Surgical procedures were described in detail in a previous publication [19 (link)]. In brief, surgeries were performed under general anesthesia using inhalation of 2.5% isoflurane and intravenous injection of alfaxan (5 mg/kg). Before incision, surgical sites were disinfected with povidone iodine, and infiltration anesthesia was carried out using 2% lidocaine with 1:80,000 adrenaline. The incision was made along the midline of the calvarium from the frontal bone to the occipital bone, and a full-thickness flap was raised. Three circular defects were made with a trephine bur of 8 mm inner-diameter and each defect was treated as allocated by the study design. Flaps were repositioned and sutured with resorbable suture material (4-0 Vicryl, Ethicon, Somerville, NJ, USA). Sutures were removed one week after surgery. After two or eight weeks of healing, rabbits were sacrificed as allocated and specimens were obtained.
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