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

项目M9的目的是开发用于溶骨性病变的材料，该材料能够有效刺激成骨细胞前体细胞（骨合成代谢轴）并抑制破骨细胞生成，旨在增加缺损内的骨量。同时，骨髓瘤细胞被吸引，并在缺陷中残留骨髓瘤细胞群（微小残留病）的局部治疗方面诱导细胞凋亡。详细地说，我们的目标是i）官能化水凝胶的制造和ii）关于它们对细胞功能的影响的体外研究。功能化通过与细胞外基质的分子以及同时与BMP-2或BMP-6同源二聚体（与异源二聚体相比）的共价结合来实现;为了增强生物活性，评估针对BMP拮抗剂的抗体（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).