Shengmao Lin

Bioink properties before, during and after 3D bioprinting

Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction.

Influence of Crosslink Density and Stiffness on Mechanical Properties of Type I Collagen Gel

The mechanical properties of type I collagen gel vary due to different polymerization parameters. In this work, the role of crosslinks in terms of density and stiffness on the macroscopic behavior of collagen gel were investigated through computational modeling. The collagen fiber network was developed in a representative volume element, which used the inter-fiber spacing to regulate the crosslink density. The obtained tensile behavior of collagen gel was validated against published experimental data. Results suggest that the cross-linked fiber alignment dominated the strain stiffening effect of the collagen gel. In addition, the gel stiffness was enhanced approximately 40 times as the crosslink density doubled. The non-affine deformation was reduced with the increased crosslink density. A positive bilinear correlation between the crosslink density and gel stiffness was obtained. On the other hand, the crosslink stiffness had much less impact on the gel stiffness. This work could enhance our understanding of collagen gel mechanics and shed lights on designing future clinical relevant biomaterials with better control of polymerization parameters.

Relevance of Blood Vessel Networks in Blast-Induced Traumatic Brain Injury.

Cerebral vasculature is a complex network that circulates blood through the brain. However, the role of this networking effect in brain dynamics has seldom been inspected. This work is to study the effects of blood vessel networks on dynamic responses of the brain under blast loading. Voronoi tessellations were implemented to represent the network of blood vessels in the brain. The brain dynamics in terms of maximum principal strain (MPS), shear strain (SS), and intracranial pressure (ICP) were monitored and compared. Results show that blood vessel networks significantly affected brain responses. The increased MPS and SS were observed within the brain embedded with vessel networks, which did not exist in the case without blood vessel networks. It is interesting to observe that the alternation of the ICP response was minimal. Moreover, the vessel diameter and density also affected brain dynamics in both MPS and SS measures. This work sheds light on the role of cerebral vasculature in blast-induced traumatic brain injury.

Fluid-Structure Interaction in Abdominal Aortic Aneurysm: Effect of Modeling Techniques

In this work, the impact of modeling techniques on predicting the mechanical behaviors of abdominal aortic aneurysm (AAA) is systematically investigated. The fluid-structure interaction (FSI) model for simultaneously capturing the transient interaction between blood flow dynamics and wall mechanics was compared with its simplified techniques, that is, computational fluid dynamics (CFD) or computational solid stress (CSS) model. Results demonstrated that CFD exhibited relatively smaller vortexes and tends to overestimate the fluid wall shear stress, compared to FSI. On the contrary, the minimal differences in wall stresses and deformation were observed between FSI and CSS models. Furthermore, it was found that the accuracy of CSS prediction depends on the applied pressure profile for the aneurysm sac. A large pressure drop across AAA usually led to the underestimation of wall stresses and thus the AAA rupture. Moreover, the assumed isotropic AAA wall properties, compared to the anisotropic one, will aggravate the difference between the simplified models with the FSI approach. The present work demonstrated the importance of modeling techniques on predicting the blood flow dynamics and wall mechanics of the AAA, which could guide the selection of appropriate modeling technique for significant clinical implications.

Eigenstrain as a mechanical set-point of cells

Cell contraction regulates how cells sense their mechanical environment. We sought to identify the set-point of cell contraction, also referred to as tensional homeostasis. In this work, bovine aortic endothelial cells (BAECs), cultured on substrates with different stiffness, were characterized using traction force microscopy (TFM). Numerical models were developed to provide insights into the mechanics of cell–substrate interactions. Cell contraction was modeled as eigenstrain which could induce isometric cell contraction without external forces. The predicted traction stresses matched well with TFM measurements. Furthermore, our numerical model provided cell stress and displacement maps for inspecting the fundamental regulating mechanism of cell mechanosensing. We showed that cell spread area, traction force on a substrate, as well as the average stress of a cell were increased in response to a stiffer substrate. However, the cell average strain, which is cell type-specific, was kept at the same level regardless of the substrate stiffness. This indicated that the cell average strain is the tensional homeostasis that each type of cell tries to maintain. Furthermore, cell contraction in terms of eigenstrain was found to be the same for both BAECs and fibroblast cells in different mechanical environments. This implied a potential mechanical set-point across different cell types. Our results suggest that additional measurements of contractility might be useful for monitoring cell mechanosensing as well as dynamic remodeling of the extracellular matrix (ECM). This work could help to advance the understanding of the cell-ECM relationship, leading to better regenerative strategies.

Towards Tuning the Mechanical Properties of Three-Dimensional Collagen Scaffolds Using a Coupled Fiber-Matrix Model

Scaffold mechanical properties are essential in regulating the microenvironment of three-dimensional cell culture. A coupled fiber-matrix numerical model was developed in this work for predicting the mechanical response of collagen scaffolds subjected to various levels of non-enzymatic glycation and collagen concentrations. The scaffold was simulated by a Voronoi network embedded in a matrix. The computational model was validated using published experimental data. Results indicate that both non-enzymatic glycation-induced matrix stiffening and fiber network density, as regulated by collagen concentration, influence scaffold behavior. The heterogeneous stress patterns of the scaffold were induced by the interfacial mechanics between the collagen fiber network and the matrix. The knowledge obtained in this work could help to fine-tune the mechanical properties of collagen scaffolds for improved tissue regeneration applications.

Case Study of Quantifying Energy Loss through Ceiling-Attic Recessed Lighting Fixtures through 3D Numerical Simulation

AbstractAir leakage through recessed lighting fixtures has been identified as a common issue that causes extra energy consumption in residential buildings. However, few quantitative studies in this area were found. As such, a preliminary assessment of the magnitude of this type of energy loss was conducted by using three-dimensional (3D) transient computational fluid dynamics (CFD) models. A hypothetical layout of recessed lighting fixtures was designed with boundary conditions of four different seasons, which were obtained from recorded roof/attic temperature data sets. The results of the study indicate that leakage of recessed lighting fixtures could be a significant channel of energy loss in such attic-related residential buildings, especially in the summer and winter.

Multiscale Modeling of Skeletal Muscle Active Contraction in Relation to Mechanochemical Coupling of Molecular Motors

In this work, a mathematical model was developed to relate the mechanochemical characterizations of molecular motors with the macroscopic manifestation of muscle contraction. Non-equilibrium statistical mechanics were used to study the collective behavior of myosin molecular motors in terms of the complex conformation change and multiple chemical states in one working cycle. The stochastic evolution of molecular motor probability density distribution during the contraction of sarcomere was characterized by the Fokker-Planck Equation. Quick muscle contraction was demonstrated by the collective dynamic behavior of myosin motors, the muscle contraction force, and the muscle contraction velocity-force relation. Our results are validated against published experiments, as well as the predictions from the Hill’s model. The quantitative relation between myosin molecular motors and muscle contraction provides a novel way to unravel the mechanism of force generation.

Evaluating Energy Loss through Recessed Lighting Fixtures (RLF) in Residential Buildings through a Case Study

Unintended air leakage through building envelope is a major source of energy loss of residential buildings. Air leakage through improperly installed recessed lighting fixtures (RLF) has been identified as one source of unintended air leakage. However, little quantitative study was found on the energy loss through improperly-installed RLF. In this paper, the authors conducted preliminary evaluation of the magnitude of such energy loss by numerical simulations using 3D transient CFD model. One case was studied using boundary conditions of four seasons, which were obtained from historical experimental data from Mississippi. The results of the simulations indicate RLF can be a very significant source of energy loss in both summer and winter conditions. The study suggests that systematic approach is needed to improve the RLF design and construction practice to reduce or remove the RLF’s negative impact on energy loss of residential buildings.