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In this report, a simple method is presented for synthesizing and casting biocompatible polyurethane\u2010poly(ethylene glycol) (PU\u2010PEG) hydrogels with tunable mechanical properties, nonfouling characteristics, and sustained tolerability as an implantable material or coating. The hydrogels are synthesized via a simple one\u2010pot method using commercially available precursors and low toxicity solvents and reagents, yielding a consistent and biocompatible gel platform primed for long\u2010term biomaterial applications. The mechanical and physical properties of the gels are easily controlled by varying the curing concentration, producing networks with complex shear moduli of 0.82\u2013190\u00a0kPa, similar to a range of human soft tissues. When evaluated against a mechanically matched poly(dimethylsiloxane) (PDMS) formulation, the PU\u2010PEG hydrogels demonstrated favorable nonfouling characteristics, including comparable adsorption of plasma proteins (albumin and fibrinogen) and significantly reduced cellular adhesion. Moreover, preliminary murine implant studies reveal a mild foreign body response after 41 days. Due to the tunable mechanical properties, excellent biocompatibility, and sustained in vivo tolerability of these hydrogels, it is proposed that this method offers a simplified platform for fabricating soft PU\u2010based biomaterials for a variety of applications.<\/jats:p>","DOI":"10.1002\/adhm.202201378","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T16:58:45Z","timestamp":1660841925000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Tailored Biocompatible Polyurethane\u2010Poly(ethylene glycol) Hydrogels as a Versatile Nonfouling Biomaterial"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-2015","authenticated-orcid":false,"given":"Alessondra T.","family":"Speidel","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics Karolinska Institutet  Stockholm 171 77 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9966-2669","authenticated-orcid":false,"given":"Phillip R. 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