperatures in the former area than in the latter. The study validates the use of cetacean skin to monitor temporal and geographical shifts in stable isotopic values and alerts that, when applying this tool to ecological research, comparisons between sample sets should take into account temporal and latitudinal scales

Local deformation in a hydrogel induced by an external magnetic field

The aim of this study is to prove the feasibility of a system able to apply local mechanical loading on cells seeded in a hydrogel for tissue engineering applications. This experimental study is based on a previously developed artificial cartilage model with different concentrations of poly(vinyl alcohol) (PVA) that simulates the cartilage extracellular matrix (ECM). Poly(l-lactic acid) (PLLA) microspheres with dispersed magnetic nanoparticles (MNPs) were produced with an emulsion method. These microspheres were embedded in aqueous PVA solutions with varying concentration to resemble increased viscosity of growing tissue during regeneration. The ability to induce a local deformation in the ECM was assessed by applying a steady or an oscillatory magnetic field gradient to different PVA solutions containing the magnetic microparticles, similarly as in ferrogels. PLLA microparticle motion was recorded, and the images were analyzed. Besides, PVA gels and PLLA microparticles were introduced into the pores of a polycaprolactone scaffold, and the microparticle distribution and the mechanical properties of the construct were evaluated. The results of this experimental model show that the dispersion of PLLA microparticles containing MNPs, together with cells in a supporting gel, will allow applying local mechanical stimuli to cells during tissue regeneration. This local stimulation can have a positive effect on the differentiation of seeded cells and improve tissue regeneration.The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the MAT2013-46467-C4-1-R project, including the Feder funds. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors thank "Servicio de Microscopia Electronica" of Universitat Politecnica de Valencia for their invaluable help. The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain.Vikingsson, L.; Vinals Guitart, Á.; Valera Martínez, A.; Riera Guasp, J.; Vidaurre Garayo, AJ.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2016). Local deformation in a hydrogel induced by an external magnetic field. Journal of Materials Science. 51(22):9979-9990. https://doi.org/10.1007/s10853-016-0226-8S997999905122Eyre D (2002) Collagen of articular cartilage. Arthritis Res 4:30–35Roughley PJ, Lee ER (1994) Cartilage proteoglycans: structure and potential functions. Microsc Res Tech 28:385–397Gillard GC, Reilly HC, Bell-Booth PG, Flint MH (1979) The influence of mechanical forces on the glycosaminoglycan content of the rabbit flexor digitorum profundus tendon. Connect Tissue Res 7:37–46Quinn TM, Grodzinsky AJ, Buschmann MD, Kim YJ, Hunziker EB (1998) Mechanical compression alters proteoglycan deposition and matrix deformation around individual cells in cartilage explants. J Cell Sci 111:573–583Banes AJ, Tsuzaki M, Yamamoto J, Fischer T, Brigman B, Brown T, Miller L (1995) Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem Cell Biol 73:349–365Appelman T, Mizrahi J, Elisseeff J, Seliktar D (2011) The influence of biological motifs and dynamic mechanical stimulation in hydrogel scaffold systems on the phenotype of chondrocytes. Biomaterials 32:1508–1516Mow VC, Ratcliffe A, Poole AR (1992) Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. Biomaterials 13:67–97Mow VC, Huiskes R (2005) Basic orthopaedic biomechanics and mechano-biology. Lippincott Williams and Wilkins, PhiladelphiaBrady MA, Waldman SD, Ethier CR (2015) The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response. Tissue Eng Part B Rev 21:1–19Valhmu WB, Stazzone EJ, Bachrach NM, Saed-Nejad F, Fischer SG, Mow VC, Ratcliffe A (1998) Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch Biochem Biophys 353:29–36Ingber DE (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Ann Rev Physiol 59:575–599Khan S, Sheetz MP (1997) Force effects on biochemical kinetics. Ann Rev Biochem 66:785–805Hutmacher DW (2000) Scaffolds in tissue engineering bone and cartilage. Biomaterials 21:2529–2543Crick FHC, Hughes AFW (1950) The physical properties of cytoplasm: a study by means of the magnetic particle method. Exp Cell Res 1:37–80Valberg PA, Albertini DF (1985) Cytoplasmic motions, rheology, and structure probed by a novel magnetic particle method. J Cell Biol 101:130–140Valberg PA, Feldman HA (1987) Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity. Biophys J 52:551–561Wang N, Ingber DE (1995) Probing transmembrane mechanical coupling and cytomechanics using magnetic twisting cytometry. Biochem Cell Biol 73:327–335Pommerenke H, Schreiber E, Durr F, Nebe B, Hahnel C, Moller W, Rychly J (1996) Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response. Eur J Cell Biol 70:157–164Bausch AR, Hellerer U, Essler M, Aepfelbacher M, Sackmann E (2001) Rapid stiffening of integrin receptor-actin linkages in endothelial cells stimulated with thrombin: a magnetic bead microrheology study. Biophys J 80:2649–2657Li L, Yang G, Li J, Ding S, Zhou S (2014) Cell behaviors on magnetic electrospun poly-d, l-lactide nano fibers. Mater Sci Eng, C 34:252–261Fuhrer R, Hofmann S, Hild N, Vetsch JR, Herrmann IK, Grass RN, Stark WJ (2013) Pressureless mechanical induction of stem cell differentiation is dose and frequency dependent. PLoS One 8:e81362Cezar CA, Roche ET, Vandenburgh HH, Duda GN, Walsh CJ, Mooney DJ (2016) Biologic-free mechanically induced muscle regeneration. Proc Natl Acad Sci USA 113:1534–1539Vikingsson L, Gallego Ferrer G, Gómez-Tejedor JA, Gómez Ribelles JL (2014) An in vitro experimental model to predict the mechanical behaviour of macroporous scaffolds implanted in articular cartilage. J Mech Behav Biomed Mater 32:125–131Vikingsson L, Gomez-Tejedor JA, Gallego Ferrer G, Gomez Ribelles JL (2015) An experimental fatigue study of a porous scaffold for the regeneration of articular cartilage. J Biomech 48:1310–1317Vikingsson L, Claessens B, Gómez-Tejedor JA, Gallego Ferrer G, Gómez Ribelles JL (2015) Relationship between micro-porosity, water permeability and mechanical behavior in scaffolds for cartilage engineering. J Mech Behav Biomed Mater 48:60–69Li F, Su YL, Shi DF, Wang CT (2010) Comparison of human articular cartilage and polyvinyl alcohol hydrogel as artificial cartilage in microstructure analysis and unconfined compression. Adv Mater Res Trans Tech Publ 87:188–193Grant C, Twigg P, Egan A, Moody A, Eagland D, Crowther N, Britland S (2006) Poly(vinyl alcohol) hydrogel as a biocompatible viscoelastic mimetic for articular cartilage. Biotechnol Prog 22:1400–1406Weeber R, Kantorovich S, Holm C (2015) Ferrogels cross-linked by magnetic nanoparticles—Deformation mechanisms in two and three dimensions studied by means of computer simulations. J Magn Magn Mater 383:262–266Lebourg M, Suay Antón J, Gómez Ribelles JL (2008) Porous membranes of PLLA–PCL blend for tissue engineering applications. Eur Polym J 44:2207–2218Santamaría VA, Deplaine H, Mariggió D, Villanueva-Molines AR, García-Aznar JM, Gómez Ribelles JL, Doblaré M, Gallego Ferrer G, Ochoa I (2012) Influence of the macro and micro-porous structure on the mechanical behavior of poly (l-lactic acid) scaffolds. J Non Cryst Solids 358:3141–3149Panadero JA, Vikingsson L, Gomez Ribelles JL, Lanceros-Mendez S, Sencadas V (2015) In vitro mechanical fatigue behaviour of poly-ε-caprolactone macroporous scaffolds for cartilage tissue engineering. Influence of pore filling by a poly(vinyl alcohol) gel. J Biomed Mater Res Part B Appl Biomater 103:1037–1043Hassan CM, Peppas NA (2000) Structure and applications of poly(vinyl alcohol) hydrogels produced by conventional crosslinking or by freezing/thawing methods. Adv Polym Sci 153:37–65Labet M, Thielemans W (2009) Synthesis of polycaprolactone: a review. Chem Soc Rev 38:3484–3504Mano JF, Gómez Ribelles JL, Alves NM, Salmerón Sanchez M (2005) Glass transition dynamics and structural relaxation of PLLA studied by DSC: influence of crystallinity. Polymer 46:8258–8265Eckstein F, Lemberger B, Gratzke C, Hudelmaier M, Glaser C, Englmeier KH, Reiser M (2005) In vivo cartilage deformation after different types of activity and its dependence on physical training status. Ann Rheum Dis 64:291–295Garlotta D (2001) A literature review of poly(lactic acid). J Polym Eng 9:63–84Kovacs AJ, Aklonis JJ, Hutchinson JM, Ramos AR (1979) Isobaric volume and enthalpy recovery of glasses. II. A transparent multiparameter theory. J Polym Sci Polym Phys 17:1097–1162Hernández F, Molina Mateo J, Romero Colomer F, Salmerón Sánchez M, Gómez Ribelles JL, Mano J (2005) Influence of low-temperature nucleation on the crystallization process of poly(l-lactide). Biomacromolecules 6:3291–3299Wang Y, Gómez Ribelles JL, Salmerón Sánchez M, Mano JF (2005) Morphological contribution to glass transition in poly(l-lactic acid). Macromolecules 38:4712–4718Salmerón Sánchez M, Vincent BM, Vanden Poel G, Gómez-Ribelles JL (2007) Effect of the cooling rate on the nucleation kinetics of poly(l-lactic acid) and its influence on morphology. Macromolecules 40:7989–7997Nobuyuki O (1975) A threshold selection method from gray-level histograms. Automatica 11:23–2

Prediction of the in vivo mechanical behavior of biointegrable acrylic macroporous scaffolds

[EN] This study examines a biocompatible scaffold series of random copolymer networks P(EA-HEA) made of Ethyl Acrylate, EA, and 2-Hydroxyl Ethyl Acrylate, HEA. The P(EA-HEA) scaffolds have been synthesized with varying crosslinking density and filled with a Poly(Vinyl Alcohol), PVA, to mimic the growing cartilaginous tissue during tissue repair. In cartilage regeneration the scaffold needs to have sufficient mechanical properties to sustain the compression in the joint and, at the same time, transmit mechanical signals to the cells for chondrogenic differentiation. Mechanical tests show that the elastic modulus increases with increasing crosslinking density of P(EA-HEA) scaffolds. The water plays an important role in the mechanical behavior of the scaffold, but highly depends on the crosslinking density of the proper polymer. Furthermore, when the scaffold with hydrogel is tested it can be seen that the modulus increases with increasing hydrogel density. Even so, the mechanical properties are inferior than those of the scaffolds with water filling the pores. The hydrogel inside the pores of the scaffolds facilitates the expulsion of water during compression and lowers the mechanical modulus of the scaffold. The P(EA-HEA) with PVA shows to be a good artificial cartilage model with mechanical properties close to native articular cartilage.This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2013-46467-C4-1-R (including the FEDER financial support). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors acknowledge the assistance and advice of Electron Microscopy Service of the UPV.Vikingsson, L.; Antolinos Turpín, CM.; Gómez-Tejedor, JA.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2016). Prediction of the in vivo mechanical behavior of biointegrable acrylic macroporous scaffolds. Materials Science and Engineering: C. 61:651-658. https://doi.org/10.1016/j.msec.2015.12.068S6516586

Mitochondrial genomics reveals the evolutionary history of the porpoises (Phocoenidae) across the speciation continuum

Historical variation in food resources is expected to be a major driver of cetacean evolution, especially for the smallest species like porpoises. Despite major conservation issues among porpoise species (e.g., vaquita and finless), their evolutionary history remains understudied. Here, we reconstructed their evolutionary history across the speciation continuum. Phylogenetic analyses of 63 mitochondrial genomes suggest that porpoises radiated during the deep environmental changes of the Pliocene. However, all intra-specific subdivisions were shaped during the Quaternary glaciations. We observed analogous evolutionary patterns in both hemispheres associated with convergent evolution to coastal versus oceanic environments. This suggests that similar mechanisms are driving species diversification in northern (harbor and Dall's) and southern species (spectacled and Burmeister's). In contrast to previous studies, spectacled and Burmeister's porpoises shared a more recent common ancestor than with the vaquita that diverged from southern species during the Pliocene. The low genetic diversity observed in the vaquita carried signatures of a very low population size since the last 5,000 years. Cryptic lineages within Dall's, spectacled and Pacific harbor porpoises suggest a richer evolutionary history than previously suspected. These results provide a new perspective on the mechanisms driving diversification in porpoises and an evolutionary framework for their conservation

An experimental fatigue study of a porous scaffold for the regeneration of articular cartilage

The aim of this experimental study is to predict the long-term mechanical behavior of a porous scaffold implanted in a cartilage defect for tissue engineering purpose. Fatigue studies were performed by up to 100,000 unconfined compression cycles in a polycaprolactone (PCL) scaffold with highly interconnected pores architecture. The scaffold compliance, stress strain response and hysteresis energy have been measured after different number of fatigue cycles, while the morphology has been observed by scanning electron microscopy at the same fatigue times. To simulate the growing tissue in the scaffold/tissue construct, the scaffold was filled with an aqueous solution of polyvinyl alcohol (PVA) and subjected to repeating cycles of freezing and thawing that increase the hydrogel stiffness. Fatigue studies show that the mechanical loading provokes failure of the dry scaffold at a smaller number of deformation cycles than when it is immersed in water, and also that 100,000 compressive dynamic cycles do not affect the scaffold/gel construct. This shows the stability of the scaffold implanted in a chondral defect and gives a realistic simulation of the mechanical performance from implantation of the empty scaffold to regeneration of the new tissue inside the scaffold's pores.This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2013-46467-C4-1-R (including the FEDER financial support). 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. The authors acknowledge the assistance and advice of Electron Microscopy Service of the UPVVikingsson, LKA.; Gómez-Tejedor, JA.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2015). An experimental fatigue study of a porous scaffold for the regeneration of articular cartilage. Journal of Biomechanics. 48(7):1310-1317. https://doi.org/10.1016/j.jbiomech.2015.02.013S1310131748

An in vitro experimental model to predict the mechanical behaviour of macroporous scaffolds implanted in articular cartilage

A model is proposed to assess mechanical behaviour of tissue engineering scaffolds and predict their performance in vivo during tissue regeneration. To simulate the growth of tissue inside the pores of the scaffold, the scaffold is swollen with a Poly (Vinyl alcohol) solution and subjected to repeated freezing and thawing cycles. In this way the Poly (Vinyl alcohol) becomes a gel whose stiffness increases with the number of freezing and thawing cycles. Mechanical properties of the construct immersed in water are shown to be determined, in large extent, by the water mobility constraints imposed by the gel filling the pores. This is similar to the way that water mobility determines mechanical properties of highly hydrated tissues, such as articular cartilage. As a consequence, the apparent elastic modulus of the scaffold in compression tests is much higher than those of the empty scaffold or the gel. Thus this experimental model allows assessing fatigue behaviour of the scaffolds under long-term dynamic loading in a realistic way, without recourse to animal experimentation.The UPV group acknowledges the support of the Spanish MICINN through project MAT2010-21611-C03-01. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors thank the microscopy service of Universitat Politecnica de Valencia for useful help and advice and Ricardo Perez Feito for technical assistance in the experimental set up.Vikingsson, LKA.; Gallego Ferrer, G.; Gómez-Tejedor, JA.; Gómez Ribelles, JL. (2014). An in vitro experimental model to predict the mechanical behaviour of macroporous scaffolds implanted in articular cartilage. Journal of the Mechanical Behavior of Biomedical Materials. 32:125-131. https://doi.org/10.1016/j.jmbbm.2013.12.024S1251313

Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesLumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10(-12)) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height. In light of presented findings, we speculate that the effect of rs6651255 on LDHsurg is driven by susceptibility to developing severe and persistent sciatica upon LDH.European Commission National Institutes of Healt

Time evolution of in vivo articular cartilage repair induced by bone marrow stimulation and scaffold implantation in rabbits

Purpose: Tissue engineering techniques were used to study cartilage repair over a 12-month period in a rabbit model. Methods: A full-depth chondral defect along with subchondral bone injury were originated in the knee joint, where a biostable porous scaffold was implanted, synthesized of poly(ethyl acrylate-co-hydroxyethyl acrylate) copolymer. Morphological evolution of cartilage repair was studied 1 and 2 weeks, and 1, 3, and 12 months after implantation by histological techniques. The 3-month group was chosen to compare cartilage repair to an additional group where scaffolds were preseeded with allogeneic chondrocytes before implantation, and also to controls, who underwent the same surgery procedure, with no scaffold implantation. Results: Neotissue growth was first observed in the deepest scaffold pores 1 week after implantation, which spread thereafter; 3 months later scaffold pores were filled mostly with cartilaginous tissue in superficial and middle zones, and with bone tissue adjacent to subchondral bone. Simultaneously, native chondrocytes at the edges of the defect started to proliferate 1 week after implantation; within a month those edges had grown centripetally and seemed to embed the scaffold, and after 3 months, hyaline-like cartilage was observed on the condylar surface. Preseeded scaffolds slightly improved tissue growth, although the quality of repair tissue was similar to non-preseeded scaffolds. Controls showed that fibrous cartilage was mainly filling the repair area 3 months after surgery. In the 12-month group, articular cartilage resembled the untreated surface. Conclusions: Scaffolds guided cartilaginous tissue growth in vivo, suggesting their importance in stress transmission to the cells for cartilage repair.This study was supported by the Spanish Ministry of Science and Innovation through MAT2010-21611-C03-00 project (including the FEDER financial support), by Conselleria de Educacion (Generalitat Valenciana, Spain) PROMETEO/2011/084 grant, and by CIBER-BBN en Bioingenieria, Biomateriales y Nanomedicina. The work of JLGR was partially supported by funds from the Generalitat Valenciana, ACOMP/2012/075 project. 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.Sancho-Tello Valls, M.; Forriol, F.; Gastaldi, P.; Ruiz Sauri, A.; Martín De Llano, JJ.; Novella-Maestre, E.; Antolinos Turpín, CM.... (2015). Time evolution of in vivo articular cartilage repair induced by bone marrow stimulation and scaffold implantation in rabbits. International Journal of Artificial Organs. 38(4):210-223. https://doi.org/10.5301/ijao.5000404S210223384Becerra, J., Andrades, J. A., Guerado, E., Zamora-Navas, P., López-Puertas, J. M., & Reddi, A. H. (2010). Articular Cartilage: Structure and Regeneration. Tissue Engineering Part B: Reviews, 16(6), 617-627. doi:10.1089/ten.teb.2010.0191Nelson, L., Fairclough, J., & Archer, C. (2009). Use of stem cells in the biological repair of articular cartilage. Expert Opinion on Biological Therapy, 10(1), 43-55. doi:10.1517/14712590903321470MAINIL-VARLET, P., AIGNER, T., BRITTBERG, M., BULLOUGH, P., HOLLANDER, A., HUNZIKER, E., … STAUFFER, E. (2003). HISTOLOGICAL ASSESSMENT OF CARTILAGE REPAIR. The Journal of Bone and Joint Surgery-American Volume, 85, 45-57. doi:10.2106/00004623-200300002-00007Hunziker, E. B., Kapfinger, E., & Geiss, J. (2007). The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development. Osteoarthritis and Cartilage, 15(4), 403-413. doi:10.1016/j.joca.2006.09.010Onyekwelu, I., Goldring, M. B., & Hidaka, C. (2009). Chondrogenesis, joint formation, and articular cartilage regeneration. Journal of Cellular Biochemistry, 107(3), 383-392. doi:10.1002/jcb.22149Ahmed, T. A. E., & Hincke, M. T. (2010). Strategies for Articular Cartilage Lesion Repair and Functional Restoration. Tissue Engineering Part B: Reviews, 16(3), 305-329. doi:10.1089/ten.teb.2009.0590Hangody, L., Kish, G., Kárpáti, Z., Udvarhelyi, I., Szigeti, I., & Bély, M. (1998). Mosaicplasty for the Treatment of Articular Cartilage Defects: Application in Clinical Practice. Orthopedics, 21(7), 751-756. doi:10.3928/0147-7447-19980701-04Steinwachs, M. R., Guggi, T., & Kreuz, P. C. (2008). Marrow stimulation techniques. Injury, 39(1), 26-31. doi:10.1016/j.injury.2008.01.042Brittberg, M., Lindahl, A., Nilsson, A., Ohlsson, C., Isaksson, O., & Peterson, L. (1994). Treatment of Deep Cartilage Defects in the Knee with Autologous Chondrocyte Transplantation. New England Journal of Medicine, 331(14), 889-895. doi:10.1056/nejm199410063311401Richter, W. (2009). Mesenchymal stem cells and cartilagein situregeneration. Journal of Internal Medicine, 266(4), 390-405. doi:10.1111/j.1365-2796.2009.02153.xBartlett, W., Skinner, J. A., Gooding, C. R., Carrington, R. W. J., Flanagan, A. M., Briggs, T. W. R., & Bentley, G. (2005). Autologous chondrocyte implantationversusmatrix-induced autologous chondrocyte implantation for osteochondral defects of the knee. The Journal of Bone and Joint Surgery. British volume, 87-B(5), 640-645. doi:10.1302/0301-620x.87b5.15905Little, C. J., Bawolin, N. K., & Chen, X. (2011). Mechanical Properties of Natural Cartilage and Tissue-Engineered Constructs. Tissue Engineering Part B: Reviews, 17(4), 213-227. doi:10.1089/ten.teb.2010.0572Vikingsson, L., Gallego Ferrer, G., Gómez-Tejedor, J. A., & Gómez Ribelles, J. L. (2014). An «in vitro» experimental model to predict the mechanical behavior of macroporous scaffolds implanted in articular cartilage. Journal of the Mechanical Behavior of Biomedical Materials, 32, 125-131. doi:10.1016/j.jmbbm.2013.12.024Weber, J. F., & Waldman, S. D. (2014). Calcium signaling as a novel method to optimize the biosynthetic response of chondrocytes to dynamic mechanical loading. Biomechanics and Modeling in Mechanobiology, 13(6), 1387-1397. doi:10.1007/s10237-014-0580-xMauck, R. L., Soltz, M. A., Wang, C. C. B., Wong, D. D., Chao, P.-H. G., Valhmu, W. B., … Ateshian, G. A. (2000). Functional Tissue Engineering of Articular Cartilage Through Dynamic Loading of Chondrocyte-Seeded Agarose Gels. Journal of Biomechanical Engineering, 122(3), 252-260. doi:10.1115/1.429656Palmoski, M. J., & Brandt, K. D. (1984). Effects of static and cyclic compressive loading on articular cartilage plugs in vitro. Arthritis & Rheumatism, 27(6), 675-681. doi:10.1002/art.1780270611Khoshgoftar, M., Ito, K., & van Donkelaar, C. C. (2014). The Influence of Cell-Matrix Attachment and Matrix Development on the Micromechanical Environment of the Chondrocyte in Tissue-Engineered Cartilage. Tissue Engineering Part A, 20(23-24), 3112-3121. doi:10.1089/ten.tea.2013.0676Agrawal, C. M., & Ray, R. B. (2001). Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. Journal of Biomedical Materials Research, 55(2), 141-150. doi:10.1002/1097-4636(200105)55:23.0.co;2-jPérez Olmedilla, M., Garcia-Giralt, N., Pradas, M. M., Ruiz, P. B., Gómez Ribelles, J. L., Palou, E. C., & García, J. C. M. (2006). Response of human chondrocytes to a non-uniform distribution of hydrophilic domains on poly (ethyl acrylate-co-hydroxyethyl methacrylate) copolymers. Biomaterials, 27(7), 1003-1012. doi:10.1016/j.biomaterials.2005.07.030Horbett, T. A., & Schway, M. B. (1988). Correlations between mouse 3T3 cell spreading and serum fibronectin adsorption on glass and hydroxyethylmethacrylate-ethylmethacrylate copolymers. Journal of Biomedical Materials Research, 22(9), 763-793. doi:10.1002/jbm.820220903Kiremitçi, M., Peşmen, A., Pulat, M., & Gürhan, I. (1993). Relationship of Surface Characteristics to Cellular Attachment in PU and PHEMA. Journal of Biomaterials Applications, 7(3), 250-264. doi:10.1177/088532829300700304Lydon, M. ., Minett, T. ., & Tighe, B. . (1985). Cellular interactions with synthetic polymer surfaces in culture. Biomaterials, 6(6), 396-402. doi:10.1016/0142-9612(85)90100-0Campillo-Fernandez, A. J., Pastor, S., Abad-Collado, M., Bataille, L., Gomez-Ribelles, J. L., Meseguer-Dueñas, J. M., … Ruiz-Moreno, J. M. (2007). Future Design of a New Keratoprosthesis. Physical and Biological Analysis of Polymeric Substrates for Epithelial Cell Growth. Biomacromolecules, 8(8), 2429-2436. doi:10.1021/bm0703012Funayama, A., Niki, Y., Matsumoto, H., Maeno, S., Yatabe, T., Morioka, H., … Toyama, Y. (2008). Repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes in a rabbit model. Journal of Orthopaedic Science, 13(3), 225-232. doi:10.1007/s00776-008-1220-zKitahara, S., Nakagawa, K., Sah, R. L., Wada, Y., Ogawa, T., Moriya, H., & Masuda, K. (2008). In Vivo Maturation of Scaffold-free Engineered Articular Cartilage on Hydroxyapatite. Tissue Engineering Part A, 14(11), 1905-1913. doi:10.1089/ten.tea.2006.0419Martinez-Diaz, S., Garcia-Giralt, N., Lebourg, M., Gómez-Tejedor, J.-A., Vila, G., Caceres, E., … Monllau, J. C. (2010). In Vivo Evaluation of 3-Dimensional Polycaprolactone Scaffolds for Cartilage Repair in Rabbits. The American Journal of Sports Medicine, 38(3), 509-519. doi:10.1177/0363546509352448Wang, Y., Bian, Y.-Z., Wu, Q., & Chen, G.-Q. (2008). Evaluation of three-dimensional scaffolds prepared from poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) for growth of allogeneic chondrocytes for cartilage repair in rabbits. Biomaterials, 29(19), 2858-2868. doi:10.1016/j.biomaterials.2008.03.021Alió del Barrio, J. L., Chiesa, M., Gallego Ferrer, G., Garagorri, N., Briz, N., Fernandez-Delgado, J., … De Miguel, M. P. (2014). Biointegration of corneal macroporous membranes based on poly(ethyl acrylate) copolymers in an experimental animal model. Journal of Biomedical Materials Research Part A, 103(3), 1106-1118. doi:10.1002/jbm.a.35249Diego, R. B., Olmedilla, M. P., Aroca, A. S., Ribelles, J. L. G., Pradas, M. M., Ferrer, G. G., & Sánchez, M. S. (2005). Acrylic scaffolds with interconnected spherical pores and controlled hydrophilicity for tissue engineering. Journal of Materials Science: Materials in Medicine, 16(8), 693-698. doi:10.1007/s10856-005-2604-7Serrano Aroca, A., Campillo Fernández, A. J., Gómez Ribelles, J. L., Monleón Pradas, M., Gallego Ferrer, G., & Pissis, P. (2004). Porous poly(2-hydroxyethyl acrylate) hydrogels prepared by radical polymerisation with methanol as diluent. Polymer, 45(26), 8949-8955. doi:10.1016/j.polymer.2004.10.033Diani, J., Fayolle, B., & Gilormini, P. (2009). A review on the Mullins effect. European Polymer Journal, 45(3), 601-612. doi:10.1016/j.eurpolymj.2008.11.017Mullins, L. (1969). Softening of Rubber by Deformation. Rubber Chemistry and Technology, 42(1), 339-362. doi:10.5254/1.3539210Jurvelin, J. S., Buschmann, M. D., & Hunziker, E. B. (2003). Mechanical anisotropy of the human knee articular cartilage in compression. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 217(3), 215-219. doi:10.1243/095441103765212712Shapiro, F., Koide, S., & Glimcher, M. J. (1993). Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. The Journal of Bone & Joint Surgery, 75(4), 532-553. doi:10.2106/00004623-199304000-00009SELLERS, R. S., ZHANG, R., GLASSON, S. S., KIM, H. D., PELUSO, D., D’AUGUSTA, D. A., … MORRIS, E. A. (2000). Repair of Articular Cartilage Defects One Year After Treatment with Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)*. The Journal of Bone and Joint Surgery-American Volume, 82(2), 151-160. doi:10.2106/00004623-200002000-00001Hunziker, E. B., Michel, M., & Studer, D. (1997). Ultrastructure of adult human articular cartilage matrix after cryotechnical processing. Microscopy Research and Technique, 37(4), 271-284. doi:10.1002/(sici)1097-0029(19970515)37:43.0.co;2-oAppelman, T. P., Mizrahi, J., Elisseeff, J. H., & Seliktar, D. (2009). The differential effect of scaffold composition and architecture on chondrocyte response to mechanical stimulation. Biomaterials, 30(4), 518-525. doi:10.1016/j.biomaterials.2008.09.063Chung, C., & Burdick, J. A. (2008). Engineering cartilage tissue. Advanced Drug Delivery Reviews, 60(2), 243-262. doi:10.1016/j.addr.2007.08.027HUNZIKER, E. B., & ROSENBERG, L. C. (1996). Repair of Partial-Thickness Defects in Articular Cartilage. The Journal of Bone & Joint Surgery, 78(5), 721-33. doi:10.2106/00004623-199605000-00012Schulze-Tanzil, G. (2009). Activation and dedifferentiation of chondrocytes: Implications in cartilage injury and repair. Annals of Anatomy - Anatomischer Anzeiger, 191(4), 325-338. doi:10.1016/j.aanat.2009.05.003Umlauf, D., Frank, S., Pap, T., & Bertrand, J. (2010). Cartilage biology, pathology, and repair. Cellular and Molecular Life Sciences, 67(24), 4197-4211. doi:10.1007/s00018-010-0498-0Karystinou, A., Dell’Accio, F., Kurth, T. B. A., Wackerhage, H., Khan, I. M., Archer, C. W., … De Bari, C. (2009). Distinct mesenchymal progenitor cell subsets in the adult human synovium. Rheumatology, 48(9), 1057-1064. doi:10.1093/rheumatology/kep192Sakaguchi, Y., Sekiya, I., Yagishita, K., & Muneta, T. (2005). Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source. Arthritis & Rheumatism, 52(8), 2521-2529. doi:10.1002/art.21212Schaefer, D., Martin, I., Jundt, G., Seidel, J., Heberer, M., Grodzinsky, A., … Freed, L. E. (2002). Tissue-engineered composites for the repair of large osteochondral defects. Arthritis & Rheumatism, 46(9), 2524-2534. doi:10.1002/art.1049

Combining self-assembling peptide gels with three-dimensional elastomer scaffolds

[EN] Some of the problems raised by the combination of porous scaffolds and self-assembling peptide (SAP) gels as constructs for tissue engineering applications are addressed for the first time. Scaffolds of poly(- ethyl acrylate) and the SAP gel RAD16-I were employed. The in situ gelation of the SAP gel inside the pores of the scaffolds was studied. The scaffold-cum-gel constructs were characterized morphologically, physicochemically and mechanically. The possibility of incorporating an active molecule (bovine serum albumin, taken here as a model molecule for others) in the gel within the scaffold’s pores was assessed, and the kinetics of its release in phosphate-buffered saline was followed. Cell seeding and colonization of these constructs were preliminarily studied with L929 fibroblasts and subsequently checked with sheep adipose-tissue-derived stem cells intended for further preclinical studies. Static (conventional) and dynamically assisted seedings were compared for bare scaffolds and the scaffold-cum-gel constructs. The SAP gel inside the pores of the scaffold significantly improved the uniformity and density of cell colonization of the three-dimensional (3-D) structure. These constructs could be of use in different advanced tissue engineering applications, where, apart from a cell-friendly extracellular matrix -like aqueous environment, a larger-scale 3-D structure able to keep the cells in a specific place, give mechanical support and/or conduct spatially the tissue growth could be required.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. Dr. J.C. Chachques (Hopital Europeen Georges Pompidou, Paris) is thanked for providing the ASCs employed in this study. MMP acknowledges support of CIBER-BBN initiative, financed by Institut de Salud Carlos III (Spain) with the assistance of the European Regional Development Fund.Vallés Lluch, A.; Arnal Pastor, MP.; Martínez Ramos, C.; Vilariño Feltrer, G.; Vikingsson, L.; Castells Sala, C.; Semino, CE.... (2013). Combining self-assembling peptide gels with three-dimensional elastomer scaffolds. Acta Biomaterialia. 9(12):9451-9460. https://doi.org/10.1016/j.actbio.2013.07.038S9451946091