Topologically Controlled Cell Differentiation Based on Vapor-Deposited Polymer Coatings

Abstract

In addition to the widely adopted method of controlling cell attachment for cell patterning, pattern formation via cell proliferation and differentiation is demonstrated using precisely defined interface chemistry and spatial topology. The interface platform is created using a maleimide-functionalized parylene coating (maleimide-PPX) that provides two routes for controlled conjugation accessibility, including the maleimide-thiol coupling reaction and the thiol-ene click reaction, with a high reaction specificity under mild conditions. The coating technology is a prime tool for the immobilization of sensitive molecules, such as growth factor proteins. Conjugation of fibroblast growth factor 2 (FGF-2) and bone morphogenetic protein (BMP-2) was performed on the coating surface by elegantly manipulating the reaction routes, and confining the conjugation reaction to selected areas was accomplished using microcontact printing (μCP) and/or UV irradiation photopatterning. The modified interface provides chemically and topologically defined signals that are recognized by cultured murine preosteoblast cells for proliferation (by FGF-2) and osteogenesis (by BMP-2) activities in specific locations. The reported technique additionally enabled synergistic pattern formation for both osteogenesis and proliferation activities on the same interface, which is difficult to perform using conventional cell attachment patterns. Because of the versatility of the coating, which can be applied to a wide range of materials and on curved and complex devices, the proposed technology is extendable to other prospective biomaterial designs and material interface modifications.

Creating Nano-engineered Biomaterials with Well-Defined Surface Descriptors

“…Biological events happening on and in the vicinity of biomaterials are governed by the material surface properties. , While the impact of microtopography and surface chemistry on cellular response has been well-studied, little is known about the exact role played by surfaces with nanosized features. − Although cells are several micrometers in size, cellular function is underpinned by interactions between nanotopographical features of the growth substrates and nanosized serum proteins, and cell surface receptors. − In fact, it is well-established that protein adsorption − and cell functions such as cell differentiation, migration, , attachment, and proliferation − are altered by nanoscale interactions at the biomaterial/media interface. − This is why significant effort has been devoted to creating sophisticated nanotextured surfaces for cell transplantation, controlling cancer cell function, − tissue engineering, gene transfection, , skin regeneration, , neural tissue engineering, , stem cell differentiation, − bone regeneration, , infection prevention and bacterial adhesion, − nanobiosensors, and biomedical devices. , …”

Proliferation of Cells with Severe Nuclear Deformation on a Micropillar Array

“…Cell–material interactions constitute important fundamental topics in the fields of biomedicine and biomaterials. − The surface topography and physicochemical environment influence the cellular behavior profoundly at the cell–substrate interface. , With the development of surface patterning techniques, − appropriate microscale and nanoscale features have been found to influence cell behavior without necessarily destroying the cellular biochemical environment. Topological controls of various cellular responses, including cell adhesion, proliferation, migration, and differentiation, have been reported in recent years. − The underlying mechanisms of the cellular responses to topological features have been proposed recently, such as the discovery of the key proteins in the membrane curvature. − …”

Vapor-Phase Fabrication of a Maleimide-Functionalized Poly-p-xylylene with a Three-Dimensional Structure

“…For vapor deposition, a maleimide-substituted [2,2]paracyclophane starting material was synthesized via the reported routes [33]; theoretically, in the conventional CVD polymerization, these starting materials were sublimated at approximately 90 • C under a reduced pressure of 100 mTorr and pyrolyzed at 540 • C, forming highly reactive monomer quinodimethanes species. Finally, these monomers underwent radical polymerization upon condensation at a low temperature (40 • C or below) and solid substrate formation of thin-film coatings [27,33,35]. However, in the experiments herein, the vapor deposition and polymerization occurred on the prepared ice substrates/templates and under the devised thermodynamic conditions (10 • C and under 100 mTorr).…”