Effects of Macrophage on Biodegradation of β-tricalcium Phosphate Bone Graft Substitute

2008 ◽  
Vol 45 (10) ◽  
pp. 618-624 ◽  
Author(s):  
Young-Hee Kim ◽  
Anirban Jyoti ◽  
In-Sun Byun ◽  
Ik-Hyun Oh ◽  
Young-Ki Min ◽  
...  
Keyword(s):  
Bone Graft ◽  
Tricalcium Phosphate ◽  
Bone Graft Substitute

Novel In Vivo Model of Multiple Myeloma Bone Disease Using ß-Tricalcium Phosphate Artificial Bone Grafts

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4200-4200
Author(s):  
Miroslav Koulnis ◽  
Homare Eda ◽  
Loredana Santo ◽  
Ka Tat Siu ◽  
Janani Ramachandran ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Growth ◽  
Bone Graft ◽  
Bone Disease ◽  
Tricalcium Phosphate ◽  
Research Funding ◽  
Bone Graft Substitute ◽  
Artificial Bone ◽  
Fetal Bone

Abstract Model systems to study Multiple Myeloma (MM) related bone disease exist but have a number of limitations. Disseminated MM models have variable cell homing and do not precisely recapitulate the human microenvironment interactions with myeloma cells. Severe combined immunodeficiency (SCID) mice engrafted with human fetal bone (SCID-hu) have been used by us, and are able to recapitulate the human bone marrow microenvironment. The fetal bone chips are however difficult to obtain, and vary in size and shape, complicating inter-sample comparison. Similarly, the poly-ε-caprolactone polymeric scaffold, previously used to seed murine or human stromal compartment, may not correctly reproduce bone destruction and inhibition of osteogenesis by MM as seen in patients, making this model difficult to test therapies targeting the MM niche. β-tricalcium phosphate (β-TCP) is a biocompatible and biodegradable bone graft substitute that is uniform in structure and easily available, and may be a viable alternative to overcome SCID-hu difficulties in modeling MM bone disease. Here, we utilized β-TCP bone graft substitute to develop a novel in vivo MM model where β-TCP permits the development of the bone microenvironment, supports MM development, and is technically feasible and highly reproducible. Using this model, we aim to better understand the biology of the niche in MM by genetically modifying its components and by testing new niche-targeting therapies. Our initial results show that osteogenesis takes place in the β-TCP bone graft, and the implant is supportive of MM tumor growth. Inter-scapular subcutaneous implantation of β-TCP alone, or co-implantation with human-derived stromal cell line HS27A in immunocompromised recipients resulted in the expression of osteogenic markers Runx2, alkaline phosphatase (ALP), Col1A1, and Osteocalcin (OCN), as well as a marker of bone resorption. Further, implants supported the growth of human-derived MM1.S and murine 5TGM1 cells, as visualized directly in vivo by serial luciferase bioluminescence imaging (BLI) and by immunohistochemistry. Modifying the niche compartment in Cre/iDTR animals with MM disease is an exciting novel strategy to understand which niche component in vivo may be targeted to suppress MM development. Mouse strains with promoter-specific Cre recombinase that induces the expression of the diphtheria toxin (DT) receptor (iDTR) can be utilized to selectively ablate a cell population of interest in vivo, via intraperitoneal DT injection. Here, we first utilized OCN-Cre/iDTR mice to test the deletion of mature osteoblasts in β-TCP artificial bone graft post-implantation. Our data show a dose-dependent reduction in osteoblastic markers OCN, ALP, Runx2, Sclerostin, Osteoprotegerin and RANKL. Importantly, DT ablation of osteoblasts in the β-TCP implant resulted in a significantly increased 5TGM1 tumor growth, as judged by BLI and tumor weight. Our data show that the mature osteocalcin-positive niche population is protective against MM disease. Ongoing studies of the β-TCP mouse model will address the relative contribution of various osteogenic populations to the course of MM development in vivo, and test the efficacy of novel MM drugs. Disclosures Raje: BMS: Consultancy; Amgen: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Onyx: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Onyx: Consultancy; BMS: Consultancy; AstraZeneca: Research Funding; Eli Lilly: Research Funding; AstraZeneca: Research Funding; Millenium: Consultancy; Eli Lilly: Research Funding; Novartis: Consultancy; Acetylon: Research Funding; Millenium: Consultancy; Novartis: Consultancy; Acetylon: Research Funding.

IN VIVO EVALUATION OF A NEW β-TRICALCIUM PHOSPHATE BONE SUBSTITUTE IN A RABBIT FEMUR DEFECT MODEL

2015 ◽  
Vol 27 (03) ◽  
pp. 1550028 ◽  
Author(s):  
Kam-Kong Chan ◽  
Chia-Hsien Chen ◽  
Lien-Chen Wu ◽  
Yi-Jie Kuo ◽  
Chun-Jen Liao ◽  
...  
Keyword(s):  
Bone Graft ◽  
Tricalcium Phosphate ◽  
Bone Substitute ◽  
Zealand White Rabbit ◽  
Bone Substitutes ◽  
Bone Graft Substitute ◽  
Defect Model ◽  
In Vivo Evaluation ◽  
Rabbit Femur

Calcium phosphate ceramics, of a similar composition to that of mineral bone, and which possess the properties of bioactivity and osteoconductivity, have been widely used as substitutes for bone graft in orthopedic, plastic and craniofacial surgeries. A synthetic β-tricalcium phosphate, Osteocera™, a recently developed bone graft substitute, has been used in this study. To evaluate the affinity and efficacy of Osteocera™ as bone defect implant, we used a New Zealand white rabbit femur defect model to test the osteoconductivity of this new bone substitute. Alternative commercially available bone substitutes, Triosite® and ProOsteon500, were used as the control materials. These three bone substitutes show good biocompatibility, and no abnormal inflammation either infection was seen at the implantation sites. In the histological and histomorphometric images, newly formed bone grew into the peripheral pores in the bone substitutes. After six months implantation, the volume of bone formation was found to be 20.5 ± 5.2%, 29.8 ± 6.5% and 75.5 ± 4.9% of the potential total cavity offered by ProOsteon500, Triosite® and Osteocera™, respectively. The newly formed bone area within the femur defect section for Osteocera™ was significantly larger than ProOsteon500 and Triosite®. We concluded that Osteocera™ shows better bioresorbability, biocompatibility and osteoconductivity in the rabbit femur defect model.

scholarly journals Silicate/zinc-substituted strontium apatite coating improves the osteoinductive properties of β-tricalcium phosphate bone graft substitute

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hironori Sugimoto ◽  
Yusuke Inagaki ◽  
Akira Furukawa ◽  
Tsutomu Kira ◽  
Sachiko Kawasaki ◽  
...  
Keyword(s):  
Bone Graft ◽  
Mrna Expression ◽  
Tricalcium Phosphate ◽  
Bone Graft Substitute ◽  
Allogeneic Bone ◽  
Qrt Pcr ◽  
Alp Activity ◽  
Apatite Coating

Abstract Background β-Tricalcium phosphate (β-TCP) is a popular synthetic bone graft substitute with excellent osteoconductive properties and bioabsorbability. However, its osteoinductive properties are inferior to those of autologous or allogeneic bone. Trace elements such as strontium (Sr), silica (Si), and zinc (Zn) have been reported to promote osteogenesis in materials. In this study, we aimed to determine whether a Si/Zn-substituted Sr apatite coating of β-TCP could enhance osteoinductive properties. Methods The apatite-coated β-TCP disks were prepared using nanoparticle suspensions of silicate-substituted Sr apatite (SrSiP) or silicate- and Zn-co-substituted Sr apatite (SrZnSiP). Bone marrow mesenchymal cells (BMSCs) from rat femur were cultured and subsequently seeded at a density of 1.0 × 106/cm2 onto apatite-coated and non-coated β-TCP disks. In vitro, the β-TCP disks were then placed in osteogenic medium, and lactate dehydrogenase (LDH) activity was measured from supernatants after culture for 2 days. Additionally, after culture for 14 days, the mRNA expression of genes encoding osteocalcin (OC), alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP-2), and vascular endothelial growth factor (VEGF) was evaluated by qRT-PCR. In vivo, the β-TCP disks were transplanted subcutaneously into rats that were sacrificed after 4 weeks. Then, the harvested disks were evaluated biochemically (ALP activity, OC content, mRNA expression of OC, ALP, BMP-2, and VEGF measured by qRT-PCR), radiologically, and histologically. Results Significantly higher mRNA expression of almost all evaluated osteogenic and angiogenic genes was observed in the SrZnSiP and SrSiP groups than in the non-coated group, with no significant cytotoxicity elicited by the apatite coating in vitro. Moreover, in vivo, the SrZnSiP and SrSiP groups showed significantly higher osteogenic and angiogenic gene expression and higher ALP activity and OC content than the non-coated group (P < 0.05). Radiological and histopathological findings revealed abundant bone formation in the apatite-coated group. Conclusions Our findings indicate that apatite coating of β-TCP improves osteoinductive properties without inducing significant cytotoxicity.

Porous Ceramics of β-Tricalcium Phosphate Composed of Rod-Shaped Particles is Highly Biodegradable and Expresses Prominent Osteoconductivity

2006 ◽  
Vol 309-311 ◽  
pp. 1063-1066 ◽  
Author(s):  
Takatoshi Okuda ◽  
Ikuho Yonezawa ◽  
Koji Ioku ◽  
Hideyuki Minagi ◽  
Hisashi Kurosawa ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Graft ◽  
Tricalcium Phosphate ◽  
Porous Ceramics ◽  
Bone Graft Substitute ◽  
Left Femur

Newly developed porous β-tricalcium phosphate composed of rod-shaped particles was grafted into distal end of the left femur of female Japan White rabbit. As a control, hydrixyapatite generated in the same size was grafted. In both implants, 350µm in diameter-sized holes were created vertically and horizontally. Three weeks after grafting, margin of the β-tricalcium phosphate was absorbed by osteoclasts and bone formation was seen near the absorbed region. Twenty-four weeks after grafting, more than 80% of the β-tricalcium phosphate was absorbed and newly formed bone was prominently observed. The hydroxyapatite was not remarkably absorbed even 24 weeks after grafting, and newly formed bone was observed only in the holes created in the implants. These results suggest that porous β-tricalcium phosphate composed of rod-shaped particles has highly biodegradable and osteoconductive nature, and appropriate to bone graft substitute.

scholarly journals Biosilicated collagen/β-tricalcium phosphate composites as a BMP-2-delivering bone‐graft substitute for accelerated craniofacial bone regeneration

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Dong Keon Lee ◽  
Mi-Ran Ki ◽  
Euy Hyun Kim ◽  
Chang-Joo Park ◽  
Jae Jun Ryu ◽  
...  
Keyword(s):  
Bone Graft ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Tricalcium Phosphate ◽  
Bone Grafting ◽  
Drug Carrier ◽  
Bone Graft Substitute ◽  
Tissue Growth ◽  
Bone Morphogenetic Protein 2 ◽  
Therapeutic Drug

Abstract Background Bioceramic β-tricalcium phosphate (β-TCP) is used as a bone-grafting material and a therapeutic drug carrier for treatment of bone defects in the oral and maxillofacial regions due to the osteoconductivity and biocompatibility. However, the low mechanical strength and limited osteoinductivity of β-TCP agglomerate restrict bone regenerating performance in clinical settings. Methods Herein, a biomimetic composite is proposed as a bone morphogenetic protein-2 (BMP-2)-delivering bone graft substitute to achieve a robust bone grafting and augmented bone regeneration. Results The sequential processes of brown algae-inspired biosilicification and collagen coating on the surface of β-TCP enable the effective incorporation of BMP-2 into the coating layer without losing its bioactivity. The sustained delivery of BMP-2 from the biosilicated collagen and β-TCP composites promoted in vitro osteogenic behaviors of pre-osteoblasts and remarkedly accelerated in vivo bone regeneration within a rat calvarial bone defect. Conclusions Our multicomposite bone substitutes can be practically applied to improve bone tissue growth in bone grafting applications with further expansion to general bone tissue engineering.

Tricalcium Phosphate as a Bone Graft Substitute in Trauma

1989 ◽  
Vol 3 (2) ◽  
pp. 158 ◽  
Author(s):  
Paul Gorman ◽  
Mark McAndrew ◽  
Thomas Lange
Keyword(s):  
Bone Graft ◽  
Tricalcium Phosphate ◽  
Bone Graft Substitute
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