{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T09:06:20Z","timestamp":1779095180727,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,14]]},"group-title":"Bioengineering","reference-count":53,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Health, USA","award":["DE032364"],"award-info":[{"award-number":["DE032364"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Human salivary stem\/progenitor cell (hS\/PC)-loaded hyaluronic acid (HA)-based hydrogels, termed 3D-salivary tissue constructs (3D-ST), hold great promise for restoring salivary gland function post-radiation injury. Here, we developed a next-generation 3D-ST using heparin-modified HA and bioactive peptide-modified hydrogels. This new formulation enables controlled pre-loading and localized presentation of heparin-binding growth factors prior to surgical implantation, providing opportunities to enhance\n                  <jats:italic>in vivo<\/jats:italic>\n                  hS\/PC bioactivity. To model clinically relevant radiation injury, we established an athymic rat model subjected to computed tomography (CT)-guided fractionated radiation, resulting in hallmark features of radiation-induced salivary dysfunction. Over 60-days post-irradiation, glands exhibited progressive loss of acini, increased fibrosis, and disruption of endothelial, neuronal, and myoepithelial compartments. Within this injured environment, a surgical pocket was created to precisely implant 3D-STs to assess graft performance. Fluorescent labeling of the 3D-STs enabled longitudinal tracking post-implantation. Over 14 days, implanted 3D-STs remained structurally stable within irradiated glands, and hS\/PCs remained viable without evidence of local inflammatory responses. Compared to non-injured glands, the irradiated microenvironment suppressed hS\/PC proliferation and phenotype, indicating alterations in the irradiated local tissue negatively impact hS\/PC bioactivity. In addition, host neurovascular migration into the 3D-ST was majorly restricted in irradiated glands, providing new opportunities to enhance biointegration. Overall, this work establishes a reproducible preclinical framework for assessing hydrogel biocompatibility and stability, cell bioactivity, and host-graft biointegration prior to scale up into preclinical large animal models. This study has successfully established a tractable approach for improving 3D-ST formulations to enhance hS\/PC expansion, differentiation, and biointegration following implantation into radiation-injured beds.\n                <\/jats:p>","DOI":"10.64898\/2026.05.11.724009","type":"posted-content","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T18:40:20Z","timestamp":1778784020000},"source":"Crossref","is-referenced-by-count":0,"title":["Assessing Bioactivity and Biointegration of Engineered Salivary Tissue Constructs in a Preclinical Unilateral Fractionated Irradiated Rat Model"],"prefix":"10.64898","author":[{"given":"Kerry P.","family":"Pernick","sequence":"first","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan, 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USA"},{"name":"Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Jia","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Nahass","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thaise C.","family":"Geremias","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warren","family":"Swegal","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, Allegheny Health Network, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew M.","family":"Farach","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Houston Methodist Hospital, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Biomedical Sciences, School of 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