Systems for binding and release of growth factors

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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.