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.

适当地恢复生长期儿童缺失的骨骼组织的形式和功能是一个值得注意的 挑战.幼儿颅颌面骨的缺陷代表了一个重要的情感和 经济负担，因为它们的恢复/再生通常需要多次骨移植手术（通常 从头骨、臀部或肋骨获得），以便随着孩子的成长获得足够的治疗效果。近期 开发定制的3D打印可降解生物活性陶瓷支架，可以适应和填充大骨 缺损和在缺损边缘内快速再生的骨可以提供新的解决方案， 具有被设计为促进更快速和完全的骨愈合的试剂的支架可以增加 生长期儿童颅颌面骨缺损的治疗这种做法将消除 用于骨移植物获取的二次手术部位，具有极大的潜力， 由于儿童生长，再生骨将跟随相邻骨的生长， 结构.开发这种骨骼缺陷治疗方案将是前所未有的 儿童和成人骨重建手术的进展。我们最近 进行了初步研究，其中定制的3D打印可降解生物活性陶瓷支架涂层 与刺激腺苷受体的药物（即双嘧达莫）一起使用，显著增强了骨再生。 目前正在1 R 01 AR 068593 -01下研究该效应的细胞和分子基础。 通过这种方法，我们成功地在兔模型中再生了血管化骨， 从长骨和下颌骨的临界尺寸节段性缺损到极薄和扁平的临界尺寸缺损 颅颌面复合体的骨头。因此，我们建议测试3D打印可降解的假设， 涂有双嘧达莫的生物活性陶瓷支架可以促进骨快速再生到缺损处， 再生骨通常会跟随邻近结构的生长和发育， 直到骨骼完全生长完成。因此，我们提出以下目标： 最大化双嘧达莫与个性化3D打印生物活性支架的组合， 未成年人颅颌面缺损的修复及骨再生监测 随着时间在成功完成目标I（R21）后，我们将把开发的技术转化为再生能源， 并在较长时间内监测临床相关（人体尺寸）颅颌面缺损， 骨骼发育不成熟的高度平移的大型动物物种，其呈现骨组织生长动力学 更像人类。Aim II. (R33)将开发的个性化3D打印生物活性 陶瓷支架治疗颅颌面骨缺损的实验研究 动物物种，并监测随着时间的推移再生骨生长。