- Goal
Our lab does "biomodeling", because it is interested in the creation of 1) experimental models using additive manufacturing technologies for the creation of tissue scaffolds and tissue engineered constructs with microstructural cues, and 2) predictive computational models of 3D tissue and cell-level mechanical effects of bioprinting cells and the effect of shear-mediated perfusion flow at a single cell. On the "biomeasurements" side, our lab is interested primarily in optical image acquisition and processing for quantitative measurement of cell morphology and tissue microarchitectures.
- Scientific Principles
RESEARCH PROJECTS:
3D Printing of spindle-like fibrous structures
Project Summary:
Advanced manufacturing of 3D-structured materials enables the production of biomimetic muscle tissues. While models of muscle tissue exist, current approaches possess a limited ability to capture essential elements of the muscle tissue microarchitecture. Therefore, this paper aims to engineer the intrinsically complex muscle spindle-like ellipsoid geometry using a polymer melt-based electrohydrodynamic (EHD) printing system. EHD systems have conventionally reported fiber deposition in a layerwise fashion. However, without mitigation, the observed fiber sagging and residual charge phenomena for the melt electrowriting (MEW) process limit the ability to produce layered fibrous 3D constructs with in-plane fiber alignment. However, in this work, fiber sagging and residual charge phenomena are leveraged as part of the design intent to deposit nonoverlapping suspended fibers between two stationary walls toward spindle-like construct fabrication. Specifically, herein the structural and mechanical properties of the MEW-enabled spindle-like constructs are analyzed as a function of the process and design parameters that govern control over fiber sagging and residual charge. The results indicate that the collector speed and wall-to-wall distance are the key parameters for tuning the spindle morphology. Moreover, cycle number and f iber diameter are identified as effective parameters for tuning the spindle mechanical properties.
Advanced manufacturing of 3D-structured materials enables the production of biomimetic muscle tissues. While models of muscle tissue exist, current approaches possess a limited ability to capture essential elements of the muscle tissue microarchitecture. Therefore, this paper aims to engineer the intrinsically complex muscle spindle-like ellipsoid geometry using a polymer melt-based electrohydrodynamic (EHD) printing system. EHD systems have conventionally reported fiber deposition in a layerwise fashion. However, without mitigation, the observed fiber sagging and residual charge phenomena for the melt electrowriting (MEW) process limit the ability to produce layered fibrous 3D constructs with in-plane fiber alignment. However, in this work, fiber sagging and residual charge phenomena are leveraged as part of the design intent to deposit nonoverlapping suspended fibers between two stationary walls toward spindle-like construct fabrication. Specifically, herein the structural and mechanical properties of the MEW-enabled spindle-like constructs are analyzed as a function of the process and design parameters that govern control over fiber sagging and residual charge. The results indicate that the collector speed and wall-to-wall distance are the key parameters for tuning the spindle morphology. Moreover, cycle number and f iber diameter are identified as effective parameters for tuning the spindle mechanical properties.
In-Situ Viscosity Monitoring of Hydrogels During Extrusion-based Bioprinting
Project Summary:
This study introduces a low-cost, in-situ viscosity measurement system (IVMS) for extrusion-based bioprinting, enabling real-time rheological characterization of shear-thinning hydrogel bioinks. The system integrates an S-beam load cell into the extrusion setup and includes precise force calibration and corrections for friction, entrance effects, wall-slip, and shear-thinning behavior. The IVMS is validated against traditional rheometry using GelMA bioinks of varying concentrations and temperatures to demonstrate its accuracy under printing conditions. This approach offers a practical, accessible tool for real-time bioink analysis, aiming to improve material design, process control, and enable adaptive bioprinting strategies for enhanced construct quality.
This study introduces a low-cost, in-situ viscosity measurement system (IVMS) for extrusion-based bioprinting, enabling real-time rheological characterization of shear-thinning hydrogel bioinks. The system integrates an S-beam load cell into the extrusion setup and includes precise force calibration and corrections for friction, entrance effects, wall-slip, and shear-thinning behavior. The IVMS is validated against traditional rheometry using GelMA bioinks of varying concentrations and temperatures to demonstrate its accuracy under printing conditions. This approach offers a practical, accessible tool for real-time bioink analysis, aiming to improve material design, process control, and enable adaptive bioprinting strategies for enhanced construct quality.
Design, fabrication, and characterization of tubular scaffolds via MEW
Project Summary:
Melt electrowriting (MEW) has emerged as a reliable additive manufacturing method for the fabrication of microscale fibrous tissue scaffolds. In order to expand the application scope of MEW, a controllable rotational mandrel is adapted as the collector for the fabrication of tubular scaffolds. Herein, the fundamental mathematical relationships among the tubular scaffold design parameters (winding angle (αw), number of pivot points (ndes), length of the tubular scaffold (L), and mandrel radius (R)) are established to enable various types of homogeneous and heterogeneous tubular scaffold designs. One type is the single-segment scaffold with a homogeneous 4-sided pore morphology. The other type is the multi-segment scaffold, which can possess multi-sided pores and spatially heterogeneous structures. Then, the printed scaffolds are structurally and mechanically evaluated. On the one hand, the scaffold design parameters (ndes, N and αw) are observed to have a negligible effect on the structural outcomes (αw, L, and fiber diameter (df)). On the other hand, increments in ndes and layer number (N), along with decrements in αw, are observed to yield enhanced mechanical outcomes. Lastly, the process parameter effects of collector speed on the tubular scaffold printing outcomes are investigated for the first time, which elaborate the most favorable conditions for obtaining highly-ordered scaffolds. Specifically, an increase in the collector speed parameter is accompanied by an observed increase in jet lag, leading to deterioration in the printing accuracy of tubular scaffolds
Melt electrowriting (MEW) has emerged as a reliable additive manufacturing method for the fabrication of microscale fibrous tissue scaffolds. In order to expand the application scope of MEW, a controllable rotational mandrel is adapted as the collector for the fabrication of tubular scaffolds. Herein, the fundamental mathematical relationships among the tubular scaffold design parameters (winding angle (αw), number of pivot points (ndes), length of the tubular scaffold (L), and mandrel radius (R)) are established to enable various types of homogeneous and heterogeneous tubular scaffold designs. One type is the single-segment scaffold with a homogeneous 4-sided pore morphology. The other type is the multi-segment scaffold, which can possess multi-sided pores and spatially heterogeneous structures. Then, the printed scaffolds are structurally and mechanically evaluated. On the one hand, the scaffold design parameters (ndes, N and αw) are observed to have a negligible effect on the structural outcomes (αw, L, and fiber diameter (df)). On the other hand, increments in ndes and layer number (N), along with decrements in αw, are observed to yield enhanced mechanical outcomes. Lastly, the process parameter effects of collector speed on the tubular scaffold printing outcomes are investigated for the first time, which elaborate the most favorable conditions for obtaining highly-ordered scaffolds. Specifically, an increase in the collector speed parameter is accompanied by an observed increase in jet lag, leading to deterioration in the printing accuracy of tubular scaffolds
Development of a low-cost quad-extrusion 3D bioprinting for multi-material constructs
Project Summary:
This study presents the development and characterization of a low-cost bioprinting system with a compact low-profile quad-extrusion bioprinting head for producing multi-material tissue constructs. The system, created by modifying an off-the-shelf three-dimensional (3D) printer, enables larger print volumes compared to extant systems. Incorporating gelatin methacrylate (GelMA) as a bioink model, the bioprinting system was systematically tested with two different printing techniques, namely the traditional in-air printing (IAP) mode along with an emerging support bath printing (SBP) paradigm. Structural fidelity was assessed by comparing printed structures under different conditions to the computer-aided design (CAD) model. To evaluate biological functionality, a placental model was created using HTR-8 trophoblasts known for their invasive phenotype. Biological assays of cell viability and invasion revealed that the cells achieved high cell proliferation rates and had over 93% cell viability for a 3-day incubation period. The multi-compartmental 3D-bioprinted in vitro placenta model demonstrates the potential for studying native cell phenotypes and specialized functional outcomes enabled by the multi-material capability of the quad-extrusion bioprinter (QEB). This work represents a significant advancement in bioprinting technology, allowing for the printing of complex and highly organized tissue structures at scale. Moreover, the system’s total build cost is only US$ 297, making it an affordable resource for researchers.
This study presents the development and characterization of a low-cost bioprinting system with a compact low-profile quad-extrusion bioprinting head for producing multi-material tissue constructs. The system, created by modifying an off-the-shelf three-dimensional (3D) printer, enables larger print volumes compared to extant systems. Incorporating gelatin methacrylate (GelMA) as a bioink model, the bioprinting system was systematically tested with two different printing techniques, namely the traditional in-air printing (IAP) mode along with an emerging support bath printing (SBP) paradigm. Structural fidelity was assessed by comparing printed structures under different conditions to the computer-aided design (CAD) model. To evaluate biological functionality, a placental model was created using HTR-8 trophoblasts known for their invasive phenotype. Biological assays of cell viability and invasion revealed that the cells achieved high cell proliferation rates and had over 93% cell viability for a 3-day incubation period. The multi-compartmental 3D-bioprinted in vitro placenta model demonstrates the potential for studying native cell phenotypes and specialized functional outcomes enabled by the multi-material capability of the quad-extrusion bioprinter (QEB). This work represents a significant advancement in bioprinting technology, allowing for the printing of complex and highly organized tissue structures at scale. Moreover, the system’s total build cost is only US$ 297, making it an affordable resource for researchers.
Analytical Modeling of Microscale Fiber Deviation in Melt Electrohydrodynamic printing
Project Summary:
This study addresses the challenge of fiber deviation in melt electrowriting (MEW), an electrohydrodynamic-based additive manufacturing technique for fabricating microscale fibrous architectures. A key limitation in MEW is the spatial lag between the nozzle position (np) and the contact point (cp), which becomes more pronounced during directional changes, leading to reduced printing accuracy—especially in curly fiber patterns. To overcome this, the authors develop an analytical model using vector analysis and differential geometry to describe the positional and velocity relationships between np and cp. The model is applied to both straight and curly fiber scenarios, with validation, and highlights the importance of real-time cp tracking and dynamic stage speed control for improving toolpath fidelity in MEW.
This study addresses the challenge of fiber deviation in melt electrowriting (MEW), an electrohydrodynamic-based additive manufacturing technique for fabricating microscale fibrous architectures. A key limitation in MEW is the spatial lag between the nozzle position (np) and the contact point (cp), which becomes more pronounced during directional changes, leading to reduced printing accuracy—especially in curly fiber patterns. To overcome this, the authors develop an analytical model using vector analysis and differential geometry to describe the positional and velocity relationships between np and cp. The model is applied to both straight and curly fiber scenarios, with validation, and highlights the importance of real-time cp tracking and dynamic stage speed control for improving toolpath fidelity in MEW.
