3D Printed Gene-Activated Sodium Alginate Hydrogel Scaffolds

Overview

Journal Gels

Date 2022 Jul 25

PMID 35877506

Authors

Maria A Khvorostina

Anton V Mironov

Irina A Nedorubova

Tatiana B Bukharova

Andrey V Vasilyev

Dmitry V Goldshtein

Vladimir S Komlev

Vladimir K Popov

Affiliations

Soon will be listed here.

Abstract

Gene therapy is one of the most promising approaches in regenerative medicine to restore damaged tissues of various types. However, the ability to control the dose of bioactive molecules in the injection site can be challenging. The combination of genetic constructs, bioresorbable material, and the 3D printing technique can help to overcome these difficulties and not only serve as a microenvironment for cell infiltration but also provide localized gene release in a more sustainable way to induce effective cell differentiation. Herein, the cell transfection with plasmid DNA directly incorporated into sodium alginate prior to 3D printing was investigated both in vitro and in vivo. The 3D cryoprinting ensures pDNA structure integrity and safety. 3D printed gene-activated scaffolds (GAS) mediated HEK293 transfection in vitro and effective synthesis of model EGFP protein in vivo, thereby allowing the implementation of the developed GAS in future tissue engineering applications.

Citing Articles

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Osteogenesis Enhancement with 3D Printed Gene-Activated Sodium Alginate Scaffolds.

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References

Chung J, Im H, Kim S, Park J, Jung Y . Toward Biomimetic Scaffolds for Tissue Engineering: 3D Printing Techniques in Regenerative Medicine. Front Bioeng Biotechnol. 2020; 8:586406. PMC: 7671964. DOI: 10.3389/fbioe.2020.586406. View

Yan X, Chen Y, Song Y, Yang M, Ye J, Zhou G . Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering. Front Pharmacol. 2020; 10:1534. PMC: 6970981. DOI: 10.3389/fphar.2019.01534. View

Sung Y, Kim S . Recent advances in the development of gene delivery systems. Biomater Res. 2019; 23:8. PMC: 6417261. DOI: 10.1186/s40824-019-0156-z. View

Honore I, Grosse S, Frison N, Favatier F, Monsigny M, Fajac I . Transcription of plasmid DNA: influence of plasmid DNA/polyethylenimine complex formation. J Control Release. 2005; 107(3):537-46. DOI: 10.1016/j.jconrel.2005.06.018. View

Remaut K, Lucas B, Raemdonck K, Braeckmans K, Demeester J, De Smedt S . Protection of oligonucleotides against enzymatic degradation by pegylated and nonpegylated branched polyethyleneimine. Biomacromolecules. 2007; 8(4):1333-40. DOI: 10.1021/bm0611578. View

Pandey A, Sawant K . Polyethylenimine: A versatile, multifunctional non-viral vector for nucleic acid delivery. Mater Sci Eng C Mater Biol Appl. 2016; 68:904-918. DOI: 10.1016/j.msec.2016.07.066. View

Song S, Choi J, Park Y, Hong S, Lee J, Ahn C . Sodium alginate hydrogel-based bioprinting using a novel multinozzle bioprinting system. Artif Organs. 2011; 35(11):1132-6. DOI: 10.1111/j.1525-1594.2011.01377.x. View

Shende P, Trivedi R . 3D Printed Bioconstructs: Regenerative Modulation for Genetic Expression. Stem Cell Rev Rep. 2021; 17(4):1239-1250. PMC: 7811392. DOI: 10.1007/s12015-021-10120-2. View

Hoover R, Folger R, Haering W, Ware B, Karnovsky M . Adhesion of leukocytes to endothelium: roles of divalent cations, surface charge, chemotactic agents and substrate. J Cell Sci. 1980; 45:73-86. DOI: 10.1242/jcs.45.1.73. View

10.

Shahriari D, Koffler J, Lynam D, Tuszynski M, Sakamoto J . Characterizing the degradation of alginate hydrogel for use in multilumen scaffolds for spinal cord repair. J Biomed Mater Res A. 2015; 104(3):611-619. DOI: 10.1002/jbm.a.35600. View

11.

Mabrouk M, Beherei H, Das D . Recent progress in the fabrication techniques of 3D scaffolds for tissue engineering. Mater Sci Eng C Mater Biol Appl. 2020; 110:110716. DOI: 10.1016/j.msec.2020.110716. View

12.

Aguilar-de-Leyva A, Linares V, Casas M, Caraballo I . 3D Printed Drug Delivery Systems Based on Natural Products. Pharmaceutics. 2020; 12(7). PMC: 7407805. DOI: 10.3390/pharmaceutics12070620. View

13.

Zheng Z, Yu C, Wei H . Injectable Hydrogels as Three-Dimensional Network Reservoirs for Osteoporosis Treatment. Tissue Eng Part B Rev. 2020; 27(5):430-454. DOI: 10.1089/ten.TEB.2020.0168. View

14.

Piras C, Smith D . Multicomponent polysaccharide alginate-based bioinks. J Mater Chem B. 2020; 8(36):8171-8188. DOI: 10.1039/d0tb01005g. View

15.

Lee Y, Lee B, Jung Y, Yoon B, Woo H, Kang B . Application of alginate microbeads as a carrier of bone morphogenetic protein-2 for bone regeneration. J Biomed Mater Res B Appl Biomater. 2018; 107(2):286-294. DOI: 10.1002/jbm.b.34119. View

16.

Chen R, Zhang H, Yan J, Bryers J . Scaffold-mediated delivery for non-viral mRNA vaccines. Gene Ther. 2018; 25(8):556-567. PMC: 6309225. DOI: 10.1038/s41434-018-0040-9. View

17.

Pan T, Song W, Xin H, Yu H, Wang H, Ma D . MicroRNA-activated hydrogel scaffold generated by 3D printing accelerates bone regeneration. Bioact Mater. 2021; 10:1-14. PMC: 8637000. DOI: 10.1016/j.bioactmat.2021.08.034. View

18.

Laird N, Acri T, Tingle K, Salem A . Gene- and RNAi-activated scaffolds for bone tissue engineering: Current progress and future directions. Adv Drug Deliv Rev. 2021; 174:613-627. PMC: 8217358. DOI: 10.1016/j.addr.2021.05.009. View

19.

Su X, Wang T, Guo S . Applications of 3D printed bone tissue engineering scaffolds in the stem cell field. Regen Ther. 2021; 16:63-72. PMC: 7868584. DOI: 10.1016/j.reth.2021.01.007. View

20.

Pecci R, Baiguera S, Ioppolo P, Bedini R, Del Gaudio C . 3D printed scaffolds with random microarchitecture for bone tissue engineering applications: Manufacturing and characterization. J Mech Behav Biomed Mater. 2020; 103:103583. DOI: 10.1016/j.jmbbm.2019.103583. View