3D Bioplotter Research Papers
Influence of surface engineering on 3D printed Ti lattice structure towards enhanced tissue integration: An in vitro and in vivo study
Reconstruction of segmental defects are popularly approached with surface engineered additively manufactured scaffolds owing to its enhanced post-surgery tissue integration properties. The present work is aimed at fabrication of Ti lattice structures using 3D printing, with a novel approach of silane chemistry-based surface modification of those Ti-surfaces with osteogenic peptides (OGP). The lattice structures with 0.6 mm strut-diameter having 0.5 mm inter-strut distance were chosen for fabrication using an extrusion-based 3D printing. Based on the evidence, it could be concluded that extrusion-based 3D printing is an optimal alternative as compared to those high cost incurring additive manufacturing processes. Therefore, OGP…
Fabrication of chitosan/alginate/hydroxyapatite hybrid scaffolds using 3D printing and impregnating techniques for potential cartilage regeneration
Three-dimensional (3D) printed hydrogel scaffolds enhanced with ceramics have shown potential applications for cartilage regeneration, but leaving biological and mechanical properties to be desired. This paper presents our study on the development of chitosan /alginate scaffolds with nano hydroxyapatite (nHA) by combining 3D printing and impregnating techniques, forming a hybrid, yet novel, structure of scaffolds for potential cartilage regeneration. First, we incorporated nHA into chitosan scaffold printing and studied the printability by examining the difference between the printed scaffolds and their designs. Then, we impregnated alginate with nHA into the printed chitosan scaffolds to forming a hybrid structure of scaffolds;…
Pattern-driven 4D printing
Self-bending actuators have time and cost reduction benefits for applications like self-assembly and self-deployable structures. Three-dimensional (3D) printing is a promising rapid and accurate manufacturing method for controlling spatial self-bending actuation in custom-designed soft structures. This paper studies the features merely imparted by 3D printing fabrication in control of self-folding actuators. It is shown that 3D printing control parameters such as different spatial patterns of hinges affect the response time and bending angle of the actuator. A polystyrene (PS) pane as a representative of thermo-responsive shape memory polymers is used as the main material for being remotely stimulated via light…
3D printing of gelatin/chitosan biodegradable hybrid hydrogel: Critical issues due to the crosslinking reaction, degradation phenomena and process parameters
Hydrogel materials are being investigated for application as scaffolds in tissue engineering owing to their many advantages, such as high water content, softness and flexibility similar to many soft tissues, tuneable physical, chemical, and biological properties, excellent biocompatibility and biodegradability, and extensive framework for cell proliferation and survival. During the past decade, because of the great versatility offered in terms of processing approach, material selection, and customization, 3D printing has become a leading technology used to fabricate hydrogel scaffolds. Furthermore, high reproducibility and unparalleled control over structural and compositional characteristics make additive manufacturing the preferred technology for the fabrication of…
4D Printing Classroom in Modern Interactive Learning Environments
The emergence of four-dimensional (4D) printing and bioprinting in additive manufacturing (AM), which require knowledge of multi-physics, chemistry, and engineering skills, are bringing many engineering applications in biomedical devices, wearables, and robotics. This newly emerging technology has become a feasible commercial proposition because of lower costs, more design freedom, and more rapid production methods. This serves as a significant multidisciplinary research and training platform for both academia and the professional world. This work aims at enhancing researchers’ interest, knowledge, and skills in the emerging field of 4D printing and bioprinting. A greater knowledge of 4D printing and promotion of its…
Taking 4D Bio/Printing To Classroom
The emergence of four-dimensional (4D) printing in additive manufacturing (AM), which requires knowledge in multi-physics, chemistry, and engineering skills, is bringing many applications in biomedical, robotics, aerospace, and food industries. The increased usage of AM technology and smart materials in industry means that companies are seeking to develop and manage production system for academics with the multidisciplinary abilities and knowledge. This enables a high interdisciplinary platform for research and project modules suitable to be used in the academic environment for hands-on students training. This paper proposed an easy to implement and follow 4D bio/printing module well designed for students and…
Solvent Mediating the in Situ Self-Assembly of Polysaccharides for 3D Printing Biomimetic Tissue Scaffolds
Intensively studied 3D printing technology is frequently hindered by the effective printable ink preparation method. Herein, we propose an elegant and gentle solvent consumption strategy to slowly disrupt the thermodynamic stability of the biopolymer (polysaccharide: cellulose, chitin, and chitosan) solution to slightly induce the molecule chains to in situ self-assemble into nanostructures for regulating the rheological properties, eventually achieving the acceptable printability. The polysaccharides are dissolved in the alkali/urea solvent. The weak Lewis acid fumed silica (as solvent mediator) is used to (i) slowly and partially consume the alkali/urea solvent to induce the polysaccharide chains to self-assemble into nanofibers to…
Extrusion-based printing of chitosan scaffolds and their in vitro characterization for cartilage tissue engineering
Researchers have looked to cartilage tissue engineering to address the lack of cartilage regenerative capability related to cartilage disease/trauma. For this, a promising approach is extrusion-based three-dimensional (3D) printing technique to deliver cells, biomaterials, and growth factors within a scaffold to the injured site. This paper evaluates the printability of chitosan scaffolds for a cartilage tissue engineering, with a focus on identifying the influence of drying technique implemented before crosslinking on the improvement of chitosan printability. First, the printability of chitosan with concentrations of 8%, 10%, and 12% (w/v) was evaluated and 10% chitosan was selected for further studies. Then,…
Hierarchical patterning via dynamic sacrificial printing of stimuli-responsive hydrogels
Inspired by stimuli-tailored dynamic processes that spatiotemporally create structural and functional diversity in biology, a new hierarchical patterning strategy is proposed to induce the emergence of complex multidimensional structures via dynamic sacrificial printing of stimuli-responsive hydrogels. Using thermally responsive gelatin (Gel) and pH-responsive chitosan (Chit) as proof-of-concept materials, we demonstrate that the initially printed sacrificial material (Gel/Chit-H+ hydrogel with a single gelatin network) can be converted dynamically into non-sacrificial material (Gel/Chit-H+–Citr hydrogel with gelatin and an electrostatic citrate–chitosan dual network) under stimulus cues (citrate ions). Complex hierarchical structures and functions can be created by controlling either the printing patterns of…
Development of novel chitosan / guar gum inks for extrusion-based 3D bioprinting: Process, printability and properties
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,…
Topology-Optimized 4D Printing of a Soft Actuator
Soft robots and actuators are emerging devices providing more capabilities in the field of robotics. More flexibility and compliance attributing to soft functional materials used in the fabrication of these devices make them ideal for delivering delicate tasks in fragile environments, such as food and biomedical sectors. Yet, the intuitive nonlinearity of soft functional materials and their anisotropic actuation in compliant mechanisms constitute an existent challenge in improving their performance. Topology optimization (TO) along with four-dimensional (4D) printing is a powerful digital tool that can be used to obtain optimal internal architectures for the efficient performance of porous soft actuators.…
Fabrication of a conductive composite structure with enhanced stretchability using direct-write 3D printing
High stretchability and mechanical stability are the key properties of a conductive polymer composite structure. In this work, an anisotropic composite is fabricated by wet 3D printing of epoxy crosslinked chitosan/carbon microtubes. The carbon microtubes were synthesized through a high temperature carbonization of chemically purified cellulose fibres. After the chemical treatment and high temperature carbonization, the removal amorphous substrates from the core of cotton fibres results in the formation of a tubular structure. Here, chitosan which is an abundant natural polymer was used as the composite matrix. It was found that the epoxy crosslinking increases the stretchability of composite filaments.
System identification and robust tracking of a 3D printed soft actuator
Current three-dimensional (3D) printing allows for the fabrication of controllable 3D printed soft actuators with growing applications in soft robotics, like cell manipulation and drug delivery. Therefore, a precise and computationally efficient control algorithm for robust trajectory tracking of the 3D printed soft actuators has become important. The results of the primary model of the soft actuator deviated from experimental results due to uncertainties such as time-varying characteristics of the actuator. Hence, a second-order type nonsingular terminal sliding mode controller (NTSMC) for robust stabilization and trajectory tracking of the 3D printed actuator is proposed. It is shown via experiments that…
Silk particles, microfibres and nanofibres: A comparative study of their functions in 3D printing hydrogel scaffolds
Silk, with highly crystalline structure and well-documented biocompatibility, is promising to be used as reinforcing material and build functionalized composite scaffolds. In the present study, we developed chitosan/silk composite scaffolds using silk particles, silk microfibres and nanofibres via 3D printing method. The three forms of silk fillers with varied shapes and dimensions were obtained via different processing methods and evaluated of their morphology, crystalline structure and thermal property. All silk fillers showed different degrees of improvement on printability in terms of ink rheology and printing shape fidelity. Different silk fillers led to different scaffold surface morphology and different roughness, while…
Wet 3‐D printing of epoxy cross‐linked chitosan/carbon microtube composite
Over the last decays, the use of conductive biopolymer composites has been growing in areas such as biosensors, soft robotics, and wound dressing applications. They are generally soft hydrophilic materials with good elastic recovery and compatible with biological environments. However, their application and removal from the host are still challenging mainly due to poor mechanical strength. This work displays a technique for the fabrication of complex‐shaped conductive structures with improved mechanical strength by wet three‐dimensional (3‐D) printing, which uses a coagulation bath to quickly solidify an epoxy cross‐linked chitosan/carbon microtube composite ink. The fabricated conductive structure demonstrated higher elongation strength…
Nanogrooved carbon microtubes for wet 3D printing of conductive composite structures
Recent advances in 3D printing have enabled the fabrication of interesting structures which were not achievable using traditional fabrication approaches. 3D printing of carbon microtube composite inks allows fabrication of conductive structures for practical applications in soft robotics and tissue engineering. However, it is challenging to achieve 3D printed structures from solution‐based composite inks which requires an additional process to solidify the ink. Here, we introduce a wet 3D printing technique which uses a coagulation bath to fabricate carbon microtube composite structures. We show that through facile nanogrooving approach which introduces cavitation and channels on carbon microtubes, enhanced interfacial interactions…
Bending Control of a 3D Printed Polyelectrolyte Soft Actuator with Uncertain Model
Introduction of 3-dimensional (3D) printing in fabrication and increasing applications of intriguing products in soft robotics have led to studies on controllable 3D printed soft actuators. Therefore, a demand for a precise and computationally efficient model for bending control of the 3D printed soft actuators has arisen. This study initially used a grey box strategy for dynamic modeling of a 3D printed soft actuator which undergoes large bending deformations. Yet, the primary model estimated results deviated from experimental results due to uncertainties such as hysteresis and time varying characteristics of the soft actuator in presence of electric field. Thus, a…
Rigid elements dynamics modeling of a 3D printed soft actuator
Due to the growing interest in three-dimensional (3D) printed soft actuators, the establishment of an appropriate mathematical model that could effectively predict the actuators’ dynamic behavior has become necessary. This study presents the development of an effective modeling strategy for the dynamic analysis of a 3D printed polyelectrolyte actuator undergoing large bending deformations. The proposed model is composed of two parts, namely electrical and mechanical dynamic models. The electrical model describes the actuator as a gray box model, whereas the mechanical model relates the stored charges to the bending displacement through considering the printed actuator as a discretized system connected…
3D printed soft parallel actuator
This paper presents a 3-dimensional (3D) printed soft parallel contactless actuator for the first time. The actuator involves an electro-responsive parallel mechanism made of two segments namely active chain and passive chain both 3D printed. The active chain is attached to the ground from one end and constitutes two actuator links made of responsive hydrogel. The passive chain, on the other hand, is attached to the active chain from one end and consists of two rigid links made of polymer. The actuator links are printed using an extrusion-based 3D-Bioplotter with polyelectrolyte hydrogel as printer ink. The rigid links are also…
Polyelectrolyte Soft Actuators: 3D Printed Chitosan and Cast Gelatin
With increasing utilization of robots in daily tasks, especially in biomedical and environmental monitoring applications, there would be demands for soft, biodegradable, or even edible actuators that provide more versatility than conventional rigid materials (e.g., metals and plastics). Polyelectrolyte hydrogels produce mechanical motion in response to electrical stimulus, making them good candidates for implementation of soft actuators. However, their conventional fabrication process has so far hindered their applicability in a broad range of controlled folding behaviors. A novel application of 3D printing in biodegradable and biocompatible soft robots is presented in this study. It is observed that the contactless electroactive…
3D Printing of Silk Particle-Reinforced Chitosan Hydrogel Structures and Their Properties
Hydrogel bioprinting is a major area of focus in the field of tissue engineering. However, 3D printed hydrogel scaffolds often suffer from low printing accuracy and poor mechanical properties because of their soft nature and tendency to shrink. This makes it challenging to process them into structural materials. In this study, natural chitosan hydrogel scaffolds were, for the first time, reinforced with milled silk particles and fabricated by 3D printing. Compared with pure chitosan scaffolds, the addition of silk particles resulted in up to a 5-fold increase in compressive modulus as well as significantly better printing accuracy and improved scaffold…
Surface nanogrooving of carbon microtubes
Extrusion processing of carbon tubes can be problematic due to their poor interfacial interactions with polymeric matrices. Surface chemical modification of carbon tubes can be utilized to create bonding sites to form networks with polymer chains. However, chemical reactions resulting in intermolecular primary bonding limit processability of extrudate, since they cause unstable rheological behaviour, and thus decrease the stock holding time, which is determinative in extrusion. This study presents a method for the synthesis of carbon microtubes with physically modified surface area to improve the filler and matrix interfacial interactions. The key concept is the formation of a nanogrooved topography,…
Engineering Human Neural Tissue by 3D Bioprinting
Bioprinting provides an opportunity to produce three-dimensional (3D) tissues for biomedical research and translational drug discovery, toxicology, and tissue replacement. Here we describe a method for fabricating human neural tissue by 3D printing human neural stem cells with a bioink, and subsequent gelation of the bioink for cell encapsulation, support, and differentiation to functional neurons and supporting neuroglia. The bioink uniquely comprises the polysaccharides alginate, water-soluble carboxymethyl-chitosan, and agarose. Importantly, the method could be adapted to fabricate neural and nonneural tissues from other cell types, with the potential to be applied for both research and clinical product development.
Iterative feedback bio-printingderived cell-laden hydrogel scaffolds with optimal geometrical fidelity and cellular controllability
For three-dimensional bio-printed cell-laden hydrogel tissue constructs, the well-designed internal porous geometry is tailored to obtain the desired structural and cellular properties. However, significant differences often exist between the designed and as-printed scaffolds because of the inherent characteristics of hydrogels and cells. In this study, an iterative feedback bio-printing (IFBP) approach based on optical coherence tomography (OCT) for the fabrication of cell-laden hydrogel scaffolds with optimal geometrical fidelity and cellular controllability was proposed. A custom-made swept-source OCT (SS-OCT) system was applied to characterize the printed scaffolds quantitatively. Based on the obtained empirical linear formula from the first experimental feedback loop,…
Rheological, In Situ Printability and Cell Viability Analysis of Hydrogels for Muscle Tissue Regeneration
Advancements in additive manufacturing have made it possible to fabricate biologically relevant architectures from a wide variety of materials. Hydrogels have garnered increased attention for the fabrication of muscle tissue engineering constructs due to their resemblance to living tissue and ability to function as cell carriers. However, there is a lack of systematic approaches to screen bioinks based on their inherent properties, such as rheology, printability and cell viability. Furthermore, this study takes the critical first-step for connecting in-process sensor data with construct quality by studying the influence of printing parameters. Alginate-chitosan hydrogels were synthesized and subjected to a systematic…
Development and Analysis of a 3D Printed Hydrogel Soft Actuator
Polyelectrolyte hydrogels produce mechanical motion in response to electrical stimulus making them a good candidate for implementation of soft actuators. However, their customary fabrication process has thus far hindered their applicability in a broad range of controlled folding behaviours. This paper employs the 3D printing technology does the development of polyelectrolyte hydrogel soft actuators. A 3D printed soft hydrogel actuator with contactless electrodes is presented for the first time. Initially chitosan as a candidate of polyelectrolytes which possess both printability and stimuli responsive is opted for ink preparation of 3D printing. The printing parameters are optimised for fabrication of desired…
3D Printing of a Photo-thermal Self-folding Actuator
The demand for rapid and accurate fabrication of light-weight, biocompatible, and soft actuators in soft robotics has perused researchers to design and fabricate such products by rapid manufacturing techniques. The self-folding origami structure is a type of soft actuator that has applications in micro electro mechanical systems, soft electronics, and biomedical devices. 3-dimentional (3D) printing is a current manufacturing process that can be used for fabrication of involute soft self-folding products by means of shape memory polymer materials. This paper presents, for the first time, a method for developing a photo thermal self-folding soft actuator using a 3D bioplotter. Easily…
A new printable and durable N,O-carboxymethyl chitosan–Ca2+–polyphosphate complex with morphogenetic activity
Biomimetic materials have been gaining increasing importance in tissue engineering since they may provide regenerative alternatives to the use of autologous tissues for transplantation. In the present study, we applied for bioprinting of a functionalized three-dimensional template, N,O-carboxymethyl chitosan (N,O-CMC), mimicking the physiological extracellular matrix. This polymer, widely used in tissue engineering, has been provided with functional activity by integration of polyphosphate (polyP), an osteogenically acting natural polymer. The two polymers, N,O-CMC and polyP, are linked together via Ca2+ bridges. This N,O-CMC + polyP material was proven to be printable and durable. The N,O-CMC + polyP printed layers and tissue…
Modular Small Diameter Vascular Grafts with Bioactive Functionalities
We report the fabrication of a novel type of artificial small diameter blood vessels, termed biomimetic tissue-engineered blood vessels (bTEBV), with a modular composition. They are composed of a hydrogel scaffold consisting of two negatively charged natural polymers, alginate and a modified chitosan, N,O-carboxymethyl chitosan (N,O-CMC). Into this biologically inert scaffold two biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP) and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly-Asp (RGD). These materials can be hardened by exposure to Ca2+ through formation of Ca2+ bridges between the polyanions, alginate, N,O-CMC, and polyP (alginate-Ca2+-N,O-CMC-polyP). The bTEBV are formed…
Bone repair by cell-seeded 3D-bioplotted composite scaffolds made of collagen treated tricalciumphosphate or tricalciumphosphate-chitosan-collagen hydrogel or PLGA in ovine critical-sized calvarial defects
The aim of this study was to investigate the osteogenic effect of three different cell-seeded 3D-bioplotted scaffolds in a ovine calvarial critical-size defect model. The choice of scaffold-materials was based on their applicability for 3D-bioplotting and respective possibility to produce tailor-made scaffolds for the use in cranio-facial surgery for the replacement of complex shaped boneparts. Scaffold raw-materials are known to be osteoinductive when being cell-seeded [poly(L-lactide-co-glycolide) (PLGA)] or having components with osteoinductive properties as tricalciumphosphate (TCP) or collagen (Col) or chitosan. The scaffold-materials PLGA, TCP/Col, and HYDR (TCP/Col/chitosan) were cell-seeded with osteoblast-like cells whether gained from bone (OLB) or from…
Angiogenic and inflammatory response to biodegradable scaffolds in dorsal skinfold chambers of mice
For tissue engineering, scaffolds should be biocompatible and promote neovascularization. Because little is known on those specific properties, we herein studied in vivo the host angiogenic and inflammatory response after implantation of commonly used scaffold materials. Porous poly(l-lactide-co-glycolide) (PLGA) and collagen–chitosan–hydroxyapatite hydrogel scaffolds were implanted into dorsal skinfold chambers of balb/c mice. Additional animals received cortical bone as an isogeneic, biological implant, while chambers of animals without implants served as controls. Angiogenesis and neovascularization as well as leukocyte–endothelial cell interaction and microvascular permeability were analyzed over 14 day using intravital fluorescence microscopy. PLGA scaffolds showed a slight increase in leukocyte…
Fabrication of soft and hard biocompatible scaffolds using 3D-Bioplotting
In Tissue Engineering and bone reconstruction, alongside the choice of materials, the scaffold design is of great importance. Three dimensional structures not only permit the tuning of chemical and mechanical properties, but they can also copy the outer form of the required bone or cartilaginous structures. While new processes that create such 3D scaffolds by means of Rapid Prototyping have been developed, they are still restricted to a limited type of materials. At the Freiburger Materialforschungszentrum, our group has developed a new process called 3D BioplottingTM. Most kinds of polymers and biopolymers can be used for the fabrication of 3D…