» Articles » PMID: 30321994

Generation of a 3D Liver Model Comprising Human Extracellular Matrix in an Alginate/Gelatin-Based Bioink by Extrusion Bioprinting for Infection and Transduction Studies

Abstract

Bioprinting is a novel technology that may help to overcome limitations associated with two-dimensional (2D) cell cultures and animal experiments, as it allows the production of three-dimensional (3D) tissue models composed of human cells. The present study describes the optimization of a bioink composed of alginate, gelatin and human extracellular matrix (hECM) to print human HepaRG liver cells with a pneumatic extrusion printer. The resulting tissue model was tested for its suitability for the study of transduction by an adeno-associated virus (AAV) vector and infection with human adenovirus 5 (hAdV5). We found supplementation of the basic alginate/gelatin bioink with 0.5 and 1 mg/mL hECM provides desirable properties for the printing process, the stability of the printed constructs, and the viability and metabolic functions of the printed HepaRG cells. The tissue models were efficiently transduced by AAV vectors of serotype 6, which successfully silenced an endogenous target (cyclophilin B) by means of RNA interference. Furthermore, the printed 3D model supported efficient adenoviral replication making it suitable to study virus biology and develop new antiviral compounds. We consider the approach described here paradigmatic for the development of 3D tissue models for studies including viral vectors and infectious viruses.

Citing Articles

Hydrogel-Based Strategies for Liver Tissue Engineering.

Zhang Y, Li L, Dong L, Cheng Y, Huang X, Xue B Chem Bio Eng. 2025; 1(11):887-915.

PMID: 39975572 PMC: 11835278. DOI: 10.1021/cbe.4c00079.


Extrusion bioprinting: meeting the promise of human tissue biofabrication?.

Holland I Prog Biomed Eng (Bristol). 2025; 7(2).

PMID: 39904058 PMC: 11894458. DOI: 10.1088/2516-1091/adb254.


Three-Dimensional Printing/Bioprinting and Cellular Therapies for Regenerative Medicine: Current Advances.

Sousa A, Alvites R, Lopes B, Sousa P, Moreira A, Coelho A J Funct Biomater. 2025; 16(1).

PMID: 39852584 PMC: 11765675. DOI: 10.3390/jfb16010028.


Three-Dimensional Printing of Hydrogel Blend Tissue Engineering Scaffolds with In Situ Delivery of Anticancer Drug for Treating Melanoma Resection-Induced Tissue Defects.

Chen X, Zhang X, Zhu H, Lu H, Wang M J Funct Biomater. 2024; 15(12).

PMID: 39728181 PMC: 11678273. DOI: 10.3390/jfb15120381.


Three-Dimensional Bioprinting of Tarsal Plates with Adipose-Derived Mesenchymal Stem Cells: Evaluation of Meibomian Gland Reconstruction in a Rat Model.

Lee H, Park Y, Kang H, Lee H Biomedicines. 2024; 12(11).

PMID: 39595133 PMC: 11591950. DOI: 10.3390/biomedicines12112567.


References
1.
Lauschke V, Hendriks D, Bell C, Andersson T, Ingelman-Sundberg M . Novel 3D Culture Systems for Studies of Human Liver Function and Assessments of the Hepatotoxicity of Drugs and Drug Candidates. Chem Res Toxicol. 2016; 29(12):1936-1955. DOI: 10.1021/acs.chemrestox.6b00150. View

2.
Grimm D, Kay M . RNAi and gene therapy: a mutual attraction. Hematology Am Soc Hematol Educ Program. 2007; :473-81. DOI: 10.1182/asheducation-2007.1.473. View

3.
Wu Z, Su X, Xu Y, Kong B, Sun W, Mi S . Bioprinting three-dimensional cell-laden tissue constructs with controllable degradation. Sci Rep. 2016; 6:24474. PMC: 4835808. DOI: 10.1038/srep24474. View

4.
Guha C, Mohan S, Roy-Chowdhury N, Roy-Chowdhury J . Cell culture and animal models of viral hepatitis. Part I: hepatitis B. Lab Anim (NY). 2004; 33(7):37-46. DOI: 10.1038/laban0704-37. View

5.
You F, Eames B, Chen X . Application of Extrusion-Based Hydrogel Bioprinting for Cartilage Tissue Engineering. Int J Mol Sci. 2017; 18(7). PMC: 5536084. DOI: 10.3390/ijms18071597. View