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。对于骨接触材料，这意味着在植入后，设备将立即诱导成骨细胞系的细胞在生物材料上或接近生物材料的地方形成骨。植入物的稳定固定和与组织的更好结合将是结果。这项研究的总体目标是开发诱导特定细胞和组织反应的生物分子表面修饰策略。例如，刺激组织再生比修复更可取，在这种情况下，植入物会整合到组织中，在修复过程中，植入物通常被纤维包膜隔开。据推测，具有表面亲骨生物分子的骨接触材料在特定的呈现方式下可以控制组织-生物材料界面的初始细胞事件。在具体目标1中，将开发双肼衍生的聚(D，L-丙交酯-乙交酯共聚)涂层、微球和多孔支架，用于定点固定化成骨生长因子。将产生不同长度和表面密度的双肼分子的表面。在具体目标2中，将设计和实施合理的方案，用于在目标1中开发的材料上定点固定生长因子。将使用重组DNA技术对胰岛素样生长因子I和骨形态发生蛋白2的氨基末端进行修饰。这些独特的位置将允许生长因子以最大限度地与细胞表面受体相互作用的方向固定。在具体目标3中，将测定合理修饰的生物材料的体外和体内生物活性。细胞培养也将用于评估固定化生长因子对适当的细胞表面受体的激活。据推测，与随机固定的蛋白质相比，定点固定化生长因子将产生更高的特定生物活性，因此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具有诱导所需界面反应能力的骨接触生物材料的发展。

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.