{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T12:49:19Z","timestamp":1782046159373,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,17]]},"group-title":"Bioengineering","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DE030480"],"award-info":[{"award-number":["DE030480"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Traumatic cranial defects often involve concurrent loss of soft and hard tissues and can progress to chronic defects due to delayed healing associated with infection or other co-morbidities. Despite autologous reconstruction remaining the clinical standard, it requires staged procedures using heterogeneous tissues, increasing operative time, costs, and surgical risks. Moreover, current tissue engineering approaches focus on single tissues or acute tissue defect models, limiting their clinical applications. Herein, we describe an acellular, material-driven 3D-printed composite scaffold designed to regenerate both bone and skin within composite cranial defects. The scaffold integrates controlled copper ion release from both organic and inorganic components with 3D-printed citrate polymer and citrate polymer\u2013ceramic composites. Integrated thermoresponsive citrate-based hydrogels further enable spatially defined dermoconductive and osteoconductive properties, supporting a one-step surgical approach. At 12 weeks post-implantation, our scaffold enhanced keratinocyte organization, collagen deposition, and defect coverage with mature bone, achieving histological outcomes comparable to autografts. Furthermore, the system suppressed bacterial burden. Thus, this acellular platform represents a clinically promising synchronized strategy to address the complex demands of traumatic craniofacial composite defects.<\/jats:p>","DOI":"10.64898\/2026.06.16.732662","type":"posted-content","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:35:14Z","timestamp":1781732114000},"source":"Crossref","is-referenced-by-count":0,"title":["Simultaneous regeneration of skin and bone in full-thickness cranial composite defects"],"prefix":"10.64898","author":[{"given":"Mirae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA"},{"name":"Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center; Chicago, IL, 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivakalyani","family":"Adepu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA"},{"name":"Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caralyn P.","family":"Collins","sequence":"additional","affiliation":[{"name":"Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, 60208, USA"},{"name":"Department of Mechanical Engineering, Northwestern University; Evanston, IL, 60208 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mendez-Santos","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA"},{"name":"Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, 60208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2744-0896","authenticated-orcid":false,"given":"Cheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, 60208, USA"},{"name":"Department of Mechanical Engineering, Northwestern University; Evanston, IL, 60208 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong-Chuan","family":"He","sequence":"additional","affiliation":[{"name":"Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL, 60208, USA"},{"name":"Molecular Oncology Laboratory, Department of Orthopedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center; Chicago, IL, 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell 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