scholarly journals The Role of Strontium Enriched Hydroxyapatite and Tricalcium Phosphate Biomaterials in Osteoporotic Bone Regeneration

Symmetry ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 229 ◽  
Author(s):  
Janis Zarins ◽  
Mara Pilmane ◽  
Elga Sidhoma ◽  
Ilze Salma ◽  
Janis Locs
Keyword(s):  
Matrix Metalloproteinase ◽  
Bone Regeneration ◽  
Tricalcium Phosphate ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Bone Morphogenetic Protein 2 ◽  
Matrix Metalloproteinase 2 ◽  
Osteoporotic Bone ◽  
Morphogenetic Protein

Background: Strontium (Sr) enriched biomaterials have been used to improve bone regeneration in vivo. However, most studies provide only two experimental groups. The aim of our study was to compare eleven different bone sample groups from osteoporotic and healthy rabbits’ femoral neck, as it is the most frequent osteoporotic fracture in humans. Methods: Osteoporotic bone defects were filled with hydroxyapatite 30% (HA) and tricalcium phosphate 70% (TCP), 5% Sr-enriched HA30/TCP70, HA70/TCP30, or Sr-HA70/TCP30 granules and were compared with intact leg, sham surgery and healthy non-operated bone. Expression of osteoprotegerin (OPG), nuclear factor kappa beta 105 (NFkB-105), osteocalcin (OC), bone morphogenetic protein 2/4 (BMP-2/4), collagen I (Col-1α), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), interleukin 1 (IL-1) and interleukin 10 (IL-10) was analyzed by histomorphometry and immunohistochemistry. Results: Our study showed that Sr-HA70/TCP30 induced higher expression of all above-mentioned factors compared to intact leg and even higher expression of OC, MMP-2 and NFkB-105 compared to Sr-HA30/TCP70. HA70/TCP30 induced higher level of NFkB-105 and IL-1 compared to HA30/TCP70. Conclusion: Sr-enriched biomaterials improved bone regeneration at molecular level in severe osteoporosis and induced activity of the factors was higher than after pure ceramic, sham or even healthy rabbits.

scholarly journals The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 979
Author(s):  
Patricia Garcia-Garcia ◽  
Ricardo Reyes ◽  
José Antonio Rodriguez ◽  
Tomas Martín ◽  
Carmen Evora ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Regeneration ◽  
Growth Promotion ◽  
Tissue Growth ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Therapeutic Molecules ◽  
Positive Effect

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.

scholarly journals Sustained Release of Bone Morphogenetic Protein-2 through Alginate Microbeads Enhances Bone Regeneration in Rabbit Tibial Metaphyseal Defect Model

Materials ◽  
2021 ◽  
Vol 14 (10) ◽  
pp. 2600
Author(s):  
Junhyung Kim ◽  
Seoyun Lee ◽  
Yonghyun Choi ◽  
Jonghoon Choi ◽  
Byung-Jae Kang
Keyword(s):  
Sustained Release ◽  
Bone Regeneration ◽  
Bone Morphogenetic Protein ◽  
Bone Volume ◽  
Bone Morphogenetic Protein 2 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Micro Computed Tomography ◽  
Combined Application ◽  
Morphogenetic Protein

Bone morphogenetic protein-2 (BMP-2) is widely used to enhance bone regeneration. However, because of its short half-life and rapid disappearance, large amounts of BMP-2 are needed, leading to unintended side effects. In this study, BMP-2-encapsulated alginate microbeads (AM) were used to enhance bone regeneration. Enzyme-linked immunosorbent assay confirmed the sustained release of BMP-2 from AM. Vascular endothelial growth factor (VEGF)-adsorbing aptamer-conjugated hydroxyapatite (Apt-HA) was used for osteoconduction and dual delivery of VEGF and BMP-2. For in vivo bone regeneration evaluation, the grafts (1) Apt-HA + phosphate-buffered saline (PBS), (2) Apt-HA + AM without BMP-2, (3) Apt-HA + BMP-2, and (4) Apt-HA + AM encapsulated with BMP-2 were implanted into rabbit tibial metaphyseal defects. After four weeks, micro-computed tomography (CT), histological, and histomorphometric analyses were performed to evaluate bone regeneration. The Apt-HA + AM with BMP-2 group revealed a significantly higher new bone volume and bone volume/total volume (BV/TV) in both cortical and trabecular bone than the others. Furthermore, as evaluated by histomorphometric analysis, BMP-2 AM exhibited a significantly higher bone formation area than the others, indicating that AM could be used to efficiently deliver BMP-2 through sustained release. Moreover, the combined application of BMP-2-encapsulated Apt-HA + AM may effectively promote bone regeneration.

Bone Morphogenetic Protein-2 Incorporated Beta-Tricalcium Phosphate Enhanced Bone Regeneration of Critical-Sized Bone Defects in Rats

2018 ◽  
Vol 782 ◽  
pp. 283-288 ◽  
Author(s):  
Ling Fei Wei ◽  
Gang Wu ◽  
Li Quan Deng ◽  
Yue Lian Liu
Keyword(s):  
Bone Regeneration ◽  
Bone Morphogenetic Protein ◽  
Tricalcium Phosphate ◽  
Histopathological Examination ◽  
Bone Defects ◽  
Biological Evaluation ◽  
Bone Morphogenetic Protein 2 ◽  
Beta Tricalcium Phosphate ◽  
Morphogenetic Protein ◽  
Autologous Bone

Although preclinical and clinical studies have shown the benefits of bone morphogenetic protein-2 (BMP2) in bone regeneration, there are increasing concerns about its side effects. These are mainly due to the high dosage of BMP2 which is necessary to obtain the desired clinical results. Previously our group has developed a novel controlled-release delivery system; the biomimetic calcium phosphate coating incorporated with BMP2. It can be used at much lower concentrations of BMP2 than those used in the commercially available product and still produce similar biological effects. In this study, we made a primarily biological evaluation of BMP2 incorporated beta-tricalcium phosphate (β-TCP) for bone regeneration in critical-sized bone defects. Critical-sized calvarial defects were created in rats. They were divided into four groups as follows: (1) empty defects (control), (2) defects filled with β-TCP, (3) defects filled with BMP2 incorporated β-TCP, (4) defects filled with autologous bone. Eight weeks after the operation, the efficiency of the materials was evaluated using histology and histomorphometry. Moreover, the safety of the materials was evaluated using routine blood examination, blood biochemistry examination and histopathological examination of viscera. BMP2 incorporated β-TCP demonstrated an efficiency of bone regeneration that was comparable with autologous bone, with the highest levels of new bone formation (38.3±8.4 mm3 versus 30.1±9.9 mm3, p < 0.05). All clinical lab index of blood in these four groups were within the normal range. Moreover, no change related to the treatment was noted in the histopathological examination of viscera. The results from the present study demonstrated that BMP2 incorporated β-TCP could be a promising substitute for autologous bone used for bone regeneration. Future clinical trials and preclinical trials with large animal models are necessary to investigate the safety and efficacy of BMP2 incorporated β-TCP.

scholarly journals Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration

2021 ◽  
Vol 7 (14) ◽  
pp. eabf6654
Author(s):  
Yizhou Zhu ◽  
Hang Liang ◽  
Xiangmei Liu ◽  
Jun Wu ◽  
Cao Yang ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Interleukin 10 ◽  
Bone Morphogenetic Protein 2 ◽  
Interleukin 4 ◽  
Macrophage Phenotype ◽  
Morphogenetic Protein ◽  
Custom Made ◽  
Cellular Behaviors

Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO2 structures were custom made on titanium (Ti) substrates to investigate cellular behaviors of RAW 264.7 macrophages and their immunomodulation on osteogenesis. We found that the reduced scale of honeycomb-like TiO2 structures could significantly activate the anti-inflammatory macrophage phenotype (M2), in which the 90-nanometer sample induced the highest expression level of CD206, interleukin-4, and interleukin-10 and released the highest amount of bone morphogenetic protein-2 among other scales. Afterward, the resulting immune microenvironment favorably triggered osteogenic differentiation of murine mesenchymal stem cells in vitro and subsequent implant-to-bone osteointegration in vivo. Furthermore, transcriptomic analysis revealed that the minimal scale of TiO2 honeycomb–like structure (90 nanometers) facilitated macrophage filopodia formation and up-regulated the Rho family of guanosine triphosphatases (RhoA, Rac1, and CDC42), which reinforced the polarization of macrophages through the activation of the RhoA/Rho–associated protein kinase signaling pathway.

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