Biomaterials with Rationally Immobilized Growth Factors

描述（由申请人提供）：理想情况下，植入物的设计应具有促进特定生物反应的能力。在骨接触材料的情况下，这意味着植入后，设备将立即诱导成骨细胞谱系在生物材料上或附近形成骨。结果是植入物的稳定固定和更好地融入组织。本研究的总体目标是开发生物分子表面修饰策略，诱导特定的细胞和组织反应。例如，刺激组织再生比修复更可取，在这种情况下，植入物与组织融为一体，而在这种情况下，植入物通常被纤维囊包围。据推测，骨接触材料表面具有特定形式的促骨生物分子，可以控制组织-生物材料界面的初始细胞事件。在Specific Aim 1中，双酰肼衍生化聚（D， l -丙交酯-羟基乙酸酯）涂层、微球和多孔支架将被开发用于定向固定促骨生长因子。双肼分子会产生不同长度和表面密度的表面。在具体目标2中，将设计和实施合理的方案，用于在目标1中开发的材料上定向固定生长因子。重组DNA技术将用于对胰岛素样生长因子I和骨形态发生蛋白2的氨基端进行修饰。这些独特的位点将允许生长因子固定在一个方向上，最大限度地与细胞表面受体相互作用。在Specific Aim 3中，将测定合理修饰的生物材料的体内和体外生物活性。细胞培养也将用于评估活化适当的细胞表面受体由固定的生长因子。据推测，位点定向固定生长因子将产生更高的特异性生物活性，因此，与随机固定蛋白质相比，将导致更大的细胞和组织反应（特别是骨形成）。这些研究的发现将影响骨接触生物材料的发展，这些材料具有诱导所需的种族间反应的能力。

DESCRIPTION (provided by applicant): Ideally, implants should be designed with the ability to promote specific biological responses. In the case of bone-contacting materials, this would mean that, immediately following implantation, the devices would induce cells of the osteoblastic lineage to form bone on or in close proximity to the biomaterial. Stable fixation of the implant and better integration into the tissue would be the result. The overall goal of this research is to develop biomolecular surface modification strategies that induce specific cell and tissue responses. For example, stimulation of tissue regeneration, in which the implant becomes integrated into the tissue, is more desirable than repair, in which the implant is generally walled off with a fibrous capsule. It is postulated that bone-contacting materials possessing surfaces with osteotropic biomolecules in a specific presentation can control initial cellular events at the tissue-biomaterial interface. In Specific Aim 1, bis-hydrazide-derivatized poly(D,L-lactide-co-glycolide) coatings, microspheres, and porous scaffolds will be developed for use in site-directed immobilization of osteotropic growth factors. Surfaces with different lengths and surface densities of bis-hydrazide molecules will be produced. In Specific Aim 2, rational schemes will be designed and implemented for site-directed immobilization of growth factors on the materials developed in Aim 1. Recombinant DNA techniques will be used to introduce modifications to the amino termini of insulin-like growth factor I and bone morphogenetic protein 2. These unique sites will allow the growth factors to be immobilized in an orientation that maximizes interaction with cell surface receptors. In Specific Aim 3, in vitro and in vivo biological activity of the rationally modified biomaterials will be determined. Cell cultures will also be used to assess activation of the appropriate cell surface receptors by the immobilized growth factors. It is hypothesized that site-directed immobilization of growth factors will yield higher specific bioactivity and, therefore, will result in greater cell and tissue responses (specifically bone formation) compared to randomly immobilized protein. The findings of these studies will impact the development of bone-contacting biomaterials having the ability to induce desired interracial responses.