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Results for “BONE REGENERATION”

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At least 973 records · Page 54Linked to original sources
PubMed2001

The importance of drug delivery to optimize the effects of bone morphogenetic proteins during periodontal regeneration.

Bone morphogenetic proteins (BMPs) include a large number of proteins belonging to the TGF-beta superfamily which are characterized by their ability to induce bone and cartilage formation. Since the isolation and purification of BMPs by recombinant technology, the effects of single BMPs can now be evaluated in animal models. Subcutanous placement of a single recombinant BMP, such as recombinant human (rh) BMP-2, in a rat ectopic assay shows recruitment of undifferentiated mesenchymal cells, cartilage formation, followed by replacement with bone, formation of its own bone marrow and physiological bone remodelling. The therapeutic use of recombinant BMPs in the treatment of periodontal disease (destruction of the tooth ligaments, surrounding bone and tooth cementum, the latter of which anchors the ligaments to the tooth surface from the adjacent tooth socket) has attracted considerable interest due to their potent ability to stimulate intramembranous bone formation without an endochondral intermediate. Their predictability in stimulating new bone may provide an alternative that has greater osteogenic potential than autogenous bone, other growth factors and bone substitutes. The biological processes and the potential role of growth factors involved in promoting regeneration are complicated by the involvement of different cell types each with their different growth rates and responses to various stimuli. The major cell types involved in periodontal regeneration include osteoblasts, cementoblasts and fibroblasts. Here, the formation of the new mineralized layers on the tooth and bone surfaces by cementoblasts and osteoblasts respectively are a prerequisite before periodontal ligament formation and attachment by fibroblasts can occur. In this regard, BMPs are likely candidates to stimulate periodontal regeneration because of their ability not only to promote osteogenesis but also to stimulate cementogenesis (new cementum formation). However, understanding when to manipulate each of the various cells differentiation pathway with the application of single or multiple doses of BMPs at the appropriate concentration is dependent upon a suitable delivery system that can be modified in order to optimize its effect during periodontal wound healing. Furthermore, treatment of intrabony periodontal defects with BMPs are likely to not only require appropriate temporal release of the agent, but also adaptation of a carrier that is robust enough to maintain its integrity around the coronal aspect of the root in order to provide space maintenance and support the mucoperiosteal flap. This review evaluates the effects of different delivery systems upon BMP-induced periodontal regeneration.

Animals↗
PubMed1976

Resorption and regeneration of alveolar bone in acute osteomyelitis of the mandible.

A 12-year-old boy developed osteomyelitis of the anterior part of the mandible subsequent to a blow on the mouth. The condition resulted in loosening of the lower incisors and considerable loss of alveolar bone. Under conservative treatment the condition subsided and the bone regenerated completely. Radiographs taken at various stages in the treatment show the loss of bone and its gradual regeneration.

Acute Disease↗
PubMed1981

[Electron microscopic study of reparative osteogenesis following electric stimulation of bony tissue regeneration].

Electron microscopy was used to study the regenerating bone tissue in experimental resection of the diaphysis fragment of the rabbit radius under osteogenesis stimulation by means of pulsed low-frequency electric current. Proliferation and differentiation of fibroblasts and osteoblasts of the bone regenerating tissue were more active under electric stimulation. Hypertrophy and hyperplasia of cell organelles occurred earlier as compared with control. Cell secretion was found to be intensified, manifesting by output of greater amounts of collagen protein. As a result of changes listed, the newly formed bone tissue rapidly filled the defect between the fragments.

Animals↗
PubMed2006

Prostaglandin E2 EP4 receptor-selective agonist facilitates sternal healing after harvesting bilateral internal thoracic arteries in diabetic rats.

OBJECTIVE: Sternal wound complications are devastating events occurring in coronary artery bypass surgery, particularly in patients with diabetes. Prostaglandin E2 receptors have 4 subtypes, and the activation of the EP4 receptor induces bone regeneration. The present study investigated the utility of a prostaglandin E2 EP4 receptor-selective agonist in sternal healing after median sternotomy with the removal of the bilateral internal thoracic arteries in diabetic rats. METHODS: Diabetic Wistar rats with blood glucose levels of greater than 400 mg/dL were established by means of a single intraperitoneal injection of streptozotocin. After median sternotomy and bilateral internal thoracic artery removal in 16 diabetic rats, 8 rats were administered the EP4 agonist (300 microg) on the posterior table of the sternum (EP4 group), whereas 8 did not receive any treatment (control group). Sternal healing and incidence of sternal wound complications were evaluated 4 weeks after the operation. RESULTS: Sternal wound complications developed in 5 rats in the control group but in only 1 rat in the EP4 group (P < .01). Histologic examination revealed an almost completely healed sternum filled with regenerated bone tissue only in the EP4 group. Both bone mineral content and bone mineral density, as assessed with dual-energy x-ray absorptiometry, were higher in the EP4 group than in the control group (71.7 +/- 12.1 vs 48.9 +/- 11.7 mg for bone mineral content [P < .01] and 66.8 +/- 14.6 vs 47.9 +/- 6.3 mg/mm2 for bone mineral density [P < .05]). CONCLUSIONS: The prostaglandin E2 EP4 agonist accelerated the sternal healing and decreased the incidence of sternal wound complications in the diabetic ischemic sternum. This method might help in decreasing sternal necrosis in high-risk patients or permit wider application of bilateral internal thoracic arteries in coronary artery bypass surgery, even in patients with diabetes.

Animals↗
PubMed2000

Stabilization of proteins encapsulated in injectable poly (lactide- co-glycolide)

Controlled release from biodegradable polymers is a novel approach to replace daily painful injections of protein drugs. A major obstacle to development of these polymers is the need to retain the structure and biological activity of encapsulated proteins during months of incubation under physiological conditions. We encapsulated bovine serum albumin (BSA) in injectable poly(DL-lactide- co-glycolide) (PLGA) 50/50 cylindrical implants and determined the mechanism of BSA instability. Simulations of the polymer microclimate revealed that moisture and acidic pH (<3) triggered unfolding of encapsulated BSA, resulting in peptide bond hydrolysis and noncovalent aggregation. To neutralize the acids liberated by the biodegradable lactic/glycolic acid-based polyester, we coincorporated into the polymer an antacid, Mg(OH)2, which increased microclimate pH and prevented BSA structural losses and aggregation for over one month. We successfully applied this stabilization approach in both cylinder- and microsphere-injectable configurations and for delivery of angiogenic basic fibroblast growth factor and bone-regenerating bone morphogenetic protein-2.

3T3 Cells↗
PubMed2005

Differentiation of transplanted mesenchymal stem cells in a large osteochondral defect in rabbit.

BACKGROUND: Although accumulating evidence shows that mesenchymal stem cells (MSC) are a promising cell source for articular cartilage repair, the fate of transplanted MSC has not been extensively studied. METHODS: To monitor their persistence and differentiation, we labeled uninduced MSC with a fluorescent dye, PKH26, and transplanted them, in a poly-glycolic-acid scaffold, to full-thickness defects made in the weight-bearing area of rabbit femoral trochleae with hyaluronate sheets. The fate of the labeled cells was monitored for up to 8 weeks. RESULTS: Two weeks after transplantation, immature cartilage containing collagen type II had formed. By 8 weeks, this cartilage had thinned and immunolabeling for collagen type II gradually disappeared from the basal region, which became positive for collagen type I. Most chondrocytes within the regenerated cartilage were PKH26-positive and, therefore, derived from transplanted MSC, whereas osteoblasts within the regenerated bone were a mixture of donor- and host-derived cells. The thickness of the cartilage became thinner up to 8 weeks and then remained stable up to 42 weeks after surgery. DISCUSSION: These results showed that uninduced MSC were able to survive osteochondral defects and differentiated according to the environment, making a major contribution to initial cartilage formation and a partial contribution to bone regeneration.

Animals↗
PubMed2000

[Facial bone reconstruction. Review of particularities and procedures].

The authors report the particularities of the cranio-maxillofacial skeleton and the aims of the reconstruction procedures: osteogenesis, osteoconduction, osteoinduction. They review the various procedures, their abilities, some technical notes, their advantages and disadvantages. They analyse in order: classical bone autografts, pedicled bone flaps (arterio-osseous, fascio-osseous, myo-osseous flaps), free bone flaps, classical and pedicled periosteal transplantations. They also describe the mechanical and biological procedures of bone stimulation: bone distraction, guided bone regeneration, bone growth factors, and the biomaterials, especially coral and enosseous implants. They conclude that, in facial reconstruction, the best material is the autologous bone membranous and vascularized.

Bone Transplantation↗
PubMed1998

Effect of allogeneic freeze-dried demineralized bone matrix on regeneration of alveolar bone and periodontal attachment in dogs.

This split-mouth study was designed to evaluate regeneration of alveolar bone and periodontal attachment following implantation of allogeneic, freeze-dried, demineralized bone matrix (DBM). Buccal fenestration defects (6x4 mm) were created on the maxillary canine teeth in 6 beagle dogs. DBM was implanted into one randomly selected defect in each animal. The contralateral defect served as surgical control. Tissue blocks were harvested following a 4-week healing interval and prepared for histometric analysis. DBM was discernible in all implanted defects with limited evidence of bone metabolic activity. The DBM particles appeared invested within a dense connective tissue, often in close contact to the instrumented root. Fenestration defect height averaged 3.8+/-0.1 and 3.7+/-0.3 mm, total bone regeneration 0.9+/-0.9 and 0.4+/-1.2 mm, and total cementum regeneration 2.3+/-1.5 and 0.6+/-0.7 mm for DBM and control defects, respectively. Differences with regards to cementum regeneration were statistically significant (p=0.03). In summary, the results of this study suggest that DBM implants may enhance cementum regeneration in this defect model, and that they have no apparent effect on alveolar bone regeneration. Enhanced cementum regeneration may be possibly be explained by provisions for guided tissue regeneration from the implant suppressing a significant influence of the gingival connective tissue on the healing process. Moreover, a 4-week healing interval appears insufficient for turnover of DBM.

Alveolar Bone Loss↗
PubMedDate not supplied

[Effect of "carbostimulin", vitamin D 3 and their mixture on bone tissue regeneration].

Healing of the bone injury in rabbits was studied as affected by carbostimulin and its mixture with vitamin D3. Some biochemical indexes: the content of sialic acids, calcium and citric acid in blood serum of the animals, intensity of 14C incorporation from NaH14CO3 into the regenerated bone tissue and its proteins as well as histological studies, data, evidence for a positive effect of the mentioned preparations on the bone substance regeneration in the animals under experiment. So. the content of sialic acids in blood serum normalizes on the 10th day after the operation mostly in the animals which were administered the mixture of the preparations and in which the most pronounced hypercalcemia is observed. Incorporation of 14C from NaH14CO3 into the regenerated tissue and its proteins is most intensive in the same animals.

Animals↗
PubMed1997

Regeneration of diaphyseal bone defects using resorbable poly(L/DL-lactide) and poly(D-lactide) membranes in the Yucatan pig model.

OBJECTIVES: To determine the effects of tubular resorbable polymer membranes on the healing of a segmental diaphyseal bone defect. DESIGN: A randomized prospective study using the minipig model. Animals were evaluated with in vivo roentgenograms on a biweekly basis until explanted at twelve weeks. SETTING: After surgery, animals were allowed unrestricted activity and weight bearing between twenty-four and forty-eight hours. ANIMALS: Fifteen yearling Yucatan minipigs. INTERVENTION: A 2.5- to 3.0-centimeter mid-diaphyseal defect was created in the middle third of the radius. Animals were assigned in groups of three to receive the following implants: (a) poly(L/DL-lactide), (b) poly(L/DL-lactide)-CaCO3, (c) poly(D-lactide), (d) poly(D-lactide)-CaCO3, and (e) an untreated defect. No adjunctive internal or external fixation was used as the ulna was left intact. MAIN OUTCOME MEASURES: The limbs were studied with in vivo anterior-posterior and lateral radiographs at biweekly intervals for the presence and pattern of bone formation. All limbs were explanted at twelve weeks postimplantation for methyl-methacrylate embedding and histologic and microradiographic study. RESULTS: The bone defects covered with membranes were completely reconstituted by six to eight weeks. Untreated defects healed with less bone formation and in a more disorganized pattern. Histologic evaluation of the implants demonstrated that the entire lumen of the implant was filled with bone, with some periosteal bone formation occurring on the outer surface of the membrane. There was direct apposition of bone onto the membrane surface or minimal fibrous tissue interposition between membrane and new bone. There was no foreign body or adverse reaction to the membrane. Untreated defects showed woven bone formation with clefts and irregularly shaped margins occupied by fibrous tissues or surrounding muscle tissues. CONCLUSIONS: This study supports the concept that a membrane enhances bone defect healing by excluding nonosseous tissues from a defect and providing structural scaffolding for periosteal and endosteal bone regeneration.

Absorption↗
PubMed2006

Pleiotropism of bone morphogenetic proteins: from bone induction to cementogenesis and periodontal ligament regeneration.

Bone morphogenetic and osteogenic proteins (BMPs/OPs), pleiotropic members of the transforming growth factor-beta (TGF-beta) supergene family, induce de novo endochondral bone formation and act as soluble signals of tissue morphogenesis, sculpting the architecture of multicellular mineralized structures, including the periodontal tissues. The presence of multiple forms of BMPs/OPs has a therapeutic significance and the choice of a suitable protein will be a formidable challenge to the practising periodontologist. Amino acid sequence variations in the carboxy terminal domain, the molecular basis of the structure/activity profile of each isoform, confer specialized and pleiotropic activities to each morphogenetic protein. Naturally derived BMPs/OPs regenerate cementum and alveolar bone in mandibular furcation defects of the primate Papio ursinus. Tissue morphogenesis induced by hOP-1 and hBMP-2 is qualitatively different when the morphogens are applied singly, indicating that the structure/activity profile amongst BMPs/OPs is controlling pleiotropic tissue induction and morphogenesis. Furcation defects of Papio ursinus with root surfaces exposed long-term to periodontal pathogens and filled with granulation tissue after inoculation of a pathogenetic human strain of Porphyromonas gingivalis twice a month for 12 months were implanted with hOP-1 osteogenic devices. Six months after surgery there was regeneration of alveolar bone and induction of cementogenesis, with Sharpey's fibres uniting the regenerated bone to the newly formed cementum. Although within the natural milieu of the bone matrix a plurality of morphogens may be required to initiate the cascade of pattern formation and the attainment of tissue form and function, recombinant y-irradiated hOP-1 delivered by a xenogeneic collagenous matrix induces complete periodontal tissue regeneration on periodontally affected root surfaces, showing an additional specific function of hOP-1 for tissue morphogenesis in clinical contexts. The pleiotropy of the signalling molecules of the TGF-beta superfamily is additionally highlighted by the redundancy of molecular signals initiating endochondral bone induction by the TGF-beta isoforms per se, powerful inducers of endochondral bone, but in the primate only. A novel approach in periodontal tissue regeneration is to induce heterotopic bone to be transplanted as morcellised autogenous grafts into established periodontal defects. The induction of bone develops a mosaic structure in which the osteogenic proteins of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis, with specific roles at different time points of the morphogenetic cascade.

Animals↗
PubMed2000

Basic fibroblast growth factor may improve devascularized sternal healing.

BACKGROUND: We have shown that a gelatin sheet incorporating basic fibroblast growth factor enhanced bone regeneration of the devascularized sternum. The purpose of this study was to determine if topical use of the gelatin sheet accelerated normal sternal regeneration and bone remodeling. METHODS: Thirty Wistar rats had median sternotomy and were divided into 3 groups: 10 had the bilateral internal thoracic arteries removed and basic fibroblast growth factor sheet applied on the sternum (group A), 10 had just the bilateral internal thoracic arteries removed (group B), and 10 had intact bilateral internal thoracic arteries (group C). RESULTS: Four weeks later the peristernal blood flow significantly increased and marked angiogenesis was seen around the sternum in group A. Histologically, the sternum was almost completely healed only in group A. In group A the bone mineral content was highest, but the bone mineral density was similar to that in other groups. The osteoclast index in group A was highest at the border zone of bone formation and remained high in regenerated bone. CONCLUSIONS: The basic fibroblast growth factor sheet offset sternal ischemia and accelerated normal sternal bone regeneration and remodeling, not only by callus formation but also by callus resorption.

Animals↗
PubMed2005

[The influence of mesenchymal stem cells on bone tissue regeneration upon implantation of demineralized bone matrix].

Mesenchymal stem cells (MSC) are resident pluripotent cells of bone marrow stroma. MSC are able to differentiate into chondroblasts, adipocytes, neurons, glia, cardiomyocytes, or osteoblasts. The problem of MSC usage in cell therapy of bone defects is widely discussed at present. The experiments were carried out using rats of inbred line Wistar-Kyoto. MSC were isolated from bone marrow and cultivated in vitro. Demineralized bone matrices (DBM) were obtained from parietal bones of rats and hens. Part of DBM was loaded with MSC. Bone defects were made in cranium parietal regions. DBM with or without MSC or metal plates were transplanted in these regions. It was shown that the application of MSC increased angiogenesis and osteogenesis in the damaged bone. The implantation of rat's DBM with MSC led to the formation of a full value bone. MSC suppressed inflammation, when transplantation of hen's DBM was carried out. The application of MSC always improved bone tissue regeneration.

Animals↗
PubMedDate not supplied

[Effect of opioid peptides on the repair regeneration of the bone tissue].

The study is made of the effects of selective agonists of opioid receptors (DAGO--the agonist of mu-receptors, DSLET--the agonist of delta-receptors, dynorphin A,I-13,--the agonist of kappa-receptors) on reparative osteogenesis in CBA mice. The drugs were injected intraperitoneally within 7 days after bone fracture in equimolar doses: DAGO--6.3 mcg/kg, DSLET--10 mcg/kg, dynorphin A (1-13)--20.2 mcg/kg. It was established that the use of DSLET and DAGO accelerates the development of newly-synthesized spongy bone tissue in the bone regenerate. This manifested with its early appearance (4 days after the fracture) as well as higher indices of specific volumes of bone tissue in the regenerate within the experiment (7, 10, 14 days after bone fracture) in comparison with the control animal group. Dynorphin A(1-13) had no influence on regenerate formation in our experiments.

Animals↗
PubMed2006

High dose glucocorticoid hampers bone formation and resorption after bone marrow ablation in rat.

We analyzed the effect of glucocorticoid on bone regeneration after bone marrow ablation in tibiae of 8-week-old rats. Methylprednisolone sodium succinate (MPSS) was injected intramuscularly at a dose of 100 mg/kg/day for 3 days. Tibiae on days 1, 3, 5, 7, 10, 12, and 14 after ablation were subjected to tartrate-resistant acid phosphatase staining, immunohistochemistry, in situ hybridization, and transmission electron microscopy (TEM), and measurement of the volume of newly-formed bone and the osteoclast number. MPSS significantly decreased the newly-formed bone volume on day 7, and immature bone still remained on day 10 in the MPSS-treated group. The volume of this bone was significantly higher than that in the control group. However, there were no differences between the groups in the osteoclast number, the expression of mRNAs for osteoblast differentiation markers, and alkaline phosphatase and cathepsin K judged by immunohistochemistry. TEM findings showed no difference in the form of osteoblasts, whereas osteoclasts in the MPSS-treated group had less developed ruffled borders, compared to those in the control group. These results suggest that MPSS treatment affects neither the differentiation nor the shape of osteoblasts, and does not change the osteoclast number or the cathepsin K level. However, high dose MPSS inhibits both bone formation and resorption during bone regeneration after rat tibial bone marrow ablation, and inhibits ruffled border formation in osteoclasts. These data will be useful to develop bone regenerative therapies for bone diseases due to high dose steroid administration.

Alkaline Phosphatase↗
PubMed2006

Enhancement of the osteogenic efficacy of osteoblast transplantation by the sustained delivery of basic fibroblast growth factor.

Previously, the sustained delivery of basic fibroblast growth factor (bFGF) has been demonstrated to promote bone regeneration in bone defects that had not been treated with osteogenic cell transplantation. In this study, we tested the hypothesis that the sustained delivery of bFGF could enhance osteoblast transplantation-mediated ectopic bone formation. Rat osteoblasts and bFGF were mixed with an injectable fibrin matrix and subcutaneously transplanted to rats (cell + bFGF group). The fibrin matrix played roles in both the cell transplantation matrix and the bFGF sustained delivery matrix. The transplantation of osteoblasts suspended in a fibrin matrix without bFGF served as a control. Twelve weeks after transplantation, histological analyses of retrieved transplants showed that new bone formation was more abundant and mature in the cell + bFGF group than in the control group. The bone formation area and the calcium content in the cell + bFGF group were two- and nine-fold higher, respectively, than those in the control group. Enhanced bone formation by the sustained delivery of bFGF may be attributed to the enhanced osteogenic gene expression of the transplanted cells and neovascularization of the transplants, as both mRNA expression of various osteogenic markers and arteriole density in the cell + bFGF group were significantly higher than those in the control group. This study demonstrates that the sustained delivery of bFGF can potentiate ectopic bone regeneration by osteoblast transplantation. This combination therapy may have effective implications for bone regeneration in large bone defects in which extensive osteogenic cell migration and angiogenesis are required.

Animals↗