Local and controlled delivery of therapeutic agents directly into focally afflicted tissues is the ideal for the treatment of diseases that require direct interventions. However, current options are obtrusive, difficult to implement, and limited in their scope of utilization; the optimal solution requires a method that may be optimized for available therapies and is designed for exact delivery. To address these needs, we propose the Biocage, a customizable implantable local drug delivery platform. The device is a needle-sized porous container capable of encasing therapeutic molecules and matrices of interest to be eluted into the region of interest over time. The Biocage was fabricated using the Nanoscribe Photonic Professional GT 3D laser lithography system, a two-photon polymerization (2PP) 3D printer capable of micron-level precision on a millimeter scale. We demonstrate the build consistency and features of the fabricated device; its ability to release molecules; and a method for its accurate, stable delivery in mouse brain tissue. The Biocage provides a powerful tool for customizable and precise delivery of therapeutic agents into target tissues.
Purpose
This paper aims to apply a robust methodology to establish relationships between user-configurable process parameters of commercial desktop stereolithography (SLA) printers and dimensional accuracy of a custom-designed test artifact.
Design/methodology/approach
A detailed response surface methodology study, Box–Behnken incomplete factorial design of four factors with three levels, was carried out to evaluate process performance of desktop SLA printers. The selected factors were as follows: printing orientation angle in x-direction, printing orientation angle in y-direction, position on build platform in spatial x-coordinate, position on build tray in spatial y-coordinate and layer thickness. The proposed artifact was designed to include 12 feature groups including thin walls, holes, bosses, bridges and overhangs. Two responses were associated with the features: the dimensional deviation according to the designed value and the minimum feature size.
Findings
Layer thickness was the most significant factor in 70% of the analyzed responses. For example, measurement deviation was reduced about 90% when cylindrical holes were printed with the lowest layer thickness. Further, in many cases, dimensional deviation was minimized for features at the center of the platform, where the beam cures the resin in a straight line. However, at distant positions, accuracy could be improved by compensating for beam deviation by changing the object orientation angle.
Originality/value
The findings of this study can serve, both generally and specifically, for SLA designers and engineers who wish to optimize printing process variables and feature location to achieve high-dimensional accuracy and further understand the many coupled considerations among part design, build configuration and process performance.
Although protein crystallization offers a promising alternative
to chromatography for lower-cost protein purification, slow nucleation
kinetics and high protein concentration requirements are major barriers
for using crystallization as a viable strategy in downstream protein
purification. Here, we demonstrate that nanoparticles functionalized
with bioconjugates can result in an in situ template for inducing
rapid crystallization of proteins at low protein concentration conditions.
We use a microbatch crystallization setup to show that the range of
successful crystallization conditions is expanded by the presence
of functionalized nanoparticles. Furthermore, we use a custom machine
learning-enabled emulsion crystallization setup to rigorously quantify
nucleation parameters. We show that bioconjugate-functionalized nanoparticles
can result in up to a 7-fold decrease in the induction time and a
3-fold increase in the nucleation rate of model proteins compared
to those in control environments. We thus provide foundational insight
that could enable crystallization to be used in protein manufacturing
by reducing both the protein concentration and the time required to
nucleate protein crystals.
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