Influence of Nonsulfated Polysaccharides on the Properties of Electrospun Poly(lactic-<i>co</i>-glycolic acid) Fibers

Biomimetic tissue engineering aspires to develop bioinspired implantable devices that would positively interact with the host. Given that glycosaminoglycans are involved in many physiological processes, whereas their deprivation is associated with pathophysiologies, functionalization of implantable devices with natural and/or synthetic carbohydrate moieties is at the forefront of scientific research and industrial innovation. Herein, we venture to assess the influence of various concentrations (0.01%, 0.1%, 1%) of hyaluronic acid and Ficoll on the structural, thermal, biomechanical and biological (human osteoblasts) properties of electrospun poly­(lactic-<i>co</i>-glycolic acid) fibers. The addition of hyaluronic acid and Ficoll reduced the fiber diameter, with the 1% hyaluronic acid exhibiting the smallest fibers diameter (<i>p</i> < 0.001). Neither the addition of hyaluronic acid nor the addition Ficoll significantly affected the onset and peak temperatures (<i>p</i> > 0.05). All hyaluronic acid and Ficoll treatments significantly reduced stress at break, strain at break and elastic modulus values (<i>p</i> < 0.001). Hyaluronic acid and Ficoll did not affect osteoblast viability and metabolic activity temperatures (<i>p</i> > 0.05); the 1% hyaluronic acid and Ficoll significantly increased (<i>p</i> < 0.001) osteoblast proliferation at day 21. By day 21, the 1% hyaluronic acid and 1% Ficoll fibers showed the highest alkaline phosphatase activity and calcium deposition. At day 21, osteocalcin was not detected, whereas osteopontin was detected on all samples. Collectively, our data clearly illustrate the biological benefit of nonsulfated polysaccharides as functionalization molecules

GDNF Gene Delivery via a 2‑(Dimethylamino)ethyl Methacrylate Based Cyclized Knot Polymer for Neuronal Cell Applications

Nonviral genetic therapeutic intervention strategies for neurological disorders hold great promise, but a lack of vector efficacy, coupled with vector toxicity, continue to hinder progress. Here we report the application of a newly developed class of polymer, distinctly different from conventional branched polymers, as a transfection agent for the delivery of glial cell line derived neurotrophic factor (GDNF) encoding gene. This new 2-(dimethylamino)­ethyl methacrylate (DMAEMA) based cyclized knot polymer was studied for neuronal cell transfection applications, in comparison to branched polyethyleneimine (PEI). While showing a similar transfection profile over multiple cell types, the cyclized knot polymer showed far lower toxicity. In addition, transfection of Neu7 astrocytes with the GDNF encoding gene was able to cause neurite outgrowth when cocultured with dorsal root ganglia (DRGs). The cyclized knot polymer assessed here (PD-E 8%PEG), synthesized via a simple one-pot reaction, was shown to have great potential for neuronal gene therapy applications