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

项目摘要/摘要 口面部裂是人类最常见的头面部出生缺陷之一，其特点是 分离鼻腔和口腔的口腔和面部结构的不完全形成。这些先天的 如果不能通过对嘴唇、牙槽、硬/软腭部的一系列手术干预成功治疗， 可能导致儿童上颌骨和面中部发育严重异常，不足 说话，呼吸功能受损，以及缺乏自尊等心理社会问题。在当前临床中 实践中，硬组织重建的金标准治疗如腭裂和牙槽裂是最多的 通常涉及自体骨移植；然而，自体组织移植的可用性有限， 需要额外的侵入性手术，并有供体部位的发病率。更关键的是， 自体骨移植包括移植后显著的骨丢失和不可预测的成功率。在这 提出的项目，我们的中心假设是在结构上，成分仿生骨支架没有 细胞接种可利用宿主干/祖细胞进行口腔裂隙原位修复。因此，目标是 目的是利用临床相关动物研究这种新型骨支架系统的临床可行性。 口腔裂隙整复模型的建立。为了实现这一点，我们将利用3D生物打印技术来制造一种 具有临床相关大小、形状和结构完整性的个性化骨支架。此外，我们还将利用 一种无创实时近红外(NIR)骨矿化监测成像平台 伴随着支架的降解而再生。我们还假设该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。 核心假设将通过追求三个具体目标来检验：1)开发和表征 应用于口腔裂隙原位修复的仿生骨支架材料的研制 使用近红外功能化骨支架的无创监测系统；3)验证3D生物打印 生物功能化骨支架在临床适用的兔口腔面裂缺损模型中的应用。总而言之，我们 将开发一种具有临床意义的3D生物打印工作流程，可用于口腔裂隙重建。使用 我们成功地完成了这个项目，我们将把这种新颖的方式应用到个性化的创作中 骨移植是治疗儿童口面部裂伤的有效方法。

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.