Increase In Material Stiffness Research Articles

Heat-inducible CAR-T overcomes adverse mechanical tumor microenvironment in a 3D bioprinted glioblastoma model

Glioblastoma (GBM) presents a significant therapeutic challenge due to the limited efficacy of existing treatments. Chimeric antigen receptor (CAR) T-cell therapy offers promise, but its potential in solid tumors like GBM is undermined by the physical barrier posed by the extracellular matrix (ECM). To address the inadequacies of traditional 2D cell culture, animal models, and Matrigel-based 3D culture in mimicking the mechanical characteristics of tumor tissues, we employed biomaterials and digital light processing-based 3D bioprinting to fabricate biomimetic tumor models with finely tunable ECM stiffness independent of ECM composition. Our results demonstrated that increased material stiffness markedly impeded CAR-T cell penetration and tumor cell cytotoxicity in GBM models. The 3D bioprinted models enabled us to examine the influence of ECM stiffness on CAR-T cell therapy effectiveness, providing a clinically pertinent evaluation tool for CAR-T cell development in stiff solid tumors. Furthermore, we developed an innovative heat-inducible CAR-T cell therapy, effectively overcoming the challenges posed by the stiff tumor microenvironment.

Ovariectomy-Induced Arterial Stiffening Differs From Vascular Aging and Is Reversed by GPER Activation.

Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of menopause increases arterial stiffness in a similar manner to aging and whether activation of the G-protein-coupled estrogen receptor could reverse stiffness. Female C57Bl/6J mice were ovariectomized at 10 weeks of age or aged to 52 weeks, and some mice were treated with G-protein-coupled estrogen receptor agonists. Ovariectomy and aging increased pulse wave velocity to a similar extent independent of changes in blood pressure. Aging increased carotid wall thickness, while ovariectomy increased material stiffness without altering vascular geometry. RNA-sequencing analysis revealed that ovariectomy downregulated smooth muscle contractile genes. The enantiomerically pure G-protein-coupled estrogen receptor agonist, LNS8801, reversed stiffness in ovariectomy mice to a greater degree than the racemic agonist G-1. In summary, ovariectomy and aging induced arterial stiffening via potentially different mechanisms. Aging was associated with inward remodeling, while ovariectomy-induced material stiffness independent of geometry and a loss of the contractile phenotype. This study enhances our understanding of the impact of estrogen loss on vascular health in a murine model and warrants further studies to examine the ability of LNS8801 to improve vascular health in menopausal women.

Improved Humoral Immunity and Protection against Influenza Virus Infection with a 3d Porous Biomaterial Vaccine.

New vaccine platforms that activate humoral immunity and generate neutralizing antibodies are required to combat emerging pathogens, including influenza virus. A slurry of antigen-loaded hydrogel microparticles that annealto form a porous scaffold with high surface area for antigen uptake by infiltrating immune cells as the biomaterial degrades is demonstrated to enhance humoral immunity. Antigen-loaded-microgels elicited a robust cellular humoral immune response, with increased CD4+ T follicular helper (Tfh) cells and prolonged germinal center (GC) B cells comparable to the commonly used adjuvant, aluminum hydroxide (Alum). Increasing the weight fraction of polymer material led to increased material stiffness andantigen-specific antibody titers superior to Alum. Vaccinating mice with inactivated influenza virus loaded into this more highly cross-linked formulation elicited a strong antibody response and provided protection against a high dose viral challenge. By tuning physical and chemical properties, adjuvanticity can be enhanced leading to humoral immunity and protection against a pathogen, leveraging two different types of antigenic material: individual protein antigen and inactivated virus. The flexibility of the platform may enable design of new vaccines to enhance innate and adaptive immune cell programming to generate and tune high affinity antibodies, a promising approach to generate long-lasting immunity.

Physics and chemistry-based phase-field constitutive framework for thermo-chemically aged elastomer

We propose a physics and chemistry-based constitutive framework to predict the stress and brittle failure responses of thermo-chemically aged elastomers. High-temperature aging in the presence of oxygen causes chemical reactions inducing significant changes in the elastomer macromolecular network. Experimental studies agree that the increase in effective chemical crosslinks is dominant, leading to increased material stiffness and ultimately causing brittle failure of aged elastomers. The main novelty of this work relies on directly connecting the evolution of the effective crosslink density to the mechanical properties which control stress and failure response of thermo-chemically aged elastomers. We equip the Arruda–Boyce hyperelastic constitutive equations to predict the stress–strain response until failure with phase-field to capture the induced brittle failure via a strain-based criterion for fracture. Four material properties associated with the stress and failure responses evolve to capture the detrimental effects of thermo-chemical aging. The evolution of the four material properties is characterized by the change in the effective crosslink density, obtained based on chemical characterization tests, for any given aging temperature and duration. The established constitutive framework is first solved analytically for the case of uniaxial tension in a homogeneous bar to highlight the interconnection between the four material properties. Then, the framework is numerically implemented within a finite element (FE) context via a user-element subroutine (UEL) in the commercial FE software Abaqus. The framework is validated versus a set of experimental results available in the literature. The comparison confirms that the proposed constitutive framework can accurately predict the stress–strain and failure responses of thermo-chemically aged elastomers. Further numerical examples are provided to demonstrate the effects of evolving material properties on the response of specimens containing pre-existing cracks exploiting the capabilities of the phase-field approach.

Probing Relative Humidity Impact on Biological Protein Bovine Serum Albumin and Bovine Submaxillary Gland Mucin by Using Contact Resonance Atomic Force Microscopy.

In biomaterials, a substantial amount of research has been placed on the mechanical properties of biomolecules and their interactions with body fluids. Bovine serum albumin (BSA) is a widely studied model protein, while bovine submaxillary gland mucin (BSM) is another cow-derived protein frequently employed in research. Films were examined with contact resonance atomic force microscopy (CR-AFM), and the results showed that the mechanical characteristics of the films were affected by the relative humidity. We quantitatively analyze the viscoelasticity of these proteins after they have been subjected to humidity by measuring the resonance frequency and quality factor. The findings indicate that prolonged humidity exposure has a different effect on the mechanical properties of BSA and BSM films. The results show that after exposure to humidity, the resonance peaks of BSA shift to the left, indicating stiffness, while those of BSM shift to the right, indicating hydration. Moreover, BSM's hydration is caused by relative humidity, leading to a constant increase in resonance frequency and material softness. Contrarily, BSA showed a decrease in contact resonance frequency due to ongoing strain-induced deformation, indicating increased material stiffness. The findings have significance for the design and development of biomaterials for a variety of applications, such as the delivery of drugs, the engineering of tissue, and the development of biosensors. Our research demonstrates that CR-AFM has the potential to become a non-invasive and sensitive method that can be used to characterize the mechanical characteristics of biomolecules and their interactions with bodily fluids.

The effect of string mechanical properties degradation on wellhead growth of offshore HPHT wells

For offshore HPHT wells, the string has been serving in a harsh environment for a long time, which leads to string mechanical properties degradation and a worse wellhead growth phenomenon. In this article, the mechanical properties of P110 and N80 strings varied with temperature through the MTS experiment. And based on wellbore temperature and pressure conduction method, a new high-accuracy wellhead growth calculation model is established combined with thermal-induced string mechanical properties degradation. The difference between the calculated results and the measured data is less than 8%. And the influence of string mechanical properties degradation on wellbore safety is studied. The results show that high temperature leads to a sudden drop in wellbore safety factors and a sharp increase in wellhead growth. And the maximum critical safety production is recommended to be 85 when the case well is worked for 500 days. Attenuation of the string elastic modulus leads to a slight decrease in axial force and a slight increase in wellhead growth. The increase in the thermal expansion coefficient of string has a noticeable influence on wellhead growth. Reducing string thermal expansion capacity and increasing material stiffness can alleviate the wellhead growth phenomenon.

Ageing-induced shrinkage of intervessel pit membranes in xylem of Clematis vitalba modifies its mechanical properties as revealed by atomic force microscopy.

Bordered pit membranes of angiosperm xylem are anisotropic, mesoporous media between neighbouring conduits, with a key role in long distance water transport. Yet, their mechanical properties are poorly understood. Here, we aim to quantify the stiffness of intervessel pit membranes over various growing seasons. By applying an AFM-based indentation technique "Quantitative Imaging" we measured the effective elastic modulus (E effective) of intervessel pit membranes of Clematis vitalba in dependence of size, age, and hydration state. The indentation-deformation behaviour was analysed with a non-linear membrane model, and paired with magnetic resonance imaging to visualise sap-filled and embolised vessels, while geometrical data of bordered pits were obtained using electron microscopy. E effective was transformed to the geometrically independent apparent elastic modulus E apparent and to aspiration pressure P b. The material stiffness (E apparent) of fresh pit membranes was with 57 MPa considerably lower than previously suggested. The estimated pressure for pit membrane aspiration was 2.20+28 MPa. Pit membranes from older growth rings were shrunken, had a higher material stiffness and a lower aspiration pressure than current year ones, suggesting an irreversible, mechanical ageing process. This study provides an experimental-stiffness analysis of hydrated intervessel pit membranes in their native state. The estimated aspiration pressure suggests that membranes are not deflected under normal field conditions. Although absolute values should be interpreted carefully, our data suggest that pit membrane shrinkage implies increasing material stiffness, and highlight the dynamic changes of pit membrane mechanics and their complex, functional behaviour for fluid transport.

Structure and rheology of oil-continuous capillary suspensions containing water-swellable cellulose beads and fibres

Cellulose particles are used in a range of materials and applications. Here, we investigated the role of cellulose sorptivity on the rheology and microstructure of oil-continuous capillary suspensions consisting of cellulose beads and fibres at volume fractions of 0.3–0.65 and water at volume fractions up to 0.2. We hypothesised that, in spite of their water-absorbent nature, cellulose particles in oil would be structured into a percolated network by water added as an immiscible secondary phase. The interplay between cellulose bead load and water content was used to generate suspensions ranging from flowable to highly elastic with moduli near 1 MPa. While capillary bridging induced a liquid to semi-solid transition, nearer particle volume fractions of 0.65, we found a transition to a solid, wet-granular material. Liquid-solid transitions occurred even if the water was absorbed by the particles, suggesting that the increase in elasticity was not solely due to the formation of capillary bridges, but also as a result of clustering and the associated increase in effective packing volume fraction. Swapping the beads with fibres increased stiffness by 4 orders whereas swapping half of the beads at the same water fraction increased material stiffness by 3 orders of magnitude. The two conclusions of this study were that, even for water-sorptive particles, capillary and hydrophilic interactions may be used to structure oil-continuous suspensions, and that the use of high aspect ratio particles can increase the rigidity of oil-continuous capillary suspensions to a greater extent than beads at an equivalent volume fraction.

Injectable pH-responsive adhesive hydrogels for bone tissue engineering inspired by the underwater attachment strategy of marine mussels

A major challenge in tissue engineering is the development of alternatives to traditional bone autografts and allografts that can regenerate critical-sized bone defects. Here we present the design of injectable pH-responsive double-crosslinked adhesive hydrogels inspired by the molecular mechanism and environmental post-processing of marine mussel adhesive. Nine adhesive hydrogel formulations were developed through the conjugation of crosslinkable catechol functional groups (DOPA) and the synthetic oligomer oligo[poly(ethylene glycol) fumarate] (OPF), varying the DOPA content (w/w%) and molecular weight (MW) of the OPF backbone to produce formulations with a range of swelling ratios, porosities, and crosslink densities. DOPA incorporation altered the surface chemistry, mechanical properties, and surface topography of hydrogels, resulting in an increase in material stiffness, slower degradation, and enhanced pre-osteoblast cell attachment and proliferation. When injected within simulated bone defects, DOPA-mediated interfacial adhesive interactions also prevented the displacement of scaffolds, an effect that was maintained even after swelling within physiological conditions. Taken together, OPF-DOPA hydrogels represent a promising new material to enhanced tissue integration and the prevention of the post-implantation migration of scaffolds that can occur due to biomechanical loading in vivo.

Mechanisms of Hypoxia-Induced Pulmonary Arterial Stiffening in Mice Revealed by a Functional Genetics Assay of Structural, Functional, and Transcriptomic Data.

Hypoxia adversely affects the pulmonary circulation of mammals, including vasoconstriction leading to elevated pulmonary arterial pressures. The clinical importance of changes in the structure and function of the large, elastic pulmonary arteries is gaining increased attention, particularly regarding impact in multiple chronic cardiopulmonary conditions. We establish a multi-disciplinary workflow to understand better transcriptional, microstructural, and functional changes of the pulmonary artery in response to sustained hypoxia and how these changes inter-relate. We exposed adult male C57BL/6J mice to normoxic or hypoxic (FiO2 10%) conditions. Excised pulmonary arteries were profiled transcriptionally using single cell RNA sequencing, imaged with multiphoton microscopy to determine microstructural features under in vivo relevant multiaxial loading, and phenotyped biomechanically to quantify associated changes in material stiffness and vasoactive capacity. Pulmonary arteries of hypoxic mice exhibited an increased material stiffness that was likely due to collagen remodeling rather than excessive deposition (fibrosis), a change in smooth muscle cell phenotype reflected by decreased contractility and altered orientation aligning these cells in the same direction as the remodeled collagen fibers, endothelial proliferation likely representing endothelial-to-mesenchymal transitioning, and a network of cell-type specific transcriptomic changes that drove these changes. These many changes resulted in a system-level increase in pulmonary arterial pulse wave velocity, which may drive a positive feedback loop exacerbating all changes. These findings demonstrate the power of a multi-scale genetic-functional assay. They also highlight the need for systems-level analyses to determine which of the many changes are clinically significant and may be potential therapeutic targets.

Combinatorial mechanical gradation and growth factor biopatterning strategy for spatially controlled bone-tendon-like cell differentiation and tissue formation

Engineering scaffolds to augment the repair of hard-to-soft multitissue musculoskeletal tissue units, such as bone-tendon, to simultaneously support tissue healing and functional movement has had limited success. Overcoming this challenge will require not only precise spatial control of bone- and tendon-like biomechanical properties, but also consideration of the resultant biomechanical cues, as well as the embedded biochemical cues imparted by these scaffolds. Here, we report on the effects of a spatially engineered combination of stiffness and growth factor (GF) cues to control bone-tendon-like differentiation in vitro and tissue formation in vivo. This was achieved using mechanically graded, bone- and tendon-like QHM polyurethane (QHM: Q: Quadrol; H: hexamethylene diisocyanate; M: methacrylic anhydride) scaffolds selectively biopatterned with osteogenic bone morphogenetic protein-2 (BMP-2) and tenogenic fibroblast growth factor-2 (FGF-2). First, material characterization, including porosity, surface roughness, contact angle, and microindentation measurements, was performed. Second, in vitro studies demonstrated that increased material stiffness promoted GF-mediated osteoblast differentiation and reduced tenocyte differentiation. Sustained GF exposure masked this stiffness effect. Third, in vivo studies involving subcutaneous implantation of mechanically graded and biochemically patterned QHM scaffolds (composed of these bone- and tendon-promoting GFs biopatterned on biphasic bone and tendon biomechanically mimicking regions) in mice demonstrated spatial control of bone- and tendon-like tissue formation. Altogether, these data provide new insights for future engineering of scaffolds to augment hard-to-soft multitissue repair.

Study of the Ultraviolet Effect and Thermal Analysis on Polypropylene Nonwoven Geotextile

The use of polymeric materials such as geosynthetics in infrastructure works has been increasing over the last decades, as they bring down costs and provide long-term benefits. However, the aging of polymers raises the question of its long-term durability and for this reason researchers have been studying a sort of techniques to search for the required renewal time. This paper examined a commercial polypropylene (PP) nonwoven geotextile before and after 500 h and 1000 h exposure to ultraviolet (UV) light by performing laboratory accelerated ultraviolet-aging tests. The state of the polymeric material after UV exposure was studied through a wide set of tests, including mechanical and physical tests and thermoanalytical tests and scanning electron microscopy analysis. The calorimetric evaluations (DSC) showed distinct behaviors in sample melting points, attributed to the UV radiation effect on the aged samples. Furthermore, after exposure, the samples presented low thermal stability in the thermomechanical analysis (TMA), with a continuing decrease in their thicknesses. The tensile tests showed an increase in material stiffness after exposition. This study demonstrates that UV aging has effects on the properties of the polypropylene polymer.

Addition of platelet-rich plasma supports immune modulation and improved mechanical integrity in Alloderm mesh for ventral hernia repair in a rat model.

The recurrence of ventral hernias continues to be a problem faced by surgeons, in spite of efforts toward implementing novel repair techniques and utilizing different materials to promote healing. Cadaveric acellular dermal matrices (Alloderm) have shown some promise in numerous surgical subspecialties, but these meshes still suffer from subsequent failure and necessitation of re-intervention. Here, it is demonstrated that the addition of platelet rich plasma to Alloderm meshes temporally modulates both the innate and cytotoxic inflammatory responses to the implanted material. This results in decreased inflammatory cytokine production at early time points, decreased matrix metalloproteinase expression, and decreased CD8+ T cell infiltration. Collectively, these immune effects result in a healing phenotype that is free from mesh thinning and characterized by increased material stiffness.

The effect of the elongation of the proximal aorta on the estimation of the aortic wall distensibility

The compliance of the proximal aortic wall is a major determinant of cardiac afterload. Aortic compliance is often estimated based on cross-sectional area changes over the pulse pressure, under the assumption of a negligible longitudinal stretch during the pulse. However, the proximal aorta is subjected to significant axial stretch during cardiac contraction. In the present study, we sought to evaluate the importance of axial stretch on compliance estimation by undertaking both an in silico and an in vivo approach. In the computational analysis, we developed a 3-D finite element model of the proximal aorta and investigated the discrepancy between the actual wall compliance to the value estimated after neglecting the longitudinal stretch of the aorta. A parameter sensitivity analysis was further conducted to show how increased material stiffness and increased aortic root motion might amplify the estimation errors (discrepancies between actual and estimated distensibility ranging from − 20 to − 62%). Axial and circumferential aortic deformation during ventricular contraction was also evaluated in vivo based on MR images of the aorta of 3 healthy young volunteers. The in vivo results were in good qualitative agreement with the computational analysis (underestimation errors ranging from − 26 to − 44%, with increased errors reflecting higher aortic root displacement). Both the in silico and in vivo findings suggest that neglecting the longitudinal strain during contraction might lead to severe underestimation of local aortic compliance, particularly in the case of women who tend to have higher aortic root motion or in subjects with stiff aortas.

Mechanochemical Adhesion and Plasticity in Multifiber Hydrogel Networks.

The extracellular matrix (ECM) has force-responsive (i.e., mechanochemical) properties that enable adaptation to mechanical loading through changes in fibrous network structure and interfiber bonding. Imparting such properties into synthetic fibrous materials will allow reinforcement under mechanical load, the potential for material self-adhesion, and the general mimicking of ECM. Multifiber hydrogel networks are developed through the electrospinning of multiple fibrous hydrogel populations, where fibers contain complementary chemical moieties (e.g., aldehyde and hydrazide groups) that form covalent bonds within minutes when brought into contact under mechanical load. These fiber interactions lead to microscale anisotropy, as well as increased material stiffness and plastic deformation. Macroscale structures (e.g., tubes and layered scaffolds) are fabricated from these materials through interfiber bonding and adhesion when placed into contact while maintaining a microscale fibrous architecture. The design principles for engineering plasticity described can be applied to numerous material systems to introduce unique properties, from textiles to biomedical applications.

A comparative study of the dynamics of laser and acoustically generated bubbles in viscoelastic media

Here, we present results from experiments comparing the first-cycle growth and collapse dynamics of acoustically and laser-nucleated single bubbles in water and agarose gels of varying stiffness. Experiments were carried out in a custom-built spherical vessel which allowed both acoustically and laser-nucleated bubbles to be generated at its center. Bubbles were nucleated in water and agarose gels with stiffnesses ranging from 1.13 kPa to 570 kPa. Acoustically nucleated bubbles were generated using pulses delivered from 1 MHz transducer elements mounted in the vessel with pulse durations of <2 acoustic cycles. Laser-nucleated bubbles were generated using a pulsed Nd:YAG laser focused to the center of the vessel through an embedded window. Bubble dynamics were measured via optical imaging. The maximum radii of generated bubbles decreased with the increasing material stiffness for bubbles nucleated by both mechanisms. The growths and collapses of the bubbles occurred symmetrically (in time) about the maximum radius in water but not in gels, where the duration of growth decreased more rapidly than collapse as gel stiffness increased. Nucleation-mechanism-dependent differences in the growth-collapse asymmetry were observed which indicated that the growth duration of the laser-nucleated bubbles was longer than the acoustically nucleated bubbles in water and high water-content gels. Here, we present results from experiments comparing the first-cycle growth and collapse dynamics of acoustically and laser-nucleated single bubbles in water and agarose gels of varying stiffness. Experiments were carried out in a custom-built spherical vessel which allowed both acoustically and laser-nucleated bubbles to be generated at its center. Bubbles were nucleated in water and agarose gels with stiffnesses ranging from 1.13 kPa to 570 kPa. Acoustically nucleated bubbles were generated using pulses delivered from 1 MHz transducer elements mounted in the vessel with pulse durations of <2 acoustic cycles. Laser-nucleated bubbles were generated using a pulsed Nd:YAG laser focused to the center of the vessel through an embedded window. Bubble dynamics were measured via optical imaging. The maximum radii of generated bubbles decreased with the increasing material stiffness for bubbles nucleated by both mechanisms. The growths and collapses of the bubbles occurred symmetrically (in time) about the maximum...

High modulus hydrogels for ophthalmic and related biomedical applications.

This paper presents three families of semi-interpenetrating polymer network (SIPN) hydrogels based on an ester-based polyurethane (EBPU) and hydrophilic monomers: N,N-dimethylacrylamide (NNDMA), N-vinyl pyrrolidone (NVP) and acryloylmorpholine (AMO) as potential materials for keratoprosthesis, orthokeratology and mini-scleral lens application. Hydrogels sheets were synthesized via free-radical polymerization with methods developed in-house. SIPN hydrogels were characterized for their equilibrium water content, mechanical and surface properties. Three families of optically clear SIPN-based hydrogels have been synthesized in the presence of water with >10% of composition attributable to EBPU. Water contents of SIPN materials ranged from 30% to 70%. SIPNs with ≤15% EBPU of total composition showed little influence to mechanical properties, whereas >15% EBPU contributed significantly to an increase in material stiffness. In the hydrated state, SIPNs with ≤15% EBPU of total composition show little difference in polar component (γp ) of surface free energy, whereas for >15% EBPU there is a decrease in γp . The EBPU SIPN hydrogels display complementary material properties for keratoprosthesis, orthokeratology, and mini-scleral applications. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1645-1653, 2019.

Carbon nanofiber-filled conductive silicone elastomers as soft, dry bioelectronic interfaces.

Soft and pliable conductive polymer composites hold promise for application as bioelectronic interfaces such as for electroencephalography (EEG). In clinical, laboratory, and real-world EEG there is a desire for dry, soft, and comfortable interfaces to the scalp that are capable of relaying the μV-level scalp potentials to signal processing electronics. A key challenge is that most material approaches are sensitive to deformation-induced shifts in electrical impedance associated with decreased signal-to-noise ratio. This is a particular concern in real-world environments where human motion is present. The entire set of brain information outside of tightly controlled laboratory or clinical settings are currently unobtainable due to this challenge. Here we explore the performance of an elastomeric material solution purposefully designed for dry, soft, comfortable scalp contact electrodes for EEG that is specifically targeted to have flat electrical impedance response to deformation to enable utilization in real world environments. A conductive carbon nanofiber filled polydimethylsiloxane (CNF-PDMS) elastomer was evaluated at three fill ratios (3, 4 and 7 volume percent). Electromechanical testing data is presented showing the influence of large compressive deformations on electrical impedance as well as the impact of filler loading on the elastomer stiffness. To evaluate usability for EEG, pre-recorded human EEG signals were replayed through the contact electrodes subjected to quasi-static compressive strains between zero and 35%. These tests show that conductive filler ratios well above the electrical percolation threshold are desirable in order to maximize signal-to-noise ratio and signal correlation with an ideal baseline. Increasing fill ratios yield increasingly flat electrical impedance response to large applied compressive deformations with a trade in increased material stiffness, and with nominal electrical impedance tunable over greater than 4 orders of magnitude. EEG performance was independent of filler loading above 4 vol % CNF (< 103 ohms).

Metal-Tunable Self-Assembly of Hierarchical Structure in Mussel-Inspired Peptide Films.

Bottom-up control over structural hierarchy from the nanoscale through the macroscale is a critical aspect of biological materials fabrication and function, which can inspire production of advanced materials. Mussel byssal threads are a prime example of protein-based biofibers in which hierarchical organization of protein building blocks coupled via metal complexation leads to notable mechanical behaviors, such as high toughness and self-healing. Using a natural amino acid sequence from byssal thread proteins, which functions as a pH-triggered self-assembly point, we created free-standing peptide films with complex hierarchical organization across multiple length scales that can be controlled by inclusion of metal ions (Zn2+ and Cu2+) during the assembly process. Additionally, analysis of film mechanical performance indicates that metal coordination bestows up to an order of magnitude increase in material stiffness, providing a paradigm for creating tunable polymeric materials with multiscale organizational structure.

Increased intrinsic stiffness and mineralization in femurs of adult rats after high intensity treadmill running training.

Physical activity plays a tremendous role in determining bone mechanical behavior, which is superimposed to gravidity. Compare the geometric and material responses of the rat femur to a high intensity treadmill running training of a relatively short duration, as assessed by 3-point mechanical test. Mature male rats (180.0± 30g) were assigned (7rats/group) to no exercise (NE) or treadmill exercise (EX). After a preconditioning period, the running speed was set at 45cm.seg-1 during 2wks, frequency 5d/wk, 2-hour sessions/day. Body weight and weight of the crural quadriceps were registered at euthanasia. The right femur was mechanically tested through 3-point bending. The left femur was ashed to estimate bone mineral content. Geometric and material bone properties were estimated directly or calculated by appropriate equations. 1)Final body weight was 14% reduced in EX rats, while the crural quadriceps was 47% increased. Yield and fracture loads, and structural stiffness were significantly higher in the EX rats, as were the apparent elastic modulus, the bone mineral content and the degree of mineralization. Geometric properties were not affected. High intensity treadmill running training increases bone strength and stiffness by increasing material stiffness and mineralization, without affecting geometric bone parameters.