A chemoenzymatic strategy has been exploited to make covalently linked alginate beads with high stability. This was achieved by grafting mannuronan (alginate with 100% mannuronic acid (M)) with methacrylate moieties and then performing two enzymatic steps converting M to guluronic acid (G) in alternating sequences (MG-blocks) and in G-blocks. In this way a methacrylate grafted alginate with better gel-forming ability was achieved. Covalent bindings were introduced into the beads by using a photoinitiating system that initiated polymerization of the methacrylate moieties. The covalent links were demonstrated by beads remaining intact after treatment with EDTA. The new chemoenzymatic photocrosslinked (CEPC) beads were compatible with cells with low post-encapsulation ability like C2C12 myoblasts and human pancreatic islets. The islets continued secreting insulin after encapsulation. On contrary, cells with a high post-encapsulation proliferative ability like 293-endo cells died within 2-week post-encapsulation. The exceptional stability and the cell compatibility of the new CEPC beads make them interesting as bioreactors for delivering therapeutic proteins in future applications.