3D Bioplotter Research Papers

Despite recent advances in extrusion bioprinting of cell-laden hydrogels, using naturally derived bioinks to biofabricate complex elastic tissues with both satisfying biological functionalities and superior mechanical properties is hitherto an unmet challenge. Here, we address this challenge with precisely designed biological tough hydrogel bioinks featuring a double-network structure. The tough hydrogels consisted of energy-dissipative dynamically crosslinked glycosaminoglycan hyaluronic acid (o-nitrobenzyl-grafted hyaluronic acid) and elastin through Schiff’s base reaction, and free-radically polymerized gelatin methacryloyl. The incorporation of elastin further improved the elasticity, stretchability (∼170% strain), and toughness (∼45 kJ m−3) of the hydrogels due to the random coiling structure. We used this novel…

Flexible and highly filled piezoelectric nanogenerators with excellent performance play an indispensable role in portable electronic devices, while the bottlenecks are hard to improve the polarization efficiency and prepare three-dimensional (3D) amplifying effect structure. Compared with other typical 3D printing technologies, direct ink writing multi-material printing (DIW-M3D), can extrude multiple viscoelastic ink materials with a wide selection of materials, which has the advantage of integrated multi-material processing. However, there are fewer reports on the use of DIW-M3D technology to print functional composite materials. Inspired from Lego block structures, we utilized DIW-M3D technology to prepare fabrications with alternating arrangements of piezoelectric…

Three-dimensional (3D) bioprinting has brought new promising strategies for the regeneration of cartilage with specific shapes. In cartilage bioprinting, chondrocyte-laden hydrogels are the most commonly used bioinks. However, the dispersion of cells and the dense texture of the hydrogel in the conventional bioink may limit cell–cell/ cell–extracellular matrix (ECM) interactions, counting against cartilage regeneration and maturation. To address this issue, in this study, we developed a functional bioink for cartilage bioprinting based on chondrocyte spheroids (CSs) and microporous hydrogels, in which CSs as multicellular aggregates can provide extensive cell– cell/cell–ECM interactions to mimic the natural cartilage microenvironment, and microporous hydrogels…

Decellularized extracellular matrix hydrogel (dECM-G) has demonstrated its significant tissue-specificity, high biocompatibility, and versatile utilities in tissue engineering. However, the low mechanical stability and fast degradation are major drawbacks for its application in three-dimensional (3D) printing. Herein, we report a hybrid hydrogel system consisting of dECM-Gs and photocrosslinkable gelatin methacrylate (GelMA), which resulted in significantly improved printability and structural fidelity. These premixed hydrogels retained high bioactivity and tissue-specificity due to their containing dECM-Gs. More specifically, it was realized that the hydrogel containing dECM-G derived from porcine peripheral nerves (GelMA/pDNM-G) effectively facilitated neurite growth and Schwann cell migration from two-dimensional cultured…

Tissue engineering provides a promising strategy for auricular reconstruction. Although the first international clinical breakthrough of tissue-engineered auricular reconstruction has been realized based on polymer scaffolds, this approach has not been recognized as a clinically available treatment because of its unsatisfactory clinical efficacy. This is mainly since reconstruction constructs easily cause inflammation and deformation. In this study, we present a novel strategy for the development of biological auricle equivalents with precise shapes, low immunogenicity, and excellent mechanics using auricular chondrocytes and a bioactive bioink based on biomimetic microporous methacrylate-modified acellular cartilage matrix (ACMMA) with the assistance of gelatin methacrylate (GelMA),…

Extrusion-based bioprinting is an emerging and most frequently used technique for the fabrication of cell-laden constructs. A suitable hydrogel-based bioink for cell encapsulation and protection is critical for printability, structural stability, and post-printing cell viability. The thiol–ene chemistry-based gelatin-norbornene (GelNB) hydrogels have drawn much attention as a promising substitution of gelatin methacryloyl (GelMA), owing to the fast and controllable step-growth polymerization mechanism, as well as a significant reduction in reactive oxygen species (ROS) accumulation. Herein, thiolated heparin (HepSH) was synthesized and used as a macromolecular crosslinker for GelNB-based bioprinting, so that GelNB gelation became less sensitive to the thiol/ene ratio.…

Advances in 3D bioprinting allows not only controlled deposition of cells or cell-laden hydrogels but also flexibility in creating constructs that match the anatomical features of the patient. This is especially the case for reconstructing the pinna (ear), which is a large feature of the face and made from elastic cartilage that primarily relies on diffusion for nutrient transfer. The selection of cell lines for reconstructing this cartilage becomes a crucial step in clinical translation. Chondrocytes and mesenchymal stem cells are both studied extensively in the area of cartilage regeneration as they are capable of producing cartilage in vitro. However,…

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…

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…

Injury of corpus cavernosa results in erectile dysfunction, but its treatment has been very difficult. Here we construct heparin-coated 3D-printed hydrogel scaffolds seeded with hypoxia inducible factor-1α (HIF-1α)-mutated muscle-derived stem cells (MDSCs) to develop bioengineered vascularized corpora. HIF-1α-mutated MDSCs significantly secrete various angiogenic factors in MDSCs regardless of hypoxia or normoxia. The biodegradable scaffolds, along with MDSCs, are implanted into corpus cavernosa defects in a rabbit model to show good histocompatibility with no immunological rejection, support vascularized tissue ingrowth, and promote neovascularisation to repair the defects. Evaluation of morphology, intracavernosal pressure, elasticity and shrinkage of repaired cavernous tissue prove that…

Engineering substantia propria (or stroma of cornea) that mimics the function and anatomy of natural tissue is vital for in vitro modelling and in vivo regeneration. There are, however, few examples of bioengineered biomimetic corneal stroma. Here we describe the construction of an orthogonally oriented 3D corneal stroma model (3D-CSM) using pure electro-compacted collagen (EC). EC films comprise aligned collagen fibrils and support primary human corneal stromal cells (hCSCs). Cell-laden constructs are analogous to the anatomical structure of native human cornea. The hCSCs are guided by the topographical cues provided by the aligned collagen fibrils of the EC films. Importantly,…

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…

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…

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…

Vascularization of engineered bone tissue is critical for ensuring its survival after implantation. In vitro pre-vascularization of bone grafts with endothelial cells is a promising strategy to improve implant survival. In this study, we pre-cultured human smooth muscle cells (hSMCs) on bone scaffolds for 3 weeks followed by seeding of human umbilical vein endothelial cells (HUVECs), which produced a desirable environment for microvasculature formation. The sequential cell-seeding protocol was successfully applied to both natural (decellularized native bone, or DB) and synthetic (3D-printed Hyperelastic “Bone” scaffolds, or HB) scaffolds, demonstrating a comprehensive platform for developing natural and synthetic-based in vitro vascularized…

Bioactive scaffolds with interconnected porous structures are essential for guiding cell growth and new bone formation. In this work, we successfully fabricated three-dimensional (3D) porous β-tricalcium phosphate (β-TCP)/calcium silicate (CS) composite scaffolds with different ratios by 3D printing technique and further investigated the physiochemical properties, in vitro apatite mineralization properties and degradability of porous β-TCP/CS scaffolds. Moreover, a series of in vitro cell experiments including the attachment, proliferation and osteogenic differentiation of mouse bone marrow stromal cells were conducted to testify their biological performances. The results showed that 3D printed β-TCP/CS scaffolds possessed of controllable internal porous structures and external…