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

Abstract

Materials chemistries for hydrogel scaffolds that are capable of programming temporal (4D) attributes of cellular decision‐making in supported 3D microcultures are described. The scaffolds are fabricated using direct‐ink writing (DIW)—a 3D‐printing technique using extrusion to pattern scaffolds at biologically relevant diameters (≤ 100 µm). Herein, DIW is exploited to variously incorporate a rheological nanoclay, Laponite XLG (LAP), into 2‐hydroxyethyl methacrylate (HEMA)‐based hydrogels—printing the LAP–HEMA (LH) composites as functional modifiers within otherwise unmodified 2D and 3D HEMA microstructures. The nanoclay‐modified domains, when tested as thin films, require no activating (e.g., protein) treatments to promote robust growth compliances that direct the spatial attachment of fibroblast (3T3) and preosteoblast (E1) cells, fostering for the latter a capacity to direct long‐term osteodifferentiation. Cell‐to‐gel interfacial morphologies and cellular motility are analyzed with spatial light interference microscopy (SLIM). Through combination of HEMA and LH gels, high‐resolution DIW of a nanocomposite ink (UniH) that translates organizationally dynamic attributes seen with 2D gels into dentition‐mimetic 3D scaffolds is demonstrated. These analyses confirm that the underlying materials chemistry and geometry of hydrogel nanocomposites are capable of directing cellular attachment and temporal development within 3D microcultures—a useful material system for the 4D patterning of hydrogel scaffolds.

pH-Dependent Nanodiamonds Enhance the Mechanical Properties of 3D-Printed Hyaluronic Acid Nanocomposite Hydrogels

“…As shown in Figure 1, the shear-thinning effect of all HA, HA/ND-COOH, and HA/ND-OH nanocomposite hydrogel precursor generated low viscosities (approximately 2 Pa•s) in the presheared zone. After the shear rate was decreased and fluids were fully structured, the viscosity of the nanocomposite hydrogel precursors increased rapidly with a stiff gradient to approximately 33 NDs showed higher viscosity and shorter response time, compared to HA only hydrogels, indicating a pH controllable lament shape in the 3D-printing process. The nanocomposite HA hydrogel precursors showed higher viscosity at pH 8, compared to those at pH 7.…”

“…Nanocomposite hydrogels that incorporate diverse nanophase inorganic particles are challenging because metastatic materials mimicking biological tissues require a variety of considerations including softness, biocompatibility, strength, and structurally compatible elasticity. The speci c functionality granted by nanocomposite hydrogels with inorganic materials would lead to improved electrical conductivity [27,28], energy absorbance [29][30][31], as well as cellular [18,26,32,33] and protein interactions [2], in addition to mechanical enhancement.…”

4D Printed Hydrogels: Fabrication, Materials, and Applications

“…[ 112 ] A great number of researchers have demonstrated the use of stimuli‐responsive hydrogels for biomedical applications such as cell culture, [ 113 ] drug delivery, [ 114,115 ] biosensing, [ 116 ] and scaffolds. [ 117,118 ] Dai et al proposed the possibility of using a Pluronic F127 diacrylate macromer (F127DA)‐based shape memory hydrogel for drug delivery actuated by NIR radiation. [ 53 ] F127DA is a thermal‐responsive hydrogel, and by adding graphene oxide that can absorb NIR light, the composite becomes light‐responsive.…”

Multifunctional Hydrogel Nanocomposites for Biomedical Applications

“…The chemical properties of hydrogels such as sensitivity to stimuli and bioactivity are an integral aspect of their applicability for biomedical use [ 6 , 21 , 33 , 45 , 62 ]. Therefore, it is not surprising that several researchers have investigated whether the incorporation of nanoparticles may also improve the chemical properties of hydrogels to expand their utility for other applications ( Table 2 ) (e.g., drug delivery, tissue engineering, adhesives, bioprinting and biowearable devices ( Figure 1 ) [ 6 , 17 , 18 , 19 , 21 , 23 , 24 , 25 , 26 , 27 ]).…”