Thank you for your intriguing questions, Dr. Shin. Wettability is a critical factor for cell interactions to determine if the cells will spread, proliferate, and reproduce on a substrate. The polarity of a surface dictates the wettability of the surface. Cells prefer moderately hydrophilic surfaces for normal cell functions. In regards to your second question, we should first realize that PEM multilayers are highly ionically crosslinked, in contrast with highly permeable hydrogels. One can embed enzymes within the polyelectrolyte multi-layers as proven in Mertz et. al., "Mechanotransductive surfaces for reversible biocatalysis activation” (Nature Materials 2009). This article illustrates the controlled release of enzymes upon an external mechanical stimulus. We would like to use similar methods to incorporate growth factors or other cell environment markers so that we can release these factors upon shape memory polymer activation.

Thank you for your question, Dr. Pfromm. You raise an interesting point about the application biocompatibility. Yes, the SMP PEM biomaterial will change as it interacts with the bio environment, but it is difficult to state the degree and extent of this change at this moment without in vivo, or at least in vitro tests. In order for free anions and cations to disrupt PEM coating structure, they must overcome (large) entropy for ion exchange within PEM macromolecular ion pairs. Though this is possible, we have not found this reported in literature to date. Nonetheless, your question has made me aware of this possibility! Furthermore, the surface charge can be tuned by the concentration of surface cation or surface anion for improved biomaterial interactions. The overall system is neutral except for the slight charge of the surface because the anions and cations are paired creating polyelectrolyte bilayers.

Thank you for your question, Dr. Albert. Shape memory polymers and polyeletrolyte multi-layers have been used as biomaterial substrates separately with several noted benefits. Shape memory polymers can mimic biological surface topography and change shape upon stimulus activation triggered by physiological conditions. Polyeletrolyte multi-layers provide improved compatibility and wettability due to a change in substrate surface charge. This project is the first project to combine the two polymer systems with the potential of synergistic benefits. Other polymer systems have been used previously; however, we believe that this novel combination will create an optimally dynamic (SMP) and biocompatible (PEM) system. In addition to this, my advisors have experience working with both polymer systems in great detail.

Thank you for your question, Dr. Buneo. Your insight has helped me think of specific applications. While the combination of SMP and PEM as a biomaterial represents a system that can be used for several internal organs and soft tissues, it may need to be tailored specifically for different applications. For example, the stiffness or roughness may need to be changed significantly for different biological applications. Despite that this biomaterial has the potential to be used as vascular or bone tissue, the stiffness and chemistry will need to be altered for the best performance for each application. Currently, we do not foresee the present biomaterial system for use in very soft biological organ system applications such as brain implants or ocular devices due to mechanical incompatibility.

Thank you Dr. McDonald for your astute questions. We are interested in tissue engineering and mechanobiology cell material interactions. Cells have the unique ability to sense their environment, elicit a response, and adapt to the environment change. We want to understand cell biological processes as this SMP-PEM biomaterial substrate changes for different stimuli thereby creating a new active cell culture technology.

Hydrophobicity and roughness (or topography) are very important properties for cell material interactions because they are the first fundamental properties that dictate if the cells will attach, spread, and grow on the substrate. However, there are many very important properties for optimal cell material interactions because of the complexity of biological systems. Growth factors and mechanical properties are examples of other extremely important properties for biomimetic environments and improved cell interactions. We can potentially embed growth proteins within the PEM and release them upon activation of the SMP. We can also change the mechanical properties of the SMP to match different biological systems.

In regards to your last question, the biomaterial substrate can be UV sterilized. Though I have not completed this part of the project yet, another student in my advisors’ lab was able to UV sterilize the same SMP biomaterial substrate for active cell culture in “Dynamic cell behavior on shape memory polymer substrates,” (Biomaterials 2011).

Thank you Allen!

Thank you Janice.