Successful Osteoinduction by Cell-Macroporous Biphasic HA-TCP Ceramic Matrix

2005 ◽  
Vol 288-289 ◽  
pp. 245-248 ◽  
Author(s):  
Hong In Shin ◽  
K.H. Kim ◽  
Inn Kyu Kang ◽  
Kyung Sik Oh

To improve the potential of osteogenic repair, we developed macroporous biphasic hydroxyapatite-tricalcium phosphate (HA-TCP) ceramic and evaluated its efficiency as a scaffold for tissue engineered bone regeneration, which allows for appropriate cellular attachment and proliferation with osteogenic differentiation by evaluating ectopic bone formation ability after the implantation of cell-matrix construct in the skid mice subcutaneous pouches for 3 weeks. The macroporous biphasic HA-TCP ceramic matrix, with an average porosity of 86% and 200 µm mean pore size, provided favorable conditions for the attachment of cultured bone marrow derived osteoblastic cells along its inner surfaces in a filed up pattern and the active proliferation of them. The implanted cell-matrix constructs in the subcutaneous pouches induced favorable ectopic bone formation without any remarkable inflammatory reactions. These findings suggest that the biphasic HA-TCP ceramic matrix with macroporous structure has excellent biocompatibility, and that it allows for favorable cellular attachment with the acceleration of cellular proliferation and osteogenic differentiation support as well. Thus, with the controlled biodegradability, the biphasic HA-TCP ceramic may be a promising scaffold for tissue engineered bone regeneration technology.

2006 ◽  
Vol 309-311 ◽  
pp. 985-988 ◽  
Author(s):  
J.H. Yoon ◽  
J.T. Kim ◽  
Eui Kyun Park ◽  
Shin Yoon Kim ◽  
Chang Kuk You ◽  
...  

As a part of the effort to develop a suitable scaffold for tissue-engineered bone regeneration, we modified calcium metaphosphate (CMP) ceramic with Na20 and evaluated its efficiency as a scaffold. We incorporate 5% Na20 into pure CMP and prepare for an average pore size of 250 or 450 µm average pore sizes. The incorporation of 5% Na2O caused reduced compressive strength and there was no change in biodegradability. The in vitro cellular attachment and proliferation rate, however, were slightly improved. The 5% Na2O-incorporated macroporous CMP ceramic-cell constructs treated with Emdogain induced ectopic bone formation more effectively than those without Emdogain treatment. These results suggest that the incorporation of 5% Na2O into pure CMP is not effective for improving the physical characteristics of pure CMP but it is positive for improving the cellular reaction and osteogenic effect with the addition of Emdogain.


2017 ◽  
Vol 41 (8) ◽  
pp. 3036-3047 ◽  
Author(s):  
Dharman Govindaraj ◽  
Mariappan Rajan ◽  
Murugan A. Munusamy ◽  
Abdullah A. Alarfaj ◽  
S. Suresh Kumar

Progress of biomimetic mineral-substituted hydroxyapatite reinforced poly(raffinose-citric acid)–polyethylene glycol–poly(raffinose-citric acid) for prospective ectopic bone formation.


2005 ◽  
Vol 284-286 ◽  
pp. 631-634
Author(s):  
Suk Young Kim ◽  
Chang Kuk You ◽  
Jae Ho Jeong ◽  
Eui Kyun Park ◽  
Shin Yoon Kim ◽  
...  

As a part of the efforts to develop a suitable scaffold optimizing bone regeneration that has similar physical properties to bone, we modified calcium metaphosphate (CMP) ceramics with K2O and evaluated their efficiency as a scaffold for tissue engineered bone tissue regeneration. Macroporous CMP ceramics modified by incorporation of 5% K2O to improve biodegradability were prepared to have 250 and 450 µm average pore sizes, respectively. The modified CMP ceramics were cultured with mouse primary calvarial osteoblastic cells in osteogenic media for 2 weeks and these cell-CMP ceramic constructs with or without Emdogain treatment were implanted in the SCID mice subcutaneous pouches. After 1, 2, and 3 weeks, the degree of ectopic bone formation was evaluated. The modified macroporous CMP ceramic-cell constructs treated with Emdogain induced ectopic bone formation, whereas the modified CMP ceramic-cell constructs without Emdogain treatment induced no ectopic bone formation. This result suggests that the Emdogain treatment on cell-scaffold constructs for tissue engineered bone regeneration may be effective for osteogenic activation of attached cells.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Haozhuo Xiao ◽  
Xiaoyu Wang ◽  
Claire Wang ◽  
Guangming Dai ◽  
Zhenglin Zhu ◽  
...  

Abstract Bone morphogenetic protein (BMP) 9 (BMP9) is one of most potent BMPs in inducing osteogenic differentiation of mesenchymal stem cells (MSCs). Recently, evidence has shown that osteogenesis and angiogenesis are coupled, however, it is unclear whether BMP9 induces MSC differentiation into endothelial-like cells and further promotes blood vessel formation. In the present study, we explored the potential of BMP9-induced angiogenic differentiation of MSCs, and the relationship between BMP9-induced osteogenic and angiogenic differentiation of MSCs. Osteogenic activities and angiogenic differentiation markers were analyzed at mRNA and protein levels. In vivo osteogenic and angiogenic differentiation of MSCs were tested by the ectopic bone formation model. We identified that adenoviral vectors effectively transduced in immortalized mouse embryonic fibroblasts (iMEFs) and expressed BMP9 with high efficiency. We found that BMP9 induces early and late osteogenic differentiation, and it up-regulated osteogenic marker expression in MSCs. Meanwhile, BMP9 induces angiogenic differentiation of MSCs via the expression of vascular endothelial growth factor a (VEGFa) and CD31 at both mRNA and protein levels. CD31-positive cells were also increased with the stimulation of BMP9. The ectopic bone formation tests found that BMP9-induced trabecular bone formation was coupled with the expression of blood vessel formation markers and sinusoid capillary formation. These findings suggest that BMP9 exhibits dual and coupled roles in inducing osteogenic and angiogenic differentiation of MSCs.


2007 ◽  
Vol 342-343 ◽  
pp. 105-108
Author(s):  
J.T. Kim ◽  
H.J. Kang ◽  
H.N. Kim ◽  
J.Y. Choi ◽  
J.M. Lee ◽  
...  

To improve ostegenic healing efficiency by demineralized bone matrix, we evaluated the ectopic bone formation induced by variously demineralized allogenic cortical bone matrices at subcutaneous and muscular sites in rats. The rat tubular cortical bone matrices were demineralized in heated 0.6N HCl at 60 °C for 5 and 20 mins, respectively, using a controlledheat ultrasonic cleaner and implanted in rat dorsal subcutaneous pouches and thigh muscles for 1-3 weeks. The influence of the demineralized condition of bone matrix on cellular proliferation and osteogenic differentiation was also evaluated in vitro by MTT assay and ALP staining. The cortical matrices were completely demineralized within 20 mins by sonication and heating of diluted 0.6 N HCl. The sonicated bone matrices in heated acidic solution at 60 °C revealed no adverse immunogenic and inflammatory response in vivo regardless of demineralized condition. Cellular proliferation and osteoblastic differentiation was facilitated by more fully demineralized. Ectopic bone formation was induced only by demineralized bone matrices and were more favorable in fully demineralized matrices. The ectopic bone induction was more favorably in subcutaneous pouches than in muscular tissue. These findings suggest that a fully demineralized cortical bone matrix maximizes osteogenic repair by exposing more bioactive molecules which in turn induce chondro- and osteognic differentiation of mesenchymal cells around the implanted matrices, and that the sonication of diluted 0.6 N HCl heated at 60 ° C is a rapid and effective method for sterile demineralized graft preparation.


2019 ◽  
Vol 116 (11) ◽  
pp. 4855-4860 ◽  
Author(s):  
Anne M. Arnold ◽  
Brian D. Holt ◽  
Leila Daneshmandi ◽  
Cato T. Laurencin ◽  
Stefanie A. Sydlik

Synthetic, resorbable scaffolds for bone regeneration have potential to transform the clinical standard of care. Here, we demonstrate that functional graphenic materials (FGMs) could serve as an osteoinductive scaffold: recruiting native cells to the site of injury and promoting differentiation into bone cells. By invoking a Lewis acid-catalyzed Arbuzov reaction, we are able to functionalize graphene oxide (GO) to produce phosphate graphenes (PGs) with unprecedented control of functional group density, mechanical properties, and counterion identity. In aqueous environments, PGs release inducerons, including Ca2+ and PO43−. Calcium phosphate graphene (CaPG) intrinsically induces osteogenesis in vitro and in the presence of bone marrow stromal cells (BMSCs), can induce ectopic bone formation in vivo. Additionally, an FGM can be made by noncovalently loading GO with the growth factor recombinant human bone morphogenetic protein 2 (rhBMP-2), producing a scaffold that induces ectopic bone formation with or without BMSCs. The FGMs reported here are intrinsically inductive scaffolds with significant potential to revolutionize the regeneration of bone.


2017 ◽  
Vol 41 (2) ◽  
pp. 484-500 ◽  
Author(s):  
Jing Wang ◽  
Junyi Liao ◽  
Fugui Zhang ◽  
Dongzhe Song ◽  
Minpeng Lu ◽  
...  

Background: BMP9 induces both osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). Nell1 is a secretory glycoprotein with osteoinductive and anti-adipogenic activities. We investigated the role of Nell1 in BMP9-induced osteogenesis and adipogenesis in MSCs. Methods: Previously characterized MSCs iMEFs were used. Overexpression of BMP9 and NELL1 or silencing of mouse Nell1 was mediated by adenoviral vectors. Early and late osteogenic and adipogenic markers were assessed by staining techniques and qPCR analysis. In vivo activity was assessed in an ectopic bone formation model of athymic mice. Results: We demonstrate that Nell1 expression was up-regulated by BMP9. Exogenous Nell1 potentiated BMP9-induced late stage osteogenic differentiation while inhibiting the early osteogenic marker. Forced Nell1 expression enhanced BMP9-induced osteogenic regulators/markers and inhibited BMP9-upregulated expression of adipogenic regulators/markers in MSCs. In vivo ectopic bone formation assay showed that exogenous Nell1 expression enhanced mineralization and maturity of BMP9-induced bone formation, while inhibiting BMP9-induced adipogenesis. Conversely, silencing Nell1 expression in BMP9-stimulated MSCs led to forming immature chondroid-like matrix. Conclusion: Our findings indicate that Nell1 can be up-regulated by BMP9, which in turn accelerates and augments BMP9-induced osteogenesis. Exogenous Nell1 may be exploited to enhance BMP9-induced bone formation while overcoming BMP9-induced adipogenesis in regenerative medicine.


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