Jessica L. Sparks

Tunable stress relaxation behavior of an alginate-polyacrylamide hydrogel: comparison with muscle tissue.

Factors controlling the time-dependent mechanical properties of interpenetrating network (IPN) hydrogel materials are not well understood. In this study, alginate-polyacrylamide IPN were synthesized to mimic the stress relaxation behavior and elastic modulus of porcine muscle tissue. Hydrogel samples were created with single-parameter chemical concentration variations from a baseline formula to establish trends. The concentration of total monomer material had the largest effect on the elastic modulus, while concentration of the acrylamide cross-linker, N,N-methylenebis(acrylamide) (MBAA), changed the stress relaxation behavior most effectively. The IPN material was then tuned to mimic the mechanical response of muscle tissue using these trends. Swelling the hydrogel samples to equilibrium resulted in a dramatic decrease in both elastic modulus and stress relaxation behavior. Collectively, the results demonstrate that alginate-polyacrylamide IPN hydrogels can be tuned to closely mimic both the elastic and the viscoelastic behaviors of muscle tissue, although swelling detrimentally affects these desired properties.

Biomechanical response of human spleen in tensile loading

Blunt splenic injuries are most frequently caused as a result of motor vehicle collisions and are associated with high mortality rates. In order to accurately assess the risk of automotive related spleen injuries using tools such as finite element models, tissue level tolerance values and suitable material models must be developed and validated based on appropriate biomechanical data. This study presents a total of 41 tension tests performed on spleen parenchyma coupons and 29 tension tests performed on spleen capsule/parenchyma coupons. Standard dog-bone coupons were obtained from fresh human spleen and tested within 48 h of death. Each coupon was tested once to failure at one of the four loading rates to investigate the effects of rate dependence. Load and acceleration data were obtained at each of the specimen grips. High-speed video and optical markers placed on the specimens were used to measure local displacement. Failure stress and strain were calculated at the location of failure in the gage length of the coupon. The results of the study showed that both the spleen parenchyma and the capsule are rate dependent, with higher loading rates yielding higher failure stresses and lower failure strains. The results also show that the failure stress of the splenic capsule is significantly greater than that of the underlying parenchyma. Overall, this study provides novel biomechanical data that demonstrate the rate dependent tissue level tolerance values of human spleen tissue in tensile loading, which can aid in the improvement of finite element models used to assess injury risk in blunt trauma.

Self-healing, malleable and creep limiting materials using both supramolecular and reversible covalent linkages

A self-healing material containing two reversible cross-linkers was made. Relatively rapidly exchanging hydrogen-bonded and slowly exchanging Diels–Alder based cross-linkers were incorporated. Two time scales allowed partial healing at room temperature, and near complete healing upon heating. Slow linkers limited creep at room temperature but allowed reshaping upon heating.

Use of silicone materials to simulate tissue biomechanics as related to deep tissue injury.

OBJECTIVE: Deep tissue injury (DTI) is caused by prolonged mechanical loading that disrupts blood flow and metabolic clearance. A patient simulator that mimics the biomechanical aspects of DTI initiation, stress and strain in deep muscle tissue, would be potentially useful as a training tool for pressure-relief techniques and testing platform for pressure-mitigating products. As a step toward this goal, this study evaluates the ability of silicone materials to mimic the distribution of stress in muscle tissue under concentrated loading. METHODS: To quantify the mechanical properties of candidate silicone materials, unconfined compression experiments were conducted on 3 silicone formulations (Ecoflex 0030, Ecoflex 0010, and Dragon Skin; Smooth-On, Inc, Easton, Pennsylvania). Results were fit to an Ogden hyperelastic material model, and the resulting shear moduli (G) were compared with published values for biological tissues. Indentation tests were then conducted on Ecoflex 0030 and porcine muscle to investigate silicone’s ability to mimic the nonuniform stress distribution muscle demonstrates under concentrated loading. Finite element models were created to quantify stresses throughout tissue depth. Finally, a preliminary patient simulator prototype was constructed, and both deep and superficial “tissue” pressures were recorded to examine stress distribution. RESULTS: Indentation tests showed similar stress distribution trends in muscle and Ecoflex 0030, but stress magnitudes were higher in Ecoflex 0030 than in porcine muscle. All 3 silicone formulations demonstrated shear moduli within the range of published values for biological tissue. For the experimental conditions reported in this work, Ecoflex 0030 exhibited greater stiffness than porcine muscle. CONCLUSION: Indentation tests and the prototype patient simulator trial demonstrated similar trends with high pressures closest to the bony prominence with decreasing magnitude toward the interfacial surface. Qualitatively, silicone mimicked the phenomenon observed in muscle of nonuniform stress under concentrated loading. Although shear moduli were within biological ranges, stress and stiffness values exceeded those of porcine muscle. This research represents a first step toward development of a preclinical model simulating the biomechanical conditions of stress and strain in deep muscle, since local biomechanical factors are acknowledged to play a role in DTI initiation. Future research is needed to refine the capacity of preclinical models to simulate biomechanical parameters in successive tissue layers of muscle, fat, dermis, and epidermis typically intervening between bone and support surfaces, for body regions at risk for DTI.

Constitutive Modeling of Rate-Dependent Stress–Strain Behavior of Human Liver in Blunt Impact Loading

An understanding of the mechanical deformation behavior of the liver under high strain rate loading conditions could aid in the development of vehicle safety measures to reduce the occurrence of blunt liver injury. The purpose of this study was to develop a constitutive model of the stress–strain behavior of the human liver in blunt impact loading. Experimental stress and strain data was obtained from impact tests of 12 unembalmed human livers using a drop tower technique. A constitutive model previously developed for finite strain behavior of amorphous polymers was adapted to model the observed liver behavior. The elements of the model include a nonlinear spring in parallel with a linear spring and nonlinear dashpot. The model captures three features of liver stress–strain behavior in impact loading: (1) relatively stiff initial modulus, (2) rate-dependent yield or rollover to viscous “flow” behavior, and (3) strain hardening at large strains. Six material properties were used to define the constitutive model. This study represents a novel application of polymer mechanics concepts to understand the rate-dependent large strain behavior of human liver tissue under high strain rate loading. Applications of this research include finite element simulations of injury-producing liver or abdominal impact events.

3D printing of an interpenetrating network hydrogel material with tunable viscoelastic properties

Interpenetrating network (IPN) hydrogel materials are recognized for their unique mechanical properties. While IPN elasticity and toughness properties have been explored in previous studies, the factors that impact the time-dependent stress relaxation behavior of IPN materials are not well understood. Time-dependent (i.e. viscoelastic) mechanical behavior is a critical design parameter in the development of materials for a variety of applications, such as medical simulation devices, flexible substrate materials, cellular mechanobiology substrates, or regenerative medicine applications. This study reports a novel technique for 3D printing alginate-polyacrylamide IPN gels with tunable elastic and viscoelastic properties. The viscoelastic stress relaxation behavior of the 3D printed alginate-polyacrylamide IPN hydrogels was influenced most strongly by varying the concentration of the acrylamide cross-linker (MBAA), while the elastic modulus was affected most by varying the concentration of total monomer material. The material properties of our 3D printed IPN constructs were consistent with those reported in the biomechanics literature for soft tissues such as skeletal muscle, cardiac muscle, skin and subcutaneous tissue.

Effect of Strain Rate on the Material Properties of Human Liver Parenchyma in Unconfined Compression

The liver is one of the most frequently injured organs in abdominal trauma. Although motor vehicle collisions are the most common cause of liver injuries, current anthropomorphic test devices are not equipped to predict the risk of sustaining abdominal organ injuries. Consequently, researchers rely on finite element models to assess the potential risk of injury to abdominal organs such as the liver. These models must be validated based on appropriate biomechanical data in order to accurately assess injury risk. This study presents a total of 36 uniaxial unconfined compression tests performed on fresh human liver parenchyma within 48 h of death. Each specimen was tested once to failure at one of four loading rates (0.012, 0.106, 1.036, and 10.708 s-1) in order to investigate the effects of loading rate on the compressive failure properties of human liver parenchyma. The results of this study showed that the response of human liver parenchyma is both nonlinear and rate dependent. Specifically, failure stress significantly increased with increased loading rate, while failure strain significantly decreased with increased loading rate. The failure stress and failure strain for all liver parenchyma specimens ranged from -38.9 kPa to -145.9 kPa and from -0.48 strain to -1.15 strain, respectively. Overall, this study provides novel biomechanical data that can be used in the development of rate dependent material models and the identification of tissue-level tolerance values, which are critical to the validation of finite element models used to assess injury risk.

Multiscale computational model of fluid flow and matrix deformation in decellularized liver

Currently little is known about the biomechanical environment in decellularized tissue. The goal of this research is to quantify the mechanical microenvironment in decellularized liver, for varying organ-scale perfusion conditions, using a combined experimental/computational approach. Needle-guided ultra-miniature pressure sensors were inserted into liver tissue to measure parenchymal fluid pressure ex-situ in portal vein-perfused native (n=5) and decellularized (n=7) ferret liver, for flow rates from 3-12mL/min. Pressures were also recorded at the inlet near the portal vein cannula to estimate total vascular resistance of the specimens. Experimental results were fit to a multiscale computational model to simulate perfusion conditions inside native versus decellularized livers for four experimental flow rates. The multiscale model consists of two parts: an organ-scale electrical analog model of liver hemodynamics and a tissue-scale model that predicts pore fluid pressure, pore fluid velocity, and solid matrix stress and deformation throughout the 3D hepatic lobule. Distinct models were created for native versus decellularized liver. Results show that vascular resistance decreases by 82% as a result of decellularization. The hydraulic conductivity of the decellularized liver lobule, a measure of tissue permeability, was 5.6 times that of native liver. For the four flow rates studied, mean fluid pressures in the decellularized lobule were 0.6-2.4mmHg, mean fluid velocities were 211-767μm/s, and average solid matrix principal strains were 1.7-6.1%. In the future this modeling platform can be used to guide the optimization of perfusion seeding and conditioning strategies for decellularized scaffolds in liver bioengineering.

Dual stimuli responsive self-healing and malleable materials based on dynamic thiol-Michael chemistry

Thiol-maleimide adducts have been used as dynamic crosslinkers to form soft, elastic, and stimuli responsive polymeric materials. Thiol-Michael adducts can undergo dynamic exchange at elevated temperature or elevated pH values. Due to the dynamic behaviour of thiol-Michael adducts, crosslinked polymeric materials display significant healing after cutting into half, and malleability upon exposure to solutions of elevated pH. These materials are also thermally responsive, showing self-healing properties and malleability at high temperatures (90 °C). The self-healing properties of these polymer materials are significantly higher than materials with non-dynamic crosslinkers. In addition, in mechanical stability experiments, these materials showed creep resistance and complete creep recovery at room temperature and pressure. These results indicate that the thiol-Michael reaction is dynamic and reversible in response to thermal and pH stimuli. These stimuli responsive self-healing, elastic, malleable, and mechanically stable polymeric materials open the door to have potential utilization in different applications such as coatings or elastomers with extended lifetimes.

Fluid Flow Regulation of Revascularization and Cellular Organization in a Bioengineered Liver Platform.

OBJECTIVE Modeling of human liver development, especially cellular organization and the mechanisms underlying it, is fundamental for studying liver organogenesis and congenital diseases, yet there are no reliable models that mimic these processes ex vivo. DESIGN Using an organ engineering approach and relevant cell lines, we designed a perfusion system that delivers discrete mechanical forces inside an acellular liver extracellular matrix scaffold to study the effects of mechanical stimulation in hepatic tissue organization. RESULTS We observed a fluid flow rate-dependent response in cell distribution within the liver scaffold. Next, we determined the role of nitric oxide (NO) as a mediator of fluid flow effects on endothelial cells. We observed impairment of both neovascularization and liver tissue organization in the presence of selective inhibition of endothelial NO synthase. Similar results were observed in bioengineered livers grown under static conditions. CONCLUSION Overall, we were able to unveil the potential central role of discrete mechanical stimulation through the NO pathway in the revascularization and cellular organization of a bioengineered liver. Last, we propose that this organ bioengineering platform can contribute significantly to the identification of physiological mechanisms of liver organogenesis and regeneration and improve our ability to bioengineer livers for transplantation.