Topographical cues play an important role in influencing cellular behavior and are considered as significant parameters to be controlled in tissue engineering applications. This work investigated the biocompatibility with regard to scaffold architecture and topographical effect of nanofibrous scaffolds on the in vivo and in vitro foreign body reaction. Random and aligned polycaprolactone (PCL) nanofibers were fabricated by electrospinning technique, with diameters of 313 +/- 5 nm and 506 +/- 24 nm, respectively. Primary monocytes isolated from five human donors were cultured on PCL nanofibers, PCL film, and RGD-coated glass in vitro and cell density and morphology was evaluated at time points of day 0 (2 h), day 3, day 7, and day 10. The in vivo study was carried out by implanting PCL nanofibers and film scaffolds subcutaneously in rats to test the biocompatibility and host response at time points of week 1, week 2, and week 4. The in vitro studies revealed that the initial monocyte adhesion on the aligned fiber scaffold was significantly less (p < 0.001) when compared to the random fiber scaffold. The in vivo study showed that the thicknesses of fibrous capsule on fibrous scaffolds were 7.55 +/- 0.54 microm for aligned fibers and 4.13 +/- 0.31 microm for random fibers, which were significantly thinner than that of film implants 37.7 +/- 0.25 microm (p < 0.001). Additionally, cell infiltration was observed in aligned fibrous scaffolds both in vitro and in vivo, while on random fibers and films, distinct fibrous capsule boundaries were found on the surfaces. These results indicate that aligned electrospun nanofibers may serve as a promising scaffold for tissue engineering by minimizing host response, enhancing tissue-scaffold integration, and eliciting a thinner fibrous capsule.
Astrocyte-nanofiber interactions are studied by culturing primary rat cortical astrocytes on poly[caprolactone-co-(ethyl ethylene phosphate)] electrospun nanofibers and solvent-cast films (two-dimensional control). The results indicate that nanofiber topography significantly suppresses astrocyte proliferation and enhances apoptosis, without altering cellular activation as compared to films. Moreover, nanofiber topography enhances gene-silencing efficiency in astrocytes. The results suggest that nanofibers may serve as potential substrates for nerve regeneration by suppressing astrocyte growth and may further facilitate the use of gene-silencing to enhance CNS regeneration.
Lastly, I want to express my biggest appreciation to my parents, for their unconditional love and selfless support through all these year. They sacrificed too much to raise me up and always give me full support to pursue my dreams. No matter where I am and what I'm going to be, I know they will always be with me. I always want to say 'thank you' to my dear friends. Those tears and laughters shared with you guys are priceless memories that I treasure deep in my heart. A special thank you to Hongfang, who helped and supported me all the way through (maybe) the darkest time. I can't imagine how worse those nights could be for me without your company. Without any of you, I can't get through this journey. v
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