Photo-crosslinking-based 3D bioprinting is a promising approach to fabricate bioactive cell-laden scaffolds for wound healing. While thiol-ene-based bioink has been developed to fabricate 3D devices with improved gelation and bioactivity, the bacterial contamination remains a threat to further application. To address this problem, we have introduced a strategy to modify ε-Polylysine (ε-PL) with thiol groups (PLSH) and combine it with norbornene-modified gelatin (GelNB). The GelNB/PLSH bioink not only holds robust photo-crosslinking reactivity but also exhibits superior antibacterial capacity. The GelNB/PLSH hydrogel showed rapid photo-crosslinking rate, tunable physicochemical properties, improved bioactivity, favorable biocompatibility, and good printability. The GelNB/PLSH antibacterial bioink, along with rat adipose-derived stem cells (rADSCs), can be used to construct 3D scaffolds that promote full-thickness skin defects healing in rats. Overall, this study preliminarily prove the potential of GelNB/PLSH as an antibacterial bioink for wound healing and tissue engineering.

Abstract Background Lymphangiogenesis plays a critical role in various liver diseases, yet its function in liver fibrosis remains controversial. This study aimed to explore the role of lymphangiogenesis in liver fibrogenesis and its underlying regulatory mechanisms. Methods Liver fibrotic mice were established by carbon tetrachloride (CCl 4 ) or Thioacetamide (TAA)-induced injection or bile duct ligation. Lymphatic vessels were marked by podoplain (Pdpn) staining in mice and D2-40 staining in clinical samples. Lymphatic vessels area and density were measured to indicate lymphangiogenesis. Multiplexing immunohistochemistry was used to detect co-localization of proteins. Results In the present study, we first verified increased lymphangiogenesis in human and murine fibrotic livers. Afterwards, we identified VEGFC rather than VEGFD as the primary driver of lymphangiogenesis in liver fibrosis. Furthermore, we demonstrated that M1 macrophages serve as the major source of VEGFC. Founctional studies revealed that VEGFC-mediated lymphangiogenesis exacerbates hepatic fibrosis, while its inhibition alleviated fibrosis. Bioinformatic analysis uncovered Midkine (MDK) as a key downstream of lymphangiogenesis. Both in vivo and in vitro studies confirmed that exogenous MDK promotes liver fibrosis via activating hepatic stellate cells (HSCs), whereas MDK inhibition counteracts the profibrotic effects of VEGFC-induced lymphangiogenesis. Importantly, we discovered that MDK activates HSCs through the Hippo/YAP signaling pathway. Conclusions M1 macrophage-mediated lymphangiogenesis aggravates liver fibrosis via MDK secretion, which activates HSCs. These findings provide novel insights into coordinated crosstalk between macrophages, lymphatic endothelial cells and HSCs in liver fibrosis and suggest lymphangiogenesis and MDK as potential therapeutic targets for fibrotic liver diseases.

In vivo three-dimensional (3D) bioprinting is a promising strategy that can enable personalized organ repair with minimal injury. The current in vivo 3D bioprinting based on upconversion nanoparticles (UCNPs) mediating near-infrared (NIR) light curing is still limited by the low hydrogel cross-linking efficiency. Herein, we introduced a bioink system that allows enhanced NIR light curing by utilizing thiol-ene cross-linkable polymers and photoinitiator-modified UCNPs@LAP nano initiator. The norbornene functionalized hyaluronic acid (NorHA) and thiolated gelatin (GelSH) were first synthesized to prepare the thiol-ene polymer solution. Compared to radical cross-linkable gelatin methacryloyl (GelMA), the NorHA/GelSH exhibited much higher reactivity under weak photoinitiating conditions. With the addition of surface-modified UCNPs@LAP nano initiator, the bioinks showed improved NIR curing performances, which is beneficial to reduce potential thermal damage. Furthermore, in vitro evaluation showed that the NIR light-cured 3D scaffolds preserved excellent bioactivity, suggesting that the hybrid bioink holds great promise to serve as a candidate for in vivo 3D bioprinting.

Liver fibrosis is a chronic progressive disease that can advance to cirrhosis or hepatocellular carcinoma if untreated. While liver transplantation remains the only curative option for end-stage fibrosis, the development of alternative therapies is urgently needed. In this study, we investigated the role of vitamin D-binding protein (VDBP) in hepatic fibrosis using clinical samples and a CCl4-induced mouse model. We observed significant downregulation of VDBP in fibrotic human and murine livers, suggesting that VDBP may serve as a potential biomarker for disease progression. VDBP knockout (VDBP-KO) mice exhibited exacerbated fibrosis, iron overload, and ferroptosis activation, accompanied by dysregulation of the Hippo-YAP pathway. In vitro, VDBP overexpression reversed these effects, while in vivo treatment with the YAP inhibitor verteporfin attenuated fibrosis, normalized iron homeostasis, and suppressed ferroptosis in VDBP-KO mice. Our findings demonstrate that VDBP plays a pivotal role in maintaining iron balance, inhibiting YAP signaling, and preventing ferroptosis during fibrogenesis. Elucidating the molecular mechanisms of VDBP and its downstream pathways may provide novel therapeutic targets for liver fibrosis. This could significantly improve the clinical management of hepatic fibrosis and offer new hope for patients suffering from this debilitating disease.

Tanshinone IIA is derived from Salvia miltiorrhiza and has multiple therapeutic targets and functions. The exact therapeutic effects on liver fibrosis as well as the underlying hepatoprotective mechanisms are still lacking. A liver fibrosis model was established via ligation of the common bile duct ligation (BDL). The mice were intraperitoneally administered different concentrations of tanshinone IIA (4 mg/kg, 8 mg/kg) for 2 weeks. Liver function was assessed through hematoxylin and eosin and Sirus red staining. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutathione (GSH) and malondialdehyde (MDA) were quantified by enzyme-linked immunosorbent assay (ELISA), via microplate reader. The total iron content of the liver was quantified via Triple Quad-ICP-MS. TGFβ-induced hepatic stellate cells (HSCs), a cell model of liver fibrosis, were treated with tanshinone IIA at different concentrations (10 mM, 20 mM, 30 mM, 40 mM). The combination of tanshinone IIA with YAP agonists was applied in activated HSCs and animal models. Tanshinone IIA treatment relieved BDL-induced liver fibrosis; mitigated histological liver damage; lowered the serum ALT and AST levels; reduced macrophage infiltration and the MDA and iron contents; and increased the GSH and GPX4 levels by inhibiting YAP signaling. tanshinone IIA also suppressed the activation of HSCs and collagen production through blocking the YAP signaling pathway. The YAP agonist reversed the therapeutic effect of tanshinone IIA on activated HSCs and BDL-induced liver fibrosis. Tanshinone IIA inhibited HSC activation and oxidative stress and alleviated liver fibrosis by inhibiting the YAP signaling pathway.

DNA N( 6-)methyladenine (6mA) demethylase ALKBH1 plays an important role in various cellular processes. Dysregulation of ALKBH1 is associated with the development of some cancer types, including gastric cancer, implicating a potential therapeutic target. However, there is still a lack of potent ALKBH1 inhibitors. Herein, we report the discovery of a highly potent ALKBH1 inhibitor, 1H-pyrazole-4-carboxylic acid derivative 29. The structure-activity relationship of this series of compounds was also discussed. Because of the poor cell membrane permeability of 29, we prepared a prodrug of 29 (29E), which showed excellent cellular activities. In gastric cancer cell lines HGC27 and AGS, 29E treatment significantly increased the abundance of 6mA, inhibited cell viability, and upregulated the AMP-activated protein kinase (AMPK) signaling pathway. In addition, the hydrolysis product 29 showed high exposure in mice after administration of 29E. Collectively, this research provides a new potent ALKBH1 inhibitor, which could serve as a lead compound for subsequent drug development.

Constructing scaffolds with the desired structures and functions is one of the main goals of tissue engineering. Three-dimensional (3D) bioprinting is a promising technology that enables the personalized fabrication of devices with regulated biological and mechanical characteristics similar to natural tissues/organs. To date, 3D bioprinting has been widely explored for biomedical applications like tissue engineering, drug delivery, drug screening, and in vitro disease model construction. Among different bioinks, photocrosslinkable bioinks have emerged as a powerful choice for the advanced fabrication of 3D devices, with fast crosslinking speed, high resolution, and great print fidelity. The photocrosslinkable biomaterials used for light-based 3D printing play a pivotal role in the fabrication of functional constructs. Herein, this review outlines the general 3D bioprinting approaches related to photocrosslinkable biomaterials, including extrusion-based printing, inkjet printing, stereolithography printing, and laser-assisted printing. Further, the mechanisms, advantages, and limitations of photopolymerization and photoinitiators are discussed. Next, recent advances in natural and synthetic photocrosslinkable biomaterials used for 3D bioprinting are highlighted. Finally, the challenges and future perspectives of photocrosslinkable bioinks and bioprinting approaches are envisaged.

Neuroprotective drugs as adjunctive therapy for adults with acute ischemic stroke (AIS) remains contentious. This study summarizes the latest evidence regarding the benefits of neuroprotective agents combined with intravenous recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis. This study conducted a structured search of PubMed, the Cochrane Library, EMBASE, Wanfang Data, and CNKI databases from their inception to March 2024. Grey literature was also searched. The outcomes included efficacy (National Institutes of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score) and safety (rate of adverse reactions). A total of 70 randomized controlled trials were selected for this network meta-analysis (NMA), encompassing 4,140 patients with AIS treated using different neuroprotective agents plus RT-PA, while 4,012 patients with AIS were in control groups. The top three treatments for NIHSS scores at the 2-week follow-up were Edaravone Dexborneo with 0.9 mg/kg rt-PA, Edaravone with 0.9 mg/kg rt-PA, and HUK with 0.9 mg/kg rt-PA. HUK with 0.9 mg/kg rt-PA, Dl-3n-butylphthalide with 0.9 mg/kg rt-PA, and Edaravone Dexborneo with 0.9 mg/kg rt-PA were ranked the top three for BI scores at the 2-week follow-up. The top three treatments with the lowest adverse effect rates were 0.6 mg/kg rt-PA, HUK with 0.9 mg/kg rt-PA, and Edaravone Dexborneo with 0.9 mg/kg rt-PA due to their excellent safety profiles. Compared to rt-PA alone, the combination treatments of Edaravone+rt-PA, Edaravone Dexborneol+rt-PA, HUK+rt-PA, Dl-3n-butylphthalide+rt-PA, and Ganglioside GM1+rt-PA have shown superior efficacy. This NMA suggest that combination therapies of neuroprotective agents and rt-PA can offer better outcomes for patients with AIS. The results support the potential integration of these combination therapies into standard AIS treatment, aiming for improved patient outcomes and personalized therapeutic approaches.

Cell delivery therapy holds great prospects in regenerative medicine. However, low cell survival and retention are still the main problems in current studies. To address these challenges, a temperature-sensitive hydrogel suitable for cell encapsulation was developed by mixing methylcellulose (MC) and polyvinyl alcohol (PVA) solution simply in this work. Based on the physical hydrogen bonds between MC and PVA chains, porous hydrogels with excellent water-retention ability were achieved at 37 °C. The hydrogels exhibited superior performances such as fast-gelling, stable modulus, great injectability, and high light transmittance. Additionally, cell viability analysis showed MC/PVA hydrogels were cytocompatible. More importantly, cell encapsulation experiments demonstrated that rabbit adipose-derived stem cells (rADSCs) cultured within the MC/PVA hydrogels remain in high viability. Taken together, these results indicated the potential of MC/PVA hydrogels as a clinically translatable delivery system for stem cells.

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common disease in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. However, there is currently no effective treatment to cure NAFLD. In addition, in 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. Recent studies have reported that the development of MAFLD is inextricably associated with mitochondrial dysfunction in hepatocytes and hepatic stellate cells (HSCs). Simultaneously, mitochondrial stress caused by structural and functional disorders stimulates the occurrence and accumulation of fat and lipo-toxicity in hepatocytes and HSCs. In addition, the interaction between mitochondrial dysfunction and the liver-gut axis has also become a new point during the development of MAFLD. In this review, we summarize the effects of several potential treatment strategies for MAFLD, including antioxidants, reagents, and intestinal microorganisms and metabolites.

Mesenchymal stromal/stem cells (MSCs) are a promising therapeutic agent for various diseases, including sepsis. However, translating MSC therapy to clinical applications remains challenging due to variations in the properties of MSCs under different preparation conditions. In this study, the gene expression profiles of human adipose-derived mesenchymal stromal/stem cells (ADSCs) under different culture conditions were compared in relation to their therapeutic efficacy for sepsis. Results showed that ADSCs cultured in media supplemented with human platelet lysates (hPL) (hPL-ADSCs) exhibited a smaller cell size and higher proliferative capacity, whereas ADSCs cultured in media supplemented with fetal bovine serum (FBS) (FBS-ADSCs) showed a broader and flatter shape. Both hPL-ADSCs and FBS-ADSCs exhibited a protective effect in a mouse model of sepsis; however, hPL-ADSCs displayed a better potency for immunosuppressive function, as evidenced by a better improvement of survival rate and further reduction of tissue injury and infectious biomarkers (alanine transaminase and procalcitonin). Furthermore, hPL-ADSCs caused a more anti-inflammatory transcriptomic shift, whereas FBS-ADSCs led to more depression of proinflammatory transcriptomic response. This study thus demonstrates that both hPL-ADSCs and FBS-ADSCs are effective for antiseptic therapy via different mechanisms of inflammatory manipulation, although hPL-ADSCs may imply a better preference.

Atherosclerosis (AS) is a chronic inflammatory disease associated with lipid deposition, which could be converted into acute clinical events by thrombosis or plaque rupture. Adipose-derived mesenchymal stem cell (ADSC)-encapsulated repair units could be an effective cure for the treatment of AS patients. In this study, we encapsulate human adipose-derived mesenchymal stem cells (hADSCs) in collagen microspheres to fabricate stem cell repair units. Besides, we show that encapsulation in collagen microspheres and cultured in vitro for 14 days maintain the viability and stemness of hADSCs. Moreover, we generate AS progression model and niche in vitro by combining hyperlipemia serum of AS patients with AS cell models. We further systematically demonstrate that hADSC-based microspheres could ameliorate AS progression by inhibiting oxidative stress injury, cell apoptosis, endothelial dysfunction, inflammation, and lipid accumulation. In addition, we perform transcriptomic analysis and functional studies to demonstrate how hADSCs (three dimensional cultured in microspheres) respond to AS niche compared with healthy microenvironment. These findings reveal a role for ADSC-based microspheres in the treatment of AS and provide new ideas for stem cell therapy in cardiovascular disease. The results may have implications for improving the efficiency of hADSC therapies by illuminating the mechanisms of hADSCs exposed in special pathological niche.

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 mixing NorHA with macro-cross-linker GelSH, the customized NorHA/GelSH bioinks exhibited fascinating superiorities over the gold standard GelMA bioinks, such as an ultrafast curing rate (1-5 s), much lowered photoinitiator concentration (0.03% w/v), and flexible physical performances. Moreover, the NorHA/GelSH hydrogel greatly avoided excess ROS generation, which is important for the survival of the encapsulated cells. Last, compared with the GelMA scaffold, the 3D-printed NorHA/GelSH scaffold not only exhibited excellent cell viability but also guaranteed cell proliferation, revealing its superior bioactivity. In conclusion, the NorHA/GelSH system is a promising candidate for 3D bioprinting and tissue engineering applications.

Abstract Background Mesenchymal stem cells (MSCs) therapy for sepsis has been extensively studied in the past decade; however, the treatment regimen and mechanism of action of MSCs remain elusive. Here, we attempted to understand the efficacy and mechanism of action of MSCs on rescuing mice with sepsis. Methods A mouse model of sepsis was produced by cecal ligation and puncture (CLP). Allogeneic adipose-derived MSCs (ADSCs) were administered by intravenous infusion at 6 h after CLP, and dose-related effects of ADSCs on these mice were determined by survival rate, histopathological changes, biochemical and coagulation parameters, bacterial load, and plasma levels of endotoxin and inflammatory cytokines. The tissue distribution of intravenously infused ADSCs in septic mice was investigated by pre-labeling ADSCs with the lipophilic membrane dye PKH26. RNA sequencing analysis was performed to assess the transcriptional changes in peripheral blood mononuclear cells (PBMCs) and the liver. Results A significant therapeutic effect of ADSCs at a dose of 2 × 107 cells/kg in septic mice was evidenced by a remarkable reduction in mortality (35.89% vs. 8.89% survival rate), blood bacterial burden, systemic inflammation, and multiple organ damage. In contrast, ADSCs at a lower dose (1 × 107 cells/kg) failed to achieve any beneficial outcomes, while ADSCs at a higher dose (4 × 107 cells/kg) caused more early death within 24 h after CLP, retaining a steady survival rate of 21.42% thereafter. PKH26-labeled ADSCs were predominantly localized in the lungs of septic mice after intravenous infusion, with only a smaller proportion of PKH26-positive signals appearing in the liver and spleen. RNA sequencing analysis identified that insufficient phagocytic activity of PBMCs in addition to a hyperactivation of the hepatic immune response was responsible for the ineffectiveness of low-dose ADSCs therapy, and acute death caused by high-dose ADSCs infusion was associated with impaired coagulation signaling in PBMCs and exacerbated hepatic hypoxic injury. Conclusions Our findings demonstrate a dose-specific effect of ADSCs on the treatment of sepsis due to dose-related interactions between exogenous stem cells and the host’s microenvironment. Therefore, a precise dosing regimen is a prerequisite for ADSCs therapy for sepsis.

In recent years, the study of lymphangiogenesis and fibrotic diseases has made considerable achievements, and accumulating evidence indicates that lymphangiogenesis plays a key role in the process of fibrosis in various organs. Although the effects of lymphangiogenesis on fibrosis disease have not been conclusively determined due to different disease models and pathological stages of organ fibrosis, its importance in the development of fibrosis is unquestionable. Therefore, we expounded on the characteristics of lymphangiogenesis in fibrotic diseases from the effects of lymphangiogenesis on fibrosis, the source of lymphatic endothelial cells (LECs), the mechanism of fibrosis-related lymphangiogenesis, and the therapeutic effect of intervening lymphangiogenesis on fibrosis. We found that expansion of LECs or lymphatic networks occurs through original endothelial cell budding or macrophage differentiation into LECs, and the vascular endothelial growth factor C (VEGFC)/vascular endothelial growth factor receptor (VEGFR3) pathway is central in fibrosis-related lymphangiogenesis. Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), as a receptor of LECs, is also involved in the regulation of lymphangiogenesis. Intervention with lymphangiogenesis improves fibrosis to some extent. In the complex organ fibrosis microenvironment, a variety of functional cells, inflammatory factors and chemokines synergistically or antagonistically form the complex network involved in fibrosis-related lymphangiogenesis and regulate the progression of fibrosis disease. Further clarifying the formation of a new fibrosis-related lymphangiogenesis network may potentially provide new strategies for the treatment of fibrosis disease.

Norbornene modified hyaluronic acid (NorHA) has attracted enormous attention in biological research for its ability to form hydrogels in a cell-friendly way. However, traditional routes to synthesis NorHA are involved with laboring and cumbersome steps. In this study, an alternative single-step approach to fabricate NorHA is reported. NorHA was first synthesized by conjugating carbic anhydride (CA) with hyaluronic acid (HA) directly and NorHA with various norbornene substitution degrees (SD) was obtained by adjusting the reaction pH, time, and the amounts of CA easily. Porous NorHA hydrogels were prepared via orthogonal thiol-norbornene reaction under blue light irradiation. Furthermore, the resulting gelation performances, swelling behaviors, and transmittance of NorHA hydrogels were adjusted by varying the content of crosslinker or NorHA. The cytocompatibility evaluation suggests that the obtained NorHA were suitable for cell encapsulation. Finally, we show that this approach also can be extended to other natural or synthesized biopolymers to prepare cytocompatible photo-crosslinked hydrogels.

Previous studies have demonstrated dysregulated mitochondrial dynamics in fibrotic livers and hepatocytes. Little is currently known about how mitochondrial dynamics are involved, nor is it clear how mitochondrial dynamics participate in hepatic stellate cell (HSC) activation. In the present study, we investigated the role of mitochondrial dynamics in HSC activation and the underlying mechanisms. We verified that mitochondrial fission was enhanced in human and mouse fibrotic livers and active HSCs. Moreover, increased mitochondrial fission driven by fis1 overexpression could promote HSC activation. Inhibiting mitochondrial fission using mitochondrial fission inhibitor-1 (Mdivi-1) could inhibit activation and induce apoptosis of active HSCs, indicating that increased mitochondrial fission is essential for HSC activation. Mdivi-1 treatment also induced apoptosis in active HSCs in vivo and thus ameliorated CCl4-induced liver fibrosis. We also found that oxidative phosphorylation (OxPhos) was increased in active HSCs, and OxPhos inhibitors inhibited activation and induced apoptosis in active HSCs. Moreover, increasing mitochondrial fission upregulated OxPhos, while inhibiting mitochondrial fission downregulated OxPhos, suggesting that mitochondrial fission stimulates OxPhos during HSC activation. Next, we found that inhibition of oxidative stress using mitoquinone mesylate (mitoQ) and Tempol inhibited mitochondrial fission and OxPhos and induced apoptosis in active HSCs, suggesting that oxidative stress contributes to excessive mitochondrial fission during HSC activation. In conclusion, our study revealed that oxidative stress contributes to enhanced mitochondrial fission, which triggers OxPhos during HSC activation. Importantly, inhibiting mitochondrial fission has huge prospects for alleviating liver fibrosis by eliminating active HSCs.

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 die-swell ratio, 2D, and 3D printing fidelities. Finally, a series of porous PCL scaffolds were fabricated using printing inks comprised of different feed ratios (20:80, 40:60, 50:50, 60:40, and 80:20) of NaCl to PCL, and the porosity, mechanical properties, degradation behaviors, and biocompatibility were discussed. The results suggested that the printing ink formulation is greatly affected the printing performances. The increasing NaCl content in printing inks reduced shear force for extrusion, enhanced the shear-thinning behavior, increased the curing time. The dropping temperature and solvent evaporation both enhanced the self-supporting ability of the printing inks and solvent evaporation is a critical factor for the curing of the printing inks. The further evaluation demonstrated that the obtained fabricated porous PCL scaffolds were endowed with good biocompatibility and controllable porosity, mechanical features, and in vitro degradation behavior related to the NaCl content in the printing inks. This study built a fabricating method of porous polymer scaffolds by 3D printing at low temperatures for regeneration medicine researches.

Research and development of artificial biliary substitutes is an indispensable part of modern biliary surgery, bearing great clinical significance on the recovery of the normal functions of the biliary system. The implantation of artificial biliary substitutes may cause the blockage or stenosis of the biliary duct at the transplantation site, which is the most urgent problem in the research of artificial biliary substitutes. The fundamental cause of the problem is tissue hyperplasia caused by chronic inflammatory stimulation of artificial biliary substitutes. The regeneration of new bile duct tissue at the transplantation site can provide a solution to this problem. By looking at the literature from China and abroad, this paper reviewed the research and development of non-degradable artificial bile duct, degradable artificial bile duct and tissue-engineered artificial bile duct in order to provide reference for the further development of biliary replacements. Future studies should focus on the rapid formation of biliary epithelial layer on the tissue-engineered artificial biliary wall, the promotion of new biliary tissue formation, and the regulation of the degradation performance and mechanical properties of artificial biliary duct in order to fundamentally solve the problems encountered in the research of artificial biliary substitutes and accelerate the development of artificial biliary duct.