The goal was to evaluate the effect of the combined growth factor of hyaluronic acid (HA) and advanced platelet-rich fibrin (A-PRF)on acceleration and maturation of bone formation around titaniumdental implants in the bone-free space (jumping distance) of anover-preparation socket. Thirty-two titanium dental implants were placed in four sheepand distributed into one control group (A) and three experimental groups (B, C, and D) in two different time periods.Each sheep received eight implants. The eight implants in each sheep were distributed into four groups. The first period was one month after the initial placement, 16 implants were used in two sheep. The second period was three months after the initial placement; another 16 implants were used in the other two sheep.All implants were placed in over-prepared implant sockets, resulting in minimal primary stability. In Group A: the space between the dental implant and the bone of the inner wall of the socket was left without a growth substrate material. In Group B: we added HA between the dental implant and the bone of the inner wall of the socket. In Group C: we added A-PRF between the dental implant and the bone of the inner wall of the socket. In Group D: we added a combination of HA and A-PRF between the dental implant and the bone of the inner wall of the socket. Data was collected for each group at one month and three months at the same time. A high-resolution, desktop micro-CT system (Bruker Skyscan 1275, Kontich, Belgium) was used to scan the specimens. The NRecon software (ver. 1.6.10.4, SkyScan) and CTAn (SkyScan) were used for the visualization and quantitative measurement of the samples. One-way analysis of variance (ANOVA) was used to compare the means of the four study groups in the same period. A post hoc test was used after ANOVA to compare the means of two samples at the same time. A p-value of ≤ 0.05 was considered statistically significant. After one month and three months of using combined HA and A-PRF on Group D, significant acceleration was observed in bone formation in all tests around dental implants compared with other groups, while no significant acceleration was observed when they were used separately; all three study groups showed significant results when compared with thecontrol group. Our data showed that using a combination of HA and A-PRF had a significanteffect on the acceleration of the bone formation and ossification process when added to bone-free space (jumping distance) around implants while leaving space without any growth substrates might delay the boneossification process.