Cell Viability and Noninvasive In Vivo MRI Tracking of 3D Cell Encapsulating Self-Assembled Microcontainers

Abstract

Several molecular therapies require the implantation of cells that secrete biotherapeutic molecules and imaging the location and microenvironment of the cellular implant to ascertain its function. We demonstrate noninvasive in vivo magnetic resonance imaging (MRI) of self-assembled microcontainers that are capable of cell encapsulation. Negative contrast was obtained to discern the microcontainer with MRI; positive contrast was obtained in the complete absence of background signal. MRI on a clinical scanner highlights the translational nature of this research. The microcontainers were loaded with cells that were dispersed in an extracellular matrix, and implanted both subcutaneously and in human tumor xenografts in SCID mice. MRI was performed on the implants, and microcontainers retrieved postimplantation showed cell viability both within and proximal to the implant. The microcontainers are characterized by their small size, three dimensionality, controlled porosity, ease of parallel fabrication, chemical and mechanical stability, and noninvasive traceability in vivo.

Self-folding micropatterned polymeric containers

“…However, in our prior work, containers had a primarily metallic composition in order to facilitate photolithographic patterning and wet etching. While the metallic containers interacted with electromagnetic fields that enabled remote heating (Ye et al 2007) and imaging (Gimi et al 2007), and containers that were coated with gold were shown to be nontoxic to cells, they lacked other important features offered by polymeric materials such as biodegradability and optical transparency. Additionally, polymers are widely used in constructing devices for cell encapsulation therapy, tissue engineering and drug delivery (Prakash and Soe-Lin 2004).…”

SU-8-based immunoisolative microcontainer with nanoslots defined by nanoimprint lithography

“…In this approach, containers are fabricated on planar substrates to have six planar faces and hinges between faces. Self-folding was realized by electrostatically driven folding of conducting polymer/gold bilayers connecting two rigid plates12 or surface tension of molten Sn/Pb solder,13 which was reported by one of the co-authors of this article. Advantages of this approach include self-folding, which greatly simplifies the assembly process and controllable dimensions as it is based on lithographic processes.…”

“…Self-folded cubic containers have also been studied for generic microassembly application12 and cell encapsulation application 13. In this approach, containers are fabricated on planar substrates to have six planar faces and hinges between faces.…”

Reconfigurable Microfluidics With Metallic Containers

“…The metallic containers behave as Faraday cages, allowing them to be readily imaged with electromagnetic fields, such as in magnetic resonance imaging (MRI) [14]. In MRI, the containers appeared as a characteristic spot of hypointensity, allowing them to be detected and tracked in concealed channels and in vivo [14], [17]. Additionally, when containers were made out of Ni (a ferromagnetic material), they could be guided using external magnetic fields from distances as far as centimeters away.…”