Objectives As a promising alternative to the traditional surgical repair of large maxillary and mandibular defects with allograft and autologous bone, we propose non-vital, 3D printed bone grafts that rely on the endogenous cells of the recipient patient. Commonly used for osseous defects, allograft has a limited capacity for in vivo colonization with bone cells, especially for large osseous defects. This study proposes to develop and test in vitro osteoinductive porous grafts, pre-designed to fit the patients-specific defects, and custom manufactured specifically to the patient to be grafted, by 3D bioprinting with specific controlled-release of selected growth factors and cytokines. Methods To this goal, Richard L. Roudebush VAMC offers expertise in clinical 3D imaging and computer-assisted design, combined with the state-of-the-art technology available in newly created 3DTissue Bioprinting Core laboratory, equipped with a regenHU 3DDiscovery ?Evolution? bioprinter. The first Specific Aim will be the generation of such constructs by creating models of patient-specific maxillary and mandibular bone defects and then of their precisely fitting grafts, using the software on our bioprinter. These models will be plotted using as structural component a calcium triphosphate/hydroxyapatite scaffold, and as bioactive component a hydrogel containing growth factors-releasing microbeads. The second Specific Aim will be the in vitro testing of this construct?s bioactivity, by assessing the kinetics of growth factors release and by determining its ability to induce cell recruitment and differentiation. If successful, this project will stand by itself by generation of an improved technology for rapid, personalized and biocompatible tissue engineering of bone implants, with applicability to maxillofacial, cleft palate and many other instances of skeletal repair throughout the body ? all are common with reconstruction of combat injuries and defects from cancer treatments. Follow-Up Study (not this study) This project contains several innovative approaches: a dual paste-hydrogel printing, addition of growth factors in microbeads within the hydrogel, testing intra-construct cell mobility and differentiation -- all will need to be first optimized before beginning the next study that will explore an elaborate systematic method of finding the best combination of growth factors, cytokines, and scaffolding for bone grafts. This will rapidly and much more efficiently lead to large animal models for an eventual rapid and easier translation to clinical use
An improved, rapid, significantly more controlled, and predicable bone grafting will be extremely useful in surgical rehabilitation for the following reasons: i) Now-frequent injuries from Iraq & Afghanistan. The Joint Theater Trauma Registry (JTTR) queried for data from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF), from January 2003 to May 2011 indicate that of the 37,523 discrete facial and penetrating neck injuries that occurred in 7,177 service members injured, fracture sites occurred in the maxilla (25%) and mandible (21%). Many of these injuries require dental restorative procedures that will include intraoral bone grafts; ii) Bone grafting significant resorption that very commonly follows extraction of teeth; iii) Reconstruction of loss from combat injuries and pathoses (such as cancer) throughout the body; iv) This proposal is primarily relevant to ridge augmentation, but also has applications for congenital cleft alveolar bone grafting as well as traumatic bone grafting after gunshot, explosive, or extirpative events.
