Hydrogels represent a class of materials suitable for numerous biomedical applications such as tissue engineering and drug
delivery. Hydrogels are by definition capable of absorbing large amount of fluid, making them adequate for cell seeding and
encapsulation as well as for implantation because of their biocompatibility and excellent diffusion properties. They also
possess other desirable properties for fundamental research as they have the ability to mimic the basic three‐dimensional
(3D) biological, chemical, and mechanical properties of native tissues. Furthermore, their biological interactions with cells
can be modified through the numerous side groups of the polymeric chains. Thus, the biological, chemical, and mechanical properties,
as well as the degradation kinetics of hydrogels can be tailored depending on the application. In addition, their fabrication
process can be combined with microtechnologies to enable precise control of cell‐scale features such as surface topography
and the presence of adhesion motifs on the hydrogel material. This ability to control the microscale structure of hydrogels
has been used to engineer tissue models and to study cell behavior mechanisms in vitro. New approaches such as bottom‐up and directed assembly of microscale hydrogels (microgels) are currently emerging as powerful
methods to enable the fabrication of 3D constructs replicating the microenvironment found in vivo. WIREs Nanomed Nanobiotechnol 2012, 4:235–246. doi: 10.1002/wnan.171
This WIREs title offers downloadable PowerPoint presentations of figures for non-profit,
educational use, provided the content is not modified and full credit is given to the author
and publication.
Hydrogel materials have the ability to recapitulate the basic properties of the extracellular matrix (ECM) found in vivo. They are particularly suitable for cell encapsulation, making them an attractive material for biomedical applications.
Microtechnologies such as photolithography and micromolding can be used to fabricate cell-scale features into hydrogels, enabling the control of the cellular microenvironment.
Tissue engineering and regenerative medicine. Cells are harvested from the patient, expanded in culture (1) and seeded into a porous scaffolding material (2). The cell-seeded scaffold (3) can then be implanted into the patient to restore tissue function (4).
Evolution of the mechanical properties of a cell-laden hydrogel as a function of time. The cell-seeded scaffolding material is degraded by the cells, which reduce its mechanical properties. In parallel, cells produce extracellular matrix (ECM) resulting in tissue regeneration and an increase in the mechanical properties of the engineered tissue. The intersection between the curves representing the degradation kinetics of the biomaterial and the ECM synthesis by the cells need to remain over the threshold required for adequate tissue function throughout the regeneration process.
Directed assembly of lock-and-key shaped microgels. Rod-shaped (a) and cross-shaped (b) microgels stained with nile-red and FITCdextran, respectively. Directed assembly of lock-and-key shaped microgels stained with FITCdextran and Nile-red (c) and cell-laden microgels stained with calcein AM and PKH26 (d) and (b). Scale bar: 200 µm (Reprinted with permission from Ref 63. Copyright 2008 National Academy of Sciences, USA)
Mesoscale assembly of microgels using a micro-masonry process. Schematic representation of a high-throughput photolithographic approach (a) (Reprinted with permission from Ref 74. Copyright 2011 Wiley-VCH Verlag GmBH&Co. KGaA). Schematic diagram of the micro-masonry assembly process (b). Microgels are assembled on a template before a second crosslinking process, resulting in a 3D structure composed of an assembly of microgels recapitulating the 3D structure of the template used for fabrication (c). Scale bar: 5 mm and 1 mm (magnification) (Reprinted with permission from Ref 72. Copyright 2010 Wiley-VCH Verlag GmBH&Co. KGaA)
Sequential assembly of microgels using a directed assembly approach. From left to right, design image of a microgel array assembled into tubular structures embedded with 3D branching lumens and phase image of the microgel assembly after secondary crosslinking (a). Scale bar: 500 µm. Fluorescence images of the cell-laden concentric microgel assemblies with endothelial (green) and smooth muscle cells (red) (b). Scale bar: 100 µm (Reprinted with permission from Ref 74. Copyright 2011 John/Wiley & Sons, Inc)
Submit a note to the editor about this article by filling in the form below.
* Required Field
Thank you for submitting your Editor note. Your information was successfully submitted.
How to Cite
Gauvin Robert, Parenteau‐Bareil Rémi, Dokmeci Mehmet R., Merryman W. David, Khademhosseini Ali. Hydrogels and microtechnologies for engineering the cellular microenvironment. WIREs Nanomed Nanobiotechnol 2012, 4: 235-246. doi: 10.1002/wnan.171
Access to this WIREs title is by subscription only.
works at the interface of biotechnology and materials science. His lab is researching many topics, such as investigating the mechanism of release from polymeric delivery systems with concomitant microstructural analysis and mathematical modeling; studying applications of these systems including the development of effective long-term delivery systems for insulin, anti-cancer drugs, growth factors, gene therapy agents and vaccines; developing controlled release systems that can be magnetically, ultrasonically, or enzymatically triggered to increase release rates; synthesizing new biodegradable polymeric delivery systems which will ultimately be absorbed by the body; creating new approaches for delivering drugs such as proteins and genes across complex barriers such as the blood-brain barrier, the intestine, the lung and the skin; stem cell research including controlling growth and differentiation; and creating new biomaterials with shape memory or surface switching properties.
