Engineering a new biomaterial for stem-cell mediated bone regeneration

描述(申请人提供)：在为期4年的培训/职业发展计划中，这位研究人员在生物材料科学方面有很强的背景，最近在正畸方面接受了临床培训，有三个具体目标：(1)发展组织工程方面的更多技能，涉及用于组织植入的多孔支架，扩展该领域先前的经验和专业知识；(2)在这类组织工程中使用MAPC(多潜能成体祖细胞)的新能力；以及(3)基于对接受不同类型牙颌面和颅面畸形治疗的患者的纵向随访的临床研究技能。总体的长期目标是开发一种替代颅面复合体(以及身体其他部位)软组织和硬组织缺陷的材料。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和生长骨骼的支架。培训计划建立在与四位导师的互动基础上，与上述每个具体目标相关，并参与北卡罗来纳大学临床科学家计划制定的课程和研讨会。导师是山内光雄博士(应用胶原交联剂在组织工程支架开发中的应用)、胡卫寿博士(干细胞生物学)和黄叶博士(应用生长因子)以及William Proffit博士(对需要正颌外科手术矫正牙面和颅面缺陷的患者进行的纵向研究)。针对短期目标提出的工作包括：(1)将MAPC培养在纳米复合HAPGEL基质上，使MAPC分化为骨细胞；(2)设计HAP-凝胶基质，以允许生长因子的受控释放，产生多个MAPC分化谱系，并最大限度地提高MAPC对基质的渗透；以及(3)设计基质，使MAPC承载支架的机械强度最大化，从而使其能够成为承载移植物。初步数据显示成骨细胞和羟基磷灰石凝胶基质之间有良好的相互作用，这似乎为提供基于MAPC的治疗提供了一种非常有利的方式。这项工作的意义在于，它可以为先天性、发育性或外伤性畸形患者提供一种新的组织修复方法。有了这种类型的移植材料，在治疗临界大小的颅骨和面部缺损时，应该可以省去多次手术。

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.