Stem Cells and 3D- printed Biomaterials for Craniofacial Critical Defect Regeneration

用于颅面严重缺损再生的干细胞和 3D 打印生物材料

基本信息

批准号：
9000891
负责人：
Hani A Awad
金额：
$ 21.1万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9000891
关键词：
3D Print Address Allografting American Animal Experiments Animal Model Animals Appearance Autologous Transplantation Biocompatible Materials Biodistribution Biological Biological Assay Biomechanics Blood Vessel Prosthesis Blood Vessels Bone Tissue Bone Transplantation Bypass Canis familiaris Cells Clinical Clinical Trials Custom Cyclic GMP Data Data Analyses Defect Development Development Plans Diagnosis Disease End stage renal failure Engineering Foundations Fracture Future Goals Gold Grant Harvest Hemodialysis Immunocompromised Host Implant In Vitro Infection Knee Lead Malignant Neoplasms Metabolic Diseases Modeling Morbidity - disease rate Muscle Mutagenesis Mycoplasma Myocardial Ischemia Natural regeneration Nature Operative Surgical Procedures Osteogenesis Osteoporosis Outcome Outcome Measure Pain Patients Periosteum Peripheral arterial disease Production Protocols documentation Reagent Recruitment Activity Regenerative Medicine Regulation Regulatory Pathway Research Design Resources Risk Rodent Rodent Model Route Safety Shipping Ships Site Stem cells Sterility Stress Urinary Incontinence Testing Therapeutic Tissue Engineering Tissues Toxic effect Trauma Tumorigenicity Virus Work adult stem cell base bone bone loss craniofacial craniomaxillofacial design experience inclusion criteria malignant mouth neoplasm mathematical model member multidisciplinary non-invasive imaging osteogenic pre-clinical preclinical study product development programs public health relevance regenerative repaired research clinical testing scaffold simulation success therapeutic target tissue regeneration tool

项目摘要

DESCRIPTION (provided by applicant): The goal of the proposed planning grant is to design the foundations for a multidisciplinary Tissue Regeneration Consortium that will conduct pre-clinical studies leading to the submission of an IND application to the U.S. FDA for craniofacial critical defect regeneration. It is estimated that 42,000 Americans and approximately 640,000 people worldwide are diagnosed with oral cancer each year, which is the main cause of maxillectomy or mandibulectomy. In these circumstances, grafts are typically used to repair the defect. Approximately 1.6 million bone grafts are used each year to regenerate bone lost due to trauma or disease, 6% of which are craniomaxillofacial in nature. Today, the `gold standard' of bone grafts is an autograft. Unfortunately, the harvest of an autograft is not always possible and might lead to co-site morbidity and excessive pain. Another option is the allograft, which is readily available but has limited bone formation capability. Therefore, there is a clear clinical need to develop new bone grafts that are both readily available and can efficiently replace the tissue that was lost. To address this major clinical problem, the members of the proposed consortium have established an array of adult stem cells and biomaterials that have been extensively tested in animal models, and some have also been evaluated in clinical trials. Here we propose to build on these therapeutic candidates in order to develop stem cell-biomaterial composites that would receive FDA approval for clinical evaluation. Our primary target product is a tissue-engineered periosteum composed of a stem cell sheet and custom 3D-printed scaffolds for craniofacial segmental defect repair. Our specific goals for the planning period are: 1. Identify the exact product profile. 2. Establish a preclinical development plan. 3. Define a CMC and Manufacturing plan. 4. Establish a regulatory plan. 5. Define a clinical development plan.

描述（由应用程序提供）：拟议的计划赠款的目标是设计一个多学科组织再生联盟的基础，该联盟将进行临床前研究，导致向美国FDA提出IND申请，以进行颅面临界临界缺陷改革。据估计，每年在全球范围内有42,000名美国人和大约64万人被诊断出患有口腔癌，这是上乳切除术或下生髓切除术的主要原因。在这种情况下，图形通常用于修复缺陷。每年使用大约160万骨移植物来再生因创伤或疾病引起的骨骼损失，其中6％的颅颌面是自然界的。如今，骨移植的“金标准”是一种自体移植。不幸的是，自体移植的收获并不总是可能的，可能会导致共同点的发病率和多余的疼痛。另一个选择是同种异体移植物，它容易获得，但骨形成能力有限。因此，很明显的临床需要开发新的骨移植物，这些骨移植物既容易获得，又可以有效地取代丢失的组织。为了解决这一主要临床问题，拟议的财团成员已经建立了一系列成年干细胞和生物材料，这些干细胞和生物材料已在动物模型中进行了广泛测试，并且在临床试验中也进行了评估。在这里，我们建议以这些治疗性候选为基础，以开发出可以获得FDA批准进行临床评估的干细胞生物材料组成。我们的主要目标产物是由干细胞片组成的组织设计的骨膜和定制的3D打印支架，用于颅面分段缺陷修复。我们在计划期间的具体目标是：1。确定确切的产品配置文件。 2。制定临床前发展计划。 3。定义CMC和制造计划。 4。制定监管计划。 5。定义临床发展计划。