Effects of VEGF on Prefabricated Vascularized Bone Allografts in Rats

Author(s):  
Sachiko Tobiume ◽  
Yoshio Kaji ◽  
Osamu Nakamura ◽  
Konosuke Yamaguchi ◽  
Kunihiko Oka ◽  
...  

Abstract Background Massive bone defects after wide resection of malignant bone tumors or a serious injury require treatment using vascularized bone grafts. Although cadaveric bone allografts combined with vascularized bone autografts are currently thought to be ideal in terms of size and durability, this treatment requires the scarification of healthy bone tissue. In a previous study, we attempted to improve this situation by prefabricating a vascularized bone allograft in recipient rats. In this study, we added vascular endothelial growth factor (VEGF)-containing hydroxyapatite/collagen composite (HAp/Col) to a prefabricated vascularized bone allograft to stimulate angiogenesis, which is known to be important for bone formation. Materials and Methods Sprague Dawley rats (n = 50) were used as donors and Wistar rats (n = 50) as recipients. All rats were 9 weeks old. The recipient rats were divided into five groups according to the use of vascular bundles, HAp/Col, and an additive substance (VEGF). The bone allografts collected from the donors were transplanted into the thigh region of the recipients, and a saphenous vein and 10 μg HAp/Col with VEGF were inserted into the bone allografts through the slit. After 4 weeks, the transplanted bone allografts were harvested, and histologic and genetic evaluations were performed in relation to bone formation and resorption. Results The results showed that, compared with the control group, the implantation of the vascular bundles and VEGF-containing HAp/Col significantly stimulated angiogenesis and bone formation in the rats with the bone allografts. However, histological and genetic evaluations of bone resorption revealed that resorption was not observed in any group. Conclusion These results suggest that VEGF-containing HAp/Col effectively stimulates angiogenesis and bone formation, but not bone resorption, in prefabricated vascularized bone allografts. This method could therefore become a useful tool for treating large bone defects.

2017 ◽  
Vol 33 (05) ◽  
pp. 367-376 ◽  
Author(s):  
Konosuke Yamaguchi ◽  
Osamu Nakamura ◽  
Sachiko Tobiume ◽  
Tetsuji Yamamoto ◽  
Yoshio Kaji

Background Basic fibroblast growth factor (bFGF) is known to stimulate bone formation and angiogenesis. Hydroxyapatite/collagen composite (HAp/Col) is also known to have very strong bone conductive activity. In this study, prefabrication of vascularized allogenic bone (allo-bone) graft was attempted in recipients by implanting vascular bundles from recipients into the transplanted allo-bone graft. Furthermore, the effect of bFGF-containing HAp/Col on the prefabricated vascularized allo-bone graft was investigated. Methods In this study, 32 Sprague-Dawley rats were used as donors, and bone grafts were collected from their femora. Thirty-two Wistar rats (recipients) were divided into four groups, and the allo-bone grafts were transplanted into the thigh region. In the experimental groups, one or both of the flow-through saphenous vascular bundles and 100-μg bFGF-containing HAp/Col were implanted into the medullary cavity of the allo-bone grafts. In the control group, neither was implanted. These rats were sacrificed at 4 weeks after transplantation, and bone formation, angiogenesis, and bone resorption in the transplanted allo-bone grafts were evaluated histologically and genetically. Results Bone formation and angiogenesis in the transplanted allo-bone graft were effectively stimulated by implanting vascular bundles or bFGF-containing HAp/Col on both histological and genetic evaluations compared with the control group. The most significant stimulation was observed in the group in which both were implanted. Bone resorption was not stimulated in any group. Conclusion By implanting a flow-through vascular bundle and bFGF-containing HAp/Col, an ideal vascularized allo-bone graft that had high bone formative and angiogenetic activities and did not stimulate bone resorptive activity was prefabricated.


2021 ◽  
Vol 9 (A) ◽  
pp. 1-6
Author(s):  
Utami Mulyaningrum ◽  
Anif Firrizki Muttaqina ◽  
Adhitama Noor Idninda ◽  
Ndilalah Pulungan ◽  
Irena Agustiningtyas ◽  
...  

AIM: The aim of this study is to provide a comparative histopathological evaluation of the regeneration of bone defect filling with perforated antibiotic-impregnated bone allograft. MATERIALS AND METHODS: Seventy-two healthy rabbits (24 rabbits in each group) were used for this study. Bone defects (3-mm diameter, 10-mm depth) were created in the femur. Human femoral head prepared according to the Marburg bone bank system was used as a bone allograft. The control group did not receive any filling. The experimental groups were as follows: Group 1 – the defects were filled with bone allografts and Group 2 – Perforated gentamycin-impregnated bone allografts. The animals were euthanized after 14, 30, and 60 days. Evaluations consisted of histology at 14-, 30-, and 60-days post-surgery. RESULTS: A mature bone formation in the group without a bone allograft occurred after 30 days and the group with an allograft after 14 days. In the groups with an allograft, a bone marrow defect was noted as complete closure after 30 days. Histomorphometric analysis showed that in the group with an antibiotic-impregnated bone, allograft leads to increased resorption of the allograft in the intramedullary space compared to group without antibiotic. CONCLUSION: We believe that a perforated allograft as a result of clinical trials may be obvious and economically affordable in the treatment of bone defects. The use of gentamycin-impregnated bone allografts may be of value in the prevention and treatment of bone infections.


2021 ◽  
Vol 9 (A) ◽  
pp. 12-18
Author(s):  
B. E. Tuleubaev ◽  
E. K. Kamyshansky ◽  
Saginova Dina Saginova ◽  
E. R. Tashmetov ◽  
A. A. Koshanova

AIM: The aim of this study is to provide a comparative histopathological evaluation of the regeneration of bone defect filling with perforated antibiotic-impregnated bone allograft. MATERIALS AND METHODS: Seventy-two healthy rabbits (24 rabbits in each group) were used for this study. Bone defects (3-mm diameter, 10-mm depth) were created in the femur. Human femoral head prepared according to the Marburg bone bank system was used as a bone allograft. The control group did not receive any filling. The experimental groups were as follows: Group 1 – the defects were filled with bone allografts and Group 2 – Perforated gentamycin-impregnated bone allografts. The animals were euthanized after 14, 30, and 60 days. Evaluations consisted of histology at 14-, 30-, and 60-days post-surgery. RESULTS: A mature bone formation in the group without a bone allograft occurred after 30 days and the group with an allograft after 14 days. In the groups with an allograft, a bone marrow defect was noted as complete closure after 30 days. Histomorphometric analysis showed that in the group with an antibiotic-impregnated bone, allograft leads to increased resorption of the allograft in the intramedullary space compared to group without antibiotic. CONCLUSION: We believe that a perforated allograft as a result of clinical trials may be obvious and economically affordable in the treatment of bone defects. The use of gentamycin-impregnated bone allografts may be of value in the prevention and treatment of bone infections.


Lupus ◽  
2021 ◽  
Vol 30 (6) ◽  
pp. 965-971
Author(s):  
Wang Tianle ◽  
Zhang Yingying ◽  
Hong Baojian ◽  
Gu Juanfang ◽  
Wang Hongzhi ◽  
...  

Objectives SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. Methods A total of 865 female subjects were recruited from Zhejiang Provincial People’s Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of β - I collagen (β-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. Results In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and β-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of β-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, β-CTX reached a high value in summer and PINP reached a low value in winter. Conclusion The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.


2012 ◽  
Vol 31 (2) ◽  
pp. 121-125
Author(s):  
Snežana Krejović ◽  
Aleksandar Živanović ◽  
Sandra Živanović ◽  
Rade Marković

Effects of Tibolone on Markers of Bone Metabolic Activity in Postmenopausal WomenOsteoporosis, a systemic disease of the bones, is a serious health and socio-economic problem because of its consequences, i.e. broken bones. It is believed that 10% of the world's population suffers from osteoporosis and it affects mostly postmenopausal women (postmenopausal osteoporosis). Tibolone is a synthetic steroid that has estrogenic, androgenic, and progestagenic properties. It has been used primarily for the prevention of postmenopausal osteoporosis and treatment of climacteric symptoms. The research included a group of 40 postmenopausal women with osteopenia treated with tibolone. The control group included 40 postmenopausal women who were not taking any medication. Control group patients were older (54.5 ± 9.84) than the patients treated with tibolone (51.6 ± 6.22). Bone metabolic activity was evaluated using osteocalcin (N-MID osteocalcin) for bone formation and CTX I for bone resorption. Blood samples were taken before therapy was introduced and 3 months after its introduction. The average value of osteocalcin after three months of tibolone therapy was 26.32 ± 3.312 ng/mL compared to the average osteocalcin value prior to therapy of 29.6 ± 3.343 ng/mL. The average value of CTX I three months after tibolone therapy of 0.2870 ± 0.0783 ng/mL was lower compared to the average CTX I value before the therapy of 0.4539 ± 0.1144 ng/mL. Our results show the efficacy of tibolone in preventing bone loss, which was highly statistically significant. They also reveal its suppressive effects on bone formation and resorption, but these effects are statistically less significant. Tibolone significantly reduces the level of bone resorption in postmenopausal women with osteopenia. Its effects on bone formation are less expressed. The parameters of bone metabolic activity are a very useful diagnostic means in the evaluation of tibolone effects on bone metabolic activity and in the prognosis of bone mass loss.


2019 ◽  
Vol 207 (3-4) ◽  
pp. 138-148 ◽  
Author(s):  
Rubia Teodoro Stuepp ◽  
Priscilla Barros Delben ◽  
Filipe Modolo ◽  
Andrea Gonçalves Trentin ◽  
Ricardo Castilho Garcez ◽  
...  

This study aimed to evaluate the use of human dental pulp stem cells (hDPSCs) in non-critical-sized mandibular bone defects in rats. hDPSCs from permanent teeth were isolated and engrafted in mandibular bone defects in rats for 7, 14, and 28 days; bone defects without cells formed the control group. Samples were evaluated by scanning electron microscopy (SEM), light microscopy (hematoxylin and eosin staining), and the regeneration area was measured by the Image J program. Before surgery procedures, the human dental pulp cells were characterized as dental pulp stem cells: fusiform morphology, plastic-adherent; expression of CD105, CD73, and CD90; lack of expression of CD45 and CD34, and differentiated into osteoblasts, adipocytes, and chondroblasts. The results indicated that within 7 days the control group presented a pronounced bone formation when compared with the treated group (p < 0.05). After 14 days, the treated group showed an increase in bone formation, but with no statistical difference among the groups (p > 0.05). In the final evaluated period there was no difference between the control group and the treated group (p > 0.05). There was a significant difference between 7 and 14 days (p < 0.05) and between 7 and 28 days (p < 0.05) in the treated group. In conclusion, there is no evidence that the use of hDPSCs in the conditions of this study could improve bone formation in non-critical-sized mandibular bone defects.


1999 ◽  
Vol 84 (1) ◽  
pp. 179-183
Author(s):  
K. M. Prestwood ◽  
D. L. Thompson ◽  
A. M. Kenny ◽  
M. J. Seibel ◽  
C. C. Pilbeam ◽  
...  

Previous studies have shown that treatment with estrogen or calcium decreases bone turnover in older women. The mechanisms by which estrogen and calcium exert their effects are probably different. We therefore examined the possibility of an additive or synergistic effect of combined treatment with calcium and low dose estrogen on bone turnover in older women, using biochemical markers. Thirty-one healthy women over 70 yr of age were randomized to 12 weeks of treatment with either micronized 17β-estradiol [0.5 mg/day Estrace (E2)] or 1500 mg/day elemental calcium, given as carbonate plus vitamin D (800 IU/day; Ca+D). At the end of the initial 12-week treatment period, both groups received both Ca+D and E2 for an additional 12 weeks. Eleven older women were followed for 36 weeks without any treatment and served as a control group. Serum and urine were collected at baseline, at 12 and 24 weeks on treatment, and at 12 weeks after treatment was terminated for measurement of biochemical markers of bone turnover. Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I procollagen peptide; markers of bone resorption were urinary cross-linked C-telopeptides and N-telopeptides of type I collagen, serum cross-linked N-telopeptides of type I collagen, urinary free deoxypyridinoline cross-links, and serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in bone turnover measures over time by group. All markers of bone resorption decreased with initial treatment and decreased further with combination therapy (P &lt; 0.001). Markers of bone formation decreased with Ca+D treatment, but not with E2 alone; there was no additional effect of combination therapy on formation markers compared to Ca+D alone. Neither markers of formation nor resorption changed in the control group. These results suggest that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation, in older women. Thus, the combination of low dose estrogen plus calcium is likely to be more effective in older women than either treatment alone.


Author(s):  
Fereydoon Sargolzaei Aval ◽  
Eshaghali Saberi ◽  
Mohammad Reza Arab ◽  
Narjes Sargolzaei ◽  
Esmaeel Zare ◽  
...  

Objective: Regeneration of bone defects remains a challenge for maxillofacial and reparative surgeons. The purpose of this histological study was to assess the osteogenic potential of octacalcium phosphate (OCP) and bone matrix gelatin (BMG) alone and in combination in artificially created mandibular bone defects in rats. The quality of the newly formed bone was also evaluated. Methods: Thirty-six male Sprague Dawley rats (6-8 weeks old with 120-150 g weight) were randomly divided into four groups. Defects (3 mm in diameter and 2 mm in depth) were created in the mandible of rats and filled with 6 mg of OCP, BMG or a combination of both (1/4 ratio), respectively. Defects were left unfilled in the control group. To assess osteoinduction and bone regeneration and determine the quality of the newly formed bone, tissue specimens were harvested at seven, 14, and 21 days post-implantation. The specimens were processed, stained with hematoxylin and eosin (H&amp;E) and histologically analyzed under light microscopy. Results: In the experimental groups, new bone formation was initiated at the margins of defects from seventh day after implantation. At the end of the study period, the amount of the newly formed bone increased and the bone was relatively mature. Osteoinduction and new bone formation were greater in OCP/BMG group. In the control group, slight amount of new bone had been formed at the defect margins (next to host bone) on day 21. Conclusion: Combination of OCP/BMG may serve as an optimal biomaterial for treatment of mandibular bone defects.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Sarah Turner ◽  
Margaret Torode ◽  
Mike Climstein ◽  
Geraldine Naughton ◽  
David Greene ◽  
...  

Purpose. To examine the effects of two doses of low-frequency (12 Hz), low-magnitude (0.3 g), whole body vibration on markers of bone formation and resorption in postmenopausal women.Methods. Women were recruited and randomized into a sham vibration control group, one time per week vibration group (1×/week), or three times per week vibration group (3×/week). Vibration exposure consisted of 20 minutes of intermittent vibration for the 1×/week and 3×/week groups, and sham vibration (<0.1 g) for the control group for eight weeks. Double-blinded primary outcome measures were urine markers of bone resorption: N-telopeptide X normalised to creatinine (NTx/Cr) and bone formation: bone-specific alkaline phosphatase (ALP).Results. Forty-six women (59.8 ± 6.2 years, median 7.3 years since menopause) were enrolled. NTx/Cr was significantly reduced (34.6%) in the 3×/wk vibration group but not in the 1×/wk vibration group compared with sham control (P<.01) group. No effect of time or group allocation was observed on the bone formation marker ALP (P=.27).Conclusion. We have shown for the first time that low-frequency, low-magnitude vibration 3×/week for eight weeks in postmenopausal women results in a significant reduction in NTx/Cr, a marker of bone resorption, when compared with sham vibration exposure.


Author(s):  
Vasilena Ivanova ◽  
Ivan Chenchev ◽  
Stefan Zlatev ◽  
Eitan Mijiritsky

The aim of the present clinical study was to assess and compare the histomorphometric results and efficacy of freeze-dried bone allograft (FDBA) in combination with platelet-rich fibrin (PRF), and PRF as a sole grafting material for socket preservation. Ninety patients in need of tooth extraction and implant restoration were included in this study. The participants were randomly divided into three groups based on post-extraction clinical protocol: socket preservation procedure with allograft in combination with a PRF membrane (PRFm), PRF as a sole grafting material, and a control group. A total of 90 implants were placed four months post-extraction. During the surgical re-entry a bone biopsy was harvested with a trephine drill. Histological samples were prepared and analyzed for percentage vital bone and connective tissue. One-way ANOVA with Bonferroni post-hoc analysis were used to assess the results. Both test groups revealed a significantly higher percentage of vital bone formation compared to the control group. No statistically significant differences regarding vital bone formation and connective tissue quantity between the tested groups were observed (FDBA + PRFm: 3.29 ± 13.03%; and PRF: 60.79 ± 9.72%). From a clinical and histological point of view, both materials in the test groups are suitable for the filling of post-extraction sockets without bone defects. Both of the tested groups revealed a significantly higher percentage of vital bone formation compared to the control group.


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