Date of Award
Doctor of Philosophy (PhD)
Miller , Richard
Thompson , Lonny
Li , Gang
Laser-assisted cell direct-write technique has been obtaining more and more attention in different biomaterial direct writing applications. A typical laser-assisted cell direct-write process can be divided into two main stages: the cell droplet ejection and cell droplet landing. The objective of this study is to model the cell mechanical profile during the cell droplet ejection and cell landing and further model the cell damage.
The possible cell damage during the droplet ejection process in laser-assisted cell direct writing may come from two different sources: the phase explosion-induced bubble expansion and the thermoelastic stress wave. The bubble expansion-induced stress wave is the dominant effect in ejection. It is found that the cell velocity increases initially and then smoothes out gradually with a constant ejection velocity. Both the cell acceleration and pressure can be very high at the beginning period of bubble expansion and then quickly approach zero in an oscillation manner. A high viscosity can lead to an observable velocity increment at the initial stage, but the ejection velocity decreases. The pressure magnitude decreases when the cell-bubble distance is large, and a larger initial pressure induces a larger cell pressure as expected. If the thermal and stress confinement conditions are satisfied, the thermoelastic stress wave may introduce an alternative impact to cells to be transferred in laser-assisted cell direct writing. It is found that a bipolar pressure pair has been developed within a finite thin coating medium. The stress waves reflected from the coating-air free surface change its sign and have decreasing magnitude when traveling inside the coating. Shorter duration laser pulses lead to higher thermoelastic stresses and higher laser fluence leads to higher thermoelastic stresses.
The impact between the cell and the receiving culture coating/substrate during the cell landing may lead to cell damage. It is found that the cell membrane usually undergoes a relatively severe deformation and the cell mechanical loading profile is dependent on the cell droplet initial velocity and the substrate coating thickness. Generally, a larger initial velocity poses a higher probability of cell damage, and a substrate coating can significantly reduce the cell mechanical damage severity.
A new mathematical approach was proposed to biophysically predict the biofabrication-induced cell damage based on the triggered molecular signaling pathway in the cellular network. The proposed cell damage model includes two characteristics: 1) the cell may be dead only when the external stress exceeds a certain threshold value. Below this value, the cell does not commit any fate decision; and 2) if the external stress is higher than the threshold stress, the signaling pathway is triggered and may cause cell death depending on the time accumulative effect of external stress. That is, cell damage depends on the stress threshold, the external stress magnitude and its duration. This cell damage model is validated in damage modeling of a muscle-skin tissue and shows a good prediction of cell viability in laser assisted cell direct writing. More importantly, the proposed methodology provides a biophysics-based approach to investigate cell damage under influences of a variety of mechanical, chemical and biological environments by considering specific molecular networks in a cell.
In summary, this work modeled the laser-assisted cell direct writing and further modeled the cell damage based on a biophysics understanding.
Wang, Wei, "Modeling of Cell Transfer and Process-Induced Cell Damage in Laser-Assisted Cell Direct Writing" (2010). All Dissertations. 590.