scholarly journals Doxycycline and Zinc Loaded Silica-Nanofibrous Polymers as Biomaterials for Bone Regeneration

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1201 ◽  
Author(s):  
Manuel Toledano ◽  
Manuel Toledano-Osorio ◽  
Raquel Osorio ◽  
Álvaro Carrasco-Carmona ◽  
José-Luis Gutiérrez-Pérez ◽  
...  

The main target of bone tissue engineering is to design biomaterials that support bone regeneration and vascularization. Nanostructured membranes of (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 loaded with 5% wt of SiO2-nanoparticles (HOOC-Si-Membrane) were doped with zinc (Zn-HOOC-Si-Membrane) or doxycycline (Dox-HOOC-Si-Membrane). Critical bone defects were effectuated on six New Zealand-bred rabbit skulls and covered with the membranes. After six weeks, the bone architecture was evaluated with micro computed tomography. Three histological analyses were utilized to analyse bone regeneration, including von Kossa silver nitrate, toluidine blue and fluorescence. All membrane-treated defects exhibited higher number of osteocytes and bone perimeter than the control group without the membrane. Zn-HOOC-Si-Membranes induced higher new bone and osteoid area than those treated with HOOC-Si-Membranes, and control group, respectively. Zn-HOOC-Si-Membranes and Dox-HOOC-Si-Membranes attained the lowest ratio M1 macrophages/M2 macrophages. Dox-HOOC-Si-Membranes caused the lowest number of osteoclasts, and bone density. At the trabecular new bone, Zn-HOOC-Si-Membranes produced the highest angiogenesis, bone thickness, connectivity, junctions and branches. Zn-HOOC-Si-Membranes enhanced biological activity, attained a balanced remodeling, and achieved the greatest regenerative efficiency after osteogenesis and angiogenesis assessments. The bone-integrated Zn-HOOC-Si-Membranes can be considered as bioactive modulators provoking a M2 macrophages (pro-healing cells) increase, being a potential biomaterial for promoting bone repair.

2021 ◽  
pp. 1-7
Author(s):  
Jin Xi Lim ◽  
Min He ◽  
Alphonsus Khin Sze Chong

BACKGROUND: An increasing number of bone graft materials are commercially available and vary in their composition, mechanism of action, costs, and indications. OBJECTIVE: A commercially available PLGA scaffold produced using 3D printing technology has been used to promote the preservation of the alveolar socket after tooth extraction. We examined its influence on bone regeneration in long bones of New Zealand White rabbits. METHODS: 5.0-mm-diameter circular defects were created on the tibia bones of eight rabbits. Two groups were studied: (1) control group, in which the bone defects were left empty; (2) scaffold group, in which the PLGA scaffolds were implanted into the bone defect. Radiography was performed every two weeks postoperatively. After sacrifice, bone specimens were isolated and examined by micro-computed tomography and histology. RESULTS: Scaffolds were not degraded by eight weeks after surgery. Micro-computed tomography and histology showed that in the region of bone defects that was occupied by scaffolds, bone regeneration was compromised and the total bone volume/total volume ratio (BV/TV) was significantly lower. CONCLUSION: The implantation of this scaffold impedes bone regeneration in a non-critical bone defect. Implantation of bone scaffolds, if unnecessary, lead to a slower rate of fracture healing.


Symmetry ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1356
Author(s):  
Elizabeth Ferreira Martinez ◽  
Ana Elisa Amaro Rodrigues ◽  
Lucas Novaes Teixeira ◽  
Andrea Rodrigues Esposito ◽  
Walter Israel Rojas Cabrera ◽  
...  

Background: The use of biomaterials is commonplace in dentistry for bone regeneration. The aim of this study was to evaluate the performance of a new alloplastic material for bone repair in critical defects and to evaluate the extent of the inflammatory process. Methods: Forty-five New Zealand rabbits were divided into five groups according to evaluation time (7, 14, 30, 60, 120 days), totaling 180 sites with six-millimeter diameter defects in their tibiae. The defects were filled with alloplastic material consisting of poly (lactide-co-caprolactone), beta-tricalcium phosphate, hydroxyapatite and nano-hydroxyapatite (BTPHP) in three different presentations: paste, block, and membrane. Comparisons were established with reference materials, such as Bio-ossTM, Bio-oss CollagenTM, and Bio-gideTM, respectively. The samples were HE-stained and evaluated for inflammatory infiltrate (scored for intensity from 0 to 3) and the presence of newly formed bone at the periphery of the defects. Results: Greater bone formation was observed for the alloplastic material and equivalent inflammatory intensity for both materials, regardless of evaluation time. At 30 days, part of the synthetic biomaterial, regardless of the presentation, was resorbed. Conclusions: We concluded that this novel alloplastic material showed osteoconductive potential, biocompatibility, low inflammatory response, and gradual resorption, thus an alternative strategy for guided bone regeneration.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yoo-Kyung Sun ◽  
Jae-Kook Cha ◽  
Daniel Stefan Thoma ◽  
So-Ra Yoon ◽  
Jung-Seok Lee ◽  
...  

This study is designed to determine the effect of collagen membrane (CM) soaked with bone morphogenetic protein-2 (rhBMP-2) for the treatment of peri-implant dehiscence defects. Material and Methods. Three treatment groups were allocated at each defect in 5 dogs: (i) collagenated synthetic bone (OC) and CM soaked with rhBMP-2 (BMP group), (ii) OC and CM soaked with saline (nonBMP group), and (iii) no further treatment (control group). Titanium pins were used to stabilize the membranes in two dogs. Radiographic and histomorphometric analyses were performed 4 weeks later. Results. The median augmented volumes were 4.27 mm3, 6.24 mm3, and 2.75 mm3 in the BMP, nonBMP, and control groups, respectively; the corresponding median first bone-to-implant contact (fBIC) distances were 3.25 mm, 3.08 mm, and 2.56 mm (P>0.05). The placement of pins (with the BMP and nonBMP groups pooled) significantly improved bone regeneration: the augmented volumes were 17.60 mm3 with pins and 3.68 mm3 without pins (P=0.024), with corresponding fBIC distances of 2.25 mm and 3.31 mm, respectively (P<0.001). Conclusions. The addition of rhBMP-2 to CM failed to improve bone regeneration of peri-implant dehiscence defects compared to using an unsoaked CM after 4 weeks. However, the stabilization of CMs using pins positively influenced the outcomes.


2019 ◽  
Vol 12 (6) ◽  
pp. 809-816
Author(s):  
Aminatun Aminatun ◽  
D.E. Fadhilah Handayani ◽  
Prihartini Widiyanti ◽  
Dwi Winarni ◽  
Siswanto Siswanto

Background: Hydroxyapatite (HA) from bovine bone has been widely used as bone filler in many fractures cases. HA can also be made from cuttlefish bone (Sepia spp.) that has abundant availability in Indonesia and contains 84% CaCO3, which is a basic ingredient of HA. However, research on the effects of HA from cuttlefish bone on bone regeneration parameters has not been done yet. Aim: This study aimed to determine femur bone regeneration of white rats (Rattus norvegicus) through the use of HA from cuttlefish bone (Sepia spp.) as bone filler. Materials and Methods: HA was made using the hydrothermal method by mixing 1M aragonite (CaCO3) from cuttlefish bone and 0.6 M NH4H2PO4 at 200°C for 12 h followed by sintering at 900°C for 1 h. In vivo test was carried out in three groups, including control group, bovine bone-derived HA group, and cuttlefish bone-derived HA group. The generation of femur bone was observed through the number of osteoblasts, osteoclasts, woven bone, lamellar bone, havers system, and repair bone through anatomical pathology test for 28 days and 56 days. Results: Anatomical pathology test results are showed that administration of bovine bone-derived HA and cuttlefish bone-derived HA increased the number of osteoblasts, osteoclasts, woven bone, lamellar bone, havers system, and bone repair at recuperation of 56 days. Statistical test using Statistical Package for the Social Sciences with Kruskal–Wallis and Mann–Whitney U-test was resulted in significant differences between the bovine bone-derived HA control group and the cuttlefish-derived HA control group. There was no significant difference toward the indication of bone formation through the growth of osteoblasts, osteoclasts, woven bone, lamellar bone, havers system, and bone repair in the bovine bone-derived HA and cuttlefish bone-derived HA groups. Conclusion: It can be concluded that cuttlefish bone-derived HA has the potential as bone filler based on the characteristics of bone regeneration through in vivo test.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiachen Sun ◽  
Lang Li ◽  
Fei Xing ◽  
Yun Yang ◽  
Min Gong ◽  
...  

Abstract Background The invasive and complicated procedures involving the use of traditional stem cells limit their application in bone tissue engineering. Cell-free, tissue-engineered bones often have complex scaffold structures and are usually engineered using several growth factors (GFs), thus leading to costly and difficult preparations. Urine-derived stem cells (USCs), a type of autologous stem cell isolated noninvasively and with minimum cost, are expected to solve the typical problems of using traditional stem cells to engineer bones. In this study, a graphene oxide (GO)-modified silk fibroin (SF)/nanohydroxyapatite (nHA) scaffold loaded with USCs was developed for immunomodulation and bone regeneration. Methods The SF/nHA scaffolds were prepared via lyophilization and cross-linked with GO using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS). Scaffolds containing various concentrations of GO were characterized using scanning electron microscopy (SEM), the elastic modulus test, Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectrometer (XPS). Examinations of cell adhesion, proliferation, viability, morphology, alkaline phosphatase activity, and osteogenesis-related gene expression were performed to compare the osteogenesis-related biological behaviors of USCs cultured on the scaffolds. The effect of USC-laden scaffolds on the differentiation of macrophages was tested using ELISA, qRT-PCR, and immunofluorescence staining. Subcutaneous implantations in rats were performed to evaluate the inflammatory response of the USC-laden scaffolds after implantation. The scaffolds loaded with USCs were implanted into a cranial defect model in rats to repair bone defects. Micro-computed tomography (μCT) analyses and histological evaluation were performed to evaluate the bone repair effects. Results GO modification enhanced the mechanical properties of the scaffolds. Scaffolds containing less than 0.5% GO had good biocompatibility and promoted USC proliferation and osteogenesis. The scaffolds loaded with USCs induced the M2-type differentiation and inhibited the M1-type differentiation of macrophages. The USC-laden scaffolds containing 0.1% GO exhibited the best capacity for promoting the M2-type differentiation of macrophages and accelerating bone regeneration and almost bridged the site of the rat cranial defects at 12 weeks after surgery. Conclusions This composite system has the capacity for immunomodulation and the promotion of bone regeneration and shows promising potential for clinical applications of USC-based, tissue-engineered bones.


Materials ◽  
2020 ◽  
Vol 13 (20) ◽  
pp. 4599
Author(s):  
Jong-Ju Ahn ◽  
Hyung-Joon Kim ◽  
Eun-Bin Bae ◽  
Won-Tak Cho ◽  
YunJeong Choi ◽  
...  

The purpose of this study was to evaluate the bone regeneration efficacy of an 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-cross-linked collagen membrane for guided bone regeneration (GBR). A non-cross-linked collagen membrane (Control group), and an EDC-cross-linked collagen membrane (Test group) were used in this study. In vitro, mechanical, and degradation testing and cell studies were performed. In the animal study, 36 artificial bone defects were formed in the mandibles of six beagles. Implants were inserted at the time of bone grafting, and membranes were assigned randomly. Eight weeks later, animals were sacrificed, micro-computed tomography was performed, and hematoxylin-eosin stained specimens were prepared. Physical properties (tensile strength and enzymatic degradation rate) were better in the Test group than in the Control group. No inflammation or membrane collapse was observed in either group, and bone volumes (%) in defects around implants were similar in the two groups (p > 0.05). The results of new bone areas (%) analysis also showed similar values in the two groups (p > 0.05). Therefore, it can be concluded that cross-linking the collagen membranes with EDC is the method of enhancing the physical properties (tensile strength and enzymatic degradation) of the collagen membranes without risk of toxicity.


2021 ◽  
Author(s):  
Bin Wang ◽  
Yanming Cao ◽  
Caiyuan Mai ◽  
Ram Ishwar Yadav ◽  
Jianliang Gao ◽  
...  

Abstract Objective: To investigate the variations in the expressions of LRP5, Runx2, Osterix, and RANKL factors in bone tissues associated with postmenopausal osteoporotic fractures (PMOPF). Method: Postmenopausal patients with femur fractures were initially divided into control (31 cases) and PMOPF groups (83 cases). All control group patients were operated within 1 day after injury. The patients with PMOPF were operated based on the time after fracture in the respective groups (patients were divided into groups A, B, and C based on the time after fracture). Samples were collected from femurs at fracture sites during the operation. The expression level of each factor in bone tissues was detected using RT-qPCR, and the bone mass samples were decalcified and then histologically analyzed by immunohistochemistry. We subsequently analyzed significant differences in the expressions of factors (LRP5, Runx2, Osterix, and RANKL) between PMOPF and control groups. Results: (1) LRP5, β-catenin, Runx2, and Osterix were under-expressed in patients with PMOPF relative to the controls (P<0.05). In contrast, RANKL was over-expressed in the PMOPF group when compared to the control group (P<0.05); (2) the expressions of LRP5 and Runx2 were lowest in Group A patients (1–3 days after fracture). Osterix expression was lowest in Group C patients (8–14 days after fracture). Conversely, RANKL expression was highest in Group B patients (4–7 days after fracture). Conclusion: The inhibition or reduction in the expressions of osteogenic factors including LRP5, Runx2, and Osterix of the Wnt/β-catenin and BMP-2/Runx2/Osterix signaling pathways are associated with PMOPF incidence. Specifically, upregulation of RANKL in the RANKL/RANK signaling pathway is associated with the incidence of PMOPF. LRP5 and Runx2 expressions decreased considerably within 1-3 days after fracture; Osterix expression decreased considerably within 8-14 days after fracture; RANKL expression was highest within 4-7 days after fracture, which could be associated with bone repair in PMOPF. The expression level of the aforementioned factors affects the development and progression of PMOPF.


2017 ◽  
Vol 24 (2) ◽  
pp. 62
Author(s):  
Yulisa Haslinda ◽  
Hendy Hendarto ◽  
Faroek Hoesin

Objectives: to measure and prove the increase of panmacrophage, macrophages M1 and M2 expression and decrease of ratio of M1/M2 in menstrual blood flakes of women with endometriosis. Materials and Methods: This study was a cross sectional observational analytic study conducted on 30 subjects with endometriosis and non-endometriosis. Immunohistochemical staining was done on a sample of menstrual blood flakes of subjects study who were taken at the second or third day of menstrual cycles with CD68 and CD163 antibody to measure the expression of panmacrophage and M2 macrophages. Expression of M1 macrophages is the approach of a reduction expression of panmacrophage with M2 macrophages.Results: Expression of  M1, M2 and the ratio M1/M2 in the both of groups had a normal distribution then continued by independent t-test with one-tailed α (0.05). Probability was considered statistically significant at p <0.05 with a confidence interval of 95%. Based on the statistical result, Mφ macrophage expression in endometriosis and control group amounted to 3.62 ± 0.50 and 2.80 ± 0.64 (p =0.0005) with non parametric test. The expression of M1 macrophages in endometriosis group and non endometriosis were respectively 1.40 ± 0.35 and 1.33 ± 0.40 (p =0.3005) and the expression of M2  in both of group, respectively of 2.23 ± 0.41 and 1.47 ± 0.36 (p =0.0005). The ratio of M1/M2, the endometriosis group and non endometriosis, respectively of 0.65 ± 0.20 and 0.92 ± 0.24 (p =0.0015).Conclusion: this study were significant increased in the panmacrophage Mφ, M2 macrophages expression on a woman's menstrual blood flakes endometriosis and significant decreased in ratio M1/M2 in the woman's menstrual blood flakes endometriosis.


2021 ◽  
Vol 8 ◽  
Author(s):  
Bin He ◽  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Bo Sun ◽  
Tian Su ◽  
...  

As one common kind of osteoporosis, postmenopausal osteoporosis (PMOP) is associated with the death and excessive loss of osteocytes. Estrogen deficiency of PMOP can cause osteocyte death by regulating necroptosis and apoptosis, but their roles in POMP have not been compared. In the present study, ovariectomy (OVX)-induced rat and murine long bone osteocyte Y4 (MLO-Y4) cells were used to compare the influence of necroptosis and apoptosis on osteocyte death and bone loss. Benzyloxycarbonyl-Val-Ala-Asp (zVAD) and necrostatin-1 (Nec-1) were used to specifically block cell apoptosis and necroptosis, respectively. OVX rats and MLO-Y4 cells were divided into zVAD group, Nec-1 group, zVAD + Nec-1 group, vehicle, and control group. The tibial plateaus of the rat model were harvested at 8 weeks after OVX and were analyzed by micro–computed tomography, transmission electron microscopy (TEM), the transferase dUTP nick end labeling assay, and western blot. The death of MLO-Y4 was stimulated by TNF-α and was measured by flow cytometry and TEM. The results found that necroptosis and apoptosis were both responsible for the death and excessive loss of osteocytes, as well as bone loss in OVX-induced osteoporosis, and furthermore necroptosis may generate greater impact on the death of osteocytes than apoptosis. Necroptotic death of osteocytes was mainly regulated by the receptor-interacting protein kinase 3 signaling pathway. Collectively, inhibition of necroptosis may produce better efficacy in reducing osteocyte loss than that of apoptosis, and combined blockade of necroptosis and apoptosis provide new insights into preventing and treating PMOP.


Materials ◽  
2020 ◽  
Vol 13 (4) ◽  
pp. 823 ◽  
Author(s):  
Hao-Hueng Chang ◽  
Chun-Liang Yeh ◽  
Yin-Lin Wang ◽  
Kang-Kuei Fu ◽  
Shang-Jye Tsai ◽  
...  

The aim of this study was to evaluate the efficacy of bone regeneration in developed bioceramics composed of dicalcium phosphate and hydroxyapatite (DCP/HA). Critical bony defects were prepared in mandibles of beagles. Defects were grafted using DCP/HA or collagen-enhanced particulate biphasic calcium phosphate (TCP/HA/Col), in addition to a control group without grafting. To assess the efficacy of new bone formation, implant stability quotient (ISQ) values, serial bone labeling, and radiographic and histological percentage of marginal bone coverage (PMBC) were carefully evaluated four, eight, and 12 weeks after surgery. Statistically significant differences among the groups were observed in the histological PMBC after four weeks. The DCP/HA group consistently exhibited significantly higher ISQ values and radiographic and histological PMCB eight and 12 weeks after surgery. At 12 weeks, the histological PMBC of DCP/HA (72.25% ± 2.99%) was higher than that in the TCP/HA/Col (62.61% ± 1.52%) and control groups (30.64% ± 2.57%). After rigorously evaluating the healing of biphasic DCP/HA bioceramics with a critical size peri-implant model with serial bone labeling, we confirmed that neutralized bioceramics exhibiting optimal compression strength and biphasic properties show promising efficacy in fast bone formation and high marginal bone coverage in peri-implant bone defects.


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