In this work, PEG–PLLA electrospun fibers were developed as a new controlled release system for macrolide antibiotic drug brefeldin A (BFA). SEM and XRD analyses of the BFA-loaded PEG–PLLA fibers revealed that the average diameter of fibers was below 950 nm with smooth surfaces, and the drug was well incorporated into the fibers in amorphous form. The release profiles of BFA in PBS were measured by HPLC, demonstrating that the controlled release of BFA could be gained for long time. The in vitro antitumor activity against human liver carcinoma HepG2 cells of the fibers containing 3%, 6%, 9%, 12% and 15% BFA were examined by MTT method, and the results showed that cell growth inhibition rates at 72 h were 64%, 77%, 80%, 81% and 85%, respectively. These results strongly suggested that the BFA/PEG–PLLA fibers had an effect of controlled release of BFA and were suitable for postoperative chemotherapy of cancers.
Despite promise in preventing peritendinous adhesion, electrospun membranes face many challenges related to their complex fabrication process, untargeted/uncontrolled drug delivery and consequently low therapeutical effect. Here, a micro-and nano-environment dual-modulated barrier membrane (MNBM) with on-demand gene delivery capability is presented. Our MNBM is developed by first preparing extracellular signal-regulated kinase-2 (ERK2) siRNA-loaded gelatin methacryloyl (GelMA) nanogels via facile nano-emulsification technique, then incorporating these nanogels into poly-L-lactic acid (PLLA) fibers via simple blending electrospinning. The GelMA nanogels offer a nano-niche for ERK2-siRNA encapsulation and allow for a nano-environment controlled siRNA release by readily tuning the GelMA concentrations during nano-emulsification, while the resultant MNBM can mediate a micro-environment controlled siRNA delivery in response to the matrix metalloproteinase-2 (MMP-2) enriched micro-environment at the tendon repair site. Such MNBM can not only biologically orchestrate fibroblast behaviors by silencing the target gene expression, but also physically shield the tendon from extrinsic cell/tissue invasion. This study provides a proof-of-concept of anti-adhesion barrier membrane as an intelligent gene delivery system to offer a spatiotemporal and biophysical dual control over tendon recovery according to disease state and ensure long-term therapeutic efficacy. We envision such MNBM represents a promising therapeutic platform with great efficacy to achieve adhesion-free tendon repair.
Biodegradable polymeric fiber membranes produced by electrospinning have been candidate for tissue engineering, but they sometimes lack the necessary mechanical stability. In the work, electrospun poly ( l -lactide) fiber membranes are chemically crosslinked by adding dicumyl peroxide (DCP) and triallylisocyanurate (TAIC). Their corresponding properties such as morphology, thermodynamics, mechanics, degradation and cytotoxicity are investigated. Morphology of PLLA fiber is maintained after crosslinking, but its crystallization and melting temperature is influenced by chemical crosslinking. The membranous tensile strength and modulus not only climb with TAIC concentration increasing, but also depend strongly on crosslinked temperature which the best is 140 °C. Compared to neat PLLA, degradation rate of the crosslinked PLLA membrane is slower. At the same time, it is also non-cytotoxic. The results suggest that the chemical crosslinking improves the mechanical properties of PLLA fiber membrane and keeps its mechanical stability longer, making it more suitable for tissue engineering.
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