Organic /Inorganic Hybrids to Guide Bone Regeneration

引导骨再生的有机/无机混合物

• 批准号: 6686717
• 负责人: DAVID H. KOHN
• 金额: $ 29.24万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6686717
• 关键词: athymic mouse; bioengineering /biomedical engineering; biomaterial development /preparation; biomimetics; biotechnology; bone marrow; bone regeneration; cell adhesion molecules; cell differentiation; cell transplantation; clinical research; connective tissue cells; extracellular matrix; growth factor; human tissue; minerals; molecular assembly /self assembly; oral facial restoration; oral facial restoration material; osteoblasts; osteogenesis; patient oriented research; precipitation; surface coating; tissue support frame

DESCRIPTION (provided by applicant): Reconstruction of orofacial defects represents a major clinical challenge. Existing treatments have limitations and lack predictability, necessitating development of new strategies to heal orofacial tissues. One new approach is to regenerate the tissue(s) of interest by seeding autogenous cells into a biomaterial which supports and may even provide cues for the cells, allowing them to grow, differentiate and secrete new extracellular matrix. Towards this end, we have developed in vitro culture methods in which human bone marrow stromal cells are expanded, and demonstrated that these cells are capable of forming new bone in vivo. The formation of bone from progenitor cells is, however, variable, especially if human cells are used, and is controlled by a number of factors in the cells' microenvironment, including the supporting biomaterial. We therefore seek to establish material parameters that could enhance bone cell function in vitro and in vivo. The global hypothesis is that bone-like mineral/organic hybrids that are co-precipitated onto scaffolds used for BMSC transplantation can be used by the cells to restructure a mineralized extracellular matrix of increased volume and structural integrity, thereby enhancing bone formation by the transplanted cells. Results from our and other laboratories support this hypothesis, which is tested by synthesizing 3 classes of organic/inorganic hybrid materials: organic templates whose surface self-assembles into a biological apatite via the co-precipitation of a mineral/poly amino acid hybrid layer; organic templates whose surface includes cell adhesion molecules co-adsorbed with a mineral phase; and incorporation of growth factors into the self-assembled mineral layer such that the biomineral serves as a controlled delivery vehicle. For each of these biomimetic strategies, we test the hypothesis that co-precipitation of organic and inorganic phases onto scaffold pore surfaces leads to increased osteoblast invasion and osteoconductivity and that the rate and extent of BMSC differentiation toward an osteoblast phenotype in-vitro and in-vivo are regulated by the type and concentration of the organic phase within the mineral. The results of these studies may lead to biomaterials that modulate bone formation by progenitor cells. This approach has implications for cell transplantation, but may also have impact on the differentiation of host cells if used as an inductive approach to tissue engineering.

描述（由申请人提供）：口面部缺陷的重建是一项重大的临床挑战。 现有的治疗方法存在局限性且缺乏可预测性，因此需要开发新的策略来治愈口面部组织。 一种新方法是通过将自体细胞接种到生物材料中来再生感兴趣的组织，该生物材料支持甚至可以为细胞提供线索，使它们能够生长、分化和分泌新的细胞外基质。 为此，我们开发了体外培养方法，在其中扩增人骨髓基质细胞，并证明这些细胞能够在体内形成新骨。 然而，祖细胞形成的骨是可变的，特别是如果使用人类细胞，并且受到细胞微环境中的许多因素（包括支持生物材料）的控制。 因此，我们寻求建立可以增强体外和体内骨细胞功能的材料参数。 普遍的假设是，细胞可以使用共沉淀到用于 BMSC 移植的支架上的骨样矿物/有机混合物来重组矿化的细胞外基质，增加体积和结构完整性，从而增强移植细胞的骨形成。 我们和其他实验室的结果支持了这一假设，该假设通过合成 3 类有机/无机杂化材料进行了测试：有机模板，其表面通过矿物/聚氨基酸杂化层的共沉淀自组装成生物磷灰石；有机模板，其表面包含与矿物相共吸附的细胞粘附分子；将生长因子掺入自组装矿物层中，使生物矿物充当受控输送载体。 对于这些仿生策略中的每一种，我们测试了以下假设：有机相和无机相共沉淀到支架孔表面会导致成骨细胞侵袭和骨传导性增加，并且 BMSC 在体外和体内向成骨细胞表型分化的速率和程度。体内的变化受矿物内有机相的类型和浓度的调节。 这些研究的结果可能会产生通过祖细胞调节骨形成的生物材料。 这种方法对细胞移植有影响，但如果用作组织工程的诱导方法，也可能对宿主细胞的分化产生影响。