3D Printed Gene-Activated Sodium Alginate Hydrogel Scaffolds

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.

Mg-Sr-Ca containing bioactive glass nanoparticles hydrogel modified mineralized collagen scaffold for bone repair

“…The combination of mineralized collagen, sodium alginate (SA) hydrogels with positive osteogenic effects addressed the challenge of achieving uniform distribution on material surface. 43,44 Therefore, in the current study, we utilized substrate materials with enhanced osteogenic activity and modified bioactive glass nanoparticles to improve biological activity and uniform distribution through sodium alginate (SA) hydrogel. This approach leveraged the strengths of both materials to achieve superior osteogenic performance.…”

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

“…The present study is aimed at a comparative assessment of neo-osteogenesis in critical-sized bone defects using SA-based hydrogel scaffolds fabricated by 3D cryoprinting. We have previously demonstrated that 3D cryoprinted gene-activated scaffolds maintain cell viability and provide a prolonged plasmid release in a high concentration sufficient for the effective transfection of cells in vitro and in vivo [ 43 ]. The focus of this study is on implementing the developed universal platform to form GASs in which the model plasmids were replaced with therapeutic ones for efficient bone regeneration enhancement.…”

“…Gene-activated sodium alginate scaffolds were fabricated using 3D cryoprinting as described earlier [ 43 ]. Briefly, 8 mg of SA was dissolved in 92 µL of distillated H 2 O, containing 20 µg pDNA/60 µg PEI for in vitro study and 100 µg pDNA/300 µg PEI for in vivo study.…”

“…Furthermore, the most commonly used method of gene incorporation via adsorption [ 40 , 41 ] does not provide adequate transfection kinetics for tissue regeneration. We have recently demonstrated the development of the gene-activated SA-based scaffold (GAS) fabrication platform using our original 3D cryoprinting technique [ 42 , 43 ] and showed it to overcome the mentioned difficulties. The present study aims to further extend this approach to demonstrate for the first time the osteogenic properties of such hydrogel scaffolds with embedded BMP-2 plasmids both in vitro and in vivo.…”

Intraoperative Creation of Tissue-Engineered Grafts with Minimally Manipulated Cells: New Concept of Bone Tissue Engineering In Situ

“…Bone tissue engineering in situ through BM-MSCs osteogenic differentiation may be performed using immobilized gene delivery nanocomplexes [ 58 ]. Bioactive scaffolds with modified surface properties or gene-activated materials have promising applications as scaffolds for cell seeding [ 59 , 60 ].…”