Three-dimensional (3D) bioprinting, known as a promising technology for bioartificial organ manufacturing, has provided unprecedented versatility to manipulate cells and other biomaterials with precise control their locations in space. Over the last decade, a number of 3D bioprinting technologies have been explored. Natural polymers have played a central role in supporting the cellular and biomolecular activities before, during and after the 3D bioprinting processes. These polymers have been widely used as effective cell-loading hydrogels for homogeneous/heterogeneous tissue/organ formation, hierarchical vascular/neural/lymphatic network construction, as well as multiple biological/biochemial/physiological/biomedical/pathological functionality realization. This review aims to cover recent progress in natural polymers for bioartificial organ 3D bioprinting. It is structured as introducing the important properties of 3D printable natural polymers, successful models of 3D tissue/organ construction and typical technologies for bioartificial organ 3D bioprinting.

Three-dimensional (3D) printing, known as the most promising approach for bioartificial organ manufacturing, has provided unprecedented versatility in delivering multi-functional cells along with other biomaterials with precise control of their locations in space. The constantly emerging 3D printing technologies are the integration results of biomaterials with other related techniques in biology, chemistry, physics, mechanics and medicine. Synthetic polymers have played a key role in supporting cellular and biomolecular (or bioactive agent) activities before, during and after the 3D printing processes. In particular, biodegradable synthetic polymers are preferable candidates for bioartificial organ manufacturing with excellent mechanical properties, tunable chemical structures, non-toxic degradation products and controllable degradation rates. In this review, we aim to cover the recent progress of synthetic polymers in organ 3D printing fields. It is structured as introducing the main approaches of 3D printing technologies, the important properties of 3D printable synthetic polymers, the successful models of bioartificial organ printing and the perspectives of synthetic polymers in vascularized and innervated organ 3D printing areas.

In bone tissue engineering, an ideal scaffold is required to have favorable physical, chemical (or physicochemical), and biological (or biochemical) properties to promote osteogenesis. Although silk fibroin (SF) and/or soy protein isolate (SPI) scaffolds have been widely used as an alternative to autologous and heterologous bone grafts, the poor mechanical property and insufficient osteoinductive capability has become an obstacle for their in vivo applications. Herein, β-tricalcium phosphate (β-TCP) and graphene oxide (GO) nanoparticles are incorporated into SF/SPI scaffolds simultaneously or individually. Physical and chemical properties of these composite scaffolds are evaluated using field emission scanning electron microscope (FESEM), X-ray diffraction (XRD) and attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR). Biocompatibility and osteogenesis of the composite scaffolds are evaluated using bone marrow mesenchymal stem cells (BMSCs). All the composite scaffolds have a complex porous structure with proper pore sizes and porosities. Physicochemical properties of the scaffolds can be significantly increased through the incorporation of β-TCP and GO nanoparticles. Alkaline phosphatase activity (ALP) and osteogenesis-related gene expression of the BMSCs are significantly enhanced in the presence of β-TCP and GO nanoparticles. Especially, β-TCP and GO nanoparticles have a synergistic effect on promoting osteogenesis. These results suggest that the β-TCP and GO enhanced SF/SPI scaffolds are promising candidates for bone tissue regeneration.

To investigate the osteogenesis of macro-pore sized bone scaffolds, biphasic calcium phosphate scaffolds with accurately controlled macro-pore size (0.8, 1.2, and 1.6 mm) and identical porosity of 70% were fabricated by the 3D printing technology. Eight New Zealand rabbits were selected in the present study, while four 8-mm-diameter calvarial defects were created in each rabbit to place BCP scaffolds with different macro-pore size. The harvested specimens of four and eight weeks were used to evaluate the bone forming ability by micro CT and histological examination. All 3D-printed BCP scaffolds exhibited excellent mechanical properties and had better bone-forming ability than the control at both four and eight weeks. Among them, scaffold with 0.8 mm pore size was superior for initial bone formation and maturation, resulting in the highest value of total bone formation.

The endogenous non‐coding microRNA (miRNA) let‐7b‐5p is highly expressed in the blood of patients with acute pulmonary embolism (PE). However, the mechanism underlying the involvement of let‐7b‐5p in acute PE remains unclear. To address this, we investigated the role of let‐7b‐5p in acute PE in both in vitro and in vivo experimental models. The results showed that let‐7b‐5p upregulated the expression of stress‐associated endoplasmic reticulum protein 1 (SERP1) at the post‐transcriptional level. SERP1 activation leads to modulation of its chaperone protein SEC61B in the response of endoplasmic reticulum (ER) stress. Furthermore, our data show that the unfolded protein response was triggered and activation of unfolded proteins GRP78, PERK, RNF121, and CHOP occurred through the PERK‐CHOP pathway, resulting in an inflammatory response and apoptosis of lung epithelial cells. These characteristics were promoted by the in vitro expression of a let‐7b‐5p mimic; conversely, transfection with a let‐7b‐5p inhibitor decreased the response of ER stress in acute PE. The results from this study thus provide evidence that let‐7b‐5p promotes protein processing during ER stress response by upregulating SERP1 expression, ultimately resulting in an inflammatory response and apoptosis of lung cells, cumulatively playing a critical role in the pathogenesis of acute PE.