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Bone has the capacity to regenerate in response to injury. During distraction osteogenesis, the renewal of bone is enhanced by gradual stretching of the soft connective tissues in the gap area between two separated bone segments. This procedure has received much clinical attention as a way to correct congenital growth retardation of bone tissue or to generate bone to fill skeletal defects. The process of bone regeneration involves a complex system of biological changes whereby mechanical stress is converted into a cascade of signals that activate cellular behavior resulting in (enhanced) formation of bone. Over the last decade, significant progress has been made in understanding the bone regeneration process during distraction osteogenesis. The mechanical and biological factors that are important for the success of the distraction treatment have been partially characterized and are discussed in this review. [ABSTRACT FROM AUTHOR]

The article presents information on a study which investigated the functions of the anion exchanger 2 (Ae2) in the development of bones and teeth and the distribution of Ae2 in cells involved in the formation of teeth and surrounding bone in young hamsters, mice and rats. It discusses the findings on immunostatining in development of incisors, molars, and bones. It explores histological changes in Ae2 mice with general Ae2 isoform disruptions. It also suggests the importance of Ae2 for tooth and bone formation.

Thrombin-related peptide 508 (TP508) accelerates bone regeneration during distraction osteogenesis (DO). We have examined the effect of TP508 on bone regeneration during DO by immunolocalization of Runx2 protein, a marker of osteoblast differentiation, and of osteopontin (OPN) and bone sialoprotein (BSP), two late markers of the osteoblast lineage. Distraction was performed in tibiae of rabbits over a period of 6 days. TP508 (30 or 300 μg) or vehicle was injected into the distraction gap at the beginning and end of the distraction period. Two weeks after active distraction, tissue samples were harvested and processed for immunohistochemical analysis. We also tested the in vitro effect of TP508 on Runx2 mRNA expression in osteoblast-like (MC3T3-E1) cells by polymerase chain reaction analysis. Runx2 and OPN protein were observed in preosteoblasts, osteoblasts, osteocytes of newly formed bone, blood vessel cells and many fibroblast-like cells of the soft connective tissue. Immunostaining for BSP was more restricted to osteoblasts and osteocytes. Significantly more Runx2- and OPN-expressing cells were seen in the group treated with 300 μg TP508 than in the control group injected with saline or with 30 μg TP508. However, TP508 failed to increase Runx2 mRNA levels significantly in MC3T3-E1 cells after 2–3 days of exposure. Our data suggest that TP508 enhances bone regeneration during DO by increasing the proportion of cells of the osteoblastic lineage. Clinically, TP508 may shorten the healing time during DO; this might be of benefit when bone regeneration is slow. [ABSTRACT FROM AUTHOR]

Vertical distraction osteogenesis has received considerable interest as a way to augment bone prior to implant placement. However, very little is known regarding the appropriate distraction protocols in the human mandible. In this study, we evaluate the effect of the distraction rate and the duration of neutrofixation on bone formation and closure of the gap in the human mandible. Vertical distraction was performed in the atrophic mandible of 16 edentulous patients, aged 62 ± 6 years. The bone was distracted for approximately 10 mm at a rate of either 0.5 or 1 mm/day. Bone biopsies were taken after 7–20 weeks of neutrofixation. Histological analysis demonstrated newly formed bone in the distraction gap in all biopsies. The bone was predominantly of the woven type. After 10 weeks of neutrofixation, the gap was bridged by new bone in two out of three intact samples in the 0.5 mm/day group, but not in two intact samples of the 1 mm/day group. Histomorphometry revealed longer bone trabeculae ( P=0.02) and a somewhat increased bone volume in the area where new bone formation started ( P=0.07) in the group of patients having the 0.5 mm/day of distraction rate than in the 1 mm/day group. We conclude that in elderly patients, a distraction rate of 0.5 mm/day results in faster osteogenesis in the distraction gap than a rate of 1 mm/day. A minimum of 10 weeks of neutrofixation seems to be needed to close a 10 mm gap after cessation of distraction. [ABSTRACT FROM AUTHOR]

We examined the effect of distraction rate on blood vessel growth in intramembraneous ossification after vertical distraction osteogenesis in the human mandible. Six edentulous patients (aged 60±9 years) with a severely atrophic mandible underwent bone augmentation with distraction osteogenesis. Two distraction rates (0.5 and 1 mm/day) were compared and for each group three patients were analyzed. Vascular histomorphometry was carried out in two different areas in the distraction gap: (1) in the first and (2) in the second 1 mm area from the osteotomy line, representing the oldest and younger new-bone area, respectively. Correlation analysis was performed between blood vessel parameters and the amount of new bone formed during distraction. Histological analysis demonstrated the presence of blood vessels throughout the soft connective tissue in the distraction gap. The volume density of blood vessels between the two investigated areas was significantly lower in the 1 mm/day groups, suggesting a delay in angiogenesis in this group of patients. A positive correlation between blood vessel volume and bone volume density was found in the younger new-bone area but not in the oldest new-bone area. This correlation was due to a higher number of blood vessels rather than to a larger size of the blood vessels. Our data suggest that the lower blood vessel density found in the patients with 1 mm/day distraction rate may be related to disruption of angiogenesis in the soft connective tissue of the gap or to a less optimal mechanical stimulation of cells involved in angiogenesis. This probably results in the slower rate of osteogenesis seen at the 1 mm/day distraction rate compared with the 0.5 mm/day distraction rate. The data support the concept that a positive relationship exists between the density of blood vessels and the formation of bone. For distraction of the human mandible in elderly patients, a distraction rate of 0.5 mm/day seems beneficial. [ABSTRACT FROM AUTHOR]