Canavan Lab- Research

Our research integrates techniques developed in biology, polymer chemistry, and surface science to study bioengineering at the cell/surface and protein/surface level. Understanding gained from this fundamental research will allow for the directed design of novel engineered cellular constructs in the future.

We are actively working in the following areas:

1. Assessment of the Biocompatibility, Stability, and Suitability of Thermoresponsive pNIPAM for Cellular Constructs. The term ?Smart Materials? refers to a class of materials that undergo a large physical change in response to environmental cues. Poly(N-isopropyl acrylamide) (pNIPAM) is one such polymer that undergoes a change in surface hydrophobicity as a response to temperature drop around physiological temperatures (~32 ?C). This change is transmitted to adhered cells and opens up the use of pNIPAM-treated surfaces for a variety of bioengineering applications, including cell-based sensors, drug delivery systems, and engineered tissues.

The popularity of the pNIPAM substrate may have led many to certain misunderstandings regarding cell detachment from pNIPAM; namely, that the sole application for which cell release from pNIPAM is used is cell sheet or tissue engineering, that the mechanism by which cell release is achieved is a well-understood phenomenon, and that there is a standard set of procedures that researchers follow to yield predictable release from pNIPAM. In fact, despite the popularity of pNIPAM and other stimulus-responsive and bioactive materials, there is a genuine lack of understanding of how these polymers? material properties direct cellular behavior, including cell/cell interactions, as well as cell/surface interactions. Much of our research has therefore focused on how an increased understanding of this fundamental relationship between material properties and resulting cellular function will lead to advances both in fundamental science, as well as improved engineered devices. This work has been highlighted in publications in Langmuir, ACS Applied Materials & Interfaces, and the Journal of Applied Biomaterials & Biomechanics.

2. Plasma Polymerization of "Smart" Materials. Depending on the application, a variety of techniques have been used to deposit pNIPAM onto surfaces. Some of the techniques that have been utilized include grafting using UV or electron beam irradiation, atom transfer radical polymerization (ATRP), solution deposition, and vapor-phase plasma polymerization. In this work, the technique used to deposit pNIPAM films is plasma polymerization of NIPAM (ppNIPAM).

One of the primary advantages of plasma polymerization of NIPAM from the vapor-phase is that surfaces of any chemistry and geometry may be used for deposition. In addition, the technique is sterile, which is important for cell culture applications. This technique is therefore extremely well-suited to the deposition of biocompatible films such as pNIPAM onto the plasticware (e.g., tissue culture polystyrene) that is used in cell culture. The reactor used for plasma polymerization (photo at left) was fabricated in house. Its fabrication and optimization for pNIPAM deposition was recently described in a publication in Plasma Polymers and Processes.

3. "Smart" Surfaces for Research in Cancer Cell Biology. Spheroids are small (~50-1000 ?m diameter) sphere-shaped aggregates of cells that have been developed as 3D models for tumors. In addition to providing a model that more closely approximates the microenvironments of tissues and tumors than 2D cultures, spheroids can be more easily controlled than tests preformed on animal models. Current approaches for spheroid formation result in spheroids with a wide size distribution, requiring the use of secondary sorting to obtain a uniformly-sized population. To increase the efficacy of these models for drug discovery in cancer therapeutics, it is necessary to develop an efficient way to fabricate a large number of uniform spheroids.

In collaboration with Angela Wandinger-Ness and Jim Freyer, we seek to develop pNIPAM-treated substrates for the gentle release of cellular spheroids into suspension for cancer cell biology studies. Preliminary studies from this project were included in the dissertation of Dr. Jamie Reed, a recent graduate from the Canavan group.


4. Investigation of the Cytotoxicity of Biocidal Polymers. The Whitten and Schanze groups synthesize, characterize, and develop applications for phenylene ethynylene-based polymers. These polymers are of interested because they are synthetic biomimetic analogs to naturally occurring antimicrobial peptides (AMPs). Because of their non-specific mode of action, the polymers are expected to be effective at killing even drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Envisioned applications of the biocidal polymer include the consumable materials used in hospitals, as they carry the potential to transfer infectious bacteria to the patient. However, prior to their use we are evaluating the potential toxicity of these polymers toward eukaryotic cells (such as humans) in such applications.
This work was recently highlighted in Biophotonics.


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