Design of porous alginate hydrogels by sacrificial CaCO3 templates: Pore formation mechanism

Fabrication of porous alginate hydrogels with a well-controlled architecture useful for tissue engineering is still a challenge. Here, CaCO3-based templating is utilized to design stable alginate gels with controlled pore dimensions in the range of 5-50 mu m. The mechanism of pore formation is studied considering two factors affecting the pore size: i) osmotic pressure generated during the dissolution of sacrificial CaCO3 templates and ii) alginate gel network density. Osmotic pressure can achieve an upper limit of 100 MPa but does not affect the gel porosity. Additional osmotic pressure (range of kPa) induced by dextrans pre-encapsulated into CaCO3 vaterite is also insufficient for pore enlargement. Pore stability depends merely on the gel network density and on the number of crosslinking calcium ions provided locally per unit time; pores are collapsed when template dissolution is too slow or if there is insufficient alginate concentration (below 2%). Young's modulus indicates the soft nature of the prepared hydrogels (tens of kPa) applicable as soft porous scaffolds with a tuned internal structure.