Microstructured biodegradable fibers for advanced controlled release

Biodegradable polymers are increasingly at the heart of therapeutic devices. Particularly in the form of thin and elongated fibers, they offer an effective strategy for controlled-release in a variety of biomedical configurations such as sutures, scaffolds, wound dressing, surgical or imaging probes, and smart textiles. So far however, the fabrication of fiber-based drug delivery systems has been unable to fulfill significant requirements of medicated fibers such as multi-functionality, adequate mechanical strength, drug loading capability and complex release profiles of multiple substances. The first part of the work consisted in, for the first time, identifying various grades of biodegradable amorphous thermoplastic polymers poly (D,L-lactic-co-glycolic acid) (PLGA) with the proper thermomechanical and rheological properties to be thermally drawn. Based on this finding, we demonstrate a variety of partially or fully biodegradable fibers with cylindrical and rectangular cross-sectional geometries integrating materials of various biodegradable properties. These fibers are capable of releasing multiples doses or substances in the span of a few weeks to a few months. We experimentally study their degradation and release behavior in vitro, and model the release mechanism via morphological evolution of the degrading polymers. We show examples of thermally drawn biodegradable fibers with high mechanical strength as a result of drawing stress adjustment, that could be used as active sutures. The second objective that arose during the course of the thesis is the tailoring of the release time from a few weeks down to a few days. A composite system comprising PLGA (degradation period of 3 months) as the matrix, and phosphate glass (PG) particles (degradation period of 3 weeks) as filers was studied. We engineered the composition to reach rheological properties similar to the PLGA matrix, so that it can be compatible with the thermal drawing process. It is demonstrated that the incorporation of various contents of phosphate glass particles (5 to 40%) lead to the acceleration of PLGA degradation. Moreover, the acidic pH of PLGA degradation products is neutralized via the suppression of PLGA bulk degradation and the alkali elements of PG particles. The integration of these composites in the release barriers of the fibers also resulted in versatile release profiles ranging from fully diffusion-controlled to erosion-controlled mechanisms. A final part of the thesis investigates the use of multi-material fibers to realize triggered release from external stimuli, the effect of temperature on the release kinetics of PLGA is first analyzed to provide insights for the realization of heat-triggered drug delivery fibers. The acceleration of release was observed upon exposing biodegradable fibers to an increase of temperature in an oven. Relying on joule heating, a novel architecture for electrically-triggered drug delivery fibers is proposed and investigated. This work establishes a novel platform for biodegradable micro-structured fibers for applications in implants, sutures, wound dressing, or tissue scaffolds as well as a step toward the future of pharmaceutics in the realization of active and advanced drug delivery systems.


Advisor(s):
Sorin, Fabien
Year:
2020
Publisher:
Lausanne, EPFL
Keywords:
Laboratories:
FIMAP




 Record created 2020-10-16, last modified 2020-10-16


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