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

• 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
• 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

 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(由申请人提供)：拟议的规划拨款的目标是为一个多学科组织再生联盟设计基础，该联盟将进行临床前研究，从而向美国FDA提交颅面关键缺陷再生的IND申请。据估计，每年有42,000名美国人和全世界约64,000人被诊断为口腔癌，这是上颌或下颌骨切除的主要原因。在这些情况下，通常使用移植物来修复缺陷。每年约有160万个骨移植用于再生因创伤或疾病而丢失的骨，其中6%是颅颌面骨。如今，骨移植的“黄金标准”是自体移植。不幸的是，自体移植物的收获并不总是可能的，可能会导致同位并发症和过度疼痛。另一种选择是同种异体骨移植，它很容易获得，但骨形成能力有限。因此，临床上显然需要开发既容易获得又能有效地替代丢失的组织的新的骨移植。为了解决这一主要的临床问题，该联盟的成员已经建立了一系列成体干细胞和生物材料，这些细胞和生物材料已经在动物模型中进行了广泛的测试，其中一些也在临床试验中进行了评估。在这里，我们建议在这些候选治疗药物的基础上开发干细胞-生物材料复合材料，该复合材料将获得FDA的批准，用于临床评估。我们的主要目标产品是一种组织工程骨膜，由干细胞片和定制的3D打印支架组成，用于修复颅面部节段性缺陷。我们在计划期间的具体目标是：1.确定准确的产品配置文件。2.制定临床前发展规划。3.定义CMC和制造计划。4.制定监管规划。5.确定临床发展计划。