Engineering a new biomaterial for stem-cell mediated bone regeneration

描述（由申请人提供）：在该研究者的4年培训/职业发展计划中，该研究者在生物材料科学方面有很强的背景，最近接受了组织工程学方面的临床培训，三个具体目标是：（1）进一步发展组织工程方面的技能，包括用于组织向内生长的多孔支架，扩展该领域的既往经验和专业知识;（2）MAPC（多能成体祖细胞）在这类组织工程中的新用途;（3）基于对各种类型的牙面和颅面畸形患者进行纵向随访的临床研究技能。总体长期目标是开发颅面复合体（和身体其他部位）软硬组织缺损的替代品。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和生长骨的承重支架。培训计划是围绕与四位导师的互动而建立的，与上述每个具体目标相关，并参与在临床科学家计划中开发的课程和研讨会。导师是Mitsuo Yamauchi博士（胶原交联在组织工程支架开发中的应用）、Wei-Shou Hu博士（干细胞生物学）、Leaf Huang博士（生长因子的应用）和William Proffit博士（需要正颌手术矫正牙面和颅面缺陷的患者的纵向研究）。针对短期目标提出的工作包括（1）在纳米复合材料HAPGEL基质上培养MAPC，使得MAPC分化成骨细胞;（2）设计HAP-GEL基质，以允许生长因子的受控释放，从而产生MAPC分化的多个谱系，并使MAPC渗透到基质中最大化;以及（3）设计基质以使承载MAPC的支架的机械强度最大化，使得其可以成为承载移植物。初步数据显示成骨细胞和HAP-GEL基质之间有希望的相互作用，并且似乎这提供了一种非常有利的方式来提供基于MAPC的治疗。这项工作的意义在于，它可以提供一种新的方法来替换先天性，发育性或创伤性畸形患者缺失的组织。使用这种类型的移植材料，在治疗关键尺寸的颅骨和面部缺损时，应该可以消除多次手术。

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.