Study of PLGA microspheres loaded with pOsx/PEI nanoparticles for repairing bone defects in vivo and in vitro

Background: The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. Materials and Methods: Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. Results: Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. Conclusions: The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects.

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Cartilage Extracellular Matrix Scaffold With Kartogenin-Encapsulated PLGA Microspheres for Cartilage Regeneration

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2020.600103 ◽

2020 ◽

Vol 8 ◽

Author(s):

Yanhong Zhao ◽

Xige Zhao ◽

Rui Zhang ◽

Ying Huang ◽

Yunjie Li ◽

...

Keyword(s):

Extracellular Matrix ◽

Composite Scaffold ◽

Rabbit Model ◽

Cartilage Tissue ◽

Cartilage Defects ◽

Specific Marker ◽

Molecular Compound ◽

Plga Microspheres

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo. Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering.

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The possibility of healing alveolar bone defects with simvastatin thermosensitive gel: in vitro/in vivo evaluation

Drug Design Development and Therapy ◽

10.2147/dddt.s163986 ◽

2018 ◽

Vol Volume 12 ◽

pp. 1997-2003 ◽

Cited By ~ 4

Author(s):

Hong Ruan ◽

Youcheng Yu ◽

Xuehua Guo ◽

Qian Jiang ◽

Ying Luo

Keyword(s):

Alveolar Bone ◽

Bone Defects ◽

In Vivo Evaluation ◽

Thermosensitive Gel

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Custom Repair of Mandibular Bone Defects with 3D Printed Bioceramic Scaffolds

Journal of Dental Research ◽

10.1177/0022034517734846 ◽

2017 ◽

Vol 97 (1) ◽

pp. 68-76 ◽

Cited By ~ 36

Author(s):

H. Shao ◽

M. Sun ◽

F. Zhang ◽

A. Liu ◽

Y. He ◽

...

Keyword(s):

Weight Loss ◽

Alveolar Bone ◽

Bone Defects ◽

Linear Shrinkage ◽

Tris Buffer ◽

Bone Tissue Regeneration ◽

3 Dimensional ◽

Flexural Resistance

Implanting artificial biomaterial implants into alveolar bone defects with individual shape and appropriate mechanical strength is still a challenge. In this study, bioceramic scaffolds, which can precisely match the mandibular defects in macro and micro, were manufactured by the 3-dimensional (3D) printing technique according to the computed tomography (CT) image. To evaluate the stimulatory effect of the material substrate on bone tissue regeneration in situ in a rabbit mandibular alveolar bone defect model, implants made with the newly developed, mechanically strong ~10% Mg-substituted wollastonite (Ca90%Mg10%SiO3; CSi-Mg10) were fabricated, implanted into the bone defects, and compared with implants made with the typical Ca-phosphate and Ca-silicate porous bioceramics, such as β-tricalcium phosphate (TCP), wollastonite (CaSiO3; CSi), and bredigite (Bred). The initial physicochemical tests indicated that although the CSi-Mg10 scaffolds had the largest pore dimension, they had the lowest porosity mainly due to the significant linear shrinkage of the scaffolds during sintering. Compared with the sparingly dissolvable TCP scaffolds (~2% weight loss) and superfast dissolvable (in Tris buffer within 6 wk) pure CSi and Bred scaffolds (~12% and ~14% weight loss, respectively), the CSi-Mg10 exhibited a mild in vitro biodissolution and moderate weight loss of ~7%. In addition, the CSi-Mg10 scaffolds showed a considerable initial flexural strength (31 MPa) and maintained very high flexural resistance during soaking in Tris buffer. The in vivo results revealed that the CSi-Mg10 scaffolds have markedly higher osteogenic capability than those on the TCP, CSi, and Bred scaffolds after 16 wk. These results suggest a promising potential application of customized CSi-Mg10 3D robocast scaffolds in the clinic, especially for repair of alveolar bone defects.

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Development of Level A in vitro-in vivo correlations for peptide loaded PLGA microspheres

Journal of Controlled Release ◽

10.1016/j.jconrel.2019.07.013 ◽

2019 ◽

Vol 308 ◽

pp. 1-13 ◽

Cited By ~ 11

Author(s):

Janki V. Andhariya ◽

Rajan Jog ◽

Jie Shen ◽

Stephanie Choi ◽

Yan Wang ◽

...

Keyword(s):

Plga Microspheres

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Improved Bioactivity of 3D Printed Porous Titanium Alloy Scaffold with Chitosan/Magnesium-Calcium Silicate Composite for Orthopaedic Applications

Materials ◽

10.3390/ma12020203 ◽

2019 ◽

Vol 12 (2) ◽

pp. 203 ◽

Cited By ~ 18

Author(s):

Chun-Hao Tsai ◽

Chih-Hung Hung ◽

Che-Nan Kuo ◽

Cheng-Yu Chen ◽

Yu-Ning Peng ◽

...

Keyword(s):

Mechanical Properties ◽

Calcium Silicate ◽

Cell Attachment ◽

Three Dimensional ◽

Bone Defects ◽

Metal Alloys ◽

Potential Candidate ◽

Natural Bone

Recently, cases of bone defects have been increasing incrementally. Thus, repair or replacement of bone defects is gradually becoming a huge problem for orthopaedic surgeons. Three-dimensional (3D) scaffolds have since emerged as a potential candidate for bone replacement, of which titanium (Ti) alloys are one of the most promising candidates among the metal alloys due to their low cytotoxicity and mechanical properties. However, bioactivity remains a problem for metal alloys, which can be enhanced using simple immersion techniques to coat bioactive compounds onto the surface of Ti–6Al–4V scaffolds. In our study, we fabricated magnesium-calcium silicate (Mg–CS) and chitosan (CH) compounds onto Ti–6Al–4V scaffolds. Characterization of these surface-modified scaffolds involved an assessment of physicochemical properties as well as mechanical testing. Adhesion, proliferation, and growth of human Wharton’s Jelly mesenchymal stem cells (WJMSCs) were assessed in vitro. In addition, the cell attachment morphology was examined using scanning electron microscopy to assess adhesion qualities. Osteogenic and mineralization assays were conducted to assess osteogenic expression. In conclusion, the Mg–CS/CH coated Ti–6Al–4V scaffolds were able to exhibit and retain pore sizes and their original morphologies and architectures, which significantly affected subsequent hard tissue regeneration. In addition, the surface was shown to be hydrophilic after modification and showed mechanical strength comparable to natural bone. Not only were our modified scaffolds able to match the mechanical properties of natural bone, it was also found that such modifications enhanced cellular behavior such as adhesion, proliferation, and differentiation, which led to enhanced osteogenesis and mineralization downstream. In vivo results indicated that Mg–CS/CH coated Ti–6Al–4V enhances the bone regeneration and ingrowth at the critical size bone defects of rabbits. These results indicated that the proposed Mg–CS/CH coated Ti–6Al–4V scaffolds exhibited a favorable, inducive micro-environment that could serve as a promising modification for future bone tissue engineering scaffolds.

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Sophoridine-loaded PLGA microspheres for lung targeting: preparation, in vitro, and in vivo evaluation

Drug Delivery ◽

10.1080/10717544.2016.1223210 ◽

2016 ◽

Vol 23 (9) ◽

pp. 3674-3680 ◽

Cited By ~ 7

Author(s):

Wenping Wang ◽

Yaqin Cai ◽

Guangxing Zhang ◽

Yanhua Liu ◽

Hong Sui ◽

...

Keyword(s):

Plga Microspheres ◽

In Vivo Evaluation ◽

Lung Targeting

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Synchronic release of two hormonal contraceptives for about one month from the PLGA microspheres: In vitro and in vivo studies

Journal of Controlled Release ◽

10.1016/j.jconrel.2008.04.022 ◽

2008 ◽

Vol 129 (3) ◽

pp. 192-199 ◽

Cited By ~ 38

Author(s):

Yi Sun ◽

JianCheng Wang ◽

Xuan Zhang ◽

ZhiJun Zhang ◽

Yan Zheng ◽

...

Keyword(s):

In Vivo Studies ◽

Hormonal Contraceptives ◽

Plga Microspheres

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In Vitro-In Vivo Relationship of Amorphous Insoluble API (Progesterone) in PLGA Microspheres

Pharmaceutical Research ◽

10.1007/s11095-017-2258-4 ◽

2017 ◽

Vol 34 (12) ◽

pp. 2787-2797 ◽

Cited By ~ 6

Author(s):

Chenguang Pu ◽

Qiao Wang ◽

Hongjuan Zhang ◽

Jingxin Gou ◽

Yuting Guo ◽

...

Keyword(s):

Plga Microspheres ◽

Relationship Of

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Development of Risperidone PLGA Microspheres

Journal of Drug Delivery ◽

10.1155/2014/620464 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 21

Author(s):

Susan D’Souza ◽

Jabar A. Faraj ◽

Stefano Giovagnoli ◽

Patrick P. DeLuca

Keyword(s):

Steady State ◽

Sustained Release ◽

Sustained Delivery ◽

Plga Microspheres ◽

Sprague Dawley ◽

Multiple Dosing ◽

Duration Of Action ◽

Sprague Dawley Rats

The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50 : 50 and 75 : 25) were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40 mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50 : 50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75 : 25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug.

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