A novel template-casting method was developed to produce completely interconnected, macroporous biodegradable beta-tricalcium phosphate (beta-TCP) scaffolds, whose architecture and chemistry can be fully manipulated by varying the templates and casting materials. The processing route includes preparation of beta-TCP slurry; casting and shaping into preformed templates comprised of paraffin beads; solidifying, drying; and sintering. Structural, chemical, and mechanical properties of the prepared macroporous scaffolds were characterized using micro computed tomography, scanning electron microscopy, x-ray diffractometry, Fourier transform infrared spectroscopy, and mechanical testing. Human embryonic palatal mesenchymal cells were used to evaluate cell proliferation within the scaffolds in vitro. The scaffolds consisted of interconnected macropores and solid struts, leading to a reticular network. Two groups of scaffolds with larger pores, approximately 600-800 microm and smaller pores approximately 350-500 microm, were demonstrated. The interconnected windows between neighboring macropores were 440 +/- 57 microm in diameter for the larger-pored scaffolds, and 330 +/- 50 microm for the smaller-pored scaffolds. The scaffolds were highly crystallized and composed dominantly of beta-tricalcium phosphate (beta-TCP) accompanied by minor phase of hydroxyapatite (HA). The hydroxyl group was clearly detected by FTIR on the scaffolds. High mechanical strength (9.3 MPa) was demonstrated by the completely interconnected scaffolds with approximately 79% porosity. The human embryonic palatal mesenchymal (HEPM) cells proliferated well on the smaller-pored and larger-pored scaffolds, exhibiting a significantly higher level of proliferation in the first 11 days of culture on the smaller pored scaffolds. High levels of differentiation were also evidenced in both pore sizes of scaffolds.