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: 7531860
• 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/7531860
• 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; Cellular biology; Cephalic; Ceramics; Characteristics; Chemical Engineering; Chemistry; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Collagen; Compatible; Compressive Strength; Congenital Abnormality; Country; Data; Defect; Deformity; Depth; Development; Differentiation Antigens; Drug Delivery Systems; Endothelial Cells; Engineering; Excision; 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; Object Attachment; 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; Program Development; Property; Proteins; Range; Research; Research Personnel; Research Project Grants; ST14 gene; Science; Scientist; Solid; Solutions; Source; Stem cells; Structure; Sus scrofa; Technology; Testing; Time; Tissue Engineering; Tissues; Training; Training Programs; Translating; Transplanted tissue; Trauma; United States Food and Drug Administration; Urination; Vesicle; Water; Weight-Bearing state; Work; Wound Healing; Xenograft procedure; base; biodegradable polymer; bone; bone cell; bone morphogenic protein; career; cell growth; cellular engineering; concept; controlled release; craniofacial; craniofacial complex; day; dentofacial; design; experience; follow-up; gene therapy; improved; in vivo; innovation; nano; nanocomposite; novel; orthognathic; physical property; programs; repaired; scaffold; size; skills; 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）：在为期4年的培训/职业发展计划中，该研究人员在生物材料科学方面具有强大的背景和正畸方面的临床培训方面有很强的背景，三个具体的目的是：（1）涉及组织工程的进一步技能，涉及涉及该领域内部经验和专业知识的多孔型号的型号； （2）在这种类型的组织工程中，使用MAPC（多能成年祖细胞）的新功能； （3）基于对各种类型的牙本质和颅面畸形治疗的患者的纵向随访的临床研究技能。总体长期目标是为颅面复合物（以及体内其他地方）的软组织缺陷构建替代。短期目标是确定仿生羟基磷灰石 - 凝胶蛋白（HAP-GEL）纳米复合材料是否可以用作承载支架的负载型支架，以携带MAPC和生长骨。该培训计划是围绕与四位导师的互动建立的，与上面的每个特定目标有关，并参与UNC临床科学家计划中开发的课程和研讨会。导师是博士。 Mitsuo Yamauchi（胶原蛋白交叉链接在支架发展中用于组织工程中），Wei-shou Hu（干细胞生物学）和叶叶叶（生长因子的应用）和William Proffit（需要对需要进行正性手术进行牙齿牙齿和颅面和颅面上的牙齿矫正的患者进行纵向研究）。提出的短期目标的工作涉及（1）在纳米复合材料的HAPGEL基质上培养MAPC，以使MAPC分化为骨细胞。 （2）设计HAP-GEL矩阵以允许受控生长因子的控制释放，以产生MAPC分化的多个谱系，并最大程度地将MAPC渗透到矩阵中； （3）矩阵的设计以最大化Mapccarrying支架的机械强度，从而可以成为载荷移植物。初步数据显示了成骨细胞与HAP-GEL矩阵之间有希望的相互作用，并且看来这提供了一种非常有利的提供基于MAPC的治疗的方法。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，发育或创伤引起的畸形患者中缺失的组织。使用这种类型的移植物材料，应该可以消除临界大小颅骨和面部缺陷的多次手术。