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ABSTRACT Two‐photon polymerization (TPP) is a powerful technique to create microscale structures with high precision, offering significant potential in tissue engineering and drug delivery. While conventional TPP‐fabricated drug carriers rely on passive encapsulation, these systems often suffer from low payload capacity and diffusion‐controlled release kinetics. To address these challenges, we present the first demonstration of TPP‐printed polyprodrug microstructures, where the therapeutic agent is covalently integrated into the polymer network as the repeating unit itself. Estrogen‐based diacrylate monomers derived from 17β‐estradiol were synthesized via one‐step esterification/transesterification to create a photocurable resin. Curing under flood UV irradiation yielded a rigid thermoset (E′ ∼2.5 GPa at 25°C) with a glass transition temperature of about 50°C. Using TPP, we fabricated various microscale needles (100 × 100 × 400 µm, 2 µm resolution) from this resin, enabling direct printing of intrinsically therapeutic microstructures without post‐processing drug loading. The cured polymer acts as both a structural matrix and a hydrolytically degradable polyprodrug, releasing estradiol through cleavage of ester bonds. By combining covalent drug‐polymer integration with high‐resolution 3D printing, this work establishes a platform for personalized transdermal drug delivery devices with spatially controlled release profiles determined by microstructure design and polymer degradation kinetics.
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Mechanistic Computational Modeling of Implantable, Bioresorbable Drug Release Systems
Abstract Implantable, bioresorbable drug delivery systems offer an alternative to current drug administration techniques; allowing for patient‐tailored drug dosage, while also increasing patient compliance. Mechanistic mathematical modeling allows for the acceleration of the design of the release systems, and for prediction of physical anomalies that are not intuitive and may otherwise elude discovery. This study investigates short‐term drug release as a function of water‐mediated polymer phase inversion into a solid depot within hours to days, as well as long‐term hydrolysis‐mediated degradation and erosion of the implant over the next few weeks. Finite difference methods are used to model spatial and temporal changes in polymer phase inversion, solidification, and hydrolysis. Modeling reveals the impact of non‐uniform drug distribution, production and transport of H+ions, and localized polymer degradation on the diffusion of water, drug, and hydrolyzed polymer byproducts. Compared to experimental data, the computational model accurately predicts the drug release during the solidification of implants over days and drug release profiles over weeks from microspheres and implants. This work offers new insight into the impact of various parameters on drug release profiles, and is a new tool to accelerate the design process for release systems to meet a patient specific clinical need.
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- Award ID(s):
- 1752366
- PAR ID:
- 10459343
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 35
- Issue:
- 51
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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