Organic/Inorganic Hybrids to Guide Bone Regeneration

引导骨再生的有机/无机混合物

• 批准号: 6897521
• 负责人: DAVID H. KOHN
• 金额: $ 29.56万
• 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/6897521
• 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）：口面缺陷的重建代表了一个主要的临床挑战。 现有治疗有局限性和缺乏可预测性，因此需要开发新的策略来治愈天质组织。 一种新的方法是通过将自动细胞播种成生物材料，从而为细胞提供线索，从而使它们能够生长，区分和分泌新的细胞外基质，从而再生感兴趣的组织。 为此，我们开发了体外培养方法，其中人骨髓基质细胞被扩展，并证明这些细胞能够在体内形成新的骨骼。 但是，祖细胞的骨骼形成是可变的，尤其是在使用人类细胞的情况下，并且受细胞微环境（包括支持生物材料）的许多因素控制。 因此，我们寻求建立可以在体外和体内增强骨细胞功能的材料参数。 全球假设是，将骨状矿物/有机杂种共沉淀在用于BMSC移植的支架上的骨状杂种，可以用细胞来重组矿物质的矿物化外部矩阵的体积和结构完整性的增加，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种有机/无机杂交材料的三类：有机模板通过矿物/聚氨基酸杂交层的共沉淀成生物磷灰石的有机模板；有机模板的表面包括细胞粘附分子与矿物相共吸附；并将生长因子纳入自组装的矿物质层，使得生物矿物具有受控的递送工具。 对于每种生物象征策略，我们检验了以下假设：有机和无机相位到脚手架孔表面上的共沉淀会导致成骨细胞的侵袭和骨导体的增加，而BMSC的速率和程度则在近代和vivo中的体积和体内的体积均在内的阶段和范围内的分类而分化。 这些研究的结果可能导致生物材料通过祖细胞调节骨骼形成。 这种方法对细胞移植具有影响，但如果用作组织工程的电感方法，也可能会影响宿主细胞的分化。