{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:20:36Z","timestamp":1778692836512,"version":"3.51.4"},"reference-count":224,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Chronic liver disease remains a major global health burden, with liver transplantation as the only definitive therapy despite severe limitations in donor availability, surgical morbidity, and patient eligibility. Although the liver has substantial intrinsic regenerative capacity, endogenous repair is often insufficient in chronic injury, cirrhosis, and acute-on-chronic liver failure. As a result, regenerative strategies that restore liver function without whole-organ replacement are increasingly pursued. This review examines controlled release biomaterial-based liver regeneration platforms, particularly those that utilize hydrogels and\/or complementary nanoparticle systems, as clinically practical tools to enhance endogenous regeneration. We include discussion of both 3D scaffold-based and injectable hydrogels to enhance regeneration. Used as biological support and controlled release mixtures, they enable local retention, entrapping and controlling the release of regenerative cues including growth factors (HGF, EGF, etc.), nucleic acids for gene expression, stem cells or other cell populations, and conditioned extracellular vesicles, overcoming poor cell engraftment, short cytokine half-lives, and other limitations. Further, synthetic nanoparticles can structure release at the protein\/molecular level as well as catalytically modulating oxidative stress and inflammation. Within the context of these systems, we structure the anatomical, engineering, and imaging considerations essential for the clinical translation of gel composite systems while highlighting remaining barriers to wider clinical adoption. Collectively, these advances position biomaterial-enabled regenerative therapies as a realistic alternative or bridge to donor restricted liver transplantation.<\/jats:p>","DOI":"10.3390\/gels12050426","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:26:37Z","timestamp":1778689597000},"page":"426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Developing a Clinically Practical Biomaterial Platform for Endogenous Liver Regeneration"],"prefix":"10.3390","volume":"12","author":[{"given":"Carter","family":"Beamish","sequence":"first","affiliation":[{"name":"Department of Material Science and Engineering, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3505-5254","authenticated-orcid":false,"given":"Faraz","family":"Abounorinejad","sequence":"additional","affiliation":[{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Material Science and Engineering, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai Phuong","family":"Tong","sequence":"additional","affiliation":[{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harika","family":"Barri","sequence":"additional","affiliation":[{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8423-9927","authenticated-orcid":false,"given":"Chris","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Material Science and Engineering, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4170-9924","authenticated-orcid":false,"given":"Daniel","family":"Lane","sequence":"additional","affiliation":[{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh","family":"McGregor","sequence":"additional","affiliation":[{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-3032","authenticated-orcid":false,"given":"Grace","family":"Laidlaw","sequence":"additional","affiliation":[{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Jeffries","sequence":"additional","affiliation":[{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ray","family":"Yeung","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Hinds","sequence":"additional","affiliation":[{"name":"Department of Material Science and Engineering, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8974-1494","authenticated-orcid":false,"given":"Miqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Material Science and Engineering, University of Washington, Seattle, WA 98195, USA"},{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan L.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Center for Developmental Biology and Regenerative Medicine, Seattle Children\u2019s Research Institute, Seattle, WA 98105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of BioEngineering, Institute of Stem Cell Regeneration and Medicine University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avik","family":"Som","sequence":"additional","affiliation":[{"name":"Department of Material Science and Engineering, University of Washington, Seattle, WA 98195, USA"},{"name":"Division of Interventional Radiology, Department of Radiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. 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