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.

scholarly journals PLGA-BMP-2 and PLA-17β-Estradiol Microspheres Reinforcing a Composite Hydrogel for Bone Regeneration in Osteoporosis

Pharmaceutics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 648 ◽  
Author(s):  
Patricia García-García ◽  
Ricardo Reyes ◽  
Elisabet Segredo-Morales ◽  
Edgar Pérez-Herrero ◽  
Araceli Delgado ◽  
...  
Keyword(s):  
Release Kinetics ◽  
In Vitro Release ◽  
Bone Morphogenetic Protein 2 ◽  
Poly Lactic Acid ◽  
Core System ◽  
Morphogenetic Protein ◽  
17Β Estradiol ◽  
Second Phases

The controlled release of active substances—bone morphogenetic protein 2 (BMP-2) and 17β-estradiol—is one of the main aspects to be taken into account to successfully regenerate a tissue defect. In this study, BMP-2- and 17β-estradiol-loaded microspheres were combined in a sandwich-like system formed by a hydrogel core composed of chitosan (CHT) collagen, 2-hidroxipropil γ-ciclodextrin (HP-γ-CD), nanoparticles of hydroxyapatite (nano-HAP), and an electrospun mesh shell prepared with two external electrospinning films for the regeneration of a critical bone defect in osteoporotic rats. Microspheres were made with poly-lactide-co-glycolide (PLGA) to encapsulate BMP-2, whereas the different formulations of 17β-estradiol were prepared with poly-lactic acid (PLA) and PLGA. The in vitro and in vivo BMP-2 delivered from the system fitted a biphasic profile. Although the in vivo burst effect was higher than in vitro the second phases (lasted up to 6 weeks) were parallel, the release rate ranged between 55 and 70 ng/day. The in vitro release kinetics of the 17β-estradiol dissolved in the polymeric matrix of the microspheres depended on the partition coefficient. The 17β-estradiol was slowly released from the core system using an aqueous release medium (Deff = 5.58·10−16 ± 9.81·10−17m2s−1) and very fast in MeOH-water (50:50). The hydrogel core system was injectable, and approximately 83% of the loaded dose is uniformly discharged through a 20G needle. The system placed in the defect was easily adapted to the defect shape and after 12 weeks approximately 50% of the defect was refilled by new tissue. None differences were observed between the osteoporotic and non-osteoporotic groups. Despite the role of 17β-estradiol on the bone remodeling process, the obtained results in this study suggest that the observed regeneration was only due to the controlled rate released of BMP-2 from the PLGA microspheres.

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 Bone Regeneration Using a Three-Dimensional Hexahedron Channeled BCP Block Combined with Bone Morphogenic Protein-2 in Rat Calvarial Defects

Materials ◽  
2019 ◽  
Vol 12 (15) ◽  
pp. 2435 ◽  
Author(s):  
So-Yeun Kim ◽  
Eun-Bin Bae ◽  
Jae-Woong Huh ◽  
Jong-Ju Ahn ◽  
Hyun-Young Bae ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Alveolar Bone ◽  
Three Dimensional ◽  
Bone Morphogenetic Protein 2 ◽  
Graft Material ◽  
Implant Placement ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
Calvarial Defects ◽  
Rat Calvarial Defect

It is important to obtain sufficient bone mass before implant placement on alveolar bone, and synthetic bone such as biphasic calcium phosphate (BCP) has been studied to secure this. This study used a BCP block bone with a specific structure of the three-dimensional (3D) hexahedron channel and coating with recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated carboxymethyl cellulose (CMC) was used to examine the enhancement of bone regeneration of this biomaterial in rat calvarial defect. After the preparation of critical-size calvarial defects in fifteen rats, defects were divided into three groups and were implanted with the assigned specimen (n = 5): Boneplant (untreated 3D hexahedron channeled BCP block), Boneplant/CMC (3D hexahedron channeled BCP block coated with CMC), and Boneplant/CMC/BMP (3D hexahedron channeled BCP block coated with CMC containing rhBMP-2). After 4 weeks, the volumetric, histologic, and histometric analyses were conducted to measure the newly formed bone. Histologically, defects in the Boneplant/CMC/BMP group were almost completely filled with new bone compared to the Boneplant and Boneplant/CMC groups. The new bone volume (P < 0.05) and area (P < 0.001) in the Boneplant/CMC/BMP group (20.12% ± 2.17, 33.79% ± 3.66) were much greater than those in the Boneplant (10.77% ± 4.8, 16.48% ± 9.11) and Boneplant/CMC (10.72% ± 3.29, 16.57% ± 8.94) groups, respectively. In conclusion, the 3D hexahedron channeled BCP block adapted rhBMP-2 with carrier CMC showed high possibility as an effective bone graft material.

scholarly journals Sequential Delivery of Dual Growth Factors from Injectable Chitosan-Based Composite Hydrogels

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 365 ◽  
Author(s):  
Qing Min ◽  
Jiaoyan Liu ◽  
Xiaofeng Yu ◽  
Yuchen Zhang ◽  
Jiliang Wu ◽  
...  
Keyword(s):  
Bone Repair ◽  
In Vitro Release ◽  
C2c12 Cells ◽  
Bone Morphogenetic Protein 2 ◽  
Temporal Separation ◽  
Composite Gels ◽  
Sequential Release ◽  
Morphogenetic Protein ◽  
Chemotactic Effect

Local administration of platelet-derived growth factor-BB (PGDF-BB) and bone morphogenetic protein-2 (BMP-2) in a sequential release manner could substantially promote bone healing. To achieve this goal, a delivery system that could sustain the release of PGDF-BB and BMP-2 by way of temporal separation was developed. One type of PGDF-BB-encapsulated alginate microsphere and another type of BMP-2-encapsulated microsphere with a core-shell structure were respectively produced using emulsification methods. These two types of microspheres were then embedded into chitosan/glycerophosphate hydrogel for constructing composite gels. Some of them were found to be injectable at ambient temperature and had thermo-sensitive features near physiological temperature and pH. The optimally formulated composite gels showed the ability to control the release of PGDF-BB and BMP-2 in a sequential fashion in which PDGF-BB was released earlier than BMP-2. In vitro release patterns indicated that the release rates could be significantly regulated by varying the embedded amount of the factor-encapsulated microspheres, which can in turn mediate the temporal separation release interval between PGDF-BB and BMP-2. The released PDGF-BB and BMP-2 were detected to be bioactive based on their respective effects on Balb/c 3T3 and C2C12 cells. These results suggest that the presently developed composite gels have the potential for bone repair by synergistically utilizing the early chemotactic effect of PDGF-BB and the subsequent osteogenic and angiogenic functions of PDGF-BB and BMP-2.

scholarly journals Biocompatible PLGA-Mesoporous Silicon Microspheres for the Controlled Release of BMP-2 for Bone Augmentation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 118 ◽  
Author(s):  
Silvia Minardi ◽  
Joseph S. Fernandez-Moure ◽  
Dongmei Fan ◽  
Matthew B. Murphy ◽  
Iman K. Yazdi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Sustained Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Bone Morphogenetic Protein 2 ◽  
Osteogenic Potential ◽  
Bone Augmentation

Bone morphogenetic protein-2 (BMP-2) has been demonstrated to be one of the most vital osteogenic factors for bone augmentation. However, its uncontrolled administration has been associated with catastrophic side effects, which compromised its clinical use. To overcome these limitations, we aimed at developing a safer controlled and sustained release of BMP-2, utilizing poly(lactic-co-glycolic acid)-multistage vector composite microspheres (PLGA-MSV). The loading and release of BMP-2 from PLGA-MSV and its osteogenic potential in vitro and in vivo was evaluated. BMP-2 in vitro release kinetics was assessed by ELISA assay. It was found that PLGA-MSV achieved a longer and sustained release of BMP-2. Cell cytotoxicity and differentiation were evaluated in vitro by MTT and alkaline phosphatase (ALP) activity assays, respectively, with rat mesenchymal stem cells. The MTT results confirmed that PLGA-MSVs were not toxic to cells. ALP test demonstrated that the bioactivity of BMP-2 released from the PLGA-MSV was preserved, as it allowed for the osteogenic differentiation of rat mesenchymal stem cells, in vitro. The biocompatible, biodegradable, and osteogenic PLGA-MSVs system could be an ideal candidate for the safe use of BMP-2 in orthopedic tissue engineering applications.

scholarly journals The Effect of NELL1 and Bone Morphogenetic Protein-2 on Calvarial Bone Regeneration

2010 ◽  
Vol 68 (2) ◽  
pp. 300-308 ◽  
Author(s):  
Tara Aghaloo ◽  
Catherine M. Cowan ◽  
Xinli Zhang ◽  
Earl Freymiller ◽  
Chia Soo ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Calvarial Bone ◽  
Morphogenetic Protein

Bone Regeneration in the Rat Mandible with Bone Morphogenetic Protein-2: A Comparison of Two Carriers

2005 ◽  
Vol 132 (4) ◽  
pp. 592-597 ◽  
Author(s):  
Oneida A. Arosarena ◽  
Wesley L. Collins
Keyword(s):  
Bone Regeneration ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Proteins ◽  
Calcium Hydroxyapatite ◽  
Bone Substitutes ◽  
Bone Morphogenetic Protein 2 ◽  
Comparable Efficacy ◽  
Sprague Dawley ◽  
Morphogenetic Protein ◽  
Rat Mandible

OBJECTIVE: To compare mandibular bone regeneration with bone morphogenetic protein-2 (BMP-2) delivered with two carriers: a hyaluronic acid polymer (HY), and a collagen carrier complexed with calcium hydroxyapatite and tricalcium phosphate (collagen/HA/TCP). STUDY DESIGN: Defects were created in the bilateral mandibular bodies of 16 Sprague-Dawley rats. The defects were filled with the HY carrier, the HY carrier loaded with BMP-2, the collagen/HA/TCP carrier, or the collagen/HA/TCP carrier loaded with BMP-2. Animals were euthanatized after 6 weeks, and the hemi-mandibles were analyzed histomorphologically. RESULTS: Specimens containing BMP-2 had significantly larger new bone and marrow volumes than control specimens. Specimens in the hyaluronan/BMP-2 group tended to have larger volumes of new bone and osteoid than collagen/HA/TCP/BMP-2 specimens, though these differences were not statistically significant. CONCLUSION: The HY and collagen/HA/TCP carriers had comparable efficacy for bone healing with BMP-2. SIGNIFICANCE: Bone morphogenetic proteins can be delivered with commercially available alloplasts as osteogenic bone substitutes for the repair of craniofacial bone defects. EBM rating: B-2.

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 Cathelicidin LL37 Promotes Osteogenic Differentiation in vitro and Bone Regeneration in vivo

2021 ◽  
Vol 9 ◽  
Author(s):  
Lunhao Li ◽  
Yiyu Peng ◽  
Qingyue Yuan ◽  
Jing Sun ◽  
Ai Zhuang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Antibacterial Properties ◽  
Bone Defects ◽  
Optimum Concentration ◽  
Calvarial Defect ◽  
Defect Model ◽  
Calvarial Bone ◽  
Rat Calvarial Defect

Different types of biomaterials have been used to repair the defect of bony orbit. However, exposure and infections are still critical risks in clinical application. Biomaterials with characteristics of osteogenesis and antibiosis are needed for bone regeneration. In this study, we aimed to characterize the antimicrobial effects of cathelicidin-LL37 and to assess any impacts on osteogenic activity. Furthermore, we attempted to demonstrate the feasibility of LL37 as a potential strategy in the reconstruction of clinical bone defects. Human adipose-derived mesenchyme stem cells (hADSCs) were cultured with different concentrations of LL37 and the optimum concentration for osteogenesis was selected for further in vitro studies. We then evaluated the antibiotic properties of LL37 at the optimum osteogenic concentration. Finally, we estimated the efficiency of a PSeD/hADSCs/LL37 combined scaffold on reconstructing bone defects in the rat calvarial defect model. The osteogenic ability on hADSCs in vitro was shown to be dependent on the concentration of LL37 and reached a peak at 4 μg/ml. The optimum concentration of LL37 showed good antimicrobial properties against Escherichia coli and Staphylococcus anurans. The combination scaffold of PSeD/hADSCs/LL37 showed superior osteogenic properties compared to the PSeD/hADSCs, PSeD, and control groups scaffolds, indicating a strong bone reconstruction effect in the rat calvarial bone defect model. In Conclusion, LL37 was shown to promote osteogenic differentiation in vitro as well as antibacterial properties. The combination of PSeD/hADSCs/LL37 was advantageous in the rat calvarial defect reconstruction model, showing high potential in clinical bone regeneration.

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