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 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 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 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.

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.

Preparation, Characterization and In Vitro Release Kinetics of Vancomycin Carried β-TCP/Chitosan Composite Microspheres Used as Bone Tissue Engineering Scaffolds

2012 ◽  
Vol 512-515 ◽  
pp. 1821-1825
Author(s):  
Lin Zhang ◽  
Xue Min Cui ◽  
Qing Feng Zan ◽  
Li Min Dong ◽  
Chen Wang ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Cross Linking ◽  
Tissue Engineering Scaffolds ◽  
Composite Microspheres ◽  
Chitosan Composite ◽  
Vitro Release

A novel microsphere scaffolds composed of chitosan and β-TCP containing vancomycin was designed and prepared. The β-TCP/chitosan composite microspheres were prepared by solid-in-water-in-oil (s/w/o) emulsion cross-linking method with or without pre-cross-linking process. The mode of vancomycin maintaining in the β-TCP/chitosan composite microspheres was detected by Fourier transform infrared spectroscopy (FTIR). The in vitro release curve of vancomycin in simulated body fluid (SBF) was estimated. The results revealed that the pre-cross-linking prepared microspheres possessed higher loading efficiency (LE) and encapsulation efficiency (EE) especially decreasing the previous burst mass of vancomycin in incipient release. These composite microspheres got excellent sphere and well surface roughness in morphology. Vancomycin was encapsulated in composite microspheres through absorption and cross-linking. While in-vitro release curves illustrated that vancomycin release depond on diffusing firstly and then on the degradation ratio later. The microspheres loading with vancomycin would be to restore bone defect, meanwhile to inhibit bacterium proliferation. These bioactive, degradable composite microspheres have potential applications in 3D tissue engineering of bone and other tissues in vitro and in vivo.

scholarly journals DESIGN AND IN VITRO/IN VIVO EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF NATEGLINIDE

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Mohini Sihare ◽  
Rajendra Chouksey
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Release Profile ◽  
Matrix Tablets ◽  
In Vivo Studies ◽  
Release Mechanism ◽  
In Vivo Evaluation

Aim: Nateglinide is a quick acting anti-diabetic medication whose potent activity lasts for a short duration. One of the dangerous side effects of nateglinide administration is rapid hypoglycemia, a condition that needs to be monitored carefully to prevent unnecessary fatalities. The aim of the study was to develop a longer lasting and slower releasing formulation of nateglinide that could be administered just once daily. Methods: Matrix tablets of nateglinide were prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC), eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release patterns were evaluated using in vitro and in vivo studies. Conclusion: Of the seventeen formulated matrix tablets tested, only one formulation labelled HA-2 that contained 15% HPMC K4M demonstrated release profile we had aimed for. Further, swelling studies and scanning electron microscopic analysis confirmed the drug release mechanism of HA-2. The optimized formulation HA-2 was found to be stable at accelerated storage conditions for 3 months with respect to drug content and physical appearance. Mathematical analysis of the release kinetics of HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the sustained drug release profile we had aimed for. Keywords: Hydroxypropylmethylcellulose, Matrix tablets, Nateglinide, Sustained release

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