Core-sheath structured fibers with pDNA polyplex loadings for the optimal release profile and transfection efficiency as potential tissue engineering scaffolds

Abstract

Emulsion electrospinning was initially applied to prepare core-sheath structured fibers with a core loading of pDNA or pDNA polyplexes inside a fiber sheath of poly(DL-lactide)-poly(ethylene glycol) (PELA). The inclusion of poly(ethylene imine) (PEI) and poly(ethylene glycol) (PEG) were expected to modulate the release profiles and achieve a balance between cytotoxicity and transfection efficiency. The core-sheath fibers enhance the structural integrity and maintain the biological activity of pDNA during the electrospinning process, incubation in release buffer and enzyme digestion. The addition of hydrophilic PEI into the fiber matrix accelerates pDNA release, while the encapsulation of pDNA polyplexes within the fibers led to no further release after an initial burst. However, sustained release of pDNA polyplexes has been achieved through PEG incorporation, and the effective release lifetime can be controlled between 6 and 25 days, dependent on the amount loaded and the molecular weight of PEG. Higher N/P ratios of PEI to DNA result in lower cell attachment, while cell viability is dependent on the effective concentration of pDNA polyplexes released from the fibers. While no apparent transfection is detected for pDNA-loaded PELA fibers, PEG incorporation into fibers containing pDNA polyplexes leads to over an order of magnitude increase in the transfection efficiency. pDNA polyplex-loaded fibers containing 10% PEG show the best performance in balancing transfection efficiency and cell viability. It is suggested that electrospun core-sheath fibers integrated with DNA condensation techniques provide the potential to produce inductive tissue engineering scaffolds able to manipulate the desired signals at effective levels within the local tissue microenvironment.