Abstract: Divided differences play a fundamental role in the construction of univariate B-splines over irregular knot sequences. Unfortunately, generalizations of divided differences to irregular knot geometries on two-dimensional domains are quite limited. As a result, most spline constructions for such domains typically focus on regular (or semi-regular) knot geometries. In the planar harmonic case, we show that the discrete Laplacian plays a role similar to that of the divided differences and can be used to define well-behaved harmonic B-splines. In our main contribution, we then construct an analogous discrete bi-Laplacian for both planar and curved domains and show that its corresponding biharmonic B-splines are also well-behaved. Finally, we derive a fully irregular, discrete refinement scheme for these splines that generalizes knot insertion for univariate B-splines.