This study is part of a global project which aims at conceiving and characterizing implantable synthetic extracellular matrices seeded with multifunctional particles for bone and cartilage tissue engineering. To date, protein encapsulation remains a challenge in the field of microencapsulation. The aim of this work is to use supercritical CO2 to generate polymeric and inorganic particles for protein encapsulation. Poly(lactic-co-glycolic) (PLGA) and calcium carbonate (CaCO3) microparticles were chosen to be investigated. In both cases, spherical particles were successfully obtained based on the formation of an emulsion in CO2 media. Most importantly, only non-toxic solvents or aqueous solution were used for the formulation of microparticles. Encapsulation experiments were carried out to provide a proof of concept. Lysozyme was chosen as a model protein and experimental designs were made in order to better understand the system and to better predict the encapsulation yield. The encapsulation yield can reach about 60% in both cases. The mechanism of particle formation and lysozyme encapsulation will also be discussed in detail.