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Intra-Operative Bioprinting of Hard,Soft, and Hard/Soft Composite Tissues for Craniomaxillofacial Reconstruction |
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| Authors: | Kazim K. Moncal Hemanth Gudapati Kevin P. Godzik Dong N. Heo Youngnam Kang Elias Rizk Dino J. Ravnic Hwabok Wee David F. Pepley Veli Ozbolat Gregory S. Lewis Jason Z. Moore Ryan R. Driskell Thomas D. Samson Ibrahim T. Ozbolat |
| Affiliation: | 1. Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA, 16802 USA Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802 USA;2. Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802 USA;3. Department of Dental Materials, School of Dentistry, Kyung Hee University, Seoul, 02447 Republic of Korea;4. Department of Neurosurgery, The Pennsylvania State University, Hershey, PA, 17033 USA;5. Department of Surgery, The Pennsylvania State University, Hershey, PA, 17033 USA;6. Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA, 16802 USA Department of Orthopedics and Rehabilitation, The Pennsylvania State University, Hershey, PA, 17033 USA;7. Department of Mechanical Engineering, The Pennsylvania State University, University Park, PA, 16802 USA;8. Mechanical Engineering Department Ceyhan Engineering Faculty, Cukurova University, Adana, 01950 Turkey;9. Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802 USA Department of Mechanical Engineering, The Pennsylvania State University, University Park, PA, 16802 USA;10. School of Molecular Biosciences, Washington State University, Pullman, WA, 99164 USA Center for Regenerative Medicine, Washington State University, Pullman, WA, 99164 USA;11. Department of Neurosurgery, The Pennsylvania State University, Hershey, PA, 17033 USA Department of Surgery, The Pennsylvania State University, Hershey, PA, 17033 USA;12. Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA, 16802 USA |
| Abstract: | Reconstruction of complex craniomaxillofacial (CMF) defects is challenging due to the highly organized layering of multiple tissue types. Such compartmentalization necessitates the precise and effective use of cells and other biologics to recapitulate the native tissue anatomy. In this study, intra-operative bioprinting (IOB) of different CMF tissues, including bone, skin, and composite (hard/soft) tissues, is demonstrated directly on rats in a surgical setting. A novel extrudable osteogenic hard tissue ink is introduced, which induced substantial bone regeneration, with ≈80% bone coverage area of calvarial defects in 6 weeks. Using droplet-based bioprinting, the soft tissue ink accelerated the reconstruction of full-thickness skin defects and facilitated up to 60% wound closure in 6 days. Most importantly, the use of a hybrid IOB approach is unveiled to reconstitute hard/soft composite tissues in a stratified arrangement with controlled spatial bioink deposition conforming the shape of a new composite defect model, which resulted in ≈80% skin wound closure in 10 days and 50% bone coverage area at Week 6. The presented approach will be absolutely unique in the clinical realm of CMF defects and will have a significant impact on translating bioprinting technologies into the clinic in the future. |
| Keywords: | bioinks craniomaxillofacial reconstruction hard/soft composite tissue bioprinting intra-operative bioprinting tissue engineering |