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.

项目总结/摘要 口面裂是人类最常见的颅面出生缺陷之一，其特征在于： 分隔鼻腔和口腔的口腔和面部结构的不完全形成。这些先天性 疾病，如果不能成功地通过对嘴唇，牙槽，硬/软腭， 可能导致儿童上颌骨和面中部生长发育严重异常， 语言障碍、呼吸功能受损以及自尊心低下等心理问题。用于目前的临床 实践中，硬组织重建的金标准治疗，如腭裂合并牙槽嵴裂， 通常涉及自体骨移植;然而，自体组织移植物的可用性有限， 需要额外的侵入性手术，并且有供体部位的发病率。更关键的是， 自体骨移植物包括移植后显著的骨损失和它们不可预测的成功率。在这 提出的项目，我们的中心假设是，结构，成分仿生骨支架， 细胞接种可以利用宿主干/祖细胞进行原位口面裂重建。因此，目标 目的是研究这种新型骨支架系统的临床可行性， 口面裂修复模型。为了实现这一目标，我们将利用3D生物打印技术制造一个 具有临床相关尺寸、形状和结构完整性的个性化骨支架。此外，我们将利用 无创实时近红外（NIR）荧光成像平台，用于监测骨矿化 再生沿着支架降解。我们还假设这种近红外成像平台可以提供 全面了解支架降解与原位骨再生的关系。 中心假设将通过追求三个具体目标进行测试：1）开发和表征 复合仿生骨支架用于口面裂原位重建; 2）开发一种新型的 使用NIR功能化骨支架的非侵入性监测系统; 3）生物打印的3D生物打印 生物功能化骨支架在临床上适用的兔口面裂缺损模型。在结束时，我们 将开发一个临床相关的3D生物打印工作流程，可用于口面裂重建。与 我们成功地完成了这个项目，我们将应用这种新颖的方法，创造个性化的 骨移植是治疗儿童口面裂的有效方法。