The significance of molecular design methodologies based upon membrane-mimetic systems lies in the ability to engineer robust materials of varying geometry with a high degree of reproducibility and molecular control over surface order and chemistry. However, non-covalently associated assemblies, in and of themselves, are often insufficiently robust for many applications. We have previously reported the in situ polymerization of a single phospholipid monolayer on a self-assembled film of octadecyltrichrolosilane (OTS) on glass, as well as the polymerization of phospholipids on an amphiphilic, dialkyl-containing terpolymer bound to a gold-coated silicon wafer. We now report the polymerization of a phospholipid monolayer assembly onto an alkylated hydrogel substrate with significant alteration in both surface chemistry and mass transport properties at the hydrogel-water interface. A general platform is thereby created for enhancing the control of either the local delivery of specific macromolecules or the immunoisolation barrier for many cell based therapies.