Controlled Release Systems Using Functional Nanofibers for Wound Healing and Tissue Engineering Applications.

摘要

Controlled release systems are of great importance for the healthcare field, with specific emphasis on drug or compound delivery for wound healing and tissue engineering applications. Nonwoven structures are already used extensively in healthcare due to their large surface area, absorbent properties, facile processing scheme, and relative cost-effectiveness. The ability to create functional nonwoven structures with well-controlled morphologies and release properties can now be achieved on the nanoscale utilizing the electrospinning method. Electrospinning utilizes the interplay between electrical forces and surface tension to create fibers with submicron diameters, collected in random mats with high porosity, by applying a strong electric field between a charged drop of polymer solution and a collection plate. These nanofibrous mats provide a compliant mesh that not only resembles the natural extracellular matrix in vivo, but also provides a material with an extremely large surface area to volume ratio for maximizing the interaction of the carrier with a surrounding medium.;The purpose of this work was to develop functional nanofibers using electrospinning system and control the release rate of a variety of compounds from such structures as desired for multiple clinical applications. In all of our experiments polylactic acid (PLA) was used as the polymeric matrix and it was loaded with different compounds such as tricalcium phosphate (TCP) nanoparticles, as an osteoconductive compound for bone tissue engineering, silver nano particles, highly porous silver microparticles, and a silver nitrate base polymeric solution as antibacterial, antimicrobial compound for wound healing application, and ibuprofen as an anti-inflammatory drug for wound healing applications. Fiber morphology, drug concentration and release medium temperature were the main parameters that we manipulated to control the release rate of drugs from nanofibrous structures. For all the drug loaded nanofibrous structures, we determined the release profile and the in vitro cytotoxicity using human skin cells. For some of the drug/nanofiber composite structures we further pursued our experiments and evaluated their toxicity and functionality in vivo .;Our finding confirmed that fiber morphology can change the release profile of drug from nanofibers and subsequently influence the activities of cells seeded on them. TCP nanoparticles encapsulated in porous fibers exhibited the highest release rate as compared to single component and core-sheath nanofibers. The differentiation of human adiposed drive stem cells (hASC) seeded on nanofibers was also influenced by fiber morphology and the highest differentiation observed for the cells seeded on porous fibers. Drug concentration also played an important role in determining the cytotoxicity of nanofibers coated with silver nitrate containing solution. Our results showed that higher silver content in nanofibers results in higher release rate as well as higher chances of cytotoxicity towards human skin cells. Same results observed when quantifying the release of ibuprofen from PLA nanofibers. Lastly, our preliminary in vivo analysis using nude mice model for ibuprofen loaded nanofibers and pig model for silver containing nanofibers showed the potential of our developed functional nanofibers to be used in clinical applications.