3D Bioplotter Research Papers
Dual-functional 3D-printed composite scaffold for inhibiting bacterial infection and promoting bone regeneration in infected bone defect models
Infection is one of the pivotal causes of nonunion in large bone defect after trauma or tumor resection. Three-dimensional (3D) composite scaffold with multifunctional-therapeutic properties offer many advantages over allogenic or xenogenic bone grafting for the restoration of challenging infected bone defects. In the previous study, we demonstrated that quaternized chitosan (HACC)-grafted polylactide-co-glycolide (PLGA)/hydroxyapatite (HA) scaffold (PLGA/HA/HACC) via 3D-printing technique exhibited significantly improved antimicrobial and osteoconductive property in vitro, together with good biocompatibility in vivo. Hence, the present study further investigated whether such an innovative bone substitute could effectively inhibit the bacterial biofilm formation and promote bone regeneration in vivo.…
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…
Customization of an Ultrafast Thiol–Norbornene Photo-Cross-Linkable Hyaluronic Acid–Gelatin Bioink for Extrusion-Based 3D Bioprinting
Light-based three-dimensional (3D) bioprinting has been widely studied in tissue engineering. Despite the fact that free-radical chain polymerization-based bioinks like hyaluronic acid methacrylate (HAMA) and gelatin methacryloyl (GelMA) have been extensively explored in 3D bioprinting, the thiol–ene hydrogel system has attracted increasing attention for its ability in building hydrogel scaffolds in an oxygen-tolerant and cell-friendly way. Herein, we report a superfast curing thiol–ene bioink composed of norbornene-modified hyaluronic acid (NorHA) and thiolated gelatin (GelSH) for 3D bioprinting. A new facile approach was first introduced in the synthesis of NorHA, which circumvented the cumbersome steps involved in previous works. Additionally, after…
Osteosarcoma progression in biomimetic matrix with different stiffness: Insights from a three-dimensional printed gelatin methacrylamide hydrogel
Recent studies on osteosarcoma and matrix stiffness are still mostly performed in a 2D setting, which is distinct from in vivo conditions. Therefore, the results from the 2D models may not reflect the real effect of matrix stiffness on cell phenotype. Here, we employed a 3D bioprinted osteosarcoma model, to study the effect of matrix stiffness on osteosarcoma cells. Through density adjustment of GelMA, we constructed three osteosarcoma models with distinct matrix stiffnesses of 50, 80, and 130 kPa. In this study, we found that osteosarcoma cells proliferated faster, migrated more actively, had a more stretched morphology, and a lower…
Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma
Current in vitro models for osteosarcoma investigation and drug screening, including two-dimensional (2D) cell culture and tumour spheroids (i.e. cancer stem-like cells), lack extracellular matrix (ECM). Therefore, results from traditional models may not reflect real pathological processes in genuine osteosarcoma histological structures. Here, we report a three-dimensional (3D) bioprinted osteosarcoma model (3DBPO) that contains osteosarcoma cells and shrouding ECM analogue in a 3D frame. Photo-crosslinkable bioinks composed of gelatine methacrylamide and hyaluronic acid methacrylate mimicked tumour ECM. We performed multi-omics analysis, including transcriptomics and DNA methylomics, to determine differences between the 3DBPO model and traditional models. Compared with 2D models…
Solvent evaporation induced fabrication of porous polycaprolactone scaffold via low-temperature 3D printing for regeneration medicine researches
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…
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…
Bioprinting of an osteocyte network for biomimetic mineralization
Osteocytes, essential regulators of bone homeostasis, are embedded in the mineralized bone matrix. Given the spatial arrangement of osteocytes, bioprinting represents an ideal method to biofabricate a 3D osteocyte network with a suitable surrounding matrix similar to native bone tissue. Here, we reported a 3D bioprinted osteocyte-laden hydrogel for biomimetic mineralization in vitro with exceptional shape fidelity, a high cell density (107 cells per ml) and high cell viability (85–90%). The bioinks were composed of biomimetic modified biopolymers, namely, gelatine methacrylamide (GelMA) and hyaluronic acid methacrylate (HAMA), with or without type I collagen. The osteocyte-laden constructs were printed and cultured…
Three-dimensional printed multiphasic scaffolds with stratified cell-laden gelatin methacrylate hydrogels for biomimetic tendon-to-bone interface engineering
Background The anatomical properties of the enthesis of the rotator cuff are hardly regained during the process of healing. The tendon-to-bone interface is normally replaced by fibrovascular tissue instead of interposition fibrocartilage, which impairs biomechanics in the shoulder and causes dysfunction. Tissue engineering offers a promising strategy to regenerate a biomimetic interface. Here, we report heterogeneous tendon-to-bone interface engineering based on a 3D-printed multiphasic scaffold. Methods A multiphasic poly(ε-caprolactone) (PCL)–PCL/tricalcium phosphate–PCL/tricalcium phosphate porous scaffold was manufactured using 3D printing technology. The three phases of the scaffold were designed to mimic the graded tissue regions in the tendon-to-bone interface—tendon, fibrocartilage, and…