Engineering Personalized Devices for Craniomaxillofacial Defects

针对颅颌面缺陷设计个性化设备

• 批准号: 10116988
• 负责人: BRUCE Neil CRONSTEIN
• 金额: $ 38.58万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116988
• 关键词: 3-Dimensional; 3D Print; Adult; Affect; Animal Model; Animals; Area; Birth; Blood Vessels; Bone Growth; Bone Morphogenetic Proteins; Bone Regeneration; Bone Tissue; Bone Transplantation; Centers for Disease Control and Prevention (U.S.); Child; Cleft Palate; Clinical Treatment; Complex; Congenital Abnormality; Craniosynostosis; Custom; Defect; Development; Devices; Differentiation and Growth; Dipyridamole; Economic Burden; Economics; Emotional; Engineering; Face; Funding; Growth; Growth and Development function; Hip region structure; Human; Incidence; Infection; Investigation; Joint structure of suture of skull; Laboratory Animal Models; Lead; Length of Stay; Life; Live Birth; Longitudinal Studies; Mandible; Mesenchymal Stem Cells; Modeling; Molecular; Monitor; Morbidity - disease rate; Natural regeneration; Nerve Pain; Operative Surgical Procedures; Organ Transplantation; Oryctolagus cuniculus; Osteitis; Osteoblasts; Osteogenesis; Pain management; Phase; Postoperative Pain; Procedures; Purinergic P1 Receptors; Reconstructive Surgical Procedures; Site; Skeletal Development; Source; Structure; Surgeon; Technology; Testing; Thinness; Time; Translating; Translations; Treatment outcome; United States; base; bioactive ceramic; bone; bone healing; bone loss; care costs; cleft lip and palate; clinically relevant; craniofacial; craniomaxillofacial; cranium; design; disability; flat bone; hip bone; implantation; improved; long bone; morphogens; mortality; novel; pre-clinical; reconstruction; repaired; restoration; rib bone structure; scaffold; side effect; skeletal; skeletal maturation; skeletal tissue; standard of care; stem cell migration

Appropriate restoration of form and function of the missing skeletal tissue of growing children is a remarkable challenge. Defects in the craniomaxillofacial bones of young children represent a significant emotional and economic burden as their restoration/regeneration often requires multiple bone grafting procedures (usually procured from the skull, hip, or ribs) for adequate treatment outcomes as the child grows. The recent development of custom 3D printed degradable bioactive ceramic scaffolds that can fit and fill large bone defects and quickly regenerate bone within defect margins may provide a novel solution and coating these scaffolds with agents designed to promote more rapid and complete bone healing may increase the efficacy of craniomaxillofacial bone defect treatment in growing children. Such an approach would eliminate the necessity for secondary surgical sites for bone graft procurement and has tremendous potential to minimize/eliminate multiple surgical procedures due to child growth, as the regenerated bone will follow the growth of adjacent structures. The development of such a treatment option for skeletal defects would be an unprecedented advance in bone reconstructive surgery of both growing children and that of adults. We have recently conducted preliminary studies where customized 3D printed degradable bioactive ceramic scaffolds coated with agents, which stimulate adenosine receptors (i.e. dipyridamole), remarkably enhanced bone regeneration. The cellular and molecular basis for this effect is currently under investigation under 1R01AR068593-01. Through this approach, we have successfully regenerated vascularized bone in rabbit models ranging from critical size segmental defects of long bones and mandible to critical size defects of extremely thin and flat bones of the craniomaxillofacial complex. Thus, we propose to test the hypothesis that 3D printed degradable bioactive ceramic scaffolds coated with dipyridamole can promote rapid bone regeneration into a defect and that the regenerated bone will normally follow adjacent structures’ growth and development in skeletally immature subjects until full skeletal growth is complete. We therefore propose the following aims: To maximize the combination of dipyridamole with personalized 3D printed bioactive scaffolds for the repair of craniomaxillofacial defects in skeletally immature subjects and monitor the regenerated bone over time. After successfully completing Aim I (R21), we will translate the developed technology to regenerate and monitor over an extended period of time clinically relevant (human size) craniomaxillofacial defects in skeletally immature highly translational large animal species, which presents bone tissue growth dynamics more similar to human. Aim II. (R33) To translate the developed personalized 3D printed bioactive ceramic scaffolds to treat craniomaxillofacial bone defects in a skeletally immature highly translational animal species and monitor the regenerated bone growth over time.

适当的形式和功能的恢复缺失的骨骼组织的成长中的儿童是一个显着的