The interplay between tissue growth and scaffold degradation in engineered tissue constructs

In vitro tissue engineering is emerging as a potential tool to meet the high demand for replacement tissue, caused by the increased incidence of tissue degeneration and damage. A key challenge in this field is ensuring that the mechanical properties of the engineered tissue are appropriate for the in vivo environment. Achieving this goal will require detailed understanding of the interplay between cell proliferation, extracellular matrix (ECM) deposition and scaffold degradation.\ud \ud In this paper, we use a mathematical model (based upon a multiphase continuum framework) to investigate the interplay between tissue growth and scaffold degradation during tissue construct evolution in vitro. Our model accommodates a cell population and culture medium, modelled as viscous fluids, together with a porous scaffold and ECM deposited by the cells, represented as rigid porous materials. We focus on tissue growth within a perfusion bioreactor system, and investigate how the predicted tissue composition is altered under the influence of (i) differential interactions between cells and the supporting scaffold and their associated ECM, (ii) scaffold degradation, and (iii) mechanotransduction-regulated cell proliferation and ECM deposition.\ud \ud Numerical simulation of the model equations reveals that scaffold heterogeneity typical of that obtained from μCT scans of tissue engineering scaffolds can lead to significant variation in the flow-induced mechanical stimuli experienced by cells seeded in the scaffold. This leads to strong heterogeneity in the deposition of ECM. Furthermore, preferential adherence of cells to the ECM in favour of the artificial scaffold appears to have no significant influence on the eventual construct composition; adherence of cells to these supporting structures does, however, lead to cell and ECM distributions which mimic and exaggerate the heterogeneity of the underlying scaffold. Such phenomena have important ramifications for the mechanical integrity of engineered tissue constructs and their suitability for implantation in vivo

In vitro evaluation of electrospun blends of gelatin and PCL for application as a partial thickness corneal graft

The advent of innovative surgical procedures utilizing partial thickness corneal grafts has created a need for the development of synthetic implants to recreate corneal stromal tissue. This work evaluates electrospun gelatin and polycaprolactone (PCL) scaffolds as a potential biomaterial suitable for use in regeneration of corneal stromal tissue. Electrospun gelatin has been used for many years in tissue engineering, however, post‐production modification, such as crosslinking, is usually required to mechanically strengthen such scaffolds. This paper aims therefore to compare glutaraldehyde (GA) cross‐linked electrospun gelatin scaffolds with electrospun blends of gelatin and PCL at different ratios. Scaffolds were fabricated using electrospinning and characterized by scanning electron microscopy, Attenuated Total Reflectance‐Fourier Transform Infrared Spectroscopy (ATR‐FTIR), and tensile testing. To evaluate biocompatibility, primary human corneal stromal cells (hCSC) were seeded upon the scaffolds to assess adherence, proliferation and phenotype. Results demonstrated that scaffolds fabricated from mixtures of gelatin and PCL showed increased mechanical strength and plasticity compared to scaffolds fabricated from GA cross‐linked gelatin alone. In addition, scaffolds fabricated from PCL and gelatin showed comparable support of hCSC adhesion and proliferation. In conclusion, blended mixtures of gelatin and PCL can be considered as an option in the selection of corneal repair materials in the future

Development and validation of broad-spectrum magnetic particle labelling processes for cell therapy manufacturing

BACKGROUND: Stem cells are increasingly seen as a solution for many health challenges for an ageing population. However, their potential benefits in the clinic are currently curtailed by technical challenges such as high cell dose requirements and point of care delivery, which pose sourcing and logistics challenges. Cell manufacturing solutions are currently in development to address the supply issue, and ancillary technologies such as nanoparticle-based labelling are being developed to improve stem cell delivery and enable post-treatment follow-up. METHODS: The application of magnetic particle (MP) labelling to potentially scalable cell manufacturing processes was investigated in a range of therapeutically relevant cells, including mesenchymal stromal cells (MSC), cardiomyocytes (CMC) and neural progenitor cells (ReN). The efficiency and the biological effect of particle labelling were analysed using fluorescent imaging and cellular assays. RESULTS: Flow cytometry and fluorescent microscopy confirmed efficient labelling of monolayer cultures. Viability was shown to be retained post labelling for all three cell types. MSC and CMC demonstrated higher tolerance to MP doses up to 100× the standard concentration. This approach was also successful for MP labelling of suspension cultures, demonstrating efficient MP uptake within 3 h, while cell viability was unaffected by this suspension labelling process. Furthermore, a procedure to enable the storing of MP-labelled cell populations to facilitate cold chain transport to the site of clinical use was investigated. When MP-labelled cells were stored in hypothermic conditions using HypoThermosol solution for 24 h, cell viability and differentiation potential were retained post storage for ReN, MSC and beating CMC. CONCLUSIONS: Our results show that a generic MP labelling strategy was successfully developed for a range of clinically relevant cell populations, in both monolayer and suspension cultures. MP-labelled cell populations were able to undergo transient low-temperature storage whilst maintaining functional capacity in vitro. These results suggest that this MP labelling approach can be integrated into cell manufacturing and cold chain transport processes required for future cell therapy approaches

Dynamic studies of biomimetic coated polycaprolactone nanofiber meshes as bone extracellular matrix analogues

This work aimed at studying the effects of dynamic culture conditions and biomimetic coating on bone cells grown on nanofiber meshes. In our previous work, biomimetic calcium phosphate coated polycaprolactone nanofibre meshes (BCP-NM) proved to be more efficient for supporting cell attachment and proliferation under static conditions, when compared to polycaprolactone nanofibre meshe (PCL-NM). However, no studies on the influence of bioreactors on the behaviour of cells cultivated on these materials were developed so far. [...]info:eu-repo/semantics/publishedVersio

The effect of reverse current on the dark properties of photovoltaic solar modules

AbstractForward and reverse dark current-voltage (I-V) and capacitance-voltage (C-V) characteristics of commercial amorphous silicon solar modules, were measured in order to study their performance under the influence of induced reverse currents. Maximum module surface temperatures were directly related to each value of the induced reverse current and in to the amount of current leakage respectively. Microscopic changes as a result of hot spots defects and overheating of the solar module, linked to reverse current effects, were also documented and discussed. Experimental evidence showed that different levels of reverse currents are confirmed to be a major degrading factor affecting the performance, efficiency, and power of solar modules

Music causes deterioration of source memory: Evidence from normal ageing

Previous research shows that music exposure can impair a wide variety of cognitive and behavioral performance. We investigated whether this is the case for source memory. Forty-one younger adults and thirty-five healthy elderly were required to retain the location in which pictures of colored objects were displayed. On a subsequent recognition test they were required to decide whether the objects were displayed in the same location as before or not. Encoding took place 1) in silence, 2) while listening to street noise, or 3) while listening to Vivaldi’s “Four seasons”. Recognition always took place during silence. A significant reduction in source memory was observed following music exposure, a reduction that was more pronounced for older adults than for younger adults. This pattern was significantly correlated with performance on an executive binding task. The exposure to music appeared to interfere with binding in working memory, worsening source recall

Parallelized Manipulation of Adherent Living Cells by Magnetic Nanoparticles-Mediated Forces

The remote actuation of cellular processes such as migration or neuronal outgrowth is a challenge for future therapeutic applications in regenerative medicine. Among the different methods that have been proposed, the use of magnetic nanoparticles appears to be promising, since magnetic fields can act at a distance without interactions with the surrounding biological system. To control biological processes at a subcellular spatial resolution, magnetic nanoparticles can be used either to induce biochemical reactions locally or to apply forces on different elements of the cell. Here, we show that cell migration and neurite outgrowth can be directed by the forces produced by a switchable parallelized array of micro-magnetic pillars, following the passive uptake of nanoparticles. Using live cell imaging, we first demonstrate that adherent cell migration can be biased toward magnetic pillars and that cells can be reversibly trapped onto these pillars. Second, using differentiated neuronal cells we were able to induce events of neurite outgrowth in the direction of the pillars without impending cell viability. Our results show that the range of forces applied needs to be adapted precisely to the cellular process under consideration. We propose that cellular actuation is the result of the force on the plasma membrane caused by magnetically filled endo-compartments, which exert a pulling force on the cell periphery

Pressure-induced phonon-freezing in the ZnBeSe alloy: a study via the percolation mesoscope

We use the 1-bond -> 2-phonon percolation doublet of zincblende alloys as a mesoscope for an unusual insight into their phonon behavior under pressure. We focus on (Zn,Be)Se and show by Raman scattering that the original Be-Se doublet at ambient pressure, of the stretching-bending type, turns into a pure-bending singlet at the approach of the high-pressure ZnSe-like rocksalt phase, an unnatural one for the Be-Se bonds. The freezing of the Be-Se stretching mode is discussed within the scope of the percolation model (mesoscopic scale), with ab initio calculations in support (microscopic scale).Comment: 11 pages, 3 figure

A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: results of a multicentre analysis.

New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines

A dynamic power-aware partitioner with task migration for multicore embedded systems

Nowadays, a key design issue in embedded systems is how to reduce the power consumption, since batteries have a limited energy budget. For this purpose, several techniques such as Dynamic Voltage Scaling (DVS) or task migration can be used. DVS allows reducing power by selecting the optimal voltage supply, while task migration achieves this effect by balancing the workload among cores. This paper first analyzes the impact on energy due to task migration in multicore embedded systems with DVS capability and using the well-known Worst Fit (WF) partitioning heuristic. To reduce overhead, migrations are only performed at the time that a task arrives to and/or leaves the system and, in such a case, only one migration is allowed. The huge potential on energy saving due to task migration, leads us to propose a new dynamic partitioner, namely DP, that migrates tasks in a more efficient way than typical partitioners. Unlike WF, the proposed algorithm examines which is the optimal target core before allowing a migration. Experimental results show that DP can improve energy consumption in a factor up to 2.74 over the typical WF algorithm. © 2011 Springer-Verlag.This work was supported by Spanish CICYT under Grant TIN2009-14475-C04-01, and by Consolider-Ingenio under Grant CSD2006-00046.March Cabrelles, JL.; Sahuquillo Borrás, J.; Petit Martí, SV.; Hassan Mohamed, H.; Duato Marín, JF. (2011). A dynamic power-aware partitioner with task migration for multicore embedded systems. En Euro-Par 2011 Parallel Processing. Springer Verlag (Germany). 2011(6852):218-229. https://doi.org/10.1007/978-3-642-23400-2_21S21822920116852AlEnawy, T.A., Aydin, H.: Energy-Aware Task Allocation for Rate Monotonic Scheduling. In: Proceedings of the 11th Real Time on Embedded Technology and Applications Symposium, March 7-10, pp. 213–223. IEEE Computer Society, San Francisco (2005)Aydin, H., Yang, Q.: Energy-Aware Partitioning for Multiprocessor Real-Time Systems. In: Proceedings of the 17th International Parallel and Distributed Processing Symposium, Workshop on Parallel and Distributed Real-Time Systems, April 22-26, p. 113. IEEE Computer Society, Nice (2003)Baker, T.P.: An Analysis of EDF schedulability on a multiprocessor. IEEE Transactions on Parallel and Distributed Systems 16(8), 760–768 (2005)Brandenburg, B.B., Calandrino, J.M., Anderson, J.H.: On the Scalability of Real-Time Scheduling Algorithms on Multicore Platforms: A Case Study. In: Proceedings of the 29th Real-Time Systems Symposium, November 30-December 3, pp. 157–169. IEEE Computer Society, Barcelona (2008)Brião, E., Barcelos, D., Wronski, F., Wagner, F.R.: Impact of Task Migration in NoC-based MPSoCs for Soft Real-time Applications. In: Proceedings of the International Conference on VLSI, October 15-17, pp. 296–299. IEEE Computer Society, Atlanta (2007)Cazorla, F., Knijnenburg, P., Sakellariou, R., Fernández, E., Ramirez, A., Valero, M.: Predictable Performance in SMT Processors: Synergy between the OS and SMTs. IEEE Transactions on Computers 55(7), 785–799 (2006)Donald, J., Martonosi, M.: Techniques for Multicore Thermal Management: Classification and New Exploration. In: Proceedings of the 33rd Annual International Symposium on Computer Architecture, June 17-21, pp. 78–88. IEEE Computer Society, Boston (2006)El-Haj-Mahmoud, A., AL-Zawawi, A., Anantaraman, A., Rotenberg, E.: Virtual Multiprocessor: An Analyzable, High-Performance Architecture for Real-Time Computing. In: Proceedings of the International Conference on Compilers, Architectures and Synthesis for Embedded Systems, September 24-27, pp. 213–224. ACM Press, San Francisco (2005)Hung, C., Chen, J., Kuo, T.: Energy-Efficient Real-Time Task Scheduling for a DVS System with a Non-DVS Processing Element. In: Proceedings of the 27th Real-Time Systems Symposium, December 5-8, pp. 303–312. IEEE Computer Society, Rio de Janeiro (2006)Kalla, R., Sinharoy, B., Tendler, J.M.: IBM Power5 Chip: A Dual-Core Multithreaded Processor. IEEE Micro 24(2), 40–47 (2004)Kato, S., Yamasaki, N.: Global EDF-based Scheduling with Efficient Priority Promotion. In: Proceedings of the 14th International Conference on Embedded and Real-Time Computing Systems and Applications, August 25-27, pp. 197–206. IEEE Computer Society, Kaohisung (2008)Malardalen Real-Time Research Center, Vasteras, Sweden: WCET Analysis Project. WCET Benchmark Programs (2006), [Online], http://www.mrtc.mdh.se/projects/wcet/March, J., Sahuquillo, J., Hassan, H., Petit, S., Duato, J.: A New Energy-Aware Dynamic Task Set Partitioning Algorithm for Soft and Hard Embedded Real-Time Systems. To be published on The Computer Journal (2011)McNairy, C., Bhatia, R.: Montecito: A Dual-Core, Dual-Thread Itanium Processor. IEEE Micro 25(2), 10–20 (2005)Seo, E., Jeong, J., Park, S., Lee, J.: Energy Efficient Scheduling of Real-Time Tasks on Multicore Processors. IEEE Transactions on Parallel and Distributed Systems 19(11), 1540–1552 (2008)Shah, A.: Arm plans to add multithreading to chip design. ITworld (2010), [Online], http://www.itworld.com/hardware/122383/arm-plans-add-multithreading-chip-designUbal, R., Sahuquillo, J., Petit, S., López, P.: Multi2Sim: A Simulation Framework to Evaluate Multicore-Multithreaded Processors. In: Proceedings of the 19th International Symposium on Computer Architecture and High Performance Computing, October 24-27, pp. 62–68. IEEE Computer Society, Gramado (2007)Watanabe, R., Kondo, M., Imai, M., Nakamura, H., Nanya, T.: Task Scheduling under Performance Constraints for Reducing the Energy Consumption of the GALS Multi-Processor SoC. In: Proceedings of the Design Automation and Test in Europe, April 16-20, pp. 797–802. ACM, Nice (2007)Wei, Y., Yang, C., Kuo, T., Hung, S.: Energy-Efficient Real-Time Scheduling of Multimedia Tasks on Multi-Core Processors. In: Proceedings of the 25th Symposium on Applied Computing, March 22-26, pp. 258–262. ACM, Sierre (2010)Wu, Q., Martonosi, M., Clark, D.W., Reddi, V.J., Connors, D., Wu, Y., Lee, J., Brooks, D.: A Dynamic Compilation Framework for Controlling Microprocessor Energy and Performance. In: Proceedings of the 38th Annual IEEE/ACM International Symposium on Microarchitecture, November 12-16, pp. 271–282. IEEE Computer Society, Barcelona (2005)Zheng, L.: A Task Migration Constrained Energy-Efficient Scheduling Algorithm for Multiprocessor Real-time Systems. In: Proceedings of the International Conference on Wireless Communications, Networking and Mobile Computing, September 21-25, pp. 3055–3058. IEEE Computer Society, Shanghai (2007