In an attempt to recreate the microenvironment necessary for directed hematopoietic stem cell differentiation, control over the amount of ions available to the cells is necessary. The release of potassium ion and calcium ion via the control of cross-linking density of a poly(2-hydroxyethyl methacrylate) (pHEMA)-based hydrogel containing 1 mol % 2-methacryloyloxyethyl phosphorylcholine (MPC) and 5 mol % oligo(ethylene glycol) (400) monomethacrylate [OEG(400)MA] was investigated. Tetra(ethylene glycol) diacrylate (TEGDA), the cross-linker, was varied over the range of 1–12 mol %. Hydrogel discs (ϕ = 4.5 mm and h = 2.0 mm) were formed by UV polymerization within silicone isolators to contain 1.0 M CaCl₂ and 0.1 M KCl, respectively. Isothermal release profiles, were measured at 37 °C in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid sodium salt (HEPES) buffer using either calcium ion or potassium ion selective electrodes (ISE). The resulting release profiles were found to be independent of cross-linking density. Average (n = 3) release profiles were fit to five different release models with the Korsmeyer-Peppas equation, a porous media transport model, exhibiting the greatest correlation (R² > 0.95). The diffusion exponent, n was calculated to be 0.24 ± 0.02 and 0.36 ± 0.04 for calcium ion and potassium ion respectively indicating non-Fickian diffusion. The resulting diffusion coefficients were calculated to be 2.6 × 10⁻⁶ and 11.2 × 10⁻⁶ cm²/s, which compare well to literature values of 2.25 × 10⁻⁶ and 19.2 × 10⁻⁶ cm²/s for calcium ion and potassium ion, respectively.