The success of implant placement will depend on the ability of the implant material to integrate with the surrounding tissue. Polymethylmethacrylate (PMMA) has been used as an implant material, but it has several fallback properties in its interaction with bone tissue. The addition of hydroxyapatite (HAp) to PMMA is expected to produce reinforced bioceramic polymers with better mechanical and biological properties. The purpose of this study was to evaluate the expression of osteopontin and osteocalcin in cultured osteoblasts when exposed to two implant candidate materials: PMMA-HApGMP, derived from bovine bone and processed under Good Manufacturing Practice by a Tissue Bank, and PMMA-HApBBK, sourced from limestone (CaCO3) and processed by Balai Besar Keramik. Twenty-four fetal rat calvariae osteoblast cell cultures were randomly divided into 6 groups: 7- and 14-day control group, 7 and 14 days PMMA-HApGMP group, 7 and 14 days PMMA-HApBBK group. The expression of osteopontin and osteocalcin was seen by immunocytochemical examination. The results showed that the average expression of osteopontin and osteocalcin in the treatment group on the 7th and 14th days was higher than the control group. The expression of osteopontin and osteocalcin in the PMMA-HApGMP group increased significantly (P < .05) on day 14. The PMMA-HAp combination material can accelerate the process of osteoblast differentiation which is characterized by an increase in osteopontin and osteocalcin which are markers of bone formation. This will support in increasing osseointegration.