Bio gide

Four or six dental implants with a length of at least 11 mm and a diameter of 4 mm were inserted in the maxillary anterior region (OsseoSpeed^™ 4.0 S dental implants, Astra Tech AB, Mölndal, Sweden). The implants were placed at crestal bone level in predefined positions (positions 15, 13, 11, 21, 23, 25 in the six implants group and positions 13, 11, 21, 23 in the four implants group) with the help of a surgical template following a submerged healing protocol. In some cases, the most distal implant position may be 16 or 26 (in the six implants group), but it is always without a large sinus floor elevation. Small dehiscences or fenestrations were covered with bone harvested from the maxillary tuberosity and organic bovine bone (Bio‐Oss^®; Geistlich Pharma AG, Wolhusen, Switzerland) and subsequently covered with a resorbable membrane (Bio‐Gide^®; Geistlich Pharma AG, Wolhusen, Switzerland). If the most distally placed implants (usually in the six implants group) were partially placed in the anterior part of the maxillary sinus, a small sinus floor elevation surgery was performed in that region to prevent a perforation of the sinus membrane by the implant. After a 3‐month osseointegration period, second‐stage surgery was performed and healing abutments (Uni Healing Abutments, Astra Tech AB) were placed.

The following treatments were performed according to the size of the bony access window and the membrane coverage on the window. In 6 rabbits, small bony access windows (SW; ø 2.8 mm) were made on the antral bone to access the bilateral maxillary sinus. In 6 other rabbits, large windows (LW; ø 6 mm) were made. After inserting bone substitute particles into both sinuses, one access window in each rabbit was covered with a native bilayer collagen membrane (CM) (Biogide; Geistlich Pharma, Wolhusen, Switzerland). Through the above treatments, 4 experimental groups were established, as follows: LW with/without CM coverage (LW+CM and LW), and SW with/without CM coverage (SW+CM and SW). Four weeks of healing were provided to all experimental animals.

A single surgeon (T.M.) performed all of the procedures. A periosteal patch was used in patients who underwent the procedure before May 2007 (n = 5), whereas a type I/III bilayer collagen membrane derived from porcine peritoneum and skin (Bio-Gide; Geistlich Pharma) was used in patients who underwent the procedure after May 2007 (n = 10). When a periosteal patch was used in conjunction with ABG, the first periosteal patch was glued with Tisseel fibrin glue (Baxter BioSurgery), and a few tacking sutures (No. 6-0 resorbable sutures) were used circumferentially over the bone graft with the cambium layer facing out. The periosteum was then covered with a neural patty, the leg was brought into full extension, and the tourniquet was let down. The knee was then gently flexed up, the neural patty was gently removed, and visual inspection was performed to ensure that the base of the defect was dry with no marrow-derived blood present. A second periosteal patch was then microsutured on the articular surface at intervals of 3 to 5 mm circumferentially, with the cambium layer facing the defect. The margins were then sealed watertight with Tisseel fibrin glue, and autologous cultured chondrocytes were injected between the 2 membranes, where they were sandwiched between the cambium layers of the periosteum or collagen membranes (Figures 1 and 2).

Three types of commercially-available porcine-derived collagen membranes: (1) Striate+^TM manufactured by Orthocell Ltd., Perth, Western Australia, Australia (30 mm × 40 mm), (2) Bio-Gide^® manufactured by Geistlich Pharma, Wolhusen, Switzerland (30 mm × 40 mm) and (3) Creos^TM Xenoprotect manufactured by Matricel GmbH, Herzogenrath, Germany (30 mm × 40 mm) were used in this study. Raw materials are porcine mesentery as positive controls for heamatoxylin and eosin staining and real-time polymerase chain reaction (PCR), and porcine aortic valve (Boatshed Butcher at Cottesloe, Perth, Western Australia, Australia) is a positive control for DNA content and immunogenic porcine α-gal by immunohistochemistry analysis.

Approximately 4 months later, CBCT images were taken with the same settings as in the first scan. Before the placing the incision, bone and soft tissue biopsy samples were retrieved with a trephine bur (2.3×10.0 mm; Genoss, Seoul, Korea) along the original root axis of the extraction socket. A periosteal flap was elevated and implants (CMI IS active, Neobiotech, Seoul, Korea) were placed. In order to maximize the initial stability, the final drill was 1 size smaller than the final drill. Additional GBR was performed using the DBBM and a resorbable collagen membrane (Bio-Oss^® and Bio-Gide^®, Geistlich Pharma) if the residual buccal thickness was less than 1 mm or the thread of the fixture was exposed. Healing abutments were connected in all of the implants. The Periotest value (PTV) was measured at the buccal surface of the healing abutment using a Periotest M device (Medizintechnik Gulden, Modautal, Germany). The patients then received the same medications described above.