A structural finite element model for lamellar unit of aortic media indicates heterogeneous stress field after collagen recruitment.

Incorporation of collagen structural information into the study of biomechanical behavior of ascending thoracic aortic (ATA) wall tissue should provide better insight into the pathophysiology of ATA. Structurally motivated constitutive models that include fiber dispersion and recruitment can successfully capture overall mechanical response of the arterial wall tissue. However, these models cannot examine local microarchitectural features of the collagen network, such as the effect of fiber disruptions and interaction between fibrous and non-fibrous components, which may influence emergent biomechanical properties of the tissue. Motivated by this need, we developed a finite element based three-dimensional structural model of the lamellar units of the ATA media that directly incorporates the collagen fiber microarchitecture. The fiber architecture was computer generated utilizing network features, namely fiber orientation distribution, intersection density and areal concentration, obtained from image analysis of multiphoton microscopy images taken from human aneurysmal ascending thoracic aortic media specimens with bicuspid aortic valve (BAV) phenotype. Our model reproduces the typical J-shaped constitutive response of the aortic wall tissue. We found that the stress state in the non-fibrous matrix was homogeneous until the collagen fibers were recruited, but became highly heterogeneous after that event. The degree of heterogeneity was dependent upon local network architecture with high stresses observed near disrupted fibers. The magnitude of non-fibrous matrix stress at higher stretch levels was negatively correlated with local fiber density. The localized stress concentrations, elucidated by this model, may be a factor in the degenerative changes in aneurysmal ATA tissue.

The Effect of Size and Location of Tears in the Supraspinatus Tendon on Potential Tear Propagation.

Rotator cuff tears are a common problem in patients over the age of 50 yr. Tear propagation is a potential contributing factor to the failure of physical therapy for treating rotator cuff tears, thus requiring surgical intervention. However, the evolution of tears within the rotator cuff is not well understood yet. The objective of this study is to establish a computational model to quantify initiation of tear propagation in the supraspinatus tendon and examine the effect of tear size and location. A 3D finite element (FE) model of the supraspinatus tendon was constructed from images of a healthy cadaveric tendon. A tear of varying length was placed at six different locations within the tendon. A fiber-reinforced Mooney-Rivlin material model with spatial variation in material properties along the anterior-posterior (AP) axis was utilized to obtain the stress state of the computational model under uniaxial stretch. Material parameters were calibrated by comparing computational and experimental stress-strain response and used to validate the computational model. The stress state of the computational model was contrasted against the spatially varying material strength to predict the critical applied stretch at which a tear starts propagating further. It was found that maximum principal stress (as well as the strain) was localized at the tips of the tear. The computed critical stretch was significantly lower for the posterior tip of the tear than for the anterior tip suggesting a propensity to propagate posteriorly. Onset of tear propagation was strongly correlated with local material strength and stiffness in the vicinity of the tear tip. Further, presence of a stress-shielded zone along the edges of the tear was observed. This study illustrates the complex interplay between geometry and material properties of tendon up to the initiation of tear propagation. Future work will examine the evolution of tears during the propagation process as well as under more complex loading scenarios.

Force production and mechanical accommodation during convergent extension.

Forces generated within the embryo during convergent extension (CE) must overcome mechanical resistance to push the head away from the rear. As mechanical resistance increases more than eightfold during CE and can vary twofold from individual to individual, we have proposed that developmental programs must include mechanical accommodation in order to maintain robust morphogenesis. To test this idea and investigate the processes that generate forces within early embryos, we developed a novel gel-based sensor to report force production as a tissue changes shape; we find that the mean stress produced by CE is 5.0±1.6 Pascal (Pa). Experiments with the gel-based force sensor resulted in three findings. (1) Force production and mechanical resistance can be coupled through myosin contractility. The coupling of these processes can be hidden unless affected tissues are challenged by physical constraints. (2) CE is mechanically adaptive; dorsal tissues can increase force production up to threefold to overcome a stiffer microenvironment. These findings demonstrate that mechanical accommodation can ensure robust morphogenetic movements against environmental and genetic variation that might otherwise perturb development and growth. (3) Force production is distributed between neural and mesodermal tissues in the dorsal isolate, and the notochord, a central structure involved in patterning vertebrate morphogenesis, is not required for force production during late gastrulation and early neurulation. Our findings suggest that genetic factors that coordinately alter force production and mechanical resistance are common during morphogenesis, and that their cryptic roles can be revealed when tissues are challenged by controlled biophysical constraints.

In vivo study of magnesium plate and screw degradation and bone fracture healing.

Each year, millions of Americans suffer bone fractures, often requiring internal fixation. Current devices, like plates and screws, are made with permanent metals or resorbable polymers. Permanent metals provide strength and biocompatibility, but cause long-term complications and may require removal. Resorbable polymers reduce long-term complications, but are unsuitable for many load-bearing applications. To mitigate complications, degradable magnesium (Mg) alloys are being developed for craniofacial and orthopedic applications. Their combination of strength and degradation make them ideal for bone fixation. Previously, we conducted a pilot study comparing Mg and titanium devices with a rabbit ulna fracture model. We observed Mg device degradation, with uninhibited healing. Interestingly, we observed bone formation around degrading Mg, but not titanium, devices. These results highlighted the potential for these fixation devices. To better assess their efficacy, we conducted a more thorough study assessing 99.9% Mg devices in a similar rabbit ulna fracture model. Device degradation, fracture healing, and bone formation were evaluated using microcomputed tomography, histology and biomechanical tests. We observed device degradation throughout, and calculated a corrosion rate of 0.40±0.04mm/year after 8 weeks. In addition, we observed fracture healing by 8 weeks, and maturation after 16 weeks. In accordance with our pilot study, we observed bone formation surrounding Mg devices, with complete overgrowth by 16 weeks. Bend tests revealed no difference in flexural load of healed ulnae with Mg devices compared to intact ulnae. These data suggest that Mg devices provide stabilization to facilitate healing, while degrading and stimulating new bone formation.

Effect of aneurysm on biomechanical properties of "radially-oriented" collagen fibers in human ascending thoracic aortic media.

We recently reported a mechanistic model to link micro-architectural information to the delamination strength (Sd) of human ascending thoracic aorta (ATA). That analysis demonstrated that the number density (N) and failure energy (Uf) of the radially-oriented collagen fibers contribute to the Sd of both aneurysmal (ATAA) and non-aneurysmal (CTRL-ATA) aortic tissue. Among the set of ATAA samples, we studied specimens from patients displaying bicuspid (BAV) and tricuspid aortic valve (TAV) morphologic phenotypes. Results from our prior work were based on the assumption that the Uf was independent of dissection direction. In the current study, we excluded that assumption and hypothesized that Uf correlates with the Sd of ATAA. To test the hypothesis, we used previously-reported experimentally-determined Sd measurements and N of radially-oriented collagen fibers as input in our validated mechanistic model to calculate Uf for BAV-ATAA, TAV-ATAA and CTRL-ATA tissue specimens. The results of our analysis revealed that Uf is significantly lower for both BAV-ATAA and TAV-ATAA compared to CTRL-ATA cases, and does not differ between BAV-ATAA and TAV-ATAA. Furthermore, we found that Uf is consistent between circumferential-radial and longitudinal-radial planes in either of BAV-ATAA, TAV-ATAA or CTRL-ATA specimens. These findings employ a novel mechanistic model to increase our understanding of the putative interrelationship between biomechanical properties, extracellular matrix biology, and failure energy of aortic dissection.

Varying degrees of nonlinear mechanical behavior arising from geometric differences of urogynecological meshes.

Synthetic polypropylene meshes were designed to restore pelvic organ support for women suffering from pelvic organ prolapse; however, the FDA released two notifications regarding potential complications associated with mesh implantation. Our aim was to characterize the structural properties of Restorelle and UltraPro subjected to uniaxial tension along perpendicular directions, and then model the tensile behavior of these meshes utilizing a co-rotational finite element model, with an imbedded linear or fiber-recruitment local stress-strain relationship. Both meshes exhibited a highly nonlinear stress-strain behavior; Restorelle had no significant differences between the two perpendicular directions, while UltraPro had a 93% difference in the low (initial) stiffness (p=0.009) between loading directions. Our model predicted that early alignment of the mesh segments in the loading direction and subsequent stretching could explain the observed nonlinear tensile behavior. However, a nonlinear stress-strain response in the stretching regime, that may be inherent to the mesh segment, was required to better capture experimental results. Utilizing a nonlinear fiber recruitment model with two parameters A and B, we observed improved agreement between the simulations and the experimental results. An inverse analysis found A=120 MPa and B=1.75 for Restorelle (RMSE=0.36). This approach yielded A=30 MPa and B=3.5 for UltraPro along one direction (RMSE=0.652), while the perpendicular orientation resulted in A=130 MPa and B=4.75 (RMSE=4.36). From the uniaxial protocol, Restorelle was found to have little variance in structural properties along these two perpendicular directions; however, UltraPro was found to behave anisotropically.

A mechanistic model on the role of "radially-running" collagen fibers on dissection properties of human ascending thoracic aorta.

Aortic dissection (AoD) is a common condition that often leads to life-threatening cardiovascular emergency. From a biomechanics viewpoint, AoD involves failure of load-bearing microstructural components of the aortic wall, mainly elastin and collagen fibers. Delamination strength of the aortic wall depends on the load-bearing capacity and local micro-architecture of these fibers, which may vary with age, disease and aortic location. Therefore, quantifying the role of fiber micro-architecture on the delamination strength of the aortic wall may lead to improved understanding of AoD. We present an experimentally-driven modeling paradigm towards this goal. Specifically, we utilize collagen fiber micro-architecture, obtained in a parallel study from multi-photon microscopy, in a predictive mechanistic framework to characterize the delamination strength. We then validate our model against peel test experiments on human aortic strips and utilize the model to predict the delamination strength of separate aortic strips and compare with experimental findings. We observe that the number density and failure energy of the radially-running collagen fibers control the peel strength. Furthermore, our model suggests that the lower delamination strength previously found for the circumferential direction in human aorta is related to a lower number density of radially-running collagen fibers in that direction. Our model sets the stage for an expanded future study that could predict AoD propagation in patient-specific aortic geometries and better understand factors that may influence propensity for occurrence.

Magnesium alloys as a biomaterial for degradable craniofacial screws.

Recently, magnesium (Mg) alloys have received significant attention as potential biomaterials for degradable implants, and this study was directed at evaluating the suitability of Mg for craniofacial bone screws. The objective was to implant screws fabricated from commercially available pure Mg and alloy AZ31 in vivo in a rabbit mandible. First, Mg and AZ31 screws were compared to stainless steel screws in an in vitro pull-out test and determined to have a similar holding strength (∼40N). A finite-element model of the screw was created using the pull-out test data, and this model can be used for future Mg alloy screw design. Then, Mg and AZ31 screws were implanted for 4, 8 and 12weeks, with two controls of an osteotomy site (hole) with no implant and a stainless steel screw implanted for 12weeks. Microcomputed tomography was used to assess bone remodeling and Mg/AZ31 degradation, both visually and qualitatively through volume fraction measurements for all time points. Histological analysis was also completed for the Mg and AZ31 at 12weeks. The results showed that craniofacial bone remodeling occurred around both Mg and AZ31 screws. Pure Mg had a different degradation profile than AZ31; however, bone growth occurred around both screw types. The degradation rate of both Mg and AZ31 screws in the bone marrow space and the muscle were faster than in the cortical bone space at 12weeks. Furthermore, it was shown that by alloying Mg, the degradation profile could be changed. These results indicate the promise of using Mg alloys for craniofacial applications.