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Pharyngoesophageal defects can cause exposure to various bacterial flora and severe inflammation. We fabricated a biodegradable polycaprolactone (PCL) patch composed of both thin film and three-dimensional (3D) printed lattice, and then investigated the efficacy of pharyngoesophageal reconstruction by using 3D printed antibiotic-releasing PCL patches that inhibited early inflammation by sustained tetracycline (TCN) release from both thin PCL films and printed rods implanted in esophageal partial defects. PCL was 3D printed in lattice form on a presolution casted PCL thin film at ∼100 μm resolution. TCN was loaded onto the PCL-printed patches by 3D printing a mixture of TCN and PCL particles melted at 100°C. TCN exhibited sustained release

Background After recognition of 3D printing and injectable hydrogel as a critical issue in tissue/organ engineering and regenerative medicine society, many hydrogels as bioinks have been developed worldwide by using polymeric biomaterials such as gelatin, alginate, hyaluronic acid and others. Even though some gels have shown good performances in 3D bioprinting, still their performances do not meet the requirements enough to be used as a bioink in tissue engineering. Method In this study, a hydrogel consisting of three biocompatible biomaterials such as hyaluronic acid (HA), hydroxyethyl acrylate (HEA) and gelatin-methacryloyl, i.e. HA-g-pHEA-gelatin gel, has been evaluated for its possibility as a bioprinting gel, a bioink. Hydrogel synthesis was obtained by graft polymerization of HEA to HA and then grafting of gelatin- methacryloyl via radical polymerization mechanism. Physical and biological properties of the HA-based hydrogels fabricated with different concentrations of methacrylic anhydride (6 and 8%) for gelatin-methacryloylation have been evaluated such as swelling, rheology, morphology, cell compatibility, and delivery of small molecular dimethyloxalylglycine. Printings of HA-g-pHEA-Gelatin gel and its bioink with bone cell loaded in lattice forms were also evaluated by using home-built multi-material (3D bio-) printing system. Conclusion The experimental results demonstrated that the HA-g-pHEA-gelatin hydrogel showed both stable rheology properties and excellent biocompatibility, and the gel showed printability in good shape. The bone cells in bioinks of the lattice-printed scaffolds were viable. This study showed HA-g-pHEA-Gelatin gel’s potential as a bioink or its tissue engineering applications in injectable and 3D bioprinting forms.

The 3D bioprinting of an advanced multicomponent bioink requires the homogeneous distribution of bioink components to control the biological and structural properties of the printed tissue engineering construct. To ensure the homogeneous mixing of micro/nanomaterials in a bioink and then bioprinting, currently, multiple preparation steps must be followed before feeding the bioink to the conventional bioprinting extruder head. To overcome these limitations, a real-time one-step process was obtained by developing a semi-automated twin-screw extruder (TSE) head to synchronously perform systematic mixing and 3D bioprinting. In this study, as a proof of concept, the parameter optimizations for semi-automated mixing of bioink components and 3D bioprinting with the TSE head were demonstrated with an ionic gel (alginate), alpha-tricalcium phosphate (α-TCP) micro/nanoparticles, and osteoblast cells. The TSE-processed bioink samples showed better bioprintability, with better mechanical and biological properties than the conventional ones. The micro/nanoparticles were uniformly dispersed in the bioink within 60 s of screw mixing them inside the barrel (with the barrel outlet closed). The live cell distribution in the printed constructs was significantly superior to conventional mixing even with continuous feeding and extrusion-based bioink printing. This novel extrusion head ensured the control of uniform micro/nanomaterials and cell distribution throughout the directly mixed printable bioink with minimal cell damage. Further, they delivered increased batch consistency in real time mixing and bioink printing owing to its highly efficient variable screw pitch design. Higher repeatability than the conventional method of bioink component mixing and its subsequent 3D bioprinting was obtained through increased automation, as well as reduced processing time, demonstrating strong potential in tissue engineering applications through the controlled mixing of bioink components and its 3D bioprinting without damaging the cells.

In this study, carboxymethyl cellulose (CMC)-glycol chitosan (GC) hydrogel, a potential three-dimensional (3D) printing biomaterial ink for tissue engineering applications was synthesized using simple, biocompatible in situ-gelling Schiff's base reaction and ionic interactions. Different grades of hydrogels (C70G30, C50G50 and C30G70) were synthesized at physiological conditions. The oxidation of CMC and imine bond formation in the hydrogel were confirmed spectroscopically. Scanning electron microscopic images revealed the crosslinked interconnected pores in the cross-sectioned hydrogels (dried). Swelling (equilibrium: 1 h), porosity (~75%), in vitro degradation (>30 days) and thermal gravimetric analyses of the dried gels were studied. Initially, cytotoxicity assay was evaluated using mouse osteoblastic cells (MC3T3). These experiments revealed that CMC-GC gels formed stable hydrogel networks and were biocompatible. Particularly, C50G50 gels showed high printability (continuous extrusion) and post-printing stability (without secondary crosslinking). Gel 3D printing was optimized by varying the air pressure, temperature, needle size and nozzle speed, to obtain stable lattice structures (2 to 16 layers). The printed (2 and 5 layers) hydrogels showed high stability in phosphate buffer saline (PBS) solution (1 h), under UV light (1 h) and after autoclaving. The strut dimensions and porosity of the printed gels before and after the stability tests were analyzed. The hydrogel stability may be attributed to both the imine bond and ionic interaction between the cationic and anionic polymer side chains. Lactoferrin (glycoprotein) incorporated C50G50 gels showed sustained release up to 21 days in PBS (pH 7.4) solution and demonstrated increased biocompatibility (>80%) during in vitro cytotoxicity assays (MC3T3 cells and bone marrow mesenchymal stem cells) and Live/Dead assay (MC3T3 cells). A higher number of live osteoblast cells on the C50G50 hydrogels with increasing lactoferrin concentration was observed. These results show that the CMC-GC gels are promising bio-ink candidates for 3D printing and loading proteins or drugs for tissue engineering applications.

Nanocellulose pellicle is produced as a byproduct during the symbiotic culture of bacteria and yeast in kombucha. It shows good mechanical strength, biocompatibility and hydrophilicity. However, it has limited application in tissue engineering due to its low processability. In this work, bacterial cellulose-based sustainable kombucha (KBC) sheet has been produced and it was acid-treated to partially hydrolyse. This controlled process improves its extrusion and shape formation ability. The physical, functional and biological properties were studied to assess its potential as a 3D printed scaffold. Two different cell lines (Human dermal fibroblast cells and mouse osteoblast cells) were used to study the cytocompatibility. Both the cell types showed good attachment, growth and proliferation on the pure and treated KBC. They attained almost full confluence within 3 days. This study indicates that the controlled partial hydrolysis of KBC can make it suitable for 3D printing retaining its mechanical strength and cytocompatibility. This sustainable microbial biopolymer shows the possibility to be used as a bioink for 3D bioprinting.