Over the years, legislation has gradually angled to replace or reduce the use of animals in scientific research. In this context, establishing more representative in vitro models of bone development would benefit mechanistic understanding and therapeutic development for bone diseases. However, it has been challenging to create functional 3D cell networks in vitro that mimic early bone tissue morphogenesis. Now, writing in Nature Communications, Xiao-Hua Qin and colleagues report a synthetic biodegradable void-forming hydrogel that allows in vitro formation of functional human bone cell networks and microfluidic integration.“We mix live cells with a few components, including 4-arm PEG vinylsulfone, matrix metalloproteinase-sensitive di-cysteine peptides for degradability, arginylglycylaspartic acid (RGD) peptides for cell attachment, hyaluronan and dextran for phase separation, and warm the mixture to 37 °C,” says Qin. One of the keys to the success of the method lies in the polymerization-induced phase separation of dextran from PEG vinylsulfone at 37 °C, which triggers the formation of hydrogels with interconnected pores even in the presence of living cells. The microporous architectures can be tailored by adjusting the molecular weight and concentration of dextran.
