Systems for binding and release of growth factors

该项目的目的是以生物活性形式释放生长因子BMP-2、TGF-β3以及转录因子Smad8 L+MH2等生物刺激。空间和时间控制释放是不同组织的适当再生所需要的。上一个授权期的结果表明，聚合纳米凝胶是由壳聚糖和三聚磷酸盐水溶液混合后自发形成的，适合于固定化BMP-2并以可控的方式释放。相应地，海藻酸盐与聚l -赖氨酸低聚物混合形成的颗粒适合作为TGF-β3的递送体系。这些颗粒可以通过类似于逐层涂层的浸渍工艺梯度固定在改性聚己内酯纤维垫（由子项目TP3和TP4提供）上。该工艺也可用于合并稳定层和缓释层。对于转录因子Smad8 L+MH2，应开发类似的释放系统，并在下一个批准期进行测试。最后，对于这三种蛋白质，合适的释放系统将可用。在即将到来的授权期内，进一步的目标将是调整释放系统的释放动力学，使其满足细胞分化和组织再生的生物学需要。释放的时空控制将与子项目TP6一起进行调查。光交联中间层将用于稳定释放系统和控制释放动力学。不同的药物释放系统将在纤维垫上组合，形成所有三种蛋白质的梯度。

The aim of the project is to release biological stimuli like the growth factors BMP-2, TGF-β3 as well as the transcription factor Smad8 L+MH2 in biologically active form. A spatially and temporally controlled release is desired for proper regeneration of the different tissues. The results of the previous granting period have shown that polymeric nanogels, which form spontaneously upon mixing of aqueous solutions of chitosan and tripolyphosphate, are suitable to immobilize BMP-2 and to release it in a controlled manner. Correspondingly, particles formed by mixing alginate and poly-L-lysin-oligomers are suited as delivery system for TGF-β3. These particles can be immobilized on modified polycaprolacton fibermats (supplied by subprojects TP3 & TP4) in gradients, by a dipping process, which is similar to the layer-by-layer coating. The process can also be used the incorporate stabilizing and release retarding layers. For the transcription factor Smad8 L+MH2 a similar release system shall be developed and tested in the next granting period. Finally, for all three proteins suitable release systems will be available. A further aim for the upcoming granting period will be to adjust the release systems in respect to the release kinetics, so that they meet the biological needs for the cell differentiation and tissue regeneration. The spatial and temporal control of the release will be investigated together with subproject TP6. Photo-crosslinkable interlayers will be used to stabilize the release system and to control the release kinetics. The different drug release systems will be combined on the fiber mats to form gradients for all three proteins.