INFLUENCE OF ETHYLENE OXIDE STERILIZATION ON NEW BONE FORMATION INDUCED BY BOVINE BONE MORPHOGENETIC PROTEIN

2000 ◽  
Vol 04 (04) ◽  
pp. 287-295
Author(s):  
Tarmo Pekkarinen ◽  
T. Sam Lindholm ◽  
Aulis Marttinen ◽  
Oili Hietala ◽  
Pekka Jalovaara
Keyword(s):  
Bone Formation ◽  
Ethylene Oxide ◽  
Bone Morphogenetic Proteins ◽  
Exposure Time ◽  
Clinical Settings ◽  
Bovine Bone ◽  
New Bone Formation ◽  
Morphogenetic Protein ◽  
Oxide Concentration ◽  
Different Temperatures

Bone morphogenetic proteins (BMPs) have the capacity to induce and accelerate bone regeneration. Before experimental and clinical settings, BMP must be sterilized. Ethylene oxide (EO) gas sterilizations at different temperatures are commonly used but the effects of that on the osteoinductive capacity of BMP have been the subject of controversy. Here, we investigated the effects of three different EO sterilization methods on the osteoinductivity of partially purified native bovine BMP (bBMP). Gelatin capsules containing 3 mg of bBMP were sterilized as follows: (i) manually inside a dessicator with 12% EO spray (20°C, exposure time 2 h); (ii) with an EO gas sterilizer (Steri-Vac 4XL, temperature 29°C, exposure time 4 h 10 min, ethylene oxide concentration 860 mg/l); (iii) with an EO gas sterilizer (Steri-Vac 5XL, temperature 42°C, exposure time 3 h, ethylene oxide concentration 700 mg/l). The sterilization processes were monitored with samples of Bacillus subtilis (3M, Attest 1264). Osteoinductivity of bBMP was verified by bioassay. After 21 days of implantation of bBMP into the muscle pouches of mice, the animals were killed and new bone formation was measured radiographically and histologically. The EO sterilization techniques used did not significantly decrease the osteoinductive activity of BMP. It is concluded that commercial EO gas equipment sterilization is effective for sterilized BMP and does not decrease the osteoinductive capacity of bovine BMP.

Gamma Irradiation and Ethylene Oxide in the Sterilization of Native Reindeer Bone Morphogenetic Protein Extract

2005 ◽  
Vol 94 (1) ◽  
pp. 67-70 ◽  
Author(s):  
T. Pekkarinen ◽  
O. Hietala ◽  
T. Jämsä ◽  
P. Jalovaara
Keyword(s):  
Ethylene Oxide ◽  
Gamma Irradiation ◽  
Bone Morphogenetic Proteins ◽  
Thigh Muscle ◽  
New Bone Formation ◽  
Morphogenetic Protein ◽  
Oxide Concentration ◽  
The Mean ◽  
Human Use ◽  
Ethylene Oxide Gas

Background and Aims: For human use, it is necessary to sterilize bone morphogenetic proteins (BMPs), in order to reduce the risk of infections and associated complications. We compared the effects of ethylene oxide and gamma irradiation in the sterilization of native reindeer BMP extract with regard to bone induction in the Balb/C mouse thigh muscle pouch model. Materials and Methods: BMP extract, sterilized with ethylene oxide gas (Steri-Vac 4XL' temperature 29°C, exposure time 4 h, ethylene oxide concentration 860 mg/l), or gamma irradiation at doses of 3.15 MRad was administered in implants containing 5 or 10 mg of BMP extract with collagen carrier. Non-sterilized collagen implants served as controls. New bone formation was evaluated based on the incorporation of Ca45 and radiographically three weeks after implantation. Results: The collagen was not able to induce new bone visible in radiographs. The mean Ca45 incorporation in the gamma sterilized group containing 5 mg of BMP extract was 30 % (p = 0.04) and that containing 10 mg of BMP extract was 60 % (p = 0.02) higher than seen in the corresponding ethylene oxide sterilized groups. The mean new bone areas were 45 % higher in the gamma sterilized groups than in the corresponding ethylene oxide sterilized groups, but the differences were not significant. The mean optical density of new bone in the gamma sterilized group containing 5 mg of BMP extract was 75 % (p = 0.00) and in that containing 10 mg of BMP extract was 70 % (p = 0.00) higher than seen in the corresponding ethylene oxide sterilized groups. Conclusion: Native reindeer BMP extract is more sensitive to the effects of ethylene oxide gas sterilization than gamma irradiation. These results suggest that gamma irradiation is recommendable for the sterilization of BMP extracts.

scholarly journals Lack of repair of rat skull critical size defect treated with bovine morphometric protein bound to microgranular bioabsorbable hydroxyapatite

2004 ◽  
Vol 15 (3) ◽  
pp. 175-180 ◽  
Author(s):  
Gabriel Ramalho Ferreira ◽  
Tania Mary Cestari ◽  
José Mauro Granjeiro ◽  
Rumio Taga
Keyword(s):  
Foreign Body ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Bone Repair ◽  
Critical Size ◽  
Bovine Bone ◽  
New Bone Formation ◽  
Body Type ◽  
Granulomatous Reaction ◽  
Post Surgery

The ability of a pool of bovine bone morphogenetic proteins bound to synthetic microgranular hydroxyapatite (BMPb-HA) to stimulate bone repair was determined in rat critical size defects. An 8-mm diameter defect was created in the calvaria of 25 rats. In 15 rats, the defects were filled with BMPb-HA homogenized with blood (experimental group), and in 10 rats the defects were filled only with blood clots (control). The calvariae of experimental rats were collected 1, 3 and 6 months after surgery and of the control rats at the end of surgery and 6 months thereafter. The morphometric results obtained in the radiographs showed an absence of new bone formation at 1 and 3 months post-surgery and, histologically, the defects were filled with fibrous connective tissue and numerous foci of a foreign body-type granulomatous reaction around hydroxyapatite agglomerates. At the end of 6 months, the number and size of the granulomatous foci decreased and the area of the defects was reduced by 22% compared to the 0-hour control due to the formation of new bone at their borders, although the mean area was similar to the 6-month control. We conclude that the use of BMPb-HA in the treatment of critical size bone defects of the rat skull leads to the formation of a foreign body-type granulomatous reaction that markedly inhibits new bone formation, suggesting that synthetic microgranular hydroxyapatite does not represent a good carrier for BMP-induced bone formation.

scholarly journals Alveolar wound healing after implantation with a pool of commercially available bovine bone morphogenetic proteins (BMPs): a histometric study in rats

2007 ◽  
Vol 18 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Romeu Felipe Elias Calixto ◽  
Juliana Mazzonetto Teófilo ◽  
Luiz Guilherme Brentegani ◽  
Teresa Lúcia Lamano-Carvalho
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Volume Fraction ◽  
Male Rats ◽  
Bovine Bone ◽  
New Bone Formation ◽  
Bovine Collagen ◽  
Histologic Pattern ◽  
Hematoxylin And Eosin ◽  
And Control

The capacity of a commercially available pool of bovine bone morphogenetic proteins (BMPs) to stimulate osteogenesis in the rat alveolar healing was investigated by histometric analysis. Male rats were anesthetized and had their upper incisor extracted. A pool of purified bovine BMPs adsorbed to microgranular resorbable hydroxyapatite was agglutinated with bovine collagen and saline before implantation into the alveolar socket. The implanted and control rats (n=30 per group) were sacrificed 1 to 9 weeks postoperatively, the hemi-maxillae were decalcified, processed for paraffin embedding and semi-serial longitudinal sections were obtained and stained with hematoxylin and eosin. The volume fraction of alveolar healing components was estimated by a differential point-counting method in histologic images. The results showed that in both, control and implanted rats, the alveolar healing followed the histologic pattern usually described in the literature. Quantitative data confirmed that the BMPs mixture did not stimulate new bone formation in the alveolar socket of implanted rats. These results suggest that the pool of BMPs adsorbed to hydroxyapatite and agglutinated with bovine collagen did not warrant incorporation of the osteoinductive proteins to a slow-absorption system that would allow a BMPs release rate compatible to that of new bone formation, and thus more adequate to osteoinduction.

Repair of Thyroid Cartilage Defect with Bone Morphogenetic Protein

1997 ◽  
Vol 106 (4) ◽  
pp. 326-328 ◽  
Author(s):  
Peng-Cheng Cui ◽  
Wen-Xuan Chen ◽  
Hui-Min Zhou
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Cartilage Defect ◽  
Thyroid Cartilage ◽  
Cartilage Defects ◽  
Bovine Bone ◽  
New Bone Formation ◽  
Morphogenetic Protein ◽  
Tissue Responses ◽  
Bone Particles

The object of this research was to investigate whether a thyroid cartilage defect can be repaired by newly formed bone induced by bovine bone morphogenetic protein (bBMP). Bilateral thyroid cartilage defects measuring 0.5 × 0.6 cm were created in 25 adult rabbits. Experimental defects were implanted with ceramic bone particles combined with bBMP, or in controls, without bBMP. The animals were painlessly killed at 2,4,8,12, and 16 weeks after implantation. The tissue responses were analyzed by routine histologic examination. An increase in the amount of new bone was observed in the interval from 4 to 12 weeks, and the defects were completely filled with new bone at 16 weeks, in contrast to a minimal new cartilage formation at the defect edges in controls. The results indicate that cartilage defects can be repaired by inducing new bone formation from mesenchymal cells in both perichondrium and muscular fascia.

scholarly journals Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation.

1992 ◽  
Vol 267 (20) ◽  
pp. 14233-14237
Author(s):  
Y Ogawa ◽  
D.K. Schmidt ◽  
R.M. Nathan ◽  
R.M. Armstrong ◽  
K.L. Miller ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Protein ◽  
Ectopic Bone Formation ◽  
Bovine Bone ◽  
Morphogenetic Protein ◽  
Ectopic Bone

scholarly journals Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3513
Author(s):  
Nikola Stokovic ◽  
Natalia Ivanjko ◽  
Drazen Maticic ◽  
Frank P. Luyten ◽  
Slobodan Vukicevic
Keyword(s):  
Animal Models ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Animal Experiments ◽  
Inorganic Materials ◽  
New Bone Formation ◽  
Segmental Bone ◽  
Posterolateral Spinal Fusion ◽  
Regenerative Therapies ◽  
Observation Period

Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.

scholarly journals The use of solvent-preserved human and bovine cancellous bone blocks for lateral defect augmentation - an experimental controlled study in vivo

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Lara Schorn ◽  
Tim Fienitz ◽  
Kathrin Berndsen ◽  
Norbert R. Kübler ◽  
Henrik Holtmann ◽  
...  
Keyword(s):  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Substitute ◽  
Bone Matrix ◽  
Human Bone ◽  
Controlled Study ◽  
Bovine Bone ◽  
New Bone Formation ◽  
Bone Substitute Material ◽  
Substitute Material

Abstract Background The aim of this study was to compare new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material in laterally augmented alveolar bone defects using allogeneic, pre-treated and cleaned human bone blocks (tested in dogs, therefore considered to be xenogeneic), and pre-treated and cleaned bovine cancellous bone blocks, both with and without a collagen membrane in order to evaluate their augmentative potential. Methods Thirty-two critical size horizontal defects were prepared in the mandible of 4 adult foxhound dogs (8 per dog, 4 on each side). After 3 months of healing, the defects were laterally augmented in a split-mouth-design with either human (HXB) or bovine solvent-preserved bone blocks (BXB). Afterwards, defects were randomly covered with a bovine collagenous membrane (HXB + M, BXB + M). After a healing interval of 6 months, percentages of new bone formation, resorbed bone matrix, and fibrous enclosed residual bone substitute material were compared. Results Results showed little new bone formation of up to 3.7 % in human bone blocks (HXB 3.7 % ± 10.2, HXB + M 0.3 %± 0.4, BXB, 0.1 % ± 0.8, BXB + M 2.6 % ± 3.2, p = > 0.05). Percentages of fibrous encapsulation were higher in human bone blocks than in bovine bone blocks (HXB 71.2 % ± 8.6, HXB + M 73.71 % ± 10.6, BXB, 60.5 % ± 27.4, BXB + M 52.5 % ± 28.4, p = > 0.05). Resorption rates differed from 44.8 % in bovine bone blocks covered with a membrane to 17.4 % in human bone blocks (HXB 17.4 % ± 7.4, HXB + M 25.9 % ± 10.7, BXB, 38.4 % ± 27.2, BXB + M 44.8 % ± 29.6, p = > 0.05). The use of additional membranes did not significantly affect results. Conclusions Within its limitations, results of this study suggest that solvent-preserved xenogenic human and bovine bone blocks are not suitable for lateral bone augmentation in dogs. Furthermore, defect coverage with a membrane does not positively affect the outcome.

Ability of Deproteinized Cancellous Bovine Bone to Induce New Bone Formation

2000 ◽  
Vol 71 (8) ◽  
pp. 1258-1269 ◽  
Author(s):  
Z. Schwartz ◽  
T. Weesner ◽  
S. Van Dijk ◽  
D.L. Cochran ◽  
J.T. Mellonig ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bovine Bone ◽  
New Bone Formation

Bioactivity of the Two Kinds of Biodegradable Composite Membrane Containing Oriented Needle-Like Apatite

2005 ◽  
Vol 284-286 ◽  
pp. 811-814 ◽  
Author(s):  
Toshiki Itoh ◽  
Seiji Ban ◽  
T. Watanabe ◽  
Shozo Tsuruta ◽  
Takahiro Kawai ◽  
...  
Keyword(s):  
Bone Formation ◽  
Composite Membrane ◽  
Composite Membranes ◽  
Bone Defects ◽  
Thigh Muscle ◽  
Poly Lactic Acid ◽  
New Bone Formation ◽  
Biodegradable Composite ◽  
Morphogenetic Protein ◽  
Old Mice

It is well known that bone morphogenetic protein (BMP) induces bone formation and requires for carriers. Poly-lactic acid / poly-glycolic acid (PLGA) is frequently used as the carriers of BMP. We developed a biodegradable composite PLGA membrane, which was containing oriented needle-like apatite with BMP. The composite membranes were implanted into the thigh muscle pouch of 3-week-old-mice. At 3 weeks after implantation, the implanted area was observed by optical microscopy. The composite membrane containing oriented needle-like apatite with BMP induced new bone formation. It seems that this composite membrane might be a scaffold of BMP and promoting the healing of bone defects.

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