Biodegradable poly (lactic acid-co-glycolic acid) scaffolds as carriers for genetically-modified fibroblasts

Abstract

Recent advances in gene delivery into cells allow improved therapeutic effects in gene therapy trials. To increase the bioavailability of applied cells, it is of great interest that transfected cells remain at the application site and systemic spread is minimized. In this study, we tested clinically used biodegradable poly(lactic acid-co-glycolic acid) (PLGA) scaffolds (Vicryl & Ethisorb) as transient carriers for genetically modified cells. To this aim, we used human fibroblasts and examined attachment and proliferation of untransfected cells on the scaffolds in vitro, as well as the mechanical properties of the scaffolds at four time points (1, 3, 6 and 9 days) of cultivation. Furthermore, the adherence of cells transfected with green fluorescent protein (GFP) and vascular endothelial growth factor (VEGF165) and also VEGF165 protein secretion were investigated. Our results show that human fibroblasts adhere on both types of PLGA scaffolds. However, proliferation and transgene expression capacity were higher on Ethisorb scaffolds most probably due to a different architecture of the scaffold. Additionally, cultivation of the cells on the scaffolds did not alter their biomechanical properties. The results of this investigation could be potentially exploited in therapeutic regiments with areal delivery of transiently transfected cells and may open the way for a variety of applications of cell-based gene therapy, tissue engineering and regenerative medicine.

Biopolymeric Materials Used as Nonviral Vectors: A Review

“…Table 2 presents the main factors evaluated in the articles about to the efficiency of gene transfection and bacterial transformation by different biopolymers and polysaccharides derivates: chitosan [19], dextran [20,21], quaternized cellulose [22] and quaternized chitosan [23]. Other types of substances were used as nonviral vectors such as: plasmid DNA nanostructures with ionic liquid [11], pegylated polyethyleneimine nanoparticles conjugated with folate and galactose [24], cationic liposomes modified with polyallylamine [25], biodegradable polylactic acid-polyethylene glycol-poly (L-lysine) copolymer [26], crotamine [27], poly (oligo-D-arginine) [28], poly (lactic acid-co-glycolic acid) scaffolds [29], polyethyleneimine/pDNA nanocomplexes with anionic hyaluronic acid [30], fourth generation cationic phosphorus (P4) containing dendrimers [31], and monosylated polyethyleneimine [32]. All the materials tested on these studies showed low cytotoxicity and enhanced significantly the efficiency (p < 0.05).…”

“…Two special types of materials used as vectors for gene transfer were observed: in the study carried out by Togo et al [20], who developed a biodegradable hydrogel composed of 20% w/w dextran aldehyde and 10% w/w ε-poly (L-lysine) (ald-dex/PLL); and in the study carried out by Perisic et al [29], who tested biodegradable poly (lactic acid-co-glycolic acid) (PLGA) scaffolds, clinically used as transient transporters for genetically modified cells. In both studies, a high rate of gene transfection was observed with the use of these materials.…”

Biodegradable polymers suitable for tissue engineering and drug delivery systems

“…It was observed [10] that poly (DL-lactic acid -co -glycolic acid) (PDLLGA) containing between 0 and 70 % glycolic acid has established amorphous structure, while crystalline copolymer of L-lactic and glycolic acid contains 25 -70 % glycolic acid [10]. Poly(lactic acid -coglycolic acid) has been considered as a suitable material in orthopaedic fixation [22], as tissue engineering scaffolds [23,24], as well as controlled drug delivery systems [25][26][27].…”

“…In addition, degradation rate of polymer matrices, corresponding to the rate of tissue restoration, makes the design of new polymer materials for tissue engineering applications a significantly challenging task [23,24].…”

Construction of functional pancreatic artificial islet tissue composed of fibroblast-modified polylactic-co-glycolic acid membrane and pancreatic stem cells

“…16,17 In vivo, PLGA can be degraded to non-toxic lactic acid and glycolic acid by natural processes, while lactic acid and glycolic acid can be excreted by H 2 O or CO 2 in the excretory system or metabolic pathway. 18 Tissue cells were inoculated onto the biocompatible materials to construct a cellbiomaterial compound, which can form an artificial tissue with corresponding functions, with material degradation and cell proliferation. 19,20 This study was designed to explore a novel technology to construct artificial islet tissue.…”