Jie Huang

This review summarizes 3D bioprinting technologies, advanced bioinks, and cellular components for constructing intestinal models, highlighting their applications in drug screening, intestinal development, diseases and tissue repair.

Conductive hydrogels are highly attractive in 3D bioprinting of tissue engineered scaffolds for skin injury repair. However, their application is limited by mismatched electrical signal conduction mode and poor printability. Herein, the 3D bioprinting‐assisted fabrication of a double‐layer ionic conductive skin scaffold using a newly designed ionic conductive biomimetic bioink (GHCM) is reported, which is composed of gelatin methacrylate (GelMA), oxidized hyaluronic acid (OHA), carboxymethyl chitosan (CMCS), and 2‐methacryloyloxyethyl phosphorylcholine (MPC) for the treatment of full‐thickness skin defects. The combination of rigid (GelMA) and dynamic (OHA‐CMCS) polymer networks imparts GHCM bioink excellent reversible thixotropy, enabling good printability, and allowing the creation of skin‐like constructs with high shape fidelity and cell activity by convenient one‐step bioprinting. Moreover, the incorporation of zwitterionic MPC endows the bioink with electrical signaling pattern similar to that of natural skin tissue. By integrating human foreskin fibroblasts (HFF‐1), human umbilical vein endothelial cells (HUVECs), and human immortalized keratinocytes (HaCaTs), a double‐layer conductive skin scaffold comprising an epidermal layer and a vascularized dermal layer is created. In vivo experiments have demonstrated that the conductive skin scaffolds provide an appropriate conductive microenvironment for cellular signaling, growth, migration, and differentiation, ultimately accelerating the re‐epithelialization, collagen deposition, and vascularization of skin wounds, which may represent a general and versatile strategy for precise engineering of electroactive tissues for regenerative medicine applications.

Accurate reproduction of human intestinal structure and function in vitro is of great significance for understanding the development and disease occurrence of the gut. However, most in vitro studies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization found in vivo. Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with in vivo-like ring folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine.

Alleviating the injury of type II alveolar epithelial cells (AEC 2s) and inhibiting the activation and differentiation of fibroblasts are significant for improving the therapeutic effect of idiopathic pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles (ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small interfering RNA targeting transforming growth factor β1 (siTGF-β1) were developed for enhanced IPF therapy. ASNPs showed high loading and intracellular delivery efficiency for AST and siTGF-β1. After the injection of ASNPs in an IPF mice model, the loaded AST largely scavenged reactive oxygen species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby ensuring the integrity of the alveolar epithelium. Meanwhile, siTGF-β1, delivered by ASNPs, significantly silenced the expression of TGF-β1 in fibroblasts, inhibiting the differentiation of fibroblasts into myofibroblasts as well as reducing the excessive deposition of extracellular matrix (ECM). The combined use of the two drugs exhibited an excellent synergistic antifibrotic effect and was conducive to minimizing alveolar epithelial damage. This work provides a codelivery strategy of AST and siTGF-β1, which shows great promise for the treatment of IPF by simultaneously reducing alveolar epithelial damage and inhibiting fibroblast activation.