Browsing by Author "Foehr, Peter"

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.

The potential of the copolymer polycaprolactone‐co‐poly‐d,l‐lactic acid (PCLLA) as a biomaterial for scaffold‐based therapy for breast tissue engineering applications was assessed. First, the synthesized PCLLA was evaluated for its processability by means of additive manufacturing (AM). We found that the synthesized PCLLA could be fabricated into scaffolds with an overall gross morphology and porosity similar to that of polycaprolactone. The PCLLA scaffolds possessed a compressive Young's modulus (ca 46 kPa) similar to that of native breast (0.5 − 25 kPa), but lacked thermal stability and underwent thermal degradation during the fabrication process. The PCLLA scaffolds underwent rapid degradation in vitro which was characterized by loss of the scaffolds' mechanical integrity and a drastic decrease in mass‐average molar mass (Mw) and number‐average molar mass (Mn) after 4 weeks of immersion in phosphate buffer solution maintained at 37 °C. The tin‐catalysed PCLLA scaffold was also found to have cytotoxic effects on cells. Although the initial mechanical properties of the PCLLA scaffolds generally showed potential for applications in breast tissue regeneration, the thermal stability of the copolymer for AM processes, biocompatibility towards cells and degradation rate is not satisfactory at this stage. Therefore, we conclude that research efforts should be geared towards fine‐tuning the copolymer synthesizing methods.