{"doi":"10.1002/marc.202500467","title":"Polymerized Pro‐Estrogen Microneedles via Two Photon Polymerization","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.","journal":"Macromolecular Rapid Communications","year":2025,"id":549276,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9492,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1434636,"name":"John T. Leman","orcid":"0000-0002-2340-8071","position":1,"is_corresponding":false},{"id":1443996,"name":"Harper Serringer","orcid":null,"position":2,"is_corresponding":false},{"id":288980,"name":"Ke Xia","orcid":"0000-0001-9699-9901","position":3,"is_corresponding":false},{"id":1443472,"name":"Christopher N. LaFratta","orcid":"0000-0003-4585-6278","position":4,"is_corresponding":false},{"id":1443473,"name":"Chaitanya K. Ullal","orcid":"0000-0002-7178-897X","position":5,"is_corresponding":false},{"id":742262,"name":"Edmund F. Palermo","orcid":"0000-0003-3656-787X","position":6,"is_corresponding":false},{"id":1443995,"name":"Lou Yang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:54:07.823422Z","pmid":"41359006","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}