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项目的目的是开发用于溶骨性病变的材料，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)，并抑制破骨细胞的形成，目的是在缺损区内净增加骨量。同时，通过局部治疗缺损区残留的骨髓瘤细胞群(微小残留病)，吸引骨髓瘤细胞并诱导细胞凋亡。具体而言，我们的目标是：1)功能化水凝胶的制造；2)体外研究其对细胞功能的影响。功能化是通过细胞外基质分子的共价结合以及与异二聚体相比同时进行BMP-2或BMP-6同源二聚体的结合来实现的；为了提高生物学活性，对BMP拮抗剂的抗体进行了评估(抗硬化素)。

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).