A method of manufacture of ECM microparticles incorporating bioactive molecules for drug delivery has been developed, using a modified emulsification method or a water-in-oil-phase-separation method. The microspheres are photochemically crosslinked to control the release of the bioactive molecules for better drug delivery usage without compromising the biocompatibility of the crosslinked structures. The method uses mild fabrication conditions and simple processes, no toxic chemical crosslinking reagent, which may cause cytotoxicity and calcification after implantation, no organic solvents, which may reduce drug availability and bioactivity, and no vigorous stirring action, which may fragmentize material with poor shape and mechanical stability and thus destabilize the emulsion. The resulting microparticles or microspheres are of controlled size, controlled release, highly biocompatible, and useful for drug delivery as well as cell culture.