Applications and Prospects of Non-viral Vectors in Bone Regeneration

Yang, Wei; Wang, Fengzhe; Feng, Longbao; Yan, Shina; Guo, Rui

doi:10.2174/1566523218666180227154232

Cited by 9 publications

(5 citation statements)

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“…When developing gene therapy based on plasmid vectors for bone tissue regeneration, it is important to ensure highly efficient cell transfection to achieve a therapeutic concentration of the osteoinductor in the area of the defect. Transfecting agents that contribute to the successful delivery of plasmids into cells are able to compact plasmids and reduce their negative charge for easy transfer through the cell membrane [ 1 , 2 ]. In our previous work, we showed that when comparing two polycationic molecules, Turbofect (TF) transfected MSCs more efficiently than polyethyleneimine (PEI).…”

Section: Discussionmentioning

confidence: 99%

“…Gene therapy is one of the most promising approaches for bone regeneration. This method ensures local, controlled and sustained production of therapeutic proteins, simulating the natural wound-healing process [ 1 , 2 ]. Bone morphogenetic proteins (BMPs) are active participants in natural osteogenesis [ 3 , 4 ], and BMP-2, in turn, is the most effective osteoinductor that promotes the differentiation of mesenchymal stem cells (MSCs) into osteoblasts [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration

Nedorubova

Бухарова

Mokrousova

et al. 2022

IJMS

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Gene therapy is one of the most promising approaches in regenerative medicine. Gene-activated matrices provide stable gene expression and the production of osteogenic proteins in situ to stimulate osteogenesis and bone repair. In this study, we developed new gene-activated matrices based on polylactide granules (PLA) impregnated with BMP2 polyplexes and included in chitosan hydrogel or PRP-based fibrin hydrogel. The matrices showed high biocompatibility both in vitro with mesenchymal stem cells and in vivo when implanted intramuscularly in rats. The use of porous PLA granules allowed the inclusion of a high concentration of polyplexes, and the introduction of the granules into hydrogel provided the gradual release of the plasmid constructs. All gene-activated matrices showed transfecting ability and ensured long-term gene expression and the production of target proteins in vitro. At the same time, the achieved concentration of BMP-2 was sufficient to induce osteogenic differentiation of MSCs. When implanted into critical-size calvarial defects in rats, all matrices with BMP2 polyplexes led to new bone formation. The most significant effect on osteoinduction was observed for the PLA/PRP matrices. Thus, the developed gene-activated matrices were shown to be safe and effective osteoplastic materials. PLA granules and PRP-based fibrin hydrogel containing BMP2 polyplexes were shown to be the most promising for future applications in bone regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration

Nedorubova

Бухарова

Mokrousova

et al. 2022

IJMS

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“…Viral vectors have a highly evolved mechanism for delivering DNA to cells, but could induce an effective immune response in host cells (Franceschi et al, 2004). Non-viral vector delivery is a promising gene therapy way, including cationic polymers, cationic polypeptides, and cationic liposomes (Yang et al, 2018). In tissue engineering applications, gene therapy can be combined with biomaterials to extend, persist and locally deliver the target protein in situ.…”

Section: Gene Deliverymentioning

confidence: 99%

Advances of Stem Cell-Laden Hydrogels With Biomimetic Microenvironment for Osteochondral Repair

Yuan

et al. 2020

Front. Bioeng. Biotechnol.

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Osteochondral damage from trauma or osteoarthritis is a general joint disease that can lead to an increased social and economic burden in the modern society. The inefficiency of osteochondral defects is mainly due to the absence of suitable tissue-engineered substrates promoting tissue regeneration and replacing damaged areas. The hydrogels are becoming a promising kind of biomaterials for tissue regeneration. The biomimetic hydrogel microenvironment can be tightly controlled by modulating a number of biophysical and biochemical properties, including matrix mechanics, degradation, microstructure, cell adhesion, and intercellular interactions. In particular, advances in stem cell-laden hydrogels have offered new ideas for the cell therapy and osteochondral repair. Herein, the aim of this review is to underpin the importance of stem cell-laden hydrogels on promoting the development of osteochondral regeneration, especially in the field of manipulation of biomimetic microenvironment and utilization growth factors with various delivery methods.

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“…15 Therefore, considerable efforts have been focused on the development of nonviral vectors with improved gene delivery efficiency. 16 Many biomaterials have been tested as nonviral vectors. For example, R 9 -LK 15 -fused cell-penetrating peptide (CPP) served as a miR-29b vector to regulate bone-marrow-derived stem cell (BMSC) differentiation.…”

Section: Introductionmentioning

confidence: 99%

“…However, the use of viral vectors has limitations, such as strong immunogenicity, high toxicity, and low loading capacity . Therefore, considerable efforts have been focused on the development of nonviral vectors with improved gene delivery efficiency …”

Section: Introductionmentioning

confidence: 99%

Delivering Multifunctional Peptide-Conjugated Gene Carrier/miRNA-218 Complexes from Monodisperse Microspheres for Bone Regeneration

Deng

Liu

2022

ACS Appl. Mater. Interfaces

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MicroRNAs (miRNAs) play a pivotal role in regulating gene expression and are considered new molecular targets in bone tissue engineering. However, effective delivery of miRNAs to the defect areas and transfection of the miRNAs into osteogenic progenitor cells has been an obstacle in the application. In this work, miRNA-218 (miR-218) was used as an osteogenic miRNA regulator, and a multifunctional peptide-conjugated gene carrier poly(lactide-co-glycolide)-g-polyethylenimine-b-polyethylene glycol-R9-G4-IKVAVW (PPP-RGI) was developed to condense with miR-218 to form PPP-RGI/miR-218 complexes that were further encapsulated into monodisperse injectable microspheres for enhanced bone regeneration. The PPP-RGI was synthesized via conjugating R9-G4-IKVAVW (RGI), a multifunctional peptide, onto poly(lactide-co-glycolide)-g-polyethylenimine-b-polyethylene glycol (PPP). A microfluidic and synchronous photo-cross-linking process was further developed to encapsulate the PPP-RGI/miR-218 complexes into monodisperse gelatin methacryloyl microspheres. The monodisperse microspheres controlled the delivery of PPP-RGI/miR-218 to the designated defect site, and PPP-RGI facilitated the transfection of miR-218 into osteogenic progenitor cells. An in vivo calvarial defect model showed that the PPP-RGI/miR-218-loaded microspheres significantly enhanced bone tissue regeneration. This work provides a novel approach to effectively deliver miRNA and transfect targeting cells in vivo for advanced regenerative therapies.

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Applications and Prospects of Non-viral Vectors in Bone Regeneration

Abstract: Thus, in this paper, we review the application and progress of non-viral gene vector therapy in bone regeneration.

Cited by 9 publications

References 0 publications

Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration

Comparative Efficiency of Gene-Activated Matrices Based on Chitosan Hydrogel and PRP Impregnated with BMP2 Polyplexes for Bone Regeneration

Advances of Stem Cell-Laden Hydrogels With Biomimetic Microenvironment for Osteochondral Repair

Delivering Multifunctional Peptide-Conjugated Gene Carrier/miRNA-218 Complexes from Monodisperse Microspheres for Bone Regeneration

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