Residual Bioprosthetic Valve Immunogenicity: Forgotten, Not Lost

Despite early realization of the need to control inherent immunogenicity of bioprosthetic replacement heart valves and thereby mitigate the ensuing host response and its associated pathology, including dystrophic calcification, the problem remains unresolved to this day. Concerns over mechanical stiffness associated with prerequisite high cross-link density to effect abrogation of this response, together with the insinuated role of leaching glutaraldehyde monomer in subsequent dystrophic mineralization, have understandably introduced compromises. These have become so entrenched as a benchmark standard that residual immunogenicity of the extracellular matrix has seemingly been relegated to a very subordinate role. Instead, focus has shifted toward the removal of cellular compartment antigens renowned for their implication in the failure of vascularized organ xenotransplants. While decellularization certainly offers advantages, this review aims to refocus attention on the unresolved matter of the host response to the extracellular matrix. Furthermore, by implicating remnant immune and inflammatory processes to bioprosthetic valve pathology, including pannus overgrowth and mineralization, the validity of a preeminent focus on decellularization, in the context of inefficient antigen and possible residual microbial remnant removal, is questioned.

Effect of Conditioning on PU Foam Matrix Materials Properties

This article deals with the characterization of the thermal-induced aging of soft polyurethane (PU) foams. There are studied thermal and mechanical properties by means of thermal analysis, tensile, compression and dynamic mechanical vibration testing. It was found in this study, that the increasing relative humidity of the surrounding atmosphere leads to the initiation of the degradation processes. This is reflected in the observed decreased mechanical stiffness. It is attributed to the plasticization of the PU foams wall material. It is in agreement with the observed increase of the permanent deformation accompanied simultaneously with the decrease of Young’s modulus of elasticity. The latter phenomenon is studied by the novel non-destructive forced oscillations vibration-damping testing, which is confirmed by observed lower mechanical stiffness thus indicating the loss of the elasticity induced by samples conditioning. In parallel, observed decreasing of the matrix hardness is confirming the loss of elastic mechanical performance as well. The effect of conditioning leads to the significant loss of the PU foam’s thermal stability.

Sustainable Bioactive Packaging Based on Thermoplastic Starch and Microalgae

This study combines the use of corn starch and Tetradesmus obliquus microalgae for the production of antioxidant starch films as flexible packaging material. Starch was plasticized with glycerol and blended with 1 w% polyallylamine chosen as an agent to modify the film physical properties. The addition of polyallylamine improved film water stability and water vapor transmission rate as well as mechanical stiffness and tenacity. The dried Tetradesmus obliquus microalgae, which showed an EC50 value of 2.8 mg/mg DPPH (2.2-Diphenyl-1-picrylhydrazyl radical), was then used as antioxidant filler. The addition of microalgae provided the films with good antioxidant activity, which increased with microalgae content increasing. To our knowledge, this is the first study reporting the development of sustainable bioactive packaging films composed of almost 100% starch, and follows the European union’s goals on plastics strategy concerning the promotion of bio-based, compostable plastics and the setting up of approaches to prevent food waste with a simple plastic packaging.

Silicon Nitride, a Bioceramic for Bone Tissue Engineering: A Reinforced Cryogel System With Antibiofilm and Osteogenic Effects

Silicon nitride (SiN [Si3N4]) is a promising bioceramic for use in a wide variety of orthopedic applications. Over the past decades, it has been mainly used in industrial applications, such as space shuttle engines, but not in the medical field due to scarce data on the biological effects of SiN. More recently, it has been increasingly identified as an emerging material for dental and orthopedic implant applications. Although a few reports about the antibacterial properties and osteoconductivity of SiN have been published to date, there have been limited studies of SiN-based scaffolds for bone tissue engineering. Here, we developed a silicon nitride reinforced gelatin/chitosan cryogel system (SiN-GC) by loading silicon nitride microparticles into a gelatin/chitosan cryogel (GC), with the aim of producing a biomimetic scaffold with antibiofilm and osteogenic properties. In this scaffold system, the GC component provides a hydrophilic and macroporous environment for cells, while the SiN component not only provides antibacterial properties and osteoconductivity but also increases the mechanical stiffness of the scaffold. This provides enhanced mechanical support for the defect area and a better osteogenic environment. First, we analyzed the scaffold characteristics of SiN-GC with different SiN concentrations, followed by evaluation of its apatite-forming capacity in simulated body fluid and protein adsorption capacity. We further confirmed an antibiofilm effect of SiN-GC against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) as well as enhanced cell proliferation, mineralization, and osteogenic gene upregulation for MC3T3-E1 pre-osteoblast cells. Finally, we developed a bioreactor to culture cell-laden scaffolds under cyclic compressive loading to mimic physiological conditions and were able to demonstrate improved mineralization and osteogenesis from SiN-GC. Overall, we confirmed the antibiofilm and osteogenic effect of a silicon nitride reinforced cryogel system, and the results indicate that silicon nitride as a biomaterial system component has a promising potential to be developed further for bone tissue engineering applications.

Study of the Mechanical, Sound Absorption and Thermal Properties of Cellular Rubber Composites Filled with a Silica Nanofiller

This paper deals with the study of cellular rubbers, which were filled with silica nanofiller in order to optimize the rubber properties for given purposes. The rubber composites were produced with different concentrations of silica nanofiller at the same blowing agent concentration. The mechanical, sound absorption and thermal properties of the investigated rubber composites were evaluated. It was found that the concentration of silica filler had a significant effect on the above-mentioned properties. It was detected that a higher concentration of silica nanofiller generally led to an increase in mechanical stiffness and thermal conductivity. Conversely, sound absorption and thermal degradation of the investigated rubber composites decreased with an increase in the filler concentration. It can be also concluded that the rubber composites containing higher concentrations of silica filler showed a higher stiffness to weight ratio, which is one of the great advantages of these materials. Based on the experimental data, it was possible to find a correlation between mechanical stiffness of the tested rubber specimens evaluated using conventional and vibroacoustic measurement techniques. In addition, this paper presents a new methodology to optimize the blowing and vulcanization processes of rubber samples during their production.

A nanoscale reciprocating rotary mechanism with coordinated mobility control

Biological molecular motors transform chemical energy into mechanical work by coupling cyclic catalytic reactions to large-scale structural transitions. Mechanical deformation can be surprisingly efficient in realizing such coupling, as demonstrated by the F1FO ATP synthase. Here, we describe a synthetic molecular mechanism that transforms a rotary motion of an asymmetric camshaft into reciprocating large-scale transitions in a surrounding stator orchestrated by mechanical deformation. We design the mechanism using DNA origami, characterize its structure via cryo-electron microscopy, and examine its dynamic behavior using single-particle fluorescence microscopy and molecular dynamics simulations. While the camshaft can rotate inside the stator by diffusion, the stator’s mechanics makes the camshaft pause at preferred orientations. By changing the stator’s mechanical stiffness, we accelerate or suppress the Brownian rotation, demonstrating an allosteric coupling between the camshaft and the stator. Our mechanism provides a framework for manufacturing artificial nanomachines that function because of coordinated movements of their components.

Age-related Aortic Stiffness Can Be Transferred and Ameliorated via Fecal Microbiota Transplant in Mice

Age-related increases in aortic stiffness contribute to the development of cardiovascular diseases (CVD). To determine whether the gut microbiome (GM) modulates age-related aortic stiffening, we performed fecal microbiota transplants (FMT) between young (Y; 3 month) and older (O; 25 month) male C57BL/6N mice. Following antibiotic treatment (to suppress endogenous microbiota), mice received weekly FMT (fecal samples collected at baseline) via oral gavage for 8-16 weeks from their own (i.e., sham condition: Y-y, O-o [RECIPIENT-donor]) or opposite age group (Y-o, O-y) (N=8-12/group). In vivo aortic stiffness (pulse wave velocity [PWV]) was higher in older vs. young mice at baseline (382±8 vs. 328±7cm/sec, mean±SE, P<0.001). Arterial phenotypes were transferred such that old microbiota transplanted into young mice increased, while young into old decreased, PWV (Y-y: 325±10 vs. Y-o: 362±10cm/sec, P=0.022; O-o: 409±10 vs. O-y: 335±6cm/sec, P<0.001). Intrinsic mechanical stiffness of excised aortic rings (elastic modulus) increased after transplant of old into young (Y-y: 2141±223 vs. Y-o: 3218±394kPA, P=0.022), and decreased with young into old (O-O: 3263±217 vs. O-y: 2602±136kPA, P=0.016), indicating the GM mediates aortic stiffening by modulating structural changes in the arterial wall. Age-related increases in aortic abundance of advanced glycation end products (AGEs), which cross-link arterial structural proteins, tended to be transferred by the GM (Y-y: 0.022±0.001 vs. Y-o: 0.038±0.006 A.U., P=0.11; O-o: 0.120±0.029 vs. O-y: 0.038±0.009 A.U., P=0.06). The aging GM can induce aortic stiffening via promoting AGEs accumulation and crosslinking of arterial structural proteins, and thus might be a promising target for preventing/treating age-related aortic stiffening and CVD.

Dendritic Cell Migration Is Tuned by Mechanical Stiffness of the Confining Space

The coordination of cell migration of immune cells is a critical aspect of the immune response to pathogens. Dendritic cells (DCs), the sentinels of the immune system, are exposed to complex tissue microenvironments with a wide range of stiffnesses. Recent studies have revealed the importance of mechanical cues in immune cell trafficking in confined 3D environments. However, the mechanism by which stiffness modulates the intrinsic motility of immature DCs remains poorly understood. Here, immature DCs were found to navigate confined spaces in a rapid and persistent manner, surveying a wide range when covered with compliant gels mimicking soft tissues. However, the speed and persistence time of random motility were both decreased by confinement in gels with higher stiffness, mimicking skin or diseased, fibrotic tissue. The impact of stiffness of surrounding tissue is crucial because most in vitro studies to date have been based on cellular locomotion when confined by microfabricated polydimethylsiloxane structures. Our study provides evidence for a role for environmental mechanical stiffness in the surveillance strategy of immature DCs in tissues.

High-temperature behavior of housed piezoelectric resonators based on CTGS

A temperature sensor based on piezoelectric single crystals allowing stable operation in harsh environments such as extreme temperatures and highly reducing or oxidizing atmospheres is presented. The temperature dependence of the mechanical stiffness of thickness shear mode resonators is used to determine temperature changes. The sensor is based on catangasite (Ca3TaGa3Si2O14 – CTGS), a member of a langasite crystal family. CTGS exhibits an ordered crystal structure and low acoustic losses, even at 1000 ∘C. The resonance frequency and quality factor of unhoused and of housed CTGS resonators are measured up to about 1030 ∘C. A temperature coefficient of the resonance frequency of about 200 Hz K−1 for a 5 MHz device is found and enables determination of temperature changes as small as 0.04 K. Housed CTGS resonators do not show any significant change in the resonance behavior during a 30 d, long-term test at 711 ∘C.

Rational Design of Peptide-based Smart Hydrogels for Therapeutic Applications

Peptide-based hydrogels have captivated remarkable attention in recent times and serve as an excellent platform for biomedical applications owing to the impressive amalgamation of unique properties such as biocompatibility, biodegradability, easily tunable hydrophilicity/hydrophobicity, modular incorporation of stimuli sensitivity and other functionalities, adjustable mechanical stiffness/rigidity and close mimicry to biological molecules. Putting all these on the same plate offers smart soft materials that can be used for tissue engineering, drug delivery, 3D bioprinting, wound healing to name a few. A plethora of work has been accomplished and a significant progress has been realized using these peptide-based platforms. However, designing hydrogelators with the desired functionalities and their self-assembled nanostructures is still highly serendipitous in nature and thus a roadmap providing guidelines toward designing and preparing these soft-materials and applying them for a desired goal is a pressing need of the hour. This review aims to provide a concise outline for that purpose and the design principles of peptide-based hydrogels along with their potential for biomedical applications are discussed with the help of selected recent reports.