2.5.2. Surgical Procedures

At first surgery, premolars and first molars of upper and lower jaws were extracted. Animals were pre-anaesthetized with atropine sulfate induction (0.05 mg/kg IM; Dai Han Pharm Co., Seoul, Korea) and maintained on isoflurane (Choongwae Co., Seoul, Korea) gas anesthesia. Lidocaine (1 mL; Yu-Han Co., Gunpo, Korea) containing 1:100,000 epinephrine was infiltrated into mucosae at surgical

sites. The upper, lower premolars, and first molars were separated into mesial and distal roots. Care was taken to preserve the lateral, lingual, and buccal walls of alveolar sockets. Teeth were extracted carefully, and extraction sites were sutured with nylon silk (4-0, Mersilk, Ethicon Co., Livingston, UK) to enhance healing. The extraction sites were allowed to heal for two months.

Implant surgery was performed when extraction sockets had completely healed. The anesthesias (local and general) were performed, as described for first surgery. The implants of each groups were implanted at edentulous mandibular alveolar ridge. Briefly, each alveolar ridge was trimmed by ~1.5 mm to create a flat ridge before implant insertion, the buccal open defect model that had 2.5 mm depth was formed. This model was not buccal bone, and there was mesial-lingual-distal 1 mm defect area around 2.5 mm upper portion of implant (Figure 1a). Implants (control (Ti) group, Hepa/Ti group, PDGF/Hepa/Ti group, BMP/Hepa/Ti group, and PDGF/BMP/Hepa/Ti group) were installed randomly on right and left mandibular alveolar ridges (8 implants per dog). To place implants at the same position on both sides, exposed bone was marked at implant placement sites using a ruler. 5 mm of implant was placed within the reduced alveolar ridge to the reference notch level (shown on the implant), which resulted in a 2.5 mm peri-implant buccal open defects (Figure 1b,c). Each implant was covered with cover-screw. Mucoperiosteal flaps were advanced, adapted, and sutured leaving the implants submerged.

**Figure 1.** (**a**) Alveolar bone was flattened without exposing cancellous bone; (**b**) 5 mm of implant was placed within the reduced alveolar ridge and upper 2.5 mm of implants was placed in supra alveolar peri-implant buccal open defects; and (**c**) Schematic diagram of the buccal open defect model.
