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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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Ink Formulation and Selection for Biological Applications of Two-Photon Polymerization
Two-photon polymerization (TPP) uses nonlinear light interactions in photo-cross-linkable precursors to create high-resolution (∼100 nm) structures and high dimensional fidelity. Using a near-infrared light source in TPP results in less scattering and a higher penetration depth, making it attractive for creating biological models and tissue scaffolds. Due to unmatched flexibility and spatial resolution, they range from microvascular constructs to microneedles and stents. This review reviews the working principles and current inks used for TPP-printed constructs. We discuss the advantages of TPP over conventional additive manufacturing methods for tissue engineering, vascularized models, and other biomedical applications. This review provides a short recipe for selecting inks and photoinitiators for a desired structure.
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- Award ID(s):
- 2234496
- PAR ID:
- 10500294
- Publisher / Repository:
- ACS Publications
- Date Published:
- Journal Name:
- ACS Applied Optical Materials
- Volume:
- 1
- Issue:
- 9
- ISSN:
- 2771-9855
- Page Range / eLocation ID:
- 1501 to 1512
- Subject(s) / Keyword(s):
- Microfabrication two-photon polymerization resolution biophotonics vascularized modeling tissue engineering
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acsaom.3c00165
