In this study, the effects of 3D-printed SiO2 and ZnO-doped tricalcium phosphate (TCP) scaffolds with interconnected pores were evaluated on the in vivo bone formation and healing properties of a rabbit tibial defect model. Pure and doped TCP scaffolds were fabricated by a ceramic powder-based 3D printing technique and implanted into critical sized rabbit tibial defects for up to 4 months. In vivo bone regeneration was evaluated using chronological radiological examination, histological evaluations, SEM micrographs, and fluorochrome labeling studies. Radiograph results showed that Si/Zn-doped samples had slower degradation kinetics than the pure TCP samples. 3D printing of TCP scaffolds improved bone formation. The addition of dopants in the TCP scaffolds improved osteogenic capabilities when compared to the pure scaffolds. In summary, our findings indicate that the addition of dopants to the TCP scaffolds enhanced bone formation and in turn leading to accelerated healing.

This work aims at providing guidance through systematic experimental characterization for the design of 3D-printed scaffolds for potential orthopedic applications, focusing on fused deposition modeling with a composite of clinically available polycaprolactone (PCL) and β-tricalcium phosphate (β-TCP). First, we studied the effect of the chemical composition (0–60% β-TCP/PCL) on the scaffold’s properties. We showed that surface roughness and contact angle were, respectively, proportional and inversely proportional to the amount of β-TCP and that degradation rate increased with the amount of ceramic. Biologically, the addition of β-TCP enhanced proliferation and osteogenic differentiation of C3H10. Second, we systematically investigated the effect of the composition and the porosity on the 3D-printed scaffold mechanical properties. Both an increasing amount of β-TCP and a decreasing porosity augmented the apparent Young’s modulus of the 3D-printed scaffolds. Third, as a proof of concept, a novel multimaterial biomimetic implant was designed and fabricated for potential disc replacement.

Wollastonite (CaSiO3)–diopside (CaMgSi2O6) glass-ceramic scaffolds have been successfully fabricated using two different additive manufacturing techniques: powder-based 3D printing (3DP) and digital light processing (DLP), coupled with the sinter-crystallization of glass powders with two different compositions. The adopted manufacturing process depended on the balance between viscous flow sintering and crystallization of the glass particles, in turn influenced by the powder size and the sensitivity of CaO–MgO–SiO2 glasses to surface nucleation. 3DP used coarser glass powders and was more appropriate for low temperature firing (800–900 °C), leading to samples with limited crystallization. On the contrary, DLP used finer glass powders, leading to highly crystallized glass-ceramic samples. Despite the differences in manufacturing technology and crystallization, all samples featured very good strength-to-density ratios, which benefit their use for bone tissue engineering applications. The bioactivity of 3D-printed glass-ceramics after immersion in simulated body fluid and the similarities, in terms of ionic releases and hydroxyapatite formation with already validated bioactive glass-ceramics, were preliminarily assessed.

Three-dimensional (3D) printing technology is a promising method for bone tissue engineering applications. For enhanced bone regeneration, it is important to have printable ink materials with appealing properties such as construct interconnectivity, mechanical strength, controlled degradation rates, and the presence of bioactive materials. In this respect, we develop a composite ink composed of polycaprolactone (PCL), poly(D,L-lactide-co-glycolide) (PLGA), and hydroxyapatite particles (HAps) and 3D print it into porous constructs. In vitro study revealed that composite constructs had higher mechanical properties, surface roughness, quicker degradation profile, and cellular behaviors compared to PCL counterparts. Furthermore, in vivo results showed that 3D-printed composite constructs had a positive influence on bone regeneration due to the presence of newly formed mineralized bone tissue and blood vessel formation. Therefore, 3D printable ink made of PCL/PLGA/HAp can be a highly useful material for 3D printing of bone tissue constructs.

PMMA/β-TCP composites were evaluated to be suitable for laser sintering earlier, but the possible after effects are not known yet. Effects of sintering on the biological nature and the influences of critical compositions and process parameters have not been investigated so far. The current research attempts this, first identifying experimentally the most suitable laser process conditions for the specific grades of PMMA and β-TCP and then subjecting single layer sintered samples to FTIR analysis and in vitro studies involving MTT and ALP assays, alizarin red S tests, and real-time PCR analyses. While the laser interactions are not detrimental, the biological responses are generally positive proving the selective laser sintering of PMMA/β-TCP composites to be a potential approach for specific medical applications.

Biomimicry is a desirable quality of tissue engineering scaffolds. While most of the scaffolds reported in the literature contain a single pore size or porosity, the native biological tissues such as cartilage and skin have a layered architecture with zone-specific pore size and mechanical properties. Thus, there is a need for functionally graded scaffolds (FGS). EHD-jet 3D printing is a high-resolution process and a variety of polymer solutions can be processed into 3D porous scaffolds at ease, overcoming the limitations of other 3D printing methods (SLS, stereolithography, and FDM) in terms of resolution and limited material choice. In this paper, a novel proof of concept study on fabrication of porous polycaprolactone-based FGS by using EHD-jet 3D printing technology is presented. Organomorphic scaffolds, multiculture systems, interfacial tissue engineering, and in vitro cancer metastasis models are some of the futuristic applications of these polymeric FGS.

3D printing has been shown to be a robust and inexpensive manufacturing tool for a range of applications within biomedical science. Here we report the design and fabrication of a 3D printer-enabled microfluidic device used to generate cell-laden hydrogel microspheres of tunable sizes. An inverse mold was printed using a 3D printer, and replica molding was used to fabricate a PDMS microfluidic device. Intersecting channel geometry was used to generate perfluorodecalin oil-coated gelatin methacrylate (GelMA) microspheres of varying sizes (35–250 μm diameters). Process parameters such as viscosity profile and UV cross-linking times were determined for a range of GelMA concentrations (7–15% w/v). Empirical relationships between flow rates of GelMA and oil phases, microspheres size, and associated swelling properties were determined. For cell experiments, GelMA was mixed with human osteosarcoma Saos-2 cells, to generate cell-laden GelMA microspheres with high long-term viability. This simple, inexpensive method does not require the use of traditional cleanroom facilities and when combined with the appropriate flow setup is robust enough to yield tunable cell-laden hydrogel microspheres for potential tissue engineering applications.

In this work, morphology, viability, and metabolism of the amniotic mesenchymal stem cells conditioned with different citric acid (CA)/media ratios were investigated using rhodamine-phalloidin/4′,6-diamidino-2-phenylindole staining, live/dead assay, proliferating cell nuclear antigen, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay). The cells cultured in 25:75 CA/media displayed well spread actin filaments with a prominent nucleus and evidenced optimum viability. The gelation kinetics of chitosan solution in CA/media (25:75) was monitored via dynamic time sweep analysis on a rheometer. The chemical cross-linking of chitosan with CA was confirmed by nuclear magnetic resonance studies. Subsequently, chitosan solution was extruded in CA/media bath containing cells under benign conditions to form cell-laden fibers (living fibers). The prelabeled cells imaged immediately after fiber formation confirmed the attachment of the cells on the fibers. This approach has several advantages including instantaneous gelation, tunable mechanical properties, and adjustable biodegradability that can provide a platform technology for creating viable three dimensional (3D) building blocks for tissue engineering applications.

The polysaccharide alginate has received most extensive attention as bioink in bioprinting applications due to its ability to undergo gelation under cell-friendly conditions. However, absence of cell-binding motifs and the erratic degradation of alginate hydrogels have remained their persistent limitations. Honey is a conveniently available natural material, known for its role in wound healing and skin tissue regeneration. However, honey blending to improve biological response of alginate-based bioprinted scaffolds has not been yet reported. In the present work, honey-alginate bioinks were evaluated for their printability property (shape fidelity). It was found that honey blending reduced alginate viscosity, which gradually affected bioprinting fidelity. Therefore, the concentration that provides for acceptable bioprinting along with improvement in cell proliferations is determined. It is concluded that honey blending improves cell response of alginate bioinks and can be a facile approach to obtain bioinks especially for in situ skin tissue engineering applications.

Recent advances in the additive manufacturing technology now enable fused filament fabrication of polyetheretherketone (PEEK). A standardized lumbar fusion cage design was 3D printed with different speeds of the printhead nozzle to investigate whether 3D-printed PEEK cages exhibit sufficient material properties for lumbar fusion applications. It was observed that the compressive and shear strength of the 3D-printed cages were 63–71% of the machined cages, whereas the torsion strength was 92%. The printing speed is an important printing parameter for 3D-printed PEEK, which resulted in up to 20% porosity at the highest speed of 3000 mm/min, leading to reduced cage strength. Printing speeds below 1500 mm/min can be chosen as the optimal printing speed for this printer to reduce the printing time while maintaining strength. The crystallinity of printed PEEK did not differ significantly from the as-machined PEEK cages from extruded rods, indicating that the processing provides similar microstructure.

We designed a resorcinol-formaldehyde (RF) sol–gel ink for direct ink writing of the microlattices. To improve the formability, the fresh microlattices were strengthened by surface catalysis with HCl atmosphere. After supercritical drying and carbonization, the sample’s specific surface area was 631 m2/g and the average pore size was 3.81 nm. Both RF aerogel and carbonized RF aerogel samples had millimeter-scale pore, micron-scale pore, and nanoscale skeleton. The pore and skeleton could provide high surface area and diffusion channels, which were beneficial to the adsorption performances. The carbonized RF aerogel sample fully adsorbed Dulbecco’s modified eagle medium in 250 min, which exhibited a good capacity of quick adsorption and indicated the potential application for cell supports.

The post-processing treatment plays an important role in tailoring the mechanical and biological properties of the three-dimensional powder-printed porous scaffolds. Depending on scaffold material composition, a combination of post-processing treatments can be used to tailor these properties. This work probes into the impact of post-processing on the microstructure and deformation behavior of 3D-printed scaffolds. In this study, we have chosen CaSO4·xH2O (POP), a system for 3D powder printing and two different post-processing methodologies, namely chemical conversion and polymer infiltration. POP-based scaffolds were fabricated using water-based binder with up to 55% interconnected microporosity and moderate compressive strength of 1.5 MPa. Microcomputed tomography (µCT) is extensively utilized to determine the accuracy and efficacy of the adopted printing and post-processing approach. It was shown that the reproducibility of the fine features depends not only on the size but also on the presence of neighboring features. Crucially, µCT-based microstructure modeling and finite elemental simulation were attempted to computationally capture the compression behavior, in silico. Finally, in situ compression coupled with µCT imaging provided us an insight into fracture behavior of 3D powder-printed scaffolds.

Seeking to improve the wear resistance of the Ti6Al4V (Ti64) alloy for biomedical applications, carbon nanotubes (CNTs) and calcium phosphate (CaP) ceramics were added to Ti64 powder and successfully 3D-printed using a commercial laser engineered net shaping (LENS™) system. It was hypothesized that CNTs would allow for in situ carbide formation during laser processing, resulting in increased surface hardness. It was also hypothesized that CaPs would allow for protective tribofilm formation during wear, reducing material loss from wear-induced damage. Scanning electron microscopy images reveal defect-free microstructures with fine carbides evenly distributed, while X-ray diffraction confirms the presence of carbides without additional unwanted intermetallic phases. Vickers microhardness shows an increase in surface hardness in coatings containing both CNTs and CaPs. In vitro tribological studies found reduced coefficient of friction, reduced wear rates, and reduced metal ion-release concentrations in coatings containing both CNTs and CaPs. This study demonstrates the efficacy of CNTs and CaPs to improve wear resistance of Ti64 for potential applications in articulating surfaces of load-bearing implants.

Surface modification by the bioactive material is a potential way to overcome the poor osseoconductivity of titanium (Ti)-based implants. A continuous wave laser source was used to deposit strontium titanate (SrTiO3)-reinforced Ti coating on the Ti substrate using the laser engineered net shaping (LENS™) process. The maximum of 10 wt% SrTiO3 could be incorporated into Ti using laser without cracking of the deposit. This study investigated the constituent phases, microstructure, compositional analysis, wettability, and electrochemical behavior of the composite coatings. XRD and EDX analyses confirmed the presence of the SrTiO3 phase in the coatings. The composite coatings also exhibited superior mechanical properties, corrosion resistance, and bioactivity compared to that of commercially pure Ti. In vitro ion release study confirmed the sustain release of Sr2+ from the composite coatings. In summary, the excellent mechanical bonding with the substrate and high in vitro bioactivity make these SrTiO3-incorporated composite coatings as a potential material to enhance osseoconductivity of Ti-based orthopedic implants.

In this investigation, an electron beam melting-processed γ-TiAl alloy (Ti–48Al–2Cr–2Nb, at.%) was oxidized in air to improve its in vitro tribological, electrochemical, and biocompatibility properties. The γ-TiAl alloy samples were oxidized at 400, 600, and 800 °C for 1 and 4 h. The oxidized layer thickness, composition, and surface morphology found to change with oxidation temperature. The oxidation thickness varied between 1.29 ± 0.2 and 2.18 ± 0.2 μm. The primary oxides on the surface were Al2O3 and TiO2 with minor concentrations of Cr2O3, Nb2O5, and nitrides of Ti. The surface hardness of the alloy increased by 1.7-fold with increasing temperature from 400 to 800 °C with 1 h soaking, and at 4 h, the maximum hardness was 12.26 GPa. The high hardness of the oxidized γ-TiAl alloy resulted in two orders of magnitude lower wear rate than the bare γ-TiAl alloy. Oxidation at 800 °C for 4 h resulted in significant reduction in corrosion current and no passivity breakdown was observed. In vitro cell culture experiments, using mouse preosteoblast cells, revealed high cell density on the oxidized γ-TiAl alloy, suggesting its enhanced cell proliferation compared to the bare γ-TiAl alloy and CP-Ti.

To increase the corrosion prevention of stainless steel implant and fast recovery due to new bone-cell formation at the orthopedic implant site, in the present investigation, a trilayered (with bioceramic interlayer sandwiched between innermost passivated surface and outermost polymer coating) 316L stainless steel (SS) implant was designed and investigated. It was inferred that this new designed implant invokes faster and more bone-cell formation than uncoated commercially available 316L SS implants. Faster bone-cell formation at the coated implant site reduces the initial threat of implant corrosion. The electrochemical corrosion study proved that this model of coated implants is able to prevent corrosion up to 90% better than uncoated commercially available 316L SS. Subsequently, preclinical studies in the rabbit bone defect model (which included histology, radiology, fluorochrome labeling, push-out test, and scanning electron microscopy taken after 45 and 90 days) proved higher rate of new bone tissue formation and better push-out strength between tissue in contact and the coated implant. The toxicological study of vital organs like liver, kidney, and heart also exhibited no abnormality. The outcome of the experimentations indicates suitability of this trilayered 316L SS implant for bone repair and healing.