Rohan Fernandes

Self-folding polymeric containers for encapsulation and delivery of drugs

Self-folding broadly refers to self-assembly processes wherein thin films or interconnected planar templates curve, roll-up or fold into three dimensional (3D) structures such as cylindrical tubes, spirals, corrugated sheets or polyhedra. The process has been demonstrated with metallic, semiconducting and polymeric films and has been used to curve tubes with diameters as small as 2nm and fold polyhedra as small as 100nm, with a surface patterning resolution of 15nm. Self-folding methods are important for drug delivery applications since they provide a means to realize 3D, biocompatible, all-polymeric containers with well-tailored composition, size, shape, wall thickness, porosity, surface patterns and chemistry. Self-folding is also a highly parallel process, and it is possible to encapsulate or self-load therapeutic cargo during assembly. A variety of therapeutic cargos such as small molecules, peptides, proteins, bacteria, fungi and mammalian cells have been encapsulated in self-folded polymeric containers. In this review, we focus on self-folding of all-polymeric containers. We discuss the mechanistic aspects of self-folding of polymeric containers driven by differential stresses or surface tension forces, the applications of self-folding polymers in drug delivery and we outline future challenges.

Self-folding micropatterned polymeric containers

We demonstrate self-folding of precisely patterned, optically transparent, all-polymeric containers and describe their utility in mammalian cell and microorganism encapsulation and culture. The polyhedral containers, with SU-8 faces and biodegradable polycaprolactone (PCL) hinges, spontaneously assembled on heating. Self-folding was driven by a minimization of surface area of the liquefying PCL hinges within lithographically patterned two-dimensional (2D) templates. The strategy allowed for the fabrication of containers with variable polyhedral shapes, sizes and precisely defined porosities in all three dimensions. We provide proof-of-concept for the use of these polymeric containers as encapsulants for beads, chemicals, mammalian cells and bacteria. We also compare accelerated hinge degradation rates in alkaline solutions of varying pH. These optically transparent containers resemble three-dimensional (3D) micro-Petri dishes and can be utilized to sustain, monitor and deliver living biological components.

Bio-Origami Hydrogel Scaffolds Composed of Photocrosslinked PEG Bilayers

We describe the self-folding of photopatterned poly (ethylene glycol) (PEG)-based hydrogel bilayers into curved and anatomically relevant micrometer-scale geometries. The PEG bilayers consist of two different molecular weights (MWs) and are photocrosslinked en masse using conventional photolithography. Self-folding is driven by differential swelling of the two PEG bilayers in aqueous solutions. We characterize the self-folding of PEG bilayers of varying composition and develop a finite element model which predicts radii of curvature that are in good agreement with empirical results. Since we envision the utility of bio-origami in tissue engineering, we photoencapsulate insulin secreting β-TC-6 cells within PEG bilayers and subsequently self-fold them into cylindrical hydrogels of different radii. Calcein AM staining and ELISA measurements are used to monitor cell proliferation and insulin production respectively, and the results indicate cell viability and robust insulin production for over eight weeks in culture.

Toward a miniaturized mechanical surgeon

Recent advances in sub-millimeter scale engineering suggest the possibility for constructing miniaturized tetherless medical tools for in vivo diagnostics and therapeutics. We review the challenges associated with the design and implementation of small, remotely controlled or autonomous surgical devices. Two key milestones are the creation of tiny mimics of macroscopic surgical devices with chemical, mechanical and electronic functionalities; and wireless strategies to control them or enable independent decision making (autonomous actuation). We summarize early results obtained in this area and discuss possible solutions with a focus on the challenges that can be addressed by innovations in materials science and engineering.

Enabling Cargo‐Carrying Bacteria via Surface Attachment and Triggered Release

The use of microorganisms to ferry cargo, previously described as microoxen by Weibel et al.,[1] provides an attractive route to propel and guide microstructures. In principle, a multitude of microorganisms could be utilized to enable motility and guidance in response to specific stimuli. Amongst these microorganisms, bacteria are small (micron sized) and especially relevant for ferrying micro and nanoscale cargo. In addition, bacteria are motile, capable of exhibiting different types of motion such as run-and-tumble, swarming, gliding and twitching.[2–5] These modes play an important role in guiding the response of bacteria to external stimuli - in phenomena such as chemotaxis, phototaxis and magnetotaxis.[6–8] There has been considerable interest in harnessing the motion of bacteria in the creation of biological motors or bioactuators on account of their small sizes, ability to respond to environmental cues, ability to convert chemical energy to motion (obviating need for external power supply) and higher swimming speed as compared to several microscopic artificially engineered devices.[1, 9] These advantages have recently been realized and there has been growing interest in utilizing the motion of intact microorganisms in propulsion.[1, 7, 10–13] However, previous use of bacterial propulsion has focused mainly on the utilization of large numbers of bacteria to propel 10–100 μm scale cargo. It is noteworthy, that in these studies, conjugation of bacteria to cargo was effected by blotting.[14]