Porous microspheres capable of delivering high payloads of biomolecules with suitable biodegradability and biocompatibility would be valuable in delivery systems to aid tissue regeneration. This study describes a facile, scalable technique to produce biodegradable porous microspheres by combining continuous ink-jetting through a piezoelectric nozzle with thermally induced phase separation (TIPS). A selection of biomaterials is investigated to suit delivery in tissue engineering, the synthetic polyesters poly(lactic-co-glycolic acid) (PLGA), and poly caprolactone (PCL) and a natural polymer, gelatin. The parameters governing the microsphere production are determined experimentally and compared to theoretical predictions derived from the fluid mechanics and heat transfer during the ink-jetting process. The microspheres produced have open interconnected pores with mean particle diameters of 80-200 mu m and no significant skin region. The physical properties, such as the mean particle diameter, pore size, and surface area could be controlled by varying production parameters including the ink-jetting pressure, nozzle height, and the size and oscillation frequency of the nozzle. The technique is demonstrated to successfully encapsulate a model hydrophobic molecule during microsphere production with uniform distribution. Porous PLGA microspheres are also used to achieve much higher adsorption capacities of a short peptide than non-porous microspheres of the same material.