Cellular Microcultures: Programming Mechanical and Physicochemical Properties of 3D Hydrogel Cellular Microcultures via Direct Ink Writing (Adv. Healthcare Mater. 9/2016)

Abstract

R. Nuzzo and co-workers show on page 1025 how compositional differences in hydrogels are used to tune their cellular compliance by controlling their polymer mesh properties and subsequent uptake of the protein poly-l-lysine (green spheres in circled inset). The cover image shows pyramid micro-scaffolds prepared using direct ink writing (DIW) that differentially direct fibroblast and preosteoblast growth in 3D, depending on cell motility and surface treatment.

3D‐Printed Hydrogel Composites for Predictive Temporal (4D) Cellular Organizations and Patterned Biogenic Mineralization

“…The current work extends our earlier studies, utilizing the ink formulation nomenclature deeply studied therein, and here providing a new set of materials chemistries that can afford effective means through which to control and spatially modulate growth compliance in 3D printed scaffolds. [9a,11] The new materials, conjoined with printing‐based capacities for grayscale patterning, provide impactful ways to control the temporal evolution of supported 3D microcultures—and offer supporting materials chemistry for biologically compliant 4DP. In biological cultures, the earlier described pHH‐i ink behaves as a blank slate material in that cells do not attach to it without a prior activating protein treatment, but for which there is no adverse material attribute that inhibits immediately adjacent cellular attachment, motility, and spreading.…”

“…In biological cultures, the earlier described pHH‐i ink behaves as a blank slate material in that cells do not attach to it without a prior activating protein treatment, but for which there is no adverse material attribute that inhibits immediately adjacent cellular attachment, motility, and spreading. [9a] In addition to this printable ink material, we previously described two compositionally distinct, yet closely related, pHH‐i‐based material compositions (pHH‐2 and pHH‐4; Table , ID2 and ID3) that are amenable to thin‐film preparations via spin‐casting. [9a] The two film compositions, following treatment with the cellular attachment mediator, poly‐ʟ‐lysine (PLL; 30k–70k MW), function as oppositional binaries for 3T3 and E1 cellular attachment outcomes, with growth positive conditions found for these cells on treated pHH‐2 and growth negative ones on pHH‐4.…”

“…[9a] In addition to this printable ink material, we previously described two compositionally distinct, yet closely related, pHH‐i‐based material compositions (pHH‐2 and pHH‐4; Table , ID2 and ID3) that are amenable to thin‐film preparations via spin‐casting. [9a] The two film compositions, following treatment with the cellular attachment mediator, poly‐ʟ‐lysine (PLL; 30k–70k MW), function as oppositional binaries for 3T3 and E1 cellular attachment outcomes, with growth positive conditions found for these cells on treated pHH‐2 and growth negative ones on pHH‐4. Such programmable states of cellular attachment and development, while useful, do not provide materials compositions suitable for printing‐based grayscale patterning.…”

“…[4f–o,8] Specifically, we incorporate a rheological modulator, a smectite nanocrystalline disc, Laponite XLG (LAP), into an 2‐hydroxyethyl methacrylate (HEMA)‐based hydrogel system. This material, LAP–HEMA (LH), is separately compared and joined with a composition, poly(2‐hydroxyethyl) methacrylate (pHEMA)–HEMA (pHH), whose rheology is suitably tuned using high molecular weight pHEMA homopolymer as a modifier . Hydrogel materials incorporating LAP and related inorganic additives confer broadly cellular compliant properties to the composites, including robust cellular attachment and (as yet less well understood) impacts on differentiation/development .…”

Deterministic Integration of Biological and Soft Materials onto 3D Microscale Cellular Frameworks

“…Multiple hydrogel filaments can be printed and affixed to the Si patterns as illustrated here for inks using the monomers N -isopropyl acrylamide (NIPAM, shown in green)—that yields a material poly( N -isopropylacrylamide) (pNIPAM) for use in hydrogel-based programmable actuators [3a] —and 2-hydroxyethyl methacrylate (HEMA, shown in red)—that yields a pHEMA material that allows for tuning cellular adhesion modes (Figure 1c). [15] The capacity to construct polymeric overlayers that bridge, span, or variously interconnect the μ -CF is enabled by DIW and is illustrated in Figure 1d by pHEMA hydrogel mesh that uses the underlying scaffold features as a structural reinforcement. In the example shown, strain release leads to 3D motifs in the hydrogel that follow (and add to) the induced buckling modes (shown schematically in Figure 1d, left, and with colorized light micrographs, Figure 1d, right).…”