Clinically Applicable Orofacial Cleft Reconstruction Using Structural, Compositional Biomimetic Bone Scaffolds

使用结构、组合仿生骨支架进行临床适用的口面裂重建

• 批准号: 10671681
• 负责人: Sang Jin Lee
• 金额: $ 60.92万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671681
• 关键词: 3-Dimensional; 3D Print; Acceleration; Affect; Alveolus; Anatomy; Animal Model; Architecture; Autologous; Biomimetics; Bone Matrix; Bone Morphogenetic Proteins; Bone Regeneration; Bone Tissue; Bone Transplantation; Cells; Characteristics; Child; Cleft Lip; Cleft Palate; Clinical; Complex; Congenital Abnormality; Congenital Disorders; Defect; Development; Environment; Extracellular Matrix; Face; Growth; Growth and Development function; Human; Imaging Techniques; Immune response; Impairment; Implant; In Situ; In Vitro; Investigation; Lip structure; Live Birth; Maxilla; Medical Imaging; Methodology; Minerals; Modeling; Monitor; Morbidity - disease rate; Nasal cavity; Near-infrared optical imaging; Operative Surgical Procedures; Oral; Oral cavity; Oryctolagus cuniculus; Osteogenesis; Outcome; Patients; Physiologic calcification; Production; Property; Respiratory physiology; Running; Series; Shapes; Site; Soft Palate; Structure; System; Technology; Testing; Therapeutic; Time; Tissue Engineering; Tissue Grafts; Tissue constructs; Tissues; Validation; Work; alveolar cleft; bioprinting; bone; bone loss; bone scaffold; clinical application; clinical practice; clinically relevant; copolymer; craniofacial; demineralization; design; effective therapy; fluorescence imaging; fluorophore; imaging platform; improved; in vivo; in vivo monitoring; interest; mineralization; non-invasive monitor; novel; novel strategies; orofacial cleft; osteogenic; peptidomimetics; psychosocial; real time monitoring; reconstruction; recruit; repaired; scaffold; self esteem; skeletal; standard care; stem cells; success; tissue reconstruction; tissue regeneration; tricalcium phosphate

PROJECT SUMMARY/ABSTRACT Orofacial clefts are one of the most prevalent craniofacial birth defects in humans, which are characterized by incomplete formation of oral and facial structures that separate the nasal and oral cavities. These congenital disorders, if not successfully managed with a series of surgical interventions on lips, alveolus, hard/soft palates, may lead to critical abnormalities of children’s growth development of the maxillary and the midface, insufficient speaking, impaired respiratory function, and psychosocial problems such as low self-esteem. In current clinical practice, the gold standard treatment for hard tissue reconstruction such as cleft palate with alveolar cleft is most commonly involved with autologous bone graft; however, autologous tissue grafts are limited in availability, require additional invasive surgery, and have donor site morbidity. More critically, the major shortcomings of the autologous bone grafts include significant bone loss after grafting and their unpredictable success rate. In this proposed project, our central hypothesis is that structurally, compositionally biomimetic bone scaffolds without cell seeding could utilize host stem/progenitor cells for in situ orofacial cleft reconstruction. Thus, the objective is to investigate the clinical feasibility of this novel bone scaffolding system using a clinically relevant animal model for orofacial cleft reconstruction. To achieve this, we will utilize 3D bioprinting technology to fabricate a personalized bone scaffold with clinically relevant size, shape, and structural integrity. In addition, we will utilize a noninvasive real-time near-infrared (NIR) fluorescence imaging platform to monitor mineralization for bone regeneration along with scaffold degradation. We also hypothesize that this NIR imaging platform can provide a comprehensive understanding of the relationship between scaffold degradation and in situ bone regeneration. The central hypothesis will be tested by pursuing three Specific Aims: 1) Develop and characterize compositionally biomimetic bone scaffolds for in situ orofacial cleft reconstruction; 2) Develop a novel noninvasive monitoring system using NIR-functionalized bone scaffolds; 3) Validate 3D bioprinted biofunctionalized bone scaffolds in a clinically applicable rabbit orofacial cleft defect model. Upon conclusion, we will develop a clinically relevant 3D bioprinting workflow that can be utilized for orofacial cleft reconstruction. With our successful completion of this project, we will apply this novel approach toward the creation of personalized bone grafts as an effective treatment for orofacial clefts in children.

项目摘要/摘要 口面裂口是人类中最普遍的颅面出生缺陷之一，其特征是 分离鼻和口腔的口服和面部结构的不完整形成。这些先天性 疾病，即使没有成功地通过嘴唇，肺泡，硬/柔软的嘴唇上的一系列手术干预进行管理， 可能导致儿童上颌和中间的成长发展的严重异常，不足 语言，呼吸功能受损和社会心理问题，例如自尊心低。在当前的临床上 练习，硬组织重建的金标准处理，例如肺泡裂口的left裂。 通常与自体骨移植有关；但是，自动组织移植物的可用性有限， 需要其他侵入性手术，并具有供体部位发病率。更重要的是， 自体骨移植物包括嫁接后明显的骨质流失和无法预测的成功率。在这个 拟议的项目，我们的中心假设是，在结构上，合成的仿生骨支架，没有 细胞播种可以利用宿主的茎/祖细胞进行原位的口面裂解重建。那，目标 是为了研究这种新型骨支架系统的临床可行性，使用临床上的动物 口面裂重建的模型。为了实现这一目标，我们将利用3D生物打印技术来制造 具有临床相关的大小，形状和结构完整性的个性化骨支架。此外，我们将使用 一个无创的实时近红外（NIR）荧光成像平台，以监测骨骼的矿化 再生以及脚手架退化。我们还假设这个NIR成像平台可以提供 对支架退化与原位骨再生之间关系的全面了解。 中心假设将通过追求三个具体目标来检验：1）发展和表征 构图仿生的骨支架，用于原位口面裂的重建； 2）发展小说 使用NIR官能化的骨支架的非侵入性监测系统； 3）验证3D生物打印 在临床上适用的兔子口腔裂口缺陷模型中的生物功能化骨支架。总结一下，我们 将开发一个与临床相关的3D生物打印工作流，该工作流可以用于口面裂解重建。和 我们成功完成了该项目，我们将采用这种新颖的方法来创建个性化 骨移植是儿童口腔裂缝的有效治疗方法。