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Nanoscale. 2019 Dec 28;11(48):23423-23437. doi: 10.1039/c9nr07170a. Epub 2019 Dec 4.

Synergistic osteogenesis promoted by magnetically actuated nano-mechanical stimuli.
Hao L 1, Li L 2, Wang P 1, Wang Z 3, Shi X 3, Guo M 3, Zhang P 1.
 
Author information
1 Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, P. R. China. zhangpb@ciac.ac.cn guomin@ciac.ac.cn and School of Applied Chemistry and Engineering, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China.
2 School of Applied Chemistry and Engineering, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026, P. R. China.
3 University of Chinese Academy of Sciences, Beijing 100039, PR China.
 

Abstract
Functional biomaterials with magnetic properties are considerably useful for regulating cell behavior and promoting bone regeneration. And the combination of such biomaterials with physical environmental cues (such as magnetic fields and mechanical stress) might be more favorable for the regulation of cell function. This study is aimed at investigating the combined effects of magnetically responsive materials and a static magnetic field (SMF) on the osteogenic differentiation of osteoblasts and the potential mechanism involved. In this study, oleic acid modified iron oxide nanoparticles (IO-OA NPs) were utilized to generate homogeneous magnetic nanocomposites with poly(lactide-co-glycolide) (PLGA) used as the base and to enhance the mechanical properties of the composites. In vitro experimental results show that in the presence of an external SMF, cell attachment and osteogenic differentiation were significantly improved using the IO-OA/PLGA composites, as indicated by enhanced alkaline phosphatase (ALP) activity, increased mineralized nodule formation, and upregulated bone-associated gene expression (ALP, OCN, and BMP2), in a dose- and time-dependent manner. Furthermore, the upregulated expression levels of piezo-type mechanosensitive ion channel component 1 (Piezo1), a key receptor for sensing mechanical stimuli, implied that the synergistically enhanced osteogenic differentiation was mainly caused as a result of the mechanical stimuli. Such magnetically actuated mechanical stimuli were induced through the nano-deformation of the magnetic substrate under a SMF, which was directly characterized via in situ scanning using atomic force microscopy (AFM). This study demonstrates that magnetically actuated nano-mechanical stimuli may underpin the synergistic effects of magnetic composites and magnetic stimuli to enhance osteogenic differentiation, and they could form the basis of a potential strategy to accelerate bone formation for bone tissue engineering and regenerative medicine applications.

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ACS Appl Mater Interfaces. 2016 Oct 12;8(40):26559-26569. Epub 2016 Sep 30.
Improved Cell Adhesion and Osteogenesis of op-HA/PLGA Composite by Poly(dopamine)-Assisted Immobilization of Collagen Mimetic Peptide and Osteogenic Growth Peptide.

Wang Z 1, Chen L 2, Wang Y 1, Chen X 1, Zhang P 1.

Author information
 1 Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, PR China.
 2 School of Pharmaceutical Sciences, Jilin University , Changchun 130021, PR China.


Abstract
A nanocomposite of poly(lactide-co-glycolide) (PLGA) and hydroxyapatite (HA) with a different grafting ratio of l-lactic acid oligomer (op-HA) showed better interface compatibility, mineralization, and osteogenetic abilities. However, surface modification of the composite is crucial to improve the osteointegration for bone regeneration. In this study, a biomimetic process via poly(dopamine) coating was utilized to prepare functional substrate surfaces with immobilized bioactive peptides that efficiently regulate the osteogenic differentiation of preosteoblasts (MC3T3-E1). Our study demonstrated that incorporation of collagen mimetic peptide significantly enhanced cell adhesion and proliferation. The immobilization of osteogenic growth peptide induced the osteodifferentiation of cells, as indicated by the alkaline phosphate activity test, quantitative real-time polymerase chain reaction analysis, and immunofluorescence staining. The mineralization on the peptide-modified substrates was also enhanced greatly. Findings from this study revealed that this biofunctionalized layer on op-HA/PLGA substrate improved mineralization and osteogenic differentiation. In conclusion, the surface modification strategy with bioactive peptides shows potential to enhance the osteointegration of bone implants.

 

KEYWORDS:
adhesion; collagen mimetic peptide; composite; dopamine; osteogenesis; osteogenic growth peptide

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Angew Chem Int Ed Engl. 2016 Jul 6. doi: 10.1002/anie.201603155.

 A Bioorthogonal Approach for the Preparationof a Titanium-Binding Insulin-like Growth-Factor-1 Derivative by using Tyrosinase.

 Zhang C1,2,3, Miyatake H1, Wang Y3, Inaba T4, Wang Y2, Zhang P3, Ito Y5,6.

 Author information

 1 Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan.

 2 School of Pharmaceutical Sciences, Jilin University, No. 1266 Fujin Road, Changchun, Jilin, 130021, P.R. China.

 3 Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun, Jilin, 130022, P.R. China.

 4 Lipid Biology Laboratory, RIKEN, Japan.

5Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan. y-ito@riken.jp.

6Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan. y-ito@riken.jp.

 

Abstract

 The generation of metal surfaces with biological properties, such as cell-growth-enhancing and differentiation-inducing abilities, could be potentially exciting for the development of functional materials for use in humans, including artificial dental implants and joint replacements. However, currently the immobilization of proteins on the surfaces of the metals are limited. In this study, we have used a mussel-inspired bioorthogonal approach to design a 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth-factor-1 using a combination of recombinant DNA technology and tyrosinase treatment for the surface modification of titanium. The modified growth factor prepared in this study exhibited strong binding affinity to titanium, and significantly enhanced the growth of NIH3T3 cells on the surface of titanium.

KEYWORDS:

bioorthogonal chemistry; cell growth; growth factors; titanium; tyrosinase

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Biomaterials. 2009 Jan;30(1):58-70. doi: 10.1016/j.biomaterials.2008.08.041. Epub 2008 Oct 5.

In vivo mineralization and osteogenesis of nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with poly(L-lactide).

Zhang P1, Hong Z, Yu T, Chen X, Jing X.


Author information

1State Key Laboratory of Polymer Physics and chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

Abstract

Nanocomposite of hydroxyapatite (HAP) surface-grafted with poly(l-lactide) (PLLA) (g-HAP) shows a wide application for bone fixation materials due to its improved interface compatibility, mechanical property and biocompatibility in our previous study. In this paper, a 3-D porous scaffold of g-HAP/poly(lactide-co-glycolide) (PLGA) was fabricated using the solvent casting/particulate leaching method to investigate its applications in bone replacement and tissue engineering. The composite of un-grafted HAP/PLGA and neat PLGA were used as controls. Their in vivo mineralization and osteogenesis were investigated by intramuscular implantation and replacement for repairing radius defects of rabbits. After surface modification, more uniform distribution of g-HAP particles but a lower calcium exposure on the surface of g-HAP/PLGA was observed. Intramuscular implantation study showed that the scaffold of g-HAP/PLGA was more stable than that of PLGA, and exhibited similar mineralization and biodegradability to HAP/PLGA at the 12-20 weeks post-surgery. The implantation study for repairing critical radius defects showed that the scaffold of g-HAP/PLGA exhibited rapid and strong mineralization and osteoconductivity, and the incorporation of BMP-2 could enhance the osteogenic process of the composite implant. The new bone formation with the intact structure of a long bone was guided by the implant of g-HAP/PLGA.


PMID: 18838160 DOI: 10.1016/j.biomaterials.2008.08.041

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Adv Healthc Mater. 2016 Jul 6. doi: 10.1002/adhm.201600249.

In Vivo MRI and X-Ray Bifunctional Imaging of Polymeric Composite Supplemented with GdPO4 ·H2 O Nanobundles for Tracing Bone Implant and Bone Regeneration.

Huang J 1,2, Lv Z 3, Wang Y 2, Wang Z 2, Gao T 2,4, Zhang N 5, Guo M 2, Zou H 1, Zhang P 2.


Author information

1College of Chemistry, Jilin University, Changchun, 130012, P. R. China.
2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
3China-Japan Union Hospital, Jilin University, Changchun, 130021, P. R. China.
4School of Public Health, Jilin University, Changchun, 130021, P. R. China.
5Department of Foot and Ankle Surgery, The Second Hospital of Shandong University, Jinan, 250000, P. R. China.

Abstract

Homogeneous and monodisperse GdPO4 ·H2 O nanobundles are successfully synthesized via a solvothermal method. Then, GdPO4 ·H2 O are incorporated into the composite of hydroxyapatite and poly(lactic-co-glycolic acid) to obtain a biodegradable and traceable bone implant. After implanted, the GdPO4 ·H2 O/HA/PLGA implant and the newly formed bone can be easily traced and observed through the combination of magnetic resonance imaging and X-ray imaging.


KEYWORDS:

MR imaging; bone repair; gadolinium phosphate; hydroxyapatite; poly(lactic-co-glycolic acid); radiography

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Macromol Biosci. 2015 Aug;15(8):1070-80. doi: 10.1002/mabi.201500069. Epub 2015 May 7.

Biodegradable Microcarriers of Poly(Lactide-co-Glycolide) and Nano-Hydroxyapatite Decorated with IGF-1 via Polydopamine Coating for Enhancing Cell Proliferation and Osteogenic Differentiation.

Gao T 1,2, Zhang N 3, Wang Z 2, Wang Y 2, Liu Y 4, Ito Y 5,6, Zhang P 7.

Author information

1School of Public Health, Jilin University, Changchun, 130021, P. R. China.
2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
3Department of Foot and Ankle Surgery, The Second Hospital of Shandong University, Jinan, 250000, P. R. China.
4School of Public Health, Jilin University, Changchun, 130021, P. R. China. liuya@jlu.edu.cn.
5Nano Medical Engineering Laboratory, RIKEN, 2-1-Hirosawa, Wako, Saitama, 351-0198, Japan.
6Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Materials Science, 2-1-Hirosawa, Wako, Saitama, 351-0198, Japan.
7Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. zhangpb@ciac.ac.cn.


Abstract

In this study, insulin-like growth factor 1 (IGF-1) was successfully immobilized on the poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and pure PLGA microcarriers via polydopamine (pDA). The results demonstrated that the pDA layer facilitated simple and highly efficient immobilization of peptides on the microcarriers within 20 min. Mouse adipose-derived stem cells (ADSCs) attachment and proliferation on IGF-1-immobilized microcarriers were much higher than non-immobilized ones. More importantly, the IGF-1-immobilized PLGA/HA microcarriers significantly increased alkaline phosphatase (ALP) activity and expression of osteogenesis-related genes of ADSCs. Therefore, it is considered that the IGF-1-decorated PLGA/HA microcarriers will be of great value in the bone tissue engineering.


 

KEYWORDS:

IGF-1; biodegradable PLGA microcarriers; bone tissue engineering; nano-hydroxyapatite; polydopamine

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Biomacromolecules. 2011 Jul 11;12(7):2667-80. doi: 10.1021/bm2004725. Epub 2011 Jun 15.

RGD-conjugated copolymer incorporated into composite of poly(lactide-co-glycotide) and poly(L-lactide)-grafted nanohydroxyapatite for bone tissue engineering.

Zhang P 1, Wu H, Wu H, Lù Z, Deng C, Hong Z, Jing X, Chen X.

Author information

1Key Laboratory of Polymer Ecobiomaterials, State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Graduate School of Chinese Academy of Sciences, Changchun 130022, People's Republic of China.

Abstract

Various surface modification methods of RGD (Arg-Gly-Asp) peptides on biomaterials have been developed to improve cell adhesion. This study aimed to examine a RGD-conjugated copolymer RGD/MPEG-PLA-PBLG (RGD-copolymer) for its ability to promote bone regeneration by mixing it with the composite of poly(lactide-co-glycotide) (PLGA) and hydroxyapatite nanoparticles surface-grafted with poly(L-lactide) (g-HAP). The porous scaffolds were prepared using solvent casting/particulate leaching method and grafted to repair the rabbit radius defects after seeding with autologous bone marrow mesenchymal cells (MSCs) of rabbits. After incorporation of RGD-copolymer, there were no significant influences on scaffold's porosity and pore size. Nitrogen of RGD peptide, and calcium and phosphor of g-HAP could be exposed on the surface of the scaffold simultaneously. Although the cell viability of its leaching liquid was 92% that was lower than g-HAP/PLGA, its cell adhesion and growth of 3T3 and osteoblasts were promoted significantly. The greatest increment in cell adhesion ratios (131.2-157.1% higher than g-HAP/PLGA) was observed when its contents were 0.1-1 wt % but only at 0.5 h after cell seeding. All the defects repaired with the implants were bridged after 24 weeks postsurgery, but the RGD-copolymer contained composite had larger new bone formation and better fusion interface. The composites containing RGD-copolymer enhanced bone ingrowth but presented more woven bones than others. The combined application of RGD-copolymer and bone morphological protein 2 (BMP-2) exhibited the best bone healing quality and was recommended as an optimal strategy for the use of RGD peptides.

 

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PLoS One. 2016 May 5;11(5):e0154924. doi: 10.1371/journal.pone.0154924. eCollection 2016.

Modulation of Osteogenesis in MC3T3-E1 Cells by Different Frequency Electrical Stimulation.

Wang Y 1,2, Cui H 1, Wu Z 1, Wu N 1, Wang Z 1, Chen X 1, Wei Y 3, Zhang P 1.


Author information

1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, People's Republic of China.
2University of Chinese Academy of Sciences, Beijing, People's Republic of China.
3Department of Chemistry, Tsinghua University, Beijing, People's Republic of China.

Abstract

Electrical stimulation (ES) is therapeutic to many bone diseases, from promoting fracture regeneration to orthopedic intervention. The application of ES offers substantial therapeutic potential, while optimal ES parameters and the underlying mechanisms responsible for the positive clinical impact are poorly understood. In this study, we assembled an ES cell culture and monitoring device. Mc-3T3-E1 cells were subjected to different frequency to investigate the effect of osteogenesis. Cell proliferation, DNA synthesis, the mRNA levels of osteosis-related genes, the activity of alkaline phosphatase (ALP), and intracellular concentration of Ca2+ were thoroughly evaluated. We found that 100 Hz could up-regulate the mRNA levels of collagen I, collagen II and Runx2. On the contrary, ES could down-regulate the mRNA levels of osteopontin (OPN). ALP activity assay and Fast Blue RR salt stain showed that 100 Hz could accelerate cells differentiation. Compared to the control group, 100 Hz could promote cell proliferation. Furthermore, 1 Hz to 10 Hz could improve calcium deposition in the intracellular matrix. Overall, these results indicate that 100Hz ES exhibits superior potentialities in osteogenesis, which should be beneficial for the clinical applications of ES for the treatment of bone diseases.

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Sci Rep. 2016 Feb 9;6:20770. doi: 10.1038/srep20770.

A comparative study on the in vivo degradation of poly(L-lactide) based composite implants for bone fracture fixation.

Wang Z 1,2, Wang Y 1, Ito Y 3,4, Zhang P 1, Chen X 1.


Author information

1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
2University of Chinese Academy of Sciences, Beijing 100039, PR China.
3Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 Japan.
4Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, 2-1 Hirosawa, Wako, Saitama 351-0198 Japan.

Abstract

Composite of nano-hydroxyapatite (n-HAP) surface grafted with poly(L-lactide) (PLLA) (g-HAP) showed improved interface compatibility and mechanical property for bone fracture fixation. In this paper, in vivo degradation of n-HAP/PLLA and g-HAP/PLLA composite implants was investigated. The mechanical properties, molecular weight, thermal properties as well as crystallinity of the implants were measured. The bending strength of the n- and g-HAP/PLLA composites showed a marked reduction from an initial value of 102 and 114 MPa to 33 and 24 MPa at 36 weeks, respectively. While the bending strength of PLLA was maintained at 80 MPa at 36 weeks compared with initial value of 107 MPa. The impact strength increased over time especially for the composites. Significant differences in the molecular weight were seen among all the materials and g-HAP/PLLA appeared the fastest rate of decrease than others. Environmental scanning electron microscope (ESEM) results demonstrated that an apparently porous morphology full of pores and hollows were formed in the composites. The results indicated that the in vivo degradation of PLLA could be accelerated by the g-HAP nanoparticles. It implied that g-HAP/PLLA composites might be a candidate for human non-load bearing bone fracture fixation which needs high initial strength and fast degradation rate.

 

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Biomacromolecules. 2016 Mar 14;17(3):818-29. doi: 10.1021/acs.biomac.5b01543.

Enhanced in Vitro Mineralization and in Vivo Osteogenesis of Composite Scaffolds through Controlled Surface Grafting of L-Lactic Acid Oligomer on Nanohydroxyapatite.

Wang Z 1,2, Xu Y 3, Wang Y 1, Ito Y 4, Zhang P 1, Chen X 1.


Author information

1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, PR China.
2University of Chinese Academy of Sciences, Beijing 100039, PR China.
3Department of Medical Cosmetology, The First Affiliated Hospital of Xiamen University , Xiamen 361003, PR China.
4Nano Medical Engineering Laboratory and ⊥Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 Japan

Abstract

Nanocomposite of hydroxyapatite (HA) surface grafted with L-lactic acid oligomer (LAc oligomer) (op-HA) showed improved interface compatibility, mechanical property, and biocompatibility in our previous study. In this paper, composite scaffolds of op-HA with controlled grafting different amounts of LAc oligomer (1.1, 5.2, and 9.1 wt %) were fabricated and implanted to repair rabbit radius defects. The dispersion of op-HA nanoparticles was more uniform than n-HA in chloroform and nanocomposites scaffold. Calcium and phosphorus exposure, in vitro biomineralization ability, and cell proliferation were much higher in the op-HA1.1 wt %/PLGA scaffolds than the other groups. The osteodifferentiation and bone fusion in animal tests were significantly enhanced for op-HA5.2 wt %/PLGA scaffolds. The results indicated that the grafted LAc oligomer of 5.2 or 9.1 wt %, which formed a barrier layer on the HA surface, prevented the exposure of nucleation sites. The shielded nucleation sites of op-HA particles (5.2 wt %) might be easily exposed as the grafted LAc oligomer was decomposed easily by enzyme systems in vivo. Findings from this study have revealed that grafting 1.1 wt % amount of LAc oligomer on hydroxyapatite could improve in vitro mineralization, and 5.2 wt % could promote in vivo osteogenesis capacity of composite scaffolds.

 

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Regen Biomater. 2015 Jun;2(2):153-8. doi: 10.1093/rb/rbv004. Epub 2015 May 25.

Important topics in the future of biomaterials and stem cells for bone tissue engineering: Comments from the participants of the International Symposium on Recent Trend of Biomaterials and Stem Cells for Bone Tissue Engineering at Changchun, China.

Zhang P 1, Zhu Q 1.

Author information

1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun, 130022, P.R.

2 China and Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, 130033, P.R. China.

Fulltext

Fundamental and clinical experts from Japan, Korea and China, warmly gathered on the beautiful ice and snow city—Changchun, the capital of Jilin Province, China—during 23-26 January 2015, to present their research findings and participated in discussion relating to progress in biomaterials, stem cells and bone tissue engineering. The International Symposium on Recent Trend of Biomaterials and Stem Cells for Bone Tissue Engineering (BTE 2015) was hosted by the Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, and co-organized by the Department of Orthopaedics, China-Japan Union Hospital, Jilin University. It provided a new platform of academic and technological communication for fundamental researchers and orthopedic surgeons to express their diverse ideas and inspiring new cooperation.
...

 

 Yoshihiro Ito, Japan

Inn-Kyu Kang, South Korea

Guoping Chen, Japan

Byung-Soo Kim, South Korea

 

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Acta Biomater. 2009 Sep;5(7):2680-92. doi: 10.1016/j.actbio.2009.03.024. Epub 2009 Mar 27.

The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with L-lactic acid oligomer for bone repair.

Cui Y1, Liu Y, Cui Y, Jing X, Zhang P, Chen X.

Author information

1State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.

Abstract

Nanohydroxyapatite (op-HA) surface-modified with l-lactic acid oligomer (LAc oligomer) was prepared by LAc oligomer grafted onto the hydroxyapatite (HA) surface. The nanocomposite of op-HA/PLGA with different op-HA contents of 5, 10, 20 and 40wt.% in the composite was fabricated into three-dimensional scaffolds by the melt-molding and particulate leaching methods. PLGA and the nanocomposite of HA/PLGA with 10wt.% of ungrafted hydroxyapatite were used as the controls. The scaffolds were highly porous with evenly distributed and interconnected pore structures, and the porosity wasaround 90%. Besides the macropores of 100-300microm created by the leaching of NaCl particles, the micropores (1-50microm) in the pore walls increased with increasing content of op-HA in the composites of op-HA/PLGA. The op-HA particles could disperse more uniformly than those of pure HA in PLGA matrix. The 20wt.% op-HA/PLGA sample exhibited the maximum mechanical strength, including bending strength (4.14MPa) and compressive strength (2.31MPa). The cell viability and the areas of the attached osteoblasts on the films of 10wt.% op-HA/PLGA and 20wt.% op-HA/PLGA were evidently higher than those on the other composites. For the animal test, there was rapid healing in the defects treated with 10 and 20wt.% op-HA/PLGA, where bridging by a large bony callus was observed at 24weeks post-surgery. There was non-union of radius defects implanted with PLGA and in the untreated group. This was verified by the Masson's trichrome staining photomicrographs of histological analysis. All the data extrapolated that the composite with 10 and 20wt.% op-HA exhibited better comprehensive properties and were the optimal composites for bone repairing.


PMID: 19376759 DOI: 10.1016/j.actbio.2009.03.024

 

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RSC Adv., 2016,6, 2131-2134, DOI: 10.1039/C5RA25142G, Communication

Improved cellular infiltration into 3D interconnected microchannel scaffolds formed by using melt-spun sacrificial microfibers

Zongliang Wang,ac Tianlin Gao,b Liguo Cui,a Yu Wang,a Peibiao Zhang*a and Xuesi Chen a


* Corresponding authors

a Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
E-mail: zhangpb@ciac.ac.cn
Fax: +86 431 85262058
Tel: +86 431 85262058

b School of Public Health, Jilin University, Changchun, P. R. China

c University of Chinese Academy of Sciences, Beijing 100039, P. R. China


Abstract


We report a novel fabrication method using melt-spun sacrificial microfibers to make 3D interconnected microchannel scaffolds for improved cellular infiltration. The uniformly distributed cells in the highly porous microchannel scaffold maintained high cellular viability and glycosaminoglycan secretion indicating the good interconnectivity facilitates the smooth delivery of cells throughout the scaffold and allows sufficient oxygen and nutrient mass transport into the scaffold.
 

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RSC Adv., 2015,5, 96725-96732,DOI: 10.1039/C5RA19183A

Methylsulfonylmethane-loaded electrospun poly(lactide-co-glycolide) mats for cartilage tissue engineering

Zongliang Wang,ab Yu Wang,*ab Peibiao Zhang*a and Xuesi Chena


* Corresponding authors

a Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, P. R. China E-mail: zhangpb@ciac.ac.cn, wydna@ciac.ac.cn

b University of Chinese Academy of Sciences, Beijing, P. R. China

Abstract

Methylsulfonylmethane (MSM) is popularly used for the therapy of arthritic and rheumatic diseases but seldom in tissue engineering applications for cartilage regeneration. In this study, biodegradable poly(lactide-co-glycolide) (PLGA) fibrous mats containing MSM with different doping levels were fabricated by electrospinning. The MSM-loaded mats were interconnected with smooth, uniform micro- and nano-fibers. In vitro drug release of MSM-loaded mats and the biological activity for chondrocytes were investigated. The results showed that the total MSM release of 0.01 wt%, 0.1 wt%, 1 wt% and 10 wt% MSM/PLGA mats within 48 hours were 83.5%, 80.7%, 72.2%, and 51.5%, respectively. Because of the excellent bioactivity of MSM, the MSM-loaded mats showed much better cell proliferation and ECM formation ability than that of the PLGA mat. Among them, the 0.1 wt% MSM/PLGA mat showed the best cell proliferation. More importantly, the MSM/PLGA mats, especially for the 10 wt% group, also promoted extracellular matrix (ECM) formation, the cartilage related gene expression of collagen type II, aggrecan, and collagen type I, and cartilage specific protein expression of collagen type II. Together, findings from this study have revealed that the electrospun MSM-loaded PLGA mat is a promising candidate for cartilage regeneration.

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