Gradient matters via filament diameter-adjustable 3D printing.

Gradient matters with hierarchical structures endow the natural world with excellent integrity and diversity. Currently, direct ink writing 3D printing is attracting tremendous interest, and has been used to explore the fabrication of 1D and 2D hierarchical structures by adjusting the diameter, spacing, and angle between filaments. However, it is difficult to generate complex 3D gradient matters owing to the inherent limitations of existing methods in terms of available gradient dimension, gradient resolution, and shape fidelity. Here, we report a filament diameter-adjustable 3D printing strategy that enables conventional extrusion 3D printers to produce 1D, 2D, and 3D gradient matters with tunable heterogeneous structures by continuously varying the volume of deposited ink on the printing trajectory. In detail, we develop diameter-programmable filaments by customizing the printing velocity and height. To achieve high shape fidelity, we specially add supporting layers at needed locations. Finally, we showcase multi-disciplinary applications of our strategy in creating horizontal, radial, and axial gradient structures, letter-embedded structures, metastructures, tissue-mimicking scaffolds, flexible electronics, and time-driven devices. By showing the potential of this strategy, we anticipate that it could be easily extended to a variety of filament-based additive manufacturing technologies and facilitate the development of functionally graded structures.

A mechanical-assisted post-bioprinting strategy for challenging bone defects repair.

Bioprinting that can synchronously deposit cells and biomaterials has lent fresh impetus to the field of tissue regeneration. However, the unavoidable occurrence of cell damage during fabrication process and intrinsically poor mechanical stability of bioprinted cell-laden scaffolds severely restrict their utilization. As such, on basis of heart-inspired hollow hydrogel-based scaffolds (HHSs), a mechanical-assisted post-bioprinting strategy is proposed to load cells into HHSs in a rapid, uniform, precise and friendly manner. HHSs show mechanical responsiveness to load cells within 4 s, a 13-fold increase in cell number, and partitioned loading of two types of cells compared with those under static conditions. As a proof of concept, HHSs with the loading cells show an enhanced regenerative capability in repair of the critical-sized segmental and osteoporotic bone defects in vivo. We expect that this post-bioprinting strategy can provide a universal, efficient, and promising way to promote cell-based regenerative therapy.

In-situmineralized homogeneous collagen-based scaffolds for potential guided bone regeneration.

For guided bone regeneration (GBR) in clinical orthopedics, the importance of a suitable scaffold which can provide the space needed for bone regeneration and simultaneously promotes the new bone formation cannot be overemphasized. Due to its excellent biocompatibility, mechanical strength, and similarity in structure and composition to natural bone, the mineralized collagen-based scaffolds have been increasingly considered as promising GBR scaffolds. Herein, we propose a novel method to fabricate anin-situmineralized homogeneous collagen-based scaffold (IMHCS) with excellent osteogenic capability for GBR by electrospinning the collagen solution in combination with essential mineral ions. The IMHCS exhibited homogeneous distribution of apatite crystals in electrospun fibers, which helped to achieve a significantly higher tensile strength than the pure collagen scaffold (CS) and the scaffold with directly added nano-hydroxyapatite particles (HAS). Furthermore, the IMHCS had significantly better cell compatibility, cell migration ratio, and osteogenic differentiation property than the HAS and CS. Therefore, the IMHCS not only retains traditional function of inhibiting fibroblast invasion, but also possesses excellent osteogenic differentiation property, indicating a robust alternative for GBR applications.

In-situ formed elastin-based hydrogels enhance wound healing via promoting innate immune cells recruitment and angiogenesis.

Harnessing the inflammation and angiogenesis is extremely important in wound healing. In this study, we developed bioactive elastin-based hydrogels which can recruit and modulate the innate immune cells and accelerate angiogenesis in the wound site and subsequently improve wound regeneration. These hydrogels were formed by visible-light cross-linking of acryloyl-(polyethylene glycol)-N-hydroxysuccinimide ester modified elastin with methacrylated gelatin, in order to mimic dermal microenvironment. These hydrogels showed highly tunable mechanical properties, swelling ratios and enzymatic degradation profiles, with moduli within the range of human skin. To mimic the in vivo degradation of the elastin by elastase from neutrophils, in vitro co-culture of the hydrogels and neutrophils was conducted. The derived conditioned medium containing elastin derived peptides (EDP-conditioned medium) promoted the expression of both M1 and M2 markers in M1 macrophages in vitro. Additionally, the EDP-conditioned medium induced superior tube formation of endothelia cells in Matrigel. In mice wound model, these elastin-based hydrogels attracted abundant neutrophils and predominant M2 macrophages to the wound and supported their infiltration into the hydrogels. The outstanding immunomodulatory effect of the elastin-based hydrogels resulted in superior angiogenesis, collagen deposition and dermal regeneration. Hence, these elastin-based hydrogels can be a promising regenerative platform to accelerate wound repair.

Fractal Design Boosts Extrusion-Based 3D Printing of Bone-Mimicking Radial-Gradient Scaffolds.

Although extrusion-based three-dimensional (EB-3D) printing technique has been widely used in the complex fabrication of bone tissue-engineered scaffolds, a natural bone-like radial-gradient scaffold by this processing method is of huge challenge and still unmet. Inspired by a typical fractal structure of Koch snowflake, for the first time, a fractal-like porous scaffold with a controllable hierarchical gradient in the radial direction is presented via fractal design and then implemented by EB-3D printing. This radial-gradient structure successfully mimics the radially gradual decrease in porosity of natural bone from cancellous bone to cortical bone. First, we create a design-to-fabrication workflow with embedding the graded data on basis of fractal design into digital processing to instruct the extrusion process of fractal-like scaffolds. Further, by a combination of suitable extruded inks, a series of bone-mimicking scaffolds with a 3-iteration fractal-like structure are fabricated to demonstrate their superiority, including radial porosity, mechanical property, and permeability. This study showcases a robust strategy to overcome the limitations of conventional EB-3D printers for the design and fabrication of functionally graded scaffolds, showing great potential in bone tissue engineering.

Generation of perfusable hollow calcium alginate microfibers with a double co-axial flow capillary microfluidic device.

This paper describes a highly controllable method to generate hollow calcium alginate microfibers using a double co-axial flow microdevice. The microdevice was fabricated by concentric assembly of two modules; each module consisted of a shortened cone-pulled glass capillary embedded in a polymethylmethacrylate fluidic block. Using this microdevice, cylindrical hollow calcium alginate microfibers with either straight or helical inner walls were stably and continuously generated. The radii of the hollow microfibers were not arbitrary, and in fact, the ratio of the outer to inner diameter was inversely correlated with the combination of core flow rate and the first sheath flow rate. The relationships between the geometrical features of the helix and the flow rates were also analyzed. The helical pitch and the spiral radius of the helical hollow microfibers were strongly influenced by the second sheath flow rate. Finally, guidelines for generating highly controllable straight and helical hollow microfibers and fabricating a seamless flow connector using this microfluidic device are suggested.