3D Bioplotter Research Papers

Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized tissues interconnect, creating fully engineered hierarchical vascular constructs for implantation. Endothelial and support cells spontaneously form microvascular networks in bioprinted tissues using a human collagen bioink. Sacrificial molds are used to create polymeric vessel-like scaffolds and endothelial cells seeded in their lumen form native-like endothelia. Assembling endothelialized scaffolds within vascularizing hydrogels incites…

The current study introduces two novel, smart polymer three-dimensional (3D)-printable interpenetrating polymer network (IPN) hydrogel biomaterials with favorable chemical, mechanical, and morphological properties for potential applications in traumatic brain injury (TBI) such as potentially assisting in the restoration of neurological function through closure of the wound deficit and neural tissue regeneration. Additionally, removal of injury matter to allow for the appropriate scaffold grafting may assist in providing a TBI treatment. Furthermore, due to the 3D printability of the IPN biomaterials, complex structures can be designed and fabricated to mimic the native shape and structure of the injury sight, which can…

The fabrication of 3D ink-printed and sintered porous Si scaffolds as electrode material for lithium-ion batteries is explored. A hierarchically-porous architecture consisting of channels (~220 μm in diameter) between microporous Si struts is created to accommodate the large volume change from Si (de)lithiation during electrochemical (dis)charging. The influence of sintering parameters on Si strut porosity and the resulting mechanical and electrochemical properties of the scaffolds are studied experimentally and computationally. Varying sintering temperatures (1150–1300 °C) and sintering times (1–16 h) the open porosity within the Si filaments can be tailored between 46 and 60%. Pore size (3–6 μm) and wall…

Although allogeneic islet transplantation has been proposed as a therapy for type 1 diabetes, its success rate remains low. Disruption of both extracellular matrix (ECM) and dense vascular network during islets isolation are referred to as some of the main causes of their poor engraftment. Therefore, the recapitulation of the native pancreatic microenvironment and its prompt revascularization should be beneficial for long-term islet survival. In this study, we developed novel bioinks suitable for the microfluidic-assisted multi-material biofabrication of 3D porous pancreatic and vascular structures. The tissue-specific bioactivity was introduced by blending alginate either with pancreatic decellularized extracellular matrix powder (A_ECM)…

The central theme of this dissertation is the observation that mechanical waves propagate and scatter at different velocities in biological tissues due to a difference in local material properties (such as viscosity and stiffness), due to the presence of inhomogeneities such as a blood vessel, an axon or a muscle filament. These scattered waves contain information about the characteristic stiffness, viscosity and the mechanical property inhomogeneity of the tissues through which they propagate; this information can aid in non-invasive diagnosis of disease and injury using novel quantitative techniques such as Insonification, Percussion and 1-Norm using Magnetic Resonance Elastography (MRE). The…

Beta-tricalcium phosphate (β-TCP)-based bioinks were developed to support direct-ink 3D printing-based manufacturing of macroporous scaffolds. Binding of the gelatin:β-TCP ink compositions was optimized by adding carboxymethylcellulose (CMC) to maximize the β-TCP content while maintaining printability. Post-sintering, the gelatin:β-TCP:CMC inks resulted in uniform grain size, uniform shrinkage of the printed structure, and included microporosity within the ceramic. The mechanical properties of the inks improved with increasing β-TCP content. The gelatin:β-TCP:CMC ink (25:75 gelatin:β-TCP and 3% CMC) optimized for mechanical strength was used to 3D print several architectures of macroporous scaffolds by varying the print nozzle tip diameter and pore spacing during…

Three-dimensional (3D) bioprinting is an emerging fabrication technique to create 3D constructs with living cells. Notably, bioprinting bioinks are limited due to the mechanical weakness of natural biomaterials and the low bioactivity of synthetic peers. This paper presents the development of a natural bioink from chicken eggwhite and sodium alginate for bioprinting cell-laden patches to be used in endothelialized tissue engineering applications. Eggwhite was utilized for enhanced biological properties, while sodium alginate was used to improve bioink printability. The rheological properties of bioinks with varying amounts of sodium alginate were examined with the results illustrating that 2.0–3.0% (w/v) sodium alginate…

Many drugs show promising results in laboratory research but eventually fail clinical trials. We hypothesize that one main reason for this translational gap is that current cancer models are inadequate. Most models lack the tumor-stroma interactions, which are essential for proper representation of cancer complexed biology. Therefore, we recapitulated the tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia. In addition, perfusable blood vessels were created using a sacrificial bioink coated with brain pericytes and endothelial cells. We observed similar growth curves, drug response, and genetic signature of glioblastoma cells grown in our…

Background: Traditionally, the iliac crest has been the most common harvesting site for autologous bone grafts; however, it has some limitations, including poor bone availability and donor-site morbidity. This study sought to explore the effect of enhanced bone marrow (eBM) in conjunction with three-dimensional (3D)-printed polylactide–hydroxyapatite (PLA-HA) scaffolds in the repair of critical-sized bone defects in a rabbit model. Methods: First, 3D-printed PLA-HA scaffolds were fabricated and evaluated using micro-computed tomography (µCT) and scanning electron microscopy (SEM). Twenty-seven New Zealand white rabbits were randomly divided into 3 groups (n=9 per group), and the defects were treated using 3D-printed PLA-HA scaffolds…

Composites are promising candidates for treating bone defects, but manufacturing of composite scaffolds is challenging. This study aimed to fabricate composite scaffolds based on polycaprolactone (PCL) and doped Hydroxyapatite (HA) via a single step melt extrusion additive manufacturing technique. Starting from the raw powder forms, the printed scaffolds were produced and then characterized for morphology, mechanical behavior and in vitro mineralization. MicroCT revealed the homogenous dispersion of ceramic particles in the PCL matrix. Also, SEM showed the ceramic particles on the surfaces of printed scaffolds. Furthermore, bioactivity assays confirmed the enhanced apatite deposit formation on composite scaffolds compared to PCL…

Auricle reconstruction is a routine surgery in the field of Otolaryngology but the design of the reconstruction is based on the clinicians guess of the correct previous anatomy. Using additive manufacturing processes to build a model the surgeon can refer to may be a good substitute for conventional surgery. The quality of the framework replicating the three-dimensional architecture of the ear and precise sculpting of the anatomical structures are necessary in order to reach a desired outcome. In this work we present the workflow to produce an individualized 3D outer ear model for use in auricle reconstruction surgery and report…

The cancer microenvironment influences tumor progression and metastasis and is pivotal to consider when designing in vivo-like cancer models. Current preclinical testing platforms for cancer drug development are mainly limited to 2D cell culture systems that poorly mimic physiological environments and traditional, low throughput animal models. The aim of this work was to produce a tunable testing platform based on 3D printed scaffolds (3DPS) with a simple geometry that, by extracellular components and response of breast cancer reporter cells, mimics patient-derived scaffolds (PDS) of breast cancer. Here, the biocompatible polysaccharide alginate was used as base material to generate scaffolds consisting…

Rupture of the scapholunate interosseous ligament can cause the dissociation of scaphoid and lunate bones, resulting in impaired wrist function. Current treatments (e.g., tendon-based surgical reconstruction, screw-based fixation, fusion, or carpectomy) may restore wrist stability, but do not address regeneration of the ruptured ligament, and may result in wrist functional limitations and osteoarthritis. Recently a novel multiphasic bone-ligament-bone scaffold was proposed, which aims to reconstruct the ruptured ligament, and which can be 3D-printed using medical-grade polycaprolactone. This scaffold is composed of a central ligament-scaffold section and features a bone attachment terminal at either end. Since the ligament-scaffold is the primary…

Soft-ionic materials with biocompatibility and 3D printability are needed to develop next-generation devices to interface between electronic and biological signals. Herein, thermoreversible and biocompatible ionic liquid gels or iongels, which can be processed by direct ink writing are reported. The iongels are designed by taking advantage of polyvinyl alcohol/phenol interactions to gelify biocompatible cholinium carboxylate ionic liquids. The obtained iongels are stable, soft, and flexible materials (Young modulus between 14 and 70 kPa) with high ionic conductivity (1.8 × 10–2 S cm–1). Interestingly, they presented thermoreversible properties with gel–sol transitions ranging from 85 and 110 °C, which allows the iongel…

Three-dimensional cell culture platforms based on decellularised patient-based microenvironments provide in vivo-like growth conditions allowing cancer cells to interact with intact structures and components of the surrounding tissue. A patient-derived scaffold (PDS) model was therefore evaluated as a testing platform for the endocrine therapies (Z)-4-Hydroxytamoxifen (4OHT) and fulvestrant as well as the CDK4/6-inhibitor palbociclib, monitoring the treatment responses in breast cancer cell lines MCF7 and T47D adapted to the patient-based microenvironments. MCF7 cells growing in PDSs showed increased resistance to 4OHT and fulvestrant treatment (100- and 20-fold) compared to 2D cultures. Quantitative PCR analyses of endocrine treated cancer cells in…

Skeletal muscle is an electrically and mechanically active tissue that contains highly oriented, densely packed myofibrils. The tissue has self-regeneration capacity upon injury, which is limited in the cases of volumetric muscle loss. Several regenerative therapies have been developed in order to enhance this capacity, as well as to structurally and mechanically support the defect site during regeneration. Among them, biomimetic approaches that recapitulate the native microenvironment of the tissue in terms of parallel-aligned structure and biophysical signals were shown to be effective. In this study, we have developed 3D printed aligned and electrically active scaffolds in which the electrical…

Stable and predictive neural cell culture models are a necessary premise for many research fields. However, conventional 2D models lack 3D cell-material/-cell interactions and hence do not reflect the complexity of the in vivo situation properly. Here two alginate/gellan gum/laminin (ALG/GG/LAM) hydrogel blends are presented for the fabrication of human induced pluripotent stem cell (hiPSC)-based 3D neural models. For hydrogel embedding, hiPSC-derived neural progenitor cells (hiNPCs) are used either directly or after 3D neural pre-differentiation. It is shown that stiffness and stress relaxation of the gel blends, as well as the cell differentiation strategy influence 3D model development. The embedded…

Piezoelectric ceramics, such as BaTiO3, have gained considerable attention in bone tissue engineering applications thanks to their biocompatibility, ability to sustain a charged surface as well as improve bone cells’ adhesion and proliferation. However, the poor processability and brittleness of these materials hinder the fabrication of three-dimensional scaffolds for load bearing tissue engineering applications. For the first time, this study focused on the fabrication and characterisation of BaTiO3 composite scaffolds by using a multi-material 3D printing technology. Polycaprolactone (PCL) was selected and used as dispersion phase for its low melting point, easy processability and wide adoption in bone tissue engineering….

3D bioprinting, a paradigm shift in tissue engineering holds a promising perspective for regenerative medicine and disease modelling. 3D scaffolds are fabricated for subsequent cell seeding or incorporated directly to the bioink to create cell-laden 3D constructs. A plethora of factors relating to bioink properties, printing parameters and post print curing play a significant role in the optimisation of the printing process. Although qualitative evaluation of printability has been investigated largely, there is a paucity of studies on quantitative approaches to assess printability. Hence, this study explores machine learning as a novel tool to evaluate printability quantitatively and to fast…

3D ink-extrusion of powders followed by sintering is an emerging additive manufacturing method capable of creating metallic microlattices. Here, we study the creation of hierarchically porous Fe or Ni scaffolds by 3D extrusion of 0/90° lattices from inks consisting of fine oxide powders (Fe2O3 or NiO, < 3 µm), coarse space-holder particles (CuSO4, < 45 µm) and a polymer binder within a solvent. After space-holder leaching and debinding of the lattices, a sintering step densifies the metallic Fe or Ni powders created by oxide reduction with H2, while maintaining the larger pores templated by the space-holder particles within the printed...

Wounds impact millions of patients every year and represent a serious cause of morbidity and mortality worldwide, yet current treatment outcomes are far from ideal. Therapies based on delivery of multiple growth factors offer a promising approach for optimal wound management; however, their high production cost, low stability, and lack of effective delivery system limits their application in the clinic. Platelet lysate is a suitable, abundant and cost-effective source of growth factors that play an important role in the healing cascade. The aim of this current work is to develop an extrusion-based bioink consisting of platelet lysate (PL) and gelatin…

Liquid deposition modeling (LDM) is an evolving three-dimensional (3D) printing approach that mainly utilizes polymer solutions to enable the fabrication of biomedical scaffolds under mild conditions. A deep understanding of the rheological properties of polymer printing inks and the features of yielded scaffolds are critical for a successful LDM based fabrication of biomedical scaffolds. In this work, polymer printing inks comprised of Poly(epsilon-caprolactone) (PCL), sodium chloride (NaCl), and trichloromethane (CHCl3) were prepared. The rheological properties, including extrudability (shear stress, viscosity, and shear-thinning) and self-supporting ability (viscosity) of all printing inks were analyzed. Then printing performance was evaluated by measuring the…

3D printing of cell laden bioinks has the potential to recapitulate the hierarchical and spatial complexity of native tissues. However, the addition of cells can alter physical properties of printable resins, which in turn may impede or induce cellular sedimentation or affect the printability and shape fidelity of the final construct. In this study we investigated these considerations by bioprinting gelatin methacrylate (GelMA) bioinks, loaded with various concentrations of mouse fibroblast cells (L929), using extrusion-based direct-write 3D printing (EDP). The impact of various cellular concentrations on viscosity, and temperature-driven gelation of GelMA was examined with a rheometer. The effect of…

Poly(ε-caprolactone) (PCL) chain cleavage results in the formation of polar terminal species, comprising hydroxy and carboxyl groups that enhance surface hydrophilicity and enable subsequent biofunctionalization. However, the direct effects of various acidic and basic treatments on 3D printed PCL scaffolds have not been studied from a functional perspective. In this study, we comprehensively assessed the influence of acid (hydrochloric, HCl) and base (sodium hydroxide, NaOH) catalyzed hydrolysis across different conditions on various properties of 3D printed PCL scaffolds. Analyses included testing of physiochemical and mechanical properties, and assessment of rate and stability of surface-nucleating bioactive apatite-like minerals. HCl exposure resulted…

Calcium silicate (CS) composite bone tissue engineering scaffolds were three-dimensionally printed using titanium metallic powders as the second strengthening phase for overcoming the inherent brittleness and fast degradability. In order to promote the sintering process of all composite scaffolds, mesoporous structure was further introduced into sol-gel-derived CS powders obtaining mesoporous CS (MCS) with larger surface area. The influences of mesoporous structure, sintering temperature and Ti content have been investigated through comparisons of the final scaffold composition, microstructure, compressive strength and in vitro stability. Results showed that CS matrix materials reacted with Ti could form less degradable CaTiO3 and TiC ceramic…

Osteochondral repair remains a significant clinical challenge due to the multiple tissue phenotypes and complex biochemical milieu in the osteochondral unit. To repair osteochondral defects, it is necessary to mimic the gradation between bone and cartilage, which requires spatial patterning of multiple tissue-specific cues. To address this need, we have developed a facile system for the conjugation and patterning of tissue-specific peptides by melt extrusion of peptide-functionalized poly(ε-caprolactone) (PCL). In this study, alkyne-terminated PCL was conjugated to tissue-specific peptides via a mild, aqueous, and Ru(II)-catalyzed click reaction. The PCL-peptide composites were then 3D printed by multimaterial segmented printing to generate…

Here, a hybrid process for the fabrication of dehydrofluorinated PVDF (dPVDF) microfiltration (MF) membranes is presented. dPVDF was fabricated through the bulk modification of PVDF using ethylenediamine. To produce inks for direct ink writing (DIW), the dPVDF was dissolved in N,N-dimethyacetamide along with a pore-forming agent, poly(vinyl pyrrolidone) (PVP) (5–30 wt%, relative to dPVDF concentration). Membranes were produced by direct ink writing of the inks into continuous films – followed by non-solvent induced phase separation (NIPS). Attenuated total reflectance – Fourier transform infrared (ATR-FTIR) and Raman spectroscopies confirmed alkene moieties within the dPVDF polymer, resulting from the dehydrofluorination process. The…

Cobalt-based superalloy microlattices with γ/γ′ microstructure are manufactured by combining two additive methods: ink-extrusion 3D-printing and pack-cementation surface alloying. First, a microlattice green structure is 3D-printed at ambient temperature from inks comprised of Co3O4, NiO, and WO3 powders, an elastomeric binder and solvents. Organic removal followed by oxide reduction under Ar-5% H2, sintering and homogenization at 1250 °C lead to a metallic microlattice with dense struts with uniform γ (fcc)-Co–22Ni–8W (at.%) composition. Second, aluminum is deposited on the strut surfaces via pack-cementation at 1000 °C, diffused at 1300 °C through the strut volume to achieve a uniform composition (Co–20Ni–6W–10Al or…

We recently developed a recombinant growth factor-free bone regenerative scaffold composed of stoichiometric hydroxyapatite (HA) ceramic particles and human demineralized bone matrix (DBM) particles (HA-DBM). Here, we performed the first pre-clinical comparative evaluation of HA-DBM relative to the industry standard and established positive control, recombinant human bone morphogenetic protein-2 (rhBMP-2), using a rat posterolateral spinal fusion model (PLF). Female Sprague–Dawley rats underwent bilateral L4-L5 PLF with implantation of the HA-DBM scaffold or rhBMP-2. Fusion was evaluated using radiography and blinded manual palpation, while biomechanical testing quantified the segmental flexion-extension range-of-motion (ROM) and stiffness of the fused segments at 8-weeks postoperatively….

Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac…

Flexible and stretchable conductors are crucial components for next-generation flexible devices. Wrinkled structures often have been created on such conductors by depositing conductive materials on the pre-stretched or organic solvent swollen samples. Herein, water swelling is first proposed to generate the wrinkled structures on silicone elastomers. By immersing silicone/sugar hybrid in water, a significant amount of swelling occurs as a result of osmosis and capillary interactions with the sugar and silicone matrix. Considering the drastic swelling effect and controllable swelling ratio, water swelling is used to replace the conventional pre-stretching and organic solvent swelling to fabricate stretchable conductors. In situ…

Detecting hydrogen peroxide (H2O2) as the side product of enzymatic reactions is of great interest in food and medical applications. Despite the advances in this field, the majority of reported H2O2 sensors are bulky, expensive, limited to only one phase detection (either gas or liquid), and require multistep fabrications. This article aims to address some of these limitations by presenting a 3D printable paper-based sensor made from poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) decorated with horseradish peroxidase, an enzyme able to interact with H2O2. Unlike most electrochemical PEDOT:PSS-based H2O2 sensors with voltametric or potentiometric mechanisms, the sensing mechanism in this technology is impedimetric, significantly…

Background We evaluated the outcome of esophageal reconstructions using tissue-engineered scaffolds. Method Partial esophageal defects were reconstructed with the following scaffolds; animals were grouped (n = 7 per group) as follows: (a) normal rats; (b) rats implanted with three-dimensional printing (3DP) polycaprolactone (PCL) scaffolds; (c) with human adipose-derived mesenchymal stem cell (ADSC)-seeded 3DP PCL scaffolds; (d) with polyurethane (PU)-nanofiber(Nf) scaffolds; and (e) with ADSC-seeded PU-Nf scaffolds. Results The esophageal defects were successfully repaired; however, muscle regeneration was greater in the 3DP PCL + ADSC groups than in the PU-Nf + ADSC groups (P 

Bone tissue plays an important role in supporting and protecting the structure and function of the human body. Bone defects are a common source of injury and there are many reconstruction challenges in clinical practice. However, 3D bioprinting of scaffolds provides a promising solution. Hydrogels have emerged as biomaterials with good biocompatibility and are now widely used as cell-loaded materials for bioprinting. This study involved three steps: First, sodium alginate (SA), gelatin (Gel), and nano-hydroxyapatite (na-HA) were mixed into a hydrogel and its rheological properties assessed to identify the optimum slurry for printing. Second, SA/Gel/na-HA bioscaffolds were printed using 3D…

A promising alternative to current treatment options for degenerative conditions of the temporomandibular joint (TMJ) is cartilage tissue engineering, using 3D printed scaffolds and mesenchymal stem cells. Gelatin, with its inherent biocompatibility and printability has been proposed as a scaffold biomaterial, but because of its thermoreversible properties, rapid degradation and inadequate strength it must be crosslinked to be stable in physiological conditions. The aim of this study was to identify non-toxic and effective crosslinking methods intended to improve the physical properties of 3D printed gelatin scaffolds for cartilage regeneration. Dehydrothermal (DHT), ribose glycation and dual crosslinking with both DHT and…

This paper reports on the hybrid process we have used for producing hierarchical scaffolds made of poly(lactic-co-glycolic) acid (PLGA) and nanohydroxyapatite (nHA), analyzes their internal structures via scanning electron microscopy, and presents the results of our in vitro proliferation of MC3T3-E1 cells and alkaline phosphatase activity (ALP) for 0 and 21 days. These scaffolds were produced by combining additive manufacturing (AM) and thermally induced phase separation (TIPS) techniques. Slow cooling at a rate of 1.5 °C/min during the TIPS process was used to enable a uniform temperature throughout the scaffolds, and therefore, a relatively uniform pore size range. We produced ten different…

Metamaterials are artificial structures with unusual and superior properties that come from their carefully designed building blocks — also called meta-atoms. Metamaterials have permeated large swatches of science, including electromagnetics and mechanics. Although metamaterials hold the promise for realizing technological advances, their potential to enhance interactions between humans and materials has remained unexplored. Here, we devise meta-atoms with tailored fracture properties to control mouthfeel sensory experience. Using chocolate as a model material, we first use meta-atoms to control the fracture anisotropy and the number of cracks and demonstrate that these properties are captured in mouthfeel experience. We further use topology…

In tissue engineering, biomaterials have been used to steer the host response. This determines the outcome of tissue regeneration, which is modulated by multiple growth factors (GFs). Hence, a sustainable delivery system for GFs is necessary to control tissue regeneration actively. A delivery technique of single and multiple GF combinations, using a layer‐by‐layer (LBL) procedure to improve tissue remodeling, is developed. TGF‐β1, PDGF‐ββ, and IGF‐1 are incorporated on tailor‐made polymeric rods, which could be used as a tool for potential tissue engineering applications, such as templates to induce the formation of in situ tissue engineered blood vessels (TEBVs). Cell response…

Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics. However, most hydrogels offer limited cell growth and tissue formation ability due to their submicron- or nano-sized gel networks, which restrict the supply of oxygen, nutrients and inhibit the proliferation and differentiation of encapsulated cells. In recent years, 3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds. In this study, we fabricated a macroporous hydrogel scaffold through horseradish peroxidase (HRP)-mediated crosslinking of silk fibroin (SF) and tyramine-substituted gelatin (GT) by extrusion-based low-temperature 3D printing. Through physicochemical characterization,…

Myocardial infarction (MI) or heart attack occurs when the bloodstream to the heart is blocked, which may destroy a part of the heart muscle (or myocardium) and form perdurable scarred tissue. The infarcted myocardial muscle nowadays has no revival treatments, and also transplantation is limited as an option. Tissue engineering has the potential to restore myocardial function after an MI by fabricating tailored tissues for treatment. For tissue engineering, three-dimensional (3D) bioprinting is a fabrication method to create 3D constructs with living cells, which would be impossible by other traditional methods. Although various biomaterials, biologically-derived or synthetic, are available, only…

3D Ti6Al4V-beta-tricalcium phosphate (TCP) hybrid scaffolds with interconnected porous network and controllable porosity and pore size were successfully produced by three-dimensional fiber deposition (3DF). The macrostructure of scaffolds was determined by the 3D design, whereas the micro- and submicron structure were derived from the Ti6Al4V powder sintering and the crystalline TCP powder, respectively. Ti6Al4V-TCP slurry was developed for 3DF by optimizing the TCP powder size, Ti6Al4V-to-TCP powder ratio and Ti6Al4V-TCP powder content. Moreover, the air pressure and fiber deposition rate were optimized. A maximum achievable ceramic content in the Ti6Al4V-TCP slurry that enables 3DF manufacturing was 10 wt%. The chemical…

Piezoelectric fluoropolymers convert mechanical energy to electricity and are ideal for sustainably providing power to electronic devices. To convert mechanical energy, a net polarization must be induced in the fluoropolymer, which is currently achieved via an energy intensive electrical poling process. Eliminating this process will enable the low-energy production of efficient energy harvesters. Here, by combining molecular dynamics simulations, piezoresponse force microscopy, and electrodynamic measurements, we reveal a hitherto unseen polarization locking phenomena of poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) perpendicular to the basal plane of two-dimensional (2D) Ti3C2Tx MXene nanosheets. This polarization locking, driven by strong electrostatic interactions enabled exceptional energy harvesting…

We report on a procedure for the preparation, printing and curing of antibacterial poly(N-isopropylacrylamide) nanocellulose-reinforced hydrogels. These composites present a highly anisotropic microstructure which allows to control and modulate the resulting mechanical properties. The incorporation of such nanoparticles enables us to modify both the strength and the humidity-dependent swelling direction of printed parts, offering a fourth-dimensional property to the resulting composite. Antibacterial properties of the hydrogels were obtained by incorporating the functionalized peptide ε-polylysine, modified with the addition of a methacrylate group to ensure UV-immobilization. We highlight the relevance of well-adapted viscoelastic properties of our material for 3D printing by…

Background It is known that a number of parameters can influence the post-printing properties of bone tissue scaffolds. Previous research has primarily focused on the effect of parameters associated with scaffold design (e.g., scaffold porosity) and specific scaffold printing processes (e.g., printing pressure). To our knowledge, no studies have investigated variations in post-printing properties attributed to the techniques used to synthesize the materials for printing (e.g., melt-blending, powder blending, liquid solvent, and solid solvent). Methods Four material preparation techniques were investigated to determine their influence on scaffold properties. Polycaprolactone/nano-hydroxyapatite 30% (wt.) materials were synthesized through melt-blending, powder blending, liquid solvent,…

Bone related diseases and disorders increasingly impact human health. Electrical stimulation (ES) has been shown to promote osteogenesis and healing of bone defects. Graphene, is an electrically conductive and biocompatible material with good mechanical properties (strength with flexibility), and therefore shows significant promise as a cell-compatible electrode for ES. Graphene-based scaffolds may therefore be used for 3D cell and tissue support, including 3D osteoinduction. We have fabricated 3D graphene electrode structures to provide ES to human adipose stem cells (ADSCs). The assemblies support ADSC growth and differentiation, with ES augmenting proliferation and osteogenesis. Our findings expand our previous work on…

3D bioprinting has been increasingly employed in skin tissue engineering for manufacturing living constructs with three-dimensional spatial precision and controlled architecture. There is however, a bottleneck in the tunability of bioinks to address specific biocompatibility challenges, functional traits and printability. Here we report on a traditional gelatin methacryloyl (GelMA) based bioink, tuned by addition of an ulvan type polysaccharide, isolated from a cultivated source of a specific Australian Ulvacean macroalgae (Ul84). Ul84 is a sulfate- and rhamnose-rich polysaccharide, resembling mammalian glycosaminoglycans that are involved in wound healing and tissue matrix structure and function. Printable bioinks were developed by addition of…

High molecular weight polyhydroxymethylene (PHM) has a repeat unit identical to that of low molecular weight sugar alcohols and exhibits carbohydrate‐like properties. Herein, cryogenic extrusion‐based 3D printing is combined with a phase separation in water to fabricate hierarchically porous PHM scaffolds containing interconnected macro‐, micro‐, and nanopores. As PHM is infusible and insoluble in common solvents, its precursor polyvinylene carbonate (PVCA) dissolved in dimethylsulfoxide (DMSO) is used to 3D print hierarchically porous PVCA scaffolds that are converted into PHM by hydrolysis without impairing the pore architectures. Similar to low‐temperature deposition manufacturing, the PVCA/DMSO freezes on a build platform at −78…

Designing bone scaffolds containing both organic and inorganic composites simulating the architecture of the bone is the most important principle in bone tissue engineering. The objective of this study was to fabricate a composite scaffold containing poly (D, l)-lactide (PDLLA) and β-tricalcium phosphate (β-TCP) as a platform for osteogenic differentiation of adipose-derived mesenchymal stem cells. In this study, PDLLA/β-TCP scaffolds were fabricated using three-dimensional printing (3D) technology through melt excursion technique. The physicomechanical characteristics, including microstructure, mechanical properties, of the customized scaffolds were investigated. Further, the in vitro biological characteristics of manufactured scaffolds were evaluated in conjugation with buccal fat…

Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three‐dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell‐free patient‐derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo‐like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front‐line chemotherapy drugs 5‐fluorouracil, doxorubicin and paclitaxel in comparison to traditional two‐dimensional cell cultures. The gene expression…

The major limitation of 3D bioprinting is the availability of inks. In order to develop new ink formulations, both their rheological behavior to obtain the best printability and the target bio-printed objects conformities must be studied. In this paper, for the first time in our knowledge, the preparation and the characterization of novel ink formulations based on two natural biocompatible polysaccharides, chitosan (CH) and guar gum (GG), are presented. Five ink formulations containing different proportions of CH and GG were prepared and characterized in terms of rheological properties and solvent evaporation. Their printability was assessed (by varying the nozzle diameter,…

Regenerative repair of craniomaxillofacial bone injuries is challenging due to both the large size and irregular shape of many defects. Mineralized collagen scaffolds have previously been shown to be a promising biomaterial implant to accelerate craniofacial bone regeneration in vivo. Here we describe inclusion of a 3D-printed polymer or ceramic-based mesh into a mineralized collagen scaffold to improve mechanical and biological activity. Mineralized collagen scaffolds were reinforced with 3D-printed Fluffy-PLG (ultraporous polylactide-co-glycolide co-polymer) or Hyperelastic Bone (90wt% calcium phosphate in PLG) meshes. We show degradation byproducts and acidic release from the printed structures have limited negative impact on the viability…

We previously developed a recombinant growth factor-free, three-dimensional (3D)-printed material comprising hydroxyapatite (HA) and demineralized bone matrix (DBM) for bone regeneration. This material has demonstrated the capacity to promote re-mineralization of the DBM particles within the scaffold struts and shows potential to promote successful spine fusion. Here, we investigate the role of geometry and architecture in osteointegration, vascularization, and facilitation of spine fusion in a preclinical model. Inks containing HA and DBM particles in a poly(lactide-co-glycolide) elastomer were 3D-printed into scaffolds with varying relative strut angles (90° vs. 45° advancing angle), macropore size (0 μm vs. 500 μm vs. 1000 μm), and strut…