Biological Activity of rhBMP-2 Released From PLGA Microspheres

2000 ◽  
Vol 122 (3) ◽  
pp. 289-292 ◽  
Author(s):  
J. B. Oldham, ◽  
L. Lu, ◽  
X. Zhu, and ◽  
B. D. Porter ◽  
T. E. Hefferan ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Body Fluids ◽  
Bone Morphogenetic Protein 2 ◽  
In Vitro Tests ◽  
Plga Microspheres ◽  
Skeletal Tissue ◽  
Morphogenetic Protein ◽  
Biodegradable Poly ◽  
Simulated Body Fluids

Human recombinant bone morphogenetic protein-2 (rhBMP-2) has been proven effective in stimulating the regeneration of bone in both skeletal and extraskeletal locations. Through encapsulation within, and release from, biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) microspheres, a proven vehicle for sustained delivery of various proteins, the local concentrations of rhBMP-2 could be maintained at optimal levels to stimulate bone regeneration and remodeling at the site of healing in diverse clinical settings. Thus the purpose of this work was to investigate the encapsulation of rhBMP-2 in PLGA microspheres and its biologic activity upon release. Using in vitro tests in simulated body fluids, the effect of rhBMP-2 released from PLGA microspheres upon osteoblast cell cultures was found to be statistically similar to the effect produced by positive controls consisting of nonencapsulated aqueous rhBMP-2 in simulated body fluids. This clarifies an important step in skeletal tissue engineering strategies aimed at the use of encapsulated rhBMP-2 to stimulate bone regeneration and remodeling. [S0148-0731(00)01303-0]

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 Efficacy of rhBMP-2 Loaded PCL/β-TCP/bdECM Scaffold Fabricated by 3D Printing Technology on Bone Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Eun-Bin Bae ◽  
Keun-Ho Park ◽  
Jin-Hyung Shim ◽  
Ho-Yun Chung ◽  
Jae-Won Choi ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Bone Morphogenetic Protein 2 ◽  
Sprague Dawley ◽  
Calvarial Bone ◽  
Decellularized Extracellular Matrix ◽  
Morphogenetic Protein ◽  
Rat Calvarial Defect

This study was undertaken to evaluate the effect of 3D printed polycaprolactone (PCL)/β-tricalcium phosphate (β-TCP) scaffold containing bone demineralized and decellularized extracellular matrix (bdECM) and human recombinant bone morphogenetic protein-2 (rhBMP-2) on bone regeneration. Scaffolds were divided into PCL/β-TCP, PCL/β-TCP/bdECM, and PCL/β-TCP/bdECM/BMP groups. In vitro release kinetics of rhBMP-2 were determined with respect to cell proliferation and osteogenic differentiation. These three reconstructive materials were implanted into 8 mm diameter calvarial bone defect in male Sprague-Dawley rats. Animals were sacrificed four weeks after implantation for micro-CT, histologic, and histomorphometric analyses. The findings obtained were used to calculate new bone volumes (mm3) and new bone areas (%). Excellent cell bioactivity was observed in the PCL/β-TCP/bdECM and PCL/β-TCP/bdECM/BMP groups, and new bone volume and area were significantly higher in the PCL/β-TCP/bdECM/BMP group than in the other groups (p<.05). Within the limitations of this study, bdECM printed PCL/β-TCP scaffolds can reproduce microenvironment for cells and promote adhering and proliferating the cells onto scaffolds. Furthermore, in the rat calvarial defect model, the scaffold which printed rhBMP-2 loaded bdECM stably carries rhBMP-2 and enhances bone regeneration confirming the possibility of bdECM as rhBMP-2 carrier.

Combined Structural Investigations of Bioactive Silicate Glasses

2007 ◽  
Vol 361-363 ◽  
pp. 257-260 ◽  
Author(s):  
Frank Malz ◽  
H. Aguiar ◽  
Eugenio Luís Solla ◽  
Julia Serra ◽  
Pio González ◽  
...  
Keyword(s):  
Silicate Glass ◽  
Body Fluids ◽  
Silicate Glasses ◽  
In Vitro Tests ◽  
Structural Investigations ◽  
Structural Characterisation ◽  
Simulated Body Fluids

The results of a combined structural characterisation (XRD, IR, NMR, SEM, TEM) of a phosphate containing Mg-Ca silicate and a phosphate containing Na-Ca silicate glass samples are presented. The structural results are also compared with in vitro tests carried out in simulated body fluids for checking bioactivity.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

BMP2 Is Required for Postnatal Maintenance of Osteochondral Tissues of the Temporomandibular Joint

Cartilage ◽  
2020 ◽  
pp. 194760352098015
Author(s):  
Mara H. O’Brien ◽  
Eliane H. Dutra ◽  
Shivam Mehta ◽  
Po-Jung Chen ◽  
Sumit Yadav
Keyword(s):  
Age Groups ◽  
Mandibular Condyle ◽  
Bone Morphogenetic Protein 2 ◽  
Matrix Synthesis ◽  
Cartilage Growth ◽  
Chondrocyte Proliferation ◽  
Conditional Deletion ◽  
Morphogenetic Protein

Objective Bone morphogenetic protein 2 (BMP2) plays important roles in cartilage growth and development. Paradoxically, elevated levels of BMP2 leads to hypertrophic differentiation and osteoarthritis of cartilage. We examined the in vivo loss of BMP2 in cells expressing aggrecan of the mandibular condyle and knee. Design Three-week-old BMP2 flox/flox- CreER-positive mice and their Cre-negative littermates were treated with tamoxifen and raised until 3 or 6 months. We also investigated the direct effects of BMP2 on chondrocytes in vitro. Cells from the mandibular condyle of mice were treated with recombinant human BMP2 (rhBMP2) or rhNoggin (inhibitor of BMP2 signaling). Results Conditional deletion of BMP2 caused breakage of the cartilage integrity in the mandibular condyle of mice from both age groups, accompanied by a decrease in cartilage thickness, matrix synthesis, mineralization, chondrocyte proliferation, and increased expression of degeneration markers, while the effects at articular cartilage were not significant. In vitro results revealed that rhBMP2 increased chondrocyte proliferation, mineralization, and differentiation, while noggin induced opposite effects. Conclusions In conclusion, BMP2 is essential for postnatal maintenance of the osteochondral tissues of the mandibular condyle.

Design of hydroxyapatite bioceramics with micro-/nano-topographies to regulate the osteogenic activities of bone morphogenetic protein-2 and bone marrow stromal cells

Nanoscale ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 7284-7300 ◽  
Author(s):  
Xiangfeng Li ◽  
Minjun Liu ◽  
Fuying Chen ◽  
Yuyi Wang ◽  
Menglu Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Regeneration ◽  
Bone Morphogenetic Protein ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Bone Morphogenetic Protein 2 ◽  
Natural Bone ◽  
Morphogenetic Protein ◽  
Bone Apatite

Biomimicking the nanostructure of natural bone apatite to enhance the bioactivity of hydroxyapatite (HA) biomaterials is an eternal topic in the bone regeneration field.

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