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Three-dimensional (3D) hydrogel printing enables production of volumetric architectures containing desired structures using programmed automation processes. Our study reports a unique method of resolution enhancement purely relying on post-printing treatment of hydrogel constructs. By immersing a 3D-printed patterned hydrogel consisting of a hydrophilic polyionic polymer network in a solution of polyions of the opposite net charge, shrinking can rapidly occur resulting in various degrees of reduced dimensions comparing to the original pattern. This phenomenon, caused by complex coacervation and water expulsion, enables us to reduce linear dimensions of printed constructs while maintaining cytocompatible conditions in a cell type-dependent manner. We anticipate our shrinking printing technology to find widespread applications in promoting the current 3D printing capacities for generating higher-resolution hydrogel-based structures without necessarily having to involve complex hardware upgrades or other printing parameter alterations.

The healing of large bone defects represents a clinical challenge, often requiring some form of grafting. 3D nanofiber aerogels could be a promising bone graft due to their biomimetic morphology and controlled porous structures and composition. miR-26a has been reported to induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and facilitate bone formation. Introducing miR-26a with a suitable polymeric vector targeting BMSCs could improve and enhance the functions of 3D nanofiber aerogels for bone regeneration. Herein, the comb-shaped polycation (HA-SS-PGEA) is first developed, carrying a targeting component, biocleavable groups, and short ethanolamine (EA)-decorated poly(glycidyl methacrylate) (PGMA) (abbreviated as PGEA) arms as miR-26a delivery vector. Thereafter, the cytotoxicity and transfection efficiency of this polycation and cellular response to miR-26a-incorporated nanoparticles (NPs) are assessed in vitro. HA-SS-PGEA exhibits a stronger ability to transport miR-26a and exert its functions than the gold standard polyethyleneimine (PEI) and low-molecular-weight linear PGEA. The efficacy of HA-SS-PGEA/ miR-26a NPs loaded 3D hybrid nanofiber aerogels showing a positive effect on the cranial bone defect healing is finally examined. Together, the combination of 3D nanofiber aerogels and functional NPs consisting of a biodegradable and targeting polycation and therapeutic miRNA could be a promising approach for bone regeneration.

Repairing large tissue defects often represents a great challenge in clinics due to issues regarding lack of donors, mismatched sizes, irregular shapes, and immune rejection. Three-dimensional (3D) printed scaffolds are attractive for growing cells and producing tissue constructs because of the intricate control over pore size, porosity, and geometric shape, but the lack of biomimetic surface nanotopography and limited biomolecule presenting capacity render them less efficacious in regulating cell responses. Herein, we report, for the first time, a facile method for coating 3D printed scaffolds with electrospun nanofiber segments. The surface morphology of modified 3D scaffolds changes dramatically, displaying a biomimetic nanofibrous structure, while the bulk mechanical property, pore size and porosity are not significantly compromised. The short nanofibers-decorated 3D printed scaffolds significantly promote adhesion and proliferation of pre-osteoblasts and bone marrow mesenchymal stem cells (BMSCs). Further immobilization of bone morphogenetic protein-2 (BMP-2) mimicking peptides to nanofiber segments-decorated 3D printed scaffolds show enhanced mRNA expressions of osteogenic markers Runx2, Alp, OCN, and BSP in BMSCs, indicating the enhancement of BMSCs osteogenic differentiation. Together, the combination of 3D printing and electrospinning is a promising approach to greatly expand the functions of 3D printed scaffolds and enhance the efficacy of 3D printed scaffolds for tissue engineering.

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