Novel Functionalization of Discrete Polymeric Biomaterial Microstructures for Applications in Imaging and Three-Dimensional Manipulation

Abstract

Adapting ways to functionalize polymer materials is becoming increasingly important to their implementation in translational biomedical sciences. By tuning the mechanical, chemical, and biological qualities of these materials, their applications can be broadened, opening the door for more advanced integration into modern medical techniques. Here, we report on a method to integrate chemical functionalizations into discrete, microscale polymer structures, which are used for tissue engineering applications, for in vivo localization, and three-dimensional manipulation. Iron oxide nanoparticles were incorporated into the polymer matrix using common photolithographic techniques to create stably functional microstructures with magnetic potential. Using magnetic resonance imaging (MRI), we can promote visualization of microstructures contained in small collections, as well as facilitate the manipulation and alignment of microtopographical cues in a realistic tissue environment. Using similar polymer functionalization techniques, fluorine-containing compounds were also embedded in the polymer matrix of photolithographically fabricated microstructures. The incorporation of fluorine-containing compounds enabled highly sensitive and specific detection of microstructures in physiologic settings using fluorine MRI techniques (19F MRI). These functionalization strategies will facilitate more reliable noninvasive tracking and characterization of microstructured polymer implants as well as have implications for remote microstructural scaffolding alignment for three-dimensional tissue engineering applications.

Probing the luminal microenvironment of reconstituted epithelial microtissues

“…We therefore used Sacrificial Micromolding 10 to pre-aggregate Caco-2 cells and polymeric microparticles within degradable microwells, before transferring these aggregates to Matrigel culture. We initially explored cuboidal microparticles (15 μm × 15 μm × 15 μm) fabricated from polyethylene glycol (PEG) and photolithographically shaped as previously described 12 . Using Sacrificial Micromolding, we found that approximately 25% of the multicellular aggregates that hosted one microcube developed into cysts incorporating that cube within their lumen, as shown in Fig.…”

“… 10 . For a detailed description of how cuboidal or rod-like PEG-microparticles were fabricated via photolithography, see refs 12 and 27 , respectively.…”

Formation of Spatially and Geometrically Controlled Three-Dimensional Tissues in Soft Gels by Sacrificial Micromolding

“…PEG-based polymeric microrods were fabricated using photolithographic techniques, as previously described. 21 To incorporate these microstructures within reconstituted cell aggregates, we mixed the (100 • 15 • 15 mm) microrods with MDCK cells at a ratio of 1:100 and loaded the mixture into sacrificial gelatin microwells molded from PDMS posts 120 mm in diameter and 80 mm in height.…”

Hybrid organic-inorganic Fe3O(TFBDC)3(H2O)3·(DMF)3 compound synthesized by slow evaporation method: Characterization and comparison of magnetic properties

“…In the area of MRI, the Fe 3 O 4 nanoparticles are widely used as contrast agents [6][7][8][9][10]. The combined method, based on susceptibility weighted images, has been developed to investigate human brains, particularly neural stem cells labelled with iron oxide.…”