Investigating design principles of micropatterned encapsulation systems containing high-density microtissue arrays

Abstract

Immunoisolation is an important strategy to protect transplanted cells from rejection by the host immune system. Recently, microfabrication techniques have been used to create hydrogel membranes to encapsulate microtissue in an arrayed organization. The method illustrates a new macroencapsulation paradigm that may allow transplantation of a large number of cells with microscale spatial control, while maintaining an encapsulation device that is easily maneuverable and remaining integrated following transplantation. This study aims to investigate the design principles that relate to the translational application of micropatterned encapsulation membranes, namely, the control over the transplantation density/quantity of arrayed microtissues and the fidelity of pre-formed microtissues to micropatterns. Agarose hydrogel membranes with microwell patterns were used as a model encapsulation system to exemplify these principles. Our results show that high-density micropatterns can be generated in hydrogel membranes, which can potentially maximize the percentage volume of cellular content and thereby the transplantation efficiency of the encapsulation device. Direct seeding of microtissues demonstrates that microwell structures can efficiently position and organize pre-formed microtissues, suggesting the capability of micropatterned devices for manipulation of cellular transplants at multicellular or tissue levels. Detailed theoretical analysis was performed to provide insights into the relationship between micropatterns and the transplantation capacity of membrane-based encapsulation. Our study lays the ground for developing new macroencapsulation systems with microscale cellular/tissue patterns for regenerative transplantation.hydrogel, micropattern, array, multi-cellular spheroids, macroencapsulation Citation:Jiang LY, Liu JY, Wang K, Gu X, Luo Y. Investigating design principles of micropatterned encapsulation systems containing high-density microtissue arrays.

From Micro to Macro: The Hierarchical Design in a Micropatterned Scaffold for Cell Assembling and Transplantation

“…Hierarchical design of the topographical and spatial features of scaffolds therefore is a critical step in facilitating the tissue‐engineering and cell‐based therapy. First, a real cell transplantation regimen may involve up to 10 9 cells for treating one patient; the three‐dimensional (3D) organization of such a large number of cells governs the volume/shape of the final transplants, a critical factor that determines the implantability of a construct . In addition, optimal organization of cells also promotes efficient vascularization and prohibits hypoxia and insufficient nutrient supply caused by random cell clumping .…”

“…On the other hand, although more and more patterned 3D matrices have been developed in the past through photo‐/soft‐lithographic and 3D printing processes, most of the resulting scaffolds may only allow for control over the localization of cells/microtissues: the desired local characteristics of the scaffolds, or the niche of cells are still hard to be incorporated . For example, the micropatterned hydrogel matrices may offer a limited range of local mass transport and mechanical properties . Similarly, plastic degradable scaffolds made from rapid‐prototyping may also lack local micro or nanotopographical features due to the resolution limitations in the fabrication process …”

“…Until now, most of the micropatterned 3D scaffolds reported in the literature were based on hydrogel materials and may lack the mechanical robustness, controllable permeability or chemical stability for real clinical applications. [5,12b,c] Although a couple of methods have been previously reported to generate micropatterned structures in electrospun membranes, few have investigated micropatterned scaffolds in vivo. Here, the combination of micromolding and electrospinning techniques was facile and the fibrous scaffolds with integrated topographical structure may facilitate the investigation of cell transplantation for tackling T1D, one of the most severe chronic illnesses diagnosed in children and young adults.…”

Pancreatic islet macroencapsulation using microwell porous membranes

“…Jiang et al . developed agarose hydrogel membranes with microwell patterns allowing for cells separation as a model encapsulation system 13 . Moreover, they suggested that micropatterned encapsulation systems may be able to minimize the transplantation volume, increase the encapsulation efficiency and improve the cell viability.…”