Fabrication of silk reservoir implants for sustained drug delivery and other applications
Abstract: In the
modern era of medicine there exist numerous approaches to safe, efficacious drug
delivery. Implantable systems containing reservoirs of drug offer several advantages
over traditional oral regimens, including improved drug bioavailability, limited
systemic toxic effects of potent therapeutics through local implantation, modulated and
multi-phase release, and reduced dosing ... read morefrequencies allowing for enhanced patient
compliance. Furthermore, sustained delivery implants have the ability to secrete drug at
a near-constant release rate over long periods, providing even more robust alternatives
to chronic oral medications. The materials used to construct these systems, however, can
exhibit several shortcomings; they are often not bioresorbable and thus require a
secondary surgery to remove from the body, and can sometimes only be generated by
fabrication processes that require harsh chemical solvents. Here, a novel fabrication
process to create biodegradable drug reservoir systems made from regenerated silk
fibroin protein solution (23% w/v) is demonstrated. Loadable systems (inner diameter 3.0
mm; wall thickness < 250µm) were developed in a reproducible manner using an
all-aqueous solution-gel-solid phase transition curing process, and released two
different clinically-relevant therapeutics at a near-constant rate for 30 days (>
100µg / day). Systems were analyzed for both their chemical and mechanical
characteristics - analysis of crystalized protein secondary structure revealed the
systems to be of similar composition compared to previously-generated solid silk
materials, while radial compression (1mm / min) testing of unloaded systems suggests
they have a range of Young's modulus values similar to cancellous (spongy) bone (100 -
250 MPa), which is relevant when considering potential implantation sites of functional
systems. These silk reservoirs demonstrated a degree of compliance when placed under
cyclic compression (12.5mHz up to 17.5% strain), and are the first solid silk materials
to be generated as "complex" shapes (hollow cylinders) via an additive molding
manufacturing process. Therefore, this fabrication approach has the potential to be
leveraged for applications outside of drug delivery including in the areas of tissue
engineering and diagnostic sensing.
Thesis (M.S.)--Tufts University, 2018.
Submitted to the Dept. of Mechanical Engineering.
Advisor: Chris Rogers.
Committee: David Kaplan, and Jeffrey Guasto.
Keywords: Biomedical engineering, Biomechanics, and Materials Science.read less
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