Gene delivery in tissue engineering and regenerative medicine

Fang, Yunlan; Chen, Xuguang; Godbey, W.T.

doi:10.1002/jbm.b.33354

Cited by 23 publications

(13 citation statements)

References 246 publications

(425 reference statements)

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“…In this context, gene therapy targeted to VSMCs and ECs is a promising therapeutic approach for the targeted inhibition of mechanisms leading to the development of vascular pathologies or to post-intervention complications [5]. Furthermore, in vitro gene delivery to primary VSMCs and ECs can be employed for tissue engineering and regeneration applications [6], and in the study of gene function and of the general physiology of vascular tissues [7].…”

Section: Introductionmentioning

confidence: 99%

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

et al. 2017

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Gene therapy targeted to vascular cells represents a promising approach for prevention and treatment of pathological conditions such as intimal hyperplasia, in-stent and post-angioplasty restenosis. In this context, polymeric non-viral gene delivery systems are a safe alternative to viral vectors but a further improvement in efficiency and cytocompatibility is needed to improve their clinical success. Herein, a library of 24 branched polyethylenimine (bPEI) derivatives modified with hydrophobic moieties was synthesised, characterised and tested in vitro on primary vascular cells, aiming to identify delivery agents with superior transfection efficiency and low cytotoxicity. Low molecular weight PEIs (0.6, 1.2 and 2 kDa) were grafted with long (C18) and short (C3) aliphatic chains, featuring different unsaturation degrees and degrees of substitution. 0.6 kDa bPEI-based derivatives were generally ineffective in transfection on vascular smooth muscle cells (VSMCs), while among the other derivatives some promising vectors were identified. Forcing polyplexes on the cell surface by means of centrifugation invariably boosted transfection levels but increased cytotoxicity as well. Of note, a propionyl-substituted derivative (PEI2-PrA1, C3:0) was the most effective on both VSMCs and endothelial cells (ECs), with higher and more sustained gene expression in combination with markedly lower cytotoxicity with respect to the gold standard 25 kDa bPEI. In addition, a linoleoyl-substituted derivative (PEI1.2-LA6, C18:2) owing to its high efficiency in VSMCs and relative inefficacy in ECs, combined with tolerable cytotoxicity was proposed as a vector for specific VSMCs targeting.

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Section: Introductionmentioning

confidence: 99%

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

et al. 2017

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“…Under the assumption that previous in vitro results are transferable to in vivo findings, we found that this limited expression level seems to be sufficient to induce NB, because of endogenous BMP‐2 release by nontransfected cells via the paracrine stimulation of cells by the gene‐activated surface within the initial 14 days postsurgery. By the gene therapeutic approach, transgene‐derived low amounts of BMP2 are produced after local transfection of cells which then can activate additional endogenous BMP2 production in non‐transfected target cells …”

Section: Discussionmentioning

confidence: 99%

“…Nonviral vectors are advantageous in that they do not tend to insert permanently into the host's genome. Furthermore, the host's immune response is not triggered at such high levels as has been observed for other approaches …”

Section: Discussionmentioning

confidence: 99%

“…Bone morphogenetic proteins (BMPs) are the most potent osseoinductive GFs and have demonstrated powerful abilities in inducing osteogenic differentiation of mesenchymal cells, orthotopic, and heterotopic new bone (NB) formation, or in accomplishing bone defect closure for which autologous bone tissue transfer would otherwise be required . On the other hand, GFs have several adverse effects, such as short half‐life, high costs, and potential systemic side‐effects, and an incompletely understood dose dependency . Because of these disadvantages, local gene therapy for bone regeneration in animal defect models has emerged as a possible alternative strategy by expressing GFs and triggering GF expression in target cells for short or long time periods to stimulate osteogenesis .…”

Section: Introductionmentioning

confidence: 99%

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Comparative analysis of bone regeneration behavior using recombinant human BMP‐2 versus plasmid DNA of BMP‐2

Kolk

Boskov

Haidari

et al. 2018

J Biomedical Materials Res

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Bone regeneration and the osteoinductive capacity of implants are challenging issues in clinical medicine. Currently, recombinant growth factors and nonviral gene transfer are the most frequently investigated methods for bone growth enhancement, although the more favorable method remains unclear. There is a lack of knowledge in literature about the in vivo comparison of these methods for bone regeneration. BMP-2, which is the most commonly used growth factor for osteogenesis, was applied at its most efficient dose as a recombinant growth factor (rhBMP-2) and as a growth-factorencoding copolymer protected gene vector (pBMP-2) in a critical size bone defect (CSD) model to determine the most suitable method for bone regeneration. CSDs were induced bilaterally in 32 Sprague-Dawley rats. RhBMP-2 (62.5 μg) or pBMP-2 (2.5 μg) was embedded in poly(D,L-)lactide-coated titanium discs. Survival times were set at 14, 28, 56, and 112 days. After euthanasia, samples were analyzed via micro-computed tomography, polychrome sequential fluorescent labeling, and immunohistochemistry. Whereas defects in both groups were bridged with new bone after 56 days, rhBMP-2 initially induced ectopic new bone formation that was later remodeled in an unorganized hypodense manner. In contrast, pBMP-2 led to slower but steady bone regeneration with physiological tissue morphology, as confirmed by high osteoblast activity shown by osteocalcin staining. CD68 and TRAP staining verified high osteoclast activity for the rhBMP-2 group. pBMP-2 successfully induced locally controlled physiological bone regeneration, whereas rhBMP-2 triggered rapid and ectopic but insufficient bone formation. Thus, nonviral gene transfer appears to be more favorable for clinical applications.

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“…As all approaches introduced above demonstrated high efficiency and therapeutic potential, still some risks prevailed, which requires further improvement for safer and superior treatment (Evans & Huard, ). Although bone loss and bone fracture are not fatal, gene therapy might induce lethal side effects such as mutagenesis and unexpected immune responses, where requires the consideration of benefits, to minimize the risks, and to ensure the safety issues associated with gene therapy (Fang et al, ).…”

Section: Osteobiologic Materialsmentioning

confidence: 99%

Advances in osteobiologic materials for bone substitutes

Hasan

Byambaa

Morshed

et al. 2018

J Tissue Eng Regen Med

109

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A significant challenge in the current orthopedics is the development of suitable osteobiologic materials that can replace the conventional allografts, autografts, and xenografts and thereby serve as implant materials as bone substitutes for bone repair or remodelling. The complex biology behind the nanostructure and microstructure of bones and their repair mechanisms, which involve various types of chemical and biomechanical signalling amongst different cells, has set strong requirements for biomaterials to be used in bone tissue engineering. This review presents an overview of various types of osteobiologic materials to facilitate the formation of the functional bone tissue and healing of the bone, covering metallic, ceramic, polymeric, and cell-based graft substitutes, as well as some biomolecular strategies including stem cells, extracellular matrices, growth factors, and gene therapies. Advantages and disadvantages of each type, particularly from the perspective of osteoinductive and osteoconductive capabilities, are discussed. Although the numerous challenges of bone regeneration in tissue engineering and regenerative medicine are yet to be entirely addressed, further advancements in osteobiologic materials will pave the way towards engineering fully functional bone replacement grafts.

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Gene delivery in tissue engineering and regenerative medicine

Cited by 23 publications

References 246 publications

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

Hydrophobe-substituted bPEI derivatives: boosting transfection on primary vascular cells

Comparative analysis of bone regeneration behavior using recombinant human BMP‐2 versus plasmid DNA of BMP‐2

Advances in osteobiologic materials for bone substitutes

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