Sintering properties of in situ Ti-TiB microlattices created by 3D extrusion printing of TiH_(2)+TiB_(2) inks

A direct 3D extrusion printing technique was used to produce Ti-TiB filaments and microlattices.The sintering properties of 3D ink extrusion and sintering of in situ Ti-TiB composite structures made from TiH_(2)+TiB_(2) ink were investigated.The sintering kinetics of TiH2+TiB2 inks was studied during densification by pressureless sintering at 1050−1200℃ for 4−24 h in Ar.The linear shrinkage,grain size,microhardness,X-ray diffraction(XRD)patterns,and microstructural evolution of the Ti-TiB composite were studied.The sintering temperature had a more pronounced influence than the sintering time on the density of the Ti-TiB composite.There were two kinds of pores,irregular and spherical,caused by the Kirkendall effect and indiffusable gases.The TiB formed by in situ synthesis existed as either separated TiB whiskers(needle-like shapes)or clusters of TiB whiskers.The results of this work could be useful for controlling microporosity through incomplete sintering within filaments,especially for the production of in situ Ti-TiB with high volume fractions of TiB or other composites.

Extrusion 3D printing of carbon nanotube-assembled carbon aerogel nanocomposites with high electrical conductivity

Carbon nanotubes(CNTs)with high aspect ratio and excellent electrical conduction offer huge functional improvements for current carbon aerogels.However,there remains a major challenge for achieving the on-demand shaping of carbon aerogels with tailored micro-nano structural textures and geometric features.Herein,a facile extrusion 3D printing strategy has been proposed for fabricating CNT-assembled carbon(CNT/C)aerogel nanocomposites through the extrusion printing of pseudoplastic carbomer-based inks,in which the stable dispersion of CNT nanofibers has been achieved relying on the high viscosity of carbomer microgels.After extrusion printing,the chemical solidification through polymerizing RF sols enables 3D-printed aerogel nanocomposites to display high shape fidelity in macroscopic geometries.Benefiting from the micro-nano scale assembly of CNT nanofiber networks and carbon nanoparticle networks in composite phases,3D-printed CNT/C aerogels exhibit enhanced mechanical strength(fracture strength,0.79 MPa)and typical porous structure characteristics,including low density(0.220 g cm^(-3)),high surface area(298.4 m^(2)g^(-1)),and concentrated pore diameter distribution(~32.8nm).More importantly,CNT nanofibers provide an efficient electron transport pathway,imparting 3D-printed CNT/C aerogel composites with a high electrical conductivity of 1.49 S cm^(-1).Our work would offer feasible guidelines for the design and fabrication of shape-dominated functional materials by additive manufacturing.

3D bioprinting of complex biological structures with tunable elastic modulus and porosity using freeform reversible embedding of suspended hydrogels

Three-dimensional(3D)bioprinting has been used widely for the construction of hard tissues such as bone and cartilage.However,constructing soft tissues with complex structures remains a challenge.In this study,complex structures characterized by both tunable elastic modulus and porosity were printed using freeform reversible embedding of suspended hydrogels(FRESHs)printing methods.A mixture of alginate and gelatin was used as the main functional component of the bioink.Rheological analysis showed that this bioink possesses shear thinning and shear recovery properties,supporting both cryogenic and FRESH printing methods.Potential printing capabilities and limitations of cryogenic and FRESH printing were then analyzed by printability tests.A series of complex structures were printed by FRESH printing methods which could not be realized using conventional approaches.Mechanical tests and scanning electron microscopy analysis showed that the printed structure is of excellent flexibility and could be applied in various conditions by adjusting its mechanical modulus and porosity.L929 fibroblast cells maintained cell viability in cell-laden-printed structures,and the addition of collagen further improved the hydrogels’biocompatibility.Overall,all results provided useful insight into the building of human soft tissue organ blocks.

An oxygenating colloidal bioink for the engineering of biomimetic tissue constructs

Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.

A gel microparticle-based self-thickening strategy for 3D printing high-modulus hydrogels skeleton cushioned with PNAGA hydrogel mimicking anisotropic mechanics of meniscus

Developing a meniscus substitute mimicking the anisotropic mechanics(higher circumferential tensile modulus and lower compressive modulus)of native tissue remains a great challenge.In this work,based on the pendant group structure-dependent H-bonding strengthening mechanism,two kinds of amide-based H-bonding crosslinked hydrogels with distinct mechanical behaviors,that is,the flexible poly(N-acryloyl glycinamide)(PNAGA)and the ultra-stiff poly(N-acryloylsemicarbazide)(PNASC)hydrogels are employed to construct the biomimetic meniscus substitute.To this end,a gel microparticle-based self-thickening strategy is first proposed to fabricate PNASC(GMP-PNASC)high-modulus hydrogels skeleton by extrusion printing technology in mimicking the collagen fibers in native meniscus to resist the circumferential tensile stress.Then,the PNAGA hydrogel is infused into the PNASC skeleton to replicate the proteoglycan,providing a lower compressive modulus.By regulating the structural features at the interior and peripheral regions,the GMP-PNASC/PNAGA hydrogel meniscus scaffold with the higher tensile modulus(87.28±6.06 MPa)and lower compressive modulus(2.11±0.28 MPa)can be constructed.In vivo outcome at 12 weeks post-implantation of rabbit’s medial meniscectomy model confirms the effects of GMP-PNASC/PNAGA meniscus scaffold on alleviating the wear of articular cartilage and ameliorating the development of osteoarthritis(OA).

3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Ulcerative colitis is a global health problem,affecting millions of individuals worldwide.As an inflammatory condition localised in the large intestine,rectal delivery of immunosuppressive therapies such as tacrolimus is a promising strategy to maximise drug concentration at the site of action whilst minimising systemic side effects.Here,for the first time,self-supporting 3D-printed tacrolimus suppositories were prepared without the aid of moulds using a pharmaceutical semi-solid extrusion(SSE)3D printer.The suppositories were printed vertically in three different sizes using combinations of two lipid pharmaceutical excipients(Gelucire 44/14 or Gelucire 48/16)and coconut oil.Although both suppository formulations had the appropriate viscosity characteristics for printing,the Gel 44 formulation required less energy and force for extrusion compared to the Gel 48 system.The Gel 44 disintegrated more rapidly but released tacrolimus more slowly than the Gel 48 suppositories.Although the tacrolimus release profiles were significantly different,both suppository systems released more than 80% drug within 120 min.DSC and XRD analysis was inconclusive in determining the solid-state properties of the drug in the suppositories.In summary,this article reports on the fabrication of 3D printed selfsupporting suppositories to deliver personalised doses of a narrow therapeutic index drug,with potential benefits for patients with ulcerative colitis.

Integrated printed BDNF/collagen/chitosan scaffolds with low temperature extrusion 3D printer accelerated neural regeneration after spinal cord injury

Recent studies have shown that 3D printed scaffolds integrated with growth factors can guide the growth of neurites and promote axon regeneration at the injury site.However,heat,organic solvents or cross-linking agents used in conventional 3D printing reduce the biological activity of growth factors.Low temperature 3D printing can incorporate growth factors into the scaffold and maintain their biological activity.In this study,we developed a collagen/chitosan scaffold integrated with brain-derived neurotrophic factor(3D-CC-BDNF)by low temperature extrusion 3D printing as a new type of artificial controlled release system,which could prolong the release of BDNF for the treatment of spinal cord injury(SCI).Eight weeks after the implantation of scaffolds in the transected lesion of T10 of the spinal cord,3D-CC-BDNF significantly ameliorate locomotor function of the rats.Consistent with the recovery of locomotor function,3D-CC-BDNF treatment could fill the gap,facilitate nerve fiber regeneration,accelerate the establishment of synaptic connections and enhance remyelination at the injury site.

Coaxial-printed small-diameter polyelectrolyte-based tubes with an electrostatic self-assembly of heparin and YIGSR peptide for antithrombogenicity and endothelialization

Low patency ratio of small-diameter vascular grafts remains a major challenge due to the occurrence of thrombosis formation and intimal hyperplasia after transplantation.Although developing the functional coating with release of bioactive molecules on the surface of small-diameter vascular grafts are reported as an effective strategy to improve their patency ratios,it is still difficult for current functional coatings cooperating with spatiotemporal control of bioactive molecules release to mimic the sequential requirements for antithrombogenicity and endothelialization.Herein,on basis of 3D-printed polyelectrolyte-based vascular grafts,a biologically inspired release system with sequential release in spatiotemporal coordination of dual molecules through an electrostatic self-assembly was first described.A series of tubes with tunable diameters were initially fabricated by a coaxial extrusion printing method with customized nozzles,in which a polyelectrolyte ink containing of ε-polylysine and sodium alginate was used.Further,dual bioactive molecules,heparin with negative charges and Tyr-Ile-Gly-Ser-Arg(YIGSR)peptide with positive charges were layer-by-layer assembled onto the surface of these 3D-printed tubes.Due to the electrostatic interaction,the sequential release of heparin and YIGSR was demonstrated and could construct a dynamic microenvironment that was thus conducive to the antithrombogenicity and endothelialization.This study opens a new avenue to fabricate a small-diameter vascular graft with a biologically inspired release system based on electrostatic interaction,revealing a huge potential for development of small-diameter artificial vascular grafts with good patency.

Three-dimensional-printed collagen/chitosan/secretome derived from HUCMSCs scaffolds for efficient neural network reconstruction in canines with traumatic brain injury

The secretome secreted by stem cells and bioactive material has emerged as a promising therapeutic choice for traumatic brain injury(TBI).We aimed to determine the effect of 3D-printed collagen/chitosan/secretome derived from human umbilical cord blood mesenchymal stem cells scaffolds(3D-CC-ST)on the injured tissue regeneration process.3D-CC-ST was performed using 3D printing technology at a low temperature(20C),and the physical properties and degeneration rate were measured.The utilization of low temperature contributed to a higher cytocompatibility of fabricating porous 3D architectures that provide a homogeneous distribution of cells.Immediately after the establishment of the canine TBI model,3D-CC-ST and 3D-CC(3D-printed collagen/chitosan scaffolds)were implanted into the cavity of TBI.Following implantation of scaffolds,neurological examination and motor evoked potential detection were performed to analyze locomotor function recovery.Histological and immunofluorescence staining were performed to evaluate neuro-regeneration.The group treated with 3D-CC-ST had good performance of behavior functions.Implanting 3D-CC-ST significantly reduced the cavity area,facilitated the regeneration of nerve fibers and vessel reconstruction,and promoted endogenous neuronal differentiation and synapse formation after TBI.The implantation of 3D-CC-ST also markedly reduced cell apoptosis and regulated the level of systemic inflammatory factors after TBI.