Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo

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.

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Preparation and Biological Characteristics of Recombinant Human Bone Morphogenetic Protein-2-Loaded Dextran-co-Gelatin Hydrogel Microspheres, in vitro and in vivo Studies

Pharmacology ◽

10.1159/000088212 ◽

2005 ◽

Vol 75 (3) ◽

pp. 133-144 ◽

Cited By ~ 25

Author(s):

Faming Chen ◽

Zhifen Wu ◽

Qintao Wang ◽

Hong Wu ◽

Yongjie Zhang ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Human Bone ◽

Bone Morphogenetic Protein 2 ◽

In Vivo Studies ◽

Gelatin Hydrogel ◽

Morphogenetic Protein ◽

Human Bone Morphogenetic Protein ◽

Recombinant Human Bone

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Recombinant human bone morphogenetic protein-2 promotes Indian hedgehog-mediated osteo-chondrogenic differentiation of a human chondrocytic cell line in vivo and in vitro

Differentiation ◽

10.1111/j.1432-0436.2004.07201001.x ◽

2004 ◽

Vol 72 (1) ◽

pp. 32-40 ◽

Cited By ~ 6

Author(s):

Yohei Uyama ◽

Kimitoshi Yagami ◽

Masashi Hatori ◽

Saburo Kakuta ◽

Masao Nagumo

Keyword(s):

Cell Line ◽

Bone Morphogenetic Protein ◽

Chondrogenic Differentiation ◽

Bone Morphogenetic Protein 2 ◽

Indian Hedgehog ◽

Morphogenetic Protein ◽

Human Bone Morphogenetic Protein ◽

Recombinant Human Bone

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Demineralized Bone Matrix as a Carrier for Bone Morphogenetic Protein-2: Burst Release Combined with Long-Term Binding and Osteoinductive Activity Evaluated In Vitro and In Vivo

Tissue Engineering Part A ◽

10.1089/ten.tea.2017.0005 ◽

2017 ◽

Vol 23 (23-24) ◽

pp. 1321-1330 ◽

Cited By ~ 18

Author(s):

Elisabeth Huber ◽

Anne-Marie Pobloth ◽

Nicole Bormann ◽

Nicolai Kolarczik ◽

Katharina Schmidt-Bleek ◽

...

Keyword(s):

Bone Morphogenetic Protein ◽

Demineralized Bone Matrix ◽

Bone Matrix ◽

Bone Morphogenetic Protein 2 ◽

Burst Release ◽

Morphogenetic Protein ◽

Demineralized Bone

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Surface Immobilization of TiO2 Nanotubes with Bone Morphogenetic Protein-2 Synergistically Enhances Initial Preosteoblast Adhesion and Osseointegration

BioMed Research International ◽

10.1155/2019/5697250 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Ying Li ◽

Yunjia Song ◽

Aobo Ma ◽

Changyi Li

Keyword(s):

Bone Morphogenetic Protein ◽

Bone Morphogenetic Protein 2 ◽

Surface Immobilization ◽

Implant Surface ◽

Cytoskeleton Organization ◽

Morphogenetic Protein ◽

Human Bone Morphogenetic Protein ◽

Collagen Type 1

Although titanium (Ti) alloys have been widely used as implant materials, the bioinertness of pristine Ti impairs their bioactivity and early osseointegration. In the present work, we prepared TiO2 nanotubes (TNT) layer on the titanium (Ti) surface by anodic oxidation. The anodized surface was functionalized with human bone morphogenetic protein-2 coating to form the hBMP-2/TNT surface. The release behavior of hBMP-2 on the hBMP-2/TNT surface displayed a controlled and sustained pattern, compared to that on the hBMP-2/Ti surface, which showed a rapid release. In vitro cellular activity tests demonstrated that both TNT and hBMP-2/Ti surfaces, particularly the hBMP-2/TNT surface, enhanced adhesion, proliferation, and differentiation of osteoblast cells. Increased cell adhesion, improved cytoskeleton organization, and immunofluorescence staining of vinculin were observed on the modified surfaces. The TNT, hBMP-2/Ti, and hBMP-2/TNT surfaces, especially the hBMP-2/TNT surface, further displayed an upregulated gene expression of adhesion and osteogenic markers vinculin, collagen type 1, osteopontin, and osteocalcin, compared to the pristine Ti surface. In vivo experiments using a rat model demonstrated that the TNT and hBMP-2/Ti surfaces, in particular the hBMP-2/TNT surface, improved osseointegration and showed a superior bone bonding ability compared to Ti. Our study revealed a synergistic role played by TiO2 nanotubes nanotopography and hBMP-2 in promoting initial osteoblast adhesion, proliferation, differentiation, and osseointegration, thus suggesting a promising method for better modifying the implant surface.

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