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WIREs Nanomed Nanobiotechnol
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Hydrogels and microtechnologies for engineering the cellular microenvironment

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Abstract 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 article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

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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.

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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)

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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)

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Directed assembly of lock‐and‐key shaped microgels. Rod‐shaped (a) and cross‐shaped (b) microgels stained with nile‐red and FITC–dextran, respectively. Directed assembly of lock‐and‐key shaped microgels stained with FITC–dextran 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)

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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.

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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).

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Microtechnologies such as photolithography and micromolding can be used to fabricate cell‐scale features into hydrogels, enabling the control of the cellular microenvironment.

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Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Nanotechnology Approaches to Biology > Cells at the Nanoscale
Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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