Cryogenic 3D Printing of w/o Pickering Emulsions Containing Bifunctional Drugs for Producing Hierarchically Porous Bone Tissue Engineering Scaffolds with Antibacterial Capability

Abstract

How to fabricate bone tissue engineering scaffolds with excellent antibacterial and bone regeneration ability has attracted increasing attention. Herein, we produced a hierarchical porous β-tricalcium phosphate (β-TCP)/poly(lactic-co-glycolic acid)-polycaprolactone composite bone tissue engineering scaffold containing tetracycline hydrochloride (TCH) through a micro-extrusion-based cryogenic 3D printing of Pickering emulsion inks, in which the hydrophobic silica (h-SiO2) nanoparticles were used as emulsifiers to stabilize composite Pickering emulsion inks. Hierarchically porous scaffolds with desirable antibacterial properties and bone-forming ability were obtained. Grid scaffolds with a macroscopic pore size of 250.03 ± 75.88 μm and a large number of secondary micropores with a diameter of 24.70 ± 15.56 μm can be fabricated through cryogenic 3D printing, followed by freeze-drying treatment, whereas the grid structure of scaffolds printed or dried at room temperature was discontinuous, and fewer micropores could be observed on the strut surface. Moreover, the impartment of β-TCP in scaffolds changed the shape and density of the micropores but endowed the scaffold with better osteoconductivity. Scaffolds loaded with TCH had excellent antibacterial properties and could effectively promote the adhesion, expansion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells afterward. The scaffolds loaded with TCH could realize the strategy to “kill bacteria first, then induce osteogenesis”. Such hierarchically porous scaffolds with abundant micropores, excellent antibacterial property, and improved bone-forming ability display great prospects in treating bone defects with infection.

3D-Printed Antibacterial Scaffolds for the Regeneration of Alveolar Bone in Severe Periodontitis

“…Specifically, in PCL-TCH scaffolds, ALP was upregulated on day 21, suggesting that PCL-TCH scaffolds promoted osteogenic differentiation, probably when a greater amount of the drug has been released from the scaffold, as shown from the in vitro dissolution study. Similar results have been reported in another study with 3D-printed composite scaffolds (β-TCP/PLGA-PCL) containing tetracycline hydrochloride after 14 days of culture [32]. Similar results were presented in a study by Dayaghi et al, in which magnesium-zinc scaffolds that had been immersed in solutions of different tetracycline concentrations (10-100% w/v), showed that ALP levels were increased in all scaffolds' concentrations with increasing incubation time [53].…”

“…With respect to the in vitro dissolution study, our findings demonstrated that TCH is released from the 3D scaffolds at a faster initial pace, followed by a more sustained release rate during the 2-72 h window. This observation is possibly associated with the hydrophilic nature of the drug in combination with the surface-bound drug molecules that get released easier [16,31,32]. Initial burst drug release is a phenomenon that is witnessed in various drug delivery platforms, and it can be controlled by modulating specific parameters, such as the surface of the drug-loaded matrix, its geometry and structure, as well as the type of materials used [33].…”

3D printed reduced graphene oxide-GelMA hybrid hydrogel scaffolds for potential neuralized bone regeneration

“…Bone scaffolds contact directly with the cells and provide the extracellular matrix (ECM) for cell adhesion, proliferation, and differentiation. 49–51 rGO has been reported to increase the stability of adsorbed proteins, such as bone morphogenetic protein 2 (BMP-2), and eventually improve cell adhesion, proliferation, and osteogenic differentiation. 52 The osteoblast phenotype is specifically obtained in two stages.…”

Numerical analysis of scaffold degradation in cryogenic environment: impact of cell migration and cell apoptosis

“…Cryogenic temperatures can significantly minimize enzymatic activity due to the slowed molecular motion and decreased metabolic rates at low temperatures. Enzymes related to scaffold degradation, such as proteases and lipases, may exhibit reduced activity, which produces to slower degradation rates , Ye et al (2022). Similarly, cryogenic temperatures can also affect the cellular metabolism and activity.…”