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物刺激物，如生长因子BMP-2，TGF-β3以及转录因子Smad 8 L+ MH 2。对于不同组织的适当再生，需要空间和时间受控的释放。先前授权期的结果已经表明，在壳聚糖和三聚磷酸盐的水溶液混合时自发形成的聚合物纳米凝胶适合于包裹BMP-2并以受控的方式释放它。相应地，通过混合藻酸盐和聚-L-赖氨酸-寡聚物形成的颗粒适合作为TGF-β3的递送系统。这些颗粒可以通过类似于逐层涂覆的浸渍工艺以梯度方式固定在改性聚己内酯纤维毡（由子项目TP 3和TP 4提供）上。该方法也可用于掺入稳定层和释放延迟层。 对于转录因子Smad 8 L+ MH 2，应在下一个授予期开发和检测类似的释放系统。最后，对于所有三种蛋白质，合适的释放系统将是可用的。即将到来的授权期的另一个目标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求。释放的空间和时间控制将与次级项目TP 6一起进行调查。可光交联的夹层将用于稳定释放系统并控制释放动力学。不同的药物释放系统将在纤维垫上组合，以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.