Engineering a new biomaterial for stem-cell mediated bone regeneration

设计用于干细胞介导的骨再生的新型生物材料

• 批准号: 7666277
• 负责人: Ching-Chang Ko
• 金额: $ 12.69万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7666277
• 关键词: Adhesions; Adult; Affect; Animal Model; Architecture; Area; Artificial Liver; Autologous Transplantation; Biochemistry; Biocompatible Materials; Biology; Biomechanics; Biomimetics; Bone Regeneration; Bone Tissue; Cell Count; Cell Differentiation process; Cell Therapy; Cells; Cephalic; Ceramics; Characteristics; Chemical Engineering; Chemistry; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Collagen; Compressive Strength; Congenital Abnormality; Country; Data; Defect; Deformity; Development; Differentiation Antigens; Drug Delivery Systems; Endothelial Cells; Engineering; Excision; FDA approved; Face; Failure; Family suidae; Fracture; Gelatin; Gene Expression; Genes; Genetic; Goals; Growth; Growth Factor; Hand; Hepatocyte; Hour; Human; Hydroxyapatites; Implant; In Vitro; Infection; Intervention; Jaw; Joints; Kinetics; Laboratories; Liposomes; Longitudinal Studies; Mechanics; Mediating; Mentors; Molecular; Multipotent Stem Cells; Natural regeneration; Non-Viral Vector; Open Fractures; Operative Surgical Procedures; Orthodontics; Osteoblasts; Osteoclasts; Patients; Penetration; Pharmaceutical Preparations; Pharmacy (field); Phase; Physiological; Plant Leaves; Polymers; Porosity; Powder dose form; Procedures; Process; Property; Proteins; Research; Research Personnel; Research Project Grants; ST14 gene; Science; Scientist; Solid; Solutions; Source; Stem cells; Structure; Technology; Testing; Time; Tissue Engineering; Tissues; Training; Training Programs; Translating; Transplanted tissue; Trauma; Vesicle; Water; Weight-Bearing state; Work; Wound Healing; Xenograft procedure; base; biodegradable polymer; bone; bone cell; bone morphogenic protein; career development; cell growth; cellular engineering; controlled release; craniofacial; craniofacial complex; dentofacial; design; experience; follow-up; gene therapy; improved; in vivo; innovation; nano; nanocomposite; novel; orthognathic; physical property; programs; repaired; scaffold; skills; stem cell biology; tumor; vector

DESCRIPTION (provided by applicant): In a 4-year training/career development program for this investigator who has a strong background in biomaterials science and more recent clinical training in orthodontics, three specific aims are: (1) the development of further skills in tissue engineering involving a porous scaffold for ingrowth of tissues, extending previous experience and expertise in this area; (2) new capabilities in use of MAPC (multipotent adult progenitor cells) in tissue engineering of this type; and (3) clinical research skills based on longitudinal follow-up of patients treated for various types of dentofacail and craniofacial deformities. The overall longterm goal is to develop a replacement for both soft and hard tissue defects in the craniofacial complex (and elsewhere in the body). The short-term goal is to determine whether a biomimetic hydroxyapatite-gelatin (HAP-GEL) nanocomposite can serve as a load bearing scaffold to carry MAPC and grow bone. The training program is built around interaction with four mentors, related to each specific aim above, and participation in courses and seminars developed in the clinical scientist program at UNC. The mentors are Drs. Mitsuo Yamauchi (application of collagen cross-linkage in scaffold development for tissue engineering), Wei-Shou Hu (stem cell biology) and Leaf Huang (application of growth factors) and William Proffit (longitudinal studies of patients requiring orthognathic surgery for correction of dentofacial and craniofacial defects). Proposed work toward the short-term goal involves (1) cultivation of MAPC on a nanocomposite HAPGEL matrix so that MAPC differentiate into bone cells; (2) design of the HAP-GEL matrix to allow controlled release of growth factors to produce multiple lineages of MAPC differentiation and maximize penetration of MAPC into the matrix; and (3) design of the matrix to maximize the mechanical strength of the MAPCcarrying scaffold so that it could become a load-carrying graft. Preliminary data show promising interactions between osteoblasts and the HAP-GEL matrix, and it appears that this offers a highly favorable way to offer MAPC-based therapy. The significance of this work is that it can provide a new way to replace missing tissues in patients with congenital, developmental or trauma-induced deformities. With a graft material of this type, it should be possible to eliminate multiple surgeries in the treatment of critical-size cranial and facial defects.

描述（由申请人提供）：该研究者在生物材料科学方面拥有深厚的背景，并且最近接受过正畸学临床培训，在为期 4 年的培训/职业发展计划中，三个具体目标是：（1）进一步发展涉及组织向内生长的多孔支架的组织工程技能，扩展该领域的先前经验和专业知识； (2) 在此类组织工程中使用 MAPC（多能成体祖细胞）的新功能； (3)基于对各种类型牙面和颅面畸形治疗的患者进行纵向随访的临床研究技能。总体长期目标是开发一种替代品来替代颅面复合体（以及身体其他部位）的软组织和硬组织缺陷。短期目标是确定仿生羟基磷灰石-明胶 (HAP-GEL) 纳米复合材料是否可以作为承载 MAPC 和生长骨骼的承载支架。该培训计划围绕与四位导师的互动（与上述每个具体目标相关）以及参与北卡罗来纳大学临床科学家计划开发的课程和研讨会而建立。导师是博士。 Mitsuo Yamauchi（胶原蛋白交联在组织工程支架开发中的应用）、Wei-Shou Hu（干细胞生物学）和 Leaf Huang（生长因子的应用）和 William Proffit（需要正颌手术矫正牙面和颅面缺陷的患者的纵向研究）。为实现短期目标，拟议的工作包括（1）在纳米复合材料 HAPGEL 基质上培养 MAPC，使 MAPC 分化为骨细胞； (2) HAP-GEL基质的设计允许生长因子的受控释放，以产生MAPC分化的多个谱系，并最大限度地提高MAPC对基质的渗透； (3)设计基质以最大化MAPC承载支架的机械强度，使其成为承载移植物。初步数据显示成骨细胞和 HAP-GEL 基质之间有良好的相互作用，这似乎为基于 MAPC 的治疗提供了一种非常有利的方法。这项工作的意义在于，它可以提供一种新的方法来替代先天性、发育性或创伤引起的畸形患者缺失的组织。使用这种类型的移植材料，应该可以消除治疗临界尺寸颅骨和面部缺陷的多次手术。