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However, their widespread adoption remains constrained by the high consumption of chemically defined cell culture media. In this study, we introduce a multi\u2010stage electrokinetic waste separation process that regenerates spent media, recovering up to 87.5% of the spent\u2010medium volume for reuse. Using a mock\u2010perfusion model, the regeneration\u2010recycle processes were shown to sustain high\u2010density Chinese hamster ovary cell growth, compared with spent media recycling without regeneration. Integration into a self\u2010recycling perfusion bioreactor (350\u2009mL working volume) operating with 75% regenerated media sustained the target viable cell density and antibody titer, with limited reductions to cell\u2010specific growth rate (~31%) and cell\u2010specific productivity (~9%), supporting the feasibility of high\u2010ratio media recycling. Techno\u2010economic modeling of large\u2010scale scenarios revealed that media regeneration could offer a path to $15\/g COGs, thereby increasing the accessibility of mAbs. Techno\u2010economic modeling of hypothetical large\u2010scale manufacturing scenarios indicated that the experimentally demonstrated process could reduce cost of goods (COG) by approximately 9%, and identified a theoretical pathway toward ~$15\/g COG contingent upon multi\u2010cycle regeneration processes that could be developed in the future. These results support regenerative perfusion as a promising process\u2010intensification strategy that, with further development, may be adaptable to other mammalian cell culture platforms where media cost and sustainability are critical bottlenecks.<\/jats:p>","DOI":"10.1002\/btpr.88550","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T02:17:41Z","timestamp":1785982661000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regenerative perfusion bioreactor for biologics production with lower\n                    <scp>COGs<\/scp>"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4866-5066","authenticated-orcid":false,"given":"Eric","family":"Wynne","sequence":"first","affiliation":[{"name":"Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science College of Engineering  Cambridge Massachusetts USA"},{"name":"Massachusetts Institute of Technology Research Laboratory of Electronics  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9356-0255","authenticated-orcid":false,"given":"Dohyun","family":"Park","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology Research Laboratory of Electronics  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2025-8573","authenticated-orcid":false,"given":"Hourieh","family":"Ahi","sequence":"additional","affiliation":[{"name":"University of Massachusetts Lowell, Department of Biomedical Engineering and Biotechnology Francis College of Engineering  Lowell Massachusetts 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