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.

PROJECT NARRATIVE We propose a novel structurally, compositionally biomimetic bone scaffolding system that possesses osteoconductive and osteoinductive characteristics for orofacial cleft reconstruction. We will utilize 3D bioprinting strategies to develop personalized bone scaffolds for long-term use that will adapt to the needs of growing children. This proposed study will explore the potential of clinically applicable 3D bioprinting workflow using clinically relevant surgical animal models and utilize NIR fluorescent imaging technique as noninvasive real-time monitoring to determine the new bone formation along with implanted scaffold degradation.