Micro-Masonry: Construction of 3D Structures by Microscale Self-Assembly
Entry by Sandeep Koshy, AP 225, Fall 2010
Title: Micro-Masonry: Construction of 3D Structures by Microscale Self-Assembly
Authors: Javier G. Fernandez and Ali Khademhosseini
Journal: Advanced Materials
There is currently significant interest in the mimicking nature in bioengineered systems. Tissue engineering, the formation of living tissue outside the body, in particularly looks towards exploiting this strategy. The authors present a method for self assembly of cell-laden micro-hydrogels into three dimensional shapes using hydrophilic-hydrophobic interactions and capillarity. The method proposed is scalable and allows the formation of complex 3D geometries composed of small gels containing any number of cell-types or soluble factors.
Soft Matter Keywords: polymer, capillarity, self assembly
Self-assembly processes are ubiquitous in biology and occur due to a decrease in system free energy as small components assemble into macro structures. Recent approaches in tissue engineering aim to mimic this strategy on the meso-scale in order to generate cell-laden structures which mimic the structure and function of biological tissue. In this approach, cells are encapsulated within a polymer gels of a precise geometry and driven to assemble using the exploitation of some natural driving force. In this work, Fernandez & Khademhosseini present a novel templating method to assemble microgels into complex 3D structures.
The authors created microgels using a common photolithographic technique. Briefly, a prepoymer containing methacrylate functionalized polyethylene glycol and photoinitiator is pipette between two glass slides. A photomask containing an array of square patterns is placed over the top slide and the entire apparatus is exposed to UV light which crosslinks exposed regions of the polymer. Excess prepolymer is rinsed away and free-floating microgels can be retrieved. This process is cell compatible and allows the encapsulation of cells, if desired.
The mesoscale self-assembly process involves the creation of a polydimethylsiloxane (PDMS) template of the desired shape (Fig. 1-A). The template is mixed with the PEG microgels and prepolymer and the microgels assemble on the PDMS surface spontaneously (Fig. 1-B,C). The structure is stabilized using another exposure to UV to polymerize the residual prepolymer between the gels (Fig. 1-E,D).
Structures made with micromasonry
The authors showed that PEG gels will assemble on their own, in the absence of a template into solid spheres (Fig. 2). After establishment of the method, the authors constructed various shapes with relevance to biology. The first, a tube, resembles a blood vessel. A hemisphere, or casquet, could also be created, which resembles the shape of the retina. They comment that the performance of the aggregation of microgels onto the PDMS template could be improved by plasma treatment, which increases the hydrophilicity of the PDMS. Since PEG gels are extremely hydrophilic, they will aggregate onto this surface. A monolayer is formed due to the residual prepolymer pulling the microgels together due to capillary forces. The authors state that smaller microgels would lead to improved resolution of the bulk shapes.
Cell encapsulation in self assembled gels
The compatibility of this technique with cells was explored. Microgels containing encapsulated cells were processed using the micromasonry technique. A stain for live and dead cells showed good viability (Fig. 3). They authors suggest that this technique could be used to create tissues containing various cell types within different blocks.
Lock and key assembly
It was shown that poorly shaped gels led to disordered assembly (Fig. 4 A,B). In order to control the spacial assembly of microgel units with different contents, a lock and key scheme was envisioned. Microgels with complementary shapes were designed and allowed to assemble in a “lock and key” type fashion. Precise assembly was observed (Fig. 4 C,E). They also show that multilayered systems can be created by repeating the micromasonry process after the stabilization of the previous layer.
The methods presented here have a wide range of applications in tissue engineering including the creation of artificial vascular structures and closely mimicking tissues with repeating structures such as the liver.