[Study of the proton magnetic relaxation in bone regenerate in dynamics according to data of nuclear magnetic resonance].
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Animals↗
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[Bone regeneration in theory and practice. A report on the continuing education course of 7 June 1993 at the Basel Exhibits and Convention Center].
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Alveolar Bone Loss↗
Effects of Delta12-prostaglandin J2 on bone regeneration and growth factor expression in rats.
OBJECTIVES: Cyclopentenone prostaglandins have been shown to promote osteoblast differentiation in vitro. The aim of this study was to examine in a rat model the effects of local delivery of Delta(12)-prostaglandin J(2) (Delta(12)-PGJ(2)) on new bone formation and growth factor expression in (i) cortical defects and (ii) around titanium implants. MATERIAL AND METHODS: Standardized transcortical defects were prepared bilaterally in the femur of 28 male Wistar rats. Ten microliters of Delta(12)-PGJ(2) at 4 concentrations (10(-9), 10(-7), 10(-5) and 10(-3) mol/l) in a collagen vehicle were delivered inside a half-cylindrical titanium chamber fixed over the defect. Contralateral defects served as vehicle controls. Ten days after surgery, the amount of new bone formation in the cortical defect area was determined by histomorphometry and expression of platelet-derived growth factor (PDGF)-A and -B, insulin-like growth factor (IGF)-I/II, bone morphogenetic protein (BMP)-2 and -6 was examined by immunohistochemistry. In an additional six rats, 24 titanium implants were inserted into the femur. Five microliters of carboxymethylcellulose alone (control) or with Delta(12)-PGJ(2) (10(-5) and 10(-3) mol/l) were delivered into surgically prepared beds prior to implant installation. RESULTS: Delta(12)-PGJ(2) (10(-5) and 10(-3) mol/l) significantly enhanced new bone formation (33%, P<0.05) compared with control cortical defects. Delivery of Delta(12)-PGJ(2) at 10(-3) mol/l significantly increased PDGF-A and -B and BMP-2 and -6 protein expression (P<0.05) compared with control defects. No significant difference was found in IGF-I/II expression compared with controls. Administration of Delta(12)-PGJ(2) also significantly increased endosteal new bone formation around implants compared with controls. CONCLUSION: Local delivery of Delta(12)-PGJ(2) promoted new bone formation in the cortical defect area and around titanium implants. Enhanced expression of BMP-2 and -6 as well as PDGF-A and -B may be involved in Delta(12)-PGJ(2)-induced new bone formation.
Absorbable Implants↗
Development and transplantation of a mineralized matrix formed by osteoblasts in vitro for bone regeneration.
The use of extracellular matrix materials as scaffolds for the repair and regeneration of tissues is receiving increased attention. The current study was undertaken to test whether extracellular matrix formed by osteoblasts in vitro could be used as a scaffold for osteoblast transplantation and induce new bone formation in critical size osseous defects in vivo. Human osteoblasts derived from alveolar bone were cultured in six-well plates until confluent and then in mineralization media for a further period of 3 weeks to form an osteoblast--mineralized matrix complex. Histologically, at this time point a tissue structure with a "connective tissue"-like morphology was formed. Type I collagen was the major extracellular component present and appeared to determine the matrix macrostructure. Other bone-related proteins such as alkaline phosphatase (ALP), bone morphogenetic protein (BMP)-2 and -4, bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN) also accumulated in the matrix. The osteoblasts embedded in this matrix expressed mRNAs for these bone-related proteins very strongly. Nodules of calcification were detected in the matrix and there was a correlation between calcification and the distribution of BSP and OPN. When this matrix was transplanted into a critical size bone defect in skulls of immunodeficient mice (SCID), new bone formation occurred. Furthermore, the cells inside the matrix survived and proliferated in the recipient sites, and were traceable by the human-specific Alu gene sequence using in situ hybridization. It was found that bone-forming cells differentiated from both transplanted human osteoblasts and activated endogenous mesenchymal cells. This study indicates that a mineralized matrix, formed by human osteoblasts in vitro, can be used as a scaffold for osteoblast transplantation, which subsequently can induce new bone formation.
Animals↗
Bone regeneration using rhBMP-2 induction in hemimandibulectomy type defects of elderly sub-human primates.
Our previous work has shown that total osseous reconstruction of large discontinuity hemimandibulectomy, critical-sized defects can be achieved easily in 8-year-old Macaca fascicularis monkeys (Boyne 1996). However the literature has indicated that animal aging decreases the BMP induction of stem cells in rats and in other rodent species. It was necessarily important that the rhBMP-2 be demonstrated in non-human primates to determine if this reduction in effectiveness also existed in the higher animals phylogenetically. The purpose of this study was to operate aged non-human primates duplicating the model used in middle-aged animals to demonstrate regeneration of hemimandibulectomy defects. This age group could be extrapolated to the 80-year-old clinic patient. Six non-human primates aged 20 years were rendered edentulous posteriorly and the mandibles allowed to heal. Three months postoperatively bilateral hemimandibulectomies were performed. The defects received BMP in a collagen sponge (Helistat) using a dose level of 0.75 mg of rhBMP-2. After the manner previously reported by Boyne (1996, 1999), at the end of four months the surgical sites were exposed by mucoperiosteal flap demonstrating complete regeneration of the critical-sized defects. The animals received two dental implants in restored areas. The implants were brought into function approximately four months later, and were allowed to function for eight months in all cases. The results indicate that the regeneration of mandibular critical-sized defects by the use of rhBMP-2 in aged animals is comparable to that of the middle-aged group. This study indicates that aged non-human primates, chronologically comparable to 80-year-old humans, respond as favorably to rhBMP-2 as do the middle-aged animals. Extrapolating the results to the clinical level, one would expect that rhBMP-2 would produce a comparable result in the regeneration of large hemimandibulectomy-type defects in clinical human patients.
Aging↗
[Bone regeneration after flap surgery--a report of 4 cases].
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Adult↗
Expression of insulin-like growth factor I messenger ribonucleic acid in regenerating bone after fracture: influence of indomethacin.
Expression of insulin-like growth factor I (IGF-I) was studied during time in the callus formed after tibial fracture in rats. Levels of IGF-I mRNA in callus peaked on the day 8 postfracture, showing a 10- to 15-fold induction compared to control bone. Levels of IGF-I mRNA tended also to be increased in the fracture-adjacent musculus tibialis anterior. IGF-I immunoreactivity was found in cartilaginous cells, osteoblasts, and myocytes 6 and 8 days after fracture. No obvious differences were found between hypophysectomized animals and control animals with regard to IGF-I immunoreactivity. Administration of the antiinflammatory drug indomethacin decreased the IGF-I mRNA expression in the tibial fracture model. Previous findings have shown that IGF-I is activated during in vivo muscle regeneration, and also in this model indomethacin administration reduces the expression of IGF-I. The finding that indomethacin administration reduces IGF-I expression could indicate that an inflammatory response may be important for activation of IGF-I during tissue regeneration.
Animals↗
Supracrestal bone regeneration around dental implants using a calcium carbonate and a fibrin-fibronectin sealing system: clinical and histologic evidence.
This study evaluated a new surgical technique for the treatment of an alveolar ridge deficiency in 11 patients. Twenty-two implants were placed, 15 of which presented with a combination of supracrestal and dehiscence kinds of defects, and seven presented only supracrestal bone loss. Surgical procedures were performed utilizing a combination of the resorbable space-making material calcium carbonate stabilized with a fibrin-fibronectin sealing system and the immediate placement of titanium dental implants. After implant placement, the mean height for supracrestal and dehiscence defects measured 2.57 +/- 1.41 mm and 2.47 +/- 1.54 mm, respectively. The defects were filled with calcium carbonate and a fibrin-fibronectin sealing system, and the flaps were sutured, avoiding any compression of the treated area. Healing was uneventful in all instances. At second-stage surgery at 6 months, a hard bone-like tissue was detectable at the defect sites. Histologic examination of four defects confirmed the presence of newly formed bone and revealed residual particles of calcium carbonate. There was a mean gain of 2.05 +/- 1.47 mm in the supracrestal defects and of 2.23 +/- 1.62 mm in the dehiscences. The results indicated that calcium carbonate, combined with a fibrin-fibronectin sealing system, is a viable alternative in the treatment of supracrestal and dehiscence bony defects.
Adult↗
Bone regeneration around a failing implant using guided tissue regeneration. A case report.
An implant was determined to be clinically and radiographically failing. The implant was treated as if it were a natural tooth with periodontal disease. The defect around the implant was degranulated and a polytetrafluoroethylene periodontal membrane placed over the implant to cover the defect. The membrane was removed 6 weeks later. A 5-month re-entry found new bone around the implant and the implant could then be used as a prosthetic abutment. Further case studies may prove this to be a predictable procedure to save failing implants.
Bone Regeneration↗
Histological morphology of the e-PTFE/tissue interface in humans subjected to guided bone regeneration in conjunction with oral implant treatment.
The purpose of the present investigation was to study the histological morphology of the e-PTFE membrane/tissue interface in 5 humans subjected to GBR treatment in conjunction with oral implant treatment. Oral implants (Brånemark System) were inserted in extraction sockets 1 to 2 months after extraction of periodontally diseased teeth. The implants were placed approximately 2 mm below the surrounding bone margins. Specially designed 3 mm high cover-screws with horizontal slits for tissue ingrowth were applied to the implants and covered with e-PTFE membranes (GoreTex Augmentation Material). Re-entry was made 7 months later, except in 1 case where the membrane was removed 1 month postoperatively due to exposure and infection. In the remaining 4 sites, circular biopsies comprising membranes, tissues and cover-screws were retrieved. The specimens were fixated, processed and sectioned for light- and transmission electron microscopy. The space between the membrane and the cover-screw was occupied by fibrous tissue and varying amounts of bone. A cell- and vessel-rich fibrous tissue separated the bone from the membrane in the majority of the specimens. The membrane itself was penetrated by fibrous tissue. Fibroblasts and macrophages were the main cell types found in the fibrous tissue. The presence of irregularly shaped cells and unevenly distributed collagen fibres, indicated that the absence of bone formation may be due either to micromovements in the e-PTFE/tissue interface or to formation of fibrous tissue underneath the membrane by penetrating fibroblasts or a combination of these 2 phenomena.
Bone Regeneration↗
Effect of insulin-like growth factor-1 on zygomatic arch bone regeneration: a preliminary histological and histometric study.
A number of physicians have attempted to pharmacologically manipulate the healing of bony fractures with a variety of agents such as growth hormone, thyroxine, chondroitin sulfate, and parathyroid hormone. Thus far, results from these experiments have been inconclusive. Previous research dealing with insulin-like growth factors has centered on cultures of osteoblast-like cells and has demonstrated a stimulatory effect on bone collagen synthesis, which may in fact play a critical role in the process of bone formation itself. The purpose of this investigation was to examine the effects of a genetically engineered growth factor, insulin growth factor type I, on midfacial fracture healing. In 24 adult male Sprague-Dawley rats, a standardized defect was created within the midportion of each zygomatic arch. One-half were treated with insulin growth factor type I administered with an osmotic infusion pump and the other half served as control subjects. At 2, 4, 8, and 12 weeks, animals from each group were killed and specimens of the defect obtained. Data were collected from radiographs and histological studies to compare the extent of bony repair. From this study, it appears that insulin growth factor type I could exert a potentiating effect on the repair of midfacial bone defects.
Animals↗
Experimental evaluation of the effects of zoledronic acid on regenerate bone formation and osteoporosis in mandibular distraction osteogenesis.
PURPOSE: The aim of this study was to evaluate the effects of systemically administered zoledronic acid (ZA) on the bone mineral density (BMD) and bone mineral content (BMC) at mandibular distraction sites in rabbits. MATERIALS AND METHODS: Eighteen New Zealand white rabbits were randomly divided into 2 groups. Bone lengthening was performed in the left portion of the mandible through distraction osteogenesis at a rate of 0.5 mm every 12 hours for 5 days. While the experimental group rabbits were administered intravenous 0.1 mg/kg ZA, control group rabbits were given only saline infusion during operation. All animals were sacrificed at the end of the consolidation period of 28 days. The mandibles of all animals were removed and both the anterior and posterior pin regions of the regenerate and regenerate region were evaluated by dual energy x-ray absorptiometry (DEXA). BMD and BMC data were statistically analyzed. RESULTS: Except for 1 rabbit from the experimental group that had an infection at the external pin region, all animals showed complete clinical healing. When the values in the group receiving ZA were compared with those of the control group, it was observed that the BMD values of the anterior pin region of regenerate, regenerate region, and posterior pin region increased by 23%, 20%, and 31%, respectively; and BMC values increased by 22%, 24%, and 32%, respectively. When data of these regions were compared, both BMD and BMC were found statistically different in all regions (P < .05). CONCLUSION: Results of this study showed that ZA had positive effects on new bone formation at and around the distraction gaps of the lengthened rabbit mandibles by distraction osteogenesis.
Absorptiometry, Photon↗
[Fibrin glue and bone regeneration].
The osteoinductive property of fibrin glue with and without admixture of aprotinin was proven in animal model. Aprotinin as an inhibitor of the fibrinolysis is supposed to be an inhibitor of the osteogenesis, too. Three holes of 4 mm diameter and 2 mm depth were placed into the diaphysis of both femura in 12 adults dogs. The defects were filled with either pure fibrin glue or with glue containing aprotinin (3000 KIE), or with nothing (vacant). After 8 weeks the quantity of the new built woven-bone was examined by plane geometry and the "Bone Metabolising Unit (BMU)" (Frost) which are crossing the border of lamellar bone and new woven bone were counted out. There was seen no statistical significantly between the three groups neither in the quantity of new bone nor in the BMU. Therefore the fibrin glue has no osteoinductive property.
Animals↗
[Factors affecting bone regeneration in Ilizarov callus distraction].
We evaluated the X-rays of 36 patients who underwent 50 callus distractions. With the aid of a computerized digitalisation system for analogue films, the relative X-ray density of the distraction area was calculated for each X-ray. These relative X-ray densities were figured graphically for the duration of treatment for each patient. In the consolidation phase, the graph of each patient had a logarithmic relationship. The gradients of the logarithmic density curves were considered an indicator of the quantity of new bone formation. These gradients were correlated to the following clinical parameters: age of the patient, beginning of distraction after corticotomy, average speed of distraction, average weight bearing during the distraction and consolidation phase, location of corticotomy (distal femur versus proximal tibia) and diclofenac medication. Except for the location of the corticotomy and diclofenac, all parameters had an influence on osteoneogenesis by callus distraction. The parameters affecting new bone formation the most were the age of the patient and weight bearing. Patients aged under 18 years (p = 0.005), beginning of distraction later than 8 days (p = 0.109), an average distraction speed below 1 mm/day (p = 0.079), and average weight bearing of more than 30 kg (p = 0.068 for the distraction phase and p = 0.089 for the consolidation phase) showed a quantitatively higher rate of new bone formation by callus distraction than the patients in the other groups. Patients with a shorter leg due to poliomyelitis and one patient with an amniotic leg tie showed a slower increase in X-ray density graphs than the other patients.
Absorptiometry, Photon↗
A histological evaluation for guided bone regeneration induced by a collagenous membrane.
This study was designed to evaluate the histological changes during ossification and cellular events including osteogenic differentiation responding to collagenous bioresorbable membranes utilized for GBR. Standardized artificial bony defects were prepared at rat maxillae, and covered with a collagenous bioresorbable membrane. These animals were sacrificed at 1, 2, 3 and 4 weeks after the GBR-operation. The paraffin sections were subject to tartrate resistant acid phosphatase (TRAP) enzyme histochemistry and immunohistochemistry for alkaline phosphatase (ALP), osteopontin (OP) and osteocalcin (OC). In the first week of the experimental group, woven bone with ALP-positive osteoblasts occupied the lower half of the cavity. The collagenous membrane included numerous ALP-negative cells and OP-immunoreactive extracellular matrices. At 2 weeks, the ALP-, OP- and OC-immunoreactivity came to be recognizable in the region of collagenous membrane. Since ALP-negative soft tissue separated the collagenous membrane and the new bone originating from the cavity bottom, the collagenous membrane appeared to induce osteogenesis in situ. At 3 weeks, numerous collagen fibers of the membrane were embedded in the adjacent bone matrix. At 4 weeks, the membrane-associated and the cavity-derived bones had completely integrated, showing the same height of the periosteal ridge as the surrounding alveolar bones. The collagen fibers of a GBR-membrane appear to participate in osteogenic differentiation.
Animals↗
The effect of basic fibroblast growth factor on bone regeneration when released from a novel in situ setting tricalcium phosphate cement.
The osteostimulative effect of the basic fibroblast growth factor is well known, but it is dose dependent, and release kinetic depends on interactions with the used carrier. The aim of our study was to determine the osteostimulative effect of a composite, consisting of an in situ setting tricalcium phosphate cement and basic fibroblast growth factor. A trepanation defect of 1.5 mm in the femur diaphysis of Sprague-Dawley rats was filled with the in situ setting TCP cement combined with 0, 0.25, 2.5, or 25 microg rh bFGF, an autologous bone graft or left empty. The rats were euthanized after 1 and 3 weeks and examined by radiography, histology, histomorphometry, and bending test. The data were analyzed by the Wilcoxon and Kruskal-Wallis test. All TCP groups with or without bFGF showed a good bony ingrowth with a close bone-cement contact. Osseous ingrowth was not influenced by the addition of the different doses of bFGF as shown by histomorphometry. Also, mechanical strength was not affected. In conclusion, the combination of this in situ setting cement with bFGF is not useful for clinical application. The reason of these negative results remains unclear: the osteostimulative effect of bFGF is well known, and the TCP-cement was used as a carrier for rhBMP-2 successfully. These negative results may be due to a too slow or too fast release of bFGF from the cement.
Animals↗
Influence of external administration of epinephrine on bone regeneration.
The effect of local administration of epinephrine was tested in a rabbit experimental model. Identical commercially pure titanium implants were inserted in the right legs of New Zealand white rabbits after pretreatment with epinephrine; the left legs served as controls. This acute administration of epinephrine was shown to have no significant impact on the incorporation of the implant as measured after 7 weeks.
Animals↗
Effect of placement of occlusive membranes on root resorption and bone regeneration during healing of circumferential periodontal defects in dogs.
Previous studies indicate that root resorption is a frequent sequela to significant amounts of periodontal repair in animal models. A model was developed in labrador dogs to study periodontal wound healing in large circumferential defects in the absence of influence from the oral environment. A polytetrafluorethylene membrane of 1 micron pore size (GORE-TEX) was used to occlude cells from specific tissues from populating the healing dentin-connective tissue wound. 3 modalities were studied: (1) control, in which no membrane and therefore no cell occlusion was used, (2) flap occlusion, in which the internal surface of the flap was lined with the membrane preventing contribution of cells from the flap, (3) bone occlusion, in which the reduced alveolar bone was lined with the membrane preventing contribution from bone cells. Wound closure included total submergence of teeth and membranes. The membranes remained incorporated and no exposure of membranes or teeth occurred during the 3 months healing period. Histology revealed bone regrowth in all 3 treatment modalities. It is suggested that inductive elements in the connective tissue or dentin, or bone cells from periosteum were responsible for bone regrowth in the bone membrane treatment modality. No significant difference was seen for root resorption between the 3 treatment modalities. This study found that physical occlusion of cells from the inside of the surgical flap, or from the pre-existing bone, is not sufficient to prevent root resorption in periodontal wound healing.
Alveolar Process↗