Cryogenic prototyping of chitosan scaffolds with controlled micro and macro architecture and their effect on in vivo neo‐vascularization and cellular infiltration

A major challenge in tissue engineering has been to develop scaffolds with controlled complex geometries, on both the macro- and micro-scale. One group of techniques, using rapid prototyping (RP) processes, has the capability to produce complex three-dimensional structures with good control over the size, geometry, and connectivity of the pores. In this article, a novel technique based on RP technology, that is, cryogenic prototyping (CP), that has the capability to fabricate scaffolds with controlled macro- and micro-structures, is presented. Our in vivo studies showed that the micro architecture (i.e., both pore size and pore orientation) and macro structures of the CP scaffolds affect both cellular infiltration and neo-vascularization. Full cellular infiltration and neo-vascularization were observed after 28 days in scaffolds with micropore sizes of 90 microm. In addition, it was observed that channels (300 microm) created in scaffolds were effective at enhancing cellular infiltration and vascularization. Our results have demonstrated that CP is a viable method for fabricating scaffolds for a wide range of tissue engineering applications.