Functionalized hydrogels presenting simultaneously β1-integrin selective ligands and bone morphogenic protein 6 to stimulate osteoblast function and induce myeloma cell apoptosis ((08) M09)

M9项目的目标是开发用于溶骨病变的材料，这种材料能够有效地刺激成骨细胞前体细胞（骨合成代谢轴）并抑制破骨细胞的发生，目的是使缺损内的骨量净增加。与此同时，骨髓瘤细胞被吸引，并在局部治疗缺陷中残留的骨髓瘤细胞群（最小残留疾病）方面诱导凋亡。详细地说，我们的目标是i)功能化水凝胶的制造和ii)在体外研究它们对细胞功能的影响。功能化是通过细胞外基质分子的共价结合以及与异源二聚体相比BMP-2或BMP-6同型二聚体同时实现的；为了提高生物活性，对bmp -拮抗剂（抗硬化蛋白）的抗体进行了评估。

Aim of project M9 is the development of materials for the use in osteolytic lesions which is able to effectively stimulate osteoblast precursor cells (osteoanabolic axis) and to inhibit osteoclastogenesis aiming at a net increase in bone mass within the defect. In parallel, myeloma cells are attracted and apoptosis is induced in terms of a local treatment of a residual myeloma cell population (minimal residual disease) in the defect. In detail our aims are i) the manufacturing of functionalized hydrogels and ii) their investigation in vitro regarding their impact on cellular functions. Functionalization is implemented via covalent binding of molecules of the extracellular matrix as well as simultaneously either BMP-2 or BMP-6 homodimer compared to the heterodimer; to enhance the biologic activity, antibodies against BMP-antagonists are evaluated (anti-sclerostin).