Research Project
9590506
PROJECT SUMMARY Cleft lips and/or palates are common craniomaxillofacial birth defects. Properly restoring severe cleft palates remains a major challenge because there are frequently insufficient autologous soft tissues to close the open wounds, causing high tension at the surgical junction and commonly leading to secondary palatal fistulas, wound contraction, scar formation, and facial growth disturbances. Furthermore, since the ideal time for renovating cleft palate is shortly after birth, surgeries should cause minimal disruption of the skeleton to allow ongoing tissue growth in children. Recent advances in 3D printing with biomaterials have shown great potential in creating living tissues for patient-specific treatments. Individualized skeletal reconstruction can be realized by combining CT techniques and 3D printing, which is especially relevant for craniomaxillofacial repair, since the craniomaxillofacial bone is the most anatomically complex and varied region of the body. To protect the implanted bone, a barrier can be employed to cover the bone grafts, preventing fibrous invasion, stabilizing the bone implant, and enhancing bone regeneration. This research aims to develop an individualized multiplex composite for severe cleft palate repair in growing children that assures single-stage defect closure and easy handling, and allows for tissue growth of the implant following the development of adjacent tissues. In doing so, we will develop a barrier and 3D bio-plotted bony composite through incorporating a synthetic polymer and bioactive molecules into a defined 3D architecture and investigate their efficacy in 1) modulating bone marrow derived mesenchymal stem cells (BM-MSCs) during the course of osteogenesis and angiogenesis in vitro, 2) guiding hard and soft tissue reconstruction during rat growth, 3) facilitating bone regeneration and revascularization and reducing associated complications in rats with critical- sized palate and cranium defects. To achieve this aim, our laboratory has developed two enabling technologies prepared for this study: 1) we have developed a poly (1,8-octanediolco-citrate) (POC) hybridized decellularized human amnion membrane (DAM) for use as the barrier for cleft palate repair. The POC incorporated DAM scaffold can better maintain the natural matrix structure and improve both hard and soft tissue remodeling during the palatal healing process, and 2) we have created a young rat model with critical-sized cleft palate that enables us to investigate the growth potential of different grafts in the oral environment as the rat grows. The significance of this research lies in our ability to develop a functional, tissue engineered, bony composite that can mimic native palate tissues, maximize cell ingrowth and function, allow ongoing tissue growth, and reduce the associated complications and healing time of surgery. We hope and expect that this technique will advance soft and hard tissue reconstruction in growing children with cleft palates and/or other craniomaxillofacial defects. Importantly, knowledge gained from the proposed research will provide a better understanding of the fundamental bioengineering techniques in the development of bio-artificial bone support systems and in bone regenerative medicine.
