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Therapeutic interventions for PAH are limited in part by the lack of\n                    <jats:italic>in vitro<\/jats:italic>\n                    screening platforms that accurately reproduce dynamic arterial wall mechanical properties. Here we present a 3D-bioprinted model of the pulmonary arterial adventitia comprised of a phototunable poly(ethylene glycol) alpha methacrylate (PEG-\u03b1MA)-based hydrogel and primary human pulmonary artery adventitia fibroblasts (HPAAFs). This unique biomaterial emulates PAH pathogenesis\n                    <jats:italic>in vitro<\/jats:italic>\n                    through a two-step polymerization reaction. First, PEG-\u03b1MA macromer was crosslinked off-stoichiometry by 3D bioprinting an acidic bioink solution into a basic gelatin support bath initiating a base-catalyzed thiol-ene reaction with synthetic and biodegradable crosslinkers. Then, matrix stiffening was induced by photoinitiated homopolymerization of unreacted \u03b1MA end groups. A design of experiments approach produced a hydrogel platform that exhibited an initial elastic modulus (\n                    <jats:italic>E<\/jats:italic>\n                    ) within the range of healthy pulmonary arterial tissue (\n                    <jats:italic>E<\/jats:italic>\n                    = 4.7 \u00b1 0.09 kPa) that was stiffened to the pathologic range of hypertensive tissue (\n                    <jats:italic>E<\/jats:italic>\n                    = 12.8 \u00b1 0.47 kPa) and supported cellular proliferation over time. A higher percentage of HPAAFs cultured in stiffened hydrogels expressed the fibrotic marker alpha-smooth muscle actin than cells in soft hydrogels (88 \u00b1 2% versus 65 \u00b1 4%). Likewise, a greater percentage of HPAAFs were positive for the proliferation marker 5-ethynyl-2\u02b9-deoxyuridine (EdU) in stiffened models (66 \u00b1 6%) compared to soft (39 \u00b1 6%). These results demonstrate that 3D-bioprinted, phototunable models of pulmonary artery adventitia are a tool that enable investigation of fibrotic pathogenesis\n                    <jats:italic>in vitro<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1088\/1758-5090\/aca8cf","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T17:18:59Z","timestamp":1670260739000},"page":"015017","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["3D-bioprinted, phototunable hydrogel models for studying adventitial fibroblast activation in pulmonary arterial hypertension"],"prefix":"10.1088","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-8018","authenticated-orcid":true,"given":"Duncan","family":"Davis-Hall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brisa","family":"Pe\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6988-8584","authenticated-orcid":true,"given":"Chelsea M","family":"Magin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"bfaca8cfbib1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1378\/chest.15-0300","type":"journal-article","article-title":"Five-year outcomes of patients enrolled in the REVEAL registry","volume":"148","author":"Farber","year":"2015","journal-title":"Chest"},{"key":"bfaca8cfbib2","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1111\/j.1582-4934.2007.00099.x","type":"journal-article","article-title":"Tissue engineering of blood vessel","volume":"11","author":"Zhang","year":"2007","journal-title":"J. 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