An Economic, Energy, and Environmental Analysis of PV/Micro-CHP Hybrid Systems: A Case Study of a Tertiary Building

Our present standard of living depends strongly on energy sources, with buildings being a primary focus when it comes to reducing energy consumption due to their large contribution, especially in tertiary buildings. The goal of the present study is to evaluate the performance of two different designs of hybrid systems, composed of natural gas engines and photovoltaic panels. This will be done through simulations in TRNSYS, considering a representative office building with various schedules of operation (8, 12, and 24 h), as well as different climates in Spain. The main contributions of this paper are the evaluations of primary energy-consumption, emissions, and economic analyses for each scenario. In addition, a sensitivity analysis is carried out to observe the influence of energy prices, as well as that of the costs of the micro-CHP engines and PV modules. The results show that the scenario with the conventional system and PV modules is the most profitable one currently. However, if electricity prices are increased in the future or natural gas prices are reduced, the scenario with micro-CHP engines and PV modules will become the most profitable option. Energy service engineers, regulators, and manufacturers are the most interested in these results

Urban integration of high speed train Institutions of support in Spain and the keys to its success

The high speed train as means of transport in Spain is extending its network to many cities. Occasionally, this situation raises the opportunity to undertake large urban integration operations, associated with urban renewal and the construction of new residential areas. In these cases it has attended an institutional architecture based on extrapolated public companies for management. This study addresses these operations identifying and classifying them with variables that have proved to be decisive to make viable operations. As conclusion this model and the keys to their success is analysed

Borax induces osteogenesis by stimulating NaBC1 transporter via activation of BMP pathway

[EN] The intrinsic properties of mesenchymal stem cells (MSCs) make them ideal candidates for tissue engineering applications. Efforts have been made to control MSC behavior by using material systems to engineer synthetic extracellular matrices and/or include soluble factors in the media. This work proposes a simple approach based on ion transporter stimulation to determine stem cell fate that avoids the use of growth factors. Addition of borax alone, transported by the NaBC1-transporter, enhanced MSC adhesion and contractility, promoted osteogenesis and inhibited adipogenesis. Stimulated-NaBC1 promoted osteogenesis via the BMP canonical pathway (comprising Smad1/YAP nucleus translocation and osteopontin expression) through a mechanism that involves simultaneous NaBC1/BMPR1A and NaBC1/alpha (5)beta (1)/alpha (v)beta (3) co-localization. We describe an original function for NaBC1 transporter, besides controlling borate homeostasis, capable of stimulating growth factor receptors and fibronectin-binding integrins. Our results open up new biomaterial engineering approaches for biomedical applications by a cost-effective strategy that avoids the use of soluble growth factors. Rico et al. propose a simple approach based on borax stimulation of NaBC1 transporter, which enhances FN-binding integrin-dependent mesenchymal stem cell adhesion and contractility, promotes osteogenesis and inhibits adipogenesis. Osteogenic differentiation depends on activation of the BMP pathway through a mechanism that involves simultaneous co-localization of NaBC1 with FN-binding integrins and BMPR1A.P.R. acknowledges support from the Spanish Ministry of Science, Innovation and Universities (RTI2018-096794), and Fondo Europeo de Desarrollo Regional (FEDER). 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. M.S.S. acknowledges support from the UK Engineering and Physical Sciences Research Council (EPSRC-EP/P001114/1).Rico Tortosa, PM.; Rodrigo Navarro, A.; Sánchez-Pérez, L.; Salmerón Sánchez, M. (2020). Borax induces osteogenesis by stimulating NaBC1 transporter via activation of BMP pathway. Communications Biology. 3(1):1-15. https://doi.org/10.1038/s42003-020-01449-4S11531Akhurst, R. J. & Hata, A. Targeting the TGFbeta signalling pathway in disease. Nat. Rev. Drug Discov. 11, 790–811 (2012).Brizzi, M. F., Tarone, G. & Defilippi, P. Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr. Opin. Cell Biol. 24, 645–651 (2012).Watt, F. M. & Huck, W. T. S. Role of extracellular matrix regulating stem cell fate. Nat. Rev. Mol. Cell Biol. 14, 467–473 (2013).Benoit, D. S. W., Schwartz, M. P., Durney, A. R. & Anseth, K. S. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat. Mater. 7, 816–823 (2008).Baker, B. M., Trappmann, B., Wang, W. Y., Sakar, M. S., Kim, I. L., Shenoy, V. B., Burdick, J. A. & Chen, C. S. Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillary microenvironments. Nat. Mater. 14, 1262–1268 (2015).Das, R. K., Gocheva, V., Hammink, R., Zouani, O. F. & Rowan, A. E. Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels. Nat. Mater. 15, 318–325 (2015).Kilian, K. A., Bugarija, B., Lahn, B. T. & Mrksich, M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl Acad. Sci. USA 107, 4872–4877 (2010).Yang, J., McNamara, L. E., Gadegaard, N., Alakpa, E. V., Burgess, K. V., Dominic Meek, R. M. & Dalby, M. J. Nanotopographical induction of osteogenesis through adhesion, bone morphogenetic protein cosignaling, and regulation of microRNAs. ACS Nano. 8, 9941–9953 (2014).Dalby, M. J., García, A. J. & Salmeron-Sanchez, M. Receptor control in mesenchymal stem cell engineering. Nat. Rev. 3, 17091 (2018).Carragee, E. J., Hurwitz, E. L. & Weiner, B. K. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J. 11, 471–491 (2011).Vining, K. H. & Mooney, D. J. Mechanical forces direct stem cell behavior in development and regeneration. Nat. Rev. 18, 728–742 (2017).Biggs, M. J., Richards, R. G., Gadegaard, N., Wilkinson, C. D., Oreffo, R. O. & Dalby, M. J. The use of nanoscale topography to modulate the dynamics of adhesion formation in primary osteoblasts and ERK/MAPK signaling in STRO-1+ enriched skeletal stem cells. Biomaterials 30, 5094–5103 (2009).McBeath, R., Pirone, D. M., Nelson, C. M., Bhadriraju, K. & Chen, C. S. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell. 6, 483–495 (2004).Hille, B. Ion Channels of Excitable Membranes. (Sinauer Associates Inc, Sunderland, MA, 2001).Lauritzen, I., Chemin, J., Honoré, E., Martine, J., Guy, N., Lazdunski, M. & Patel, A. J. Cross-talk between the mechano-gated K2p channel TREK-1 and the actin cytoskeleton. EMBO Rep. 6, 642–648 (2005).Gasparski, A. N. & Beningo, K. A. Mechanoreception at the cell membrane: more than the integrins. Arch. Biochem. Biophys. 586, 20–26 (2015).Pillozzi, S. & Becchetti, A. Ion channels in hematopoietic and mesenchymal stem cells. Stem Cells Int. 2012, 217910 (2012).Park, M., Li, Q., Shcheynikov, N., Zeng, W. & Muallem, S. NaBC1 is a ubiquitous electrogenic Na+-coupled borate transporter essential for cellular boron homeostasis and cell growth and proliferation. Mol. Cell. 16, 331–341 (2004).Vithana, E. N., Morgan, P., Sundaresan, P., Ebenezer, N. D., Tan, D. T., Mohamed, M. D., Anand, S., Khine, K. O., Venkataraman, D., Yong, V. H., Salto-Tellez, M., Venkatraman, A., Guo, K., Hemadevi, B., Srinivasan, M., Prajna, V., Khine, M., Casey, J. R., Inglehearn, C. F. & Aung, T. Mutations in sodium-borate cotransporter SLC4A11 cause recessive congenital hereditary endotelial dystrophy (CHED2). Nat. Genet. 38, 755–757 (2006).Lopez, I. A., Rosenblatt, M. I., Kim, C., Galbraith, G. C., Jones, S. M., Kao, L., Newman, D., Liu, W., Yeh, S., Pushkin, A., Abuladze, N. & Kurtz, I. Slc4a11 gene disruption in mice: cellular targets of sensorineural abnormalities. J. Biol. Chem. 284, 26882–26896 (2009).Rico, P., Rodrigo-Navarro, A. & Salmeron-Sanchez, M. Borax-loaded PLLA for promotion of myogenic differentiation. Tissue Eng. Part A. 21, 2662–2672 (2015).Rico, P., Rodrigo-Navarro, A., de la Peña, M., Moulisová, V., Costell, M. & Salmeron-Sanchez, M. Simultaneous boron ion-channel activation for enhanced vascularization. Adv. Biosyst. 3, 1800220 (2019).Cifti, E., Köse, S., Korkusuz, P., Timuçin, M. & Korkusuz, F. Boron containing nano hydroxyapatites (Bn-HAp) stimulate mesenchymal stem cell adhesion, proliferation and differentiation. Key Eng. Mater. 631, 373–378 (2015).Li, X., Wang, X., Jiang, X., Yamaguchi, M., Ito, A., Bando, Y. & Golberg, D. Boron nitride nanotube-enhanced osteogenic differentiation of mesenchymal stem cells. J. Biomed. Res. 104, 323–329 (2015).Liu, Y. J., Su, W. T. & Chen, P. H. Magnesium and zinc borate enhance osteoblastic differentiation of stem cells from human exfoliated deciduous teeth in vitro. J. Biomater. Appl. 32, 765–774 (2018).Dogan, A., Demirci, S., Apdik, H., Bayrak, O. F., Gulluoglu, S., Tuysuz, E. C., Gusev, O., Rizanov, A. A., Nikerel, E. & Sahin, F. A new hope for obesity management: boron inhibits adipogenesis in progenitor cells through the Wnt/β-catenin pathway. Metabolism 69, 130–142 (2017).Abdik, E. A., Abdik, H., Tasli, P. N., Asli, A., Deniz, H. & Sahin, F. Suppressive role of boron on adipogenic differentiation and fat deposition in human mesenchymal stem cells. Biol. Trace Elem. Res. 188, 384–392 (2018).Humphries, M. J., Travis, M. A., Clark, K. & Mould, A. P. Mechanisms of integration of cells and extracellular matrices by integrins. Biochem. Soc. Trans. 32, 822–825 (2004).Burns, A. E. & Varin, J. Poly-L-lactic acid rod fixation results in foot surgery. J. Foot Ankle Surg. 37, 37–41 (1998).Harada, S. & Rodan, G. A. Control of osteoblast function and regulation of bone mass. Nature 423, 349–355 (2003).Gregory, C. A., Ylostalo, J. & Prockop, D. J. Adult bone marrow stem/progenitor cells (MSCs) are preconditioned by microenvironmental niches in culture: a two-stage hypothesis for regulation of MSC fate. Sci. Stke. 294, pe37 (2005).Jones, D. R. H. & Ashby, M. F. Engineering Materials 1. (Butterworth-Heinemann, 2019).Farah, S., Anderson, D. G. & Langer, R. Physical and mechanical properties of PLA, and their functions in widespread applications-A comprehensive review. Adv. Drug Deliv. Rev. 107, 367–392 (2016).González-García, C., Moratal, D., Oreffo, R. O. C., Dalby, M. J. & Salmeron-Sanchez, M. Surface mobility regulates skeletal stem cell differentiation. Integr. Biol. 4, 531–539 (2012).Liddington, R. C. & Ginsberg, M. H. Integrin activation takes shape. J. Cell Biol. 158, 833–839 (2002).Ganor, Y., Besser, M. & Ben-Zakay, N. et al. Human T cells express a functional ionotropic glutamate receptor GluR3, and glutamate by itself triggers integrin-mediated adhesion to laminin and fibronectin and chemotactic migration. J. Immunol. 170, 4362–4372 (2003).Puklin-Faucher, E. & Sheetz, M. P. The mechanical integrin cycle. J. Cell Sci. 122, 179–186 (2009).Liao, S. F., Monegue, J. S., Lindemann, M. D., Cromwell, G. L. & Matthews, J. C. Dietary supplementation of boron differentially alters expression of borate transporter (NaBC1) mRNA by jejunum and kidney of growing pigs. Biol. Trace Elem. Res. 143, 901–912 (2011).Saidak, Z., Le Henaff, C., Azzi, S., Marty, C., Da Nascimento, S., Sonnet, P. & Marie, P. J. Wnt/β-catenin signaling mediates osteoblast differentiation triggered by peptide-induced α5β1 integrin priming in Mesenchymal Skeletal Cells. J. Biol. Chem. 290, 6903–6912 (2015).Chen, Q., Shou, P., Zhang, L., Xu, C., Zheng, C., Han, Y., Li, W., Huang, Y., Zhang, X., Shao, C., Roberts, A. I., Rabson, A. B., Ren, G., Zhang, Y., Wang, Y., Denhardt, D. T. & Shi, Y. An osteopontine-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells. Stem Cells 32, 327–337 (2014).Hofmann, G., Bernabei, P. A. & Crociani, O. et al. HERG K+ channels activation during β1 integrin-mediated adhesion to fibronectin induces an up-regulation of αvβ3 integrin in the preosteoclastic leukemia cell line FLG 29.1. J. Biol. Chem. 276, 4923–4931 (2001).Becchetti, A. et al. Response to fibronectin-integrin interaction in leukaemia cells: delayed enhancing of a K + current. Proc. R. Soc. Lond. 248, 235–240 (1992).Arcangeli, A. & Becchetti, A. Complex functional interaction between integrin receptors and ion channels. TRENDS Cell Biol. 16, 631–639 (2006).Jing, J., Hinton, R. J. & Feng, J. Q. BMR1A signaling in cartilage development and endochondral bone formation. Vitam. Hormones. 99, 273–291 (2015).Kimura, M., Ito, M., Amano, K., Chihara, Y., Fukata, M., Nakafuku, B., Yamamori, J., Feng, J., Nakano, T. & Okawa, K. et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science 273, 245–248 (1996).Pelham, R. J. & Wang, Y. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Natl Acad. Sci. USA 94, 13661–13665 (1997).Kovacs, M., Tóth, J., Hetényi, C., Málnási-Csizmadia, A. & Sellers, J. Mechanism of blebbistatin inhibition of myosin II. J. Biol. Chem. 279, 35557–35563 (2004).Narumiya, S., Ishizaki, T. & Ufhata, M. Use and properties of ROCK-specific inhibitor Y-27632. Methods Enzymol. 325, 273–284 (2000).Schmierer, B. & Hill, C. S. TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat. Rev. 8, 970–982 (2007).Zhao, B., Li, L. & Guan, K. L. Hippo signaling at a glance. J. Cell Sci. 123, 4001–4006 (2010).Varelas, X. The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease. Development 141, 1614–1626 (2014).Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S. & Marshak, D. R. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143–147 (1999).Kirkham, G. R. & Cartmell, S. H. Genes and proteins involved in the regulation of osteogenesis. Top. Tissue Eng. 3, 1–22 (2007).Chamberlain, G., Fox, J., Ashton, B. & Middleton, J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25, 2739–2749 (2007).Lowe, C. E., O´Rahilly, S. & Rochford, J. J. Adipogenesis at a glance. J. Cell Sci. 124, 2681–2686 (2011).MacQueen, L., Sun, Y. & Simmons, C. A. Mesenchymal stem cell mechanobiology and emerging experimental platforms. J. R. Soc. Interface 10, 20130179 (2013).Ivanovska, I. L., Shin, J. W., Swift, J. & Discher, D. E. Stem cell mechanobiology: diverse lessons from bone marrow. Trends Cell Biol. 25, 523–532 (2015).Phimphilai, M., Zhao, Z., Boules, H., Roca, H. & Franceschi, R. T. BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype. J. Bone Miner. Res. 21, 637–646 (2006).Comoglio, P. M., Boccaccio, C. & Trusolino, L. Interactions between growth factor receptors and adhesion molecules: breaking the rules. Curr. Opin. Cell Biol. 15, 565–571 (2003).Fourel, L., Valat, A., Faurobert, E., Guillot, R., Bourrin-Reynard, I., Ren, K., Lafanechère, L., Planus, E., Picart, C. & Albiges-Rizo, C. β3 integrin-mediated spreading induced by matrix-bound BMP-2 controls Smad signaling in a stiffness-independent manner. J. Cell Biol. 212, 693–706 (2016).Morandi, E. M., Verstappen, R., Zwierzina, M. E., Geley, S., Pierer, G. & Ploner, C. ITGAV and ITGA5 diversely regulate proliferation and adipogenic differentiation of human adipose derived stem cells. Sci. Rep. 6, 28889 (2016).Brazil, D. P., Church, R. H., Surae, S., Godson, C. & Martin, F. BMP signalling: agony and antagony in the family. Trends Cell Biol. 25, 249–264 (2015).Nardone, G., Oliver-De La Cruz, J., Vrbsky, J., Martini, C., Pribyl, J., Skla´dal, P., Pesl, M., Caluori, G., Pagliari, S., martino, F., Maceckova, Z., Hajduch, M., Sanz-Garcia, A., Pugno, N. M., Stokin, G. B. & Forte, G. YAP regulates cell mechanics by controlling focal adhesion assembly. Nat. Commun. 8, 15321 (2017).Miyazono, K., Maeda, S. & Imamura, T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 16, 251–263 (2005).Rico, P., Rodrigo-Navarro, A., Sánchez Pérez, L. & Salmeron-Sanchez, M. Borax induces osteogenesis by stimulating NaBC1 transporter via activation of BMP pathway. Commun. Biol. https://doi.org/10.5525/gla.researchdata.1076 (2020)

Criticism of illusionism and defense of plurifocality. Plato's influence

[EN] In general, there are two ways to account for reality: tragically or epically. Plato criticized the first one and applauded the second one. To these forms correspond two modes of representation in perspective: conical or illusionist, and axonometric or reflective. We propose to remark that, unlike some illusionist authors of the Renaissance and Baroque, certain artists of twentieth-century Modernity opted for the epic representation of reality, whose plurifocal objectivity guarantees axonometry.[ES] En general, hay dos formas de dar cuenta de la realidad: trágica o épicamente. Platón criticó la primera y aplaudió la segunda. A esas formas corresponden dos modos de representación en perspectiva: cónica o ilusionista, y axonométrica o reflexiva. Nos proponemos reseñar que, a diferencia de algunos autores ilusionistas del Renacimiento y Barroco, ciertos artistas de la Modernidad del siglo XX optaron por la representación épica de la realidad, cuya objetividad plurifocal garantiza la axonometría.García Sánchez, R.; Salmerón Núñez, JM.; García Martínez, P. (2023). Crítica al ilusionismo y defensa de la plurifocalidad. La influencia de Platón. EGA Expresión Gráfica Arquitectónica. 28(49):36-47. https://doi.org/10.4995/ega.2023.180763647284

Analysis of the economic feasibility and reduction of a building’s energy consumption and emissions when integrating hybrid solar thermal/PV/micro-CHP systems

The aim of this paper is to assess the performance of several designs of hybrid systems composed of solar thermal collectors, photovoltaic panels and natural gas internal combustion engines. The software TRNSYS 17 has been used to perform all the calculations and data processing, as well as an optimisation of the tank volumes through an add-in coupled with the GENOPT® software. The study is carried out by analysing the behaviour of the designed systems and the conventional case in five different locations of Spain with diverse climatic characteristics, evaluating the same building in all cases. Regulators, manufacturers and energy service engineers are the most interested in these results. Two major contributions in this paper are the calculations of primary energy consumption and emissions and the inclusion of a Life Cycle Cost analysis. A table which shows the order of preference regarding those criteria for each considered case study is also included. This was fulfilled in the interest of comparing between the different configurations and climatic zones so as to obtain conclusions on each of them. The study also illustrates a sensibility analysis regarding energy prices. Finally, the exhaustive literature review, the novel electricity consumption profile of the building and the illustration of the influence of the cogeneration engine working hours are also valuable outputs of this paper, developed in order to address the knowledge gap and the ongoing challenges in the field of distributed generation

El termómetro de globo en estudios de confort y medioambiente en los edificios

The reasons for the inferior performance of many existing buildings and associated energy systems are diverse, but an important part-cause is insufficient attention to the influence of occupant behaviour. In smart buildings it is necessary to allow for the integration of human behaviour in the HVAC system. In addition, many researchers are limited in their investigation by not having low cost tools that can provide information for their studies. This article is a review of the present state of art about the globe thermometer. It describes how to build your own globe temperature sensor and describes experiments that illustrate the feasibility of using a black globe thermometer with 40 mm diameter.Las razones del rendimiento inferior de muchos de los edificios actuales y sus sistemas energéticos relacionados son diversas y estas son en una parte importante causada por una atención insuficiente a la influencia del comportamiento de los ocupantes. En los edificios inteligentes es necesario implementar nuevas oportunidades para integrar el comportamiento humano en el sistema de climatización. Además, muchos investigadores están limitados en su investigación al no contar con herramientas de bajo coste que puedan proporcionar información a sus estudios. En este artículo se presenta una revisión del estado actual del arte sobre el termómetro de globo, se describe cómo construir su propio sensor de temperatura de globo y los experimentos descritos ilustran la viabilidad de utilizar un termómetro de globo negro con 40 mm de diámetro

Migration and cultural and artistic political heteronomy

[SPA] Las migraciones pueden ser: de personas y culturas, de mercancías, de datos, de dinero, etc. Todo ello no ha hecho más que aumentar la complejidad, en un mundo que cultural y paradójicamente huye de la uniformidad. Sea complejo aquello que no es posible abordar, en exclusiva, desde un solo ámbito. Con ello aumenta el incremento de posibilidades en cada sistema y esfera social, multiplicándose la complejidad al tiempo que aumenta la autonomía de cada uno de esos ámbitos. Si la política, la arquitectura y el urbanismo pretenden “entrometerse”, han de hacerlo acudiendo a procedimientos no jerárquicos, sino heterónomos, con inéditos sistemas de negociación. Las nuevas sociedades de “la modernidad avanzada” son sistemas carentes de vértice jerárquico. Y cada ámbito funcional reduce el campo de los acontecimientos relevantes de acuerdo con la lógica de su propia función. Cada uno de ellos tiende a incluir toda la sociedad en su propio ámbito, de modo que la idea de unidad, más que desaparecer, se multiplica en un elenco de unidades de variada procedencia. Un sistema parcial no es representante de la totalidad (economía, salud, tecnología, moral, comunicación, arte, arquitectura, urbanismo, etc.). Cada una de estas concepciones toma la parte por el todo y olvida la interdependencia fundamental a la que están sometidos todos los sistemas funcionales. Valorar la dinámica centrífuga de los sistemas diferenciados y jerárquicos de la primera modernidad, es el debate de la nueva política, cultura y arquitectura de las sociedades complejas. [ENG] Migrations can be: people and cultures, goods, data, money, etc. All of these have done no more than increase complexity, in a world which paradoxically and culturally escapes from uniformity. Be complex that which cannot be addressed, exclusively from a single field. It increases the growth of possibilities in each system and the social sphere, to multiply the complexity at the time which increases the autonomy of each of these areas. If politics, architecture and urban planning are intended to "meddle", they must do so attending procedures not hierarchical, but self-instituting, with new trading systems. New "Advanced modernity" societies are lacking systems of hierarchical vertex. And each functional area reduces the field of relevant events according to the logic of its own function. Each of them tends to include all the society in their own field, so the idea of unity, rather than disappear, it multiplies in a cast of varied provenance units. A partial system is not representative of the whole (economics, health, technology, morale, communication, art, architecture, urban planning, etc.). Each of these conceptions takes the part for the whole, and forgets the fundamental interdependence to which all functional systems are subjected. Counterbalancing the centrifugal dynamics of differentiated and hierarchical systems of first modernity is the debate on the new policy, culture and architecture of complex societies

Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks

[EN] Poly-l-lactic acid (PLLA) has been used as a biodegradable polymer for many years; the key characteristics of this polymer make it a versatile and useful resource for regenerative medicine. However, it is not inherently bioactive. Thus, here, a novel process is presented to functionalize PLLA surfaces with poly(ethyl acrylate) (PEA) brushes to provide biological functionality through PEA's ability to induce spontaneous organization of the extracellular matrix component fibronectin (FN) into physiological-like nanofibrils. This process allows control of surface biofunctionality while maintaining PLLA bulk properties (i.e., degradation profile, mechanical strength). The new approach is based on surface-initiated atomic transfer radical polymerization, which achieves a molecularly thin coating of PEA on top of the underlying PLLA. Beside surface characterization via atomic force microscopy, X-ray photoelectron spectroscopy and water contact angle to measure PEA grafting, the biological activity of this surface modification is investigated. PEA brushes trigger FN organization into nanofibrils, which retain their ability to enhance adhesion and differentiation of C2C12 cells. The results demonstrate the potential of this technology to engineer controlled microenvironments to tune cell fate via biologically active surface modification of an otherwise bioinert biodegradable polymer, gaining wide use in tissue engineering applications.The authors acknowledge the EPSRC (EP/P001114/1) and MRC (MR/S005412/1) funding. The authors also acknowledge the EPSRC funding as part of the Doctoral Training Centre EP/F500424/1. This work was also funded by a grant from the UK Regenerative Medicine Platform. X-ray photoelectron spectroscopy was conducted by the National EPSRC XPS Users' Service (NEXUS), Newcastle.Sprott, MR.; Ferrer, G.; Dalby, MJ.; Salmerón Sánchez, M.; Cantini, M. (2019). Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks. Advanced Healthcare Materials (Online). 8(3):1-12. https://doi.org/10.1002/adhm.201801469S11283A. J. Rincon Lasprilla G. A. Rueda Martinez B. H. Lunelli J. E. Jaimes Figueroa A. L. Jardini R. Maciel Filho Chem. Eng. Trans 2011 985Khan, F., Tanaka, M., & Ahmad, S. R. (2015). Fabrication of polymeric biomaterials: a strategy for tissue engineering and medical devices. Journal of Materials Chemistry B, 3(42), 8224-8249. doi:10.1039/c5tb01370dXu, F. J., Yang, X. C., Li, C. Y., & Yang, W. T. (2011). Functionalized Polylactide Film Surfaces via Surface-Initiated ATRP. Macromolecules, 44(7), 2371-2377. doi:10.1021/ma200160hKhan, F., & Tanaka, M. (2017). Designing Smart Biomaterials for Tissue Engineering. International Journal of Molecular Sciences, 19(1), 17. doi:10.3390/ijms19010017Zhao, P., Gu, H., Mi, H., Rao, C., Fu, J., & Turng, L. (2017). Fabrication of scaffolds in tissue engineering: A review. Frontiers of Mechanical Engineering, 13(1), 107-119. doi:10.1007/s11465-018-0496-8Zou, Y., Zhang, L., Yang, L., Zhu, F., Ding, M., Lin, F., … Li, Y. (2018). «Click» chemistry in polymeric scaffolds: Bioactive materials for tissue engineering. Journal of Controlled Release, 273, 160-179. doi:10.1016/j.jconrel.2018.01.023Pyun, J., Kowalewski, T., & Matyjaszewski, K. (2005). Polymer Brushes by Atom Transfer Radical Polymerization. Polymer Brushes, 51-68. doi:10.1002/3527603824.ch2Matyjaszewski, K., Dong, H., Jakubowski, W., Pietrasik, J., & Kusumo, A. (2007). Grafting from Surfaces for «Everyone»:  ARGET ATRP in the Presence of Air. Langmuir, 23(8), 4528-4531. doi:10.1021/la063402eDatta, H., Bhowmick, A. K., & Singha, N. K. (2008). Tailor-made hybrid nanostructure of poly(ethyl acrylate)/clay by surface-initiated atom transfer radical polymerization. Journal of Polymer Science Part A: Polymer Chemistry, 46(15), 5014-5027. doi:10.1002/pola.22829Simakova, A., Averick, S. E., Konkolewicz, D., & Matyjaszewski, K. (2012). Aqueous ARGET ATRP. Macromolecules, 45(16), 6371-6379. doi:10.1021/ma301303bSiegwart, D. J., Oh, J. K., & Matyjaszewski, K. (2012). ATRP in the design of functional materials for biomedical applications. Progress in Polymer Science, 37(1), 18-37. doi:10.1016/j.progpolymsci.2011.08.001Liu, P., & Su, Z. (2005). Surface-initiated atom transfer radical polymerization (SI-ATRP) of n-butyl acrylate from starch granules. Carbohydrate Polymers, 62(2), 159-163. doi:10.1016/j.carbpol.2005.07.018Yu, Q., Johnson, L. M., & López, G. P. (2014). Nanopatterned Polymer Brushes for Triggered Detachment of Anchorage-Dependent Cells. Advanced Functional Materials, 24(24), 3751-3759. doi:10.1002/adfm.201304274Zhu, A., Zhang, M., Wu, J., & Shen, J. (2002). Covalent immobilization of chitosan/heparin complex with a photosensitive hetero-bifunctional crosslinking reagent on PLA surface. Biomaterials, 23(23), 4657-4665. doi:10.1016/s0142-9612(02)00215-6Matyjaszewski, K. (2012). Atom Transfer Radical Polymerization (ATRP): Current Status and Future Perspectives. Macromolecules, 45(10), 4015-4039. doi:10.1021/ma3001719Zhu, Y., Gao, C., Liu, X., He, T., & Shen, J. (2004). Immobilization of Biomacromolecules onto Aminolyzed Poly(L-lactic acid) toward Acceleration of Endothelium Regeneration. Tissue Engineering, 10(1-2), 53-61. doi:10.1089/107632704322791691Tsuji, H., Ogiwara, M., Saha, S. K., & Sakaki, T. (2006). Enzymatic, Alkaline, and Autocatalytic Degradation of Poly(l-lactic acid):  Effects of Biaxial Orientation. Biomacromolecules, 7(1), 380-387. doi:10.1021/bm0507453He, Y., Wang, W., & Ding, J. (2013). Effects of L-lactic acid and D,L-lactic acid on viability and osteogenic differentiation of mesenchymal stem cells. Chinese Science Bulletin, 58(20), 2404-2411. doi:10.1007/s11434-013-5798-yM. Cantini C. González‐García V. Llopis‐Hernández M. Salmerón‐Sánchez T. Horbett J. L. Brash W. Norde Proteins at Interfaces III State of the Art ACS Symposium Series 2012 American Chemical Society Washington DC USA 471 496Llopis-Hernández, V., Rico, P., Moratal, D., Altankov, G., & Salmerón-Sánchez, M. (2013). Role of Material-Driven Fibronectin Fibrillogenesis in Protein Remodeling. BioResearch Open Access, 2(5), 364-373. doi:10.1089/biores.2013.0017Salmerón-Sánchez, M., Rico, P., Moratal, D., Lee, T. T., Schwarzbauer, J. E., & García, A. J. (2011). Role of material-driven fibronectin fibrillogenesis in cell differentiation. Biomaterials, 32(8), 2099-2105. doi:10.1016/j.biomaterials.2010.11.057Vanterpool, F. A., Cantini, M., Seib, F. P., & Salmerón-Sánchez, M. (2014). A Material-Based Platform to Modulate Fibronectin Activity and Focal Adhesion Assembly. BioResearch Open Access, 3(6), 286-296. doi:10.1089/biores.2014.0033Bathawab, F., Bennett, M., Cantini, M., Reboud, J., Dalby, M. J., & Salmerón-Sánchez, M. (2016). Lateral Chain Length in Polyalkyl Acrylates Determines the Mobility of Fibronectin at the Cell/Material Interface. Langmuir, 32(3), 800-809. doi:10.1021/acs.langmuir.5b03259Lozano Picazo, P., Pérez Garnes, M., Martínez Ramos, C., Vallés-Lluch, A., & Monleón Pradas, M. (2014). New Semi-Biodegradable Materials from Semi-Interpenetrated Networks of Poly(ϵ-caprolactone) and Poly(ethyl acrylate). Macromolecular Bioscience, 15(2), 229-240. doi:10.1002/mabi.201400331Schulz, A. S., Gojzewski, H., Huskens, J., Vos, W. L., & Julius Vancso, G. (2017). Controlled sub-10-nanometer poly(N -isopropyl-acrylamide) layers grafted from silicon by atom transfer radical polymerization. Polymers for Advanced Technologies, 29(2), 806-813. doi:10.1002/pat.4187Müllner, M., Dodds, S. J., Nguyen, T.-H., Senyschyn, D., Porter, C. J. H., Boyd, B. J., & Caruso, F. (2015). Size and Rigidity of Cylindrical Polymer Brushes Dictate Long Circulating Properties In Vivo. ACS Nano, 9(2), 1294-1304. doi:10.1021/nn505125fKreyling, W. G., Abdelmonem, A. M., Ali, Z., Alves, F., Geiser, M., Haberl, N., … Parak, W. J. (2015). In vivo integrity of polymer-coated gold nanoparticles. Nature Nanotechnology, 10(7), 619-623. doi:10.1038/nnano.2015.111Pankov, R. (2002). Fibronectin at a glance. Journal of Cell Science, 115(20), 3861-3863. doi:10.1242/jcs.00059Garcı́a, A. J., Vega, M. D., & Boettiger, D. (1999). Modulation of Cell Proliferation and Differentiation through Substrate-dependent Changes in Fibronectin Conformation. Molecular Biology of the Cell, 10(3), 785-798. doi:10.1091/mbc.10.3.785Gattazzo, F., Urciuolo, A., & Bonaldo, P. (2014). Extracellular matrix: A dynamic microenvironment for stem cell niche. Biochimica et Biophysica Acta (BBA) - General Subjects, 1840(8), 2506-2519. doi:10.1016/j.bbagen.2014.01.010Hay, J. J., Rodrigo-Navarro, A., Hassi, K., Moulisova, V., Dalby, M. J., & Salmeron-Sanchez, M. (2016). Living biointerfaces based on non-pathogenic bacteria support stem cell differentiation. Scientific Reports, 6(1). doi:10.1038/srep21809Zhu, Y., Gao, C., Liu, X., & Shen, J. (2002). Surface Modification of Polycaprolactone Membrane via Aminolysis and Biomacromolecule Immobilization for Promoting Cytocompatibility of Human Endothelial Cells. Biomacromolecules, 3(6), 1312-1319. doi:10.1021/bm020074yMacDonald, R. T., McCarthy, S. P., & Gross, R. A. (1996). Enzymatic Degradability of Poly(lactide):  Effects of Chain Stereochemistry and Material Crystallinity. Macromolecules, 29(23), 7356-7361. doi:10.1021/ma960513jTokiwa, Y., & Calabia, B. P. (2006). Biodegradability and biodegradation of poly(lactide). Applied Microbiology and Biotechnology, 72(2), 244-251. doi:10.1007/s00253-006-0488-1Hu, X., Su, T., Li, P., & Wang, Z. (2017). Blending modification of PBS/PLA and its enzymatic degradation. Polymer Bulletin, 75(2), 533-546. doi:10.1007/s00289-017-2054-7Gee, E. P. S., Yüksel, D., Stultz, C. M., & Ingber, D. E. (2013). SLLISWD Sequence in the 10FNIII Domain Initiates Fibronectin Fibrillogenesis. Journal of Biological Chemistry, 288(29), 21329-21340. doi:10.1074/jbc.m113.462077Roach, P., Eglin, D., Rohde, K., & Perry, C. C. (2007). Modern biomaterials: a review—bulk properties and implications of surface modifications. Journal of Materials Science: Materials in Medicine, 18(7), 1263-1277. doi:10.1007/s10856-006-0064-3Dalby, M. J., Gadegaard, N., & Oreffo, R. O. C. (2014). Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate. Nature Materials, 13(6), 558-569. doi:10.1038/nmat3980Neděla, O., Slepička, P., & Švorčík, V. (2017). Surface Modification of Polymer Substrates for Biomedical Applications. Materials, 10(10), 1115. doi:10.3390/ma10101115Ngandu Mpoyi, E., Cantini, M., Reynolds, P. M., Gadegaard, N., Dalby, M. J., & Salmerón-Sánchez, M. (2016). Protein Adsorption as a Key Mediator in the Nanotopographical Control of Cell Behavior. ACS Nano, 10(7), 6638-6647. doi:10.1021/acsnano.6b01649Cantini, M., Rico, P., Moratal, D., & Salmerón-Sánchez, M. (2012). Controlled wettability, same chemistry: biological activity of plasma-polymerized coatings. Soft Matter, 8(20), 5575. doi:10.1039/c2sm25413aChu, P. (2002). Plasma-surface modification of biomaterials. Materials Science and Engineering: R: Reports, 36(5-6), 143-206. doi:10.1016/s0927-796x(02)00004-9Zoppe, J. O., Ataman, N. C., Mocny, P., Wang, J., Moraes, J., & Klok, H.-A. (2017). Surface-Initiated Controlled Radical Polymerization: State-of-the-Art, Opportunities, and Challenges in Surface and Interface Engineering with Polymer Brushes. Chemical Reviews, 117(3), 1105-1318. doi:10.1021/acs.chemrev.6b00314Yasuda, H., & Yasuda, T. (2000). The competitive ablation and polymerization (CAP) principle and the plasma sensitivity of elements in plasma polymerization and treatment. Journal of Polymer Science Part A: Polymer Chemistry, 38(6), 943-953. doi:10.1002/(sici)1099-0518(20000315)38:63.0.co;2-3Ma, H., Textor, M., Clark, R. L., & Chilkoti, A. (2006). Monitoring kinetics of surface initiated atom transfer radical polymerization by quartz crystal microbalance with dissipation. Biointerphases, 1(1), 35-39. doi:10.1116/1.2190697Ohno, S., & Matyjaszewski, K. (2006). Controlling grafting density and side chain length in poly(n-butyl acrylate) by ATRP copolymerization of macromonomers. Journal of Polymer Science Part A: Polymer Chemistry, 44(19), 5454-5467. doi:10.1002/pola.21669Kang, C., Crockett, R. M., & Spencer, N. D. (2013). Molecular-Weight Determination of Polymer Brushes Generated by SI-ATRP on Flat Surfaces. Macromolecules, 47(1), 269-275. doi:10.1021/ma401951wXiao, D., & Wirth, M. J. (2002). Kinetics of Surface-Initiated Atom Transfer Radical Polymerization of Acrylamide on Silica. Macromolecules, 35(8), 2919-2925. doi:10.1021/ma011313xShinoda, H., & Matyjaszewski, K. (2001). Structural Control of Poly(Methyl Methacrylate)-g-poly(Lactic Acid) Graft Copolymers by Atom Transfer Radical Polymerization (ATRP). Macromolecules, 34(18), 6243-6248. doi:10.1021/ma0105791Xu, F. J., Zhao, J. P., Kang, E. T., & Neoh, K. G. (2007). Surface Functionalization of Polyimide Films via Chloromethylation and Surface-Initiated Atom Transfer Radical Polymerization. Industrial & Engineering Chemistry Research, 46(14), 4866-4873. doi:10.1021/ie0701367Zhou, T., Qi, H., Han, L., Barbash, D., & Li, C. Y. (2016). Towards controlled polymer brushes via a self-assembly-assisted-grafting-to approach. Nature Communications, 7(1). doi:10.1038/ncomms11119Guo, W., Zhu, J., Cheng, Z., Zhang, Z., & Zhu, X. (2011). Anticoagulant Surface of 316 L Stainless Steel Modified by Surface-Initiated Atom Transfer Radical Polymerization. ACS Applied Materials & Interfaces, 3(5), 1675-1680. doi:10.1021/am200215xIgnatova, M., Voccia, S., Gilbert, B., Markova, N., Mercuri, P. S., Galleni, M., … Jérôme, C. (2004). Synthesis of Copolymer Brushes Endowed with Adhesion to Stainless Steel Surfaces and Antibacterial Properties by Controlled Nitroxide-Mediated Radical Polymerization. Langmuir, 20(24), 10718-10726. doi:10.1021/la048347tTaran, E., Donose, B., Higashitani, K., Asandei, A. D., Scutaru, D., & Hurduc, N. (2006). ATRP grafting of styrene from benzyl chloride functionalized polysiloxanes: An AFM and TGA study of the Cu(0)/bpy catalyst. European Polymer Journal, 42(1), 119-125. doi:10.1016/j.eurpolymj.2005.06.030Liu, F., Du, C.-H., Zhu, B.-K., & Xu, Y.-Y. (2007). Surface immobilization of polymer brushes onto porous poly(vinylidene fluoride) membrane by electron beam to improve the hydrophilicity and fouling resistance. Polymer, 48(10), 2910-2918. doi:10.1016/j.polymer.2007.03.033Ulery, B. D., Nair, L. S., & Laurencin, C. T. (2011). Biomedical applications of biodegradable polymers. Journal of Polymer Science Part B: Polymer Physics, 49(12), 832-864. doi:10.1002/polb.22259Saito, E., Liao, E. E., Hu, W., Krebsbach, P. H., & Hollister, S. J. (2011). Effects of designed PLLA and 50:50 PLGA scaffold architectures on bone formation in vivo. Journal of Tissue Engineering and Regenerative Medicine, 7(2), 99-111. doi:10.1002/term.497Wang, Z., Wang, Y., Ito, Y., Zhang, P., & Chen, X. (2016). A comparative study on the in vivo degradation of poly(L-lactide) based composite implants for bone fracture fixation. Scientific Reports, 6(1). doi:10.1038/srep20770Armentano, I., Dottori, M., Fortunati, E., Mattioli, S., & Kenny, J. M. (2010). Biodegradable polymer matrix nanocomposites for tissue engineering: A review. Polymer Degradation and Stability, 95(11), 2126-2146. doi:10.1016/j.polymdegradstab.2010.06.007Cantini, M., Gomide, K., Moulisova, V., González-García, C., & Salmerón-Sánchez, M. (2017). Vitronectin as a Micromanager of Cell Response in Material-Driven Fibronectin Nanonetworks. Advanced Biosystems, 1(9), 1700047. doi:10.1002/adbi.201700047Pelta, J., Berry, H., Fadda, G. C., Pauthe, E., & Lairez, D. (2000). Statistical Conformation of Human Plasma Fibronectin. Biochemistry, 39(17), 5146-5154. doi:10.1021/bi992770xGugutkov, D., González-García, C., Rodríguez Hernández, J. C., Altankov, G., & Salmerón-Sánchez, M. (2009). Biological Activity of the Substrate-Induced Fibronectin Network: Insight into the Third Dimension through Electrospun Fibers. Langmuir, 25(18), 10893-10900. doi:10.1021/la9012203P. Rico Tortosa M. Cantini G. Altankov M. Salmeron‐Sanchez M. Monleón Pradas M. J. Vicent Polymers in Regenerative Medicine: Biomedical Applications from Nano‐ to Macro‐Structures 2014 John Wiley & Sons Inc Hoboken New Jersey 91 146Schwarzbauer, J. E., & DeSimone, D. W. (2011). Fibronectins, Their Fibrillogenesis, and In Vivo Functions. Cold Spring Harbor Perspectives in Biology, 3(7), a005041-a005041. doi:10.1101/cshperspect.a005041Martino, M. M., Tortelli, F., Mochizuki, M., Traub, S., Ben-David, D., Kuhn, G. A., … Hubbell, J. A. (2011). Engineering the Growth Factor Microenvironment with Fibronectin Domains to Promote Wound and Bone Tissue Healing. Science Translational Medicine, 3(100), 100ra89-100ra89. doi:10.1126/scitranslmed.3002614Keselowsky, B. G., Collard, D. M., & García, A. J. (2003). Surface chemistry modulates fibronectin conformation and directs integrin binding and specificity to control cell adhesion. Journal of Biomedical Materials Research Part A, 66A(2), 247-259. doi:10.1002/jbm.a.10537Keselowsky, B. G., Collard, D. M., & Garcı́a, A. J. (2004). Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding. Biomaterials, 25(28), 5947-5954. doi:10.1016/j.biomaterials.2004.01.062Keselowsky, B. G., Collard, D. M., & Garcia, A. J. (2005). Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation. Proceedings of the National Academy of Sciences, 102(17), 5953-5957. doi:10.1073/pnas.0407356102Llopis-Hernández, V., Cantini, M., González-García, C., Cheng, Z. A., Yang, J., Tsimbouri, P. M., … Salmerón-Sánchez, M. (2016). Material-driven fibronectin assembly for high-efficiency presentation of growth factors. Science Advances, 2(8), e1600188. doi:10.1126/sciadv.1600188Ballester-Beltrán, J., Moratal, D., Lebourg, M., & Salmerón-Sánchez, M. (2014). Fibronectin-matrix sandwich-like microenvironments to manipulate cell fate. Biomater. Sci., 2(3), 381-389. doi:10.1039/c3bm60248fRedick, S. D., Settles, D. L., Briscoe, G., & Erickson, H. P. (2000). Defining Fibronectin’s Cell Adhesion Synergy Site by Site-Directed Mutagenesis. Journal of Cell Biology, 149(2), 521-527. doi:10.1083/jcb.149.2.521Tanaka, K., Sato, K., Yoshida, T., Fukuda, T., Hanamura, K., Kojima, N., … Watanabe, H. (2011). Evidence for cell density affecting C2C12 myogenesis: possible regulation of myogenesis by cell-cell communication. Muscle & Nerve, 44(6), 968-977. doi:10.1002/mus.22224Allingham, J. S., Smith, R., & Rayment, I. (2005). The structural basis of blebbistatin inhibition and specificity for myosin II. Nature Structural & Molecular Biology, 12(4), 378-379. doi:10.1038/nsmb908Kovács, M., Tóth, J., Hetényi, C., Málnási-Csizmadia, A., & Sellers, J. R. (2004). Mechanism of Blebbistatin Inhibition of Myosin II. Journal of Biological Chemistry, 279(34), 35557-35563. doi:10.1074/jbc.m405319200Cai, Y., Rossier, O., Gauthier, N. C., Biais, N., Fardin, M.-A., Zhang, X., … Sheetz, M. P. (2010). Cytoskeletal coherence requires myosin-IIA contractility. Journal of Cell Science, 123(3), 413-423. doi:10.1242/jcs.058297González-García, C., Moratal, D., Oreffo, R. O. C., Dalby, M. J., & Salmerón-Sánchez, M. (2012). Surface mobility regulates skeletal stem cell differentiation. Integrative Biology, 4(5), 531. doi:10.1039/c2ib00139jHorzum, U., Ozdil, B., & Pesen-Okvur, D. (2014). Step-by-step quantitative analysis of focal adhesions. MethodsX, 1, 56-59. doi:10.1016/j.mex.2014.06.004Selinummi, J., Seppälä, J., Yli-Harja, O., & Puhakka, J. A. (2005). Software for quantification of labeled bacteria from digital microscope images by automated image analysis. BioTechniques, 39(6), 859-863. doi:10.2144/000112018Leahy, D. J., Aukhil, I., & Erickson, H. P. (1996). 2.0 Å Crystal Structure of a Four-Domain Segment of Human Fibronectin Encompassing the RGD Loop and Synergy Region. Cell, 84(1), 155-164. doi:10.1016/s0092-8674(00)81002-

Moments and associated measures of copulas with fractal support

Copulas are closely related to the study of distributions and the dependence between random variables. In this paper we develop a recurrence formula for the moments of a measure associated with a copula (a bivariate distribution function with uniform one-dimensional marginals) in the case that its support is a fractal set. We do the same for its principal and secondary diagonals. We also study certain measures of dependence or association for these copulas with fractal supports

Maintenance of chondrocyte phenotype during expansion on PLLA microtopographies

[EN] Articular chondrocytes are difficult to grow, as they lose their characteristic phenotype following expansion on standard tissue culture plates. Here, we show that culturing them on surfaces of poly(L-lactic acid) of well-defined microtopography allows expansion and maintenance of characteristic chondrogenic markers. We investigated the dynamics of human chondrocyte dedifferentiation on the different poly(L-lactic acid) microtopographies by the expression of collagen type I, collagen type II and aggrecan at different culture times. When seeded on poly(L-lactic acid), chondrocytes maintained their characteristic hyaline phenotype up to 7days, which allowed to expand the initial cell population approximately six times without cell dedifferentiation. Maintenance of cell phenotype was afterwards correlated to cell adhesion on the different substrates. Chondrocytes adhesion occurs via the (51) integrin on poly(L-lactic acid), suggesting cell-fibronectin interactions. However, (21) integrin is mainly expressed on the control substrate after 1day of culture, and the characteristic chondrocytic markers are lost (collagen type II expression is overcome by the synthesis of collagen type I). Expanding chondrocytes on poly(L-lactic acid) might be an effective solution to prevent dedifferentiation and improving the number of cells needed for autologous chondrocyte transplantation.The support received from the European Research Council (ERC 306990) and the UK EPSRC (EP/P001114/1) is acknowledged. J.L.G.R. acknowledges support of the Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2016-76039-C4-1 (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 Programme, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Costa Martínez, E.; González García, C.; Gómez Ribelles, JL.; Salmerón Sánchez, M. (2018). Maintenance of chondrocyte phenotype during expansion on PLLA microtopographies. Journal of Tissue Engineering. 9. https://doi.org/10.1177/2041731418789829S9Hunziker, E. B. (1999). Articular cartilage repair: are the intrinsic biological constraints undermining this process insuperable? Osteoarthritis and Cartilage, 7(1), 15-28. doi:10.1053/joca.1998.0159Benya, P. D., Padilla, S. R., & Nimni, M. E. (1978). Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture. Cell, 15(4), 1313-1321. doi:10.1016/0092-8674(78)90056-9Mayne, R., Vail, M. S., Mayne, P. M., & Miller, E. J. (1976). Changes in type of collagen synthesized as clones of chick chondrocytes grow and eventually lose division capacity. Proceedings of the National Academy of Sciences, 73(5), 1674-1678. doi:10.1073/pnas.73.5.1674VON DER MARK, K., GAUSS, V., VON DER MARK, H., & MÜLLER, P. (1977). Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature, 267(5611), 531-532. doi:10.1038/267531a0Darling, E. M., & Athanasiou, K. A. (2005). Rapid phenotypic changes in passaged articular chondrocyte subpopulations. Journal of Orthopaedic Research, 23(2), 425-432. doi:10.1016/j.orthres.2004.08.008Brodkin, K. R., Garcı́a, A. J., & Levenston, M. E. (2004). Chondrocyte phenotypes on different extracellular matrix monolayers. Biomaterials, 25(28), 5929-5938. doi:10.1016/j.biomaterials.2004.01.044Martin, I., Suetterlin, R., Baschong, W., Heberer, M., Vunjak-Novakovic, G., & Freed, L. E. (2001). Enhanced cartilage tissue engineering by sequential exposure of chondrocytes to FGF-2 during 2D expansion and BMP-2 during 3D cultivation. Journal of Cellular Biochemistry, 83(1), 121-128. doi:10.1002/jcb.1203Curtis, A. S., Forrester, J. V., McInnes, C., & Lawrie, F. (1983). Adhesion of cells to polystyrene surfaces. Journal of Cell Biology, 97(5), 1500-1506. doi:10.1083/jcb.97.5.1500Wyre, R. M., & Downes, S. (2002). The role of protein adsorption on chondrocyte adhesion to a heterocyclic methacrylate polymer system. Biomaterials, 23(2), 357-364. doi:10.1016/s0142-9612(01)00113-2Loty, C., Forest, N., Boulekbache, H., Kokubo, T., & Sautier, J. M. (1997). Behavior of fetal rat chondrocytes cultured on a bioactive glass-ceramic. Journal of Biomedical Materials Research, 37(1), 137-149. doi:10.1002/(sici)1097-4636(199710)37:13.0.co;2-dSHAKIBAEI, M. (1997). INTEGRIN EXPRESSION AND COLLAGEN TYPE II IMPLICATED IN MAINTENANCE OF CHONDROCYTE SHAPE IN MONOLAYER CULTURE: AN IMMUNOMORPHOLOGICAL STUDY. Cell Biology International, 21(2), 115-125. doi:10.1006/cbir.1996.0118Kuettner, K. E., Memoli, V. A., Pauli, B. U., Wrobel, N. C., Thonar, E. J., & Daniel, J. C. (1982). Synthesis of cartilage matrix by mammalian chondrocytes in vitro. II. Maintenance of collagen and proteoglycan phenotype. Journal of Cell Biology, 93(3), 751-757. doi:10.1083/jcb.93.3.751G., S.-T., Souza, P. de, Castrejon, H. V., T., J., H.-J., M., A., S., & M., S. (2002). Redifferentiation of dedifferentiated human chondrocytes in high-density cultures. Cell and Tissue Research, 308(3), 371-379. doi:10.1007/s00441-002-0562-7Woodfield, T. B. F., Miot, S., Martin, I., van Blitterswijk, C. A., & Riesle, J. (2006). The regulation of expanded human nasal chondrocyte re-differentiation capacity by substrate composition and gas plasma surface modification. Biomaterials, 27(7), 1043-1053. doi:10.1016/j.biomaterials.2005.07.032Benya, P. D., Brown, P. D., & Padilla, S. R. (1988). Microfilament modification by dihydrocytochalasin B causes retinoic acid-modulated chondrocytes to reexpress the differentiated collagen phenotype without a change in shape. Journal of Cell Biology, 106(1), 161-170. doi:10.1083/jcb.106.1.161Brown, P. D., & Benya, P. D. (1988). Alterations in chondrocyte cytoskeletal architecture during phenotypic modulation by retinoic acid and dihydrocytochalasin B-induced reexpression. Journal of Cell Biology, 106(1), 171-179. doi:10.1083/jcb.106.1.171Martínez, E. C., Hernández, J. C. R., Machado, M., Mano, J. F., Ribelles, J. L. G., Pradas, M. M., & Sánchez, M. S. (2008). Human Chondrocyte Morphology, Its Dedifferentiation, and Fibronectin Conformation on Different PLLA Microtopographies. Tissue Engineering Part A, 14(10), 1751-1762. doi:10.1089/ten.tea.2007.0270Hernández Sánchez, F., Molina Mateo, J., Romero Colomer, F. J., Salmerón Sánchez, M., Gómez Ribelles, J. L., & Mano, J. F. (2005). Influence of Low-Temperature Nucleation on the Crystallization Process of Poly(l-lactide). Biomacromolecules, 6(6), 3283-3290. doi:10.1021/bm050323tZhang, T., Gong, T., Xie, J., Lin, S., Liu, Y., Zhou, T., & Lin, Y. (2016). Softening Substrates Promote Chondrocytes Phenotype via RhoA/ROCK Pathway. ACS Applied Materials & Interfaces, 8(35), 22884-22891. doi:10.1021/acsami.6b07097Schuh, E., Hofmann, S., Stok, K. S., Notbohm, H., Müller, R., & Rotter, N. (2011). The influence of matrix elasticity on chondrocyte behavior in 3D. Journal of Tissue Engineering and Regenerative Medicine, 6(10), e31-e42. doi:10.1002/term.501Parreno, J., Bianchi, V. J., Sermer, C., Regmi, S. C., Backstein, D., Schmidt, T. A., & Kandel, R. A. (2018). Adherent agarose mold cultures: An in vitro platform for multi-factorial assessment of passaged chondrocyte redifferentiation. Journal of Orthopaedic Research®, 36(9), 2392-2405. doi:10.1002/jor.23896Mao, Y., Hoffman, T., Wu, A., & Kohn, J. (2017). An Innovative Laboratory Procedure to Expand Chondrocytes with Reduced Dedifferentiation. CARTILAGE, 9(2), 202-211. doi:10.1177/1947603517746724Shao, X., Lin, S., Peng, Q., Shi, S., Wei, X., Zhang, T., & Lin, Y. (2017). Tetrahedral DNA Nanostructure: A Potential Promoter for Cartilage Tissue Regeneration via Regulating Chondrocyte Phenotype and Proliferation. Small, 13(12), 1602770. doi:10.1002/smll.201602770Li, S., Wang, X., Cao, B., Ye, K., Li, Z., & Ding, J. (2015). Effects of Nanoscale Spatial Arrangement of Arginine–Glycine–Aspartate Peptides on Dedifferentiation of Chondrocytes. Nano Letters, 15(11), 7755-7765. doi:10.1021/acs.nanolett.5b04043Rosenzweig, D. H., Matmati, M., Khayat, G., Chaudhry, S., Hinz, B., & Quinn, T. M. (2012). Culture of Primary Bovine Chondrocytes on a Continuously Expanding Surface Inhibits Dedifferentiation. Tissue Engineering Part A, 18(23-24), 2466-2476. doi:10.1089/ten.tea.2012.0215Hoshiba, T., Yamada, T., Lu, H., Kawazoe, N., & Chen, G. (2011). Maintenance of cartilaginous gene expression on extracellular matrix derived from serially passaged chondrocytes during in vitro chondrocyte expansion. Journal of Biomedical Materials Research Part A, 100A(3), 694-702. doi:10.1002/jbm.a.34003SIPE, J. D. (2002). Tissue Engineering and Reparative Medicine. Annals of the New York Academy of Sciences, 961(1), 1-9. doi:10.1111/j.1749-6632.2002.tb03040.xGriffith, L. G. (2002). Tissue Engineering--Current Challenges and Expanding Opportunities. Science, 295(5557), 1009-1014. doi:10.1126/science.1069210Grinnell, F. (1986). Focal adhesion sites and the removal of substratum-bound fibronectin. Journal of Cell Biology, 103(6), 2697-2706. doi:10.1083/jcb.103.6.2697Altankov, G., & Groth, T. (1994). Reorganization of substratum-bound fibronectin on hydrophilic and hydrophobic materials is related to biocompatibility. Journal of Materials Science: Materials in Medicine, 5(9-10), 732-737. doi:10.1007/bf00120366Altankov, G., & Groth, T. (1996). Fibronectin matrix formation and the biocompatibility of materials. Journal of Materials Science: Materials in Medicine, 7(7), 425-429. doi:10.1007/bf00122012Werner, C., Pompe, T., & Salchert, K. (2006). Modulating Extracellular Matrix at Interfaces of Polymeric Materials. Advances in Polymer Science, 63-93. doi:10.1007/12_089Baugh, L., & Vogel, V. (2004). Structural changes of fibronectin adsorbed to model surfaces probed by fluorescence resonance energy transfer. Journal of Biomedical Materials Research, 69A(3), 525-534. doi:10.1002/jbm.a.30026González-García, C., Sousa, S. R., Moratal, D., Rico, P., & Salmerón-Sánchez, M. (2010). Effect of nanoscale topography on fibronectin adsorption, focal adhesion size and matrix organisation. Colloids and Surfaces B: Biointerfaces, 77(2), 181-190. doi:10.1016/j.colsurfb.2010.01.021Garcı́a, A. J., Vega, M. D., & Boettiger, D. (1999). Modulation of Cell Proliferation and Differentiation through Substrate-dependent Changes in Fibronectin Conformation. Molecular Biology of the Cell, 10(3), 785-798. doi:10.1091/mbc.10.3.785Bergkvist, M., Carlsson, J., & Oscarsson, S. (2003). Surface-dependent conformations of human plasma fibronectin adsorbed to silica, mica, and hydrophobic surfaces, studied with use of Atomic Force Microscopy. Journal of Biomedical Materials Research, 64A(2), 349-356. doi:10.1002/jbm.a.10423Johnson, K. J., Sage, H., Briscoe, G., & Erickson, H. P. (1999). The Compact Conformation of Fibronectin Is Determined by Intramolecular Ionic Interactions. Journal of Biological Chemistry, 274(22), 15473-15479. doi:10.1074/jbc.274.22.15473Gugutkov, D., González-García, C., Rodríguez Hernández, J. C., Altankov, G., & Salmerón-Sánchez, M. (2009). Biological Activity of the Substrate-Induced Fibronectin Network: Insight into the Third Dimension through Electrospun Fibers. Langmuir, 25(18), 10893-10900. doi:10.1021/la9012203Garciadiego-Cazares, D. (2004). Coordination of chondrocyte differentiation and joint formation by  5 1 integrin in the developing appendicular skeleton. Development, 131(19), 4735-4742. doi:10.1242/dev.01345Kurtis, M. S., Schmidt, T. A., Bugbee, W. D., Loeser, R. F., & Sah, R. L. (2003). Integrin-mediated adhesion of human articular chondrocytes to cartilage. Arthritis & Rheumatism, 48(1), 110-118. doi:10.1002/art.10704Enomoto-Iwamoto, M., Iwamoto, M., Nakashima, K., Mukudai, Y., Boettiger, D., Pacifici, M., … Suzuki, F. (1997). Involvement of α5β1 Integrin in Matrix Interactions and Proliferation of Chondrocytes. Journal of Bone and Mineral Research, 12(7), 1124-1132. doi:10.1359/jbmr.1997.12.7.1124Millward-Sadler, S. J., & Salter, D. M. (2004). Integrin-Dependent Signal Cascades in Chondrocyte Mechanotransduction. Annals of Biomedical Engineering, 32(3), 435-446. doi:10.1023/b:abme.0000017538.72511.48Käpylä, J., Ivaska, J., Riikonen, R., Nykvist, P., Pentikäinen, O., Johnson, M., & Heino, J. (2000). Integrin α2I Domain Recognizes Type I and Type IV Collagens by Different Mechanisms. Journal of Biological Chemistry, 275(5), 3348-3354. doi:10.1074/jbc.275.5.3348Nykvist, P., Tu, H., Ivaska, J., Käpylä, J., Pihlajaniemi, T., & Heino, J. (2000). Distinct Recognition of Collagen Subtypes by α1β1and α2β1Integrins. Journal of Biological Chemistry, 275(11), 8255-8261. doi:10.1074/jbc.275.11.8255Tulla, M., Pentikäinen, O. T., Viitasalo, T., Käpylä, J., Impola, U., Nykvist, P., … Heino, J. (2001). Selective Binding of Collagen Subtypes by Integrin α1I, α2I, and α10I Domains. Journal of Biological Chemistry, 276(51), 48206-48212. doi:10.1074/jbc.m10405820