*Absorbable Implants ; Biocompatible Materials/*pharmacology ; Bone Regeneration/*drug effects ; Bone Regeneration/physiology ; Bone Substitutes/*pharmacology ; Calcium Phosphates/*pharmacology ; Structure-Activity Relationship

BACKGROUNDCurrently, the most commonly used treatment methods for repairing alveolar furcation defects are periodontal guided tissue regeneration (GTR) and bone grafting. The objective of this study was to investigate the effects of simvastatin/methylcellulose gel on bone regeneration in alveolar defects in miniature pigs.

METHODSAlveolar defects were produced in 32 teeth (the third and fourth premolars) of 4 miniature pigs. The 32 experimental teeth were divided into 5 groups comprising control (C) and treatment (T) teeth: (1) empty defects without gel (group C0, n = 4); (2) defects injected with methylcellulose gel (group C1, n = 4); (3) defects injected with 0.5 mg/50 µl simvastatin/methylcellulose gel (group T1, n = 8); (4) defects injected with 1.5 mg/50 µl simvastatin/methylcellulose gel (group T2, n = 8); and (5) defects injected with 2.2 mg/50 µl simvastatin/methylcellulose gel (group T3, n = 8). Every week after surgery, the furcation sites were injected once with gel. At the eighth week after surgery, the 4 pigs were sacrificed and underwent macroscopic observation, descriptive histologic examination, and regenerate bone quantitative histologic examination.

RESULTSAt 8 weeks after surgery, the defect sites in the treatment groups were completely filled in with new bone and fibrous tissue. There was little new bone in the C0 and C1 groups, and only a small number of osteoblasts and proliferative vessels could be seen on microscopic examination.

CONCLUSIONSMiniature pigs are an ideal experimental animal for establishing a model of alveolar defects using a surgical method. Local application of simvastatin/methylcellulose gel can stimulate the regeneration of alveolar bone in furcation defect sites, because it promotes the proliferation of osteoblasts. The best dose of simvastatin gel to stimulate bone regeneration is 0.5 mg.

Alveolar Bone Loss ; drug therapy ; surgery ; Animals ; Bone Regeneration ; drug effects ; Guided Tissue Regeneration, Periodontal ; methods ; Simvastatin ; therapeutic use ; Swine ; Swine, Miniature

BACKGROUNDThe treatment for long bone defects has been a hot topic in the field of regenerative medicine. This study aimed to evaluate the therapeutic effects of calcium sulfate (CS) combined with platelet-rich plasma (PRP) on long bone defect restoration.

METHODSA radial bone defect model was constructed through an osteotomy using New Zealand rabbits. The rabbits were randomly divided into four groups (n = 10 in each group): a CS combined with PRP (CS-PRP) group, a CS group, a PRP group, and a positive (recombinant human bone morphogenetic protein-2) control group. PRP was prepared from autologous blood using a two-step centrifugation process. CS-PRP was obtained by mixing hemihydrate CS with PRP. Radiographs and histologic micrographs were generated. The percentage of bone regenerated bone area in each rabbit was calculated at 10 weeks. One-way analysis of variance was performed in this study.

RESULTSThe radiographs and histologic micrographs showed bone restoration in the CS-PRP and positive control groups, while nonunion was observed in the CS and PRP groups. The percentages of bone regenerated bone area in the CS-PRP (84.60 ± 2.87%) and positive control (52.21 ± 4.53%) groups were significantly greater than those in the CS group (12.34 ± 2.17%) and PRP group (16.52 ± 4.22%) (P < 0.001). In addition, the bone strength of CS-PRP group (43.10 ± 4.10%) was significantly greater than that of the CS group (20.10 ± 3.70%) or PRP group (25.10 ± 2.10%) (P < 0.001).

CONCLUSIONCS-PRP functions as an effective treatment for long bone defects through stimulating bone regeneration and enhancing new bone strength.

Animals ; Bone Regeneration ; drug effects ; Calcium Sulfate ; pharmacology ; Male ; Platelet-Rich Plasma ; Rabbits

OBJECTIVETo investigate the Effect of recombinant adenovirus vectors containing human Bone morphogenetic proteins-2 (Ad-hBMP-2) on the for mandibular distraction osteogenesis (DO) in rabbits.

METHODSTwenty-four New Zealand white rabbits were randomly divided into experimental group, and control group and underwent mandibular distraction osteogenesis. After 5 days latency, the distracters were activated at a speed of 0.5 mm every 12 hours for 7 days, then on the first day in the consolidation period, the distraction gaps of experimental group were injected with 0.2 ml Ad-hBMP2 10(12) pfu/L, while the animals of control group were injected with 0.2 ml Ad-EGFP 10(12) pfu/L. At the 7 th and 28 th day of consolidation period, specimens were obtained, X-ray and histomorphology were performed. The bone density and the quantity of new bone formation in the distraction gaps were observed and compared between the two groups at different consolidation period.

RESULTSAd-hBMP-2 treated specimens demonstrated an increased amount of new bone formation

CONCLUSIONSAdenovirally-mediated delivery of BMP-2 can locally increase bone deposition during DO, which may potentially shorten the consolidation period.

Animals ; Bone Morphogenetic Protein 2 ; pharmacology ; Bone Regeneration ; drug effects ; physiology ; Humans ; Male ; Mandible ; drug effects ; surgery ; Osteogenesis ; drug effects ; physiology ; Osteogenesis, Distraction ; Rabbits ; Recombinant Proteins ; pharmacology

Clinically, there has been so far no effective way to repair the bone-missing of large extent due to gash, infection and removal of tumor. The solution of this problem can be assisted by the addition of bioactive substances to substrate materials, because the growth of peripheral tissue and the fiber tissue growing the materials can be induced to the direction of bone-tissue by these biomaterials with bioactive peptides. The peptide Arg-Gly-Asp is the point between the integrin which comes from membrane and the ligand. In certain cases, the artificially synthesized RGD can be competitively combined with the integrin on cell surface, and outer-cell information is transmitted into cells, which will cause a series of physiological changes in cells. Presently, it is reported that the RGD has the ability to induce the growth of osteoblasts, restrain the adhesion between osteoclasts and substrates. This paper reviews and introduces the progress made with the work of RGD-inducing bone regeneration.
Biocompatible Materials ; Bone Regeneration ; drug effects ; physiology ; Cell Adhesion ; drug effects ; Oligopeptides ; administration & dosage ; chemistry ; pharmacology ; Osteoblasts ; drug effects ; physiology ; Osteoclasts ; drug effects ; physiology ; Tissue Engineering ; methods

These studies sought to evaluate the promoting effect of the exterior bFGF on membrane guided bone regeneration (MGBR). Animal models of MGBR covered with PDLLA membrane tube in bilateral radii were established in 40 New Zealand white rabbits. The membrane tubes on the left side were filled with bFGF 40 microg/100 microl and those on the contralateral side were filled with 100 microl 0.9% NaCl solution as control. The specimens were collected at 2, 4, 8, 12 weeks postoperatively. General observation, X-ray, histological grading and HE staining,and biomechanical examination were applied to studies on the repair of the models of MGBR in the two groups. Two weeks after operation, a sealed room was formed between the two bone fragments where the soft tissues covered the membrane tube. Twelve weeks after operation, PDLLA membrane became fragile and its tube shape was being maintained. Histologically, in the bFGF group numerous newly formed bone trabeculae were seen at 2 weeks after operation the radial defects had healed and the bone reconstruction and remodling had begun by the 12th week. The histological image analysis showed that the values of mean diameter and the area of new bone trabeculae in the bFGF group were higher than those in the control group (P<0.05) at 2 weeks and 4 weeks; however, there were no significant differences in these aspects between the two groups (P>0.05) at 8 and 12 weeks. The strength of the newly formed bone in the bFGF group was higher than that in the control group at 12 weeks postoperatively (P<0.05). Therefore, the authors concluded that bFGF could promote the new bone formation and biomechanical strength in the MGBR model.
Animals ; Biomechanical Phenomena ; Bone Regeneration ; drug effects ; Female ; Fibroblast Growth Factor 2 ; pharmacology ; Guided Tissue Regeneration ; Lactic Acid ; Male ; Osteogenesis ; drug effects ; Polyesters ; Polymers ; Rabbits ; Radius ; injuries ; pathology

OBJECTIVETo explore the effect of recombinant human parathyroid hormone 1-34 [rhPTH(1-34)] on bone regeneration rabbit mandible during distraction osteogenesis (DO).

METHODS40 Japanese white rabbit (weight 2.0-2.5 kg) were randomly divided into control group and groups. The experimental groups were divided inito 12.5, 25 and 50 µg/kg group according to the dosage of rhPTH (1-34) in each group. Each group involved 10 rabbits, and unilateral DO models were established at the right mandible of the rabbits. From the first day of distraction to the day of execution, the rabbits in the experimental groups were injected subcutaneously rhPTH (1-34) of the corresponding dose respectively, and the rabbits in the control group were injected subcutaneously 2% heat inactivated rabbit serum 1 ml respectively.. Five rabbits in each group were executed respectively at 1 week and 3 weeks after completion of distraction, and the specimens of DO were harvested. The gross observation, X-ray examination, and histological study were performed.

RESULTSGross appearance: At the first week of consolidation, the dense and opaque white tissue was seen in the distraction gap of the 50 µg/kg group, and the white translucent tissue was seen in the distraction gaps of the rest groups. At the third week of consolidation, the greyish white tissue was seen in the distraction gap of the control group, while the cartilage-like tissue was seen in the buccal side of the distraction gap of the 12.5 µg/kg group, the color of new-formed tissues was close to that of normal bone tissue in the lingual side. The buccal tissue at the edge of the distraction gap of the 25 µg/kg group fitted together with the primary bone tissue in its two sides. It was difficult to distinguish the boundaries between the distraction gap and the bone tissues in its two sides in the 50 µg/kg group. X-ray findings: At the first week of consolidation, a sparse opaque image was seen in the distraction gap of the 50 µg/kg group, and a low-density image was seen in the distraction gap of the rest groups. At the third week of consolidation, a sparse bone image was seen in the control group, and the edge of the bone was not continuous. With the increase of the dose in the experimental groups, the image of the distraction gap became more and more opaque, and the image of the distraction gap in the 50 µg/kg group was close to that of the normal bone tissue. HISTOLOGICAL FINDINGS: At the first week of consolidation, few osteoblasts were present at the edge of the distraction gap of the control group. A large number of bone cells and bone trabecular were present in the distraction gap of the 12.5 µg/kg group, the network of the bone trabecula was present in the 25 µg/kg group, and a few new bones were found in the 50 µg/kg group. At the third week of consolidation, the network of the trabecular bone was present in the distraction gap of the control group, while the network of the bone trabecula was present in the 12.5 µg/kg group, a lot of bone-like tissues in the 25 µg/kg group, and near-mature bone in the 50 µg/kg group.

CONCLUSIONSrhPTH(1-34) can promote the formation of new bone in the distracted gap during mandibular DO in rabbits.

Animals ; Bone Density ; Bone Regeneration ; drug effects ; physiology ; Humans ; Mandible ; drug effects ; surgery ; Osteogenesis, Distraction ; methods ; Parathyroid Hormone ; pharmacology ; Rabbits ; Random Allocation ; Recombinant Proteins ; pharmacology

OBJECTIVETo study the effect of Eupolyphaga Sinensis Walker on mandibular distraction osteogenesis (DO) in rabbits.

METHODS30 Japanese white rabbits (weight 2.0-2.5 kg, about 3 months old) were divided randomly into control group (n = 15) and experimental group (n = 15). Unilateral mandibular DO models were established at the right mandible of the rabbits. Distraction was started 7 days after the surgery at the speed of 0.4 mm per time twice a day and continued for 10 days. From the first day of distraction to the day of execution, the experimental group rabbits were fed with 2 g of ESW power once a day at 9 o' clock. Three animals in each group were executed respectively at 24 hours, 72 hours, 1 week, 4 weeks and 7 weeks after completion of distraction, and the specimens of DO were harvested. The general observation, X-ray examination, histological study and immunohistochemical staining of bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) were performed. The images of immunohistochemical staining of BMPs and VEGF were analyzed by the image analysis software, and the results were analyzed by statistical software SPSS 17.0.

RESULTSThe rate of the new bone formation in the experimental group was faster than that in the control group, and the immunohistochemical staining of BMPs and VEGF in the experimental group was higher than that in the control group.

CONCLUSIONSESW can promote the formation of the new bone in the distracted gap during mandibular DO in rabbits, which may be due to its enhancement effect on the expression of BMPs and VEGF.

Animals ; Bone Morphogenetic Proteins ; metabolism ; Bone Regeneration ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Osteogenesis ; drug effects ; Osteogenesis, Distraction ; methods ; Rabbits ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo evaluate the effect of parathyroid hormone (1-34) [PTH(1-34)] and coralline hydroxyapatite (CHA) on bone regeneration of peri- implant bone defects.

METHODSTwo implant sites were prepared on both sides of tibia in 8 mongrel dogs. The bone defect was created along one bone wall of each implant site. Implants were implanted into the implant sites, then CHA was grafted into the bone defects. After surgery, the animals were randomly divided into two groups. PTH (1-34) (40 µg/kg) was used for subcutaneous injection to the experimental group for three consecutive days, meanwhile the same amount of saline was given to the control group. Half of the animals of each group were sacrificed after 4 weeks and 8 weeks respectively. Specimens were subjected to implant pull- out strength tests, X-ray picture and histological observation.

RESULTSThe bone density of bone defects in the experimental group were higher than that in the control group. No low-density images was observed between the implants and bone at 4 weeks and 8 weeks. The maximum pull-out force value of the experimental group (199.8 N, 411.5 N) was higher at 4 weeks and 8 weeks than that of the control group (100.1 N, 184.5 N) (P < 0.05). The pull-out force value of the experimental group at 4 weeks and the pull-out force value of the control group at 8 weeks were similar. The new bone trabecular around CHA of experimental group was thicker at 4 weeks. Implant surface contacted to the new bone directly without fiber. CHA granules of the experimental group at 8 weeks were fewer than that of the control group. New bone tissue of the experimental group was denser. The contact area between implant surface and new bone was wider in experimental group than in the control group.

CONCLUSIONSPTH (1-34) and CHA can promote bone regeneration of peri-implant bone defects, shorten the implants and bone healing cycle and improve the implants osseointegration.

Animals ; Bone Density ; Bone Regeneration ; drug effects ; physiology ; Ceramics ; pharmacology ; Dental Implants ; Dogs ; Hydroxyapatites ; pharmacology ; Injections, Subcutaneous ; Osseointegration ; drug effects ; physiology ; Parathyroid Hormone ; pharmacology ; Random Allocation

Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.
Animals ; Bone Regeneration/*drug effects ; Bone Substitutes/*therapeutic use ; Bone and Bones/*drug effects/pathology/physiopathology ; Ceramics/therapeutic use ; Diffusion of Innovation ; Fracture Healing/drug effects ; Humans ; Hydrogels ; Polymers/therapeutic use ; Regenerative Medicine/*trends ; Tissue Engineering/*trends ; Treatment Outcome