Publications by authors named "Yonggang Yan"

65 Publications

Effects of bovine cancellous bone powder/poly amino acid composites on cellular behaviors and osteogenic performances.

Biomed Mater 2021 Jul 6;16(5). Epub 2021 Jul 6.

School of Automation and Information Engineering, Sichuan University of Science and Engineering, Zigong, People's Republic of China.

Xenogeneic bone has good biological activity, but eliminating immunogenicity, while retaining osteogenic abilities, is a challenge. By combining xenogeneic bone with poly amino acid (PAA) that has an amide bond structure, a new type of composite conforming to bionics and low immunogenicity may be obtained. In this study, according to the principles of component bionics, three composites of delipidized cancellous bone powder (DCBP) and PAA were designed and obtained by anpolycondensation method, an extrusion molding (EM) method, and a solution-blend method. The three composites were all macroscopically uniform, non-cytotoxic, and demonstrated low immunogenicity by effective removal of residual antigens during preparation. Compared with PAA, mouse bone marrow mesenchymal stem cells (BMSCs) on the surfaces of three composites showed different cellular morphologies. The effects of different preparation methods and cellular morphology on cellular differentiation were confirmed by alkaline phosphatase activity, calcium nodule formation and the expression levels of osteogenic differentiation-related genes (bone morphogenetic protein 2, runt-related transcription factor 2, osteopontin and osteocalcin). Among these composites, DCBP/PAA EM showed best cell proliferation and osteogenic differentiation, and possessed greater bone formation than PAA in a rabbit femoral condyle study. This study may provide a new method for preparing bioactive bone repair materials with low immunogenicity and superior ability to stimulate differentiation of BMSCsand osteogenesis. DCBP/PAA EM might be a promising bone repair material for bone defect treatment.
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http://dx.doi.org/10.1088/1748-605X/ac0d94DOI Listing
July 2021

A novel degradable tricalcium silicate/calcium polyphosphate/polyvinyl alcohol organic-inorganic composite cement for bone filling.

J Biomater Appl 2021 Jun 9:8853282211020399. Epub 2021 Jun 9.

College of Physical Science and Technology, Sichuan University, Chengdu, P.R. China.

In this study, tricalcium silicate (CS) calcium/polyphosphate/polyvinyl alcohol organic-inorganic self-setting composites were successfully designed. A variety of tests were conducted to characterize their self-setting properties, mechanical properties, degradation properties, and related biological properties. The composite bone cements showed a short setting time (5.5-37.5 min) with a 5:5-6:4 ratio of CS/CPP to maintain a stable compressive strength (28 MPa). In addition, PVA effectively reduced the brittleness of the inorganic phase. Degradation experiments confirmed the sustainable surface degradation of bone cement. A maximum degradation rate of 49% was reached within 56 days, and the structure remained intact without collapse. Culturing MC3T3 cells with bone cement extracts revealed that the composite bone cements had excellent biological properties . The original extract showed a proliferation promotion effect on cells, whereas most of the other original extracts of degradable bone cements were toxic to the cells. Meanwhile, extracellular matrix mineralization and alkaline phosphatase expression showed remarkable effects on cell differentiation. In addition, a good level of adhesion of cells to the surfaces of materials was observed. Taken together, these results indicate that CS/CPP/PVA composite bone cements have great potential in bone defect filling for fast curing.
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http://dx.doi.org/10.1177/08853282211020399DOI Listing
June 2021

Effects of pullulan on the biomechanical and anti-collapse properties of dicalcium phosphate dihydrate bone cement.

J Biomater Appl 2021 Jun 1:8853282211020158. Epub 2021 Jun 1.

School of Chemical Engineering, Sichuan University, Chengdu, China.

In this work, a modified dicalcium phosphate dihydrate (DCPD) bone cement with unique biodegradable ability in a calcium phosphate cement system was prepared by the hydration reaction of monocalcium phosphate monohydrate and calcium oxide and integration with pullulan (Pul), a non-toxic, biocompatible, viscous, and water-soluble polysaccharide that has been successfully used to improve defects in DCPD bone cement, especially its rapid solidification, fragile mechanical properties, and easy collapse. The effect of different contents of Pul on the structure and properties of DCPD were also studied in detail. The modified cement was characterised by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, ultraviolet-visible absorption, X-ray photoelectron spectroscopy analysis, and rheological property measurements. The results indicated that Pul promoted the hydration formation of DCPD, and interface bonding occurred between Pul and DCPD. With increasing content of Pul, the setting time of the DCPD bone cement increased from 2.6 min to 42.3 min, the compressive strength increased from 0 MPa to 20.4 MPa, and the anti-collapse ability also improved owing to the strong interface bonding, implying that the DCPD bone cement improved by Pul has better potential for application in the field of non-loading bone regenerative medicine compared to unmodified DCPD bone cement.
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http://dx.doi.org/10.1177/08853282211020158DOI Listing
June 2021

Developing a novel magnesium calcium phosphate/sodium alginate composite cement with high strength and proper self-setting time for bone repair.

J Biomater Appl 2021 May 30:8853282211021535. Epub 2021 May 30.

College of Physics, Sichuan University, Chengdu, China.

In this work, novel magnesium calcium phosphate/sodium alginate composite cements were successfully fabricated with a proper setting time (5-24 min) and high compressive strength (91.1 MPa). The physicochemical and biological properties of the cement in vitro were fully characterized. The composite cements could gradually degrade in PBS as the soaking time increase, and the weight loss reached 20.74% by the end of 56th day. The cements could induce the deposition of Ca-P layer in SBF. Cell experiments proved that the extracts of the composite cements can effectively promote the proliferation and differentiation of the mouse bone marrow mesenchymal stem cells (MSCs). These preliminary results indicate that the magnesium calcium phosphate/sodium alginate composite cements could be promising as potential bone repair candidate materials.
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http://dx.doi.org/10.1177/08853282211021535DOI Listing
May 2021

Experimental study on repair of large segmental bone defects of goat femur by nano calcium-deficient hydroxyapatite-multi (amino acid) copolymer membrane tubes.

J Biomater Appl 2021 Mar 5:8853282211000298. Epub 2021 Mar 5.

College of Physical Science and Technology, Sichuan University, Sichuan, China.

Objective: The purpose of this study was to observe feasibility of nano calcium-deficient hydroxyapatite-multi (amino acid) copolymer (n-CDHA-MAC) membrane tubes in repairing goat femurs' large defects.

Methods: Twelve goats were divided into two groups, whose femurs were created 30 mm segmental bone defects and then implants were performed. In experimental group, the bone defect of right femur was reconstructed by n-CDHA-MAC membrane tube, while left side was reconstructed by allogenic bone tube in control group. Every three goats were sacrificed at 4, 8, 16, 24 weeks after operation respectively. General observation, X-ray analysis, histology, Scanning electron microscope (SEM) examination and protein level comparison of BMP-2 were conducted to evaluate the effects of repairing segmental bone defects.

Results: All goats recovered well from anesthesia and surgical interventions. The radiographic evaluations showed that periosteal reaction outside of the membrane tubes and allogenic bone tubes were observed 4 weeks after surgery. At 16 weeks, callus was continuously increased in experimental group, which was more obvious than control group. At 24 weeks, callus outside of the membrane tubes connected together. Histologic evaluation showed fibro-cartilage callus was evolved into bony callus in experimental group, which was more obvious than control group at 8 and 16 weeks. The protein expression level of BMP-2 increased at 4, 8 weeks and peaked at 16 weeks in experimental groups. There were statistical differences at 8 and 16 weeks ( < 0.05). At each time point in 8, 16, 24 weeks after surgery, the bending stiffness, torsional stiffness and compressive strength of the two groups were similar, and there was no significant difference ( > 0.05).

Conclusions: This novel surface degradation n-CDHA-MAC membrane tube has good ability to maintain enough membrane space, which can provide long-term and stable biomechanical support for large bone defects and integrate well with the surrounding bone.
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http://dx.doi.org/10.1177/08853282211000298DOI Listing
March 2021

Preparation, characterization, and in vitro and in vivo biocompatibility evaluation of polymer (amino acid and glycolic acid)/hydroxyapatite composite for bone repair.

Biomed Mater 2021 02 18;16(2):025004. Epub 2021 Feb 18.

Medical College, Yan'an University, Yan'an 716000, People's Republic of China.

A composite of hydroxyapatite (HA) and polymers prepared from amino acids and glycolic acid (PAG) was synthesized using an in situ melting polycondensation method. The in vitro degradability and bioactivity of the composite were evaluated, as well as its in vitro and in vivo biocompatibility based on subcutaneous and osseous implantation of samples in New Zealand white rabbits for 8 weeks. The results showed that the PAG/HA composite had higher degradability than PAG and showed a typical apatite morphology after immersion in simulated body fluid for 5 d. Both the PAG/HA composite and PAG alone showed excellent in vitro biocompatibility. In the rabbit model, PAG/HA composite could induce formation of new bone tissue after 4 weeks implantation, mainly owing to the excellent in vivo bioactivity of the implant. These results suggest that PAG/HA composites have the potential to guide bone regeneration and could be used as biodegradable biomaterials for bone repair.
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http://dx.doi.org/10.1088/1748-605X/abdbddDOI Listing
February 2021

Analysis of synonymous codon usage of transcriptome database in .

PeerJ 2021 4;9:e10450. Epub 2021 Jan 4.

College of Traditional Chinese Medicine, Hebei University, Baoding, China.

Background: is an endangered and important medicinal plant in Asian countries, especially in China. However, there is little knowledge about the codon usage bias for CDSs. In this project, codon usage bias was determined based on the 2,626 predicted CDSs from R. palmatum transcriptome.

Methods: In this study, all codon usage bias parameters and nucleotide compositions were calculated by Python script, Codon W, DNA Star, CUSP of EMBOSS.

Results: The average GC and GC3 content are 46.57% and 46.6%, respectively, the results suggested that there exists a little more AT than GC in the genes, and the codon bias of genes preferred to end with A/T. We concluded that the codon bias in was affect by nucleotide composition, mutation pressure, natural selection, gene expression levels, and the mutation pressure is the prominent factor. In addition, we figured out 28 optimal codons and most of them ended with A or U. The project here can offer important information for further studies on enhancing the gene expression using codon optimization in heterogeneous expression system, predicting the genetic and evolutionary mechanisms in .
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http://dx.doi.org/10.7717/peerj.10450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789865PMC
January 2021

Biological evaluation of the modified nano-amorphous phosphate calcium doped with citrate/poly-amino acid composite as a potential candidate for bone repair and reconstruction.

J Mater Sci Mater Med 2021 Jan 25;32(1):16. Epub 2021 Jan 25.

College of Physics, Sichuan University, Chengdu, 610064, China.

Large numbers of research works related to fabricating organic-inorganic composite materials have been carried out to mimic the natural structure of bone. In this study, a new modified n-ACP doped with citrate (n-ACP-cit)/poly (amino acids) (PAA) composite (n-ACP-cit/PAA) was synthesized by employing high bioactive n-ACP-cit and the biodegradable and biocompatible PAA copolymer. Its basic structure was characterized by X-ray diffraction spectroscopy, Fourier transformed infrared spectroscopy, and X-ray photoelectron spectroscopy. Moreover, the degradability, bioactivity, biocompatibility, and osteoconductivity of n-ACP-cit/PAA composite were evaluated in vitro and in vivo, using simulated body fluid (SBF) solution soaking test, mouse bone marrow mesenchymal stem cells proliferation and differentiation, morphological observation test, expression of genes associated with osteogenesis, and bone defect model repair test, respectively. The modified n-ACP-cit/PAA composite exhibited a much higher weight loss rate (36.01 wt.%) than that of PAA (23.99 wt.%) after immersing in SBF solution for 16 weeks and the pH values of local environment restored to neutral condition. Moreover, cells co-culturing with composites exhibited higher alkaline phosphatase activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes (Bmp-2, Colla I, OCN, OPN, and Runx-2) than that of PAA. Furthermore, the bone defect model repair test revealed that the composite could be intimately incorporated with the surrounding bone without causing any deleterious reaction and capable of guiding new bone formation. Together, these results indicated that the new modified bone repair n-ACP-cit/PAA composite material with specific characteristics may be designed for meeting diverse requirements from biomedical applications.
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http://dx.doi.org/10.1007/s10856-020-06482-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829244PMC
January 2021

The complete chloroplast genome of (Rose) D.R.Hunt.

Mitochondrial DNA B Resour 2020 Jul 24;5(3):2932-2933. Epub 2020 Jul 24.

College of Pharmacy, Shaanxi Qinling Application Development and Engineering Center of Chinese Herbal Medicine, Shaanxi University of Chinese Medicine, Xi'an, China.

In this study, the complete chloroplast genome of (Rose) D.R.Hunt was investigated. The whole chloroplast genome sequence is 166,086 bp in length, which consists of a 94,376 bp large single copy (LSC) and an 18,678 bp small single copy (SSC) regions, separated by a pair of 26,518 bp inverted repeat (IR) regions. The chloroplast genome of encodes 131 annotated known unique genes including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis based on chloroplast genome sequences demonstrated that is most closely related to .
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http://dx.doi.org/10.1080/23802359.2020.1787262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782135PMC
July 2020

Preparation, characterization, andandbiocompatibility evaluation of polymer (amino acid and glycolic acid)/hydroxyapatite composite for bone repair.

Biomed Mater 2021 Jan 14. Epub 2021 Jan 14.

College of Physical Science and Technology, Sichuan University, Sichuan University, No.24 South Section 1, Yihuan Road, Chengdu , China, Chengdu, 610065, CHINA.

A composite of hydroxyapatite (HA) and polymers prepared from amino acids and glycolic acid (PAG) was synthesized using an in situ melting polycondensation method. The in vitro degradability and bioactivity of the composite were evaluated, as well as its in vitro and in vivo biocompatibility based on subcutaneous and osseous implantation of samples in New Zealand white rabbits for 8 weeks. The results showed that the PAG/HA composite had higher degradability than PAG and showed a typical apatite morphology after immersion in simulated body fluid for 5 days. Both the PAG/HA composite and PAG alone showed excellent in vitro biocompatibility. In the rabbit model, PAG/HA composite could induce formation of new bone tissue after 4 weeks implantation, mainly owing to the excellent in vivo bioactivity of the implant. These results suggest that PAG/HA composites have the potential to guide bone regeneration and could be used as biodegradable biomaterials for bone repair.
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http://dx.doi.org/10.1088/1748-605X/abdbddDOI Listing
January 2021

Complete plastid genome of the Chinese medicinal herb subsp. (Paeoniaceae): characterization and phylogeny.

Mitochondrial DNA B Resour 2020 Jan 24;5(1):845-847. Epub 2020 Jan 24.

College of Pharmacy, Shaanxi Qinling Application Development and Engineering Center of Chinese Herbal Medicine, Shaanxi University of Chinese Medicine, Xi'an, China.

The plastid genome (plastome) of the endemic Chinese medicinal herb subsp. (Paeoniaceae) was sequenced and investigated in this study. The complete plastome is 152,713 bp in length with the typical quadripartite structure, which consists of a large single-copy region (LSC, 84,419 bp), a small single-copy region (SSC, 16,982 bp), and a pair of inverted repeat regions (IRs, 25,656 bp). The overall GC content is 33.2%, and the IR regions are more GC rich (43.2%) than the LSC (36.7%) and SSC (32.8%) regions. A total of 114 unique genes, including 79 protein-coding genes, 31 tRNAs, and four rRNAs were identified. Phylogenetic reconstruction based on complete plastome sequences demonstrated that subsp. is phylogenetically closest to .
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http://dx.doi.org/10.1080/23802359.2020.1716641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748467PMC
January 2020

The complete chloroplast genome sequence of , an endangered Chinese medicinal plant ().

Mitochondrial DNA B Resour 2019 Nov 13;4(2):4055-4056. Epub 2019 Nov 13.

College of Traditional Chinese Medicine, Hebei University, Baoding, PR China.

is a valuable medicinal plant endemic to the Qinghai-Tibetan Plateau. It has been listed classified under the IUCN Red List categories of Vulnerable due to the low reproductive rate and heavy exploitation. In this study, the complete chloroplast (cp) genome of has been assembled using data from the whole-genome Illumina sequencing. The cp genome is 161,515 bp in size and contains two inverted repeat regions of 30,823 bp each, which is separated by a large single-copy region of 86,675 bp and a small single-copy region of 13,194 bp. The cp genome contains 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis revealed that the cp genome of was closely related to that of the .
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http://dx.doi.org/10.1080/23802359.2019.1688722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707752PMC
November 2019

Developing a biodegradable tricalcium silicate/glucono-delta-lactone/calcium sulfate dihydrate composite cement with high preliminary mechanical property for bone filling.

Mater Sci Eng C Mater Biol Appl 2021 Feb 9;119:111621. Epub 2020 Oct 9.

College of Physics, Sichuan University, Chengdu 610065, China. Electronic address:

Bone cements with the feature of easily shaping could ideally match the defect site and prevent the ingrowth of fibrous tissue. In this manuscript, a biodegradable tricalcium silicate (CS)/glucono-delta-lactone (GDL)/calcium sulfate dihydrate (CSD) organic-inorganic composite cement was fabricated with shorter setting time (less than 15 min) and high preliminary mechanical property (5.27 MPa in the first hour). Many methods were applied to study the physicochemical and biological properties of the cement in vitro. The weight loss in PBS can reach 58% after 12 weeks soaking indicating the better biodegradability. The excellent bioactivity in vitro was emerging after the cement was soaked in the simulated body fluid. The cell experiments showed that suitable concentration of the extract liquid of cement was conducive to the proliferation, differentiation and extracellular matrix calcification of the mouse bone marrow stromal cells. Briefly, the CS/GDL/CSD composite cement would have the bright capacity for bone filling.
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http://dx.doi.org/10.1016/j.msec.2020.111621DOI Listing
February 2021

Preparation of a novel bovine cancellous bone/poly-amino acid composite with low immunogenicity, proper strength, and cytocompatibility in vitro.

J Biomed Mater Res A 2021 Aug 7;109(8):1490-1501. Epub 2020 Dec 7.

College of Physics, Sichuan University, Chengdu, Sichuan, China.

In this work, the delipidized and deproteinized bovine cancellous bone powder/poly-amino acid (DDBP/PAA) composite was fabricated by extrusion-injection molding method for the first time. After about 70% clearance rate by the delipidization and deproteinization procedures, the residual antigens of galactosyl α-(1, 3)-galactosyl β-1,4-N-aeetylglueosaminyl (α-Gal) and major histocompatibility complex (MHC) II were basically eliminated by the extrusion-injection molding process, which may cause high titer of antibody and lead to hyperacute rejection or chronic immune toxicity. Meanwhile, the natural BMP II and apatite in bovine bone were kept in DDBP/PAA composite. After 26 weeks of immersion in simulated body fluid, the DDBP/PAA composite remained the intact appearance, 96.4% of weight, and 69.2% of compressive strength, and these showed sufficient degradation stability. The composite also exhibited excellent attachment and proliferation abilities of mouse bone marrow mesenchymal stem cells (mMSCs). The results herein suggested that the DDBP/PAA composite was expected to be a load-bearing transplant with some natural ingredients for hard tissue repair.
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http://dx.doi.org/10.1002/jbm.a.37139DOI Listing
August 2021

Increased phenolic acid and tanshinone production and transcriptional responses of biosynthetic genes in hairy root cultures of Salvia przewalskii Maxim. treated with methyl jasmonate and salicylic acid.

Mol Biol Rep 2020 Nov 13;47(11):8565-8578. Epub 2020 Oct 13.

Shaanxi University of Chinese Medicine, Xianyang, 712046, China.

The purpose of this study is to reveal the impact of the plant hormone salicylic acid (SA) and methyl jasmonate (MeJA) on the growth, effective components accumulation, and related gene expression of the hairy root of Salvia przewalskii Maxim. Various concentrations of SA (0, 25, 50, 100, 200 μM) or MeJA (0, 50, 100, 200, 400, 600 μM) were added to the culture medium of Salvia przewalskii Maxim. Low concentrations of SA promoted the growth of hairy root, while a high concentration inhibited it. 0 to 400 μM MeJA promoted the growth of hairy root, but 600 μM MeJA starts to inhibit its growth. 50 μM SA and 400 μM MeJA significantly enhanced the production of caffeic acid, rosmarinic acid, salvianolic acid B, cryptotanshinone, and tanshinone IIA. In general, 50 μM SA can be used to accumulate of tanshinone in hairy roots of S. przewalskii with 6 days. 400 μM MeJA can be used to accumulate of phenolic acids in hairy roots of S. przewalskii with 3 days. The selected genes in the tanshinone and phenolic acid biosynthetic pathway were upregulated with elicitation. To obtain a higher yield and content of secondary metabolites, it is advisable to use 50 μM SA or 400 μM MeJA as the optimal doses to cultivate the hairy root of S. przewalskii. This study provides, for the first time, an efficient tanshinone and phenolic acid production method for S. przewalskii.
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http://dx.doi.org/10.1007/s11033-020-05899-1DOI Listing
November 2020

Iterative Deep Neighborhood: A Deep Learning Model Which Involves Both Input Data Points and Their Neighbors.

Comput Intell Neurosci 2020 2;2020:9868017. Epub 2020 Jan 2.

New York University Abu Dhabi, Abu Dhabi, UAE.

Deep learning models, such as deep convolutional neural network and deep long-short term memory model, have achieved great successes in many pattern classification applications over shadow machine learning models with hand-crafted features. The main reason is the ability of deep learning models to automatically extract hierarchical features from massive data by multiple layers of neurons. However, in many other situations, existing deep learning models still cannot gain satisfying results due to the limitation of the inputs of models. The existing deep learning models only take the data instances of an input point but completely ignore the other data points in the dataset, which potentially provides critical insight for the classification of the given input. To overcome this gap, in this paper, we show that the neighboring data points besides the input data point itself can boost the deep learning model's performance significantly and design a novel deep learning model which takes both the data instances of an input point and its neighbors' classification responses as inputs. In addition, we develop an iterative algorithm which updates the neighbors of data points according to the deep representations output by the deep learning model and the parameters of the deep learning model alternately. The proposed algorithm, named "Iterative Deep Neighborhood (IDN)," shows its advantages over the state-of-the-art deep learning models over tasks of image classification, text sentiment analysis, property price trend prediction, etc.
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http://dx.doi.org/10.1155/2020/9868017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199621PMC
February 2021

Enhancement of osteoblast cells osteogenic differentiation and bone regeneration by hydroxyapatite/phosphoester modified poly(amino acid).

Mater Sci Eng C Mater Biol Appl 2020 Jun 22;111:110769. Epub 2020 Feb 22.

College of Physics, Sichuan University, Chengdu, Sichuan 610065, China. Electronic address:

Hydroxyapatite/poly(amino acid) (HA/PAA) has been used to treat a variety of long bone and vertebral bony defects, and a further biocompatibility improvement is a key for better application. Phosphoester (PE) contained materials are highly biocompatible but could hardly treat massive bone defects due to its fast-degradation-derived mechanical instability. To address the problems of the two materials, we have incorporated PE molecule into the main chain of PAA by chemical bonding. As a result, the compressive strength of HA/PAA with 1 wt% and 2.5 wt% PE maintained in the range of 80-150 MPa after soaking in PBS for 12 weeks, which could be attributed to the amplified hydrogen-bonding inside composites. Besides, the PE-containing HA/PAAs with increased hydrophilic function groups (O=P-O bonds and O=P-N), created a more favourable surface for cell adhesion. Meanwhile, compared with HA/PAA, the PE-containing HA/PAAs had a fast minerlization speed and promoted cell osteogenic differentiation. Furthermore, the in vivo study indicated that PE-containing HA/PAAs could facilitate bone formation (4 weeks), and form a complete bone bridging (12 weeks) in a rabbit cranial bone defect. In summary, the HA/PE-m-PAAs possessed good mechanical stability, improved cytocompatibility and osteoconductivity, so the composites have a great potential for massive bone defect treatment.
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http://dx.doi.org/10.1016/j.msec.2020.110769DOI Listing
June 2020

Absorbable nanocomposites composed of mesoporous bioglass nanoparticles and polyelectrolyte complexes for surgical hemorrhage control.

Mater Sci Eng C Mater Biol Appl 2020 Apr 13;109:110556. Epub 2019 Dec 13.

Department of Orthopaedics, Zhongye Hospital, Shanghai 200941, China.

Absorbable polyelectrolyte complexes-based hemostats are promising for controlling hemorrhage in iatrogenic injuries during surgery, whereas their hemostatic efficacy and other performances require further improvement for clinical application. Herein, spherical mesoporous bioglass nanoparticles (mBGN) were fabricated, and mBGN-polyelectrolyte complexes (composed of carboxymethyl starch and chitosan oligosaccharide) nanocomposites (BGN/PEC) with different mBGN contents were prepared via in situ coprecipitation followed by lyophilization. The effect of various mBGN content (10 and 20 wt%) on morphology, zeta potential, water absorption, degradation behavior and ion release were systematically evaluated. The in vitro degradability was dramatically promoted and a more neutral environment was achieved with the incorporation of mBGN, which is preferable for surgical applications. The in vitro coagulation test with whole blood demonstrated that the incorporation of mBGN facilitated blood clotting process. The plasma coagulation evaluation indicated that BGN/PEC had increased capability to accelerate coagulation cascade via the intrinsic pathway than that of the PEC, while have inapparent influence on the extrinsic and common pathway. The in vivo hemostatic evaluation in a rabbit hepatic hemorrhage model revealed that BGN/PEC with 10 wt% mBGN (10BGN/PEC) treatment group had the lowest blood loss, although its hemostatic time is close to that of 20BGN/PEC treatment group. The cytocompatibility evaluation with MC3T3-L1 fibroblasts indicated that 10BGN/PEC induced a ~25% increase of cell viability compared to the PEC at days 4 and 7, indicating improved biocompatibility. These findings support the promising application of absorbable BGN/PEC with optimized mBGN content as internal hemostats and present a platform for further development of PEC-based hemostats.
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http://dx.doi.org/10.1016/j.msec.2019.110556DOI Listing
April 2020

Virtual Screening of the Multi-pathway and Multi-gene Regulatory Molecular Mechanism of Dachengqi Decoction in the Treatment of Stroke Based on Network Pharmacology.

Comb Chem High Throughput Screen 2020 ;23(8):775-787

School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China.

Background: Stroke is ranked second among diseases that cause mortality worldwide. Owing to its complicated pathogenesis, no satisfactory treatment strategies for stroke are available. Dachengqi decoction (DCQD), a traditional Chinese herbal medicine, has been widely used in China for a long time, as it has a good effect on stroke. However, the molecular mechanism underlying this effect of DCQD is unclear.

Objective: In the present study, we aimed to reveal and explore the multi-pathway and multi-gene regulatory molecular mechanism of Dachengqi decoction in the treatment of stroke.

Methods: In this study, a network pharmacology method, in combination with oral bioavailability prediction and drug-likeness evaluation, was employed to predict the active ingredients of DCQD. The target genes of the active components and the traced pathways related to these target genes were predicted. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using clusterProfiler software package on the R platform and ClueGo+CluePedia plug-ins. Finally, the key DCQD targets were verified using the Gene Expression Omnibus (GEO) dataset.

Results And Discussion: According to the ADME model, 52 active components were screened from 296 active components of DCQD. After prediction and screening, 215 stroke-related targets were obtained and analyzed via GO and KEGG analyses. GO analysis showed that DCQD targets were mainly involved in the regulation of oxidative stress, lipid metabolism, inflammation, and other biological processes. KEGG pathway analysis further revealed pathways involved in stroke, such as arachidonic acid metabolic, HIF-1 signaling pathway, estrogen signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, platelet activation pathway, VEGF signaling pathway, and cAMP signaling pathway. Network analysis revealed that DCQD might be involved in the regulation of lipid metabolism, blood pressure, inflammation, angiogenesis, neuroprotection, platelet aggregation, apoptosis, and oxidation in stroke treatment. GEO dataset analysis showed that DCQD's therapeutic effects might be exerted via the bidirectional regulation principle.

Conclusion: Based on the methods of network pharmacology and GEO analysis, it was found that, during stroke treatment, DCQD regulates and controls multiple genes and multiple pathways in a synergistic manner, providing a new strategy for stroke treatment.
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http://dx.doi.org/10.2174/1386207323666200311113747DOI Listing
July 2021

Vitamin D3-loaded calcium citrate/calcium sulfate composite cement with enhanced physicochemical properties, drug release, and cytocompatibility.

J Biomater Appl 2020 05 12;34(10):1343-1354. Epub 2020 Feb 12.

College of Physics, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1177/0885328220904498DOI Listing
May 2020

Simonkolleite Coating on Poly(Amino Acids) to Improve Osteogenesis and Suppress Osteoclast Formation in Vitro.

Polymers (Basel) 2019 Sep 16;11(9). Epub 2019 Sep 16.

College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

Zinc can enhance osteoblastic bone formation and stimulate osteogenic differentiation, suppress the differentiation of osteoclast precursor cells into osteoclasts, and inhibit pathogenic bacterial growth in a dose-dependent manner. In this study, simonkolleite, as a novel zinc resource, was coated on poly (amino acids) (PAA) via suspending PAA powder in different concentrations of zinc chloride (ZnCl) solution, and the simonkolleite-coated PAA (Zn-PAA) was characterized by SEM, XRD, FT-IR and XPS. Zinc ions were continuously released from the coating, and the release behavior was dependent on both the concentration of the ZnCl immersing solution and the type of soak solutions (SBF, PBS and DMEM). The Zn-PAA was cultured with mouse bone marrow stem cells (BMSCs) through Transwell plates, and the results indicated that the relative cell viability, alkaline phosphatase (ALP) activity and mineralization of BMSCs were significantly higher with Zn-PAA as compared to PAA. Moreover, the Zn-PAA was cultured with RAW264.7 cells, and the results suggested an inhibiting effect of Zn-PAA on the cell differentiation into osteoclasts. In addition, Zn-PAA exhibited an antibacterial activity against both and . These findings suggest that simonkolleite coating with certain contents could promote osteogenesis, suppress osteoclast formation and inhibit bacteria, indicating a novel way of enhancing the functionality of synthetic bone graft material and identifying the underline principles for designing zinc-containing bone grafts.
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http://dx.doi.org/10.3390/polym11091505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780185PMC
September 2019

Characterization of the complete chloroplast genome of medicinal plant (Polygonaceae).

Mitochondrial DNA B Resour 2019 Jul 10;4(2):2144-2145. Epub 2019 Jul 10.

College of Pharmacy, Shaanxi Qinling Application Development and Engineering Center of Chinese Herbal Medicine, Shaanxi University of Chinese Medicine, Xi'an, China.

The complete chloroplast (cp) genome of Baill. was determined based on the Illumina Sequencing data. The cp genome is 161,563 bp in length. The overall G + C content of the cp genome was 37.31%. The cp genome contains 129 genes, including 84 protein-coding genes, eight rRNA genes (four rRNA species), and 37 tRNA genes (20 tRNA species). A neighbour-joining phylogenetic tree clarified that the cp genome of was closely related to that of in Polygonaceae.
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http://dx.doi.org/10.1080/23802359.2019.1623102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687616PMC
July 2019

Preparation, Characterization and In Vitro Biological Evaluation of a Novel Pearl Powder/Poly-Amino Acid Composite as a Potential Substitute for Bone Repair and Reconstruction.

Polymers (Basel) 2019 May 8;11(5). Epub 2019 May 8.

College of Physical Science and Technology, Sichuan University, Chengdu 610064, China.

Many studies about fabricating organic-inorganic composite materials have been carried out in order to mimic the natural structure of bone. Pearl, which has a special block-and-mortar hierarchical structure, is a superior bone repair material with high osteogenic activity, but it shows few applications in the clinical bone repair and reconstruction because of its brittle and uneasily shaped properties. In this work, pearl powder (P)/poly (amino acid) (PAA) composites were successfully prepared by a method of in situ melting polycondensation to combine the high osteogenic activity of the pearl and the pliability of the PAA. The mechanical properties, in vitro bioactivity and biocompatibility as well as osteogenic activity of the composites were investigated. The results showed that P/PAA composites have both good mechanical properties and bioactivity. The compressive strength, bending strength and tensile strength of the composites reached a maximum of 161 MPa, 50 MPa and 42 MPa, respectively; in addition, apatite particles successfully deposited on the composites surface after immersion in simulated body fluid (SBF) for 7 days indicated that P/PAA composites showed an enhanced mineralization capacity and bioactivity due to incorporation of pearl powder and PAA. The cell culture results revealed that higher cell proliferation and better adhesion morphology of mouse bone marrow mesenchymal stem cells (MSCs) appeared on the composite surface. Moreover, cells growing on the surface of the composites exhibited higher alkaline phosphatase (ALP) activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes (COL 1, RunX2, OCN, and OPN) than cells grown on PAA surface. The P/PAA composites exhibited both superior mechanical properties to the pearl powder, higher bioactivity and osteogenic capability compared with those of PAA.
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http://dx.doi.org/10.3390/polym11050831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572604PMC
May 2019

Nano-amorphous calcium phosphate doped with citrate: Fabrication, structure, and evaluation of the biological performance.

J Biomater Appl 2019 08 2;34(2):273-283. Epub 2019 May 2.

College of Physical Science and Technology, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1177/0885328219845969DOI Listing
August 2019

Design of novel organic-inorganic composite bone cements with high compressive strength, in vitro bioactivity and cytocompatibility.

J Biomed Mater Res B Appl Biomater 2019 10 28;107(7):2365-2377. Epub 2019 Jan 28.

College of Physical Science and Technology, Sichuan University, Chengdu, Sichuan, 610065, China.

In this work, novel bioactive organic-inorganic composite bone cements consisting of tricalcium silicate (C S), sodium alginate (SA), and calcium sulfate hemihydrate (CS) were successfully fabricated for the first time via a special method designing material composition and internal structure simultaneously, which was intended to enhance mechanical performance by combining progressive hydration process of C S with distinctive gelation capacity of SA and further improve degradability and self-setting properties with the addition of CS. Depending on the synergistic combination of hydration and gelation, the C S/SA/CS composite cements (45/45/10 wt %) obtained extremely higher compressive strength up to 92.41 MPa as compared with each single component. The reinforcing mechanisms involving interfacial interaction and interior microstructure were proposed to explain this enhancement phenomenon. Additionally, the final setting time could be reduced from 68 min to 21 min with the increasing CS content. The composite cements possessed good apatite mineralization ability in simulated body fluid solution and moderate degradation rate in phosphate buffer solution. What's more, the composite cements exhibited excellent cytocompatibility and increased proliferation of rat bone-marrow stem cells. This study could provide guidelines for the preparation of bioactive composite cements with enhanced mechanical performance, which may be suitable for load-bearing bone repair. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2365-2377, 2019.
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http://dx.doi.org/10.1002/jbm.b.34330DOI Listing
October 2019

Reconstruction of calvarial bone defects using poly(amino acid)/hydroxyapatite/calcium sulfate composite.

J Biomater Sci Polym Ed 2019 02 9;30(2):107-121. Epub 2019 Jan 9.

a College of Physical Science and Technology, Sichuan University , Chengdu , China.

The aim of this study was to evaluate the thermal properties and in vivo interface performance of poly(amino acid) (PAA) and a composite containing PAA, hydroxyapatite (HA), and calcium sulfate (CS), with respect to their suitability for skull repair. Biocompatibility was evaluated by implantation of materials into muscles of rabbits for eight weeks. Skull repair was assessed by implanting PAA, the compact PAA/HA/CS composite (c-PAA/HA/CS), and a one-side-porous PAA/HA/CS composite (p-PAA/HA/CS) into rabbit calvarial defects. The results showed that the PAA/HA/CS composite possessed good heat resistance and possessed excellent biocompatibility and osteoconductivity. Guided bone regeneration and calvarial repair were observed, with excellent integration between calvarial tissue and implant. The p-PAA/HA/CS composite performed best in terms of stability and bone bonding between implant and host bone tissue. Thus, the present work provides new information for the potential use of osteoconductive PAA/HA/CS composites with a macrostructure in calvarial bone repair.
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http://dx.doi.org/10.1080/09205063.2018.1554833DOI Listing
February 2019

Developing novel Ca-zeolite/poly(amino acid) composites with hemostatic activity for bone substitute applications.

J Biomater Sci Polym Ed 2018 11 24;29(16):1994-2010. Epub 2018 Nov 24.

a College of Physical Science and Technology , Sichuan University , Chengdu , China.

The novel Ca-zeolite/poly(amino acid) (CaY/PAA) composites for bone substitute applications with hemostatic activity were prepared using the in situ melting polymerization method. In this study, Ca-zeolite (CaY) loaded with Ca was obtained from Y-type zeolite (NaY) by ion-exchange method. The properties of the CaY/PAA composites and PAA, including composition, structure, compressive strength, in vitro degradability in phosphate-buffered solution (PBS), bioactivity, cytocompatibility and in vitro coagulation tests were characterized and investigated. The results showed that compressive strength of the CaY/PAA composites ranged from 145 to 186 MPa, demonstrating sufficient mechanical strength for load-bearing bone substitute. After soaking in PBS for 16 weeks, the weight loss of 25CaY/PAA and 50CaY/PAA were 4.1 and 1.6 wt%, respectively, and the pH values for CaY/PAA composites increased to about 8.0 in 2 weeks and then gradually stabilized around 7.4, indicating good stability in PBS. Scanning electron microscope and energy dispersive spectrometer results showed that the composites were bioactive and new apatite layers attached on their surfaces. Mesenchymal stem cells (MSCs) exhibited high-proliferation in the extract solution of the CaY/PAA composites and were well spread on the surfaces of the composites. Cells on the CaY/PAA composite groups showed higher alkaline phosphatase (ALP) activity indicating the potential to promote cell differentiation. The in vitro coagulation tests showed that CaY/PAA composites have shorter clotting time and better performance of promoting blood coagulation than other samples, presenting improved hemostatic activity. In summary, the results demonstrated that the CaY/PAA composites had good mechanical strength, stability, bioactivity, cytocompatibility and hemostatic activity for bone substitute applications.
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http://dx.doi.org/10.1080/09205063.2018.1521688DOI Listing
November 2018

Evaluation of the internal fixation effect of nano-calcium-deficient hydroxyapatite/poly-amino acid composite screws for intraarticular fractures in rabbits.

Int J Nanomedicine 2018 18;13:6625-6636. Epub 2018 Oct 18.

College of Physical Science and Technology, Sichuan University, Chengdu, People's Republic of China,

Objective: To evaluate the internal fixation effect of nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) composite screws in the intraarticular fracture model.

Materials And Methods: A total of 35 New Zealand White rabbits were used in a bilateral femoral intercondylar fracture model and randomly divided into two groups. n-CDHA/PAA screws were used in the experimental group, and medical metal screws were used in the control group. The fracture condition, range of motion, and the screw push-out strength were assessed, and an arthroscopic examination of knee joint was performed at 4, 8, and 12 weeks after surgery. The biodegradation of the n-CDHA/PAA screws in vivo was tested through weighing, and changes in screw structure were assessed by X-ray diffraction at 12 weeks after surgery.

Results: The general situation of all animals was good and showed no incision infection and dehiscence after surgery. X-ray scanning showed that significant callus growth was present in both groups at 4 weeks after surgery, and there was no significant difference (>0.05) in the Lane-Sandhu score between the experimental and control groups at all time points after surgery. There were no statistically significant differences (>0.05) in the range of motion and Oswestry Arthroscopy Score of arthroscopic examination of the knee joints between the two groups. The screw push-out strength of the control group was stronger than that of the experimental group at 4 weeks after surgery (<0.05), but after that, there was no significant difference between the groups (>0.05). The degradation tests showed that the n-CDHA/PAA screws degraded gradually after implantation, and the weight loss rate was approximately 16% at 12 weeks after surgery. The X-ray diffraction results showed that the crystal structure of the outer surface of the n-CDHA/PAA screw has changed at 12 weeks after surgery.

Conclusion: The n-CDHA/PAA screw is an effective and safe implant as a potential internal fixation device for an intercondylar fracture of the femur, and its internal fixation effect was similar to that of medical metal screw.
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http://dx.doi.org/10.2147/IJN.S173358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201990PMC
December 2018

Evaluation of absorbable hemostatic agents of polyelectrolyte complexes using carboxymethyl starch and chitosan oligosaccharide both in vitro and in vivo.

Biomater Sci 2018 Nov;6(12):3332-3344

College of Physical Science and Technology, Sichuan University, Chengdu 610064, China.

Absorbable hemostatic agents with a high hemostatic efficacy play an important role in surgical and severely traumatic hemostasis. In the present study, by applying polyelectrolyte assembly, polyelectrolyte complexes (PECs), using carboxymethyl starch (CMS) and chitosan oligosaccharide (COS), with controllable physicochemical properties were prepared and optimized for hemorrhage control. Particle size, zeta potential, morphology and water absorption of the PECs with different CMS/COS ratios were systematically evaluated. The results of in vitro degradation in PBS suggested that CMS/COS PECs were degradable and their degradation rates, which decreased with the increase of the COS content, were suitable for absorbable hemostatic agents. The in vivo hemostatic efficacy of the PECs with 10 wt% COS content (PEC 10), which was evaluated in a rabbit hepatic hemorrhage model, was better than CMS but decreased with the increase of the COS content. The plasma coagulation evaluation revealed that the PECs could significantly activate and accelerate the coagulation cascade through both the intrinsic and extrinsic pathways but could not directly affect the common pathway. CMS/COS PECs also showed antimicrobial activity against S. aureus, which enhanced with the increase of the COS content, but failed against E. coli. Moreover, PEC 10 displayed excellent cytocompatibility with MC3T3-L1 and good tissue compatibility in a rabbit liver model. These findings not only suggest that CMS/COS PECs with a suitable COS content were promising absorbable hemostatic agents for internal use but they are also useful to understand the underlying principles for designing PEC based hemostatic agents.
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http://dx.doi.org/10.1039/c8bm00628hDOI Listing
November 2018