Fabrication and study of patterned polymer brushes for controlling cell behavior

Abstract

Thorough understanding of how to control cell behaviors including cell adhesion, proliferation, orientation, migration, and differentiation on an artificial surface is critical in materials and life sciences such as biomedical engineering, tissue engineering, and cell-based bioassay. In vivo, extracellular matrix (ECM) consists of a combination of proteoglycans, glycosaminoglycans, fibrous proteins and adhesion proteins, which not only provide mechanical support to cells but also profoundly affect cell behaviors and cell functions. The three major cues in ECM, namely chemical, topographical and mechanical cues, can interact and communicate with cells to influence cell behaviors. Functional polymer brushes, which exhibit excellent mechanical properties, abundant chemical species, and remarkable capability to form various topographical surfaces, have superior advantages over many other materials for generating artificial ECM. This thesis studies the fabrication of biomimetic binary polymer brush patterns and their applications in controlling cell behaviors. Two new approaches are developed to generate binary polymer brush patterns for controlling cell behaviors. One is two-dimensional bench-top parallel dip-pen nanodisplacement lithography (DNL) (2D p-DNL) technique, by which the nano-micro binary polymer brush patterns are prepared. The nano-micro binary polymer brush patterns consist of lateral patterned centimeter-sized nanolines of gelatin-modified poly (glycidyl methacrylate) (gelatin-PGMA) brushes which are spaced by microstripes of poly (N-isopropylacrylamide) (PNIPAm) brushes. Cells can adhere and align well with the binary polymer brush patterns, and detach from the substrate with well-preserved ECM and aligned morphology upon the external thermal stimulus. Another method is microcontact printing (µCP) which is applied to generate a micropatterned binary polymer brush systems based on the serendipitous initiator-sticky ability of poly [oligo (ethylene glycol) methyl ether methacrylate] (POEGMA), poly (2-hydroxyethyl methacrylate) (PHEMA), and PGMA brushes. Briefly, initiator micropatterns are printed onto three kinds of polymer brush surfaces, and vertically patterned second-layer polymer brushes are then grown from the pre-patterned initiators. Cell micropatterning and orientation can be realized on the binary polymer brush patterns. For the content, the research background, challenges, objectives, and originality are introduced at the beginning of the thesis. Subsequently, a comprehensive literature review on polymer brushes for controlling cell behaviors and state-of-the-art lithography techniques for preparing patterned polymer brushes is presented. Chapter 3 gives a general description of research methodologies. In chapter 4, the DNL technique and the fabrication of single-component 3D-patterned polymer brushes are elaborately presented. Chapter 5 states the fabrication of binary 3D polymer brush structures by DNL. Chapter 6 focuses on the fabrication of nano-micro binary polymer brush patterns and the application in manipulating cell behaviors. Chapter 7 described a binary polymer brush micropatterns fabricated based on the initiator stickiness for cell micropatterning and orientation. Finally, the conclusions and outlook of this thesis are presented in Chapter 8.