Recently, we have reported enhanced permeability of tissues due to in vivo treatment with pulsed high intensity focused ultrasound (pHIFU). This new therapy has shown promise as a way of increasing the penetration of large drug molecules, both out of the vasculature and through the tissue. To date, no clear physical model of tissue exists that can account for these effects.

A new model is proposed that clearly establishes the link between tissue structure and fluid flow properties on one hand, and the history of applied mechanical forces on the other. The model draws inspiration from two different theoretical fields of materials science, multi-phase theory and continuum damage mechanics. The theory differs from the traditional bi-phasic solid-fluid model of tissues in that the fluid part here is broken into trapped (moving with the solid) and free (moving through the solid) parts. A damage-like variable links the effective elasticity of the tissue to the ratio of the trapped to free fluids. As the damage increases, the tissue becomes, in effect, less stiff and more permeable. Release of elastic energy drives the process. A distribution of energy barriers opposes the process and governs how the fluid is released as damage increases.

Bone is an anisotropic material, and its mechanical properties are determined by its microstructure as well as its composition. Mechanical properties of bone are a consequence of the proportions of, and the interactions between, mineral, collagen and water. Water plays an important role in maintaining the mechanical integrity of the composite, but the manner in which water interacts within the ultrastructure is unclear. Dentine being an isotropic two-dimensional structure presents a homogenous composite to examine the dehydration effects. Nanoindentation methods for determining the viscoelastic properties have recently been developed and are a subject of great interest. Here, one method based on elastic-viscoelastic correspondence for ‘ramp and hold’ creep testing (Oyen, J. Mater. Res., 2005) has been used to analyze viscoelastic behavior of polymeric and biological materials. The method of ‘ramp and hold’ allows the shear modulus at time zero to be determined from fitting of the displacement during the maximum load hold. Changes in the viscoelastic properties of bone and dentine were examined as the material was systematically dehydrated in a series of water:solvent mixes. Samples of equine dentine were sectioned and cryo-polished. Shear modulus was obtained by nanoindentation using spherical indenters with a maximum load hold of 120s. Samples were tested in different solvent concentrations sequentially, 70% ethanol to 50% ethanol, 70 % ethanol to 100% ethanol, 70% ethanol to 70% methanol to 100% methanol, and 70% ethanol to 100% acetone, after storage in each condition for 24h. By selectively removing and then replacing water from the composite, insights in to the ultrastructure of the tissue can be gained from the corresponding changes in the experimentally determined moduli, as well as an understanding of the complete reversibility of the dehydration process.

The mechanical behavior of the red blood cell membrane is governed by the lipid bilayer which resists changes in surface area and the underlying spectrin network which resists changes in shape. The spectrin network can be modeled as an idealized triangulated network. Each spectrin chain consists of folded domains along the length of the chain which can unfold during stretching of the chain. A domain will completely unfold under the application of a chain force of 20 to 35 pN depending on the rate of imposed chain stretch. During macroscopic stretch of a network, individual chains within the network will experience different levels of chain stretch since the network chains will collectively stretch and rotate to accommodate the imposed stretch. Hence, the stretch on any individual chain will depend on the magnitude and state of macroscopic strain. A microstructurally informed continuum level constitutive model is developed which tracks individual chain deformation behavior as a function of macroscopic strain and also determines the overall macroscopic network stress-strain behavior. Using the introduced continuum approach and statistical mechanics based models of individual chain force-extension behavior, the stress-stretch behavior of the membrane under uniaxial tension is simulated at large stretches and the behavior of the constituent chains is monitored. Domain unfolding occurs within constituent chains during network deformation and the effects of this domain unfolding on the overall macroscopic stress-strain behavior of the network subject to deformation at different strain rates is revealed.

Nacre, the inner iridescent layer of mollusks shell is a bio-nanocomposite with the mineral aragonite as a major constituent and 2-5% of organics mainly in the form of proteins. Our multiscale modeling and experimental studies reveal that the microstructure and the small weight percent of organics are the key parameters attributed to the extreme toughness of nacre. We report that the presence of platelet interlocks nacre have a significant role in the enhancement of mechanical properties. Molecular simulation study is conducted to understand the behavior of aragonite-organic interface. The mechanical behavior of organics and inorganics in presence of each other is described using steered molecular dynamics simulations. This provides some understanding on the deformation mechanisms of the protein present between the aragonite layers. Our nanoindentation results indicate that the elastic modulus and hardness of nacre decreases as it is exposed to a denaturing temperature for proteins. The changes in the organic inorganic interaction have been experimentally described using Fourier Transform Infrared Spectroscopy. This work gives insight into the contribution of the various factors existing at different length scales on the overall mechanical behavior of nacre.

Self-healing ability is a fascinating property of some materials. Structural materials with self-healing ability require a subtle combination of flow and stiffness characteristics. A vivid demonstration of self-healing is the automatic sealing of the bullet hole after bullet penetration of the target material. The ionomer Surlyn® satisfies the needs of both structural requirements and self-healing to a certain extent. The viscosity of Surlyn is very high at room temperature, a favorable property for structural applications but unfavorable for self-healing. However, when it was heated to 100°C and then cooled back down to room temperature, its viscosity remains temporarily low at room temperature for a few minutes, a favorable condition for healing. Here we report the measurement of such short-time relaxation effects on flow properties in Surlyn using an atomic force microscope (AFM)-based local thermal mechanical analyzer (LTA).

A biomimetic reactor has been developed to synthesize hydroxyapatite-gelatin (HAP-GEL) nanocomposites that mimic ultra-structures of natural bone. We hypothesize that in the reactor, gelatin concentration controls morphology and packing structures of HAP crystals. To test the hypothesis, three types of mechanical tests were conducted, including nanoindentation, compression, and fracture tests. Nanoindentation tests in conjunction with computer modeling were used to assess effects on gelatin-induced microstructures of HAP. The results showed that increasing gelatin content increased both the plane strain modulus and the fracture toughness. The gelatin appeared to shorten the HAP crystal distance, which consolidated the internal structure of the composite and made the material more rigid. The fracture toughness KIC increased partially due to the effect of fiber bridging between gelatin molecules. The highest fracture toughness (1.12 MPa·m1/2) was equivalent to that of pure hydroxyapatite. The compressive strength of the HAP-GEL (107.7±6.8 MPa) was, however, less sensitive to microstructural changes and was within the range of natural cortical bone (human 170 MPa, pig: 100 MPa). The compression strength was dominated by void inclusions while the nanoindentation response reflected ultra-structural arrangement of the crystals. The gelatin concentration is likely to modify crystal arrangement as demonstrated in TEM experiments but not void distribution at macroscopic levels.

The manner in which liquid interacts with collagen is unclear, with changes in hydration presenting ambiguity. At present, elastic modulus values for collagen quoted range from MPa to GPa. Dynamic mechanical analysis (DMA) of collagen in isolation provides an insight into the mechanical changes due to altered hydration states.

Changes in the viscoelastic properties of collagen were examined as the material was systematically dehydrated in a series of water:solvent mixes to examine effects of dehydration. The effect of solvents with varying polarity was also examined. Tails from 11-week old wild type mice were used. Mouse tail is a tissue with a well-defined, hierarchical organization of type I collagen. The viscoelastic response of collagen was measured using dynamic mechanical analysis (DMA) in fiber extension mode over the frequency range of 1Hz to 10Hz. Samples were sequentially dehydrated in a series of solvent concentrations: 70% ethanol to 100% ethanol to 100% acetone and 70% ethanol to 70% methanol to 100% methanol for at least 1h. Selectively removing and then replacing water from collagen samples provides insight into the role of water in the ultrastructure of the tissue from the corresponding changes in the experimentally determined elastic modulus and viscous energy.

Polytrimethylene carbonate (PTMC) and poly ε-caprolactone are conventional biodegradable, biocompatible polymers. Their friction response against cartilage and surface attraction forces were studied toward using them as artificial cartilage materials. Their behavior was compared to that of natural cartilage and a conventional joint replacement material, ultrahigh molecular weight polyethylene. It was possible to polymerize these materials using a calcium based catalyst. Simulated body fluid (SBF) was used as lubricant between surfaces in the friction tests. It was found that higher surface attractive forces on a silicon tip AFM related to lower friction coefficients. This confirs the fact that hydrophilic surfaces enhance the effectiveness of boundary lubrication of simulated body fluid. PTMC and PTMC-ε-caprolactone co-polymer showed lower hydrophilicity and higher friction coefficients and need to be modified in order to bring them closer in behavior to natural cartilage.

Mechanical properties of cortical human bone have been investigated for more than over three decades. The objectives of the present study were 1) to investigate the influence of multiscale structural characteristics of the bone tissue on its mechanical behavior and 2) to perform a micro-macro numerical modelling based on the experimental data. It should be noted that variations of the osteon lamellae elastic properties are higher (40%) at the microstructural level than those found at the macroscopic level (about 15%) for measurements performed in the same anatomical direction. Physico-chemical analyses found that organic components were found to be higher for femurs exhibiting lower mechanical properties. There is a consistency between changes observed at the different levels. These results contribute to a basic understanding of the multiscale mechanical behavior of human cortical bone.

Biphasic calcium phosphates have received considerable attention due to their optimum dissolution rate in the human body after implantation. These materials are composed of hydroxyapatite (HA) and resorbable tricalcium phosphate (TCP). In the present investigation, HA whiskers are reinforced into TCP to enhance the mechanical properties of this biphasic composite. Various amounts (30-50 wt%) HA whiskers are reinforced in TCP matrix. Microstructural characterization has been carried out using field-emission scanning electron microscope. Mechanical properties have been investigated by microindentation in a universal testing machine (UTM). As TCP is resorbable, it will dissolve in body fluid and there is a strong possibility for the faceted HA whiskers to interact with functional groups present in the body fluid surroundings.

Most aspects of the structure and composition of the principal mineralised tissue types [in teeth = enamel, dentine and cementum; in bone organs = woven and lamellar and extrinsic (Sharpey) fibre bone and calcified growth plate cartilage and articular calcified cartilage and calcified fibrocartilage and calcified ligament or tendon] and of the all-important junctions between them can be best understood from a knowledge of developmental mechanisms and the rules and constraints that these generate. We should consider the interface between formative cells and the organic matrices where these are secreted by an appositional mechanism; possible influences of cell movements; mineral crystal orientation and size and maturation; junctions formed by simple apposition of one tissue upon another; junctions involving a prior resorptive (partial destruction and 'etching') step; and interstitial matrix expansion, NB in cartilage.

Stimulus-responsive biomolecules have attracted a large research interest because of their potential application in various areas such as drug delivery, actuators and sensing devices at the nanoscale. Using single-molecule force spectroscopy (SMFS) we studied elastin-like polypeptides (ELPs). These stimulus-responsive polypeptides undergo an inverse temperature transition, accompanied by a large conformational change, when the solvent quality is changed by increasing the temperature or by addition of salt. Understanding the relationship between peptide sequence and mechanisms of force generation can provide a route to engineer ELPs with desirable mechano-chemical properties. Here we studied the effect of solvent quality and type of guest residue on the mechanical properties of ELPs on the single-molecule level. We used a statistical approach to estimate polymer elasticity parameters from model fits to the data. With this approach we were able to resolve small changes in the Kuhn segment length distributions associated with different molecular architectures. We then show that these mechanical differences likely arise from differences in the hydrophobic hydration of sidegoups, in line with recent predictions from molecular dynamics simulations.

Brachiopod shells consist of low-magnesium calcite and belong to one of the most intriguing species for studies of marine paleoenvironments, variations in oceanographic conditions and ocean chemistry [6, 7, 11 – 13]. We have investigated the ultrastructure together with nano- and microhardness properties of modern brachiopod shells with transmission electron microscopy (TEM), scanning electron microscopy (SEM), nanoindentation and Vickers microhardness analyses. Brachiopod shells are structured into several layers, a thin, outer, hard, protective primary layer composed of randomly oriented nanocrystalline calcite, which is followed inward towards the soft tissue of the animal by a much softer shell segment (secondary layer) built of long calcite fibres, stacked parallely into blocks. The hardness distribution pattern within the shells is non-uniform and varies on scales as small as a few tens of microns. Our results show that the hardness of this biomaterial is controlled by two predominant features: (1.) The morphological orientation of the calcite fibres (not by the crystallographic orientation of the fibres), and (2.) the amount and distribution pattern of organic material between and within the calcite crystals.

Interfaces play an important role in controlling the mechanical properties of composites. Optimum mechanical strength of scaffolds is of prime importance for bone tissue engineering. In the present work, molecular dynamics simulations and experimental studies have been conducted to study effect of interfacial interactions on mechanical properties of composites for bone replacement. In order to mimic biological processes, hydroxyapatite (HAP) is mineralized in presence of polyacrylic acid (PAAc) (in situ HAP). Further, solid and porous composites of in situ HAP with polycaprolactone (PCL) are made. Mechanical tests of composites of in situ HAP with PAAc have shown improved strain recovery, higher modulus/density ratio and also improved mechanical response in simulated body fluid (SBF). Simulation studies indicate potential for calcium bridging between –COO− of PAAc and surface calcium of HAP. This fact is also supported by infrared spectroscopic studies. PAAc modified surfaces of in situ HAP offer means to control the microstructure and mechanical response of porous composites. Nanoindentation experiments indicate that apatite grown on in situ HAP/PCL composites from SBF has improved elastic modulus and hardness. This work gives insight into the interfacial mechanisms responsible for mechanical response as well as bioactivity in biomaterials.

Experimental observations of the time-dependent mechanical responses of collagenous tissues have demonstrated behavior that deviates from standard treatments of linear or quasi-linear viscoelasticity. In particular, time-dependent deformation can be strongly coupled to strain level, and strain-rate independence can be observed under monotonic loading, even for a tissue with dramatic stress relaxation. It was postulated that this nonlinearity is fundamentally associated with gradual recruitment of individual collagen fibrils during applied mechanical loading. Based on previously observed experimental results for the time-dependent response of collagenous soft tissues, a model is developed to describe the mechanical behavior of these tissues under uniaxial loading. Tissue stresses, under applied strain-controlled loading, are assumed to be a sum of elastic and viscoelastic stress contributions. The relative contributions of elastic and viscoelastic stresses is assumed to vary with strain level, leading to strain- and time-dependent mechanical behavior. The model formulation is examined under conditions of monotonic loading at varying constant strain rates and stress-relaxation at different applied strain levels. The model is compared with experimental data for a membranous biological soft tissue, the amniotic sac, and is found to agree well with experimental results. The limiting behavior of the novel model, at large strains relative to the collagen recruitment, is consistent with the quasi-linear viscoelastic approach.

Accumulation of microdamage during fatigue can lead to increased fracture susceptibility in bone. Current techniques for imaging microdamage in bone are inherently destructive and two-dimensional. A non-destructive, three-dimensional technique is needed to measure the spatial density of microdamage accumulation. Therefore, the objective of this study was to image microdamage accumulation in cortical bone during fatigue using micro-computed tomography (micro-CT) with a barium sulfate (BaSO4) contrast agent. Bovine cortical bone beams were loaded under four-point bending fatigue. Two symmetric notches were machined on the tensile surface in order to generate damage at the stress concentrations during loading. Specimens were loaded to a specified number of cycles or until one notch fractured, such that the other notch exhibited accumulated microdamage just prior to fracture. Microdamage ahead of the notch was stained by precipitation of BaSO4 and imaged using micro-CT. Reconstructed images showed a distinct region of bright voxels around the notch tip or along propagating cracks due to the presence of BaSO4, which was verified by backscattered electron imaging and energy dispersive spectroscopy. The stained region exhibited a characteristic kidney shape perpendicular to the notch tip, which was correlated to principal strain contours calculated by finite element analysis. The area of stained regions was positively correlated with the number of loading cycles.

Investigation of bone mechanical properties is of importance for bone pathology researches, development of biomaterials and prosthesis. Due to the bone complex multi-scale structure, assessment of bone microstructure is an important step of bone mechanical behaviour understanding. In this study, we performed dynamic nanoindentation tests in order to investigate visco-plastic and visco-elastic properties of bone interstitial lamellae.

The structure and behavior of proteins plays an overarching role in determining their function in biological systems. In recent years, proteins have also been proposed as basis for new materials to be used in technological applications (Langer and Tirrell, Nature, 2004). It is known that protein crystals show very interesting mechanical behavior, as some of them are extremely fragile, while others can be quite sturdy. However, unlike other crystalline materials like silicon or copper, the mechanical properties of protein crystals have rarely been studied by atomistic computer modeling. As a first step towards more fundamental understanding of the mechanics of those materials, we report atomistic studies of mechanical properties of protein crystals using empirical potentials focusing on elasticity, plasticity and fracture behavior. Here we consider the mechanics of a small protein α-conotoxin PnIB from conus pennaceus. We use large-scale atomistic simulations to determine the low-strain elastic constants for different crystallographic orientations. We also study large-strain elastic properties including plastic deformation. Furthermore, we perform systematic studies of the effect of mutations on the elastic properties of the protein crystal. Our results indicate a strong impact of mutations on elastic properties, showing the potential of mutations to tailor mechanical properties. We conclude with a study of mode I fracture of protein crystals, relating our atomistic modeling results with Griffith's theory of fracture.

The hierarchical structure of type I collagen fibrils is a key contributor to the mechanical properties of the extracellular matrix (ECM). It is known that the process of in vitro fibrillogenesis strongly depends on the pH of the collagen solution. To date, there are few methods available for precisely controlling and investigating the dependence of collagen fibril assembly on the local pH. The objective of this work was to create highly defined pH gradients to systematically determine the effects of local pH on microscale collagen fibrillogenesis and alignment. We use a microfluidic mixing device to create a diffusion controlled pH gradient, which in turn initiates the self-assembly and concurrent flow-alignment of soluble collagen. Finite element method simulations of the hydrodynamic and diffusive phenomena are used to calculate the local concentrations of the components involved in the reaction. We develop a model to analytically calculate the local pH in the microfluidic device from these concentrations. A comparison with the experimental results from polarized light microscopy are in good agreement with the simulations.

With the continual development of new dental materials and treatment techniques, dental materials research is now more important than ever. Although the traditional method of materials and treatment technique assessment was laboratory based, there is a need for investigations into the clinical outcomes of in-vitro research. The aim of this paper is to discuss the micromechanical and structural analysis of compromised dental tissues that affect young children, using a biomaterial and clinical approach.