Crystal templating dendritic pore networks and fibrillar microstructure into hydrogels

Native tissues contain space-filling dendritic pore networks, such as vasculature, for the efficient distribution of oxygen and nutrients; however, it is not yet possible to create tissue-engineered scaffolds with dendritic porosity. Fibers are also important structural features of native tissues because they provide sites for cell anchorage, promote cell guidance and contribute to mechanical stability. Here, we have developed a “crystal templating” technique, which is simple and inexpensive, for fabricating polymer scaffolds with space-filling dendritic pore networks and fibrillar microtopography. To do this, we grow dendritic urea crystals in solution cast films of hyaluronic acid (HA), photocrosslink the HA around the crystal network to lock in the dendritic configuration, and dissolve the crystals to obtain empty pores. During in situ crystal growth the HA biopolymer is phase separated from the long narrow urea crystals and shaped into a fibrillar microstructure. The porous fibrillar HA scaffolds created by crystal templating may be applicable as regenerative patches for skin and other tissues.