Organic/Inorganic Hybrids to Guide Bone Regeneration

描述（由申请人提供）：口腔面部缺损的重建是一项重大的临床挑战。现有的治疗方法有局限性，缺乏可预测性，需要开发新的策略来治疗口腔面部组织。一种新的方法是通过将自体细胞植入支持细胞甚至可能为细胞提供线索的生物材料中，使其生长、分化并分泌新的细胞外基质，从而再生组织。为此，我们开发了体外培养人类骨髓基质细胞的方法，并证明这些细胞能够在体内形成新骨。然而，祖细胞骨的形成是可变的，特别是如果使用人类细胞，并且受细胞微环境中的许多因素控制，包括支持生物材料。因此，我们寻求建立能够在体外和体内增强骨细胞功能的材料参数。普遍的假设是，骨样矿物/有机杂交体共沉淀到用于骨髓间充质干细胞移植的支架上，可以被细胞用来重组矿化的细胞外基质，从而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这一假设，并通过合成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，其表面包括与矿物相共吸附的细胞粘附分子；并将生长因子结合到自组装的矿物层中，使生物矿物充当受控的运载工具。对于每一种仿生策略，我们测试了有机相和无机相在支架孔表面的共沉淀导致成骨细胞侵袭和骨导电性增加的假设，以及体外和体内BMSC向成骨细胞表型分化的速度和程度受到矿物中有机相的类型和浓度的调节。这些研究的结果可能导致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意义，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。

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.