Prefabrication of Vascularized Allogenic Bone Graft in a Rat by Implanting a Flow-Through Vascular Pedicle and Basic Fibroblast Growth Factor Containing Hydroxyapatite/Collagen Composite

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.

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.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yan Wei ◽  
Guixin Zhu ◽  
Zifan Zhao ◽  
Chengcheng Yin ◽  
Qin Zhao ◽  
...  

AbstractMineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration. At present, autograft harvest procedures may cause secondary trauma to patients, while bone scaffold materials lack osteogenic activity, resulting in a limited application. Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft, but the explosive release of growth factor may also cause side effects. In this study, we innovatively used platelet-rich fibrin (PRF)-modified bone scaffolds (Bio-Oss®) to replace autograft, and used cytokine (BMP-2) to enhance osteogenesis. Encouragingly, this mixture, which we named “Autograft Mimic (AGM)”, has multiple functions and advantages. (1) The fiber network provided by PRF binds the entire bone scaffold together, thereby shaping the bone grafts and maintaining the space of the defect area. (2) The sustained release of BMP-2 from bone graft promoted bone regeneration continuously. (3) AGM recruited bone marrow mesenchymal stem cells (BMSCs) and promote their proliferation, migration, and osteogenic differentiation. Thus, AGM developed in this study can improve osteogenesis, and provide new guidance for the development of clinical bone grafts.


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.


Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 849 ◽  
Author(s):  
Huang ◽  
Liu ◽  
Zhao ◽  
Fu ◽  
Wang ◽  
...  

Estimation of the skeleton-protective effects of Ca in Cd-induced bone damage is helpful in the assessment of Cd health risk. The aim of this study was to identify whether Ca supplementation during exposure to different population-relevant doses of Cd can prevent Cd-induced bone damage under the tolerable upper intake level of Ca supplementation. Young female Sprague-Dawley rats were given different population-relevant doses of Cd (1, 5, and 50 mg Cd/kg diet) and Ca supplementation (0.4% Ca supplementation) intervention. Ca supplementation significantly decreased Cd-induced bone microstructure damage, increased bone biomechanics (p < 0.05), serum bone formation marker level (p < 0.05) and expression of osteogenic gene markers exposure to the 5 and 50 mg Cd/kg diets. However, it had no impact on these indicators under the 1 mg Cd/kg diets, with the exception of expression of osteogenic marker genes. Ca supplementation significantly decreased serum Klotho level (p < 0.05), and fibroblast growth factor 23/Klotho-associated gene expression in the kidney and bone showed significant changes. In conclusion, Ca supplementation has a positive effect on bone formation and bone quality against the damaging impact of Cd, especially with exposure to the 5 mg and 50 mg Cd/kg diet, which may be related to its impact on the fibroblast growth factor 23/Klotho axis.


2021 ◽  
pp. 194338752110483
Author(s):  
Jonathan Ribeiro da Silva ◽  
Maria Cristina de Moraes Balbas ◽  
Caroline Águeda Corrêa ◽  
Manuella Zanela ◽  
Roberta Okamoto ◽  
...  

Objective: To evaluate the effects of inorganic bovine bone graft (Lumina Bone, Criteria, Brazil) and beta-tricalcium phosphate (β-TCP) graft (ChronOS, Synthes, Brazil) in rats with the risk of developing post-extraction medication-related osteonecrosis of the jaw (MRONJ). Methods: Eighteen male Wistar rats weighing 350 to 450 g were induced to develop MRONJ using zoledronic acid for 5 weeks. In the sixth week, the right maxillary first molar was extracted. The animals in Group I (G1) did not receive bone grafts after tooth extraction, while Group II (G2) animals received inorganic bovine bone grafts, and Group III (G3) animals received beta-tricalcium phosphate (β-TCP) grafts. Clinical evaluation and histomorphometric and immunohistochemical analyses were performed. ANOVA and Tukey’s statistical tests were used and a level of significance was considered to be 5%. Results: In the clinical evaluation, animals from G2 and G3 did not present clinical manifestations of osteonecrosis, unlike the control group (G1) animals, which presented necrotic bone tissue exposure in all samples. In the histomorphometric evaluation, animals in G3 showed greater formation of bone tissue (66%) and less formation of bone lacuna (18%) than animals in G1 (58%/32%) and in G2 (59%/27%) ( P < 0.05). Moderate (++) immunostaining was observed in G2 and G3 for RANKL, TRAP, and OC, while G1 showed moderate (++) labeling for OC and mild (+) immunostaining for TRAP and RANKL. Conclusions: Greater formation of bone tissue and fewer bone lacunae were found in animals treated with β-TCP. In clinical evaluation, bone graft groups presented with the clinical manifestation of MRONJ and showed higher intensity of immunostaining for TRAP and RANKL. Despite the limitations of experimental animal studies, the results of this work may assist in the development of future clinical research for the prevention of MRONJ.


Author(s):  
Elham Shakerian ◽  
Narges Mohammad Taghvaei ◽  
Zohre Askari ◽  
Reza Afarin

Background: Activated hepatic stellate cells (HSCs) are the primary mediators in the progression of hepatic fibrosis. The activation of toll-like receptor 4 (TLR4) signaling leads to the downregulation of the transmembrane inhibitory transforming growth factor-beta (TGF-β) pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) on HSCs. Fibroblast growth factor 21 (FGF21) is a natural secretory protein in the body with effects, such as the reduction of fat accumulation and oxidation of lipids; however; no study has investigated FGF21 ability to prevent the progression of liver fibrosis. Objectives: This study aimed to examine the beneficial effects of FGF21 to reduce cholesterol-activated human HSCs. Methods: The human HSCs were incubated in media containing different concentrations of cholesterol, including 25, 50, 75, 100, 125, and 150 μM, for 24 h and then incubated with FGF21 for 24 h. Total ribonucleic acids were extracted and reversely transcribed into complementary deoxyribonucleic acid. A quantitative real-time polymerase chain reaction was performed in this study. Results: The results showed that the messenger ribonucleic acid (mRNA) expression of TGF-β, collagen, type I, alpha 1 (collagen1α), and TLR4 genes increased significantly in the presence of cholesterol (75 and 100 μM), compared to that of the control group (* P < 0.05, ** P < 0.01, and *** P < 0.001); nevertheless, the mRNA expression of the BAMBI gene significantly reduced, compared to that of the control group (* P < 0.05). The FGF21 significantly reduced the mRNA expression of TGF-β, collagen1α, and TLR4 genes (# P < 0.05). The mRNA expression of the BAMBI gene significantly increased with FGF21 (# P < 0.05). Conclusions: It was concluded that the treatment with FGF21 reduces the cholesterol-activated HSCs by decreasing the mRNA expression of the TLR4, TGF-β, and collagen1α genes and increasing the mRNA expression of the BAMBI gene.


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