Defining the role of matrix compliance and proteolysis in three-dimensional cell spreading and remodeling.

Recent studies have identified extracellular matrix (ECM) compliance as an influential factor in determining the fate of anchorage-dependent cells. We explore a method of examining the influence of ECM compliance on cell morphology and remodeling in three-dimensional culture. For this purpose, a biological ECM analog material was developed to pseudo-independently alter its biochemical and physical properties. A set of 18 material variants were prepared with shear modulus ranging from 10 to 700 Pa. Smooth muscle cells were encapsulated in these materials and time-lapse video microscopy was used to show a relationship between matrix modulus, proteolytic biodegradation, cell spreading, and cell compaction of the matrix. The proteolytic susceptibility of the matrix, the degree of matrix compaction, and the cell morphology were quantified for each of the material variants to correlate with the modulus data. The initial cell spreading into the hydrogel matrix was dependent on the proteolytic susceptibility of the materials, whereas the extent of cell compaction proved to be more correlated to the modulus of the material. Inhibition of matrix metalloproteinases profoundly affected initial cell spreading and remodeling even in the most compliant materials. We concluded that smooth muscle cells use proteolysis to form lamellipodia and tractional forces to contract and remodel their surrounding microenvironment. Matrix modulus can therefore be used to control the extent of cellular remodeling and compaction. This study further shows that the interconnection between matrix modulus and proteolytic resistance in the ECM may be partly uncoupled to provide insight into how cells interpret their physical three-dimensional microenvironment.

Author Correction: Active Printed Materials for Complex Self-Evolving Deformations.

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The effect of structural alterations of PEG-fibrinogen hydrogel scaffolds on 3-D cellular morphology and cellular migration.

The need for alternative scaffolds in tissue engineering has motivated the establishment of advanced biomaterial technologies based on biosynthetic polymers. Networks of synthetic and biologic building blocks are created into a biomimetic environment for enhanced tissue compatibility with precise structural properties. The current investigation describes a unique biosynthetic hybrid scaffold comprised of synthetic polyethylene glycol (PEG) and endogenous fibrinogen precursor molecules. The PEGylated fibrinogen is cross-linked using photoinitation in the presence of cells to form a dense cellularized hydrogel network. The fibrin-like scaffold material maintains its biofunctionality through the fibrinogen backbone, while changes in the molecular architecture of the synthetic precursor are used to alter the nanostructrual properties of the scaffold, including mesh size and permeability. The structural properties of 6- and 10-kDa PEG-fibrinogen hydrogels are characterized by measuring the swelling properties and relating them to the degradation kinetics of the scaffold. Increased concentrations of the synthetic PEG are used to further alter the network structure of the PEG-fibrinogen hydrogel. Experiments using smooth muscle cells cultured inside the PEG-fibrinogen scaffold demonstrates a qualitative relationship between the molecular architecture of the matrix and the cellular morphology. A quantitative assessment of cell migration into the hydrogel network demonstrates a strong correlation between rate of cellular invasion and the network structure of the matrix. The ability to regulate cellular characteristics using structural modifications to the PEG-fibrinogen scaffold can be a valuable tool in tissue engineering and tissue regeneration.

Active printed materials for complex self-evolving deformations.

We propose a new design of complex self-evolving structures that vary over time due to environmental interaction. In conventional 3D printing systems, materials are meant to be stable rather than active and fabricated models are designed and printed as static objects. Here, we introduce a novel approach for simulating and fabricating self-evolving structures that transform into a predetermined shape, changing property and function after fabrication. The new locally coordinated bending primitives combine into a single system, allowing for a global deformation which can stretch, fold and bend given environmental stimulus.