3D Bioplotter Research Papers
Anti-infective efficacy, cytocompatibility and biocompatibility of a 3D-printed osteoconductive composite scaffold functionalized with quaternized chitosan
Contaminated or infected bone defects remain serious challenges in clinical trauma and orthopaedics, and a bone substitute with both osteoconductivity and antibacterial properties represents an improvement for treatment strategy. In this study, quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) was grafted to 3D-printed scaffolds composed of polylactide-co-glycolide (PLGA) and hydroxyapatite (HA), in order to design bone engineering scaffolds endowed with antibacterial and osteoconductive properties. We found that both the PLGA/HA/HACC and PLGA/HACC composite scaffolds decreased bacterial adhesion and biofilm formation under in vitro and in vivo conditions. Additionally, ATP leakage assay indicated that immobilizing HACC on the scaffolds could effectively…
A dual-crosslinking electroactive hydrogel based on gelatin methacrylate and dibenzaldehyde-terminated telechelic polyethylene glycol for 3D bio-printing
Gelatin was widely used as scaffold materials in 3D bio-printing due to its excellent bioactivity and availability and especially that their arginine–glycine–aspartic acid (RGD) sequences could efficiently promote cell adhesion and proliferation. In this study, an electroactive and 3D bio-printable hydrogel was prepared through a two-step chemical cross-linking process. Specifically, residual free amino groups of methacrylated gelatin (GelMA) were cross-linked with the aldehyde groups of dibenzaldehyde-terminated telechelic polyethylene glycol (DF-PEG) via Schiff base bonds, forming a gel at 37 °C. During the subsequent 3D bio-printing process, GelMA underwent UV curing, forming a secondary cross-linked network to the mechanical strength and stability…
Cucurbit[8]uril Mediated Supramolecular and Photocrosslinked Interpenetrating Network Hydrogel Matrices for 3D-Bioprinting
Printing of biologically functional constructs is significant for applications in tissue engineering and regenerative medicine. Designing bioinks remains remarkably challenging due to the multifaceted requirements in terms of the physical, chemical, and biochemical properties of the three-dimensional matrix, such as cytocompatibility, printability, and shape fidelity. In order to promote matrix and materials stiffness, while not sacrificing stress relaxation mechanisms which support cell spreading, migration, and differentiation, this work reports an interpenetrating network (IPN) bioink design. The approach makes use of a chemically defined network, combining physical and chemical crosslinking units with a tunable composition and network density, as well as…
Optimization of 3D Printing Parameters of Polylactic-Co-Glycolic Acid-Based Biodegradable Antibacterial Materials Using Fused Deposition Modeling
A high incidence of ureteral diseases was needed to find better treatments such as implanting ureteral stents. The existing ureteral stents produced a series of complications such as bacterial infection and biofilm after implantation. The fused deposition modeling (FDM) of 3D printing biodegradable antibacterial ureteral stents had gradually become the trend of clinical treatment. But it was necessary to optimize the FDM 3D printing parameters of biodegradable bacteriostatic materials to improve the precision and performance of manufacturing. In this study, polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), and nanosilver (AgNP) were mixed by the physical blending method, and the 3D printing parameters…
3D-printed porous functional composite scaffolds with polydopamine decoration for bone regeneration
Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately. 3D printing technology has attracted substantial attention for preparing penetrable multifunctional scaffolds to promote bone reconditioning and regeneration. Inspired by the spongy structure of natural bone, novel porous degradable scaffolds have been printed using polymerization of lactide and caprolactone (PLCL) and bioactive glass 45S5 (BG), and polydopamine (PDA) was used to decorate the PLCL/BG scaffolds. The physicochemical properties of the PLCL/BG and PLCL/BG/PDA scaffolds were measured, and their osteogenic and angiogenic effects were characterized through a series of experiments both in…
Enhanced bone regeneration by low-intensity pulsed ultrasound and lipid microbubbles on PLGA/TCP 3D-printed scaffolds
Background To investigate the effect of low-intensity pulsed ultrasound (LIPUS) combined with lipid microbubbles on the proliferation and bone regeneration of bone marrow mesenchymal stem cells (BMSCs) in poly (lactic-glycolic acid copolymer) (PLGA)/α-tricalcium phosphate (TCP) 3D-printed scaffolds. Methods BMSCs were irradiated with different LIPUS parameters and microbubble concentrations, and the best acoustic excitation parameters were selected. The expression of type I collagen and the activity of alkaline phosphatase were detected. Alizarin red staining was used to evaluate the calcium salt production during osteogenic differentiation. Results BMSCs proliferation was the most significant under the condition of 0.5% (v/v) lipid microbubble concentration,…
Crystal Growth of 3D Poly(ε-caprolactone) Based Bone Scaffolds and Its Effects on the Physical Properties and Cellular Interactions
Extrusion additive manufacturing is widely used to fabricate polymer-based 3D bone scaffolds. However, the insight views of crystal growths, scaffold features and eventually cell-scaffold interactions are still unknown. In this work, melt and solvent extrusion additive manufacturing techniques are used to produce scaffolds considering highly analogous printing conditions. Results show that the scaffolds produced by these two techniques present distinct physiochemical properties, with melt-printed scaffolds showing stronger mechanical properties and solvent-printed scaffolds showing rougher surface, higher degradation rate, and faster stress relaxation. These differences are attributed to the two different crystal growth kinetics, temperature-induced crystallization (TIC) and strain-induced crystallization (SIC),…
3D-printed high-density polyethylene scaffolds with bioactive and antibacterial layer-by-layer modification for auricle reconstruction
High-density polyethylene (HDPE) is a promising material for the development of scaffold implants for auricle reconstruction. However, preparing a personalized HDPE auricle implant with favorable bioactive and antibacterial functions to promote skin tissue ingrowth is challenging. Herein, we present 3D-printed HDPE auricle scaffolds with satisfactory pore size and connectivity. The layer-by-layer (LBL) approach was applied to achieve the improved bioactive and antibacterial properties of these 3D printed scaffolds. The HDPE auricle scaffolds were fabricated using an extrusion 3D printing approach, and the individualized macrostructure and porous microstructure were both adjusted by the 3D printing parameters. The polydopamine (pDA) coating method…
The effect of enhanced bone marrow in conjunction with 3D-printed PLA-HA in the repair of critical-sized bone defects in a rabbit model
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…
MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration
Bone defects remain a major threat to human health and bone tissue regeneration has become a prominent clinical demand worldwide. The combination of microRNA (miRNA) therapy with 3D printed scaffolds has always posed a challenge. It can mimic physiological bone healing processes, in which a biodegradable scaffold is gradually replaced by neo-tissue, and the sustained release of miRNA plays a vital role in creating an optimal osteogenic microenvironment, thus achieving promising bone repair outcomes. However, the balance between two key factors – scaffold degradation behavior and miRNA release profile – on osteogenesis and bone formation is still poorly understood. Herein,…
3D bioprinted multiscale composite scaffolds based on gelatin methacryloyl (GelMA)/chitosan microspheres as a modular bioink for enhancing 3D neurite outgrowth and elongation
The integration of multiscale micro- and macroenvironment has been demonstrated as a critical role in designing biomimetic scaffolds for peripheral nerve tissue regeneration. While it remains a remarkable challenge for developing a biomimetic multiscale scaffold for enhancing 3D neuronal maturation and outgrowth. Herein, we present a 3D bioprinted multiscale scaffold based on a modular bioink for integrating the 3D micro- and macroenvironment of native nerve tissue. Gelatin methacryloyl (GelMA)/Chitosan Microspheres (GC-MSs) were prepared by a microfluidic approach, and the effect of these microspheres on enhancing neurite outgrowth and elongation of PC12 cells was demonstrated. The 3D multiscale composite scaffolds were…
SnO2-Ag composites with high thermal cycling stability created by Ag infiltration of 3D ink-extruded SnO2 microlattices
SnO2-Ag composites with designed architectures with sub-millimeter feature sizes can provide enhanced functionality in electrical applications. SnO2-Ag composites consisting of a ceramic SnO2 micro-lattice filled with metallic Ag are created via a hybrid additive manufacturing method. The multistep process includes: (i) 3D extrusion printing of 0/90° cross-ply micro-lattices from SnO2-7%CuO nanoparticle-loaded ink; (ii) thermal treatment in air to burn the binders and sinter struts of the SnO2 micro-lattice to ~94% relative density; (iii) Ag melt infiltration of channels of sintered micro-lattices. Densification of the SnO2 struts during air-sintering is accelerated by CuO liquid phase forming at 1100°C. During the subsequent…
The effect of induced membranes combined with enhanced bone marrow and 3D PLA-HA on repairing long bone defects in vivo
The repair of large bone defects has always been a challenge, especially with respect to regeneration capacity and autogenous bone availability. To address this problem, we fabricated a 3D-printed polylactic acid (PLA) and hydroxyapatite (HA) scaffold (3D-printed PLA-HA, providing scaffold) loaded with enhanced bone marrow (eBM, providing seed cells) combined with induced membrane (IM, providing grow factors) to repair large radial defects in rabbits. in vitro assays, we demonstrated that 3D-printed PLA-HA had excellent biocompatibility, as shown by co-culturing with mesenchymal stem cells (MSCs); eBM-derived MSCs exhibited considerable differentiation potential, as shown in trilineage differentiation assays. To investigate bone formation…
The performance of 3D bioscaffolding based on a human periodontal ligament stem cell printing technique
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…
Development of a Photocrosslinkable Methacrylated Methylcellulose and Gelatin bioink for Cartilage Tissue Regeneration
Articular cartilage disease can cause pain, mobility issues, and disability. Clinical treatment includes microfracture, subchondral drilling, graft transplantation, and eventually total joint replacement implant. However, these approaches can present specific problems and limitations. Three-dimensional (3D) bioprinted scaffolds utilising hydrogels can provide a suitable 3D biochemical and biophysical environment, thus is a promising strategy for cartilage tissue therapy and regeneration. This study aims to develop a new hydrogel bioink with improved printability, mechanical, and biological properties for cartilage regeneration. A photocrosslinkable methacrylated methylcellulose (MCMA) and gelatin (GelMA) hybrid bioink is evaluated in this preliminary investigation. The results showed that methylcellulose and…
3D-printable self-healing and mechanically reinforced hydrogels with host–guest non-covalent interactions integrated into covalently linked networks
Natural polymer hydrogels are one of the best biomaterials for soft tissue repair because of their excellent biocompatibility, biodegradability and low immune rejection. However, they lack mechanical strength matching that of natural tissue and desired functionality (e.g., self-healing and 3D-printability). To solve these problems, we developed a host–guest supramolecule (HGSM) with three arms covalently crosslinked with a natural polymer to construct a novel hydrogel with non-covalent bonds integrated into a covalently crosslinked network. This unique structure enabled the hydrogel to exhibit improved mechanical properties and show both self-healing and 3D printing capabilities. The three-armed HGSM was first prepared via efficient…
3D Bioprinting of Breast Cancer Models for Drug Resistance Study
Adipose-derived mesenchymal stem/stromal cells (ADMSC) are one of the major stromal cells in the breast cancer microenvironment that promote cancer progression. Previous studies on the effects of ADMSC on breast cancer metastasis and drug resistance, using two-dimensional (2D) cultures, remained inconclusive. In the present study, we compared cocultured ADMSC and human epidermal receptor 2 positive breast primary breast cancer cells (21PT) in 2D and three-dimensional (3D) cultures and then examined their response to doxorubicin (DOX). We examined 3D bioprinted constructs with breast cancer cells in the middle and ADMSC in the edge region, which were made by using dual hydrogel-based…
Prevascularization of 3D printed bone scaffolds by bioactive hydrogels and cell co-culture
Vascularization is a fundamental prerequisite for large bone construct development and remains one of the main challenges of bone tissue engineering. Our current study presents the combination of 3D printing technique with a hydrogel-based prevascularization strategy to generate prevascularized bone constructs. Human adipose derived mesenchymal stem cells (ADMSC) and human umbilical vein endothelial cells (HUVEC) were encapsulated within our bioactive hydrogels, and the effects of culture conditions on in vitro vascularization were determined. We further generated composite constructs by forming 3D printed polycaprolactone/hydroxyapatite scaffolds coated with cell-laden hydrogels and determined how the co-culture affected vascularization and osteogenesis. It was demonstrated…
Short-term hypoxic preconditioning promotes prevascularization in 3D bioprinted bone constructs with stromal vascular fraction derived cells
Reconstruction of complex, craniofacial bone defects often requires autogenous vascularized bone grafts, and still remains a challenge today. In order to address this issue, we isolated the stromal vascular fraction (SVF) from adipose tissues and maintained the phenotypes and the growth of endothelial lineage cells within SVF derived cells (SVFC) by incorporating an endothelial cell medium. We 3D bioprinted SVFC within our hydrogel bioinks and conditioned the constructs in either normoxia or hypoxia. We found that short-term hypoxic conditioning promoted vascularization-related gene expression, whereas long-term hypoxia impaired cell viability and vascularization. 3D bioprinted bone constructs composed of polycaprolactone/hydroxyapatite (PCL/HAp) and…
Osteogenic Differentiation of Three-Dimensional Bioprinted Constructs Consisting of Human Adipose-Derived Stem Cells In Vitro and In Vivo
Here, we aimed to investigate osteogenic differentiation of human adipose-derived stem cells (hASCs) in three-dimensional (3D) bioprinted tissue constructs in vitro and in vivo. A 3D Bio-plotter dispensing system was used for building 3D constructs. Cell viability was determined using live/dead cell staining. After 7 and 14 days of culture, real-time quantitative polymerase chain reaction (PCR) was performed to analyze the expression of osteogenesis-related genes (RUNX2, OSX, and OCN). Western blotting for RUNX2 and immunofluorescent staining for OCN and RUNX2 were also performed. At 8 weeks after surgery, osteoids secreted by osteogenically differentiated cells were assessed by hematoxylin-eosin (H&E) staining,…
3D Bioplotting of Gelatin/Alginate Scaffolds for Tissue Engineering: Influence of Crosslinking Degree and Pore Architecture on Physicochemical Properties
Gelatin/Alginate hydrogels were engineered for bioplotting in tissue engineering. One major drawback of hydrogel scaffolds is the lack of adequate mechanical properties. In this study, using a bioplotter, we constructed the scaffolds with different pore architectures by deposition of gelatin/alginate hydrogels layer-by-layer. The scaffolds with different crosslinking degree were obtained by post-crosslinking methods. Their physicochemical properties, as well as cell viability, were assessed. Different crosslinking methods had little influence on scaffold architecture, porosity, pore size and distribution. By contrast, the water absorption ability, degradation rate and mechanical properties of the scaffolds were dramatically affected by treatment with various concentrations of…