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In this investigation periodontal destruction was produced by a combination of inflammatory and traumatic factors. After the inflammation was resolved and the trama stopped, a significant amount of alveolar bone regeneration took place. The implications of these findings for the management of advanced periodontal disease are discussed.
Angiogenesis and biomineral substrates play major roles in bone development and regeneration. We hypothesized that macroporous scaffolds of biomineralized 85:15 poly(lactide-co-glycolide), which locally release vascular endothelial growth factor-165 (VEGF), would direct simultaneous regeneration of bone and vascular tissue. The presence of a bone-like biomineral substrate significantly increased regeneration of osteoid matrix (32 +/- 7% of total tissue area; mean +/- SD; p < 0.05) and mineralized tissue (14 +/- 2%; P < 0.05) within a rat cranium critical defect compared with a non-mineralized polymer scaffold (19 +/- 8% osteoid and 10 +/- 2% mineralized tissue). Further, the addition of VEGF to a mineralized substrate significantly increased the generation of mineralized tissue (19 +/- 4%; P < 0.05) compared with mineralized substrate alone. This appeared to be due to a significant increase in vascularization throughout VEGF-releasing scaffolds (52 +/- 9 vessels/mm(2); P < 0.05) compared with mineralized scaffolds without VEGF (34 +/- 4 vessels/mm(2)). Surprisingly, there was no significant difference in total osteoid between the two samples, suggesting that increased vascularization enhances mineralized tissue generation, but not necessarily osteoid formation. These results indicate that induced angiogenesis can enhance tissue regeneration, supporting the concept of therapeutic angiogenesis in tissue-engineering strategies.
A 28-year-old man developed compartment syndrome in the right lower leg after fracture of the tibia and fibula. Despite fasciotomy, many arteries collapsed and union of the tibial and fibula fractures did not occur. Autologous bone marrow mononuclear cell (BMMNC) implantation for therapeutic angiogenesis and subsequent bone regeneration was performed and 4 weeks later, angiography showed a marked increase in collateral vessels surrounding the tibial fracture, and union was completed 6 months later. BMMNC implantation therapy might provide therapeutic angiogenesis and osteogensis in patients with compartment syndrome.
This study compares non-absorbable, ethyl cellulose (EC) membranes and absorbable, chitosan (CH) membranes in a rabbit model. Bone regeneration, evaluated by radiological and pathological parameters, was seen in both groups. In the EC group the process was faster but was followed by a sharp decrease, whereas in the CH group it was slower and continuous.
OBJECTIVE: The aim of this study is to compare the effects of traditional nonsteroidal anti-inflammatory drugs with nonsteroidal anti-inflammatory drugs that are selective cyclooxygenase-2 (COX-2) inhibitors in the process of bone regeneration in a rat model. MATERIALS AND METHODS: Forty-four Wistar strain rats were subjected to osteotomy of the right femur and randomly divided into 3 groups according to the drug to be given (diclofenac, rofecoxib, or placebo). Each group was divided into 2 subgroups according to the time to euthanasia after the surgery. The animals of Subgroup 1 were submitted to euthanasia 2 weeks after surgery, and those of Subgroup 2, underwent euthanasia 4 weeks after surgery. Radiographic examinations and bone callus histomorphometry were analyzed. RESULTS: No intergroup statistical difference was found in the bone callus area or in bone formation area 2 and 4 weeks after surgery. Intra-group analysis concerning the bone neoformation area inside the callus showed a significant difference within the diclofenac group, which presented less tissue. CONCLUSIONS: Fracture consolidation in Wistar rats occurs within less than 2 weeks, and the use of nonsteroidal anti-inflammatory drugs does not significantly influence this process.
This study investigated the bone-regenerative potential of a demineralized bone and acellular matrix (DBM/AM) composite (AlloCraft DBM) in comparison with autologous bone using an in vivo model. Critical-sized calvarial defects (5 mm) were created in athymic rats. The defects were grafted with either the DBM/AM composite or the acellular human dermal matrix (AM), and compared with the defects filled with autologous bone (positive control) and the empty defect (negative control). Histological and radiographic assessments were carried out at 4 and 8 weeks after surgery to determine the biological healing, the amount and type of new bone formation and the percentage of new bone filled in the critical defects. At 4 weeks, DBM/AM composite group had the highest percentage of the defect filled with new bone (84%), which was significantly greater than autologous bone (62%), AM (41%), and untreated control (32%) groups. At 8 weeks, the DBM/AM continued to have the highest percentage of the defect filled with new bone (91%). The autologous bone group increased the percentage of bone fill to 83%. The defects either filled with AM or left untreated still had less of the defect filled with new bone, 57% and 33%, respectively. The total healing of defects grafted with DBM/AM was comparable with autologous bone group at 8 weeks. The results demonstrated that the DBM/AM composite promoted new bone formation more rapidly than autologous bone at calvarial defect in athymic rats. The study supports that DBM/AM is a potential substitute of autologous bone for bone repair.
The purpose of the study was to compare the efficacy of a non-resorbable polytetrafluoroethylene (e-PTFE) membrane (Gore-Tex) versus a resorbable polyglactin membrane (Vicryl) and a newly designed collagenic membrane for enhancing bone regeneration on rat skull defects. The study was conducted on 30 adult Wistar rats. On each animal, two symmetrical, 6 mm wide, full-thickness, skull defects were created in the parietal regions. The right defect was chosen as the experimental site and the left one was left empty as a control. Each experimental site was covered by an inner and outer membrane. The 30 rats were divided into three groups: In group 1 (n=10), a non-resorbable polytetrafluoroethylene (e-PTFE) membrane was used. In group 2 (n= 10), a resorbable polyglactin 910 membrane was used. In group 3 (n= 10), a collagen membrane processed from avian eggshell was used. In each group, the animals were euthanized at 60 days. The harvested specimens were processed for contact radiography and standard histological examination. The results were assessed by a Fisher's exact test. In group 1, partial bone healing was observed in seven out of 10 animals and complete in three out of 10 animals (P<0.001). In group 2, no or minimal bone healing was observed in seven out of 10 animals and partial bone healing was observed in three out of 10 animals. In group 3, no or minimal bone healing was observed in nine out of 10 cases and partial bone healing in only one animal. In conclusion, only the non-resorbable e-PTFE membrane group exhibited a favourable result in this study. This study suggests that the structure of the membrane is at least as important as its composition.
There is strong evidence that nonsteroidal antiinflammatory drugs (NSAID) may exert a significant antiproliferative effect. This study evaluated the influence of NSAID on specific parameters of fibroblastic cells, in vitro, over two-guided bone regeneration (GBR) barrier materials. Fibroblast cells were cultured on bioabsorbable membrane made of collagen (Bio-Gide(R)- BG) and the most common nonresorbable membrane which is made of expanded polytetrafluoroethylene (ePTFE, Gore-Tex(R)- GT). Naproxen sodium (10 mM) was used as an analgesic drug. The fibroblast cells were cultured in vitro for 24 h and examined by scanning electron microscopy (SEM). Cells were cultured in the presence of (3)H-thymidine to study cell proliferation. And also cell numbers and viabilities were measured. The difference between the means for each group were analyzed for statistical significance by Kruskal-Wallis one-way ANOVA followed by post hoc comparisons using the Dunn statistical method. Of all the six groups, the control group stimulated DNA synthesis more than the others. With respect to cell numbers, there was statistically significant difference between the control group and naproxen planted BG membrane group. The interpretation of our SEM images is that these two barriers and naproxen seem to have had the least effect on cellular morphology. These data suggest naproxen have an inhibitory effect on stimulation of DNA synthesis, cell numbers and viabilities. And also lacking adherence of cells to the membranes may be due to the physical properties of the materials.
This study evaluates a prototype bioabsorbable physical barrier material for guided bone regeneration. Nonspacemaking dehiscence-type defects were surgically created in the right and left mandibles of six adult dogs. Each animal received six root-form threaded titanium implants. The osseous defects were randomized to receive treatment by either the prototype bioabsorbable barrier composed of a copolymer of lactide and glycolide, an expanded polytetrafluoroethylene nonresorbable barrier, or no barrier (control), Clinical and histologic results after 3.5 months of wound healing indicated that exposed threads were covered when treated with the expanded polytetrafluoroethylene barrier. Minimal thread coverage was evident with the bioabsorbable barrier and the control.
In the development of 3-dimensional cell-polymer matrices for tissue engineering, the ability of osteoblast cells to maintain their phenotypic properties and form a mineralized matrix while seeded on the polymer surface is very important. Osteoblast cell differentiation and bone formation using rat calvaria cells were studied on the surface of a porous poly(lactide/glycolide)/hydroxyapatite (PLAGA/HA) 3-dimensional polymer matrix. Cell adhesion and proliferation were determined at 24 hr, 3, 7, 14, and 21 days. Cell attachment and proliferation were observed to increase throughout the first two weeks of the study, followed by a period of gradual plateauing of cell numbers. Environmental scanning electron microscopy demonstrated that cells grown on the surface of the 3-dimensional porous PLAGA/HA matrix retained their characteristic morphology and grew in a multi-layer fashion. Light microscopy observations of experiment cultures revealed active osteoblastic cells forming a characteristic mineralized matrix in the presence of beta-glycerophosphate as a phosphate donor. Mineralization did not occur in media either not supplemented with beta-glycerophosphate or when the matrix without cells was incubated with the reagents, indicating that the mineralization was due to the cells and not the HA in the matrix. These results suggest that the 3-dimensional PLAGA/HA matrix could provide a matrix for bone cell differentiation and mineralization in vitro and, therefore, may be a candidate as a synthetic implant for bone regeneration.
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A gelatin sponge was formed by foaming and heat treating a gelatin solution, followed by coating the solid with poly(D,L-lactic-co-glycolic acid) to reinforce the gelatin framework. This sponge was tested for its suitability as a biodegradable porous, recombinant human bone morphogenetic protein (rhBMP)-2 carrier. Incorporation of rhBMP-2 into the sponge was closely related to its bulk density of gelatin sponge. The calcium content in the sponges, as assessed by an ectopic bone formation assay in rats, increased with the increasing sponge bulk density. Histologic and peripheral quantitative computed tomography analysis of implants in this ectopic assay system revealed cell growth throughout the carrier in 4 weeks after implantation regardless gelatin bulk density. The carrier containing rhBMP-2 maintained its three-dimensional structure after implantation; the carrier resisted collapse caused by soft tissue pressure during rapid bone formation as assessed by soft X-ray photographs. These results indicate that this newly developed sponge has excellent carrier characteristics to introduce rhBMP-2 into areas needed for bone regeneration.
In an experimental study using the Göttingen minipig, Gore-Tex, Gore Resolut, and Vicryl barrier membranes were tested for their efficacy in guided bone regeneration. The results were compared to those of autologous periosteum. The strongest reossification was seen in the bone defects covered with Gore-Tex; however, time-dependent disintegration phenomena, which had already been observed in preliminary examinations, were clearly established. After investigations of cell cultures to which human macrophages were added, the latter findings can be interpreted as the result of a physicochemical process, since a direct attack by the macrophages was not seen in vitro. Of the membranes used, the absorbable ones tended to collapse, depending on the size of the defect that was used, and they did not enhance reossification as much as did the permanent membranes. The periosteum-covered defects showed a satisfactory degree of regeneration, and no differences were observed between freely transplanted and pedunculate periosteum.
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In this study, new type of guided bone regeneration (GBR) membranes were fabricated by polycaprolactone (PCL)/CaCO3 composite nano-fibers with two different PCL to calcium carbonate (CaCO3) ratios (PCL:CaCO3=75:25 wt% and 25:75 wt%). The composite nano-fibers were successfully fabricated by electrospinning method and CaCO3 nano-particles on the surface of nano-fibers were confirmed by energy disperse X-ray (EDX) analysis. In order to achieve mechanical stability of GBR membranes, composite nano-fibers were spun on PCL nano-fibrous membranes which has high tensile strength, i.e., the membranes consist of two layers of functional layer (PCL/CaCO3) and mechanical support layer (PCL). Two different GBR membranes were prepared, i.e., GBR membrane (A)=PCL:CaCO3=75:25 wt%+PCL, GBR membrane (B)=PCL:CaCO3=25:75 wt%+PCL. Osteoblast attachment and proliferation of GBR membrane (A) and (B) were discussed by MTS assay and scanning electron microscope (SEM) observation. As a result, absorbance intensity of GBR membrane (A) and tissue culture polystyrene (TCPS) increased during 5 days seeding time. In contrast, although absorbance intensity of GBR membrane (B) also increased, its value was lower than membrane (A). SEM observation showed that no significant difference in osteoblast attachment manner was seen on GBR membrane (A) and (B). Because of good cell attachment manner, there is a potential to utilize PCL/CaCO3 composite nano-fibers to GBR membranes.
Regeneration of periodontal and alveolar ridge defects utilizing membranes is a well-established procedure in reconstructive surgery. Biomaterial characteristics and membrane design employed in guided tissue regeneration (GTR) techniques play an important role in good results. The purpose of this histologic experimental study in rats was to compare the use of two physical barriers in the osteopromotion by using GTR principles in bone defects created in tibias. Fifteen animals divided into 3 groups were used: group I (non-porous polytetrafluoroethylene (PTFE) barrier), group II (coral hydroxyapatite (HA) blocks), and group III (defects that received no physical barrier). Histological examination showed varied amounts of newly formed bone beneath both types of barriers. The non-porous PTFE barrier showed better results than the HA group. The results of this study suggest that bone regeneration can be successfully enhanced by a submerged membrane technique.
The osteogenic behavior of three-dimensional collagenic and anionic matrices (M3DGA) implanted in critical bone defects of 8 mm diameter was morphologically assessed. The defects were performed in the calvaria of 48 adult male (Wistar) rats, and observed at days 15, 30, and 60. The animals were distributed in four groups of equal number: GA1 (M3DGA with 60 min of cross-linking in glutaraldehyde [GA]); GA2 (M3DGA with 30 min of cross-linking in GA); GA3 (M3DGA with 15 min of cross-linking in GA); and G4 (control group, without any implanted biomaterial). The M3DGAs were biocompatible, with mild and regressive chronic granulomatous inflammation, associated with the degradation of their fibers. Furthermore, tissue neovascularization and neomineralization was noted, with statistically significant differences in these amounts among the groups (GA1, GA2, and GA3) and G4. In G4 neoformation was limited to the edges of the defect as well as interstitial fibrosis. Under the experimental conditions and for the parameters analyzed, the M3DGAs had osteogenic behavior, which was more evident in M3DGA 15 min.
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