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Conventional methods to introduce porosity\u2014such as particulate leaching, gas foaming, and freeze\u2010drying\u2014can leave cytotoxic residues. We propose a scalable, cytocompatible approach to tune hydrogel porosity using lipid\u2010shelled gas microbubbles as a transient porogen. In this study, we demonstrate that lipid\u2010shelled microbubbles can be incorporated into alginate, poly(ethylene glycol) diacrylate (PEGDA), or gelatin methacrylate (GelMA) precursors, and subsequently expanded post\u2010gelation with mild heat or vacuum to yield controlled porosity. In alginate fibers, the vacuum expansion of embedded microbubbles increased the swelling capacity by approximately 74% relative to nonporous control, without reducing compressive strength. Porous PEGDA hydrogels showed faster degradation (approximately 40% reduction in degradation time) and a lower compressive modulus compared to the dense PEGDA control, reflecting a tunable trade\u2010off between porosity and stiffness. Unlike traditional porogen\u2010based or 3D\u2010printing techniques, this microbubble method requires no toxic additives or specialized equipment and is compatible with both ionic (alginate) and photo\u2010crosslinked (PEGDA, GelMA) systems. We further demonstrate integration of this approach with a microfluidic fiber production platform. We validate that porosity modulation via microbubbles does not adversely affect the viability of mesenchymal stem cells on GelMA hydrogels. Overall, this work establishes a broadly applicable and easily scaled strategy in which porosity can be tuned post\u2010gelation with simple triggers (heat or vacuum), enabling application\u2010specific control of nutrient transport, degradation, and mechanics across multiple biomaterials.<\/jats:p>","DOI":"10.1002\/jbmb.70022","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:07:36Z","timestamp":1767866856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microbubble\u2010Infused Hydrogel Scaffolds With Tunable Porosity for Regenerative\u2010Medicine Applications"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8948-9460","authenticated-orcid":false,"given":"Niloofar","family":"Ghasemzaie","sequence":"first","affiliation":[{"name":"Keenan Research Centre for Biomedical Science St. Michael's Hospital, Unity Health Toronto  Toronto Ontario Canada"},{"name":"Institute for Biomedical Engineering Science and Technology (iBEST)  Toronto Ontario Canada"},{"name":"Biomedical Engineering Graduate Program Toronto Metropolitan University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basel A.","family":"Khader","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science St. Michael's Hospital, Unity Health Toronto  Toronto Ontario Canada"},{"name":"Institute for Biomedical Engineering Science and Technology (iBEST)  Toronto Ontario Canada"},{"name":"Department of Chemical and Biological Engineering American University of Sharjah  Sharjah UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Tran","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science St. Michael's Hospital, Unity Health Toronto  Toronto Ontario Canada"},{"name":"Institute for Biomedical Engineering Science and Technology (iBEST)  Toronto Ontario Canada"},{"name":"Biomedical Engineering Graduate Program Toronto Metropolitan University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saira","family":"Khan","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science St. Michael's Hospital, Unity Health Toronto  Toronto Ontario Canada"},{"name":"Institute for Biomedical Engineering Science and Technology (iBEST)  Toronto Ontario Canada"},{"name":"Department of Electrical, Computer, and Biomedical Engineering Toronto Metropolitan University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar M.","family":"Rahman","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science St. Michael's Hospital, Unity Health Toronto  Toronto Ontario Canada"},{"name":"Institute for Biomedical Engineering Science and Technology (iBEST)  Toronto Ontario Canada"},{"name":"Biomedical Engineering Graduate Program Toronto Metropolitan University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-0246","authenticated-orcid":false,"given":"Dae Kun","family":"Hwang","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science St. Michael's Hospital, Unity Health Toronto  Toronto Ontario Canada"},{"name":"Institute for Biomedical Engineering Science and Technology (iBEST)  Toronto Ontario Canada"},{"name":"Department of Chemical Engineering, Toronto Metropolitan University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Kolios","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science St. Michael's Hospital, Unity Health Toronto  Toronto Ontario Canada"},{"name":"Institute for Biomedical Engineering Science and Technology (iBEST)  Toronto Ontario Canada"},{"name":"Department of Physics Toronto Metropolitan University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott S. 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