Synthetic Biodegradable Hydrogels with Excellent Mechanical Properties and Good Cell Adhesion Characteristics Obtained by the Combinatorial Synthesis of Photo-Cross-Linked Networks

摘要

Major drawbacks of synthetic hydrogels are their poor mechanical properties and their limited ability to allow cell attachment and proliferation. By photo-cross-linking mixtures of dimethacrylate-functionalized oligomers (macromers) in a combinatorial manner in solution, synthetic hydrogels with high water uptake and the remarkable ability to promote cell adhesion and proliferation were prepared. A total of 255 different networks based on poly(trimethylene carbonate) (PTMC)-, poly(D,L-lactide) (PDLLA)-, poly(epsilon-caprolactone) (PCL)- and poly(ethylene glycol) (PEG) macromers were synthesized simultaneously and screened for their ability to allow the adhesion of human mesenchymal stem cells (hMSCs) in a high throughput-like manner. Of these networks, several hydrogels could be identified that were able to take up large amounts of water while at the same time allowed the adhesion of cells. By synthesizing these hydrogel networks anew and analyzing the cell adhesion and proliferation behavior of human mesenchymal stem cells to these synthetic hydrogels in more detail, it was confirmed that mixed-macromer hydrogel networks prepared from equal amounts of PTMC-dMA 4k, PDLLA-dMA 4k, PCL-dMA 4k, PEG-dMA 4k, and PEG-dMA 10k and hydrogel networks prepared from PTMC-dMA 4k, PDLLA 4k, PEG-dMA 4k, PTMC-dMA 10k and PEG-dMA 10k were highly hydrophilic (water uptake was respectively 181 +/- 2 and 197 +/- 18 wt % water) and allowed very good cell adhesion and proliferation. Furthermore, these networks were extremely resilient in the hydrated state, with tearing energies of respectively 0.64 +/- 0.34 and 0.27 +/- 0.04 kJ/m(2). This is much higher than other synthetic hydrogels described in literature and close to articular cartilage (1 kJ/m(2)).