Guided bone regeneration (GBR) has been used to promote osteogenesisin a bone defect surrounding a dental implant. While bone quantity at the implant interface has been investigated to evaluate stability of the implant system, bone quality is also responsible for determining mechanical response of bone around the implant. The objective of this study is to examine the nanoindentation based elastic modulus (E) and plastic hardness (H) at different bone regions adjacent to titanium dental implants with GBR treated with demineralized bone matrix (DBM) and bone morphogenetic protein (BMP) during different post-implantation periods. Six adult male beagle dogs were used to create circumferential defects (Ø6.3 mm x 4 mm) with buccal bone removal at each implantation site of mandibles following 3 months post-extraction healing periods. Four titanium dental implants were bilaterally placed in each dog mandible. The implant systems were randomly assigned to only GBR (control), GBR with DBM (DBM), and GBR with DBM+rhBMP-2 (BMP) groups. Three animals were sacrificed at each 4 and 8 weeks of post-implantation healing periods. The bone-implant constructs were buccolingually dissected for nanoindentation. The E and H values were assessed by 980 indentations at the defects (Defect), interfacial bone tissue adjacent to the implant (Interface), and pre-existing bone tissue away from the implant (Pre-existing). The E and H values of BMP group had significantly higher than control and DBM groups for interface and defect regions at 4 weeks of post-implantation period and for the defect region at 8 weeks (p<0.043). The DBM group had higher E and H values than control group only for the defect region at 4 weeks (p<0.001). The current results indicate that treatment of rhBMP-2 with GBR accelerates bone tissue mineralization, which enhances bone quality of the defect region during early post-implantation healing and maintain it for longer healing period. The GBR likely facilitate a microenvironment to provide more metabolites with the open space of the defect region adjacent the titanium implant.