Controlled Assembly of Macromolecular β-Sheet Fibrils

Construction of functional molecular devices by directed assembly processes is one of the main challenges in the field of nanotechnology. Many approaches to this challenge use biological assembly as a source of inspiration for the build up of new materials with controlled organization at the nanoscale. In particular, the self-assembly properties of β-sheet peptides have been used in the design of supramolecular materials, such as tapes, nanotubes, and fibrils

Dynamic Power Management for Reactive Stream Processing on the SCC Tiled Architecture

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Dynamic voltage and frequency scaling} (DVFS) is a means to adjust the computing capacity and power consumption of computing systems to the application demands. DVFS is generally useful to provide a compromise between computing demands and power consumption, especially in the areas of resource-constrained computing systems. Many modern processors support some form of DVFS. In this article we focus on the development of an execution framework that provides light-weight DVFS support for reactive stream-processing systems (RSPS). RSPS are a common form of embedded control systems, operating in direct response to inputs from their environment. At the execution framework we focus on support for many-core scheduling for parallel execution of concurrent programs. We provide a DVFS strategy for RSPS that is simple and lightweight, to be used for dynamic adaptation of the power consumption at runtime. The simplicity of the DVFS strategy became possible by sole focus on the application domain of RSPS. The presented DVFS strategy does not require specific assumptions about the message arrival rate or the underlying scheduling method. While DVFS is a very active field, in contrast to most existing research, our approach works also for platforms like many-core processors, where the power settings typically cannot be controlled individually for each computational unit. We also support dynamic scheduling with variable workload. While many research results are provided with simulators, in our approach we present a parallel execution framework with experiments conducted on real hardware, using the SCC many-core processor. The results of our experimental evaluation confirm that our simple DVFS strategy provides potential for significant energy saving on RSPS.Peer reviewe

Computer-aided design of elastin-like polypeptides with controlled viscoelastic and structural properties

The biofabrication of structural proteins with controllable properties via amino acid sequence design is interesting for biomedicine and biotechnology, yet design rules that link amino acid sequence to material properties remain largely unknown. Molecular dynamics (MD) simulations can help in unveiling such rules, but the lack of a standardised framework to interpret the outcome of those simulation hinders their predictive value for the design of de novo structural proteins, To address this, we developed a model that unambiguously classifies a library of de novo elastin-like polypeptides (ELPs) with varying numbers and locations of hydrophobic/hydrophilic and physical/chemical-crosslinking blocks according to their thermoresponsiveness at physiological temperature. Our approach does not require long simulation times or advanced sampling methods. Instead, we apply (un)supervised data analysis methods to a dataset of molecular properties from relatively short MD simulations (150 ns). We also investigate the rheological properties and microstructure of ELP hydrogels, revealing handles to tune them: chain hydrophilicity/hydrophobicity or block distribution control the viscoelasticity and thermoresponsiveness, whereas ELP concentration defines the network permeability. Our findings provide an avenue to accelerate the design of de novo ELPs with bespoke material properties

Sequence Control of the Self-Assembly of Elastin-Like Polypeptides into Hydrogels with Bespoke Viscoelastic and Structural Properties

The biofabrication of structural proteins with controllable properties via amino acid sequence design is interesting for biomedicine and biotechnology, yet a complete framework that connects amino acid sequence to material properties is unavailable, despite great progress to establish design rules for synthesizing peptides and proteins with specific conformations (e.g., unfolded, helical, β-sheets, or β-turns) and intermolecular interactions (e.g., amphipathic peptides or hydrophobic domains). Molecular dynamics (MD) simulations can help in developing such a framework, but the lack of a standardized way of interpreting the outcome of these simulations hinders their predictive value for the design of de novo structural proteins. To address this, we developed a model that unambiguously classifies a library of de novo elastin-like polypeptides (ELPs) with varying numbers and locations of hydrophobic/hydrophilic and physical/chemical-cross-linking blocks according to their thermoresponsiveness at physiological temperature. Our approach does not require long simulation times or advanced sampling methods. Instead, we apply (un)supervised data analysis methods to a data set of molecular properties from relatively short MD simulations (150 ns). We also experimentally investigate hydrogels of those ELPs from the library predicted to be thermoresponsive, revealing several handles to tune their mechanical and structural properties: chain hydrophilicity/hydrophobicity or block distribution control the viscoelasticity and thermoresponsiveness, whereas ELP concentration defines the network permeability. Our findings provide an avenue to accelerate the design of de novo ELPs with bespoke phase behavior and material properties. BN/Gijsje Koenderink La

Polymers in Cartilage Defect Repair of the Knee: Current Status and Future Prospects

Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based techniques using a wide variety of polymers, cell sources, and signaling molecules have been evaluated. We start this review with basic background information on cartilage structure, its intrinsic repair, and an overview of the cartilage repair treatments from a historical perspective. Next, we thoroughly discuss polymer construct components and their current use in commercially available constructs. Finally, we provide an in-depth discussion about construct considerations such as degradation rates, cell sources, mechanical properties, joint homeostasis, and non-degradable/hybrid resurfacing techniques. As future prospects in cartilage repair, we foresee developments in three areas: first, further optimization of degradable scaffolds towards more biomimetic grafts and improved joint environment. Second, we predict that patient-specific non-degradable resurfacing implants will become increasingly applied and will provide a feasible treatment for older patients or failed regenerative treatments. Third, we foresee an increase of interest in hybrid construct, which combines degradable with non-degradable materials

In vitro and in vivo study on the osseointegration of BCP-coated versus uncoated nondegradable thermoplastic polyurethane focal knee resurfacing implants

Focal knee resurfacing implants (FKRIs) are intended to treat cartilage defects in middle-aged patients. Most FKRIs are metal-based, which hampers follow-up of the joint using magnetic resonance imaging and potentially leads to damage of the opposing cartilage. The purpose of this study was to develop a nondegradable thermoplastic polyurethane (TPU) FKRI and investigate its osseointegration. Different surface roughness modifications and biphasic calcium phosphate (BCP) coating densities were first tested in vitro on TPU discs. The in vivo osseointegration of BCP-coated TPU implants was subsequently compared to uncoated TPU implants and the titanium bottom layer of metal control implants in a caprine model. Implants were implanted bilaterally in stifle joints and animals were followed for 12 weeks, after which the bone-to-implant contact area (BIC) was assessed. Additionally, 18F-sodium-fluoride (18F-NaF) positron emission tomography PET/CT-scans were obtained at 3 and 12 weeks to visualize the bone metabolism over time. The BIC was significantly higher for the BCP-coated TPU implants compared to the uncoated TPU implants (p= .03), and did not significantly differ from titanium (p= .68). Similar 18F-NaF tracer uptake patterns were observed between 3 and 12 weeks for the BCP-coated TPU and titanium implants, but not for the uncoated implants. TPU FKRIs with surface modifications could provide the answer to the drawbacks of metal FKRIs

Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs ("placebo") (n = 10) and evaluated by clinical examination, gait analysis, owners' questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24-2.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10-3.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study; disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc