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.

适当地恢复成长儿童缺失的骨骼组织的形式和功能是一个显着的 挑战。幼儿的颅骨骨骼骨骼中的缺陷代表着一种重要的情感和 经济燃烧，因为他们的恢复/再生通常需要多个骨移植程序（通常 随着孩子的成长，从颅骨，臀部或肋骨中获得的适当治疗结果。最近 定制的3D印刷降解生物活性陶瓷脚手架的开发，可以适合和填充大骨头 缺陷和迅速在缺陷边缘内再生骨骼可能会提供新的解决方案并涂上这些解决方案 具有旨在促进更快和完整骨骼愈合的代理的脚手架可能会提高 成长中的儿童的颅颌面骨缺损治疗。这种方法将消除必要的 用于骨纹采购的次级手术部位，并具有最小化/消除的巨大潜力 由于儿童生长而引起的多项手术程序，因为再生的骨骼将遵循相邻的生长 结构。这种骨骼缺陷的治疗选择的开发将是前所未有的 在成长中的儿童和成年人的骨骼重建手术方面进行改进。我们最近有 进行了初步研究 用刺激腺苷受体（即二吡啶胺）的药物，骨骼再生的增强。 该作用的细胞和分子基础目前正在1R01AR068593-01下投资。 通过这种方法，我们在兔模型中成功再生血管化骨 长骨头的临界尺寸分段缺陷，下颌骨的临界尺寸缺陷非常薄和平坦 颅颌面复合物的骨骼。这是我们建议测试3D打印可降解的假设 用二吡啶胺覆盖的生物活性陶瓷支架可以将快速骨再生促进缺陷和 再生骨通常会遵循相邻的结构的生长和骨骼的发展 未成熟的受试者直到完整的骨骼生长完成。因此，我们提出以下目的： 最大化二吡啶胺与个性化的3D印刷生物活性支架的结合 修复骨骼不成熟受试者中颅颌面缺陷并监测再生的骨骼 随着时间的推移。成功完成AIM I（R21）后，我们将转换开发的技术以再生 并在很长一段时间内进行监测 骨骼不成熟的高度翻译大型动物物种，呈现骨组织生长动力学 与人类更相似。目标II。 （R33）翻译开发的个性化3D印刷生物活性 在骨骼不成熟的高度翻译中，陶瓷支架治疗颅颌面骨缺陷 动物物种并监测随着时间的推移而重生的骨骼生长。