Sutures impregnated with carbazate-activated polyvinyl alcohol reduce intraperitoneal adhesions.

BACKGROUND: Intraperitoneal adhesions cause significant morbidity. They occur after peritoneal trauma, which induces oxidative stress with production of inflammatory cytokines, peroxidized proteins (carbonyls) and lipids (aldehydes). This study aimed to investigate if carbazate-activated polyvinyl alcohol (PVAC), an aldehyde-carbonyl inhibitor, can reduce intraperitoneal adhesions in an experimental model. MATERIAL AND METHODS: Male Sprague-Dawley rats (n=110) underwent laparotomy, cecal abrasion and construction of a small bowel anastomosis. They either were treated with intraperitoneal instillation of PVAC or were sutured with PVAC-impregnated sutures. Thromboelastography analysis was performed using human blood and PVAC. The lipid peroxidation product malondialdehyde (MDA) and inflammatory cytokines IL-1ß and IL-6 were quantified in peritoneal fluid. At day 7, bursting pressure of the anastomosis was measured and adhesions were blindly scored. RESULTS: PVAC in human blood decreased the production of the fibrin-thrombocyte mesh without affecting the coagulation cascade. MDA, IL-1ß and IL-6 were increased after 6h without significant difference between the groups. PVAC-impregnated sutures reduced intraperitoneal adhesions compared to controls (p=0.0406) while intraperitoneal instillation of PVAC had no effect. Anastomotic bursting pressure was unchanged. CONCLUSIONS: Intervention with an aldehyde-carbonyl inhibitor locally in the wound by PVAC-impregnated sutures might be a new strategy to reduce intraperitoneal adhesions.

Cartilage repair of experimentally 11 induced osteochondral defects in New Zealand White rabbits.

Articular cartilage has a limited capacity for self-repair in adult humans, and methods used to stimulate regeneration often result in re-growth of fibrous cartilage, which has lower durability. No current treatment option can provide complete repair. The possibility of growth factor delivery into the joint for cartilage regeneration after injury would be an attractive treatment option. A full thickness osteochondral defect of 4 mm in diameter and 2 mm deep was created by mechanical drilling in the medial femoral condyle in 20 female adult New Zealand White rabbits. In an attempt to improve regeneration a hyaluronic hydrogel system, with or without bone morphogenetic protein-2 (BMP-2) was delivered intraarticularly. The contralateral joint defect was treated with saline as control. Throughout the study, rabbits were clinically examined and after 12 (n = 6) or 24 (n = 9) weeks, the rabbits were euthanized and the joints evaluated by histology. The defects healed with fibrocartilage like tissue, and the filling of the defects ranged from less than 25% to complete. The healing of the defects varied both inter- and intra-group wise. Treatment with hyaluronan gel with or without BMP-2 had no effect on cartilage regeneration compared with controls. Instead, severe ectopic bone formation was found in seven joints treated with BMP-2. In conclusion, the present study shows that neither treatment with hyaluronic gel alone, nor in combination with BMP-2, improves the healing of an induced cartilage defect in rabbits. It further shows that BMP-2 can induce ectopic bone formation, which severely affects the functionality of the joint.

Alveolar bone healing accompanied by severe swelling in cleft children treated with bone morphogenetic protein-2 delivered by hydrogel.

BACKGROUND: The use of osteoinductive growth factors may be preferable for alveolar cleft repair because it eliminates the need of bone harvesting. In the present prospective randomised pilot study, patients with alveolar clefts were treated with either bone morphogenetic protein 2 (BMP-2) delivered by a hyaluronan-based hydrogel or autologous bone from the iliac crest. METHODS: Seven patients with cleft lip or cleft lip and palate were included. Computed tomography (CT) was performed preoperatively and 6 months postoperatively. The residual cleft volume was compared with the initial volume. Surgery time, bleeding and hospital stay were compared between the two groups. RESULTS: Four patients were randomised to treatment with BMP-2. A low BMP-2 concentration of 50 µg ml(-1) hydrogel did not induce bone formation in treated patients (n = 2) after 6 months, as seen by CT scans. Therefore, the BMP-2 concentration was raised to 250 µg ml(-1) hydrogel in the subsequently randomised patients (n = 2). Bone formation with volume ratio of 59% and 33% was here verified by CT scans after 6 months. However, a severe gingival swelling appeared during the first week in patients treated with higher BMP-2 doses. In the autologous bone group (n = 3), the volume ratio was 29%, 48%, and 69%. Mean surgery time was 100 min in the BMP-2 group and 123 min in the autologous bone group. The mean hospital stay was 2.75 and 3.33 days, respectively. CONCLUSIONS: BMP-2 at a concentration of 250 µg ml(-1) delivered by a hydrogel can be used to treat alveolar cleft defects with good bone quantity and comparable to autologous bone grafts. However, severe gingival swelling may limit the use of BMP-2 for these patients. Therefore, the study was prematurely closed.

Bone morphogenetic protein-3 is a negative regulator of bone density.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily. Many BMPs are produced in bone and show osteogenic activity, suggesting that they may be determinants of bone mass. BMP3 was originally purified from bone as osteogenin, which induces osteogenic differentiation. Recombinant BMP3 (rhBMP3) has no biological activity, however, leaving its role in skeletal growth unclear. Here we show that BMP3 is an antagonist of osteogenic BMPs: BMP3 dorsalizes Xenopus laevis embryos, inhibits BMP2-mediated induction of Msx2 and blocks BMP2-mediated differentiation of osteoprogenitor cells into osteoblasts. These effects appear to be mediated through activin receptors. Finally, Bmp3(-/-) mice have twice as much trabecular bone as wild-type littermates, indicating that BMP3, the most abundant BMP in adult bone, is a negative determinant of bone density.

Transient production of bone morphogenetic protein 2 by allogeneic transplanted transduced cells induces bone formation.

The aim of this study was to evaluate the use of transplantation of genetically modified allogeneic cells as a method to induce bone formation. In this study, we infected a murine osteoprogenitor cell line with a retroviral vector containing the human bone morphogenic protein 2 (BMP2) gene. Transduced cells exhibited more alkaline phosphatase activity than cells treated with any of the tested doses of recombinant human BMP2 protein (rhBMP2). The transduced cells were suspended in a collagen solution and injected into the quadriceps muscle in immunocompetent outbred mice. Radiographic and histological examinations demonstrate abundant ectopic bone formation in 85% of the transplanted animals (n = 13). PCR and Southern blot analysis for the puromycin resistance gene revealed that the transplanted cells were detectable for up to 1 week, but not at later time points. None of the animals developed tumors. Our results suggest that allogeneic BMP2-expressing transduced cells may have therapeutic potential for enhancing new bone formation. This model also provides a simple, inexpensive, and sensitive assay for evaluating in vivo the osteoinductive potentials of secreted proteins without the requirement of protein purification or the use of immunodeficient animals.