Year: 2026
Type: preprint
Abstract: 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-ceramic 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.
Authors: Mirae Kim, Yi Zhu, Shivakalyani Adepu, Caralyn P. Collins, Maria Mendez-Santos, Cheng Sun, Tong-Chuan He, Russell R. Reid, Guillermo A. Ameer
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, Northwestern University, National Institutes of Health, Materials Research Science and Engineering Center, Harvard University, National Cancer Institute, National Institute of Dental and Craniofacial Research, Division of Materials Research, Division of Electrical, Communications and Cyber Systems, National Center for Advancing Translational Sciences
Awards: G1082487289, NNCI: Soft Hybrid Nanotechnology Experimental (SHyNE) Resource, G1284175734, G1382277591, G1697802790, G2233802770, G2343375527, G2788453484, G3010471893, G317886719, G3203750490, The Institute for Translational Medicine, Northwestern University Materials Research Science and Engineering Center, G4958141111, G5162417229, G6038498354, G6540817556, G6544658276, G8015433099, G9000046704, G9000243610, The Robert H. Lurie Comprehensive Cancer Center, Multi-Tissue Craniofacial Engineering using 3D-BMP9-Notch-Synergized Graphene Citrate Composite Scaffolds
OpenAlex ID: W7164987376
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