## 4 Discussion  
Surface modification of dental implants is essential in increasing the interaction between the implant and the surrounding bone, which will affect the osseointegration through the increasing number of cells adhering to the surface of the implant. The IDCT-Ti implants, coated with GRGD peptide, allow the increase in osteoblast adhesion and proliferation. The formation of bone around a foreign object such as an implant is a very complicated process. Both implants and substances that induce bone formation must function to support one another. Dental implants based on titanium are carriers of substances that can increase bone formation, and have characteristics that include high biocompatibility, good mechanical properties, can be combined with various inducing factors for bone formation, and do not inhibit bone formation induced by inducing factors [22]. The IDCT-Ti itself has facilitated the implant surface to simulate the ECM, which is crucial for cell attachment [13]. The  
Figure 7: The panoramic of IDCT-Ti/GRGD-1 implant in (**a**) mandibular, (**b**) maxillary, and (**c**) maxillary and mandibular region, immediately and six months after placement. Note: figure (**b**) after immediate implant placement is the picture that was reconstructed from the cone-beam computed tomography. peptide represents a small part of the protein that is responsible for intercellular and ECM adhesion, while RGD is a peptide motif found in ECM proteins whose adhesion is integrin-mediated [11; 23]. The ECM consists of various cell identification motifs such as fibronectin, vitronectin, laminin, collagen I, and bone sialoprotein, whereas the small peptide only provides a single motif [16; 24; 25; 26]. Hence, the RGD peptide motif can selectively determine the type of cell adhesion receptor [16]. As a sequence of RGD, the GRGD peptide was reported to bind mostly to osteoblast cell activity [21]. The increase in GRGD peptide concentration appears to be directly proportional to cell death. Accordingly, GRGD in low concentrations emerges to be the best option for modifying the implant surface. This finding matches with our earlier study that also used low concentrations of GRGD to increase the adherence of fibroblast cells, and human hair follicle-derived mesenchymal stem cells [19]. Interestingly, not all RGD sequences show this phenomenon. Possible reasons for cell death include: (1) Cells have several integrin binding-receptors to RGD. If the binding receptors are related to the activation of the apoptotic response, there will be differences in cell sensitivity to RGD and its sequence. Conversely, if the binding is unrequired, the integrin receptor can still bind to peptides. (2) Osteoblast cells are sensitive to GRGD sequences, and in high concentrations they can cause loss of cell viability. (3) Peptide concentrations are associated with the formation of a peptide solution. The increase in peptide solution causes elevation in the detachment rate of focal adhesions at the back of the cell, which will increase cell migration and prevent cell reconvene [27; 28]. The surface topography of the implant also affects cell characteristics. The nano-surface will alter the adhesion, motility, spread, proliferation, and differentiation of cells [1; 10; 29; 30]. The nano-surface can also influence cell adhesion selectively, which is why osteoblast adhesion was more than fibroblast [30]. The topography of the implant also affects its success, not only in terms of cell adhesion but more towards the stability of the implant itself. Bone loss is one of the signs of implant failure, the major cause of which is excessive stress, while after insertion and when the implant is starting its functioning, it will be subject to various pressures [31; 32; 33]. Therefore, the implant should transfer the stress to the surrounding bone fairly. A study shows that threaded dental implants produce twice the stress of implants with a porous surface [34]. In the present study, the IDCT-Ti/GRGD-1 implant exhibited a uniform nano-porous surface.