Abstract
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.
Highlights
One of the greatest challenges in modern medicine is the manufacturing of therapies that maximize the precision and personalization for individual patients
In identifying a delivery method that provides maximal versatility, we wanted to design a device that (1) is capable of holding therapeutic agents in a fixed container; (2) can release agents over time based on the design of the tool, materials used in its production, and contents of the device; (3) is able to be tailored according to different situational needs; and (4) is local in its direct effect
We developed a device we call the Biocage (Fig. 1): a hollow cylinder with perforated holes on the exterior designed for the delivery of therapeutic agents for precise and controlled release (Fig. 1a)
Summary
One of the greatest challenges in modern medicine is the manufacturing of therapies that maximize the precision and personalization for individual patients. The integration of pharmacological agents within these materials is a challenge, as the printing process may affect the stability of the drugs and its ability to elute in surrounding tissues[25,41,54] Given these current shortcomings, there exists a need for a customizable drug delivery device that offers both a precise means of delivery along with a flexibility of design. We demonstrate the consistency and resolution of the printed Biocages; its ability to release materials through its pores; its direct and local delivery into brain tissue; its stability in placement after delivery into tissues; and its effects after in vivo implantation This strategy has the potential for focal and minimally invasive delivery of desired therapeutic agents into tissues of interest, while offering immense flexibility in designing and filling the device dependent on the situational need
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