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PubMed1998

Importance of the critical-size bone defect in testing bone-regenerating materials.

A substantial interest exists in developing substitute materials and human recombinant bone-inducing factors to enhance bone regeneration both in the craniofacial complex and in other parts of the skeleton. A persistent problem has been to find an animal model that allows for the comparison of different osteopromotive materials. The purpose of this investigation was 1) to determine whether a 5-mm calvarial defect in adult rats fulfilled the requirements of a critical-size bone defect and 2) to discuss the use of this animal model in assessing bone repair in the craniofacial region. Bilateral full-thickness calvarial defects were trephined in the calvarial bone of 56 5- to 6-month-old Wistar rats. Except for minor amounts of bone formation limited to the margins of the defect, none of the defects revealed any signs of spontaneous bone regeneration 6 and 12 months after surgery. The full-thickness 5-mm calvarial defects thus fulfill the criteria for a critical-size bone defect. This animal model allows for an experiment with a paired design, it avoids inclusion of the sagittal suture in the osseous defect, and it thereby minimizes morbidity by reducing the risk of damaging the midsagittal sinus. An adequate experimental model has been developed to evaluate the efficiency of osteopromotive materials in the healing of bone defects in the craniomaxillofacial region.

Animals↗
PubMed1983

[Stromal cells of the regenerating bone marrow in rats (an immunocytochemical electron microscopy study)].

Process of the bone marrow regeneration has been studied after its removal out of the rat femoral bone cavity. The stage of stroma formation precedes hemopoiesis. The stromal cells during its reconstruction (the 4th-5th day after removal of the bone marrow) are analyzed by means of the indirect immune-peroxidase electron microscopical method with antiserum applied against insoluble antigens of the rat bone marrow cells. Most of the stromal cells do not fix the antiserum used, as do the hemopoietic cells, macrophages and preosteoclasts. Some part of the stromal cells (not more than 30%) demonstrate the immune-peroxidase label. The labelled stromal cells have some ultrastructural signs of poorly differentiated elements of fibroblastic and osteoblastic raws. In the regeneration area, there are non-labelled poorly differentiated cells, which do not differ, at the ultrastructural level, from labelled poorly differentiated stromal elements. Possible causes of the difference revealed among the poorly differentiated stromal cells concerning their fixing of the anti-bone-marrow antiserum are discussed.

Animals↗
PubMed1999

Skull bone regeneration in primates in response to basic fibroblast growth factor.

OBJECT: The feasibility of using a biodegradable hydrogel incorporating basic fibroblast growth factor (bFGF) to induce bone regeneration at the site of a skull defect in monkeys was investigated. METHODS: Basic fibroblast growth factor was incorporated into a bioabsorbable hydrogel, which was prepared through glutaraldehyde crosslinking of gelatin. Following treatment of monkey skull defects measuring 6 mm in diameter (six defects/experimental group) with gelatin hydrogel incorporating bFGF, skull bone regeneration was evaluated using soft x-ray studies, dual x-ray absorptometry, and histological examinations. The water content of the hydrogels varied according to the glutaraldehyde concentration in the hydrogel preparation. Gelatin hydrogels incorporating 100 microg of bFGF significantly promoted bone regeneration and the skull defect was completely closed 21 weeks after implantation. This is in marked contrast with the effect of the same dose of bFGF in solution form. Bone mineral density (BMD) measured at the sites of skull defect was enhanced by the bFGF-incorporating hydrogels. The BMD enhancement was more prominent at lower water contents of hydrogel. Empty gelatin hydrogels neither induced nor interfered with skull bone regeneration. CONCLUSIONS: The findings of this study indicate that bFGF coupled with bioabsorbable hydrogel is a very promising tool to assist in the regrowth of bone at the site of a skull defect, which clinically has been recognized as almost impossible.

Absorptiometry, Photon↗
PubMed1977

Bile salts secretion in cirrhosis.

The bile salts secretion was studied in ten normal subjects and sixteen patients with alcoholic cirrhosis, in a basal period and during 60 minutes after Secretin injection. Total bile salts were measured by a modification of the enzymatic method of Iwata and Yamasaki and the individual bile salts were separated by silica gel thin-layer chromatography. During the 60 minutes after Secretin the mean concentration was 2.88 +/- 2.58 muM/ml in normals and 1.96 +/- 1.25 muM/ml in cirrhotics. The difference is not significant. During the first 20 minutes however the concentration was higher than 3 muM/ml in 8 out of 10 normals and lower than 2 muM/ml in 10 out 16 cirrhotics. The ratios of tri-to dihydroxy bile salts was similar in both groups. The ratios between bile salts conjugated with glycine and with taurine was higher in normals, and the ratio between free to conjugated bile salts was higher in cirrhotics. The lower concentration of total bile salts immediatly after Secretin, the higher proportion of taurin conjugates and of free bile salts could be important factors in the difficulties of fact digestion and absorption frequently found in patients with alcoholic cirrhosis.

Adult↗
PubMedDate not supplied

Guided bone regeneration around exposed implants: a new bioresorbable device and bioresorbable membrane pins.

This article presents the principles and the clinical procedure of utilizing a new bioresorbable collagen barrier device, bioresorbable membrane pins, and a new bone substitute for bone regeneration around exposed implants. Three cases are used to illustrate the clinical procedure. In all three cases, the regeneration of bone around the implants was successful, and upon clinical examination the newly regenerated material resembled natural bone. Histologic data regarding the new bioresorbable collagen barrier itself and the time range in which the collagen device functioned as a barrier are still lacking, and the studies are currently being conducted. The learning objective of this article is to introduce a combination of options available for successful regeneration of bone around the implants and avoiding the second-stage surgery.

Adult↗
PubMed1993

The role of the dura in cranial bone regeneration in the immature animal.

In an animal model, the effect of transferring mature pericranial tissues to immature animals with cranial bone defects was tested. Isogeneic guinea pigs of different ages were used: "infants" (3-4 weeks) and "adults" (> 18 months). Bilateral parietal cranial defects were made in infant guinea pigs and the guinea pigs were divided into three groups. In group 1 (n = 6), the infant periosteum was resected and replaced as an autograft on one side (control), and adult periosteum was transplanted as an isograft on the other (experiment). In group 2 (n = 5), dura was used as the variable. In group 3 (n = 5), combined dura and periosteum were the variables. After 8 weeks, there was complete or near complete bone regeneration in all animals in which infant dura was present. There was minimal to no bone regeneration in defects in which adult dura was present. Unlike dura, periosteum had little influence on the capacity of the bone to regenerate.

Animals↗
PubMed1999

Histological examination of regenerated bone through craniofacial bone distraction in clinical studies.

The process of bone formation by distraction osteogenesis of the craniofacial bone has been studied in animals. To our knowledge there are no published findings in which histological examination of craniofacial distraction in humans has been reported. Specimens were obtained from 10 patients who underwent craniofacial distraction: 2 patients who underwent mandibular distraction, 7 patients who underwent midface distraction, and 1 patient who underwent nasal bone distraction. These specimens were examined histologically. The results revealed that 8 of 10 patients exhibited new bone formation. No cartilaginous callus formation was observed in any of the specimens, which strongly suggests that new bone was produced by intramembranous ossification during human craniofacial bone distraction.

Adolescent↗
PubMedDate not supplied

Success and failure rates of osseointegrated implants in function in regenerated bone for 72 to 133 months.

PURPOSE: Guided bone regenerative therapy has become a significant component of clinical implant practice. Initial reports have demonstrated success rates of implants in regenerated bone under function comparable to the success rates of implants placed in native nonregenerated host bone. This report documents the success and failure rates of osseointegrated implants placed in regenerated bone for up to 133 months in function. MATERIALS AND METHODS: A retrospective analysis of a group of 607 titanium plasma-sprayed cylindric implants placed in regenerated bone, the success and failure rates of which were previously reported at 6 to 51 months in function, were assessed. RESULTS: The implants demonstrated cumulative success rates of 97.2% for the maxilla and 97.4% for the mandible, yielding an overall cumulative success rate of 97.4% for up to 133 months in function. DISCUSSION AND CONCLUSIONS: Titanium plasma-sprayed osseointegrated implants of various diameters, lengths, and designs, utilized in a variety of clinical scenarios, demonstrated functional cumulative success rates comparable to those of implants placed in nonregenerated host bone for extended periods of time in this patient population.

Adult↗
PubMed1993

Bone regeneration by the osteopromotion technique using bioabsorbable membranes: an experimental study in rats.

An osteopromotive technique has been developed that allows improved bone regeneration as well as bone neogenesis using porous, inert, nondegradable membranes made of expanded polytetrafluoroethylene (e-PTFE). For certain applications, however, it would be advantageous to use bioabsorbable membranes (BAMs), thus avoiding a surgical reentry for membrane removal. In this randomized comparison study the osteopromotive potential of BAMs was investigated in standardized "critical size defects" (5 mm in diameter) in the rat mandible. Three membrane types were tested and comparisons were made with e-PTFE membrane. The BAMs consisted of polylactic/polyglycolic acid copolymers designed to give the membranes different absorption times when implanted in the tissue. Histologic analysis after healing periods of 1 to 12 weeks demonstrated the BAMs to be well tolerated by the tissue, causing just a mild inflammatory reaction along the membrane surfaces as long as the material remained in the tissue. The BAMs were found to be as efficient as e-PTFE membranes in that the bone repair was not significantly different with any of the four membrane types. However, healing in conjunction with one type of BAM seemed to occur somewhat more rapidly. Some cartilage was present at the early healing stages in the defects treated with BAMs, but disappeared at later stages. The results of this study show that BAMs are a valid alternative to e-PTFE membranes to improve bone regeneration, but indicate that further technical development of the membrane material is necessary.

Absorption↗
PubMedDate not supplied

[Clinical experience with the implantation of collagen-apatite for local bone regeneration].

After a short review of the problematic of bone substitution the possibility of bone regeneration induced by implantation of synthetic Apatite and reaffined heterogenic Collagen is displayed especially with an industrial manufactured mixed preparation called "Collapat". Firstly it is referred especially to the comparing animal experience and histological results by Nizard. According to this research fine dispersed Apatite powder has obviously a remarkable osteoinductive effect, which is inhenced by the Collagen component, used especially as a distribution medium. The tract mainly concerns the clinical experiences in human patients with Collagen-Apatite-implantation since October 1979 with the indication of larger bone defects. In 85 patients with totally 94 Collagen-Apatite-implantations in different age groups no incompatibility was seen. In X-ray controls a rapid reestablishment of natural bone structures was observed. The Collagen-Apatite product seems particularly to be apt for the reconstruction of defect cavities as well as for an additive to autologous bone transplantation which by this method can be limited as well in number as in quantity.

Adolescent↗
PubMed2002

Bone regeneration of localized chronic alveolar defects utilizing cell binding peptide associated with anorganic bovine-derived bone mineral: a clinical and histological study.

BACKGROUND: Osteoinduction to treat osseous defects has been attempted by several means. Some clinical studies have demonstrated that a synthetic cell binding peptide (P-15) with anorganic bovine derived bone matrix (ABM) has the ability to enhance bone regeneration. These studies suggest that more histological data are necessary to better understand this process. We have developed a Class III chronic alveolar defect animal model to investigate space-maintaining regenerative materials. The objective of this study was to clinically and histologically evaluate the use of P-15/ABM with or without a bioabsorbable membrane (M) to regenerate localized chronic alveolar ridge defects in dogs. METHODS: Six adult, male mongrel dogs were used in this study. Bilateral, Class III, alveolar defects were surgically produced following extraction of the mandibular second premolar teeth and local reduction of the alveolar ridge. After an 8-week healing interval, mucoperiosteal flaps were elevated. P-15/ABM with or without bioabsorbable membranes were implanted into contralateral defects in 10 sites. Two sites received no biomaterial (controls). Mucoperiosteal flaps were advanced over the P-15/ABM or P-15/ABM/M constructs and sutured. Pre- and postaugmentation clinical evaluation was done utilizing periodontal probes and calipers. The animals were sacrificed 12 weeks postaugmentation and block specimens processed for histologic evaluation. RESULTS: Clinical results showed no significant statistical augmentation on the control group (0.0 +/- 0.6 mm). In all experimental sites utilizing P-15/ABM or P-15/ABM/M, relevant ridge augmentation was observed (3.6 +/- 2.0 mm and 2.9 +/- 1.9 mm, respectively). Histologically, all experimental sites showed active bone formation with plump osteoblast and osteoid matrix deposition in the treated area. Bone ingrowth filled the area of the defects treated with P-15/ABM/M. Few P-15/ABM particles were seen in the cellular fibrous tissue surrounding the new formed bone trabeculae. CONCLUSIONS: P-15/ABM with or without membranes can produce a significant clinical ridge augmentation. Bone formation was histologically observed in all test areas. The association of a membrane with P-15/ABM seemed to enhance the process of bone formation.

Absorbable Implants↗
PubMed2005

Bone regeneration in the hard palate after cleft palate surgery.

BACKGROUND: The purpose of this study was to observe bony healing in the hard palate after cleft palate repair and to discuss the factors affecting it. METHODS: Fifty-two patients with repaired cleft palate were examined at least 1 year postoperatively by means of computed tomographic scanning. The incidence of bone regeneration automatically after repair was calculated, and the region of bone formation and the quality of bone tissue were measured according to the scanned image. RESULTS: The formation of a bone bridge was found in 37 of 52 patients (71 percent). The length of regenerated bone tissue (in the anteroposterior direction) ranged from 2 to 20 mm, with an average length of 8.3 mm. The male-to-female ratio of the patients who had a bone bridge was 1:1. There was no obvious difference between the two different cleft types. Considering the relationship of age at operation and bone formation, the most popular age at which bone bridging occurred was 4 to 7 years, and the location in the hard palate with the highest percentage of bone formation was the area between the premolar and anterior part of the molar. CONCLUSIONS: Regenerated bone tissue can occur after palatal repair in cleft palate patients. The age at operation could be an important factor affecting regeneration of bone tissue. The authors were not able to find a significant effect of sex or clinical type of cleft palate based on the sample size in this study.

Adolescent↗
PubMed1998

Comparison of bone regeneration in a rabbit skull defect by recombinant human BMP-2 incorporated in biodegradable hydrogel and in solution.

The objective of this study is to compare bone regeneration induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated into a biodegradable gelatin hydrogel with that by rhBMP-2 in aqueous solution. After treating rabbit skull defects of 6 mm diameter with the two rhBMP-2 dosage forms, both of them increased the bone mineral density (BMD) at the skull defects with implantation time to a significantly higher extent than a rhBMP-2-free aqueous solution and a rhBMP-2-free empty gelatin hydrogel (p < 0.05). There was no quantifiable difference in BMD between the two dosage forms of rhBMP-2. Histological examination revealed that the integrity of newly generated bone increased with the rhBMP-2 dose, irrespective of the dosage form. The bone defect was filled with regenerated bone 21 days after treatment.

Absorptiometry, Photon↗
PubMed2006

Biomimetic artificial ECMs stimulate bone regeneration.

We demonstrate that a biomimetic polymer network is capable of affecting bone regeneration in vivo. Starting with a foundation consisting of an environmentally responsive poly(N-isopropylacrylamide-co-acrylic acid) hydrogel, we incorporated matrix metalloproteinase-13 (MMP-13) degradable crosslinkers and peptides containing integrin-binding domains (i.e., Arg-Gly-Asp) to create a biomimetic matrix designed to encourage osteoblast migration and proliferation. We independently tuned matrix stiffness and peptide concentration to generate a response surface model of osteoblast proliferation on different types of matrices. Osteoblast proliferation was significantly influenced by matrix stiffness (i.e., its complex modulus) and peptide concentration. When implanted in a rat femoral ablation model, these matrices induced bone regeneration only when protease degradable crosslinks were used to create the network. For the matrices with MMP-13 degradable crosslinkers, the bone formed had a trabecular-like structure and was distributed throughout the marrow space. Based on the correlated effects of matrix stiffness and ligand concentration, the response surface model will facilitate improvements in the regenerative capacity of these artificial extracellular matrices.

Animals↗
PubMed1998

Bone regeneration and fracture healing. Experience with distraction osteogenesis model.

The relation between physical forces and the processes of bone regeneration and healing remains incompletely understood. Gaps in understanding of these processes stem in part from models that produce inadequate amounts of new bone for study. Bone created through the use of distraction osteogenesis provides an attractive substrate for the study of mechanical forces and their effects on bone formation because this technique produces large volumes of new bone in a controlled fashion. The optimal mechanical environment in which bone formation occurs clinically has not been fully determined. In laboratory studies, however, the mechanical environment can be manipulated, and resultant changes in bone formation can be measured. To investigate how changes in strain environment influence patterns of bone formation, a bilateral New Zealand White rabbit model of bilateral distraction osteogensis was implemented. When a stiffener was applied to the external distractor, computation analyses predicted a sevenfold to eightfold decrease in all strain measures. These reductions in gap strains appeared to induce significant decreases in bone volume fraction and mean trabecular thickness. When osteotomies were created at a 30 degrees angle to the bony axis to generate more shear within the gap tissue, changes in the distribution of gap strains and resultant new bone architecture were observed. Specific correlations between changes in tissue level strains and the pattern of bone regeneration were seen in both experiments. These results provide direct in vivo evidence that pluripotential gap tissues are sensitive to their physical surroundings. Mechanisms responsible for this sensitivity might include vascularity, stem cell supply, and scaffolding architecture. The process of bone formation in distraction osteogenesis appears to be related to bone formation processes associated with more common conditions. The distraction osteogenesis model described suggests a mechanism for bone formation that seems applicable to other more common processes associated with bone formation, including fracture healing and impaired fracture healing.

Adult↗