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In this work, we report a multifunctional co-drug delivery coating approach that modifies native PCL to enhance hemocompatibility. A nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), is incorporated within the PCL substrate to provide sustained antiplatelet, antithrombotic, and antibacterial activity, while a hydrophilic HydroMed D4 polyurethane coating loaded with the antiplatelet drug ticagrelor (TIC) forms an antibiofouling interface and enables controlled drug elution. The performance of this integrated system was evaluated as a function of TIC loading and compared with relative controls to assess its antifoulant and thromboresistant properties under plasma protein and whole-blood exposure. The layered coating significantly reduced protein adsorption, platelet adhesion\/activation, and bacterial attachment compared with single-component surfaces, demonstrating complementary effects that enhance hemocompatibility. This platform establishes a scalable approach to engineer biodegradable polymers into multifunctional coatings suitable for blood-contacting medical devices, such as catheters and vascular interfaces.<\/jats:p>","DOI":"10.1021\/acsami.6c10964","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:33:11Z","timestamp":1785853991000},"page":"42404-42416","source":"Crossref","is-referenced-by-count":0,"title":["Antiplatelet Co-drug Delivery System Surface Coating for Improved Hemocompatibility on a Nitric Oxide-Releasing Medical-Grade Polymer"],"prefix":"10.1021","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9028-6010","authenticated-orcid":true,"given":"Tia N.","family":"Shorter","sequence":"first","affiliation":[{"name":"University of Georgia , , , ,","place":["Athens, Gerogia, United States, 30602"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Marx","sequence":"additional","affiliation":[{"name":"University of Georgia , , , ,","place":["Athens, Gerogia, United States, 30602"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9369-7374","authenticated-orcid":true,"given":"Hitesh","family":"Handa","sequence":"additional","affiliation":[{"name":"University of Georgia , , , ,","place":["Athens, Gerogia, United States, 30602"]},{"name":"University of Georgia , , , ,","place":["Athens, Georgia, United States, 30602"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-5448","authenticated-orcid":true,"given":"Elizabeth J.","family":"Brisbois","sequence":"additional","affiliation":[{"name":"University of Georgia , , , ,","place":["Athens, Gerogia, United States, 30602"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"issue":"3","key":"2026081706071709600_cit1","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1182\/blood.2019002260","article-title":"Peripherally inserted central catheters lead to a high risk of venous thromboembolism in children","volume":"135","author":"Jaffray","year":"2020","journal-title":"Blood"},{"issue":"1","key":"2026081706071709600_cit2","doi-asserted-by":"publisher","DOI":"10.1177\/0300060518820744","article-title":"Risk factors associated with peripherally inserted central catheter-related venous thrombosis in hospitalized patients of advanced age","volume":"48","author":"Song","year":"2020","journal-title":"J. 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