3D printing of step-gradient nanocomposite hydrogels for controlled cell migration

Abstract

In this study, we report the step-gradient nanocomposite (NC) hydrogel generated easily by spatial connection of different nanocomposite hydrogel pastes varying in the concentrations of nanomaterials with the aid of a 3D printing technique. The prepared 3D printed gradient NC hydrogel has self-adhesive properties and is used to direct the migration of fibroblast cells towards the higher concentration of biopolymer-coated silica-based nanomaterials (NMs) within the 3D network of the hydrogel. Furthermore, we demonstrate the potential application of our gradient NC hydrogel in migration and subsequent enhanced osteogenic differentiation of human bone marrow derived mesenchymal stem cells (hBM MSC). The osteogenic differentiation of hBM MSC is achieved in the absence of osteogenic differentiation medium due to the silica-based NMs. The increase in the NM content in the gradient construct promotes hBM MSC migration and results in higher Ca2+ deposition.

Gradient Hydrogels—The State of the Art in Preparation Methods

“…Control of precursor composition or of precursor combinations during 3D printing can be used to create gradients. The fabrication of a step-gradient nanocomposite hydrogel was reported by Motealleh et al [21]. Hydrogels were generated by the spatial connection of different nanocomposite hydrogel pastes, in which the concentration of nanomaterials was modulated by means of the 3D printing technique.…”

Recent Strategies in Fabrication of Gradient Hydrogels for Tissue Engineering Applications

“…In addition, protein-related bone levels significantly increased with higher concentration of PMO in GradNC hydrogel. [53] These results suggested that the physical and biochemical gradients in hydrogel could be fine-tuned by bio-printing fabrication technique, and the fabricated gradient hydrogels could mimic the ECM of various cellular microenvironment.…”

“…Biosci. 2020, 20,1900300 TGF-ß1 [34] siRNA-PEI [41] PDGF-BB [42,43] VEGF158 [51] BP + cyt c [44] Migration of cell PMO [53] Cell attachment NCAD [39] RGD [34,46,50] IKVAV [40] HAV [50] Cell Gradient tissue formation Chondrocyte [52] Mimicking cancer environment U87MG cell [47] Materials and mechanical property…”

“…[52] Motealleh et al fabricated step-gradient nanocomposite (NC) hydrogel scaffolds (GradNC) by sequential conjugation of Alginine/Laponite (AlgL) paste containing different periodic mesoporous organosilica nanomaterials (PMOs) by 3D printing technique. [53] A series of three different pastes of AlgL, PMO 0.3 -AlgL (0.3 mg of PMO per 1 mL), and PMO 0.9 -AlgL (0.9 mg of PMO per 1 mL) were separately prepared. The pastes were printed in a side by side orientation in a horizontal (XY) plane to form a hexagonal prism shape.…”

Recent Advances in Injectable Hydrogels for Controlled and Local Drug Delivery

“…[35] Several examples of an ionic crosslinked injectable alginate-based NC hydrogel for different applications have been reported from the Kehr's group. [36][37][38][39][40] Here, NC hydrogels were formed by Ca 2+ crosslinking of the negatively charged polysaccharide alginate and by incorporating periodic mesoporous organosilica (PMO) into the alginate network. The PMO surfaces were modified with polycations or with amino acids to achieve a positive charge on the PMO surfaces, thus allowing for a physical interaction with alginate.…”