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Synthetic molecules and all\u2010natural or semisynthetic hemoglobin\u2010based oxygen carriers (HBOCs) have seen success as potential circulating oxygen carriers. However, many early HBOC products stalled in development due to side effects from excess hemoglobin in the blood stream and hemoglobin entering the tissue. To overcome these issues, research has focused on increasing the molecular diameter of hemoglobin by polymerizing hemoglobin molecules or encapsulating hemoglobin in liposomal carriers. This work leverages the properties of silk fibroin, a cytocompatible and nonthrombogenic biopolymer, known to entrap protein\u2010based cargo, to engineer a fully protein\u2010based oxygen carrier. Herein, an all\u2010aqueous solvent evaporation technique is used to form silk particles via phase separation from a bulk polyvinyl alcohol phase. Particle size is tuned, and particles are formed with and without hemoglobin. The encapsulation efficiency and ferrous state of hemoglobin are analyzed, resulting in 60% encapsulation efficiency and a maximum of 20% ferric hemoglobin, yielding 100\u2009\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup> active hemoglobin in certain silk fibroin\u2010HBOCs formulations. The system does not elicit a strong inflammation response in\u2009vitro, demonstrating the potential for this particle system to serve as an injectable HBOC.<\/jats:p>","DOI":"10.1002\/anbr.202300019","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:45:49Z","timestamp":1690505149000},"source":"Crossref","is-referenced-by-count":15,"title":["Silk Fibroin Particles as Carriers in the Development of Hemoglobin\u2010Based Oxygen Carriers"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-5050","authenticated-orcid":false,"given":"Marisa O.","family":"Pacheco","sequence":"first","affiliation":[{"name":"Departmentof Chemical Engineering University of Florida  Gainesville FL 32611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9454-0248","authenticated-orcid":false,"given":"Henry M.","family":"Lutz","sequence":"additional","affiliation":[{"name":"Departmentof Chemical Engineering University of Florida  Gainesville FL 32611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jostin","family":"Armada","sequence":"additional","affiliation":[{"name":"Departmentof Chemical Engineering University of Florida  Gainesville FL 32611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6984-0938","authenticated-orcid":false,"given":"Nickolas","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology College of Medicine University of Florida  Gainesville FL 32611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle K.","family":"Gerzenshtein","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Science University of Florida  Gainesville FL 32611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaura S.","family":"Cakley","sequence":"additional","affiliation":[{"name":"Departmentof Chemical Engineering University of Florida  Gainesville FL 32611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-3007","authenticated-orcid":false,"given":"Bruce D.","family":"Spiess","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology College of Medicine University of Florida  Gainesville FL 32611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7467-1737","authenticated-orcid":false,"given":"Whitney L.","family":"Stoppel","sequence":"additional","affiliation":[{"name":"Departmentof Chemical Engineering University of Florida  Gainesville FL 32611 USA"},{"name":"J. 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