Narrative review of gene modification: applications in three-dimensional (3D) bioprinting

Abstract

Objective: This article focused on the application scenarios of three-dimensional (3D) bioprinting and gene-editing technology in various medical fields, including gene therapy, tissue engineering, tumor microenvironment simulation, tumor model construction, cancer regulation and expression, osteogenesis, and skin and vascular regeneration, and summarizing its development prospects and shortcomings.

Background: 3D bioprinting is a process based on additive manufacturing that uses biological materials as the microenvironment living cells. The scaffolds and carriers manufactured by 3D bioprinting technology provide a safe, efficient, and economical platform for genes, cells, and biomolecules. Gene modification refers to replacing, splicing, silencing, editing, controlling or inactivating genes and delivering new genes. The combination of this technology that changes cell function or cell fate or corrects endogenous mutations and 3D bioprinting technology has been widely used in various medical field.

Methods: We conducted a literature search for papers published up to March 2021 on the gene modification combined with 3D bioprinting in various medical fields via PubMed, Web of Science, China National Knowledge Infrastructure (CNKI). The following medical subject heading terms were included for a MEDLINE search: "3D printing/gene editing", "3D printing/genetic modification", "3D printing/seed cell", "bioprinting/gene editing", "bioprinting/genetic modification", "bioprinting/seed cell", "scaffold/gene editing", "scaffold/genetic modification", "scaffold/seed cell", "gene/scaffold", "gene/bioprinting", "gene/3D printing". Quantitative and qualitative data was extracted through interpretation of each article.

Conclusions: We have reviewed the application scenarios of 3D bioprinting and gene-editing technology in various medical fields, it provides an efficient and accurate delivery system for personalized tumor therapy, enhancing the targeting effect while maintaining the integrity of the fabricated structure. It exhibits significant application potential in developing tumor drugs. In addition, scaffolds obtained via 3D bioprinting provide gene therapy applications for skin and bone healing and repair and inducing stem cell differentiation. It also considers the future development direction in this field, such as the emergence and development of gene printing, 4D printing. The combination of nanotechnology and gene printing may provide a new way for future disease research and treatment.

Keywords: Three-dimensional bioprinting (3D bioprinting); genetic modification; scaffold.

Figure 1

Preparation methods of gene editing and gene therapy scaffolds. PCL, poly(E-caprolactone); PLGA, polylactic acid-glycolic acid; PSiNP, porous silicon nanoparticles.

Figure 2

Overall summary of 3D printed scaffolds used in gene therapy. BMP-12, bone morphogenetic protein 12; BM-MSCs, bone marrow-derived mesenchymal stem cells; GeIMA, gelatin methacryloyl; GM-CSF, granulocyte-macrophage colony-stimulating factor; HGF, hepatocyte growth factor; IL-7, interleukin-7; PCL, poly(E-caprolactone); VEGF, vascular endothelial growth factor.