The important factor in the design and realization of tissue engineering is the structure of three-dimensional (3D) synthetic scaffold that functions as synthetic extracellular matrix (ECM) which mimicking natural cell environment and preserve bioactive signal molecules such as growth factors (GFs). In this study, formulation of synthetic three-dimensional (3D) coral matrices was developed, characterized, and screened to obtain the most ideal formulation. Consecutively matrix ability to induce MSCs (mesenchymal stem cells) to differentiate into osteoblast both in vitro and in vivo was investigated. The potential matrix was observed for its capability in enhancing bone regeneration process within various culture conditions involving either standard culture medium or osteogenic medium, with the presence or absence of GFs cocktail in platelet rich plasma (PRP) and MSCs. Expressions of Runx, Osterix, and Osteocalcin markers were measured following the analysis on cell attachment and proliferations. Among several fabricated synthetic 3D coral matrices in various concentrations, SC-05 formulation was found preferable with the lowest degradability rate of 39.31 ± 3.55 % even after 96 h immersion in phosphate buffer saline continued by 6 h in acid solution. The release profile of PRP from the SC-05 matrix was also found preferable at 81.55 ± 1.15 %. The matrix loaded with growth factors cocktail from PRP provided ideal microenvironment for MSCs to attach, proliferate, and differentiate into osteoblast indicated by high expression level of Runx2, Osterix, and Osteocalcin. This verified that engineered microenvironment based on SCM loaded with growth factors can enhance bone tissue regeneration.