Wetspun poly-L-(lactic acid)-borosilicate bioactive glass scaffolds for guided bone regeneration

International Nuclear Information System (INIS)

Fernandes, João S.; Reis, Rui L.; Pires, Ricardo A.

2017-01-01

We developed a porous poly-L-lactic acid (PLLA) scaffold compounded with borosilicate bioactive glasses (BBGs) endowing it with bioactive properties. Porous PLLA-BBG fibre mesh scaffolds were successfully prepared by the combination of wet spinning and fibre bonding techniques. Micro-computed tomography (μCT) confirmed that the PLLA-BBG scaffolds containing ≈ 25% of BBGs (w/w) exhibited randomly interconnected porous (58 to 62% of interconnectivity and 53 to 67% of porosity) with mean pore diameters higher that 100 μm. Bioactivity and degradation studies were performed by immersing the scaffolds in simulated body fluid (SBF) and ultrapure water, respectively. The PLLA-BBG scaffolds presented a faster degradation rate with a constant release of inorganic species, which are capable to produce calcium phosphate structures at the surface of the material after 7 days of immersion in SBF (Ca/P ratio of ~ 1.7). Cellular in vitro studies with human osteosarcoma cell line (Saos-2) and human adipose-derived stem cells (hASCs) showed that PLLA-BBGs are not cytotoxic to cells, while demonstrating their capacity to promote cell adhesion and proliferation. Overall, we showed that the proposed scaffolds present a tailored kinetics on the release of inorganic species and controlled biological response under conditions that mimic the bone physiological environment. - Highlights: • We prepared borosilicate glasses and their PLLA composites in the form of fibres. • These glasses imparted bioactivity and controlled degradability to the fibres. • The prepared fibres did not elicit cytotoxicity. • hASCs attached and proliferated in the surface and inner sections of the scaffolds. • The composites present appropriate properties to be used in bone tissue engineering.

Improved mechanical properties of hydroxyapatite whisker-reinforced poly(L-lactic acid) scaffold by surface modification of hydroxyapatite.

Science.gov (United States)

Fang, Zhou; Feng, Qingling

2014-02-01

To improve the mechanical properties of porous hydroxyapatite/poly(L-lactic acid) (HA/PLLA) composites, HA whiskers with high crystallinity and high aspect ratio were synthesized. HA whiskers were modified with γ-aminopropyltriethoxysilane (APTES) to improve the interface between HA whiskers and PLLA. The composite scaffold consists of a porous PLLA matrix with HA whiskers distributed homogeneously. The morphology and the distributions of pore sizes of PLLA scaffold was not influenced by introducing HA whiskers, while the mechanical properties were improved. Both the compressive strength and compressive modulus were increased with the weight ratio of APTES-modified HA whiskers up to 30 wt.%, but only up to 15 wt.% for non-modified HA whiskers. With more than 15 wt.% HA whiskers, the mechanical properties of HA/PLLA scaffold were better improved with APTES-modified HA whiskers than non-modified. The HA whisker/PLLA scaffold with high porosity and improved mechanical properties is attractive in the application of tissue engineering. Copyright © 2013 Elsevier B.V. All rights reserved.

Electrospun nanofibrous scaffolds of poly (L-lactic acid)-dicalcium silicate composite via ultrasonic-aging technique for bone regeneration

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Dong, Shengjie [Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006 (China); Sun, Junying, E-mail: wodaoshi@sohu.com [Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006 (China); Li, Yadong [College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu 215123 (China); Li, Jun [Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006 (China); Cui, Wenguo [Orthopedic Institute, Soochow University, 708 Renmin Rd, Suzhou, Jiangsu 215007 (China); Li, Bin, E-mail: binli@suda.edu.cn [Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu 215006 (China)

2014-02-01

Polymeric nanofibrous composite scaffolds incorporating bioglass and bioceramics have been increasingly promising for bone tissue engineering. In the present study, electrospun poly (L-lactic acid) (PLLA) scaffolds containing dicalcium silicate (C{sub 2}S) nanoparticles (approximately 300 nm) were fabricated. Using a novel ultrasonic dispersion and aging method, uniform C{sub 2}S nanoparticles were prepared and they were homogenously distributed in the PLLA nanofibers upon electrospinning. In vitro, the PLLA-C{sub 2}S fibers induced the formation of HAp on the surface when immersed in simulated body fluid (SBF). During culture, the osteoblastic MC3T3-E1 cells adhered well on PLLA-C{sub 2}S scaffolds, as evidenced by the well-defined actin stress fibers and well-spreading morphology. Further, compared to pure PLLA scaffolds without C{sub 2}S, PLLA-C{sub 2}S scaffolds markedly promoted the proliferation of MC3T3-E1 cells as well as their osteogenic differentiation, which was characterized by the enhanced alkaline phosphatase (ALP) activity. Together, findings from this study clearly demonstrated that PLLA-C{sub 2}S composite scaffold may function as an ideal candidate for bone tissue engineering. - Highlights: • Dicalcium silicate (C{sub 2}S) nanoparticles were prepared via a sol–gel process. • C{sub 2}S nanoparticles were stabilized using ultrasonic-aging technique. • PLLA-C{sub 2}S composite nanofibers were fabricated through electrospinning technique. • C{sub 2}S nanoparticles could be homogenously distributed in nanofibers. • The composite scaffolds enhanced proliferation and differentiation of osteoblasts.

Negative Outcomes of Poly(l-Lactic Acid) Fiber-Reinforced Scaffolds in an Ovine Total Meniscus Replacement Model.

Science.gov (United States)

Patel, Jay M; Merriam, Aaron R; Kohn, Joachim; Gatt, Charles J; Dunn, Michael G

2016-09-01

Our objective was to test the efficacy of collagen-hyaluronan scaffolds reinforced with poly(l-lactic acid) (PLLA) fibers in an ovine total meniscus replacement model. Scaffolds were implanted into 9 sheep (n = 1 at 8 weeks, n = 2 at 16 weeks, n = 3 at both 24, 32 weeks) following total medial meniscectomy. From 16 weeks on, explants were characterized by confined compression creep, histological, and biochemical analyses. Articular surfaces were observed macroscopically and damage was ranked histologically using the Mankin score. At sacrifice, three of the nine PLLA scaffolds had completely ruptured, and the intact scaffolds experienced progressive shape changes and severe narrowing in the body region at 16, 24, and 32 weeks. Aggregate compressive modulus and permeability did not improve with time. Histological and biochemical analyses showed significantly less extracellular matrix and less matrix organization compared to native tissue. Osteophytes, bone erosion, and cartilage damage were observed, increasing with time postimplantation. A buildup of lactic acid and/or the rapid loss of scaffold mechanical integrity due to PLLA degradation are probable causes for the joint abnormalities observed in this study. These results are in sharp contrast to those of our previous successful total meniscus replacement studies using polyarylate [p(DTD DD)] fiber-reinforced scaffolds. This suggests that PLLA fiber as produced in this study cannot be used as reinforcement for a meniscus replacement scaffold.

Novel biologically-inspired rosette nanotube PLLA scaffolds for improving human mesenchymal stem cell chondrogenic differentiation

International Nuclear Information System (INIS)

Childs, Allie; Castro, Nathan J; Zhang, Lijie Grace; Hemraz, Usha D; Fenniri, Hicham

2013-01-01

Cartilage defects are a persistent issue in orthopedic tissue engineering where acute and chronic tissue damage stemming from osteoarthritis, trauma, and sport injuries, present a common and serious clinical problem. Unlike bone, cartilage repair continues to be largely intractable due to the tissue's inherently poor regenerative capacity. Thus, the objective of this study is to design a novel tissue engineered nanostructured cartilage scaffold via biologically-inspired self-assembling rosette nanotubes (RNTs) and biocompatible non-woven poly (l-lactic acid) (PLLA) for enhanced human bone marrow mesenchymal stem cell (hMSC) chondrogenic differentiation. Specifically, RNTs are a new class of biomimetic supramolecular nanomaterial obtained through the self-assembly of low-molecular-weight modified guanine/cytosine DNA base hybrids (the G∧C motif) in an aqueous environment. In this study, we synthesized a novel twin G∧C-based RNT (TB-RGDSK) functionalized with cell-favorable arginine–glycine–aspartic acid–serine–lysine (RGDSK) integrin binding peptide and a twin G∧C based RNT with an aminobutane linker molecule (TBL). hMSC adhesion, proliferation and chondrogenic differentiation were evaluated in vitro in scaffold groups consisting of biocompatible PLLA with TBL, 1:9 TB-RGDSK:TBL, and TB-RGDSK, respectively. Our results show that RNTs can remarkably increase total glycosaminoglycan, collagen, and protein production when compared to PLLA controls without nanotubes. Furthermore, the TB-RGDSK with 100% well-organized RGDSK peptides achieved the highest chondrogenic differentiation of hMSCs. The current in vitro study illustrated that RNT nanotopography and surface chemistry played an important role in enhancing hMSC chondrogenic differentiation thus making them promising for cartilage regeneration. (paper)

Gum tragacanth/poly(l-lactic acid) nanofibrous scaffolds for application in regeneration of peripheral nerve damage.

Science.gov (United States)

Ranjbar-Mohammadi, Marziyeh; Prabhakaran, Molamma P; Bahrami, S Hajir; Ramakrishna, Seeram

2016-04-20

Nanofibrous nerve guides have gained huge interest in supporting the peripheral nerve regeneration due to their abilities to simulate the topography, mechanical, biological and extracellular matrix morphology of native tissue. Gum tragacanth (GT) is a biocompatible mixture of polysaccharides that has been used in biomedical applications. During this study, we fabricated aligned and random nanofibers from poly(l-lactic acid) and gum tragacanth (PLLA/GT) in various ratios (100:0, 75:25, and 50:50) by electrospinning. Scanning electron microscope demonstrated smooth and uniform nanofibers with diameters in the range of 733±65nm and 226±73nm for align PLLA and random PLLA/GT 50:50 nanofibers, respectively. FTIR analysis, contact angle, in vitro biodegradation and tensile measurements were carried out to evaluate the chemical and mechanical properties of the different scaffolds. PLLA/GT 75:25 exhibited the most balanced properties compared to other scaffolds and was used for in vitro culture of nerve cells (PC12) to assess the potential of using these scaffolds as a substrate for nerve regeneration. The cells were found to attach and proliferate on aligned PLLA/GT 75:25 scaffolds, expressing bi-polar neurite extensions and the orientation of nerve cells was along the direction of the fiber alignment. Results of 8 days of in vitro culture of PC12 cells on aligned PLLA/GT 75:25 nanofibers, showed 20% increase in cell proliferation compared to PLLA/GT 75:25 random nanofibers. PLLA/GT 75:25 aligned nanofibers acted as a favorable cue to support neurite outgrowth and nerve cell elongation compared with PLLA nanofibers. Our results showed that aligned PLLA/GT 75:25 nanofibers are promising substrates for application as bioengineered grafts for nerve tissue regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Intermolecular interactions between B. mori silk fibroin and poly(L-lactic acid) in electrospun composite nanofibrous scaffolds

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Taddei, Paola, E-mail: paola.taddei@unibo.it [Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Via Belmeloro 8/2, 40126 Bologna (Italy); Tozzi, Silvia [Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Via Belmeloro 8/2, 40126 Bologna (Italy); Zuccheri, Giampaolo [Dipartimento di Farmacia e Biotecnologie e Centro Interdipartimentale di Ricerca Industriale Scienze della Vita e Tecnologie per la Salute, Università di Bologna, Via Irnerio 48, 40126 Bologna (Italy); Centro S3, Istituto Nanoscienze, Consiglio Nazionale delle Ricerche, Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (Italy); Martinotti, Simona; Ranzato, Elia [Dipartimento di Scienze e Innovazione Tecnologica, DiSIT, Università del Piemonte Orientale, viale Teresa Michel 11, 15121 Alessandria (Italy); Chiono, Valeria; Carmagnola, Irene [Dipartimento di Ingegneria Meccanica e Aerospaziale, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino (Italy); Tsukada, Masuhiro [Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University, 3-15-1, Tokida, Ueda, Nagano 386-8567 (Japan)

2017-01-01

In this study, composite nanofibrous scaffolds were obtained by electrospinning a trifluoroacetic acid solution containing B. mori silk fibroin (SF) and poly(L-lactic acid) (PLLA) in a 1:1 weight ratio. SF, PLLA and SF/PLLA nanofibres were prepared with average diameter sizes of 360 ± 90 nm, 470 ± 240 nm and 580 ± 220 nm, respectively, as assessed by SEM analysis. Vibrational and thermal analyses showed that upon blending in the SF/PLLA nanofibres, the crystallisation of PLLA was hindered by the presence of SF, which crystallized preferentially and underwent conformational changes that did not significantly change its prevailing β-sheet structure. The two components were thermodynamically compatible and the intermolecular interactions between them were revealed for the first time. Human keratinocytes were cultured on nanofibres and their viability and proliferation were determined. Preliminary in vitro tests showed that the incorporation of SF into the PLLA component enhanced cell adhesion and proliferation with respect to the unfunctionalised material. SF has been successfully used to modify the biomaterial properties and confirmed to be an efficient bioactive protein to mediate cell-biomaterial interaction. - Highlights: • Composite silk fibroin-poly(L-lactic acid) scaffolds were obtained by electrospinning. • Intermolecular interactions between SF and PLLA were revealed for the first time. • Upon blending, the crystallisation of PLLA was hindered by the presence of SF. • SF crystallized preferentially and maintained its prevailing β-sheet structure. • The incorporation of SF into PLLA enhanced human keratinocytes adhesion and proliferation.

Establishment of novel meniscal scaffold structures using polyglycolic and poly-l-lactic acids.

Science.gov (United States)

Murakami, Tomohiko; Otsuki, Shuhei; Nakagawa, Kosuke; Okamoto, Yoshinori; Inoue, Tae; Sakamoto, Yuki; Sato, Hideki; Neo, Masashi

2017-08-01

The purpose of this study was to evaluate various types of meniscus scaffolds that mimic the meniscus structure, and to establish a novel cell-free meniscus scaffold with polyglycolic acid or poly-l-lactic acid. Four types of scaffolds were implanted into Japanese white rabbits: poly-l-lactic acid sponge poly-l-lactic acid, PGA-coated PLLA sponge, PGA lamination, and film-coated PGA lamination. Samples were harvested at 8 and 12 weeks after implantation, and a compression stress test was performed. The meniscus size and Ishida scores were evaluated for regenerated tissue. Immunohistochemistry was analyzed by anti-type I, II and X collagen antibodies to investigate the structure of the regenerated tissue, and by anti-iNOS antibody to investigate the inflammatory tissue of the meniscus. The cell nuclei of lymphocytes and foreign body multinucleated giant cells were counted in hematoxylin and eosin staining. Modified Mankin scores for cartilage degeneration were used for assessment after Safranin-O/Fast Green staining. The biomechanical test showed that l- and film-coated PGA lamination exhibited greater strength than s- and PGA-coated PLLA sponge. At 12 weeks, the size of meniscus and the Ishida score in implanted film-coated PGA lamination were improved significantly compared with the defect groups. The type II collagen staining intensity in the PGA lamination lamination is significantly higher than the defect at eight weeks. The staining intensity of iNOS and number of lymphocytes significantly increased in sponge poly-l-lactic acid at eight weeks, and increased in p-PLLA at 12 weeks. Foreign body multinucleated giant cells in implantation groups appeared, especially at eight weeks. The Mankin score for film-coated PGA lamination was significantly lower than for the defect at 12 weeks. Novel meniscal scaffolds especially PGA should possess not only biological but also biomechanical functions. In conclusions, film-coated PGA lamination was the beneficial property

Growth on poly(L-lactic acid) porous scaffold preserves CD73 and CD90 immunophenotype markers of rat bone marrow mesenchymal stromal cells.

Science.gov (United States)

Zamparelli, Alessandra; Zini, Nicoletta; Cattini, Luca; Spaletta, Giulia; Dallatana, Davide; Bassi, Elena; Barbaro, Fulvio; Iafisco, Michele; Mosca, Salvatore; Parrilli, Annapaola; Fini, Milena; Giardino, Roberto; Sandri, Monica; Sprio, Simone; Tampieri, Anna; Maraldi, Nadir M; Toni, Roberto

2014-10-01

Few data are available on the effect of biomaterials on surface antigens of mammalian bone marrow-derived, adult mesenchymal stromal cells (MSCs). Since poly(L-lactic acid) or PLLA is largely used in tissue engineering of human bones, and we are developing a reverse engineering program to prototype with biomaterials the vascular architecture of bones for their bioartificial reconstruction, both in humans and animal models, we have studied the effect of porous, flat and smooth PLLA scaffolds on the immunophenotype of in vitro grown, rat MSCs in the absence of any coating, co-polymeric enrichment, and differentiation stimuli. Similar to controls on plastic, we show that our PLLA scaffold does not modify the distribution of some surface markers in rat MSCs. In particular, the maintained expression of CD73 and CD90 on two different subpopulations (small and large cells) is consistent with their adhesion to the PLLA scaffold through specialized appendages, and to their prominent content in actin. In addition, our PLLA scaffold favours retention of the intermediate filament desmin, believed a putative marker of undifferentiated state. Finally, it preserves all rat MSCs morphotypes, and allows for their survival, adhesion to the substrate, and replication. Remarkably, a subpopulation of rat MSCs grown on our PLLA scaffold exhibited formation of membrane protrusions of uncertain significance, although in a size range and morphology compatible with either motility blebs or shedding vesicles. In summary, our PLLA scaffold has no detrimental effect on a number of features of rat MSCs, primarily the expression of CD73 and CD90.

Plasma treatment induces internal surface modifications of electrospun poly(L-lactic) acid scaffold to enhance protein coating

International Nuclear Information System (INIS)

Jin Seo, Hyok; Hee Lee, Mi; Kwon, Byeong-Ju; Kim, Hye-Lee; Park, Jong-Chul; Jin Lee, Seung; Kim, Bong-Jin; Wang, Kang-Kyun; Kim, Yong-Rok

2013-01-01

Advanced biomaterials should also be bioactive with regard to desirable cellular responses, such as selective protein adsorption and cell attachment, proliferation, and differentiation. To enhance cell-material interactions, surface modifications have commonly been performed. Among the various surface modification approaches, atmospheric pressure glow discharge plasma has been used to change a hydrophobic polymer surface to a hydrophilic surface. Poly(L-lactic acid) (PLLA)-derived scaffolds lack cell recognition signals and the hydrophobic nature of PLLA hinders cell seeding. To make PLLA surfaces more conducive to cell attachment and spreading, surface modifications may be used to create cell-biomaterial interfaces that elicit controlled cell adhesion and maintain differentiated phenotypes. In this study, (He) gaseous atmospheric plasma glow discharge was used to change the characteristics of a 3D-type polymeric scaffold from hydrophobic to hydrophilic on both the outer and inner surfaces of the scaffold and the penetration efficiency with fibronectin was investigated. Field-emission scanning electron microscope images showed that some grooves were formed on the PLLA fibers after plasma treatment. X-ray photoelectron spectroscopy data also showed chemical changes in the PLLA structure. After plasma treatment, -CN (285.76 eV) was increased in C1s and -NH 2 (399.70 eV) was increased significantly and –N=CH (400.80 eV) and –NH 3 + (402.05 eV) were newly appeared in N1s. These changes allowed fibronectin to penetrate into the PLLA scaffold; this could be observed by confocal microscopy. In conclusion, helium atmospheric pressure plasma treatment was effective in modifying the polymeric scaffold, making it hydrophilic, and this treatment can also be used in tissue engineering research as needed to make polymers hydrophilic

Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies.

Science.gov (United States)

Lu, Helen H; Cooper, James A; Manuel, Sharron; Freeman, Joseph W; Attawia, Mohammed A; Ko, Frank K; Laurencin, Cato T

2005-08-01

The anterior cruciate ligament (ACL) is the most commonly injured intra-articular ligament of the knee, and limitations in existing reconstruction grafts have prompted an interest in tissue engineered solutions. Previously, we reported on a tissue-engineered ACL scaffold fabricated using a novel, three-dimensional braiding technology. A critical factor in determining cellular response to such a graft is material selection. The objective of this in vitro study was to optimize the braided scaffold, focusing on material composition and the identification of an appropriate polymer. The selection criteria are based on cellular response, construct degradation, and the associated mechanical properties. Three compositions of poly-alpha-hydroxyester fibers, namely polyglycolic acid (PGA), poly-L-lactic acid (PLLA), and polylactic-co-glycolic acid 82:18 (PLAGA) were examined. The effects of polymer composition on scaffold mechanical properties and degradation were evaluated in physiologically relevant solutions. Prior to culturing with primary rabbit ACL cells, scaffolds were pre-coated with fibronectin (Fn, PGA-Fn, PLAGA-Fn, PLLA-Fn), an important protein which is upregulated during ligament healing. Cell attachment and growth were examined as a function of time and polymer composition. While PGA scaffolds measured the highest tensile strength followed by PLLA and PLAGA, its rapid degradation in vitro resulted in matrix disruption and cell death over time. PLLA-based scaffolds maintained their structural integrity and exhibited superior mechanical properties over time. The response of ACL cells was found to be dependent on polymer composition, with the highest cell number measured on PLLA-Fn scaffolds. Surface modification of polymer scaffolds with Fn improved cell attachment efficiency and effected the long-term matrix production by ACL cells on PLLA and PLAGA scaffolds. Therefore based on the overall cellular response and its temporal mechanical and degradation properties

Morphology evolution of poly(L-lactic acid) (PLLA), poly(.epsilon.-caprolactone) (PCL) and polyethylene oxide (PEO) ternary blend and their effects on mechanical properties for bio scaffold applications

Czech Academy of Sciences Publication Activity Database

Ezzati, P.; Ghasemi, I.; Karrabi, M.; Azizi, H.; Fortelný, Ivan

2014-01-01

Roč. 38, č. 4 (2014), s. 449-456 ISSN 0379-153X Institutional support: RVO:61389013 Keywords : PLLA/PCL/PEO ternary blend * bio scaffold * melt blending Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.528, year: 2014

Facile fabrication of poly(L-lactic acid) microsphere-incorporated calcium alginate/hydroxyapatite porous scaffolds based on Pickering emulsion templates.

Science.gov (United States)

Hu, Yang; Ma, Shanshan; Yang, Zhuohong; Zhou, Wuyi; Du, Zhengshan; Huang, Jian; Yi, Huan; Wang, Chaoyang

2016-04-01

In this study, we develop a facile one-pot approach to the fabrication of poly(L-lactic acid) (PLLA) microsphere-incorporated calcium alginate (ALG-Ca)/hydroxyapatite (HAp) porous scaffolds based on HAp nanoparticle-stabilized oil-in-water Pickering emulsion templates, which contain alginate in the aqueous phase and PLLA in the oil phase. The emulsion aqueous phase is solidified by in situ gelation of alginate with Ca(2+) released from HAp by decreasing pH with slow hydrolysis of D-gluconic acid δ-lactone (GDL) to produce emulsion droplet-incorporated gels, followed by freeze-drying to form porous scaffolds containing microspheres. The pore structure of porous scaffolds can be adjusted by varying the HAp or GDL concentration. The compressive tests show that the increase of HAp or GDL concentration is beneficial to improve the compressive property of porous scaffolds, while the excessive HAp can lead to the decrease in compressive property. Moreover, the swelling behavior studies display that the swelling ratios of porous scaffolds reduce with increasing HAp or GDL concentration. Furthermore, hydrophobic drug ibuprofen (IBU) and hydrophilic drug bovine serum albumin (BSA) are loaded into the microspheres and scaffold matrix, respectively. In vitro drug release results indicate that BSA has a rapid release while IBU has a sustained release in the dual drug-loaded scaffolds. In vitro cell culture experiments verify that mouse bone mesenchymal stem cells can proliferate on the porous scaffolds well, indicating the good biocompatibility of porous scaffolds. All these results demonstrate that the PLLA microsphere-incorporated ALG-Ca/HAp porous scaffolds have a promising potential for tissue engineering and drug delivery applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Biocompatibility and biomechanical characteristics of loofah based scaffolds combined with hydroxyapatite, cellulose, poly-L-lactic acid with chondrocyte-like cells

International Nuclear Information System (INIS)

Cecen, Berivan; Kozaci, Leyla Didem; Yuksel, Mithat; Ustun, Ozcan; Ergur, Bekir Ugur; Havitcioglu, Hasan

2016-01-01

The current study reports the biocompatibility and biomechanical characteristics of loofah-based scaffolds combined with hydroxyapatite (HA), cellulose, poly-L-lactic acid (PLLA) with chondrocytes-like cells. Scanning electron microscope (SEM) micrographs of the scaffolds showed that the addition of PLLA usually resulted in an increase in cell's attachment on scaffolds. Mechanical and elemental analyzes were assessed using tensile test and Energy Dispersive X-ray spectrometry (EDS), respectively. In summary, we showed that the loofah + PLLA + HA scaffolds perform significantly better than other loofah–based scaffolds employed in terms of increasing a diversity of mechanical properties including tensile strength and Young's modulus. Based on the analysis of the differential scanning calorimetry (DSC) thermograms and EDS spectrums that give an idea about the calcium phosphate (CaP) ratios, the improvement in the mechanical properties could principally be recognized to the strong interaction formed between loofah, PLLA and HA. The viability of chondrocytes on loofah–based scaffolds was analyzed by XTT tests. However, none of the scaffolds have proved to be toxic in metabolic activity. The histological evaluation obtained by hematoxylin and eosin (H&E), Masson trichrome, toluidine blue and immunohistochemistry methods showed that cells in all scaffolds produced extracellular matrix that defined proteoglycan and type I-II collagens. The results of this study suggest that the loofah-based scaffold with desirable properties can be considered as an ideal candidate for cartilage tissue engineering applications. - Highlights: • In this study we designed a new scaffold and characterized it using biochemical and biomechanical assays. • Our manuscript with the novelty of the scaffold design will add new perspective in the literature about loofah based scaffolds. • The objective of the study is to investigate the natural and novel loofah based scaffolds with

Biocompatibility and biomechanical characteristics of loofah based scaffolds combined with hydroxyapatite, cellulose, poly-L-lactic acid with chondrocyte-like cells

Energy Technology Data Exchange (ETDEWEB)

Cecen, Berivan, E-mail: berivan.erik@deu.edu.tr [Dokuz Eylul University, The Institute of Health Science, Department of Biomechanics, 35340 Izmir (Turkey); Kozaci, Leyla Didem [Yildirim Beyazit University, Medical Faculty, Department of Medical Biochemistry, 06800 Ankara (Turkey); Yildirim Beyazit University, Musculoskeletal System Studies Research Center, 06800 Ankara (Turkey); Yuksel, Mithat [Ege University, Engineering Faculty, Department of Chemical Engineering, 35100 Izmir (Turkey); Ustun, Ozcan; Ergur, Bekir Ugur [Dokuz Eylul University, Department of Histology & Embryology, 35340 Izmir (Turkey); Havitcioglu, Hasan [Dokuz Eylul University, The Institute of Health Science, Department of Biomechanics, 35340 Izmir (Turkey); Dokuz Eylul University, Medicine Faculty, Department of Orthopaedics and Traumatology, 35340 Izmir (Turkey)

2016-12-01

The current study reports the biocompatibility and biomechanical characteristics of loofah-based scaffolds combined with hydroxyapatite (HA), cellulose, poly-L-lactic acid (PLLA) with chondrocytes-like cells. Scanning electron microscope (SEM) micrographs of the scaffolds showed that the addition of PLLA usually resulted in an increase in cell's attachment on scaffolds. Mechanical and elemental analyzes were assessed using tensile test and Energy Dispersive X-ray spectrometry (EDS), respectively. In summary, we showed that the loofah + PLLA + HA scaffolds perform significantly better than other loofah–based scaffolds employed in terms of increasing a diversity of mechanical properties including tensile strength and Young's modulus. Based on the analysis of the differential scanning calorimetry (DSC) thermograms and EDS spectrums that give an idea about the calcium phosphate (CaP) ratios, the improvement in the mechanical properties could principally be recognized to the strong interaction formed between loofah, PLLA and HA. The viability of chondrocytes on loofah–based scaffolds was analyzed by XTT tests. However, none of the scaffolds have proved to be toxic in metabolic activity. The histological evaluation obtained by hematoxylin and eosin (H&E), Masson trichrome, toluidine blue and immunohistochemistry methods showed that cells in all scaffolds produced extracellular matrix that defined proteoglycan and type I-II collagens. The results of this study suggest that the loofah-based scaffold with desirable properties can be considered as an ideal candidate for cartilage tissue engineering applications. - Highlights: • In this study we designed a new scaffold and characterized it using biochemical and biomechanical assays. • Our manuscript with the novelty of the scaffold design will add new perspective in the literature about loofah based scaffolds. • The objective of the study is to investigate the natural and novel loofah based scaffolds with

Developing bioactive composite scaffolds for bone tissue engineering

Science.gov (United States)

Chen, Yun

Poly(L-lactic acid) (PLLA) films were fabricated using the method of dissolving and evaporation. PLLA scaffold was prepared by solid-liquid phase separation of polymer solutions and subsequent sublimation of solvent. Bonelike apatite coating was formed on PLLA films, PLLA scaffolds and poly(glycolic acid) (PGA) scaffolds in 24 hours through an accelerated biomimetic process. The ion concentrations in the simulated body fluid (SBF) were nearly 5 times of those in human blood plasma. The apatite formed was characterized using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The apatite formed in 5SBF was similar in morphology and composition to that formed in the classical biomimetic process employing SBF or 1.5SBF, and similar to that of natural bone. This indicated that the biomimetic apatite coating process could be accelerated by using concentrated simulated body fluid at 37°C. Besides saving time, the accelerated biomimetic process is particularly significant to biodegradable polymers. Some polymers which degrade too fast to be coated with apatite by a classical biomimetic process, for example PGA, could be coated with bone-like apatite in an accelerated biomimetic process. Collagen and apatite were co-precipitated as a composite coating on poly(L-lactic acid) (PLLA) in an accelerated biomimetic process. The incubation solution contained collagen (1g/L) and simulated body fluid (SBF) with 5 times inorganic ionic concentrations as human blood plasma. The coating formed on PLLA films and scaffolds after 24 hours incubation was characterized using EDX, XRD, FTIR, and SEM. It was shown that the coating contained carbonated bone-like apatite and collagen, the primary constituents of natural bone. SEM showed a complex composite coating of submicron bone-like apatite particulates combined with collagen fibrils. This work provided an efficient process to obtain

Modulation of physical and biological properties of a composite PLLA and polyaspartamide derivative obtained via thermally induced phase separation (TIPS) technique

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Carfì Pavia, Francesco [Department of Civil, Environmental, Aerospace, Materials Engineering, University of Palermo, 90142 Palermo (Italy); Palumbo, Fabio Salvatore, E-mail: fabiosalvatore.palumbo@unipa.it [Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo (Italy); La Carrubba, Vincenzo [Department of Civil, Environmental, Aerospace, Materials Engineering, University of Palermo, 90142 Palermo (Italy); Istituto Euro Mediterraneo di Scienza e Tecnologia (IEMEST) Via Michele Miraglia, 20 - 90139, Palermo (Italy); Bongiovì, Flavia [Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo (Italy); Brucato, Valerio [Department of Civil, Environmental, Aerospace, Materials Engineering, University of Palermo, 90142 Palermo (Italy); Pitarresi, Giovanna; Giammona, Gaetano [Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo (Italy)

2016-10-01

In the present study, blend of poly L-lactic acid (PLLA) with a graft copolymer based on α,β-poly(N-hydroxyethyl)-DL-aspartamide and PLA named PHEA-PLA, has been used to design porous scaffold by using Thermally Induced Phase Separation (TIPS) technique. Starting from a homogeneous ternary solution of polymers, dioxane and deionised water, PLLA/PHEA-PLA porous foams have been produced by varying the polymers concentration and de-mixing temperature in metastable region. Results have shown that scaffolds prepared with a polymer concentration of 4% and de-mixing temperature of 22.5 °C are the best among those assessed, due to their optimal pore size and interconnection. SEM and DSC analysis have been carried out respectively to study scaffold morphology and the influence of PHEA-PLA on PLLA crystallization, while DMF extraction has been carried out in order to quantify PHEA-PLA into the final scaffolds. To evaluate scaffold biodegradability, a hydrolysis study has been performed until 56 days by incubating systems in a media mimicking physiological environment (pH 7.4). Results obtained have highlighted a progressive increase in weight loss with time in PLLA/PHEA-PLA scaffolds, conceivably due to the presence of PHEA-PLA and polymers interpenetration. Viability and adhesion of bovine chondrocytes seeded on the scaffolds have been studied by MTS test and SEM analysis. From results achieved it appears that the presence of PHEA-PLA increases cells affinity, allowing a faster adhesion and proliferation inside the scaffold. - Highlights: • Blended scaffolds of PLLA and PHEA-PLA were successfully obtained with TIPS technique. • Scaffolds with an open porosity and a good interconnection were formed. • PHEA-PLA improved water affinity accelerating rate of hydrolysis of blended scaffold. • Preliminary assay suggests that PHEA-PLA improved chondrocytes uptake and viability.

Modulation of physical and biological properties of a composite PLLA and polyaspartamide derivative obtained via thermally induced phase separation (TIPS) technique

International Nuclear Information System (INIS)

Carfì Pavia, Francesco; Palumbo, Fabio Salvatore; La Carrubba, Vincenzo; Bongiovì, Flavia; Brucato, Valerio; Pitarresi, Giovanna; Giammona, Gaetano

2016-01-01

In the present study, blend of poly L-lactic acid (PLLA) with a graft copolymer based on α,β-poly(N-hydroxyethyl)-DL-aspartamide and PLA named PHEA-PLA, has been used to design porous scaffold by using Thermally Induced Phase Separation (TIPS) technique. Starting from a homogeneous ternary solution of polymers, dioxane and deionised water, PLLA/PHEA-PLA porous foams have been produced by varying the polymers concentration and de-mixing temperature in metastable region. Results have shown that scaffolds prepared with a polymer concentration of 4% and de-mixing temperature of 22.5 °C are the best among those assessed, due to their optimal pore size and interconnection. SEM and DSC analysis have been carried out respectively to study scaffold morphology and the influence of PHEA-PLA on PLLA crystallization, while DMF extraction has been carried out in order to quantify PHEA-PLA into the final scaffolds. To evaluate scaffold biodegradability, a hydrolysis study has been performed until 56 days by incubating systems in a media mimicking physiological environment (pH 7.4). Results obtained have highlighted a progressive increase in weight loss with time in PLLA/PHEA-PLA scaffolds, conceivably due to the presence of PHEA-PLA and polymers interpenetration. Viability and adhesion of bovine chondrocytes seeded on the scaffolds have been studied by MTS test and SEM analysis. From results achieved it appears that the presence of PHEA-PLA increases cells affinity, allowing a faster adhesion and proliferation inside the scaffold. - Highlights: • Blended scaffolds of PLLA and PHEA-PLA were successfully obtained with TIPS technique. • Scaffolds with an open porosity and a good interconnection were formed. • PHEA-PLA improved water affinity accelerating rate of hydrolysis of blended scaffold. • Preliminary assay suggests that PHEA-PLA improved chondrocytes uptake and viability.

The influence of type-I collagen-coated PLLA aligned nanofibers on growth of blood outgrowth endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Feng Zhangqi; Huang Ningping; Wang Yichun; Gu Zhongze [State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096 (China); Lu Huijun [Department of Vascular Surgery, Wuxi People' s Hospital, Wuxi 214023 (China); Leach, Michelle K [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Liu Changjian, E-mail: gu@seu.edu.c [Department of Vascular Surgery, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008 (China)

2010-12-15

Nanofibrous scaffolds have been applied widely in tissue engineering to simulate the nanostructure of natural extracellular matrix (ECM) and promote cell bioactivity. The aim of this study was to design a biocompatible nanofibrous scaffold for blood outgrowth endothelial cells (BOECs) and investigate the interaction between the topography of the nanofibrous scaffold and cell growth. Poly(l-lactic acid) (PLLA) random and aligned nanofibers with a uniform diameter distribution were fabricated by electrospinning. NH{sub 3} plasma etching was used to create a hydrophilic surface on the nanofibers to improve type-I collagen adsorption; the conditions of the NH{sub 3} plasma etching were optimized by XPS and water contact angle analysis. Cell attachment, proliferation, viability, phenotype and morphology of BOECs cultured on type-I collagen-coated PLLA film (col-Film), random fibers (col-RFs) and aligned fibers (col-AFs) were detected over a 7 day culture period. The results showed that collagen-coated PLLA nanofibers improved cell attachment and proliferation; col-AFs induced the directional growth of cells along the aligned nanofibers and enhanced endothelialization. We suggest that col-AFs may be a potential implantable scaffold for vascular tissue engineering.

Influence of Poly-(L-Lactic Acid Nanofiber Functionalization on Maximum Load, Young's Modulus, and Strain of Nanofiber Scaffolds Before and After Cultivation of Osteoblasts: An In Vitro Study

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Jürgen Paletta

2009-01-01

Full Text Available The aim of this study was to characterize the influence of functionalization of synthetic poly-(L-lactic acid (PLLA nanofibers on mechanical properties such as maximum load, elongation, and Young's modulus. Furthermore, the impact of osteoblast growth on the various nanofiber scaffolds stability was determined. Nanofiber matrices composed of PLLA, PLLA-collagen, or BMP-2–incorporated PLLA were produced from different solvents by electrospinning. Standardized test samples of each nanofiber scaffold were subjected to failure protocol before or after incubation in the presence of osteoblasts over a period of 22 days under osteoinductive conditions. PLLA nanofibers electrospun from hexafluoroisopropanol (HFIP showed a higher strain and tended to have increased maximum loads and Young's modulus compared to PLLA fibers spun from dichloromethane. In addition, they had a higher resistance during incubation in the presence of cells. Functionalization by incorporation of growth factors increased Young's modulus, independent of the solvent used. However, the incorporation of growth factors using the HFIP system resulted in a loss of strain. Similar results were observed when PLLA was blended with different ratios of collagen. Summarizing the results, this study indicates that different functionalization strategies influence the mechanical stability of PLLA nanofibers. Therefore, an optimization of nanofibers should not only account for the optimization of biological effects on cells, but also has to consider the stability of the scaffold.

Investigation of silk fibroin nanoparticle-decorated poly(L-lactic acid composite scaffolds for osteoblast growth and differentiation

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Chen BQ

2017-03-01

Full Text Available Biao-Qi Chen,1 Ranjith Kumar Kankala,1,2 Ai-Zheng Chen,1,2 Ding-Zhu Yang,1 Xiao-Xia Cheng,1 Ni-Na Jiang,1,2 Kai Zhu,3,4 Shi-Bin Wang1,2 1Institute of Biomaterials and Tissue Engineering, 2Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen, Fujian, 3Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, 4Shanghai Institute of Cardiovascular Disease, Shanghai, People’s Republic of China Abstract: Attempts to reflect the physiology of organs is quite an intricacy during the tissue engineering process. An ideal scaffold and its surface topography can address and manipulate the cell behavior during the regeneration of targeted tissue, affecting the cell growth and differentiation significantly. Herein, silk fibroin (SF nanoparticles were incorporated into poly(L-lactic acid (PLLA to prepare composite scaffolds via phase-inversion technique using supercritical carbon dioxide (SC-CO2. The SF nanoparticle core increased the surface roughness and hydrophilicity of the PLLA scaffolds, leading to a high affinity for albumin attachment. The in vitro cytotoxicity test of SF/PLLA scaffolds in L929 mouse fibroblast cells indicated good biocompatibility. Then, the in vitro interplay between mouse preosteoblast cell (MC3T3-E1 and various topological structures and biochemical cues were evaluated. The cell adhesion, proliferation, osteogenic differentiation and their relationship with the structures as well as SF content were explored. The SF/PLLA weight ratio (2:8 significantly affected the MC3T3-E1 cells by improving the expression of key players in the regulation of bone formation, ie, alkaline phosphatase (ALP, osteocalcin (OC and collagen 1 (COL-1. These results suggest not only the importance of surface topography and biochemical cues but also the potential of applying SF/PLLA composite scaffolds as biomaterials in bone tissue engineering. Keywords: super critical fluids, surface topography, bone

Investigation on thermomechanical properties of poly (l-lactic acid) for the stretch blow moulding process of bioresorbable vascular scaffold

Science.gov (United States)

Wei, Huidong; Menary, Gary

2017-10-01

Stretch blow moulding process has been used for the manufacture of bioresorbable vascular scaffold (BVS) made by poly (l-lactic acid) (PLLA) to improve its mechanical performance. In order to better understand the process, thermomechanical properties of PLLA were investigated by experimental method. Extruded PLLA sheets were biaxial stretched under strain rate of 1s-1, 4s-1 and 16s-1 to simulate the deformation process applicable in the blow moulding process. Both the equal-biaxial stretch and constant-width stretch were conducted by an in-house developed equipment. By differential scanning calorimeter (DSC), thermal analysis for materials before and after stretch were compared to evaluate the microstructural change of PLLA materials in the deformation process. A constitutive model based on glass rubber model was presented to simulate the mechanical behaviour of PLLA above glass transition under biaxial deformation.

Biomimetic scaffolds containing nanofibers coated with willemite nanoparticles for improvement of stem cell osteogenesis

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Ramezanifard, Rouhallah [Department of Biotechnology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of); Seyedjafari, Ehsan, E-mail: seyedjafari@ut.ac.ir [Department of Biotechnology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of); Ardeshirylajimi, Abdolreza [Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Soleimani, Masoud [Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)

2016-05-01

Nowadays, discovering osteogenesis stimulating effectors is one of the major topics in bone tissue engineering and regenerative medicine. In this study, the proliferation rate and osteogenic differentiation potency of adipose-derived mesenchymal stem cells (AT-MSCs) cultured on poly (L-lactide acid) (PLLA) and willemite-coated PLLA were investigated by MTT assay and common osteogenic markers such as alkaline phosphatase (ALP) activity, calcium mineral deposition and bone-related genes expression. Willemite-coated PLLA showed a higher proliferation support to AT-MSCs in comparison to PLLA and TCPS. During the period of study, AT-MSCs cultured on willemite-coated PLLA scaffolds exhibited the greatest ALP activity and mineralization. Gene expression analysis demonstrated that the highest expression of four important osteogenic-related genes, osteonectin, Runx2, collagen type 1 and osteocalcin was observed in stem cells cultured on willemite-coated PLLA nanofibrous scaffolds. According to the results, willemite-coated PLLA could be a suitable substrate to support the proliferation and osteogenic differentiation of stem cells and holds promising potential for bone tissue engineering and regenerative medicine applications. - Highlights: • Biodegradable PLLA eletrospun nanofibrous scaffold was prepared. • PLLA nanofibers were treated with plasma and coated with willemite nanoparticles. • MSC on willemite-coated PLLA showed greater osteogenic differentiation than those on uncoated PLLA and TCPS. • Willemite-coated nanofibers hold promising potential for bone tissue engineering application.

Biomimetic scaffolds containing nanofibers coated with willemite nanoparticles for improvement of stem cell osteogenesis

International Nuclear Information System (INIS)

Ramezanifard, Rouhallah; Seyedjafari, Ehsan; Ardeshirylajimi, Abdolreza; Soleimani, Masoud

2016-01-01

Nowadays, discovering osteogenesis stimulating effectors is one of the major topics in bone tissue engineering and regenerative medicine. In this study, the proliferation rate and osteogenic differentiation potency of adipose-derived mesenchymal stem cells (AT-MSCs) cultured on poly (L-lactide acid) (PLLA) and willemite-coated PLLA were investigated by MTT assay and common osteogenic markers such as alkaline phosphatase (ALP) activity, calcium mineral deposition and bone-related genes expression. Willemite-coated PLLA showed a higher proliferation support to AT-MSCs in comparison to PLLA and TCPS. During the period of study, AT-MSCs cultured on willemite-coated PLLA scaffolds exhibited the greatest ALP activity and mineralization. Gene expression analysis demonstrated that the highest expression of four important osteogenic-related genes, osteonectin, Runx2, collagen type 1 and osteocalcin was observed in stem cells cultured on willemite-coated PLLA nanofibrous scaffolds. According to the results, willemite-coated PLLA could be a suitable substrate to support the proliferation and osteogenic differentiation of stem cells and holds promising potential for bone tissue engineering and regenerative medicine applications. - Highlights: • Biodegradable PLLA eletrospun nanofibrous scaffold was prepared. • PLLA nanofibers were treated with plasma and coated with willemite nanoparticles. • MSC on willemite-coated PLLA showed greater osteogenic differentiation than those on uncoated PLLA and TCPS. • Willemite-coated nanofibers hold promising potential for bone tissue engineering application.

Synthesis of PDLLA/PLLA-bentonite nanocomposite through sonication

International Nuclear Information System (INIS)

Sitompul, Johnner; Setyawan, Daru; Kim, Daniel Young Joon; Lee, Hyung Woo

2016-01-01

This paper concerns the synthesis of poly(D,L-lactic acid)/poly(L-lactic acid) bentonite nanocomposites. Poly (D,L-lactic acid) (PDLLA) was synthesized using lactic acid through the ZnO-catalyzed direct polycondensation method at vacuum pressure and poly(L-lactic acid) (PLLA) was synthesized with L-lactide by ring-opening polymerization method. The PDLLA/PLLA-bentonite nanocomposite films were synthesized using the solvent casting method. The nanoclay, bentonite, was prepared using the solution-intercalation method by dissolving the nanoparticles into chloroform before sonication. In this study, PDLLA/PLLA-bentonite nanocomposite films were produced using variable amounts of nanoclay and sonication times during the mixing of PDLLA/PLLA and bentonite. The properties of the PDLLA/PLLA nanocomposites were then characterized using the X-ray Diffraction (XRD), Universal Testing Machine (UTM), Water Vapor Permeability (WVP) tests, and the enzymatic biodegradability test. The XRD test was used to measure the intercalation of nanoclay layers in the PDLLA/PLLA matrix and the PDLLA/PLLA-bentonite intercalated nanocomposite films. It was found through these various tests that adding bentonite to the PDLLA/PLLA increases tensile strength to 56.76 MP. Furthermore, the biodegradability increases as well as the barrier properties of the polymers The different sonication time used during the mixing of the polymer solution with bentonite also affected the properties of the PDLLA/PLLA-bentonite nanocomposite films.

Synthesis of PDLLA/PLLA-bentonite nanocomposite through sonication

Energy Technology Data Exchange (ETDEWEB)

Sitompul, Johnner, E-mail: sitompul@che.itb.ac.id; Setyawan, Daru, E-mail: daru.setyawan@gmail.com; Kim, Daniel Young Joon, E-mail: daniel.kim12321@gmail.com [Department of Chemical Engineering, Faculty of Industrial Technology, Institute of Technology Bandung Jl. Ganesha 10, Bandung, West Java, 40132 (Indonesia); Lee, Hyung Woo, E-mail: leehw@che.itb.ac.id [Department of Chemical Engineering, Faculty of Industrial Technology, Institute of Technology Bandung Jl. Ganesha 10, Bandung, West Java, 40132 (Indonesia); Research and Business Foundation, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi, 440-746 (Korea, Republic of)

2016-04-19

This paper concerns the synthesis of poly(D,L-lactic acid)/poly(L-lactic acid) bentonite nanocomposites. Poly (D,L-lactic acid) (PDLLA) was synthesized using lactic acid through the ZnO-catalyzed direct polycondensation method at vacuum pressure and poly(L-lactic acid) (PLLA) was synthesized with L-lactide by ring-opening polymerization method. The PDLLA/PLLA-bentonite nanocomposite films were synthesized using the solvent casting method. The nanoclay, bentonite, was prepared using the solution-intercalation method by dissolving the nanoparticles into chloroform before sonication. In this study, PDLLA/PLLA-bentonite nanocomposite films were produced using variable amounts of nanoclay and sonication times during the mixing of PDLLA/PLLA and bentonite. The properties of the PDLLA/PLLA nanocomposites were then characterized using the X-ray Diffraction (XRD), Universal Testing Machine (UTM), Water Vapor Permeability (WVP) tests, and the enzymatic biodegradability test. The XRD test was used to measure the intercalation of nanoclay layers in the PDLLA/PLLA matrix and the PDLLA/PLLA-bentonite intercalated nanocomposite films. It was found through these various tests that adding bentonite to the PDLLA/PLLA increases tensile strength to 56.76 MP. Furthermore, the biodegradability increases as well as the barrier properties of the polymers The different sonication time used during the mixing of the polymer solution with bentonite also affected the properties of the PDLLA/PLLA-bentonite nanocomposite films.

Ligament regeneration using an absorbable stent-shaped poly-L-lactic acid scaffold in a rabbit model.

Science.gov (United States)

Nishimoto, Hanako; Kokubu, Takeshi; Inui, Atsuyuki; Mifune, Yutaka; Nishida, Kotaro; Fujioka, Hiroyuki; Yokota, Kumiko; Hiwa, Chiaki; Kurosaka, Masahiro

2012-11-01

Ligaments are frequently damaged in sports activities and trauma, and severe ligament injury can lead to joint instability and osteoarthritis. In this study, we aimed to regenerate the medial collateral ligament (MCL) using an absorbable stent-shaped poly-L-lactic acid (PLLA) scaffold in a rabbit model to examine the biocompatibility and mechanical properties. Twenty-three Japanese white rabbits were used in this study. MCL defects were surgically created in the knee joints and then reconstructed using stent-shaped PLLA scaffolds. As controls, flexor digitorum longus (FDL) tendons were implanted into the contralateral knees. Seven rabbits were sacrificed at three time points, conducted four, eight and 16 weeks after the operation. The regenerated tissues were histologically evaluated using fibre alignment scoring, morphology of fibroblast scoring and immunohistochemical analysis of types I and III collagen. The regenerated tissues were also biomechanically evaluated by measuring the ultimate failure load and stiffness. At four weeks post-operation, spindle-shaped cells were observed on the inside of the scaffolds. At eight weeks, maturation of the regenerated tissues and collagen fibre alignment parallel to the ligaments was observed. At 16 weeks, the fibre alignment had become denser. The fibre alignment and morphology of fibroblast scores significantly increased in a time-dependent manner. Expression of type I collagen was more strongly observed in the scaffold group at eight and 16 weeks post-operation than at four weeks. Type III collagen was also observed at four, eight and 16 weeks post-operation. A thin layer of fibrocartilage was observed at the ligament-bone junction at eight and 16 weeks. The ultimate failure load of the scaffold group was 46.7 ± 20.7 N, 66.5 ± 11.0 N and 74.3 ± 11.5 N at four, eight and 16 weeks post-operation, respectively. There was no statistical difference between the normal MCL and the scaffold group at 16 weeks post

A structural model for the flexural mechanics of nonwoven tissue engineering scaffolds.

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Engelmayr, George C; Sacks, Michael S

2006-08-01

The development of methods to predict the strength and stiffness of biomaterials used in tissue engineering is critical for load-bearing applications in which the essential functional requirements are primarily mechanical. We previously quantified changes in the effective stiffness (E) of needled nonwoven polyglycolic acid (PGA) and poly-L-lactic acid (PLLA) scaffolds due to tissue formation and scaffold degradation under three-point bending. Toward predicting these changes, we present a structural model for E of a needled nonwoven scaffold in flexure. The model accounted for the number and orientation of fibers within a representative volume element of the scaffold demarcated by the needling process. The spring-like effective stiffness of the curved fibers was calculated using the sinusoidal fiber shapes. Structural and mechanical properties of PGA and PLLA fibers and PGA, PLLA, and 50:50 PGA/PLLA scaffolds were measured and compared with model predictions. To verify the general predictive capability, the predicted dependence of E on fiber diameter was compared with experimental measurements. Needled nonwoven scaffolds were found to exhibit distinct preferred (PD) and cross-preferred (XD) fiber directions, with an E ratio (PD/XD) of approximately 3:1. The good agreement between the predicted and experimental dependence of E on fiber diameter (R2 = 0.987) suggests that the structural model can be used to design scaffolds with E values more similar to native soft tissues. A comparison with previous results for cell-seeded scaffolds (Engelmayr, G. C., Jr., et al., 2005, Biomaterials, 26(2), pp. 175-187) suggests, for the first time, that the primary mechanical effect of collagen deposition is an increase in the number of fiber-fiber bond points yielding effectively stiffer scaffold fibers. This finding indicated that the effects of tissue deposition on needled nonwoven scaffold mechanics do not follow a rule-of-mixtures behavior. These important results underscore

Characterization of a PLLA-Collagen I Blend Nanofiber Scaffold with Respect to Growth and Osteogenic Differentiation of Human Mesenchymal Stem Cells

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Markus D. Schofer

2009-01-01

Full Text Available The aim of this study was to enhance synthetic poly(L-lactic acid (PLLA nanofibers by blending with collagen I (COLI in order to improve their ability to promote growth and osteogenic differentiation of stem cells in vitro. Fiber matrices composed of PLLA and COLI in different ratios were characterized with respect to their morphology, as well as their ability to promote growth of human mesenchymal stem cells (hMSC over a period of 22 days. Furthermore, the course of differentiation was analyzed by gene expression of alkaline phosphatase (ALP, osteocalcin (OC, and COLI. The PLLA-COLI blend nanofibers presented themselves with a relatively smooth surface. They were more hydrophilic as compared to PLLA nanofibers alone and formed a gel-like structure with a stable nanofiber backbone when incubated in aqueous solutions. We examined nanofibers composed of different PLLA and COLI ratios. A composition of 4:1 ratio of PLLA:COLI showed the best results. When hMSC were cultured on the PLLA-COLI nanofiber blend, growth as well as osteoblast differentiation (determined as gene expression of ALP, OC, and COLI was enhanced when compared to PLLA nanofibers alone. Therefore, the blending of PLLA with COLI might be a suitable tool to enhance PLLA nanofibers with respect to bone tissue engineering.

Culture of equine fibroblast-like synoviocytes on synthetic tissue scaffolds towards meniscal tissue engineering: a preliminary cell-seeding study

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Jennifer J. Warnock

2014-04-01

Full Text Available Introduction. Tissue engineering is a new methodology for addressing meniscal injury or loss. Synovium may be an ideal source of cells for in vitro meniscal fibrocartilage formation, however, favorable in vitro culture conditions for synovium must be established in order to achieve this goal. The objective of this study was to determine cellularity, cell distribution, and extracellular matrix (ECM formation of equine fibroblast-like synoviocytes (FLS cultured on synthetic scaffolds, for potential application in synovium-based meniscal tissue engineering. Scaffolds included open-cell poly-L-lactic acid (OPLA sponges and polyglycolic acid (PGA scaffolds cultured in static and dynamic culture conditions, and PGA scaffolds coated in poly-L-lactic (PLLA in dynamic culture conditions.Materials and Methods. Equine FLS were seeded on OPLA and PGA scaffolds, and cultured in a static environment or in a rotating bioreactor for 12 days. Equine FLS were also seeded on PGA scaffolds coated in 2% or 4% PLLA and cultured in a rotating bioreactor for 14 and 21 days. Three scaffolds from each group were fixed, sectioned and stained with Masson’s Trichrome, Safranin-O, and Hematoxylin and Eosin, and cell numbers and distribution were analyzed using computer image analysis. Three PGA and OPLA scaffolds from each culture condition were also analyzed for extracellular matrix (ECM production via dimethylmethylene blue (sulfated glycosaminoglycan assay and hydroxyproline (collagen assay. PLLA coated PGA scaffolds were analyzed using double stranded DNA quantification as areflection of cellularity and confocal laser microscopy in a fluorescent cell viability assay.Results. The highest cellularity occurred in PGA constructs cultured in a rotating bioreactor, which also had a mean sulfated glycosaminoglycan content of 22.3 µg per scaffold. PGA constructs cultured in static conditions had the lowest cellularity. Cells had difficulty adhering to OPLA and the PLLA

An in vivo evaluation of PLLA/PLLA-gHA nano-composite for internal fixation of mandibular bone fractures.

Science.gov (United States)

Peng, Weihai; Zheng, Wei; Shi, Kai; Wang, Wangshu; Shao, Ying; Zhang, Duo

2015-11-09

Internal fixation of bone fractures using biodegradable poly(L-lactic-acid) (PLLA)-based materials has attracted the attention of many researchers. In the present study, 36 male beagle dogs were randomly assigned to two groups: PLLA/PLLA-gHA (PLLA-grafted hydroxyapatite) group and PLLA group. PLLA/PLLA-gHA and PLLA plates were embedded in the muscular bags of the erector spinae and also implanted to fix mandibular bone fractures in respective groups. At 1, 2, 3, 6, 9, and 12 months postoperatively, the PLLA/PLLA-gHA and PLLA plates were evaluated by adsorption and degradation tests, and the mandibles were examined through radiographic analysis, biomechanical testing, and histological analysis. The PLLA/PLLA-gHA plates were non-transparent and showed a creamy white color, and the PLLA plates were transparent and faint yellow in color. At all time points following surgery, adsorption and degradation of the PLLA/PLLA-gHA plates were significantly less than those of the PLLA plates, and the lateral and longitudinal bending strengths of the surgically treated mandibles of the beagle dogs in the PLLA/PLLA-gHA group were significantly greater than those of the PLLA group and reached almost the value of intact mandibles at 12 months postoperatively. Additionally, relatively rapid bone healing was observed in the PLLA/PLLA-gHA group with the formation of new lamellar bone tissues at 12 months after the surgery. The PLLA/PLLA-gHA nano-composite can be employed as a biodegradable material for internal fixation of mandibular bone fractures.

An in vivo evaluation of PLLA/PLLA-gHA nano-composite for internal fixation of mandibular bone fractures

International Nuclear Information System (INIS)

Peng, Weihai; Shi, Kai; Wang, Wangshu; Shao, Ying; Zhang, Duo; Zheng, Wei

2015-01-01

Internal fixation of bone fractures using biodegradable poly(L-lactic-acid) (PLLA)-based materials has attracted the attention of many researchers. In the present study, 36 male beagle dogs were randomly assigned to two groups: PLLA/PLLA-gHA (PLLA-grafted hydroxyapatite) group and PLLA group. PLLA/PLLA-gHA and PLLA plates were embedded in the muscular bags of the erector spinae and also implanted to fix mandibular bone fractures in respective groups. At 1, 2, 3, 6, 9, and 12 months postoperatively, the PLLA/PLLA-gHA and PLLA plates were evaluated by adsorption and degradation tests, and the mandibles were examined through radiographic analysis, biomechanical testing, and histological analysis. The PLLA/PLLA-gHA plates were non-transparent and showed a creamy white color, and the PLLA plates were transparent and faint yellow in color. At all time points following surgery, adsorption and degradation of the PLLA/PLLA-gHA plates were significantly less than those of the PLLA plates, and the lateral and longitudinal bending strengths of the surgically treated mandibles of the beagle dogs in the PLLA/PLLA-gHA group were significantly greater than those of the PLLA group and reached almost the value of intact mandibles at 12 months postoperatively. Additionally, relatively rapid bone healing was observed in the PLLA/PLLA-gHA group with the formation of new lamellar bone tissues at 12 months after the surgery. The PLLA/PLLA-gHA nano-composite can be employed as a biodegradable material for internal fixation of mandibular bone fractures. (paper)

Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration

Science.gov (United States)

Halima Shamaz, Bibi; Anitha, A.; Vijayamohan, Manju; Kuttappan, Shruthy; Nair, Shantikumar; Nair, Manitha B.

2015-10-01

Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)-polyvinyl alcohol (PVA) were incorporated into a gelatin-nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin-HA matrix. The incorporation of PLLA microfibers within the gelatin-nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (Surgiwear™). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics.

Stereocomplexation of low molecular weight poly(L-lactic acid) and high molecular weight poly(D-lactic acid), radiation crosslinking PLLA/PDLA stereocomplexes and their characterization

International Nuclear Information System (INIS)

Quynh, Tran Minh; Mai, Hoang Hoa; Lan, Pham Ngoc

2013-01-01

Poly(L-lactic acid)s (PLLAx) were synthesized from L-lactic acid by polycondensation. Different stereocomplexes were also obtained with equimolar mixtures of synthesized PLLAx and a commercial PDLA. The stereocomplexes were crosslinked with triallyl isocyanurate (TAIC) by gamma irradiation. Crosslinking density increased with radiation doses, the heavier the crosslinking network, the lower its swelling degree. The crosslinking structures were introduced in the stereocomplexes inhibiting the mobility for crystallization of PLLA molecules. Thermal and mechanical properties of PLA stereocomplexes were remarkably enhanced by radiation induced crosslinking. PLA stereocomplex does not seem to be degraded by PLLA degrading microorganisms existing in compost at room temperature, but the synthesized PLLA was significantly degraded. - Highlights: ► Complete PLA stereocomplex was obtained from synthesized PLLA and a commercial PDLA. ► Melting temperature of stereocomplex were much improved by gamma irradiation. ► Crosslinking network inhibited the mobility of polymeric chains for crystallization. ► Biodegradability of PLLA was reduced by stereocomplexation and crosslinking.

A mesoporous silica composite scaffold: Cell behaviors, biomineralization and mechanical properties

Science.gov (United States)

Xu, Yong; Gao, Dan; Feng, Pei; Gao, Chengde; Peng, Shuping; Ma, HaoTian; Yang, Sheng; Shuai, Cijun

2017-11-01

Mesoporous structure is beneficial to cellular response due to the large specific surface area and high pore volume. In this study, mesoporous silica (SBA15) was incorporated into poly-L-lactic acid (PLLA) to construct composite scaffold by selective laser sintering. The results showed that SBA15 facilitated cells proliferation, which was mainly attributed to its unique intrinsic mesoporous structure and the released bioactive silicon. Moreover, the hydrolyzate of soluble mesoporous silica can adsorb ions to form nucleation sites that promote biomineralization, leading to improve biological activity of the composite scaffold. In addition, the compressive strength, compressive modulus and Vickers hardness of the scaffold were increased by 47.6%, 35.5% and 29.53% respectively with 1.5 wt.% SBA15. It was found that the particle enhancement of uniform distributed SBA15 accounted for the mechanic reinforcement of the composite scaffold. It indicated that the PLLA-SBA15 composite scaffold had potential applications in bone tissue engineering.

Preparation of porous PLLA/PCL blend by a combination of PEO phase and NaCl particulate leaching in PLLA/PCL/PEO/NaCl blend

Czech Academy of Sciences Publication Activity Database

Ezzati, P.; Ghasemi, I.; Karrabi, M.; Azizi, H.; Fortelný, Ivan

2014-01-01

Roč. 23, č. 10 (2014), s. 757-766 ISSN 1026-1265 Institutional support: RVO:61389013 Keywords : PLLA/PCL/PEO ternary blend * bio -scaffold * melts blending Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.806, year: 2014

LBL coating of type I collagen and hyaluronic acid on aminolyzed PLLA to enhance the cell-material interaction

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M. Y. Zhao

2014-05-01

Full Text Available The aim of the present work is to assemble extracellular matrix components onto poly (L-lactic acid (PLLA films using layer-by-layer (LBL depositing method to enhance the cell-material interaction. To introduce charges onto the hydrophobic and neutral PLLA surface so that the electronic assembly can be processed, poly (ethylene imine (PEI was covalently bonded to modify the PLLA films. Positively charged collagen I (Col I was then deposited onto the aminolyzed PLLA film surface in a LBL assembly manner using hyaluronic acid (HA as a negatively charged polyelectrolyte. The PEI modification efficiency was monitored via X-ray photoelectron spectroscopy (XPS measurements. The results of Surface Plasmon Resonance (SPR and Water contact angle (WCA monitoring the LBL assemble process presented that the HA/Col I deposited alternately onto the PLLA surface. The surface topography of the films was observed by Atomic force microscope (AFM. In vitro osteoblast culture found that the presence of Col I layer greatly improved the cytocompatibility of the PLLA films in terms of cell viability, cell proliferation and Alkaline Phosphatase (ALP expression. Furthermore, osteoblast extensions were found to be directed by contact guidance of the aligned Col I fibrils. Thus, these very flexible systems may allow broad applications for improve the bioactivity of polymeric materials, which might be a potential application for bone tissue engineering.

Poly (L-lactic acid) porous scaffold-supported alginate hydrogel with improved mechanical properties and biocompatibility.

Science.gov (United States)

Chu, Jiaqi; Zeng, Shaodong; Gao, Liyang; Groth, Thomas; Li, Zhiwen; Kong, Junchao; Zhao, Mingyan; Li, Lihua

2016-10-10

Polymer porous scaffolds and hydrogels have been separately employed and explored for a wide range of applications including cell encapsulation, drug delivery, and tissue engineering. In this study, a three-dimensional poly (L-lactic acid) (PLLA) scaffold with interconnected and homogeneously distributed pores was fabricated to support the alginate hydrogel (Alg). The gels were filled into the porous scaffold, which acted as an analogue of native extracellular matrix (ECM) for entrapment of cells within a support of predefined shape. The mechanical strength of the composite scaffold was characterized by compression testing. The chondrocyte behavior in the scaffold was determined by inverted microscopy, scanning electron microscopy (SEM) and MTT viability assay. The repair efficiency of such a composite scaffold was further investigated in dog spinal defects by histological evaluation after implantation for 4 weeks. Results showed that the composite scaffold possessed superior mechanical properties and hierarchical porous structure in comparison to pure Alg. Cell culture revealed that the cells presented a specific cartilage status in the composite scaffold in line with higher adherence and proliferation ratio. The histological analyses suggested that the composite scaffold substantially promotes its integration in the host tissue accompanied with a low inflammatory reaction and new tissue formation. The method thus provides a useful pathway for scaffold preparation that can simultaneously achieve suitable mechanical properties and good biocompatibility.

Preparation of PLLA/PMMA and PLLA/PS binary blend nanoparticles by incorporation of PLLA in methyl methacrylate or styrene miniemulsion homopolymerization

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Luana Becker Peres

2015-02-01

Full Text Available Miniemulsion homopolymerization reactions of methyl methacrylate (MMA and styrene (STY using poly(L-lactide as co-stabilizer were carried out in order to prepare poly(L-lactide/poly(methyl methacrylate (PLLA/PMMA and poly(L-lactide/polystyrene (PLLA/PS binary blend nanoparticles. The effect of PLLA concentration on methyl methacrylate (MMA and styrene (STY homopolymerization reactions was evaluated. It was found that the incorporation of PLLA resulted on acceleration of MMA and STY homopolymerization reactions and led to a molar mass increase of up to 70% for PS in PLLA/PS blend nanoparticles in relation to those prepared without PLLA, which can be attributed to an increase of reaction loci viscosity (gel effect. PLLA also acted as an efficient co-stabilizer, since it was able to retard diffusional degradation of droplets when no other kind of co-stabilizer was used. Two isolated Tgs were found in both PLLA/PMMA and PLLA/PS blend nanoparticles which can be associated to blend immiscibility. TEM images corroborate these results, suggesting that immiscible PLLA/PMMA and PLLA/PS blend nanoparticles could be formed with two segregated phases and core-shell morphology.

Preparation and characterization of dense nanohydroxyapatite/PLLA composites

International Nuclear Information System (INIS)

Gay, Sandrine; Arostegui, Saioa; Lemaitre, Jacques

2009-01-01

Synthetic bone graft substitutes based on PLLA have been largely studied during the past decade. PLLA/hydroxyapatite composites appear as promising materials for large bone defect healing. In this study dense PLLA/nano-hydroxyapatite composites were prepared by hot pressing. Dense samples were investigated rather than porous scaffolds, in order to shed light on possible correlations between intrinsic mechanical properties and nano-hydroxyapatite concentration. Hydroxyapatite deagglomerated by wet attrition milling, and further dispersed into chloroform was used (median diameter = 80 nm). Particle size distribution measurements and transmission electron microscopy show evidence that particle size and dispersion are maintained throughout the successive steps of composite processing. Mechanical properties were tested (uni-axial and diametral compression tests) as a function of nano-hydroxyapatite content. Increasing concentrations of nano-hydroxyapatite (0, 25 and 50 wt.%) increase the Young's modulus and the mechanical strength of the composite; at the same time, the failure mechanism of the material changes from plastic to brittle. Young's modulus over 6 GPa and uniaxial compressive strength over 100 MPa have been achieved. These values expressed in terms of intrinsic tensile and shear strengths indicate that 50 wt.% nano-hydroxyapatite containing samples develop properties comparable to those of cortical bone. PLLA/nano-hydroxyapatite composites are thus promising candidates to develop bioresorbable porous bone substitutes showing superior mechanical performance

Fabrication and characterization of electrospun poly-L-lactide/gelatin graded tubular scaffolds: Toward a new design for performance enhancement in vascular tissue engineering

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A. Yazdanpanah

2015-10-01

Full Text Available In this study, a new design of graded tubular scaffolds have been developed for the performance enhancement in vascular tissue engineering. The graded poly-L-lactide (PLLA and gelatin fibrous scaffolds produced by electrospining were then characterized. The morphology, degradability, porosity, pore size and mechanical properties of four tubular scaffolds (graded PLLA/gelatin, layered PLLA/gelatin, PLLA and gelatin scaffolds have been investigated. The tensile tests demonstrated that the mechanical strength and also the estimated burst pressure of the graded scaffolds were significantly increased in comparison with the layered and gelatin scaffolds. This new design, resulting in an increase in the mechanical properties, suggested the widespread use of these scaffolds in vascular tissue engineering in order to prepare more strengthened vessels.

Innovative biodegradable poly(L-lactide/collagen/hydroxyapatite composite fibrous scaffolds promote osteoblastic proliferation and differentiation

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Zhou GQ

2017-10-01

Full Text Available Guoqiang Zhou,1–3 Sudan Liu,1 Yanyan Ma,1 Wenshi Xu,1 Wei Meng,1 Xue Lin,1 Wenying Wang,1,3 Shuxiang Wang,1–3 Jinchao Zhang1–3 1College of Chemistry and Environmental Science, 2Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, 3Key Laboratory of Chemical Biology of Hebei Province, Hebei University, Baoding, Hebei, People’s Republic of China Abstract: The development of an artificial bone graft which can promote the regeneration of fractures or diseased bones is currently the most challenging aspect in bone tissue engineering. To achieve the purpose of promoting bone proliferation and differentiation, the artificial graft needs have a similar structure and composition of extracellular matrix. One-step electrospinning method of biocomposite nanofibers containing hydroxyapatite (HA nanoparticles and collagen (Coll were developed for potential application in bone tissue engineering. Nanocomposite scaffolds of poly(L-lactide (PLLA, PLLA/HA, PLLA/Coll, and PLLA/Coll/HA were fabricated by electrospinning. The morphology, diameter, elements, hydrophilicity, and biodegradability of the composite scaffolds have been investigated. The biocompatibility of different nanocomposite scaffolds was assessed using mouse osteoblasts MC3T3-E1 in vitro, and the proliferation, differentiation, and mineralization of cells on different nanofibrous scaffolds were investigated. The results showed that PLLA/Coll/HA nanofiber scaffolds enhanced cell adhesion, spreading, proliferation, differentiation, mineralization, and gene expression of osteogenic markers compared to other scaffolds. In addition, the nanofibrous scaffolds maintained a stable composition at the beginning of the degradation period and morphology wastage and weight loss were observed when incubated for up to 80 days in physiological simulated conditions. The PLLA/Coll/HA composite nanofibrous scaffolds could be a potential material for guided bone regeneration

In vivo bioluminescence imaging for prolonged survival of transplanted human neural stem cells using 3D biocompatible scaffold in corticectomized rat model.

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Do Won Hwang

Full Text Available Stem cell-based treatment of traumatic brain injury has been limited in its capacity to bring about complete functional recovery, because of the poor survival rate of the implanted stem cells. It is known that biocompatible biomaterials play a critical role in enhancing survival and proliferation of transplanted stem cells via provision of mechanical support. In this study, we noninvasively monitored in vivo behavior of implanted neural stem cells embedded within poly-l-lactic acid (PLLA scaffold, and showed that they survived over prolonged periods in corticectomized rat model. Corticectomized rat models were established by motor-cortex ablation of the rat. F3 cells expressing enhanced firefly luciferase (F3-effLuc were established through retroviral infection. The F3-effLuc within PLLA was monitored using IVIS-100 imaging system 7 days after corticectomized surgery. F3-effLuc within PLLA robustly adhered, and gradually increased luciferase signals of F3-effLuc within PLLA were detected in a day dependent manner. The implantation of F3-effLuc cells/PLLA complex into corticectomized rats showed longer-lasting luciferase activity than F3-effLuc cells alone. The bioluminescence signals from the PLLA-encapsulated cells were maintained for 14 days, compared with 8 days for the non-encapsulated cells. Immunostaining results revealed expression of the early neuronal marker, Tuj-1, in PLLA-F3-effLuc cells in the motor-cortex-ablated area. We observed noninvasively that the mechanical support by PLLA scaffold increased the survival of implanted neural stem cells in the corticectomized rat. The image-guided approach easily proved that scaffolds could provide supportive effect to implanted cells, increasing their viability in terms of enhancing therapeutic efficacy of stem-cell therapy.

Enhanced human bone marrow mesenchymal stem cell functions in novel 3D cartilage scaffolds with hydrogen treated multi-walled carbon nanotubes

Science.gov (United States)

Holmes, Benjamin; Castro, Nathan J.; Li, Jian; Keidar, Michael; Zhang, Lijie Grace

2013-09-01

Cartilage tissue is a nanostructured tissue which is notoriously hard to regenerate due to its extremely poor inherent regenerative capacity and complex stratified architecture. Current treatment methods are highly invasive and may have many complications. Thus, the goal of this work is to use nanomaterials and nano/microfabrication methods to create novel biologically inspired tissue engineered cartilage scaffolds to facilitate human bone marrow mesenchymal stem cell (MSC) chondrogenesis. To this end we utilized electrospinning to design and fabricate a series of novel 3D biomimetic nanostructured scaffolds based on hydrogen (H2) treated multi-walled carbon nanotubes (MWCNTs) and biocompatible poly(L-lactic acid) (PLLA) polymers. Specifically, a series of electrospun fibrous PLLA scaffolds with controlled fiber dimension were fabricated in this study. In vitro MSC studies showed that stem cells prefer to attach in the scaffolds with smaller fiber diameter. More importantly, the MWCNT embedded scaffolds showed a drastic increase in mechanical strength and a compressive Young’s modulus matching to natural cartilage. Furthermore, our MSC differentiation results demonstrated that incorporation of the H2 treated carbon nanotubes and poly-L-lysine coating can induce more chondrogenic differentiations of MSCs than controls. After two weeks of culture, PLLA scaffolds with H2 treated MWCNTs and poly-L-lysine can achieve the highest glycosaminoglycan synthesis, making them promising for further exploration for cartilage regeneration.

Enhanced human bone marrow mesenchymal stem cell functions in novel 3D cartilage scaffolds with hydrogen treated multi-walled carbon nanotubes

International Nuclear Information System (INIS)

Holmes, Benjamin; Castro, Nathan J; Li Jian; Keidar, Michael; Zhang, Lijie Grace

2013-01-01

Cartilage tissue is a nanostructured tissue which is notoriously hard to regenerate due to its extremely poor inherent regenerative capacity and complex stratified architecture. Current treatment methods are highly invasive and may have many complications. Thus, the goal of this work is to use nanomaterials and nano/microfabrication methods to create novel biologically inspired tissue engineered cartilage scaffolds to facilitate human bone marrow mesenchymal stem cell (MSC) chondrogenesis. To this end we utilized electrospinning to design and fabricate a series of novel 3D biomimetic nanostructured scaffolds based on hydrogen (H 2 ) treated multi-walled carbon nanotubes (MWCNTs) and biocompatible poly(L-lactic acid) (PLLA) polymers. Specifically, a series of electrospun fibrous PLLA scaffolds with controlled fiber dimension were fabricated in this study. In vitro MSC studies showed that stem cells prefer to attach in the scaffolds with smaller fiber diameter. More importantly, the MWCNT embedded scaffolds showed a drastic increase in mechanical strength and a compressive Young’s modulus matching to natural cartilage. Furthermore, our MSC differentiation results demonstrated that incorporation of the H 2 treated carbon nanotubes and poly-L-lysine coating can induce more chondrogenic differentiations of MSCs than controls. After two weeks of culture, PLLA scaffolds with H 2 treated MWCNTs and poly-L-lysine can achieve the highest glycosaminoglycan synthesis, making them promising for further exploration for cartilage regeneration. (paper)

L. inermis-loaded nanofibrous scaffolds for wound dressing applications.

Science.gov (United States)

Vakilian, Saeid; Norouzi, Mohammad; Soufi-Zomorrod, Mahsa; Shabani, Iman; Hosseinzadeh, Simzar; Soleimani, Masoud

2018-04-01

Since ancient times, some herbal medicines have been extensively used for burn and wound treatments, showing preference to the common synthetic medications by virtue of having less side effects and faster healing rate. In this study, hybrid nanofibrous scaffolds of poly-l-lactic-acid (PLLA) and gelatin incorporated L. inermis were fabricated via electrospinning technique. Morphology and characteristics of the scaffolds were studied by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR), respectively. The release profile of the L. inermis from the nanofibers was also assessed in vitro. Moreover, the structural stability of the released L. inermis from the nanofibers was evaluated using high-performance liquid chromatography (HPLC). The nanofibers showed a gradual release of L. inermis up to two days while the intact structure was preserved. Furthermore, antibacterial assay demonstrated that L. inermis-loaded nanofibrous scaffolds could effectively kill E. coli and S. aureus within 2 h. Finally, biocompatibility of the nanofibers was proven on 3T3 fibroblasts. Therefore, the L. inermis loaded PLLA-Gelatin nanofibers showed a potential application as a wound dressing in order to control wound infections. Copyright © 2018. Published by Elsevier Ltd.

PCL-PLLA Semi-IPN Shape Memory Polymers (SMPs): Degradation and Mechanical Properties.

Science.gov (United States)

Woodard, Lindsay N; Page, Vanessa M; Kmetz, Kevin T; Grunlan, Melissa A

2016-12-01

Thermoresponsive shape memory polymers (SMPs) based on poly(ε-caprolactone) (PCL) whose shape may be actuated by a transition temperature (T trans ) have shown utility for a variety of biomedical applications. Important to their utility is the ability to modulate mechanical and degradation properties. Thus, in this work, SMPs are formed as semi-interpenetrating networks (semi-IPNs) comprised of a cross-linked PCL diacrylate (PCL-DA) network and thermoplastic poly(l-lactic acid) (PLLA). The semi-IPN uniquely allows for requisite crystallization of both PCL and PLLA. The influence of PLLA (PCL:PLLA wt% ratio) and PCL-DA molecular weight (n) on film properties are investigated. PCL-PLLA semi-IPNs are able to achieve enhanced mechanical properties and accelerated rates of degradation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of novel hybrid poly(l-lactide)/chitosan scaffolds using the rapid freeze prototyping technique

Energy Technology Data Exchange (ETDEWEB)

Zhu, N; Chen, X B [Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, Saskatchewan (Canada); Li, M G [Department of Mechanical Engineering, University of Saskatchewan, Saskatoon, Saskatchewan (Canada); Cooper, D, E-mail: xbc719@mail.usask.ca [Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan (Canada)

2011-09-15

Engineered scaffolds have been shown to be critical to various tissue engineering applications. This paper presents the development of a novel three-dimensional scaffold made from a mixture of chitosan microspheres (CMs) and poly(l-lactide) by means of the rapid freeze prototyping (RFP) technique. The CMs were used to encapsulate bovine serum albumin (BSA) and improve the scaffold mechanical properties. Experiments to examine the BSA release were carried out; the BSA release could be controlled by adjusting the crosslink degree of the CMs and prolonged after the CMs were embedded into the PLLA scaffolds, while the examination of the mechanical properties of the scaffolds illustrates that they depend on the ratio of CMs to PLLA in the scaffolds as well as the cryogenic temperature used in the RFP fabrication process. The chemical characteristics of the PLLA/chitosan scaffolds were evaluated by Fourier transform infrared (FTIR) spectroscopy. The morphological and pore structure of the scaffolds were also examined by scanning electron microscopy and micro-tomography. The results obtained show that the scaffolds have higher porosity and enhanced pore size distribution compared to those fabricated by the dispensing-based rapid prototyping technique. This study demonstrates that the novel scaffolds have not only enhanced porous structure and mechanical properties but also showed the potential to preserve the bioactivities of the biomolecules and to control the biomolecule distribution and release rate.

Direct printing of patterned three-dimensional ultrafine fibrous scaffolds by stable jet electrospinning for cellular ingrowth

International Nuclear Information System (INIS)

Yuan, Huihua; Zhou, Qihui; Li, Biyun; Bao, Min; Lou, Xiangxin; Zhang, Yanzhong

2015-01-01

Electrospinning has been widely used to produce ultrafine fibers in microscale and nanoscale; however, traditional electrospinning processes are currently beset by troublesome limitations in fabrication of 3D periodic porous structures because of the chaotic nature of the electrospinning jet. Here we report a novel strategy to print 3D poly(L-lactic acid) (PLLA) ultrafine fibrous scaffolds with the fiber diameter of approximately 2 μm by combining a stable jet electrospinning method and an X-Y stage technique. Our approach allows linearly deposited electrospun ultrafine fibers to assemble into 3D structures with tunable pore sizes and desired patterns. Process conditions (e.g., plotting speed, feeding rate, and collecting distance) were investigated in order to achieve stable jet printing of ultrafine PLLA fibers. The proposed 3D scaffold was successfully used for cell penetration and growth, demonstrating great potential for tissue engineering applications. (paper)

Fabrication and characterization of electrospun osteon mimicking scaffolds for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Andric, T. [Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Sampson, A.C. [Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Freeman, J.W., E-mail: jwfreeman@vt.edu [Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States)

2011-01-01

Skeletal loss and bone deficiencies are a major worldwide problem with over 600,000 procedures performed in the US alone annually, making bone one of the most transplanted tissues, second to blood only. Bone is a composite tissue composed of organic matrix, inorganic bone mineral, and water. Structurally bone is organized into two distinct types: trabecular (or cancellous) and cortical (or compact) bones. Trabecular bone is characterized by an extensive interconnected network of pores. Cortical bone is composed of tightly packed units, called osteons, oriented parallel along to the axis of the bone. While the majority of scaffolds attempt to replicate the structure of the trabecular bone, fewer attempts have been made to create scaffolds to mimic the structure of cortical bone. The aim of this study was to develop a technique to fabricate scaffolds that mimic the organization of an osteon, the structural unit of cortical bone. We successfully built a rotating stage for PGA fibers and utilized it for collecting electrospun nanofibers and creating scaffolds. Resulting scaffolds consisted of concentric layers of electrospun PLLA or gelatin/PLLA nanofibers wrapped around PGA microfiber core with diameters that ranged from 200 to 600 {mu}m. Scaffolds were mineralized by incubation in 10x simulated body fluid, and scaffolds composed of 10%gelatin/PLLA had significantly higher amounts of calcium phosphate. The electrospun scaffolds also supported cellular attachment and proliferation of MC3T3 cells over the period of 28 days.

PLLA-PHB fiber membranes obtained by solvent-free electrospinning for short-time drug delivery.

Science.gov (United States)

Cao, K; Liu, Y; Olkhov, A A; Siracusa, V; Iordanskii, A L

2018-02-01

Fibers of poly(L-lactic acid) (PLLA)/polyhydroxybutyrate (PHB) with different concentrations of the drug dipyridamole (DPD) were prepared using solvent-free melt electrospinning to obtain a polymeric drug delivery system. The electrospun fibers were morphologically, structurally, thermally, and dynamically characterized. Crazes that resemble lotus root crevices were interestingly observed in the 7:3 PLLA/PHB fibers with 1% DPD. The crystallinity of PLLA slightly decreased as PHB was incorporated, and the addition of DPD significantly reduced the melting temperature of the composite. The interactions between PLLA and PHB mainly occurred at a proportion of 7:3, and drug encapsulation in the fibers was verified. The kinetic profiles of drug release demonstrated the predominant multiple patterns involving a diffusional stage in the short-term mode of release and kinetic process related to the hydrolysis of the biopolymers. Furthermore, the dynamic behavior of the polymer molecules was evaluated based on the segmental mobility using probe electron spin resonance spectroscopy. The segmental mobility in the amorphous fraction of PLLA decreased with increasing PLLA content. The 9:1 PLLA/PHB system was more resistant to polymer hydrolysis than to the 7:3 system and the rate of diffusion transport was approximately two times higher for the 7:3 PLLA/PHB fibers than for the 9:1 PLLA/PHB fibers.

Fabrication and Protein Conjugation of Aligned Polypyrrole-Poly(L-lactic acid) Fibers Film with the Conductivity and Stability.

Science.gov (United States)

Qin, Jiabang; Huang, Zhongbing; Yin, Guangfu; Yang, Anneng; Han, Wei

2016-03-01

The conducting composite scaffold, including fiber-cores of aligned poly(L-lactic acid) (PLLA) and shell-layer of polypyrrole (PPy), was fabricated, and then bovine serum albumin (BSA) was conjugated on the PPy shell-layer. Aligned PLLA fibers (about 300 nm diameter) were obtained by electrospinning and rotating drum collection, and then coated by PPy nanoparticles (NPs, about 50 nm diameter) via chemical oxidation. The surface resistivity of PPy-PLLA fibers film were 0.971, 0.874 kΩ. cm at the fiber's vertical and parallel directions, respectively. The results of PPy-PLLA fibers film immersed in phosphate buffer saline for 8 d indicated that the fibers morphology and the film conductivity were not significantly changed, and the fluorescent images showed that FITC-labeled BSA (FITC-BSA) were successfully conjugated in the fibers film with carbodiimide chemistry, and the largest amount of FITC-BSA conjugated in the fibers film from 100 μg/mL proteins solution was 31.31 μg/cm2 due to lots of poly(glutamic acid) in surface-nanogrooves of the fibers surface. Under electrical stimulation of 100 mV, the fibers film was accompanied the release of all conjugated FITC-BSA with the detachment of some PPy NPs. These results suggested that PPy-PLLA fibers film would be potentially applied in the construction of degradable tissue engineering scaffold with protein factors, especially neurotrophic factors for nerve tissue repair.

Bone regeneration by means of a three-dimensional printed scaffold in a rat cranial defect.

Science.gov (United States)

Kwon, Doo Yeon; Park, Ji Hoon; Jang, So Hee; Park, Joon Yeong; Jang, Ju Woong; Min, Byoung Hyun; Kim, Wan-Doo; Lee, Hai Bang; Lee, Junhee; Kim, Moon Suk

2018-02-01

Recently, computer-designed three-dimensional (3D) printing techniques have emerged as an active research area with almost unlimited possibilities. In this study, we used a computer-designed 3D scaffold to drive new bone formation in a bone defect. Poly-L-lactide (PLLA) and bioactive β-tricalcium phosphate (TCP) were simply mixed to prepare ink. PLLA + TCP showed good printability from the micronozzle and solidification within few seconds, indicating that it was indeed printable ink for layer-by-layer printing. In the images, TCP on the surface of (and/or inside) PLLA in the printed PLLA + TCP scaffold looked dispersed. MG-63 cells (human osteoblastoma) adhered to and proliferated well on the printed PLLA + TCP scaffold. To assess new bone formation in vivo, the printed PLLA + TCP scaffold was implanted into a full-thickness cranial bone defect in rats. The new bone formation was monitored by microcomputed tomography and histological analysis of the in vivo PLLA + TCP scaffold with or without MG-63 cells. The bone defect was gradually spontaneously replaced with new bone tissues when we used both bioactive TCP and MG-63 cells in the PLLA scaffold. Bone formation driven by the PLLA + TCP30 scaffold with MG-63 cells was significantly greater than that in other experimental groups. Furthermore, the PLLA + TCP scaffold gradually degraded and matched well the extent of the gradual new bone formation on microcomputed tomography. In conclusion, the printed PLLA + TCP scaffold effectively supports new bone formation in a cranial bone defect. Copyright © 2017 John Wiley & Sons, Ltd.

The influence of gamma radiation on the molecular weight and glass transition of PLLA and HAp/PLLA nanocomposite

International Nuclear Information System (INIS)

Milicevic, D.; Trifunovic, S.; Dojcilovic, J.; Ignjatovic, N.; Suljovrujic, E.

2010-01-01

The influence of gamma radiation on the molecular weight and glass transition behaviour of poly-L-lactide (PLLA) and hydroxyapatite/poly-L-lactide (HAp/PLLA) nanocomposite has been studied. Since PLLA exposed to high-energy radiation in the presence of air is prone to chain scission reactions and large degradation, changes in molecular weight were obtained by gel permeation chromatography (GPC). Alterations in the glass transition behaviour were investigated by differential scanning calorimetry (DSC). The apparent activation energy (ΔH*) for glass transition was determined on the basis of the heating rate dependence of the glass transition temperature (T g ). Our findings support the fact that chain scission is the main reason for the decrease of T g and ΔH* with the absorbed dose. Furthermore, more intensive chain scission degradation of PLLA was observed in HAp/PLLA and can only be ascribed to the presence of HAp nanoparticles. Consequently, initial differences in the glass transition temperature and/or apparent activation energy of PLLA and HAp/PLLA became more pronounced with absorbed dose. This study reveals that radiation-induced changes in molecular weight and glass transition temperature occur in a predictable and fairly accurate manner. Therefore, gamma radiation can be used not only for sterilization but also for tailoring desirable end-use properties of these biomaterials.

3D Biofabrication of Thermoplastic Polyurethane (TPU/Poly-l-lactic Acid (PLLA Electrospun Nanofibers Containing Maghemite (γ-Fe2O3 for Tissue Engineering Aortic Heart Valve

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Ehsan Fallahiarezoudar

2017-11-01

Full Text Available Valvular dysfunction as the prominent reason of heart failure may causes morbidity and mortality around the world. The inability of human body to regenerate the defected heart valves necessitates the development of the artificial prosthesis to be replaced. Besides, the lack of capacity to grow, repair or remodel of an artificial valves and biological difficulty such as infection or inflammation make the development of tissue engineering heart valve (TEHV concept. This research presented the use of compound of poly-l-lactic acid (PLLA, thermoplastic polyurethane (TPU and maghemite nanoparticle (γ-Fe2O3 as the potential biomaterials to develop three-dimensional (3D aortic heart valve scaffold. Electrospinning was used for fabricating the 3D scaffold. The steepest ascent followed by the response surface methodology was used to optimize the electrospinning parameters involved in terms of elastic modulus. The structural and porosity properties of fabricated scaffold were characterized using FE-SEM and liquid displacement technique, respectively. The 3D scaffold was then seeded with aortic smooth muscle cells (AOSMCs and biological behavior in terms of cell attachment and proliferation during 34 days of incubation was characterized using MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and confocal laser microscopy. Furthermore, the mechanical properties in terms of elastic modulus and stiffness were investigated after cell seeding through macro-indentation test. The analysis indicated the formation of ultrafine quality of nanofibers with diameter distribution of 178 ± 45 nm and 90.72% porosity. In terms of cell proliferation, the results exhibited desirable proliferation (109.32 ± 3.22% compared to the control of cells over the 3D scaffold in 34 days of incubation. The elastic modulus and stiffness index after cell seeding were founded to be 22.78 ± 2.12 MPa and 1490.9 ± 12 Nmm2, respectively. Overall, the fabricated 3D

Carbon nanotubes reinforced poly(L-lactide) scaffolds fabricated by thermally induced phase separation

International Nuclear Information System (INIS)

Ma, Haiyun; Xue, Li

2015-01-01

In tissue engineering, porous nanocomposite scaffolds can potentially mimic aspects of the nanoscale architecture of the extra-cellular matrix, as well as enhance the mechanical properties required for successful weight-bearing implants. In this paper, we demonstrate that highly porous thermoplastic poly(L-lactide) nanocomposite scaffolds containing different types of functionalized multi-walled carbon nanotubes (CNTs). The nanocomposite scaffolds were manufactured by a thermally induced phase separation method. This experiment produced an uniform distribution of CNTs throughout the scaffold without obvious aggregations for funtionalized CNTs filled scaffolds by scanning electron microscope observation. The CNTs were frequently located on the pore surface, forming rough, hairy nano-textures. The pore size was reduced with the increasing of CNT loading. Parts of PLLA matrix was induced into nanofibrous structures from solid-walled state, which reduced the crystallinity of the PLLA characterized by DSC measurement. The CNT incorporation significantly improved the compression modulus of the nanocomposite scaffolds, especially the functionalized CNTs. The capacity of protein adsorption is significantly improved when the concentration of the CNTs was higher than 1.0 wt.% and the cell attachment was also enhanced by the addition of CNTs, especially N-CNT. (paper)

[Anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines in vitro].

Science.gov (United States)

Gu, Jun; Li, Maolan; Wu, Xiangsong; Wu, Wenguang; Zhang, Lin; Ding, Qichen; Yang, Jiahua; Weng, Hao; Ding, Qian; Bao, Runfa; Shu, Yijun; Liu, Yingbin

2014-04-01

To prepare cisPLLAtin-loaded polylactic acid/cnts, and to study the anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines(MGC803 and MNK45). 5-FU-PLLA-CNTs were prepared with ultrasound emulsification. The morphology of 5-FU-PLLA-CNTs was determined by scanning electron microscope(SEM), and its drug loading and drug release curve in vitro were detected by UV-Vis-NIR spectrophotometer. Cells were divided into experiment, positive control and negative control groups. CCK8 method was used to test the cytotoxic effect of 5-FU-PLLA-CNTs in different concentrations on MGC803 and MNK45 cell proliferation. Flow cytometry was employed to measure the apoptotic rate of MGC803 and MNK45 cells before and after the intervention of 5-FU-PLLA-CNTs. Deep layer film of 5-FU-PLLA-CNTs was successfully established, whose drug-load rate was(4.54±0.43)%, entrapment rate was(21.56±2.36)%. In vitro release test showed release rate within 24 h of 5-FU-PLLA-CNTs was 23.9% in a as lowly increasing manner, and accumulating release rate was 85.3% at day 31. CCk8 experiment revealed, as compared to control group, 5-FU-PLLA-CNTs significantly inhibited the proliferation of two cell lines in dose-dependent and time-dependent manner. The best 5-FU-PLLA-CNTs concentration of inhibition for human gastric cancer cell lines was 1 mg/well. Flow cytometry indicated the apoptotic rate of MGC803 and MNK45 cells in experiment group treated by 1 mg/well 5-FU-PLLA-CNTs significantly increased as compared to negative control group (P0.05). The 5-FU-PLLA-CNTs has good drug sustained-release capacity, and can significantly kill and inhibit the proliferation of MGC803 and MNK45 cell lines.

A proteomic analysis of the interactions between poly(L-lactic acid nanofibers and SH-SY5Y neuronal-like cells

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Ana Marote

2016-11-01

Full Text Available Poly (L-lactic acid (PLLA is a biodegradable and biocompatible polymer that has been put forward as a promising material for therapeutic approaches aiming to restore neuronal function. The topographic cues present in PLLA-based scaffolds, defined by the technique used in their preparation, have been shown to play a role on the cellular behavior of adherent cells. Even though this interaction has been shown to influence the regenerative output of the scaffold, there is a lack of studies addressing this response at the proteomic level. Hence, this work focuses on the effect of electrospun PLLA-based nanofibers on the proteome, cellular processes and signaling pathways of SH-SY5Y neuroblastoma cells. It also further explores how these molecular mediators might influence cell proliferation and differentiation upon in vitro culture. For that, mass spectrometry followed by bioinformatics analysis was firstly performed and further complemented with Western blot, cell viability and imaging assays. Results show that PLLA nanofibers differentially activate and inhibit specific cellular functions and signaling pathways related to cell division, apoptosis, actin remodeling, among others. These ultimately block cellular proliferation and induce morphological rearrangements through cytoskeleton remodeling, adaptations that turn cells more prone to differentiate. In synthesis, PLLA nanofibers shift the SH-SY5Y cells proteome towards a state more responsive to differentiation-inductive cues such as the retinoic acid. Unveiling cells responses to nanomaterials is an important step to increase the tools available for their manipulation and potentiate their use in neural tissue engineering. Further studies should be performed to compare the effects of other topographic cues on cellular behavior.

Surface changes of biopolymers PHB and PLLA induced by Ar+ plasma treatment and wet etching

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Slepičková Kasálková, N.; Slepička, P.; Sajdl, P.; Švorčík, V.

2014-08-01

Polymers, especially group of biopolymers find potential application in a wide range of disciplines due to their biodegradability. In biomedical applications these materials can be used as a scaffold or matrix. In this work, the influence of the Ar+ plasma treatment and subsequent wet etching (acetone/water) on the surface properties of polymers were studied. Two biopolymers - polyhydroxybutyrate with 8% polyhydroxyvalerate (PHB) and poly-L-lactic acid (PLLA) were used in these experiments. Modified surface layers were analyzed by different methods. Surface wettability was characterized by determination of water contact angle. Changes in elemental composition of modified surfaces were performed by X-ray Photoelectron Spectroscopy (XPS). Surface morphology and roughness was examined using Atomic Force Microscopy (AFM). Gravimetry method was used to study the mass loss. It was found that the modification from both with plasma and wet etching leads to dramatic changes of surface properties (surface chemistry, morphology and roughness). Rate of changes of these features strongly depends on the modification parameters.

Experimental and computational studies of poly-L-lactic acid for cardiovascular applications: recent progress

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Naseem, Raasti; Zhao, Liguo; Liu, Yang; Silberschmidt, Vadim V.

2017-12-01

Stents are commonly used in medical procedures to alleviate the symptoms of coronary heart disease, a prevalent modern society disease. These structures are employed to maintain vessel patency and restore blood flow. Traditionally stents are made of metals such as stainless steel or cobalt chromium; however, these scaffolds have known disadvantages. An emergence of transient scaffolds is gaining popularity, with the structure engaged for a required period whilst healing of the diseased arterial wall occurs. Polymers dominate a medical device sector, with incorporation in sutures, scaffolds and screws. Thanks to their good mechanical and biological properties and their ability to degrade naturally. Polylactic acid is an extremely versatile polymer, with its properties easily tailored to applications. Its dominance in the stenting field increases continually, with the first polymer scaffold gaining FDA approval in 2016. Still some challenges with PLLA bioresorbable materials remain, especially with regard to understanding their mechanical response, assessment of its changes with degradation and comparison of their performance with that of metallic drug-eluting stent. Currently, there is still a lack of works on evaluating both the pre-degradation properties and degradation performance of these scaffolds. Additionally, there are no established material models incorporating non-linear viscoelastic behaviour of PLLA and its evolution with in-service degradation. Assessing these features through experimental analysis accompanied by analytical and numerical studies will provide powerful tools for design and optimisation of these structures endorsing their broader use in stenting. This overview assesses the recent studies investigating mechanical and computational performance of poly(l-lactic) acid and its use in stenting applications.

Surface changes of biopolymers PHB and PLLA induced by Ar{sup +} plasma treatment and wet etching

Energy Technology Data Exchange (ETDEWEB)

Slepičková Kasálková, N. [Department of Solid State Engineering, Institute of Chemical Technology, 166 28 Prague (Czech Republic); Slepička, P., E-mail: petr.slepicka@vscht.cz [Department of Solid State Engineering, Institute of Chemical Technology, 166 28 Prague (Czech Republic); Sajdl, P. [Department of Power Engineering, Institute of Chemical Technology, 166 28 Prague (Czech Republic); Švorčík, V. [Department of Solid State Engineering, Institute of Chemical Technology, 166 28 Prague (Czech Republic)

2014-08-01

Polymers, especially group of biopolymers find potential application in a wide range of disciplines due to their biodegradability. In biomedical applications these materials can be used as a scaffold or matrix. In this work, the influence of the Ar{sup +} plasma treatment and subsequent wet etching (acetone/water) on the surface properties of polymers were studied. Two biopolymers – polyhydroxybutyrate with 8% polyhydroxyvalerate (PHB) and poly-L-lactic acid (PLLA) were used in these experiments. Modified surface layers were analyzed by different methods. Surface wettability was characterized by determination of water contact angle. Changes in elemental composition of modified surfaces were performed by X-ray Photoelectron Spectroscopy (XPS). Surface morphology and roughness was examined using Atomic Force Microscopy (AFM). Gravimetry method was used to study the mass loss. It was found that the modification from both with plasma and wet etching leads to dramatic changes of surface properties (surface chemistry, morphology and roughness). Rate of changes of these features strongly depends on the modification parameters.

Modification of bone graft by blending with lecithin to improve hydrophilicity and biocompatibility

International Nuclear Information System (INIS)

Wang, Y; Cui, F Z; Jiao, Y P; Hu, K; Fan, D D

2008-01-01

Lecithin was blended to improve the hydrophilicity and biocompatibility of bone graft containing poly(l-lactic acid) (PLLA). Solution blending and freeze drying were used to fabricate symmetrical scaffolds containing different percentages of lecithin (lecithin: PLLA = 0, 5, 10 wt%). Scanning electron microscopy showed that the scaffolds maintained the three-dimensional porous structure. A water uptake experiment proved the significant improvement of hydrophilicity of the blend scaffold. With the addition of lecithin, the compressive strength and compressive modulus decreased. When the weight ratio of lecithin to PLLA was up to 10%, the compressive strength was still more than the lower limit of natural cancellous bone. To test the biocompatibility of the scaffolds, cell culture in vitro and subcutaneous implantation in vivo were performed. MC3T3-E1 preosteoblastic cells were cultured on the scaffolds for 7 days. Methylthiazol tetrazolium assay and laser scanning confocal microscopy were used to exhibit proliferation and morphology of the cells. The subcutaneous implantation in rats tested inflammatory response to the scaffolds. The results proved the better biocompatibility and milder inflammatory reactions of the blend scaffold (lecithin: PLLA = 5%) compared with the scaffold without lecithin. The modified scaffold containing lecithin is promising for bone tissue engineering

Obtaining and characterization of films of stereo complexes PLLA-PDLA; Obtencao e caracterizacao de filmes de estereocomplexos de PLLA-PDLA

Energy Technology Data Exchange (ETDEWEB)

Goncalves, R.P.; Dias, M.L.; Picciani, P.H.S., E-mail: raquelpires@ima.ufrj.b [Universidade Federal do Rio de Janeiro (IMA/UFRJ), RJ (Brazil). Inst. de Macromoleculas Professora Eloisa Mano

2010-07-01

Polilactides stereorregulars as poly (L-lactide) (PLLA) has wide application in biomedical and packaging, but despite the structure regular, have relatively low crystallization rate, which limits some applications. The formation of stereocomplexes the mixture of PLLA with poly (D-lactide) (PDLA) has been a strategy used to modify the crystalline structure of these materials, which has an important role in controlling its degradation. In this work we prepared films of PLLA and PDLA alone and their mixtures, aiming to produce stereocomplexes. The PLLA and PDLA were synthesized using different catalysts: tin octoate and calcium methoxide, to investigate the effect of microstructure of polymers in the formation of stereocomplex. The films were obtained by pressing at different temperatures. The materials were characterized by X-ray diffraction and GPC. The results indicate that stereocomplexes with different characteristics are obtained when synthesized with two types of catalysts. (author)

Preparation of porous carbon nanofibers derived from PBI/PLLA for supercapacitor electrodes.

Science.gov (United States)

Jung, Kyung-Hye; Ferraris, John P

2016-10-21

Porous carbon nanofibers were prepared by electrospinning blend solutions of polybenzimidazole/poly-L-lactic acid (PBI/PLLA) and carbonization. During thermal treatment, PLLA was decomposed, resulting in the creation of pores in the carbon nanofibers. From SEM images, it is shown that carbon nanofibers had diameters in the range of 100-200 nm. The conversion of PBI to carbon was confirmed by Raman spectroscopy, and the surface area and pore volume of carbon nanofibers were determined using nitrogen adsorption/desorption analyses. To investigate electrochemical performances, coin-type cells were assembled using free-standing carbon nanofiber electrodes and ionic liquid electrolyte. cyclic voltammetry studies show that the PBI/PLLA-derived porous carbon nanofiber electrodes have higher capacitance due to lower electrochemical impedance compared to carbon nanofiber electrode from PBI only. These porous carbon nanofibers were activated using ammonia for further porosity improvement and annealed to remove the surface functional groups to better match the polarity of electrode and electrolyte. Ragone plots, correlating energy density with power density calculated from galvanostatic charge-discharge curves, reveal that activation/annealing further improves energy and power densities.

Morphology characterization and biocompatibility study of PLLA (Poly-L-Llactid-Acid) coating chitosan as stent for coronary heart disease

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Widiyanti, Prihartini; Paramadini, Adanti W.; Jabbar, Hajria; Fatimah, Inas; Nisak, Fadila N. K.; Puspitasari, Rahma A.

2016-03-01

Cardiovascular disease is a global disease with high urgency. In the severe case of coronary heart disease while a blockage in the coronary arteries reach 75% or more, the patient required stent implantation. Stents are made of metal which has many limitations that can lead to blood clots and stent incompatibility toward the size of the blood vessels. There is a metal stent replacement solution that made from polymer material which is biocompatible. PLLA also has biocompatibility and good mechanical strength. PLLA stent will be coated with chitosan as a candidate for drug-coated stents which is able to work as a drug carrier. The aim of this study is to know the morphology information and biocompability status of PLLA coating chitosan as candidate of heart stent. Morphological results using SEM showed a smooth surface structure which reinforced clinical standard of stent material. Results of cytotoxicity test by MTT Assay method showed that the result of four samples in this experiment living cells is reached 90% which is non toxic and safe to use in the human body. %). The conclusion of this study is PLLA is polymer has potency to be used as stent material.

Fabrication of high-performance poly(l-lactic acid)/lignin-graft-poly(d-lactic acid) stereocomplex films.

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Liu, Rui; Dai, Lin; Hu, Li-Qiu; Zhou, Wen-Qin; Si, Chuan-Ling

2017-11-01

The need for green renewable alternatives such as lignin to traditional fillers has driven recent interest in polylactic acid blend materials. Herein, lignin-graft-polylactic acid copolymers (LG-g-PDLA, LG-g-PDLLA, and LG-g-PLLA) have been synthesized via ring-opening polymerization of d-, dl-, and l-lactic acid. Then poly(l-lactic acid)/lignin-graft-polylactic acid (PLLA/LG-g-PDLA, /LG-g-PDLLA, and /LG-g-PLLA) complex films have been prepared. The results showed that, compared with LG-g-PDLA and LG-g-PLLA, a small amount of LG-g-PDLA addition could improve the crystallization rate, reduce the glass transition temperature and cold crystallization temperature of PLLA due to the stereocomplex crystallites. The thermal stability, tensile strength and strain of the stereocomplex films were also enhanced. Moreover, the PLLA/LG-g-PDLA films have good ultraviolet resistance and excellent biocompatibility. This study provides a green approach to design advanced polylactic acid-based blends with renewable natural resources. Copyright © 2017 Elsevier B.V. All rights reserved.

Fabrication and characterization of novel biomimetic PLLA/cellulose/hydroxyapatite nanocomposite for bone repair applications

Energy Technology Data Exchange (ETDEWEB)

Eftekhari, Samin [Department of Chemical Engineering, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3 (Canada); El Sawi, Ihab; Bagheri, Zahra Shaghayegh [Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3 (Canada); Turcotte, Ginette [Department of Chemical Engineering, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3 (Canada); Bougherara, Habiba, E-mail: habiba.bougherara@ryerson.ca [Department of Mechanical and Industrial Engineering, Ryerson University, 350 Victoria Street, Toronto, ON M5B 2K3 (Canada)

2014-06-01

The purpose of this research is to develop and characterize a novel biomimetic nanocomposite that closely mimics the properties of real bone such as morphology, composition and mechanical characteristics. This novel porous nanocomposite is composed of cotton-sourced cellulose microcrystals, hydroxyapatite nanoparticles and poly L-lactide acid. A unique combination of commonly used fabrication procedures has been developed including pre-treatment of particles using a coupling agent. The effect of various weight ratios of the reinforcing agents was evaluated to assess their influence on the chemical, thermal, and mechanical properties of the nanocomposites. The prepared nanocomposites were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and compression testing. Our results indicated the presence of molecular interactions between all components leading to an increase of the crystallinity of the polymer from 50% to 80%. Compression test results revealed that increasing the weight ratio of microcrystalline cellulose/poly L-lactide acid and hydroxyapatite/poly L-lactide acid from 0.1 to 0.5 enhanced the compressive yield stress from 0.127 to 2.2 MPa and The Young's modulus from 6.6 to 38 MPa, respectively. It was found that the fabricated nanocomposites are comparable with the trabecular bone from compositional, structural, and mechanical point of view. - Highlights: • Fabrication of PLLA/HA/cellulose composites that mimic the spongeous bone • Homogenous dispersion of the reinforcing agents in the PLLA matrix was attained. • More efficient interface between the PLLA and the reinforcing agents was achieved. • Preliminary in vitro biocompatibility test showed the nontoxicity of the composite. • The crystallinity, the compressive strength and modulus were investigated.

Cryogenic 3D printing for producing hierarchical porous and rhBMP-2-loaded Ca-P/PLLA nanocomposite scaffolds for bone tissue engineering.

Science.gov (United States)

Wang, Chong; Zhao, Qilong; Wang, Min

2017-06-07

The performance of bone tissue engineering scaffolds can be assessed through cell responses to scaffolds, including cell attachment, infiltration, morphogenesis, proliferation, differentiation, etc, which are determined or heavily influenced by the composition, structure, mechanical properties, and biological properties (e.g. osteoconductivity and osteoinductivity) of scaffolds. Although some promising 3D printing techniques such as fused deposition modeling and selective laser sintering could be employed to produce biodegradable bone tissue engineering scaffolds with customized shapes and tailored interconnected pores, effective methods for fabricating scaffolds with well-designed hierarchical porous structure (both interconnected macropores and surface micropores) and tunable osteoconductivity/osteoinductivity still need to be developed. In this investigation, a novel cryogenic 3D printing technique was investigated and developed for producing hierarchical porous and recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate (Ca-P) nanoparticle/poly(L-lactic acid) nanocomposite scaffolds, in which the Ca-P nanoparticle-incorporated scaffold layer and rhBMP-2-encapsulated scaffold layer were deposited alternatingly using different types of emulsions as printing inks. The mechanical properties of the as-printed scaffolds were comparable to those of human cancellous bone. Sustained releases of Ca 2+ ions and rhBMP-2 were achieved and the biological activity of rhBMP-2 was well-preserved. Scaffolds with a desirable hierarchical porous structure and dual delivery of Ca 2+ ions and rhBMP-2 exhibited superior performance in directing the behaviors of human bone marrow-derived mesenchymal stem cells and caused improved cell viability, attachment, proliferation, and osteogenic differentiation, which has suggested their great potential for bone tissue engineering.

[Anti-tumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line in vitro].

Science.gov (United States)

Li, Maolan; Lu, Wei; Zhang, Fei; Ding, Qichen; Wu, Xiangsong; Tan, Zhujun; Wu, Wenguang; Weng, Hao; Wang, Xuefeng; Shi, Weibin; Dong, Ping; Gu, Jun; Liu, Yingbin

2014-11-04

To explore the antitumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line. DDP-PLLA-CNTs were prepared with the method of ultrasound emulsification. The morphology of DDP-PLLA-CNTs was determined by scanning electron microscope (SEM). And its drug loading and drug release curve in vitro was detected by UV-Vis-NIR spectrophotometer. CCK8 was used to test the cytotoxic effects of DDP-PLLA-CNTs at different concentrations on QBC939 cell proliferation.Flow cytometry was employed to measure the changes of apoptotic rate. With excellent controlled-release characteristic of in vitro drug release, DDP-PLLA-CNTs inhibited the proliferation and significantly increased the apoptotic rate of QBC939 cell line. DDP-PLLA-CNTs have drug sustained-release characteristics and can significantly inhibit the proliferation of QBC939 cell line.

Enhancement of cell-based therapeutic angiogenesis using a novel type of injectable scaffolds of hydroxyapatite-polymer nanocomposite microspheres.

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Yohei Mima

Full Text Available BACKGROUND: Clinical trials demonstrate the effectiveness of cell-based therapeutic angiogenesis in patients with severe ischemic diseases; however, their success remains limited. Maintaining transplanted cells in place are expected to augment the cell-based therapeutic angiogenesis. We have reported that nano-hydroxyapatite (HAp coating on medical devices shows marked cell adhesiveness. Using this nanotechnology, HAp-coated poly(l-lactic acid (PLLA microspheres, named nano-scaffold (NS, were generated as a non-biological, biodegradable and injectable cell scaffold. We investigate the effectiveness of NS on cell-based therapeutic angiogenesis. METHODS AND RESULTS: Bone marrow mononuclear cells (BMNC and NS or control PLLA microspheres (LA were intramuscularly co-implanted into mice ischemic hindlimbs. When BMNC derived from enhanced green fluorescent protein (EGFP-transgenic mice were injected into ischemic muscle, the muscle GFP level in NS+BMNC group was approximate fivefold higher than that in BMNC or LA+BMNC groups seven days after operation. Kaplan-Meier analysis demonstrated that NS+BMNC markedly prevented hindlimb necrosis (P<0.05 vs. BMNC or LA+BMNC. NS+BMNC revealed much higher induction of angiogenesis in ischemic tissues and collateral blood flow confirmed by three-dimensional computed tomography angiography than those of BMNC or LA+BMNC groups. NS-enhanced therapeutic angiogenesis and arteriogenesis showed good correlations with increased intramuscular levels of vascular endothelial growth factor and fibroblast growth factor-2. NS co-implantation also prevented apoptotic cell death of transplanted cells, resulting in prolonged cell retention. CONCLUSION: A novel and feasible injectable cell scaffold potentiates cell-based therapeutic angiogenesis, which could be extremely useful for the treatment of severe ischemic disorders.

Effect of tissue scaffold topography on protein structure monitored by fluorescence spectroscopy.

Science.gov (United States)

Portugal, Carla A M; Truckenmüller, Roman; Stamatialis, Dimitrios; Crespo, João G

2014-11-10

The impact of surface topography on the structure of proteins upon adhesion was assessed through non-invasive fluorescence monitoring. This study aimed at obtaining a better understanding about the role of protein structural status on cell-scaffold interactions. The changes induced upon adsorption of two model proteins with different geometries, trypsin (globular conformation) and fibrinogen (rod-shaped conformation) on poly-l-lactic acid (PLLA) scaffolds with different surface topographies, flat, fibrous and surfaces with aligned nanogrooves, were assessed by fluorescence spectroscopy monitoring, using tryptophan as structural probe. Hence, the maximum emission blue shift and the increase of fluorescence anisotropy observed after adsorption of globular and rod-like shaped proteins on surfaces with parallel nanogrooves were ascribed to more intense protein-surface interactions. Furthermore, the decrease of fluorescence anisotropy observed upon adsorption of proteins to scaffolds with fibrous morphology was more significant for rod-shaped proteins. This effect was associated to the ability of these proteins to adjust to curved surfaces. The additional unfolding of proteins induced upon adsorption on scaffolds with a fibrous morphology may be the reason for better cell attachment there, promoting an easier access of cell receptors to initially hidden protein regions (e.g. RGDS sequence), which are known to have a determinant role in cell attaching processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and characterization of a coronary polylactic acid stent prototype generated by selective laser melting.

Science.gov (United States)

Flege, Christian; Vogt, Felix; Höges, Simon; Jauer, Lucas; Borinski, Mauricio; Schulte, Vera A; Hoffmann, Rainer; Poprawe, Reinhart; Meiners, Wilhelm; Jobmann, Monika; Wissenbach, Konrad; Blindt, Rüdiger

2013-01-01

In-stent restenosis is still an important issue and stent thrombosis is an unresolved risk after coronary intervention. Biodegradable stents would provide initial scaffolding of the stenosed segment and disappear subsequently. The additive manufacturing technology Selective Laser Melting (SLM) enables rapid, parallel, and raw material saving generation of complex 3- dimensional structures with extensive geometric freedom and is currently in use in orthopedic or dental applications. Here, SLM process parameters were adapted for poly-L-lactid acid (PLLA) and PLLA-co-poly-ε-caprolactone (PCL) powders to generate degradable coronary stent prototypes. Biocompatibility of both polymers was evidenced by assessment of cell morphology and of metabolic and adhesive activity at direct and indirect contact with human coronary artery smooth muscle cells, umbilical vein endothelial cells, and endothelial progenitor cells. γ-sterilization was demonstrated to guarantee safety of SLM-processed parts. From PLLA and PCL, stent prototypes were successfully generated and post-processing by spray- and dip-coating proved to thoroughly smoothen stent surfaces. In conclusion, for the first time, biodegradable polymers and the SLM technique were combined for the manufacturing of customized biodegradable coronary artery stent prototypes. SLM is advocated for the development of biodegradable coronary PLLA and PCL stents, potentially optimized for future bifurcation applications.

Estudo da Degradação In Vitro de Blendas de Poli(p-dioxanona/Poli(l-Ácido Láctico (PPD/PLLA Preparadas por Evaporação de Solvente Degradation of Poly (L-Lactic Acid (PLLA and Poly-p-Dioxanone (PPD Blends Prepared by Casting: In Vitro Study

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Ana P. T. Pezzin

2002-10-01

Full Text Available Blendas de dois polímeros semi-cristalinos biorreabsorvíveis, o poli(ácido láctico (PLLA e a poli(p-dioxanona (PPD, foram preparadas por evaporação de solvente em diferentes composições. As blendas foram imersas em tubos de ensaio contendo solução tampão fosfato (pH = 7,4 em um banho termostatizado a 37 ± 1 °C e avaliadas por calorimetria diferencial de varredura (DSC, análise termogravimétrica (TGA e microscopia eletrônica de varredura (MEV. Foi observado através do estudo in vitro que o PLLA apresenta uma taxa de degradação mais lenta que a PPD e que as blendas apresentam taxa de degradação intermediária, mostrando que é possível variar a taxa de degradação das blendas alterando sua composição.Blends of two crystalline bioreabsorbable polymers, poly(L-lactic acid (PLLA and poly(p-dioxanone (PPD, have been prepared by solvent casting in different compositions. The blends were immersed in tubes containing a phosphate buffer solution (pH = 7.4 in a thermally controlled bath of 37 ± 1°C and studied by differential scanning calorimetry (DSC, thermogravimetric analysis (TGA and scanning electron microscopy (SEM. It was observed by in vitro study that PLLA has a slower degradation rate than PPD and the blends presented an intermediate degradation rate. This shows that it is possible to vary the degradation rate of the blend by changing its composition.

Computational molecular modeling and structural rationalization for the design of a drug-loaded PLLA/PVA biopolymeric membrane

International Nuclear Information System (INIS)

Sibeko, B; Pillay, V; Choonara, Y E; Khan, R A; Danckwerts, M P; Modi, G; Iyuke, S E; Naidoo, D

2009-01-01

The purpose of this study was to design, characterize and assess the influence of triethanolamine (TEA) on the physicomechanical properties and release of methotrexate (MTX) from a composite biopolymeric membrane. Conjugated poly(L-lactic acid) (PLLA) and poly(vinyl alcohol) (PVA) membranes were prepared by immersion precipitation with and without the addition of TEA. Drug entrapment efficiency (DEE) and release studies were performed in phosphate buffered saline (pH 7.4, 37 deg. C). Scanning electron microscopy elucidated the membrane surface morphology. Computational and structural molecular modeling rationalized the potential mechanisms of membrane formation and MTX release. Bi-axial force-distance (F-D) extensibility profiles were generated to determine the membrane toughness, elasticity and fracturability. Membranes were significantly toughened by the addition of TEA as a discrete rubbery phase within the co-polymer matrix. MTX-TEA-PLLA-PVA membranes were tougher (F = 89 N) and more extensible (D = 8.79 mm) compared to MTX-PLLA-PVA (F = 35 N, D = 3.7 mm) membranes as a greater force of extension and fracture distance were required (N = 10). DEE values were relatively high (>80%, N = 5) for both formulations. Photomicrographs revealed distinct crystalline layered morphologies with macro-pores. MTX was released by tri-phasic kinetics with a lower fractional release of MTX from MTX-TEA-PLLA-PVA membranes compared to MTX-PLLA-PVA. TEA provided a synergistic approach to improving the membrane physicomechanical properties and modulation of MTX release. The composite biopolymeric membrane may therefore be suitable for the novel delivery of MTX in the treatment of chronic primary central nervous system lymphoma.

In vitro evaluation of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds for bone tissue engineering.

Science.gov (United States)

Jiang, Tao; Abdel-Fattah, Wafa I; Laurencin, Cato T

2006-10-01

A three-dimensional (3-D) scaffold is one of the major components in many tissue engineering approaches. We developed novel 3-D chitosan/poly(lactic acid-glycolic acid) (PLAGA) composite porous scaffolds by sintering together composite chitosan/PLAGA microspheres for bone tissue engineering applications. Pore sizes, pore volume, and mechanical properties of the scaffolds can be manipulated by controlling fabrication parameters, including sintering temperature and sintering time. The sintered microsphere scaffolds had a total pore volume between 28% and 37% with median pore size in the range 170-200microm. The compressive modulus and compressive strength of the scaffolds are in the range of trabecular bone making them suitable as scaffolds for load-bearing bone tissue engineering. In addition, MC3T3-E1 osteoblast-like cells proliferated well on the composite scaffolds as compared to PLAGA scaffolds. It was also shown that the presence of chitosan on microsphere surfaces increased the alkaline phosphatase activity of the cells cultured on the composite scaffolds and up-regulated gene expression of alkaline phosphatase, osteopontin, and bone sialoprotein.

Biodegradable poly (lactic acid-co-glycolic acid scaffolds as carriers for genetically-modified fibroblasts.

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Tatjana Perisic

Full Text Available Recent advances in gene delivery into cells allow improved therapeutic effects in gene therapy trials. To increase the bioavailability of applied cells, it is of great interest that transfected cells remain at the application site and systemic spread is minimized. In this study, we tested clinically used biodegradable poly(lactic acid-co-glycolic acid (PLGA scaffolds (Vicryl & Ethisorb as transient carriers for genetically modified cells. To this aim, we used human fibroblasts and examined attachment and proliferation of untransfected cells on the scaffolds in vitro, as well as the mechanical properties of the scaffolds at four time points (1, 3, 6 and 9 days of cultivation. Furthermore, the adherence of cells transfected with green fluorescent protein (GFP and vascular endothelial growth factor (VEGF165 and also VEGF165 protein secretion were investigated. Our results show that human fibroblasts adhere on both types of PLGA scaffolds. However, proliferation and transgene expression capacity were higher on Ethisorb scaffolds most probably due to a different architecture of the scaffold. Additionally, cultivation of the cells on the scaffolds did not alter their biomechanical properties. The results of this investigation could be potentially exploited in therapeutic regiments with areal delivery of transiently transfected cells and may open the way for a variety of applications of cell-based gene therapy, tissue engineering and regenerative medicine.

Nitrate removal properties of solid-phase denitrification processes using acid-blended poly(L-lactic acid) as the sole substrate

International Nuclear Information System (INIS)

Yamada, T; Matsuoka, H; Sun, J; Tsuji, H; Hiraishi, A; Yoshikawa, S

2013-01-01

The large amount of waste that is discharged along with the diffusion of poly(L-lactic acid) (PLLA) articles in use is persistent concern. Previously, we studied solid-phase denitrification (SPD) processes using PLLA to establish an effective re-use of PLLA waste. We found that PLLA with a weight-average molecular weight (M w ) of approximately 10,000 was suitable for SPD processes; however, the recycling of PLLA waste consumes a high energy. A new PLLA plastic including 5% poly(ethylene oxalate) (PEOxPLLA) as a blend material has attracted attention because recycling of PEOxPLLA consumes less electricity than that of PLLA. In this study, our main objectives were to evaluate whether PEOxPLLA can be used for SPD processes by changing its M w and to investigate the bioavailability for denitrification of hydrolysates released from PEOxPLLA. The predicted hydrolysates, including oxalic acid, ethylene glycol, and lactate, are abiotically released, leading to different biological nitrate removal rates. Consequently, the nitrate removal rate of PEOxPLLA ranged from 0.9–4.1 mg-NO 3 − -N·g-MLSS·h −1 by changing the M w in the range of 8,500–238,000. In culture-dependent approaches, denitrifying bacteria using each substrate as an electron donor are found in activated sludge, suggesting that all hydrolysates functioned in the SPD processes using PEOxPLLA.

Evaluation of magnesium ions release, biocorrosion, and hemocompatibility of MAO/PLLA-modified magnesium alloy WE42.

Science.gov (United States)

Lu, Ping; Cao, Lu; Liu, Yin; Xu, Xinhua; Wu, Xiangfeng

2011-01-01

Magnesium alloys may potentially be applied as biodegradable metallic materials in cardiovascular stent. However, the high corrosion rate hinders its clinical application. In this study, a new approach was adopted to control the corrosion rate by fabricating a biocompatible micro-arc oxidation/poly-L-lactic acid (MAO/PLLA) composite coating on the magnesium alloy WE42 substrate and the biocompatibility of the modified samples was investigated. The scanning electronic microscope (SEM) images were used to demonstrate the morphology of the samples before and after being submerged in hanks solution for 4 weeks. The degradation was evaluated through the magnesium ions release rate and electrochemical impedance spectroscopy (EIS) test. The biocompatibility of the samples was demonstrated by coagulation time and hemolysis behavior. The result shows that the poly-L-lactic acid (PLLA) effectively improved the corrosion resistance by sealing the microcracks and microholes on the surface of the MAO coating. The modified samples had good compatibility. © 2010 Wiley Periodicals, Inc.

Characterization of Electrospun Nanofibrous Scaffolds for Nanobiomedical Applications

Science.gov (United States)

Emul, E.; Saglam, S.; Ates, H.; Korkusuz, F.; Saglam, N.

2016-08-01

The electrospinning method is employed in the production of porous fiber scaffolds, and the usage of electrospun scaffolds especially as drug carrier and bone reconstructive material such as implants is promising for future applications in tissue engineering. The number of publications has grown very rapidly in this field through the fabrication of complex scaffolds, novel approaches in nanotechnology, and improvements of imaging methods. Hence, characterization of these materials has also grown significantly important for getting satisfied and accurate results. This advantageous and versatile method is ideal for mimicking bone extracellular matrix, and many biodegradable and biocompatible polymers are preferred in the field of bone reconstruction. In this study, gelatin, gelatin/nanohydroxyapatite (nHAp) and gelatin/PLLA/nHAp scaffolds were fabricated by the electrospinning process. These composite fibers showed clear and continuous morphology according to observation through a scanning electron microscope and their component analyses were also determined by Fourier transform infrared spectrometer analyses. These characterization experiments revealed the great effects of the electrospinning method for biomedical applications and have an especially important role in bone reconstruction and production of implant coating material.

In-situ polymerized cellulose nanocrystals (CNC)-poly(l-lactide) (PLLA) nanomaterials and applications in nanocomposite processing.

Science.gov (United States)

Miao, Chuanwei; Hamad, Wadood Y

2016-11-20

CNC-PLLA nanomaterials were synthesized via in-situ ring-opening polymerization of l-lactide in the presence of CNC, resulting in hydrophobic, homogeneous mixture of PLLA-grafted-CNC and free PLLA homopolymer. The free PLLA serves two useful functions: as barrier to further prevent PLLA-g-CNC from forming aggregates, and in creating improved interfacial properties when these nanomaterials are blended with other polymers, hence enhancing their performance. CNC-PLLA nanomaterials can be used for medical or engineering applications as-they-are or by compounding with suitable biopolymers using versatile techniques, such as solution casting, co-extrusion or injection molding, to form hybrid nanocomposites of tunable mechanical properties. When compounded with commercial-grade PLA, the resulting CNC-PLA nanocomposites appear transparent and have tailored (dynamic and static) mechanical and barrier properties, approaching those of poly(ethylene terephthalate), PET. The effect of reaction conditions on the properties of CNC-PLLA nanomaterials have been carefully studied and detailed throughout the paper. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

Directory of Open Access Journals (Sweden)

Markus D. Schofer

2009-01-01

Full Text Available Growth factors like bone morphogenetic protein 2 (BMP-2 and vascular endothelial growth factor (VEGF play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid (PLLA nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2–enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers.

Lack of Obvious Influence of PLLA Nanofibers on the Gene Expression of BMP-2 and VEGF during Growth and Differentiation of Human Mesenchymal Stem Cells

Science.gov (United States)

Schofer, Markus D.; Fuchs-Winkelmann, S.; Wack, C.; Rudisile, M.; Dersch, R.; Leifeld, I.; Wendorff, J.; Greiner, A.; Paletta, J. R. J.; Boudriot, U.

2009-01-01

Growth factors like bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) play an important role in bone remodeling and fracture repair. Therefore, with respect to tissue engineering, an artificial graft should have no negative impact on the expression of these factors. In this context, the aim of this study was to analyze the impact of poly(L-lactic acid) (PLLA) nanofibers on VEGF and BMP-2 gene expression during the time course of human mesenchymal stem cell (hMSC) differentiation towards osteoblasts. PLLA matrices were seeded with hMSCs and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of VEGF and BMP-2. Furthermore, BMP-2–enwoven PLLA nanofibers were used in order to elucidate whether initial down-regulation of growth factor expression could be compensated. Although there was a great interpatient variability with respect to the expression of VEGF and BMP-2, PLLA nanofibers tend to result in a down-regulation in BMP-2 expression during the early phase of cultivation. This effect was diminished in the case of VEGF gene expression. The initial down-regulation was overcome when BMP-2 was directly incorporated into the PLLA nanofibers by electrospinning. Furthermore, the incorporation of BMP-2 into the PLLA nanofibers resulted in an increase in VEGF gene expression. Summarized, the results indicate that the PLLA nanofibers have little effect on growth factor production. An enhancement in gene expression of BMP-2 and VEGF can be achieved by an incorporation of BMP-2 into the PLLA nanofibers. PMID:19412560

Investigation of microstructure and mechanical properties of PLLA/HA system

Science.gov (United States)

Nik Hanyn N., H.; Ahmad, K. Z. Ku; Yusof, Mohd Reusmaazran; Kamarolzaman, A. A.

2017-12-01

The poly(L-lactide) (PLLA), carboxymethyl starch (CMS) and hydroxyapatite (HAp) nanofibers have been prepared by electrospinning technique. The PLLA/CMS formulations applied at various voltage were studied for electrospinning into nanofibers. It was found that the morphology of the fibers became finer with the increment of voltage applied. The formulation with 10 kV voltage was selected as it shows promising result based on the morphology observation. The PLLA/CMS/HA formulation with HA loading concentration (i.e. 0.25, 0.50, 0.75 and 1.00 wt%) was fabricated in the next stage, and the effect of HA addition was studied. Observation showed that the electrospun nanofibers' diameters were reduced with the addition of HAp concentration from 0.25 wt% HAp to 1.00 wt% Hap.

Scaffolding along Nucleic Acid Duplexes Using 2'-Amino-Locked Nucleic Acids

DEFF Research Database (Denmark)

Astakhova, I Kira; Wengel, Jesper

2014-01-01

-LNA nucleotides. By application of different chemical reactions, modification of 2'-amino-LNA scaffolds can be efficiently performed in high yields and with various tags, postsynthetically or during the automated oligonucleotide synthesis. The choice of a synthetic method for scaffolding along 2'-amino-LNA mainly....../DNA probes bind nucleic acid targets with advantages of high affinity and specificity. Thus, molecular motion of nanodevices and programmable self-assembly of chemically modified LNA/DNA nanomaterials can be followed by bright fluorescence signaling from the functionalized LNA units. Another appealing aspect...

Biodegradability and Biocompatibility Study of Poly(Chitosan-g-lactic Acid Scaffolds

Directory of Open Access Journals (Sweden)

Zhe Zhang

2012-03-01

Full Text Available A biodegradable, biocompatible poly(chitosan-g-lactic acid (PCLA scaffold was prepared and evaluated in vitro and in vivo. The PCLA scaffold was obtained by grafting lactic acid (LA onto the amino groups on chitosan (CS without a catalyst. The PCLA scaffolds were characterized by Fourier Transform infrared spectroscopy (FT-IR and scanning electron microscopy (SEM. The biodegradabilty was determined by mass loss in vitro, and degradation in vivo as a function of feed ratio of LA/CS. Bone marrow mesenchymal stem cell (BMSC culture experiments and histological examination were performed to evaluate the PCLA scaffolds’ biocompatibility. The results indicated that PCLA was promising for tissue engineering application.

Regulating performance of poly(L-lactic acid) by Addition of N, N‧-Bis(Salicyloyl) p-phthalic acid dihydrazide

Science.gov (United States)

Cai, Yan-Hua; Tian, Liang-Liang; Zhao, Li-Sha; Zhang, Mei-Xia

2017-10-01

Within this work, the influence of a crystallization accelerator N, N‧-bis(salicyloyl) p-phthalic acid dihydrazide (PAS) on the non-isothermal crystallization behavior, melting behavior, thermal stability, and light transmittance of poly(L-lactic acid) (PLLA) was investigated by differential scanning calorimetry (DSC), x-ray diffraction (XRD), thermogravimetric analysis (TGA), and light transmittance meter. Comparative analysis of the non-isothermal crystallization behavior of the primary PLLA and PLLA/PAS samples revealed an important role of PAS in promoting the crystallization of PLLA in cooling. Additionally, the concentration of PAS and cooling rate also exhibited significant effect on the non-isothermal crystallization process, and the 3 wt% PAS causes the PLLA to have the highest the onset crystallization temperature and the crystallization peak temperature, and the largest non-isothermal crystallization enthalpy. However, the increase of cooling rate resulted in the decrease of crystal growth ability, weakening the crystallization of PLLA. The investigating on the melting behavior under different conditions further confirmed the crystallization promoting effect of PAS for PLLA, and the crystallization temperature, resulting from the different crystal growth rate, affected remarkably the melting behavior of PLLA/3%PAS sample. The addition of PAS could not change the thermal decomposition behavior of the primary PLLA, but decreased the onset decomposition temperature with an increase of PAS concentration in PLLA matrix. Similarly, the incorporation of PAS is unfavourable to the light transmittance of the primary PLLA.

Nucleated Poly(L-lactic acid) with N, N‧-oxalyl bis(benzoic acid) dihydrazide

Science.gov (United States)

Tian, Liang-Liang; Cai, Yan-Hua

2018-04-01

One of the major challenges in the field of Poly(L-lactic acid) (PLLA) is the enhancement of crystallization. In the present work, the evaluation of the influence of N, N‧-oxalyl bis(benzoic acid) dihydrazide (TBOD), as a novel organic nucleating agent, on the non-isothermal crystallization, melting behavior, and thermal stability of PLLA was performed using differential scanning calorimeter and thermogravimetric analysis. Non-isothermal crystallization measurement revealed that TBOD had an excellent accelerating effect for the crystallization of PLLA in cooling, and upon the addition of 3 wt% TBOD, PLLA exhibited the highest onset crystallization temperature and the crystallization peak temperature, as well as the largest non-isothermal crystallization enthalpy. In particular, when the TBOD concentration was 1 wt% ∼ 3 wt%, the onset crystallization temperatures were higher than the theoretical ceiling temperature of crystallization, thoroughly demonstrating the powerful crystallization promoting ability of TBOD. Additionally, the non-isothermal crystallization behavior of PLLA/TBOD depended on the TBOD concentration, cooling rate as well as the final melting temperature. The melting behavior of PLLA/TBOD after non-isothermal crystallization further confirmed the effect of TBOD on the crystallization process and crystal structure of PLLA, and the appearance of the double melting peaks during melting stages was attribute to the melting-recrystallization. For melting behavior after isothermal crystallization, the crystallization temperature and crystallization time significantly affected the melting behavior of PLLA/TBOD. The addition of TBOD could not change the thermal decomposition profile of the PLLA, but the thermal stability did not regularly decrease with increasing of TBOD concentration, indicating that there might exist intermolecular interaction between PLLA and TBOD.

Polylactic acid organogel as versatile scaffolding technique

NARCIS (Netherlands)

Punet, Xavier; Levato, Riccardo; Bataille, Isabelle; Letourneur, Didier; Engel, Elisabeth; Mateos-Timoneda, Miguel A

2017-01-01

Tissue engineering requires scaffolding techniques based on non-toxic processes that permits the fabrication of constructs with tailored properties. Here, a two-step methodology based on the gelation and precipitation of the poly(lactic) acid/ethyl lactate organogel system is presented. With this

Morphology, rheology and electrical resistivity of PLLA/HDPE/CNT nanocomposites: Effect of maleic anhydride

Energy Technology Data Exchange (ETDEWEB)

Shao, Li-na; Chen, Jie; Dai, Jian; Chen, Hai-ming; Yang, Jing-hui [Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Wang, Yong, E-mail: yongwang1976@163.com [Key Laboratory of Advanced Technologies of Materials (Ministry of Education), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Zhang, Chao-liang [State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041 (China)

2015-02-15

As a part of serial work about tuning the selective location of carbon nanotubes (CNTs) in immiscible polymer blends, this work reports the effects of component polarity and viscosity ratio between components on the selective location of CNTs and the resultant electrical resistivity of the nanocomposites. To achieve the research aim, maleic anhydride (MA) was grafted onto poly(L-lactide) (PLLA) main chain through a reactive compounding processing. After that, different contents of CNTs were incorporated into blends of high density polyethylene (HDPE) and PLLA (or PLLA-g-MA). The morphologies of the ternary nanocomposites and the selective location of CNTs in the nanocomposites were characterized using scanning electron microscope (SEM) and transmission electron microscope (TEM). The microstructure of nanocomposites and the dispersion of CNTs were further proved by rheological measurement. Finally, the electrical resistivity of nanocomposites containing different CNT contents was measured. The results showed that through increasing the polarity of PLLA and decreasing the melt viscosity, CNTs were kinetically trapped at the blend interface region. Consequently, largely decreased percolation threshold was achieved for the PLLA-g-MA/HDPE/CNT nanocomposites. The morphological changes as well as the rheological properties were also comparatively analyzed. - Highlights: • PLLA/HDPE/CNT and PLLA-g-MA/HDPE/CNT composites were prepared. • Different selective location states of CNTs were achieved in different composites. • Selectively located CNTs at the interface resulted in lower percolation threshold.

Functionalization of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering.

Science.gov (United States)

Jiang, Tao; Khan, Yusuf; Nair, Lakshmi S; Abdel-Fattah, Wafa I; Laurencin, Cato T

2010-06-01

Scaffolds exhibiting biological recognition and specificity play an important role in tissue engineering and regenerative medicine. The bioactivity of scaffolds in turn influences, directs, or manipulates cellular responses. In this study, chitosan/poly(lactic acid-co-glycolic acid) (chitosan/PLAGA) sintered microsphere scaffolds were functionalized via heparin immobilization. Heparin was successfully immobilized on chitosan/PLAGA scaffolds with controllable loading efficiency. Mechanical testing showed that heparinization of chitosan/PLAGA scaffolds did not significantly alter the mechanical properties and porous structures. In addition, the heparinized chitosan/PLAGA scaffolds possessed a compressive modulus of 403.98 +/- 19.53 MPa and a compressive strength of 9.83 +/- 0.94 MPa, which are in the range of human trabecular bone. Furthermore, the heparinized chitosan/PLAGA scaffolds had an interconnected porous structure with a total pore volume of 30.93 +/- 0.90% and a median pore size of 172.33 +/- 5.89 mum. The effect of immobilized heparin on osteoblast-like MC3T3-E1 cell growth was investigated. MC3T3-E1 cells proliferated three dimensionally throughout the porous structure of the scaffolds. Heparinized chitosan/PLAGA scaffolds with low heparin loading (1.7 microg/scaffold) were shown to be capable of stimulating MC3T3-E1 cell proliferation by MTS assay and cell differentiation as evidenced by elevated osteocalcin expression when compared with nonheparinized chitosan/PLAGA scaffold and chitosan/PLAGA scaffold with high heparin loading (14.1 microg/scaffold). This study demonstrated the potential of functionalizing chitosan/PLAGA scaffolds via heparinization with improved cell functions for bone tissue engineering applications.

Sequential crystallization and morphology of triple crystalline biodegradable PEO-b-PCL-b-PLLA triblock terpolymers

KAUST Repository

Palacios, Jordana

2016-01-05

The sequential crystallization of poly(ethylene oxide)-b-poly(e-caprolactone)-b-poly(L-lactide) (PEO-b-PCL-b-PLLA) triblock terpolymers, in which the three blocks are able to crystallize separately and sequentially from the melt, is presented. Two terpolymers with identical PEO and PCL block lengths and two different PLLA block lengths were prepared, thus the effect of increasing PLLA content on the crystallization behavior and morphology was evaluated. Wide angle X-Ray scattering (WAXS) experiments performed on cooling from the melt confirmed the triple crystalline nature of these terpolymers and revealed that they crystallize in sequence: the PLLA block crystallizes first, then the PCL block, and finally the PEO block. Differential scanning calorimetry (DSC) analysis further demonstrated that the three blocks can crystallize from the melt when a low cooling rate is employed. The crystallization process takes place from a homogenous melt as indicated by small angle X-Ray scattering (SAXS) experiments. The crystallization and melting enthalpies and temperatures of both PEO and PCL blocks decrease as PLLA content in the terpolymer increases. Polarized light optical microscopy (PLOM) demonstrated that the PLLA block templates the morphology of the terpolymer, as it forms spherulites upon cooling from the melt. The subsequent crystallization of PCL and PEO blocks occurs inside the interlamellar regions of the previously formed PLLA block spherulites. In this way, unique triple crystalline mixed spherulitic superstructures have been observed for the first time. As the PLLA content in the terpolymer is reduced the superstructural morphology changes from spherulites to a more axialitic-like structure.

A Comparison of Degradable Synthetic Polymer Fibers for Anterior Cruciate Ligament Reconstruction

Science.gov (United States)

Tovar, Nick; Bourke, Sharon; Jaffe, Michael; Murthy, N. Sanjeeva; Kohn, Joachim; Gatt, Charles; Dunn, Michael G.

2009-01-01

We compared mechanical properties, degradation rates, and cellular compatibilities of two synthetic polymer fibers potentially useful as ACL reconstruction scaffolds: poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate)(12,10), p(DTD DD) and poly(L-lactic acid), PLLA. The yield stress of ethylene oxide (ETO) sterilized wet fibers was 150 ± 22 MPa and 87 ± 12 MPa for p(DTD DD) and PLLA, respectively, with moduli of 1.7 ± 0.1 MPa and 4.4 ± 0.43 MPa. Strength and molecular weight retention were determined after incubation under physiological conditions at varying times. After 64 weeks strength decreased to 20 and 37% of the initial sterile fiber values and MW decreased to 41% and 36% of the initial values for p(DTD DD) and PLLA, respectively. ETO sterilization had no significant effect on mechanical properties. Differences in mechanical behavior may be due to the semicrystalline nature of PLLA and the small degree of crystallinity induced by mesogenic ordering in p(DTD DD) suggested by DSC analysis. Fibroblast growth was similar on 50-fiber scaffolds of both polymers through 16 days in vitro. These data suggest that p(DTD DD) fibers, with higher strength, lower stiffness, favorable degradation rate and cellular compatibility, may be a superior alternative to PLLA fibers for development of ACL reconstruction scaffolds. PMID:19623532

Development of mechanically expanded gelatin-AAc-PLLA/PLCL nanofibers for vascular tissue engineering by radiation-based techniques

Energy Technology Data Exchange (ETDEWEB)

Jeong, Jin Oh; Jeong, Sung In; Seo, Da Eun; Park, Jong Seok; Gwon, Hui Jeong; Ahn, Sung Jun; Lim, Youn Mook [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Shin, Young Min [Dept. of Bioengineering, Division of Applied Chemical and Bio Engineering, Hanyang University, Seoul (Korea, Republic of)

2015-12-15

Vascular tissue engineering has been accessed to mimic the natural composition of the blood vessel containing inmate, media, and adventitia layers. We fabricated mechanically expanded PLLA/PLCL nanofibers using electrospinning and UTM. The pore size of the meshes was increased the gelatin immobilized AAc-PLLA/PLCL nanofibers (203.30±49.62 microns) than PLLA/PLCL nanofibers (59.99±8.66 microns) after mechanical expansion. To increase the cell adhesion and proliferation, we introduced carboxyl group, and gelatin was conjugated on them. The properties of the PLLA/PLCL nanofibers were analyzed with SEM, ATR-FTIR, TBO staining, and water contact angle measurement, general cell responses on the PLLA/PLCL nanofibers such as adhesion, proliferation, and infiltration were also investigated using smooth muscle cell (SMC). During the SMC culture, the initial viability of the cells was significantly increased on the gelatin immobilized AAc-PLLA/PLCL nanofibers, and infiltration of the cells was also enhanced on them. Therefore, gelatin immobilized AAc-PLLA/PLCL nanofibers and mechanically expanded meshes may be a good tool for vascular tissue engineering application.

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

Energy Technology Data Exchange (ETDEWEB)

Shafiee, Abbas [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD (Australia); Seyedjafari, Ehsan [Department of Biotechnology, College of Science, University of Tehran, Tehran (Iran, Islamic Republic of); Sadat Taherzadeh, Elham [Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); Dinarvand, Peyman [Stem Cell biology and Tissue Engineering Departments, Stem Cell Technology Research Center, Tehran (Iran, Islamic Republic of); The Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO (United States); Soleimani, Masoud [Hematology Department, Faculty of Medical Science, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ai, Jafar, E-mail: jafar_ai@tums.ac.ir [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Brain and Spinal Injury Research Center, Imam Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2014-07-01

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (L-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. - Highlights: • Electrospun nanofiber scaffolds with different topographies were fabricated. • Aligned nanofiber scaffolds had better tensile strength properties. • Nasal septum derived progenitors were cultured on nanofibrous scaffolds. • Both topographies support proliferation and chondrogenic differentiation. • Better chondrogenic differentiation was observed on aligned nanofibers.

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

International Nuclear Information System (INIS)

Shafiee, Abbas; Seyedjafari, Ehsan; Sadat Taherzadeh, Elham; Dinarvand, Peyman; Soleimani, Masoud; Ai, Jafar

2014-01-01

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (L-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. - Highlights: • Electrospun nanofiber scaffolds with different topographies were fabricated. • Aligned nanofiber scaffolds had better tensile strength properties. • Nasal septum derived progenitors were cultured on nanofibrous scaffolds. • Both topographies support proliferation and chondrogenic differentiation. • Better chondrogenic differentiation was observed on aligned nanofibers

Piezoelectric antibacterial fabric comprised of poly(l-lactic acid) yarn

Science.gov (United States)

Ando, Masamichi; Takeshima, Satoshi; Ishiura, Yutaka; Ando, Kanako; Onishi, Osamu

2017-10-01

A lactic acid monomer has an asymmetric carbon in the molecule, so there are optical isomer l- and d-type. The most widely used poly(lactic acid) (PLA) for commercial applications is poly(l-lactic acid) (PLLA). PLLA is the polymerization product of l-lactide. Certain treatments of PLLA can yield a film that exhibits shear piezoelectricity. Thus, piezoelectric PLLA fiber can be generated by micro slitting piezoelectric PLLA films or by a melt spinning method. We prepared left-handed helical multi fiber yarn (S-yarn) and right-handed helical yarn (Z-yarn) using piezoelectric PLLA fiber. PLLA exhibited shear mode piezoelectricity, causing the electric polarity of the yarn surface to be reversed on the S-yarn and Z-yarn when tension was applied. An SZ-yarn was produced by combining the S-yarn and Z-yarn, and fabric was prepared using the SZ-yarn. This study demonstrated that the fabric has a strong antibacterial effect, which is thought to be due to the strong electric field between the yarns. The field is generated by a piezoelectric effect when the fabric was extended and contracted.

Experimental study of 32P-CP-PLLA microparticle on human pancreatic carcinoma in nude mice

International Nuclear Information System (INIS)

Wang Lizhen; Yang Min; Xu Yuping; Pan Donghui; Huang Peilin; Liu Lu; Shao Guoqiang

2011-01-01

Objective: To study the therapeutic and toxic effects of 32 P-chromic phosphate-poly (L-lactic) acid ( 32 P-CP-PLLA) microparticle intratumoral administration into BALB/c nude mice bearing BxPc-3 human pancreatic carcinoma. Methods: Twenty four nude mice bearing tumors were injected with 0, 9.3, 18.5 and 37.0 M Bq 32 P-CP-PLLA microparticle, respectively. The relative tumor growth rates were observed every day, and white blood cells, platelets and body weight were measured. At 14 d after administration, the tumors were removed, histological examination and immunohistochemical analysis were performed. Results: The relative tumor growth rates of each treatment group was lower than 40%. Histological examination showed the degenerative necrosis at the site nearby the microparticle. Immunohistochemical analysis showed that the Microvessel density (MVD) and the expression of Bcl-2 in treated group were lower than those in control group.In contrast, the expression of bax in treated group were higher than those in control group. The ratio of Bcl-2/Bax protein significantly decreased in the treatment group,which were 3.83 ± 0.43, 0.47 ± 0.13, 1.10 ± 0.32, 2.19 ± 0.57 for 0, 9.3, 18.5 and 37.0 MBq 32 P-CP-PLLA microparticle, respectively (t=2.36-2.77, P<0.05). MVD were 31.2 ± 2.3, 23.8 ± 1.5, 14.8 ±0.8, 11.0 ± 1.2, respectively. Dose dependence was observed in both HE and IHC staining after 14 d treatment (t=2.30-2.57, P<0.05). Conclusions: Intratumoral injection of 32 P-CP-PLLA microparticle might be a safe, easy and effective radionuclide interventional therapy for pancreatic carcinoma. (authors)

PLLA-grafted cellulose nanocrystals: Role of the CNC content and grafting on the PLA bionanocomposite film properties.

Science.gov (United States)

Lizundia, Erlantz; Fortunati, Elena; Dominici, Franco; Vilas, José Luis; León, Luis Manuel; Armentano, Ilaria; Torre, Luigi; Kenny, Josè M

2016-05-20

Cellulose nanocrystals (CNC), extracted from microcrystalline cellulose by acid hydrolysis, were grafted by ring opening polymerization of L-Lactide initiated from the hydroxyl groups available at their surface and two different CNC:L-lactide ratios (20:80 and 5:95) were obtained. The resulting CNC-g-PLLA nanohybrids were incorporated in poly(lactic acid) (PLA) matrix by an optimized extrusion process at two different content (1 wt.% and 3 wt.%) and obtained bionanocomposite films were characterized by thermal, mechanical, optical and morphological properties. Thermal analysis showed CNC grafted with the higher ratio of lactide play a significant role as a nucleating agent. Moreover, they contribute to a significant increase in the crystallization rate of PLA, and the best efficiency was revealed with 3 wt.% of CNC-g-PLLA. This effect was confirmed by the increased in Young's modulus, suggesting the CNC graft ratio and content contribute significantly to the good dispersion in the matrix, positively affecting the final bionanocomposite properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thermal Annealing to Modulate the Shape Memory Behavior of a Biobased and Biocompatible Triblock Copolymer Scaffold in the Human Body Temperature Range.

Science.gov (United States)

Merlettini, Andrea; Gigli, Matteo; Ramella, Martina; Gualandi, Chiara; Soccio, Michelina; Boccafoschi, Francesca; Munari, Andrea; Lotti, Nadia; Focarete, Maria Letizia

2017-08-14

A biodegradable and biocompatible electrospun scaffold with shape memory behavior in the physiological temperature range is here presented. It was obtained starting from a specifically designed, biobased PLLA-based triblock copolymer, where the central block is poly(propylene azelate-co-propylene sebacate) (P(PAz60PSeb40)) random copolymer. Shape memory properties are determined by the contemporary presence of the low melting crystals of the P(PAz60PSeb40) block, acting as switching segment, and of the high melting crystal phase of PLLA blocks, acting as physical network. It is demonstrated that a straightforward annealing process applied to the crystal phase of the switching element gives the possibility to tune the shape recovery temperature from about 25 to 50 °C, without the need of varying the copolymer's chemical structure. The thermal annealing approach here presented can be thus considered a powerful strategy for "ad hoc" programming the same material for applications requiring different recovery temperatures. Fibroblast culture experiments demonstrated scaffold biocompatibility.

Fabrication and mechanical characterization of 3D electrospun scaffolds for tissue engineering

International Nuclear Information System (INIS)

Wright, L D; Young, R T; Andric, T; Freeman, J W

2010-01-01

Electrospinning is a polymer processing technique that produces fibrous structures comparable to the extracellular matrix of many tissues. Electrospinning, however, has been severely limited in its tissue engineering capabilities because this technique has produced few three-dimensional structures. Sintering of electrospun materials provides a method to fabricate unique architectures and allow much larger structures to be made. Electrospun mats were sintered into strips and cylinders, and their tensile and compressive mechanical properties were measured. In addition, electrospun materials with salt pores (salt embedded within the material and then leached out) were fabricated to improve porosity of the electrospun materials for tissue engineering scaffolds. Sintered electrospun poly(d,l-lactide) and poly(l-lactide) (PDLA/PLLA) materials have higher tensile mechanical properties (modulus: 72.3 MPa, yield: 960 kPa) compared to unsintered PLLA (modulus: 40.36 MPa, yield: 675.5 kPa). Electrospun PDLA/PLLA cylinders with and without salt-leached pores had compressive moduli of 6.69 and 26.86 MPa, respectively, and compressive yields of 1.36 and 0.56 MPa, respectively. Sintering of electrospun materials is a novel technique that improves electrospinning application in tissue engineering by increasing the size and types of electrospun structures that can be fabricated.

Stem cell differentiation on electrospun nanofibrous substrates for vascular tissue engineering

International Nuclear Information System (INIS)

Jia, Lin; Prabhakaran, Molamma P.; Qin, Xiaohong; Ramakrishna, Seeram

2013-01-01

Nanotechnology has enabled the engineering of a variety of materials to meet the current challenges and requirements in vascular tissue regeneration. In our study, poly-L-lactide (PLLA) and hybrid PLLA/collagen (PLLA/Coll) nanofibers (3:1 and 1:1) with fiber diameters of 210 to 430 nm were fabricated by electrospinning. Their morphological, chemical and mechanical characterizations were carried out using scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared (ATR-FTIR), and tensile instrument, respectively. Bone marrow derived mesenchymal stem cells (MSCs) seeded on electrospun nanofibers that are capable of differentiating into vascular cells have great potential for repair of the vascular system. We investigated the potential of MSCs for vascular cell differentiation in vitro on electrospun PLLA/Coll nanofibrous scaffolds using endothelial differentiation media. After 20 days of culture, MSC proliferation on PLLA/Coll(1:1) scaffolds was found 256% higher than the cell proliferation on PLLA scaffolds. SEM images showed that the MSC differentiated endothelial cells on PLLA/Coll scaffolds showed cobblestone morphology in comparison to the fibroblastic type of undifferentiated MSCs. The functionality of the cells in the presence of ‘endothelial induction media’, was further demonstrated from the immunocytochemical analysis, where the MSCs on PLLA/Coll (1:1) scaffolds differentiated to endothelial cells and expressed the endothelial cell specific proteins such as platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) and Von Willebrand factor (vWF). From the results of the SEM analysis and protein expression studies, we concluded that the electrospun PLLA/Coll nanofibers could mimic the native vascular ECM environment and might be promising substrates for potential application towards vascular regeneration. - Highlights: • PLLA and PLLA/Coll nanofibers were electrospun. • Incorporation of collagen reduced fiber

Stem cell differentiation on electrospun nanofibrous substrates for vascular tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Jia, Lin [Key Laboratory of Textile Science and Technology, Ministry of Education, College of Textiles, Donghua University, No. 2999 North Renmin Road, Songjiang, Shanghai 201620 (China); Center for Nanofibers and Nanotechnology, E3-05-14, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Prabhakaran, Molamma P., E-mail: nnimpp@nus.edu.sg [Center for Nanofibers and Nanotechnology, E3-05-14, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Qin, Xiaohong, E-mail: xhqin@dhu.edu.cn [Key Laboratory of Textile Science and Technology, Ministry of Education, College of Textiles, Donghua University, No. 2999 North Renmin Road, Songjiang, Shanghai 201620 (China); Ramakrishna, Seeram [Center for Nanofibers and Nanotechnology, E3-05-14, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)

2013-12-01

Nanotechnology has enabled the engineering of a variety of materials to meet the current challenges and requirements in vascular tissue regeneration. In our study, poly-L-lactide (PLLA) and hybrid PLLA/collagen (PLLA/Coll) nanofibers (3:1 and 1:1) with fiber diameters of 210 to 430 nm were fabricated by electrospinning. Their morphological, chemical and mechanical characterizations were carried out using scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared (ATR-FTIR), and tensile instrument, respectively. Bone marrow derived mesenchymal stem cells (MSCs) seeded on electrospun nanofibers that are capable of differentiating into vascular cells have great potential for repair of the vascular system. We investigated the potential of MSCs for vascular cell differentiation in vitro on electrospun PLLA/Coll nanofibrous scaffolds using endothelial differentiation media. After 20 days of culture, MSC proliferation on PLLA/Coll(1:1) scaffolds was found 256% higher than the cell proliferation on PLLA scaffolds. SEM images showed that the MSC differentiated endothelial cells on PLLA/Coll scaffolds showed cobblestone morphology in comparison to the fibroblastic type of undifferentiated MSCs. The functionality of the cells in the presence of ‘endothelial induction media’, was further demonstrated from the immunocytochemical analysis, where the MSCs on PLLA/Coll (1:1) scaffolds differentiated to endothelial cells and expressed the endothelial cell specific proteins such as platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) and Von Willebrand factor (vWF). From the results of the SEM analysis and protein expression studies, we concluded that the electrospun PLLA/Coll nanofibers could mimic the native vascular ECM environment and might be promising substrates for potential application towards vascular regeneration. - Highlights: • PLLA and PLLA/Coll nanofibers were electrospun. • Incorporation of collagen reduced fiber

Synthesis and characterization of semi-IPNs based on PVP and PLLA; Sintese e caracterizacao de semi-IPNs envolvendo os homopolimeros PVP e PLLA

Energy Technology Data Exchange (ETDEWEB)

Camilo, A.P.R.; Mano, V., E-mail: mano@ufsj.edu.b [Universidade Federal de Sao Joao del Rei (UFSJ), MG (Brazil). Dept. de Ciencias Naturais; Felisberti, M.I. [Universidade Estadual de Campinas (IQ/UNICAMP), SP (Brazil). Inst. de Quimica

2010-07-01

The specific interest in the synthesis of semi-IPNs based on PLLA and PVP homopolymers due to the fact these are biodegradable and biocompatible, which allows us to infer applications in the medical field as sutures, implants, matrices for controlled release of drugs etc. The objective was to prepare a multicomponent material amphiphile in the form of semi-interpenetrating polymer networks, based on poly (L-lactide), PLLA, hydrophobic homopolymer, and poly (vinylpyrrolidone), PVP, hydrophilic component. The preparation of semi-IPN combined the polymerization and crosslinking of N-vinylpyrrolidone in the presence of poly (L-lactide). The products were characterized by spectroscopic and thermal methods. (author)

Magmaris: a new generation metallic sirolimus-eluting fully bioresorbable scaffold: present status and future perspectives.

Science.gov (United States)

Rapetto, Claudio; Leoncini, Massimo

2017-08-01

Drug-eluting stents (DES) have reached a high safety and efficacy profile, becoming the best option for percutaneous coronary interventions (PCI) based revascularization. However, despite their optimal performance, a few concerns remain regarding their use, mainly due to permanent caging of the vessels and its consequences, first of all late stent thrombosis (ST). Bioresorbable scaffolds (BRS) aim to overcome these issues. The results achieved in randomized controlled trials (RCT) by the first generation of poly-L-lactic acid (PLLA) based scaffolds were promising at 1 year, but the first long term reports (albeit flawed by non-optimal implantation technique) have been disappointing, showing, for instance, an increased risk of ST and target vessel myocardial infarction (TV-MI). In such a scenario the advent of a newer generation magnesium (Mg) based BRS is welcome, mainly because of its innovative mechanical and chemical features coupled with well proven biocompatibility. Despite being in its infancy, this technology seems to promise a great potential. In our article, we review the Magmaris (Biotronik AG, Bülach, Switzerland) Mg BRS development from animal models to human use, underscore its best qualities and weaknesses, and provide hints of its possible future perspectives.

How the Complex Interplay between Different Blocks Determines the Isothermal Crystallization Kinetics of Triple-Crystalline PEO-b-PCL-b-PLLA Triblock Terpolymers

KAUST Repository

Palacios, Jordana K.

2017-12-05

PEO-b-PCL-b-PLLA triblock terpolymers are fascinating triple-crystalline materials. In this work, the isothermal crystallization kinetics of these terpolymers evaluated by differential scanning calorimetry (DSC) is presented for the first time and compared to analogous PCL-b-PLLA diblock copolymers and to PLLA, PCL, and PEO homopolymers. The results are complemented by in situ SAXS/WAXS synchrotron experiments. One-, two-, and three-step crystallization protocols were employed to study the crystallization kinetics of the blocks. At PLLA block crystallization temperatures, both PCL and PEO molten chains caused a strong plasticizing effect on the PLLA block crystallization, and the overall crystallization rate of the PLLA block in the terpolymers was higher than that in the PLLA-b-PCL diblock copolymers. In the case of the PCL block, the crystallization was followed after PLLA was fully crystallized (two-step crystallization). A nucleating effect induced by the previously formed PLLA crystals was observed. However, an antiplasticizing effect on PCL crystallization was detected if the sample is quenched directly from the melt to the PCL crystallization temperature (one-step crystallization). Finally, the crystallization of the PEO block was followed after PLLA and PCL had fully crystallized (three-step crystallization). The PEO crystallization rate highly decreased due to the confinement imposed by the previously formed PLLA and PCL crystals. Complex competitive effects such as plasticization, nucleation, antiplasticization, and confinement occurred during the isothermal crystallization of tricrystalline PEO-b-PCL-b-PLLA triblock terpolymers.

How the Complex Interplay between Different Blocks Determines the Isothermal Crystallization Kinetics of Triple-Crystalline PEO-b-PCL-b-PLLA Triblock Terpolymers

KAUST Repository

Palacios, Jordana K.; Zhao, Junpeng; Hadjichristidis, Nikolaos; Mü ller, Alejandro J.

2017-01-01

PEO-b-PCL-b-PLLA triblock terpolymers are fascinating triple-crystalline materials. In this work, the isothermal crystallization kinetics of these terpolymers evaluated by differential scanning calorimetry (DSC) is presented for the first time and compared to analogous PCL-b-PLLA diblock copolymers and to PLLA, PCL, and PEO homopolymers. The results are complemented by in situ SAXS/WAXS synchrotron experiments. One-, two-, and three-step crystallization protocols were employed to study the crystallization kinetics of the blocks. At PLLA block crystallization temperatures, both PCL and PEO molten chains caused a strong plasticizing effect on the PLLA block crystallization, and the overall crystallization rate of the PLLA block in the terpolymers was higher than that in the PLLA-b-PCL diblock copolymers. In the case of the PCL block, the crystallization was followed after PLLA was fully crystallized (two-step crystallization). A nucleating effect induced by the previously formed PLLA crystals was observed. However, an antiplasticizing effect on PCL crystallization was detected if the sample is quenched directly from the melt to the PCL crystallization temperature (one-step crystallization). Finally, the crystallization of the PEO block was followed after PLLA and PCL had fully crystallized (three-step crystallization). The PEO crystallization rate highly decreased due to the confinement imposed by the previously formed PLLA and PCL crystals. Complex competitive effects such as plasticization, nucleation, antiplasticization, and confinement occurred during the isothermal crystallization of tricrystalline PEO-b-PCL-b-PLLA triblock terpolymers.

Mechanical properties of electrospun bilayer fibrous membranes as potential scaffolds for tissue engineering.

Science.gov (United States)

Pu, Juan; Komvopoulos, Kyriakos

2014-06-01

Bilayer fibrous membranes of poly(l-lactic acid) (PLLA) were fabricated by electrospinning, using a parallel-disk mandrel configuration that resulted in the sequential deposition of a layer with fibers aligned across the two parallel disks and a layer with randomly oriented fibers, both layers deposited in a single process step. Membrane structure and fiber alignment were characterized by scanning electron microscopy and two-dimensional fast Fourier transform. Because of the intricacies of the generated electric field, bilayer membranes exhibited higher porosity than single-layer membranes consisting of randomly oriented fibers fabricated with a solid-drum collector. However, despite their higher porosity, bilayer membranes demonstrated generally higher elastic modulus, yield strength and toughness than single-layer membranes with random fibers. Bilayer membrane deformation at relatively high strain rates comprised multiple abrupt microfracture events characterized by discontinuous fiber breakage. Bilayer membrane elongation yielded excessive necking of the layer with random fibers and remarkable fiber stretching (on the order of 400%) in the layer with fibers aligned in the stress direction. In addition, fibers in both layers exhibited multiple localized necking, attributed to the nonuniform distribution of crystalline phases in the fibrillar structure. The high membrane porosity, good mechanical properties, and good biocompatibility and biodegradability of PLLA (demonstrated in previous studies) make the present bilayer membranes good scaffold candidates for a wide range of tissue engineering applications. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

microRNA regulatory mechanism by which PLLA aligned nanofibers influence PC12 cell differentiation

Science.gov (United States)

Yu, Yadong; Lü, Xiaoying; Ding, Fei

2015-08-01

Objective. Aligned nanofibers (AFs) are regarded as promising biomaterials in nerve tissue engineering. However, a full understanding of the biocompatibility of AFs at the molecular level is still challenging. Therefore, the present study focused on identifying the microRNA (miRNA)-mediated regulatory mechanism by which poly-L-lactic acid (PLLA) AFs influence PC12 cell differentiation. Approach. Firstly, the effects of PLLA random nanofibers (RFs)/AFs and PLLA films (control) on the biological responses of PC12 cells that are associated with neuronal differentiation were examined. Then, SOLiD sequencing and cDNA microarray were employed to profile the expressions of miRNAs and mRNAs. The target genes of the misregulated miRNAs were predicted and compared with the mRNA profile data. Functions of the matched target genes (the intersection between the predicted target genes and the experimentally-determined, misregulated genes) were analyzed. Main results. The results revealed that neurites spread in various directions in control and RF groups. In the AF group, most neurites extended in parallel with each other. The glucose consumption and lactic acid production in the RF and AF groups were higher than those in the control group. Compared with the control group, 42 and 94 miRNAs were significantly dysregulated in the RF and AF groups, respectively. By comparing the predicted target genes with the mRNA profile data, five and 87 matched target genes were found in the RF and AF groups, respectively. Three of the matched target genes in the AF group were found to be associated with neuronal differentiation, whereas none had this association in the RF group. The PLLA AFs induced the dysregulation of miRNAs that regulate many biological functions, including axonal guidance, lipid metabolism and long-term potentiation. In particular, two miRNA-matched target gene-biological function modules associated with neuronal differentiation were identified as follows: (1) miR-23b, mi

Collagen-chitosan scaffold - Lauric acid plasticizer for skin tissue engineering on burn cases

Science.gov (United States)

Widiyanti, Prihartini; Setyadi, Ewing Dian; Rudyardjo, Djony Izak

2017-02-01

The prevalence of burns in the world is more than 800 cases per one million people each year and this is the second highest cause of death due to trauma after traffic accident. Many studies are turning to skin substitute methods of tissue engineering. The purpose of this study is to determine the composition of the collagen, chitosan, and lauric acid scaffold, as well as knowing the results of the characterization of the scaffold. The synthesis of chitosan collagen lauric acid scaffold as a skin tissue was engineered using freeze dried method. Results from making of collagen chitosan lauric acid scaffold was characterized physically, biologically and mechanically by SEM, cytotoxicity, biodegradation, and tensile strength. From the morphology test, the result obtained is that pore diameter size ranges from 94.11 to 140.1 µm for samples A,B,C,D, which are in the range of normal pore size 63-150 µm, while sample E has value below the standard which is about 37.87 to 47.36 µm. From cytotoxicity assay, the result obtained is the percentage value of living cells between 20.11 to 21.51%. This value is below 50% the standard value of living cells. Incompatibility is made possible because of human error mainly the replication of washing process over the standard. Degradation testing obtained values of 19.44% - 40% by weight which are degraded during the 7 days of observation. Tensile test results obtained a range of values of 0.192 - 3.53 MPa. Only sample A (3.53 MPa) and B (1.935 MPa) meet the standard values of skin tissue scaffold that is 1-24 MPa. Based on the results of the characteristics of this study, composite chitosan collagen scaffold with lauric acid plasticizer has a potential candidate for skin tissue engineering for skin burns cases.

Processing large-diameter poly(L-lactic acid) microfiber mesh/mesenchymal stromal cell constructs via resin embedding: an efficient histologic method

International Nuclear Information System (INIS)

D’Alessandro, Delfo; Danti, Serena; Pertici, Gianni; Moscato, Stefania; Metelli, Maria Rita; Petrini, Mario; Danti, Sabrina; Berrettini, Stefano; Nesti, Claudia

2014-01-01

In this study, we performed a complete histologic analysis of constructs based on large diameter ( > 100 μm) poly-L-lactic acid (PLLA) microfibers obtained via dry-wet spinning and rat Mesenchymal Stromal Cells (rMSCs) differentiated towards the osteogenic lineage, using acrylic resin embedding. In many synthetic polymer-based microfiber meshes, ex post processability of fiber/cell constructs for histologic analysis may face deterring difficulties, leading to an incomplete investigation of the potential of these scaffolds. Indeed, while polymeric nanofiber (fiber diameter = tens of nanometers)/cell constructs can usually be embedded in common histologic media and easily sectioned, preserving the material structure and the antigenic reactivity, histologic analysis of large polymeric microfiber/cell constructs in the literature is really scant. This affects microfiber scaffolds based on FDA-approved and widely used polymers such as PLLA and its copolymers. Indeed, for such constructs, especially those with fiber diameter and fiber interspace much larger than cell size, standard histologic processing is usually inefficient due to inhomogeneous hardness and lack of cohesion between the synthetic and the biological phases under sectioning. In this study, the microfiber/MSC constructs were embedded in acrylic resin and the staining/reaction procedures were calibrated to demonstrate the possibility of successfully employing histologic methods in tissue engineering studies even in such difficult cases. We histologically investigated the main osteogenic markers and extracellular matrix molecules, such as alkaline phosphatase, osteopontin, osteocalcin, TGF-β1, Runx2, Collagen type I and the presence of amorphous, fibrillar and mineralized matrix. Biochemical tests were employed to confirm our findings. This protocol permitted efficient sectioning of the treated constructs and good penetration of the histologic reagents, thus allowing distribution and expression of

Lysine-doped polypyrrole/spider silk protein/poly(l-lactic) acid containing nerve growth factor composite fibers for neural application.

Science.gov (United States)

Zhang, Hong; Wang, Kefeng; Xing, Yiming; Yu, Qiaozhen

2015-11-01

Lysine-doped polypyrrole (PPy)/regenerated spider silk protein (RSSP)/poly(l-lactic) acid (PLLA)/nerve growth factor (NGF) (L-PRPN) composite scaffold was fabricated by co-axial electrospraying and electrospinning. This L-PRPN composite scaffold had a structure of microfibers with a core-shell structure as the stems and nanofibers as branches. Assessment in vitro demonstrated that the L-PRPN composite micro/nano-fibrous scaffold could maintain integrated structure for at least 4months and the pH value of PBS at about 7.28. It had good biocompatibility and cell adhesion and relatively stable conductivity. PC 12 cells cultured on this scaffold, anisotropic cell-neurite-cell-neurite or neurite-neurite sheets were formed after being cultured for 6days. Evaluations in vivo also showed that L-PRPN composite fibrous conduit was effective at bridging 2.0cm sciatic nerve gap in adult rat within 10months. This conduit and electrical stimulation (ES) through it promoted Schwann cell migration and axonal regrowth. Copyright © 2015 Elsevier B.V. All rights reserved.

The Melting Behavior and Thermal Stability of Green Poly(L-lactic acid) with N, N, N, N'-Tetra(benzoyl) Ethylene Diamine Tetraacetic Acid Dihydrazide

International Nuclear Information System (INIS)

Cai, Y.; Qiang Xu, Q.; Ren, L.; Zhao, L.

2015-01-01

The thermal properties of green poly(L-lactic acid) (PLLA) with N, N, N, N'-tetra(benzoyl) ethylene diamine tetraacetic acid dihydrazide (NA) at different conditions were investigated. The melting behavior of PLLA/NA sample after isothermal crystallization at 100 degree C showed that the low-temperature melting peak shifted to high temperature with increasing of crystallization time. However, the high-temperature melting peak did not show any change. Meantime, the melting enthalpy of cold crystallization was higher than that of hot crystallization, and the difference between cold crystallization and hot crystallization increased from 0.31 J/g to 0.89 J/g with increasing of crystallization time. Heating or cooling rate affected the melting behavior of PLLA, the low-temperature and high-temperature melting peak shifted to low temperature with increasing of rate, and the ratio of melting peak area between low-temperature melting peak and high-temperature melting peak decreased. Thermal stability of PLLA/NA indicated that PLLA/NA only exhibited one decomposition stage as decomposition of PLLA. (author)

Does magnesium compromise the high temperature process ability of novel biodegradable and bioresorbables PLLA/Mg composites?

International Nuclear Information System (INIS)

Cifuentes, S. C.; Benavemente, R.; Gonzalez-Carrasco, J. L.

2014-01-01

This paper addresses the influence of magnesium on melting behaviour and thermal stability of novel bioresorbable PLLA/Mg composites as a way to investigate their processability by conventional techniques, which likely will require a melt process at high temperature to mould the material by using a compression, extrusion or injection stage. For this purpose, and to avoid any high temperature step before analysis, films of PLLA loaded with magnesium particles of different sizes and volume fraction were prepared by solvent casting. DSC, modulated DSC and thermogravimetry analysis demonstrate that although thermal stability of PLLA is reduced, the temperature window for processing the PLLA/Mg composites by conventional thermoplastic routes is wide enough. Moreover, magnesium particles do not alter the crystallization behaviour of the polymer from the melt, which allows further annealing treatments to optimize the crystallinity in terms of the required combination of mechanical properties and degradation rate. (Author)

Does magnesium compromise the high temperature process ability of novel biodegradable and bioresorbables PLLA/Mg composites?

Energy Technology Data Exchange (ETDEWEB)

Cifuentes, S. C.; Benavemente, R.; Gonzalez-Carrasco, J. L.

2014-10-01

This paper addresses the influence of magnesium on melting behaviour and thermal stability of novel bioresorbable PLLA/Mg composites as a way to investigate their processability by conventional techniques, which likely will require a melt process at high temperature to mould the material by using a compression, extrusion or injection stage. For this purpose, and to avoid any high temperature step before analysis, films of PLLA loaded with magnesium particles of different sizes and volume fraction were prepared by solvent casting. DSC, modulated DSC and thermogravimetry analysis demonstrate that although thermal stability of PLLA is reduced, the temperature window for processing the PLLA/Mg composites by conventional thermoplastic routes is wide enough. Moreover, magnesium particles do not alter the crystallization behaviour of the polymer from the melt, which allows further annealing treatments to optimize the crystallinity in terms of the required combination of mechanical properties and degradation rate. (Author)

Novel bioactive polyester scaffolds prepared from unsaturated resins based on isosorbide and succinic acid

Energy Technology Data Exchange (ETDEWEB)

Śmiga-Matuszowicz, Monika, E-mail: monika.smiga-matuszowicz@polsl.pl [Silesian University of Technology, Department of Physical Chemistry and Technology of Polymers, M. Strzody Street 9, 44-100 Gliwice (Poland); Janicki, Bartosz; Jaszcz, Katarzyna; Łukaszczyk, Jan [Silesian University of Technology, Department of Physical Chemistry and Technology of Polymers, M. Strzody Street 9, 44-100 Gliwice (Poland); Kaczmarek, Marcin [Silesian University of Technology, Department of Biomaterials and Medical Devices Engineering, de Gaulle' a Street 66, 41-800 Zabrze (Poland); Lesiak, Marta; Sieroń, Aleksander L. [Medical University of Silesia, Department of General and Molecular Biology and Genetics, Medyków Street 18, 40-752 Katowice (Poland); Simka, Wojciech [Silesian University of Technology, Department of Chemistry, Inorganic Technology and Fuels, B. Krzywoustego Street 6, 44-100 Gliwice (Poland); Mierzwiński, Maciej; Kusz, Damian [Medical University of Silesia, Department of Orthopedics and Traumatology, Ziołowa Street 45, 40-635 Katowice (Poland)

2014-12-01

In this study new biodegradable materials obtained by crosslinking poly(3-allyloxy-1,2-propylene succinate) (PSAGE) with oligo(isosorbide maleate) (OMIS) and small amount of methyl methacrylate were investigated. The porous scaffolds were obtained in the presence of a foaming system consisted of calcium carbonate/carboxylic acid mixture, creating in situ porous structure during crosslinking of liquid formulations. The maximum crosslinking temperature and setting time, the cured porous materials morphology as well as the effect of their porosity on mechanical properties and hydrolytic degradation process were evaluated. It was found that the kind of carboxylic acid used in the foaming system influenced compressive strength and compressive modulus of porous scaffolds. The MTS cytotoxicity assay was carried out for OMIS using hFOB1.19 cell line. OMIS resin was found to be non-toxic in wide range of concentrations. On the ground of scanning electron microscopy (SEM) observations and energy X-ray dispersive analysis (EDX) it was found that hydroxyapatite (HA) formation at the scaffolds surfaces within short period of soaking in phosphate buffer solution occurs. After 3 h immersion a compact layer of HA was observed at the surface of the samples. The obtained results suggest potential applicability of resulted new porous crosslinked polymeric materials as temporary bone void fillers. - Highlights: • Isosorbide-based resin was used as a component of biodegradable scaffolds. • CAC/carboxylic acid system was proven as facile method to obtain porous scaffolds. • Porous scaffolds displayed the formation of hydroxyapatite at their surfaces.

Fabrication of chitosan/gallic acid 3D microporous scaffold for tissue engineering applications.

Science.gov (United States)

Thangavel, Ponrasu; Ramachandran, Balaji; Muthuvijayan, Vignesh

2016-05-01

This study explores the potential of gallic acid incorporated chitosan (CS/GA) 3D scaffolds for tissue engineering applications. Scaffolds were prepared by freezing and lyophilization technique and characterized. FTIR spectra confirmed the presence of GA in chitosan (CS) gel. DSC and TGA analysis revealed that the structure of chitosan was not altered due to the incorporation of GA, but thermal stability was significantly increased compared to the CS scaffold. SEM micrographs showed smooth, homogeneous, and microporous architecture of the scaffolds with good interconnectivity. CS/GA scaffolds exhibited approximately 90% porosity on average, increased swelling (600-900%) and controlled biodegradation (15-40%) in PBS (pH 7.4 at 37°C) with 1 mg/mL of lysozyme. CS/GA scaffolds showed 2-4 fold decrease in CFUs (p < 0.05) for both gram positive and gram negative bacteria compared to the CS scaffold. Cytotoxicity of these scaffolds was evaluated using NIH 3T3 L1 fibroblast cells. CS/GA 0.25% scaffold showed similar viability with CS scaffold at 24 and 48 h. CS/GA scaffolds (0.5-1.0%) showed 60-75% viability at 24 h and 90% at 48 h. SEM images showed that an increased cell attachment was observed for CS/GA scaffolds compared to CS scaffolds. These findings authenticate that CS/GA scaffolds were cytocompatible and would be useful for tissue engineering applications. © 2015 Wiley Periodicals, Inc.

A Comparison of Degradable Synthetic Polymer Fibers for Anterior Cruciate Ligament Reconstruction

OpenAIRE

Tovar, Nick; Bourke, Sharon; Jaffe, Michael; Murthy, N. Sanjeeva; Kohn, Joachim; Gatt, Charles; Dunn, Michael G.

2010-01-01

We compared mechanical properties, degradation rates, and cellular compatibilities of two synthetic polymer fibers potentially useful as ACL reconstruction scaffolds: poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate)(12,10), p(DTD DD) and poly(L-lactic acid), PLLA. The yield stress of ethylene oxide (ETO) sterilized wet fibers was 150 ± 22 MPa and 87 ± 12 MPa for p(DTD DD) and PLLA, respectively, with moduli of 1.7 ± 0.1 MPa and 4.4 ± 0.43 MPa. Strength and molecular weight retention were...

Does magnesium compromise the high temperature processability of novel biodegradable and bioresorbables PLLA/Mg composites?

Directory of Open Access Journals (Sweden)

Cifuentes, Sandra C.

2014-06-01

Full Text Available This paper addresses the influence of magnesium on melting behaviour and thermal stability of novel bioresorbable PLLA/Mg composites as a way to investigate their processability by conventional techniques, which likely will require a melt process at high temperature to mould the material by using a compression, extrusion or injection stage. For this purpose, and to avoid any high temperature step before analysis, films of PLLA loaded with magnesium particles of different sizes and volume fraction were prepared by solvent casting. DSC, modulated DSC and thermogravimetry analysis demonstrate that although thermal stability of PLLA is reduced, the temperature window for processing the PLLA/Mg composites by conventional thermoplastic routes is wide enough. Moreover, magnesium particles do not alter the crystallization behaviour of the polymer from the melt, which allows further annealing treatments to optimize the crystallinity in terms of the required combination of mechanical properties and degradation rate.Este trabajo aborda la influencia de magnesio en el comportamiento a fusión y en la estabilidad térmica de nuevos compuestos de PLLA / Mg biorreabsorbibles como una forma de investigar su procesabilidad mediante técnicas convencionales, lo que probablemente requerirá una etapa en estado fundido a alta temperatura para moldear el material mediante el uso de una etapa de compresión, extrusión o inyección. Para este fin, los materiales de PLLA cargados con partículas de magnesio, de diferentes tamaños y fracción de volumen, se prepararon por la técnica de disolución y colada, evitando así el procesado a alta temperatura antes del análisis. El análisis mediante DSC, DSC modulada y termogravimetría demuestra que, aunque la estabilidad térmica de PLLA se reduce, el intervalo de temperatura para su procesado por rutas convencionales es suficientemente amplio. Además, las partículas de magnesio no alteran la cristalización del pol

Synthesis and characterization of semi-IPNs based on PVP and PLLA

International Nuclear Information System (INIS)

Camilo, A.P.R.; Mano, V.; Felisberti, M.I.

2010-01-01

The specific interest in the synthesis of semi-IPNs based on PLLA and PVP homopolymers due to the fact these are biodegradable and biocompatible, which allows us to infer applications in the medical field as sutures, implants, matrices for controlled release of drugs etc. The objective was to prepare a multicomponent material amphiphile in the form of semi-interpenetrating polymer networks, based on poly (L-lactide), PLLA, hydrophobic homopolymer, and poly (vinylpyrrolidone), PVP, hydrophilic component. The preparation of semi-IPN combined the polymerization and crosslinking of N-vinylpyrrolidone in the presence of poly (L-lactide). The products were characterized by spectroscopic and thermal methods. (author)

A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair.

Science.gov (United States)

Chen, Xi; Li, Yan; Gu, Ning

2010-08-01

A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair.

A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair

International Nuclear Information System (INIS)

Chen Xi; Li Yan; Gu Ning

2010-01-01

A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair.

Bladder tissue engineering using biocompatible nanofibrous electrospun constructs: feasibility and safety investigation.

Science.gov (United States)

Shakhssalim, Nasser; Dehghan, Mohammad Mehdi; Moghadasali, Reza; Soltani, Mohammad Hossein; Shabani, Iman; Soleimani, Masoud

2012-01-01

To investigate the feasibility and safety of using biocompatible, nanofibrous electrospun polycaprolactone (PCL) and combination of polylactic acid (PLLA) and PCL mats in a canine model. Plasma-treated electrospun unseeded mats were implanted in three dogs. The first dog was sacrificed after 3 months and the second and third ones after 4 months, and then, the graft was examined macroscopically with subsequent morphological and histochemical evaluation. Both films showed high levels of cell infiltration and tissue formation, but body response to PLLA/PCL mat in comparison to PCL mat was very low. All three implantation models showed the same light microscopic morphology, immunohistochemistry, and scanning electron microscopy results; nevertheless, only the PCL/PLLA model showed favorable clinical results. Based on these data, nanofibrous PLLA/PCL scaffolding could be a suitable material for the bladder tissue engineering; however, it deserves further investigations.

ZnO-PLLA Nanofiber Nanocomposite for Continuous Flow Mode Purification of Water from Cr(VI

Directory of Open Access Journals (Sweden)

T. Burks

2015-01-01

Full Text Available Nanomaterials of ZnO-PLLA nanofibers have been used for the adsorption of Cr(VI as a prime step for the purification of water. The fabrication and application of the flexible ZnO-PLLA nanofiber nanocomposite as functional materials in this well-developed architecture have been achieved by growing ZnO nanorod arrays by chemical bath deposition on synthesized electrospun poly-L-lactide nanofibers. The nanocomposite material has been tested for the removal and regeneration of Cr(IV in aqueous solution under a “continuous flow mode” by studying the effects of pH, contact time, and desorption steps. The adsorption of Cr(VI species in solution was greatly dependent upon pH. SEM micrographs confirmed the successful fabrication of the ZnO-PLLA nanofiber nanocomposite. The adsorption and desorption of Cr(VI species were more likely due to the electrostatic interaction between ZnO and Cr(VI ions as a function of pH. The adsorption and desorption experiments utilizing the ZnO-PLLA nanofiber nanocomposite have appeared to be an effective nanocomposite in the removal and regeneration of Cr(VI species.

Effects of poly(L-lactide-ε-caprolactone) and magnesium hydroxide additives on physico-mechanical properties and degradation of poly(L-lactic acid).

Science.gov (United States)

Kang, Eun Young; Lih, Eugene; Kim, Ik Hwan; Joung, Yoon Ki; Han, Dong Keun

2016-01-01

Biodegradable poly(L-lactic acid) (PLLA) is one of the most widely used polymer in biomedical devices, but it still has limitations such as inherent brittleness and acidic degradation products. In this work, PLLA blends with poly(L-lactide-ε-caprolactone) (PLCL) and Mg(OH)2 were prepared by the thermal processing to improve their physico-mechanical and thermal properties. In addition, the neutralizing effect of Mg(OH)2 was evaluated by degradation study. The elongation of PLLA remarkably increased from 3 to 164.4 % and the glass transition temperature (Tg) of PLLA was slightly reduced from 61 to 52 °C by adding PLCL additive. Mg(OH)2 in polymeric matrix not only improved the molecular weight reduction and mechanical strength of PLLA, but also neutralized the acidic byproducts generated during polyester degradation. Therefore, the results demonstrated that the presence of PLCL and Mg(OH)2 additives in PLLA matrix could prevent the thermal decomposition and control degradation behavior of polyester.

Minimally invasive injectable short nanofibers of poly(glycerol sebacate) for cardiac tissue engineering

International Nuclear Information System (INIS)

Ravichandran, Rajeswari; Venugopal, Jayarama Reddy; Sundarrajan, Subramanian; Mukherjee, Shayanti; Sridhar, Radhakrishnan; Ramakrishna, Seeram

2012-01-01

Myocardial tissue lacks the ability to appreciably regenerate itself following myocardial infarction (MI) which ultimately results in heart failure. Current therapies can only retard the progression of disease and hence tissue engineering strategies are required to facilitate the engineering of a suitable biomaterial to repair MI. The aim of this study was to investigate the in vitro properties of an injectable biomaterial for the regeneration of infarcted myocardium. Fabrication of core/shell fibers was by co-axial electrospinning, with poly(glycerol sebacate) (PGS) as core material and poly-l-lactic acid (PLLA) as shell material. The PLLA was removed by treatment of the PGS/PLLA core/shell fibers with DCM:hexane (2:1) to obtain PGS short fibers. These PGS short fibers offer the advantage of providing a minimally invasive injectable technique for the regeneration of infarcted myocardium. The scaffolds were characterized by SEM, FTIR and contact angle and cell–scaffold interactions using cardiomyocytes. The results showed that the cardiac marker proteins actinin, troponin, myosin heavy chain and connexin 43 were expressed more on short PGS fibers compared to PLLA nanofibers. We hypothesized that the injection of cells along with short PGS fibers would increase cell transplant retention and survival within the infarct, compared to the standard cell injection system. (paper)

Peracetic Acid: A Practical Agent for Sterilizing Heat-Labile Polymeric Tissue-Engineering Scaffolds

Science.gov (United States)

Yoganarasimha, Suyog; Trahan, William R.; Best, Al M.; Bowlin, Gary L.; Kitten, Todd O.; Moon, Peter C.

2014-01-01

Advanced biomaterials and sophisticated processing technologies aim at fabricating tissue-engineering scaffolds that can predictably interact within a biological environment at the cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed before clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam, and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone, a low melting polymer, and employing spores of Bacillus atrophaeus as biological indicators, we compared ethylene oxide, autoclaving and 80% ethanol to a known chemical sterilant, peracetic acid (PAA), for their ability to sterilize as well as their effects on scaffold properties. PAA diluted in 20% ethanol to 1000 ppm or above sterilized electrospun scaffolds in 15 min at room temperature while maintaining nano-architecture and mechanical properties. Scaffolds treated with PAA at 5000 ppm were rendered hydrophilic, with contact angles reduced to 0°. Therefore, PAA can provide economical, rapid, and effective sterilization of heat-sensitive polymeric electrospun scaffolds that are used in tissue engineering. PMID:24341350

Thermal Stability and Surface Wettability Studies of Polylactic Acid/Halloysite Nanotube Nanocomposite Scaffold for Tissue Engineering Studies

Science.gov (United States)

Nizar, M. Mohd; Hamzah, M. S. A.; Razak, S. I. Abd; Mat Nayan, N. H.

2018-03-01

This paper reports the preliminary study about the incorporation of halloysite nanotubes (HNT) into polylactic acid (PLA) scaffold to improve the thermal resistance and surface wettability properties. The fabrication of the porous scaffold requires a simple yet effective technique with low-cost materials within freeze extraction method. The thermal stability of PLA/HNT scaffold compared to neat PLA scaffold achieved with increased content of HNT by 5 wt%. Moreover, the surface wettability of the scaffold also shows a positive impact with high content of HNT by 5 wt%. This new nanocomposite scaffold may have high potential as a suitable template for tissue regeneration.

Thermo-mechanical properties of poly ε-caprolactone/poly L-lactic acid blends: addition of nalidixic acid and polyethylene glycol additives.

Science.gov (United States)

Douglas, P; Albadarin, Ahmad B; Al-Muhtaseb, Ala'a H; Mangwandi, Chirangano; Walker, G M

2015-05-01

The search for ideal biomaterials is still on-going for tissue regeneration. In this study, blends of poly ε-caprolactone (PCL) with poly l-lactic acid (PLLA), nalidixic acid (NA) and polyethylene glycol (PEG) were prepared. Mechanical and thermal properties of the blends were investigated by tensile and flexural analysis, DSC, TGA, WXRD, MFI, BET, SEM and hot stage optical microscopy. Results showed that the loading of PLLA caused a significant decrease in tensile strength and almost total eradication of the elongation at break of PCL matrix, especially after PEG and NA addition. Increased stiffness was also noted with additional NA, PEG and PLLA, resulting in an increase in the flexural modulus of the blends. Isothermal degradation indicated that bulk PCL, PLLA and the blends were thermally stable at 200°C for the duration of 2h making extrusion of the blends at this temperature viable. Morphological study showed that increasing the PLLA content and addition of the very low viscosity PEG and powder NA decreased the Melt Flow Indexer and increased the viscosity. At the higher temperature, the PLLA begins to soften and eventually melts allowing for increased flow and, coupling this with, the natural increase in MFI caused by temperature is enhanced further. The PEG and NA addition increased dramatically the pore volume which is important for cell growth and flow transport of nutrients and metabolic waste. Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiation-induced crosslinking and post-processing of poly(L-lactic acid) composite

International Nuclear Information System (INIS)

Nagasawa, Naotsugu; Kasai, Noboru; Yagi, Toshiaki; Yoshii, Fumio; Tamada, Masao

2011-01-01

Poly(L-lactic acid), PLLA, was irradiated using electron beams (EBs) in the presence of triallyl isocyanurate (TAIC) at 5% concentration as crosslinking agent. The crosslinked PLLA obtained has heat resistance, as demonstrated by retention of its original shape at glass transition temperature or even higher than 200 o C. As an application of this fact, crosslinked PLLA is applied in spectacle lens to prevent shape deformation of eyeglass frames in displaying and transporting. However, in this application to lens, it is not enough to improve the thermal deformation of PLLA under stress at 70 o C. Radiation-induced crosslinking of a PLLA/silicon dioxide (SiO 2 ) composite with TAIC and post-processing of the crosslinked PLLA composite by heating were further investigated from the viewpoint of thermal deformation. The PLLA materials have several advantages such as high heat resistance and transparency. It is therefore proved that the combination of radiation-induced crosslinking, composition of SiO 2 and post-heating is beneficial for expanding the applications of PLLA.

Radiation-induced crosslinking and post-processing of poly(L-lactic acid) composite

Energy Technology Data Exchange (ETDEWEB)

Nagasawa, Naotsugu, E-mail: nagasawa.naotsugu@jaea.go.j [Japan Atomic Energy Agency (JAEA), Quantum Beam Science Directorate, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan); Kasai, Noboru; Yagi, Toshiaki; Yoshii, Fumio; Tamada, Masao [Japan Atomic Energy Agency (JAEA), Quantum Beam Science Directorate, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

2011-02-15

Poly(L-lactic acid), PLLA, was irradiated using electron beams (EBs) in the presence of triallyl isocyanurate (TAIC) at 5% concentration as crosslinking agent. The crosslinked PLLA obtained has heat resistance, as demonstrated by retention of its original shape at glass transition temperature or even higher than 200 {sup o}C. As an application of this fact, crosslinked PLLA is applied in spectacle lens to prevent shape deformation of eyeglass frames in displaying and transporting. However, in this application to lens, it is not enough to improve the thermal deformation of PLLA under stress at 70 {sup o}C. Radiation-induced crosslinking of a PLLA/silicon dioxide (SiO{sub 2}) composite with TAIC and post-processing of the crosslinked PLLA composite by heating were further investigated from the viewpoint of thermal deformation. The PLLA materials have several advantages such as high heat resistance and transparency. It is therefore proved that the combination of radiation-induced crosslinking, composition of SiO{sub 2} and post-heating is beneficial for expanding the applications of PLLA.

Evaluation of mechanical and morphologic features of PLLA membranes as supports for perfusion cells culture systems

Energy Technology Data Exchange (ETDEWEB)

Montesanto, S., E-mail: salvatore.montesanto1985@gmail.com [Department of Civil, Environmental, Aerospace, Materials Engineering (DICAM), University of Palermo, Viale delle Scienze Ed. 8, 90128 Palermo (Italy); Brucato, V. [Department of Civil, Environmental, Aerospace, Materials Engineering (DICAM), University of Palermo, Viale delle Scienze Ed. 8, 90128 Palermo (Italy); La Carrubba, V. [Department of Civil, Environmental, Aerospace, Materials Engineering (DICAM), University of Palermo, Viale delle Scienze Ed. 8, 90128 Palermo (Italy); Euro-Mediterranean Institute of Science and Technology (IEMEST), Via Michele Miraglia, 20, 90128 Palermo (Italy)

2016-12-01

Porous biodegradable PLLA membranes, which can be used as supports for perfusion cell culture systems were designed, developed and characterized. PLLA membranes were prepared via diffusion induced phase separation (DIPS). A glass slab was coated with a binary PLLA–dioxane solution (8 wt.% PLLA) via dip coating, then pool immersed in two subsequent coagulation baths, and finally dried in a humidity-controlled environment. Surface and mechanical properties were evaluated by measuring pore size, porosity via scanning electron microscopy, storage modulus, loss modulus and loss angle by using a dynamic mechanical analysis (DMA). Cell adhesion assays on different membrane surfaces were also performed by using a standard count method. Results provide new insights into the foaming methods for producing polymeric membranes and supply indications on how to optimise the fabrication parameters to design membranes for tissue cultures and regeneration. - Highlights: • Design, development and characterization of porous biodegradable PLLA membranes via DIPS technology. • Easy-to-tune processing parameters in terms of surface and volumetric properties and cell adhesion. • Evaluation of the impact of the interconnection degree on membrane's mechanical properties. • Evaluation of cell adhesion on different membrane surface textures.

Evaluation of mechanical and morphologic features of PLLA membranes as supports for perfusion cells culture systems

International Nuclear Information System (INIS)

Montesanto, S.; Brucato, V.; La Carrubba, V.

2016-01-01

Porous biodegradable PLLA membranes, which can be used as supports for perfusion cell culture systems were designed, developed and characterized. PLLA membranes were prepared via diffusion induced phase separation (DIPS). A glass slab was coated with a binary PLLA–dioxane solution (8 wt.% PLLA) via dip coating, then pool immersed in two subsequent coagulation baths, and finally dried in a humidity-controlled environment. Surface and mechanical properties were evaluated by measuring pore size, porosity via scanning electron microscopy, storage modulus, loss modulus and loss angle by using a dynamic mechanical analysis (DMA). Cell adhesion assays on different membrane surfaces were also performed by using a standard count method. Results provide new insights into the foaming methods for producing polymeric membranes and supply indications on how to optimise the fabrication parameters to design membranes for tissue cultures and regeneration. - Highlights: • Design, development and characterization of porous biodegradable PLLA membranes via DIPS technology. • Easy-to-tune processing parameters in terms of surface and volumetric properties and cell adhesion. • Evaluation of the impact of the interconnection degree on membrane's mechanical properties. • Evaluation of cell adhesion on different membrane surface textures.

Temperature-responsive PLLA/PNIPAM nanofibers for switchable release

Energy Technology Data Exchange (ETDEWEB)

Elashnikov, Roman; Slepička, Petr [Department of Solid State Engineering, University of Chemistry and Technology, Prague 166 28 (Czech Republic); Rimpelova, Silvie; Ulbrich, Pavel [Department of Biochemistry and Microbiology, University of Chemistry and Technology, 16628 Prague (Czech Republic); Švorčík, Vaclav [Department of Solid State Engineering, University of Chemistry and Technology, Prague 166 28 (Czech Republic); Lyutakov, Oleksiy, E-mail: lyutakoo@vscht.cz [Department of Solid State Engineering, University of Chemistry and Technology, Prague 166 28 (Czech Republic)

2017-03-01

Smart antimicrobial materials with on-demand drug release are highly desired for biomedical applications. Herein, we report about temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) nanospheres doped with crystal violet (CV) and incorporated into the poly-L-lactide (PLLA) nanofibers. The nanofibers were prepared by electrospinning, using different initial polymers ratios. The morphology of the nanofibers and polymers distribution in the nanofibers were characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The interaction between PNIPAM and PLLA in the nanofibers was studied by Fourier transform infrared spectroscopy (FTIR) and its effect on the PNIPAM phase transition was also investigated. It was shown that by the changing of the environmental temperature across the lower critical solution temperature (LCST) of PNIPAM, the switchable wettability and controlled CV release can be achieved. The temperature-dependent release kinetics of CV from polymer nanofibers was investigated by ultraviolet-visible spectroscopy (UV–Vis). The temperature-responsive release of antibacterial CV was also tested for triggering of antibacterial activity, which was examined on Staphylococcus epidermidis (S. epidermidis) and Escherichia coli (E. coli). Thus, the proposed material is promising value for controllable drug-release.

Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity

International Nuclear Information System (INIS)

Entekhabi, Elahe; Haghbin Nazarpak, Masoumeh; Moztarzadeh, Fathollah; Sadeghi, Ali

2016-01-01

Given the large differences in nervous tissue and other tissues of the human body and its unique features, such as poor and/or lack of repair, there are many challenges in the repair process of this tissue. Tissue engineering is one of the most effective approaches to repair neural damages. Scaffolds made from electrospun fibers have special potential in cell adhesion, function and cell proliferation. This research attempted to design a high porous nanofibrous scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions for nerve regeneration by applying proper physicochemical and mechanical signals. Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds were measured by FTIR and tensile test. Morphology, swelling behavior, and biodegradability of the scaffolds were evaluated too. Porosity of various layers of scaffolds was measured by image analysis method. To assess the cell–scaffold interaction, SH-SY5Y human neuroblastoma cell line were cultured on the electrospun scaffolds. Taken together, these results suggest that the blended nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet all of the required specifications for neural cells and have potential application in neural tissue engineering. - Highlights: • This paper focuses on design a high porous nanofibrous scaffold. • Hyaluronic acid and polycaprolactone were used as materials to provide ideal conditions for nerve regeneration. • Proper physicochemical and mechanical signals applied for improving cell attachment

Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity

Energy Technology Data Exchange (ETDEWEB)

Entekhabi, Elahe [Department of Biomedical Engineering, Amirkabir University of Technology, P.O. Box: 15875/4413, Tehran 159163/4311 (Iran, Islamic Republic of); Haghbin Nazarpak, Masoumeh, E-mail: mhaghbinn@gmail.com [New Technologies Research Center (NTRC), Amirkabir University of Technology, Tehran 15875-4413 (Iran, Islamic Republic of); Moztarzadeh, Fathollah; Sadeghi, Ali [Department of Biomedical Engineering, Amirkabir University of Technology, P.O. Box: 15875/4413, Tehran 159163/4311 (Iran, Islamic Republic of)

2016-12-01

Given the large differences in nervous tissue and other tissues of the human body and its unique features, such as poor and/or lack of repair, there are many challenges in the repair process of this tissue. Tissue engineering is one of the most effective approaches to repair neural damages. Scaffolds made from electrospun fibers have special potential in cell adhesion, function and cell proliferation. This research attempted to design a high porous nanofibrous scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions for nerve regeneration by applying proper physicochemical and mechanical signals. Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds were measured by FTIR and tensile test. Morphology, swelling behavior, and biodegradability of the scaffolds were evaluated too. Porosity of various layers of scaffolds was measured by image analysis method. To assess the cell–scaffold interaction, SH-SY5Y human neuroblastoma cell line were cultured on the electrospun scaffolds. Taken together, these results suggest that the blended nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet all of the required specifications for neural cells and have potential application in neural tissue engineering. - Highlights: • This paper focuses on design a high porous nanofibrous scaffold. • Hyaluronic acid and polycaprolactone were used as materials to provide ideal conditions for nerve regeneration. • Proper physicochemical and mechanical signals applied for improving cell attachment.

Radiation induced crosslinking of poly(L-lactic acid) for making the polymeric materials having high thermal stability and improved mechanical properties

International Nuclear Information System (INIS)

Tran Minh Quynh; Tran Bang Diep; Nguyen Van Binh; Nguyen Quang Long; Pham Duy Duong; Hoang Phuong Thao; Hoang Dang Sang; Pham Ngoc Lan

2013-01-01

Different poly(L-lactic acid) (PLLA) have been synthesized from L-lactic acid as well as L-lactide by direct polycondensation and ring opening polymerization. Depending on reaction time, the resulting products having viscosity average molecular weight ranging from 5 to 25,000 g.mol -1 . Plasticization effects of some popular plasticizer, especially is polyethylene glycols (PEG) for the synthesized PLLA were determined. The results suggested that PEG 1000 is a good plasticizer with relative high plasticization effect. The crosslinking plasticized materials were prepared form the plasticized PLLA by irradiation with various radiation doses. The crosslinking structures were introduced in different formulation of PLLA/PEG/TAIC, the crosslinking density increased with radiation dose and seemed to be saturated at 50 kGy. The stable crosslinking structure inhibited the mobility for crystallization of PLLA chains, thermal stability of plasticized PLLA crosslinked with TAIC at 50 kGy become higher than that of initial PLLA with very small endothermic peak at its melting temperature. The stress-strain curves of the crosslinking plasticized PLLA showed that the toughness of the materials reduced but still higher than that of initial PLLA, whereas its tensile strength was much improved by radiation crosslinking. The results also revealed that the crosslinking plasticized PLLA can be completely degraded by proteinase K as well as microorganisms existing in compost. (author)

Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano-hydroxyapatite composite microsphere-based scaffolds for bone tissue engineering in rotating bioreactors.

Science.gov (United States)

Lv, Qing; Nair, Lakshmi; Laurencin, Cato T

2009-12-01

Dynamic flow culture bioreactor systems have been shown to enhance in vitro bone tissue formation by facilitating mass transfer and providing mechanical stimulation. Our laboratory has developed a biodegradable poly (lactic acid glycolic acid) (PLAGA) mixed scaffold consisting of lighter-than-water (LTW) and heavier-than-water (HTW) microspheres as potential matrices for engineering tissue using a high aspect ratio vessel (HARV) rotating bioreactor system. We have demonstrated enhanced osteoblast differentiation and mineralization on PLAGA scaffolds in the HARV rotating bioreactor system when compared with static culture. The objective of the present study is to improve the mechanical properties and bioactivity of polymeric scaffolds by designing LTW polymer/ceramic composite scaffolds suitable for dynamic culture using a HARV bioreactor. We employed a microsphere sintering method to fabricate three-dimensional PLAGA/nano-hydroxyapatite (n-HA) mixed scaffolds composed of LTW and HTW composite microspheres. The mechanical properties, pore size and porosity of the composite scaffolds were controlled by varying parameters, such as sintering temperature, sintering time, and PLAGA/n-HA ratio. The PLAGA/n-HA (4:1) scaffold sintered at 90 degrees C for 3 h demonstrated the highest mechanical properties and an appropriate pore structure for bone tissue engineering applications. Furthermore, evaluation human mesenchymal stem cells (HMSCs) response to PLAGA/n-HA scaffolds was performed. HMSCs on PLAGA/n-HA scaffolds demonstrated enhanced proliferation, differentiation, and mineralization when compared with those on PLAGA scaffolds. Therefore, PLAGA/n-HA mixed scaffolds are promising candidates for HARV bioreactor-based bone tissue engineering applications. Copyright 2008 Wiley Periodicals, Inc.

Incorporation of hyaluronic acid into collagen scaffolds for the control of chondrocyte-mediated contraction and chondrogenesis

Energy Technology Data Exchange (ETDEWEB)

Tang Shunqing [Department of Biomedical Engineering, Jinan University, Guangzhou 510632 (China); Spector, Myron [Tissue Engineering, VA Boston Healthcare System, Boston, MA 02130 (United States)

2007-09-15

Hyaluronic acid (HA), a principal matrix molecule in many tissues, is present in high amounts in articular cartilage. HA contributes in unique ways to the physical behavior of the tissue, and has been shown to have beneficial effects on chondrocyte activity. The goal of this study was to incorporate graduated amounts of HA into type I collagen scaffolds for the control of chondrocyte-mediated contraction and chondrogenesis in vitro. The results demonstrated that the amount of contraction of HA/collagen scaffolds by adult canine articular chondrocytes increased with the HA content of the scaffolds. The greatest amount of chondrogenesis after two weeks was found in the scaffolds which had undergone the most contraction. HA can play a useful role in adjusting the mechanical behavior of tissue engineering scaffolds and chondrogenesis in chondrocyte-seeded scaffolds.

Bimodal Porous Scaffolds by Sequential Electro spinning of Poly(glycolic acid) with Sucrose Particles

International Nuclear Information System (INIS)

Wulkersdorfer, B.; Kao, K.K.; Agopian, V.G.; Ahn, A.; Dunn, J.C.; Wu, B.M.; Stelzner, M.; Kao, K.K.; Agopian, K.J.; Dunn, J.C.; Wu, B.M.; Stelzner, M.; Dunn, J.C.; Wu, B.M.

2009-01-01

Electro spinning is a method to produce fine, bio polymer mesh with a three-dimensional architecture that mimics native extra-cellular matrix. Due to the small fiber diameter created in this process, conventional electro spun scaffolds have pore sizes smaller than the diameter of most cells. These scaffolds have limited application in tissue engineering due to poor cell penetration. We developed a hybrid electro spinning/particulate leaching technique to create scaffolds with increased porosity and improved cellular ingrowth. Poly(glycolic acid) (PGA) and a sucrose-ethanol suspension were electro spun in equal, alternating sequences at intervals of one, two, and ten minutes each. The scaffolds revealed fiber mesh with micropores of 10 μm and uniformly distributed sucrose particles. Particulate leaching of sucrose from the one- or two-minute scaffolds revealed honeycomb structures with interconnected macro pores between 50 and 250 μm. Sucrose leaching from the ten-minute scaffolds resulted in laminated structures with isolated macro pores between 200 and 350 μm. Macro pore size was directly proportional to the duration of the sucrose spinning interval. After 24 hours of cell culture, conventionally spun scaffolds demonstrated no cellular penetration. Conversely, the PGA/sucrose scaffolds demonstrated deep cellular penetration. This hybrid technique represents a novel method of generating electro spun scaffolds with interconnected pores suitable for cellular ingrowth.

Mimicked cartilage scaffolds of silk fibroin/hyaluronic acid with stem cells for osteoarthritis surgery: Morphological, mechanical, and physical clues

International Nuclear Information System (INIS)

Jaipaew, Jirayut; Wangkulangkul, Piyanun; Meesane, Jirut; Raungrut, Pritsana; Puttawibul, Puttisak

2016-01-01

Osteoarthritis is a critical disease that comes from degeneration of cartilage tissue. In severe cases surgery is generally required. Tissue engineering using scaffolds with stem cell transplantation is an attractive approach and a challenge for orthopedic surgery. For sample preparation, silk fibroin (SF)/hyaluronic acid (HA) scaffolds in different ratios of SF/HA (w/w) (i.e., 100:0, 90:10, 80:20, and 70:30) were formed by freeze-drying. The morphological, mechanical, and physical clues were considered in this research. The morphological structure of the scaffolds was observed by scanning electron microscope. The mechanical and physical properties of the scaffolds were analyzed by compressive and swelling ratio testing, respectively. For the cell experiments, scaffolds were seeded and cultured with human umbilical cord-derived mesenchymal stem cells (HUMSCs). The cultured scaffolds were tested for cell viability, histochemistry, immunohistochemistry, and gene expression. The SF with HA scaffolds showed regular porous structures. Those scaffolds had a soft and elastic characteristic with a high swelling ratio and water uptake. The SF/HA scaffolds showed a spheroid structure of the cells in the porous structure particularly in the SF80 and SF70 scaffolds. Cells could express Col2a, Agg, and Sox9 which are markers for chondrogenesis. It could be deduced that SF/HA scaffolds showed significant clues for suitability in cartilage tissue engineering and in surgery for osteoarthritis. - Highlights: • Silk fibroin/Hyaluronic acid was fabricated into mimicked scaffolds. • Mimicked scaffolds were incorporated with stem cells for chondrogenesis. • Mimicked scaffolds showed the clues for chondrogenic regulation. • Mimicked scaffolds had suitable performance for cartilage tissue engineering • Mimicked scaffolds showed promise for osteoarthritis surgery.

Mimicked cartilage scaffolds of silk fibroin/hyaluronic acid with stem cells for osteoarthritis surgery: Morphological, mechanical, and physical clues

Energy Technology Data Exchange (ETDEWEB)

Jaipaew, Jirayut [Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Wangkulangkul, Piyanun [Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Department of Surgery, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Meesane, Jirut, E-mail: jirutmeesane999@yahoo.co.uk [Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Raungrut, Pritsana [Department of Biomedical Science, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Puttawibul, Puttisak [Institute of Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand); Department of Surgery, Faculty of Medicine, Prince of Songkla University, 15 Karnjanavanich Road, Hat Yai, Songkhla, Thailand 90110 (Thailand)

2016-07-01

Osteoarthritis is a critical disease that comes from degeneration of cartilage tissue. In severe cases surgery is generally required. Tissue engineering using scaffolds with stem cell transplantation is an attractive approach and a challenge for orthopedic surgery. For sample preparation, silk fibroin (SF)/hyaluronic acid (HA) scaffolds in different ratios of SF/HA (w/w) (i.e., 100:0, 90:10, 80:20, and 70:30) were formed by freeze-drying. The morphological, mechanical, and physical clues were considered in this research. The morphological structure of the scaffolds was observed by scanning electron microscope. The mechanical and physical properties of the scaffolds were analyzed by compressive and swelling ratio testing, respectively. For the cell experiments, scaffolds were seeded and cultured with human umbilical cord-derived mesenchymal stem cells (HUMSCs). The cultured scaffolds were tested for cell viability, histochemistry, immunohistochemistry, and gene expression. The SF with HA scaffolds showed regular porous structures. Those scaffolds had a soft and elastic characteristic with a high swelling ratio and water uptake. The SF/HA scaffolds showed a spheroid structure of the cells in the porous structure particularly in the SF80 and SF70 scaffolds. Cells could express Col2a, Agg, and Sox9 which are markers for chondrogenesis. It could be deduced that SF/HA scaffolds showed significant clues for suitability in cartilage tissue engineering and in surgery for osteoarthritis. - Highlights: • Silk fibroin/Hyaluronic acid was fabricated into mimicked scaffolds. • Mimicked scaffolds were incorporated with stem cells for chondrogenesis. • Mimicked scaffolds showed the clues for chondrogenic regulation. • Mimicked scaffolds had suitable performance for cartilage tissue engineering • Mimicked scaffolds showed promise for osteoarthritis surgery.

Gelatin crosslinked with dehydroascorbic acid as a novel scaffold for tissue regeneration with simultaneous antitumor activity

International Nuclear Information System (INIS)

Falconi, M; Salvatore, V; Teti, G; Focaroli, S; Durante, S; Nicolini, B; Mazzotti, A; Orienti, I

2013-01-01

A porous scaffold was developed to support normal tissue regeneration in the presence of residual tumor disease. It was prepared by gelatin crosslinked with dehydroascorbic acid (DHA). A physicochemical characterization of the scaffold was carried out. SEM and mercury porosimetry revealed a high porosity and interconnection of pores in the scaffold. Enzymatic degradation provided 56% weight loss in ten days. The scaffold was also evaluated in vitro for its ability to support the growth of normal cells while hindering tumor cell development. For this purpose, primary human fibroblasts and osteosarcoma tumor cells (MG-63) were seeded on the scaffold. Fibroblasts attached the scaffold and proliferated, while the tumor cells, after an initial attachment and growth, failed to proliferate and progressively underwent cell death. This was attributed to the progressive release of DHA during the scaffold degradation and its cytotoxic activity towards tumor cells. (paper)

Fabrication and characterization of poly(L-lactic acid) gels induced by fibrous complex crystallization with solvents

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Yasuhiro [ORNL; Fukatsu, Akinobu [Shizuoka University, Hamamatsu, Japan; Wang, Yangyang [ORNL; Miyamoto, Kazuaki [Shizuoka University, Hamamatsu, Japan; Mays, Jimmy [University of Tennessee, Knoxville (UTK); Tasaka, Shigeru [Shizuoka University, Hamamatsu, Japan

2014-01-01

Complex crystal induced gelation of poly(L-lactic acid) (PLLA) solutions was studied for a series of solvents, including N,N-dimethylformamide (DMF). By cooling the solutions prepared at elevated temperatures, PLLA gels were produced in solvents that induced complex crystals ( -crystals) with PLLA. Fibrous structure of PLLA in the gel with DMF was observed by polarizing optical microscopy, field emission electron microscopy, and atomic force microscopy. Upon heating, the crystal form of PLLA in the DMF gel changed from -crystal to a-crystal, the major crystal form in common untreated PLLA films, but the morphology and high elastic modulus of the gel remained until the a-crystal dissolved at higher temperature. In addition, a solvent exchanging method was developed, which allowed PLLA gels to be prepared in other useful solvents that do not induce -crystals without losing the morphology and mechanical properties.

Chitosan-Based Hyaluronic Acid Hybrid Polymer Fibers as a Scaffold Biomaterial for Cartilage Tissue Engineering

Directory of Open Access Journals (Sweden)

Shintarou Yamane

2010-12-01

Full Text Available An ideal scaffold material is one that closely mimics the natural environment in the tissue-specific extracellular matrix (ECM. Therefore, we have applied hyaluronic acid (HA, which is a main component of the cartilage ECM, to chitosan as a fundamental material for cartilage regeneration. To mimic the structural environment of cartilage ECM, the fundamental structure of a scaffold should be a three-dimensional (3D system with adequate mechanical strength. We structurally developed novel polymer chitosan-based HA hybrid fibers as a biomaterial to easily fabricate 3D scaffolds. This review presents the potential of a 3D fabricated scaffold based on these novel hybrid polymer fibers for cartilage tissue engineering.

Effect of Zinc Oxide Addition on Antibacterial Behavior of Hydroxyapatite-Poly lactic-co-glycolic acid Scaffold for Bone Tissue Engineering Applications

Directory of Open Access Journals (Sweden)

Narges Abotalebi

2018-03-01

Full Text Available Introduction: Infection after the surgery is one of the problems of bone scaffolds implants which is normally treated by systemic administration of antibiotics. But due to the poor blood circulation in bone tissue, large antibiotic doses are needed which lead to further drawbacks to renal and hepatic systems. Material and method: In this study, the effect of zinc oxide addition on antibacterial behavior of hydroxyapatite- Poly lactic-co-glycolic acid scaffold was evaluated. The synthesized composite was characterized by X-ray diffraction, scanning electron microscopy equipped with elemental analysis and Fourier transform infrared spectra. In order to determine the antibacterial activity of the fabricated scaffold, Staphylococcus aureus (ATTC 25922 and Escherichia coli (ATTC 25923 were used as test microorganisms. Results: The results showed that Hydroxyapatite- Poly lactic-co-glycolic acid scaffold did not make inhibition zone in culture medium but the modification of Hydroxyapatite- Poly lactic-co-glycolic acid scaffold’s surface by zinc oxide particles caused Hydroxyapatite- Poly lactic-co-glycolic acid- zinc oxide scaffold to have antibacterial inhibition zone of 12 and 20 mm for Escherichia coli and Staphylococcus aureus, respectively. Discussion and conclusion: This study revealed that the addition of antibacterial agent to applicable bone tissue engineering scaffolds could be considered as an appropriate way to prevent the growth of infection at the scaffold site.

Selective Depolymerization and Effects of Homolysis of Poly(L-lactic acid) in a Blend with Polypropylene

International Nuclear Information System (INIS)

Nishida, H.; Tsukegi, T.; Shirai, Y.; Arazoe, Y.; Yan, W.; Shirai, Y.

2009-01-01

Blends of poly(L-lactic acid) (PLLA) and polypropylene (PP), which are candidates for the practical use of PLLA, were investigated for selective degradation of PLLA, resulting in quantitative conversion of PLLA components into cyclic monomers, lactide, using magnesium oxide (Mg O) as a depolymerization catalyst. Obviously, the catalyst Mg O selectively accelerated only the PLLA depolymerization in the blends, dominantly generating L,L-lactide as a volatile product and separating the PP component. Expected effects of homolysis in the blend system were also determined as slight changes in activation energy of degradation for both the components and through the suppression of degradation by an antioxidant.

Facial volumetric correction with injectable poly-L-lactic acid.

Science.gov (United States)

Vleggaar, Danny

2005-11-01

Polymers of lactic acid'have been widely used for many years in different types of medical devices, such as resorbable sutures, intrabone implants, and soft tissue implants. Injectable poly-L-lactic acid (PLLA; Sculptra), a synthetic, biodegradable polymer, has gained widespread popularity in Europe for the treatment of facial changes associated with aging. To provide background information on injectable PLLA and to describe clinical experience with its use in Europe for facial volume enhancement. Technique varies with site of injection. Generally, the product is implanted subcutaneously or intradermally in a series of treatments. No allergy testing is required. Based on experience in more than 2,500 patients, injectable PLLA has been used successfully for the correction of nasolabial folds, mid- and lower facial volume loss, jawline laxity, and other signs of facial aging. Correction lasts for 18 to 24 months in most patients. Injectable PLLA treatment provides an excellent and prolonged correction of a variety of facial wrinkles, depressions, and laxity with a minimally invasive procedure that does not require allergy testing or a recovery period.

Film Sensor Device Fabricated by a Piezoelectric Poly(L-lactic acid) Film

Science.gov (United States)

Ando, Masamichi; Kawamura, Hideki; Kageyama, Keisuke; Tajitsu, Yoshiro

2012-09-01

Synthetic piezoelectric polymer films produced from petroleum feedstock have long been used as thin-film sensors and actuators. However, the fossil fuel requirements for synthetic polymer production and carbon dioxide emission from its combustion have raised concern about the environmental impact of its continued use. Eco-friendly biomass polymers, such as poly(L-lactic acid) (PLLA), are made from plant-based (vegetable starch) plastics and, thus, have a much smaller carbon footprint. Additionally, PLLA does not exhibit pyroelectricity or unnecessary poling. This suggests the usefulness of PLLA films for the human-machine interface (HMI). As an example of a new HMI, we have produced a TV remote control using a PLLA film. The intuitive operation provided by this PLLA device suggests that it is useful for the elderly or handicapped.

Fabrication and characterization of novel multilayered structures by stereocomplexion of poly(D-lactic acid)/poly(L-lactic acid) and self-assembly of polyelectrolytes

OpenAIRE

Elena Dellacasa; Li Zhao; Gesheng Yang; Laura Pastorino; Gleb B. Sukhorukov

2016-01-01

The enantiomers poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) were alternately adsorbed directly on calcium carbonate (CaCO3) templates and on poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) multilayer precursors in order to fabricate a novel layer-by-layer (LBL) assembly. A single layer of poly(L-lysine) (PLL) was used as a linker between the (PDLA/PLLA)n stereocomplex and the cores with and without the polymeric (PSS/PAH)n/PLL multilayer precursor (PEM). N...

Borax-Loaded PLLA for Promotion of Myogenic Differentiation.

Science.gov (United States)

Rico, Patricia; Rodrigo-Navarro, Aleixandre; Salmerón-Sánchez, Manuel

2015-11-01

Boron is an essential metalloid, which plays a key role in plant and animal metabolisms. It has been reported that boron is involved in bone mineralization, has some uses in synthetic chemistry, and its potential has been only recently exploited in medicinal chemistry. However, in the area of tissue engineering, the use of boron is limited to works involving certain bioactive glasses. In this study, we engineer poly(l-lactic acid) (PLLA) substrates with sustained release of boron. Then, we analyze for the first time the uniqueness effects of boron in cell differentiation using murine C2C12 myoblasts and discuss a potential mechanism of action in cooperation with Ca(2+). Our results demonstrate that borax-loaded materials strongly enhance myotube formation at initial steps of myogenesis. Furthermore, we demonstrate that Ca(2+) plays an essential role in combination with borax as chelating or blocking Ca(2+) entry into the cell leads to a detrimental effect on myoblast differentiation observed on borax-loaded materials. This research identifies borax-loaded materials to trigger differentiation mechanisms and it establishes a new tool to engineer microenvironments with applications in regenerative medicine for muscular diseases.

Triptycene: A Nucleic Acid Three-Way Junction Binder Scaffold

Science.gov (United States)

Yoon, Ina

Nucleic acids play a critical role in many biological processes such as gene regulation and replication. The development of small molecules that modulate nucleic acids with sequence or structure specificity would provide new strategies for regulating disease states at the nucleic acid level. However, this remains challenging mainly because of the nonspecific interactions between nucleic acids and small molecules. Three-way junctions are critical structural elements of nucleic acids. They are present in many important targets such as trinucleotide repeat junctions related to Huntington's disease, a temperature sensor sigma32 in E. coli, Dengue virus, and HIV. Triptycene-derived small molecules have been shown to bind to nucleic acid three-way junctions, resulting from their shape complementary. To develop a better understanding of designing molecules for targeting different junctions, a rapid screening of triptycene-based small molecules is needed. We envisioned that the installation of a linker at C9 position of the bicyclic core would allow for a rapid solid phase diversification. To achieve this aim, we synthesized 9-substituted triptycene scaffolds by using two different synthetic routes. The first synthetic route installed the linker from the amidation reaction between carboxylic acid at C9 position of the triptycene and an amine linker, beta-alanine ethyl ester. This new 9-substituted triptycene scaffold was then attached to a 2-chlorotrityl chloride resin for solid-phase diversification. This enabled a rapid diversification and an easy purification of mono-, di-, and tri-peptide triptycene derivatives. The binding affinities of these compounds were investigated towards a (CAG)˙(CTG) trinucleotide repeat junction. In the modified second synthetic route, we utilized a combined Heck coupling/benzyne Diels-Alder strategy. This improved synthetic strategy reduced the number of steps and total reaction times, increased the overall yield, improved solubilities of

Multiscale Modeling of Poly(lactic acid) Production: From Reaction Conditions to Rheology of Polymer Melt

DEFF Research Database (Denmark)

Zubov, Alexandr; Sin, Gürkan

2018-01-01

Abstract Poly(L-lactic acid) (PLLA) is a fully biodegradable bioplastic with promising market potential. The paper deals with systematic development and analysis of the modeling framework allowing direct mapping between PLLA production process conditions and rheological properties of the polymer ...

Radiation induced crystallinity damage in poly(L-lactic acid)

CERN Document Server

Kantoglu, O

2002-01-01

The radiation-induced crystallinity damage in poly(L-lactic acid) (PLLA) in the presence of air and in vacuum, is studied. From the heat of fusion enthalpy values of gamma irradiated samples, some changes on the thermal properties were determined. To identify these changes, first the glass transition temperature (T sub g) of L-lactic acid polymers irradiated to various doses in air and vacuum have been investigated and it is found that it is independent of irradiation atmosphere and dose. The fraction of damaged units of PLLA per unit of absorbed energy has been measured. For this purpose, SAXS and differential scanning calorimetry methods were used, and the radiation yield of number of damaged units (G(-u)) is found to be 0.74 and 0.58 for PLLA samples irradiated in vacuum and air, respectively.

Logic gates and antisense DNA devices operating on a translator nucleic Acid scaffold.

Science.gov (United States)

Shlyahovsky, Bella; Li, Yang; Lioubashevski, Oleg; Elbaz, Johann; Willner, Itamar

2009-07-28

A series of logic gates, "AND", "OR", and "XOR", are designed using a DNA scaffold that includes four "footholds" on which the logic operations are activated. Two of the footholds represent input-recognition strands, and these are blocked by complementary nucleic acids, whereas the other two footholds are blocked by nucleic acids that include the horseradish peroxidase (HRP)-mimicking DNAzyme sequence. The logic gates are activated by either nucleic acid inputs that hybridize to the respective "footholds", or by low-molecular-weight inputs (adenosine monophosphate or cocaine) that yield the respective aptamer-substrate complexes. This results in the respective translocation of the blocking nucleic acids to the footholds carrying the HRP-mimicking DNAzyme sequence, and the concomitant release of the respective DNAzyme. The released product-strands then self-assemble into the hemin/G-quadruplex-HRP-mimicking DNAzyme that biocatalyzes the formation of a colored product and provides an output signal for the different logic gates. The principle of the logic operation is, then, implemented as a possible paradigm for future nanomedicine. The nucleic acid inputs that bind to the blocked footholds result in the translocation of the blocking nucleic acids to the respective footholds carrying the antithrombin aptamer. The released aptamer inhibits, then, the hydrolytic activity of thrombin. The system demonstrates the regulation of a biocatalytic reaction by a translator system activated on a DNA scaffold.

The effect of thermal treatment on the mechanical properties of PLLA tubular specimens

Directory of Open Access Journals (Sweden)

Arbeiter Daniela

2016-09-01

Full Text Available Conventional permanent stent systems for vascular applications are associated with long-term risks, such as restenosis and thrombosis. To overcome these limitations, novel approaches using various biodegradable materials for stent construction have been investigated. In this context, thermal treatment of polymer materials is investigated to adjust the mechanical properties of biodegradable stents. In this work polymeric tubular specimens of biodegradable poly(L-lactide (PLLA were extruded and subjected to a molding process using different temperatures above glass transition temperature TG. Physicochemical properties of the molded samples were analyzed using DSC measurements and uniaxial tensile tests. The molding process resulted in a weakening of the PLLA tubular specimens with a simultaneous increase in the degree of crystallinity (χ.

Effect of beta-tricalcium phosphate/poly-l-lactide composites on radial bone defects of rabbit

Institute of Scientific and Technical Information of China (English)

Zhao-Jin Zhu; Hao Shen; Yong-Ping Wang; Yao Jiang; Xian-Long Zhang; Guang-Yin Yuan

2013-01-01

Objective:To explore the effect ofβ-TCP/PLLA scaffold in repairing rabbit radial bone defects. Methods: Thirty New Zealand rabbits were divided intoβ-TCP/PLLA group (group A), pure PLLA group (group B) and contrast group (group C) randomly. The rabbits were sacrificed respectively after 4, 8, 12, 24 weeks and the X-ray film was performed at the same time to evaluate the repair effect in different groups. Results:X-ray film showed there was uneven low density bone callus development in defect region after 4 weeks in group A. The defect region was filled with neonate osseous tissue completely during 12-24 weeks. X-ray score revealed that repair of bone defect results significantly better than group B and group C. Conclusions: Theβ-TCP/PLLA composite is capable of repairing radial bone bone defects.β-TCP/PLLA scaffold is significant because of rapid degradation ability, good histocompatibility and osteogenic action.

Poly(dopamine) coating of 3D printed poly(lactic acid) scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Kao, Chia-Tze; Lin, Chi-Chang; Chen, Yi-Wen; Yeh, Chia-Hung; Fang, Hsin-Yuan; Shie, Ming-You

2015-01-01

3D printing is a versatile technique to generate large quantities of a wide variety of shapes and sizes of polymer. The aim of this study is to develop functionalized 3D printed poly(lactic acid) (PLA) scaffolds and use a mussel-inspired surface coating to regulate cell adhesion, proliferation and differentiation of human adipose-derived stem cells (hADSCs). We prepared PLA 3D scaffolds coated with polydopamine (PDA). The chemical composition and surface properties of PDA/PLA were characterized by XPS. PDA/PLA modulated hADSCs' responses in several ways. Firstly, adhesion and proliferation, and cell cycle of hADSCs cultured on PDA/PLA were significantly enhanced relative to those on PLA. In addition, the collagen I secreted from cells was increased and promoted cell attachment and cell cycle progression were depended on the PDA content. In osteogenesis assay, the ALP activity and osteocalcin of hADSCs cultured on PDA/PLA were significantly higher than seen in those cultured on pure PLA scaffolds. Moreover, hADSCs cultured on PDA/PLA showed up-regulation of the ang-1 and vWF proteins associated with angiogenic differentiation. Our results demonstrate that the bio-inspired coating synthetic PLA polymer can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to direct the specific responses of hADSCs. - Highlights: • A simple method of 3D printed poly(lactic acid) scaffold coated with PDA • Promoted proliferation of hADSCs on PDA/PLA scaffolds • Increased collagen I, cell cycle, and cell adhesion with a high PDA content • Up-regulation of angiogenic and osteogenic of hADSCs • A promising method for bioinspired surface modification on PLA using PDA

Poly(dopamine) coating of 3D printed poly(lactic acid) scaffolds for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Kao, Chia-Tze [School of Dentistry, Chung Shan Medical University, Taichung City, Taiwan (China); Department of Stomatology, Chung Shan Medical University Hospital, Taichung City, Taiwan (China); Lin, Chi-Chang [Department of Chemical and Materials Engineering, Tunghai University, Taichung City, Taiwan (China); Chen, Yi-Wen; Yeh, Chia-Hung [3D Printing Medical Research Center, China Medical University Hospital, Taichung City, Taiwan (China); Fang, Hsin-Yuan [3D Printing Medical Research Center, China Medical University Hospital, Taichung City, Taiwan (China); Department of Thoracic Surgery, China Medical University Hospital, Taichung City, Taiwan (China); School of Medicine, College of Medicine, College of Public Health, Taichung City, Taiwan (China); Shie, Ming-You, E-mail: eviltacasi@gmail.com [3D Printing Medical Research Center, China Medical University Hospital, Taichung City, Taiwan (China)

2015-11-01

3D printing is a versatile technique to generate large quantities of a wide variety of shapes and sizes of polymer. The aim of this study is to develop functionalized 3D printed poly(lactic acid) (PLA) scaffolds and use a mussel-inspired surface coating to regulate cell adhesion, proliferation and differentiation of human adipose-derived stem cells (hADSCs). We prepared PLA 3D scaffolds coated with polydopamine (PDA). The chemical composition and surface properties of PDA/PLA were characterized by XPS. PDA/PLA modulated hADSCs' responses in several ways. Firstly, adhesion and proliferation, and cell cycle of hADSCs cultured on PDA/PLA were significantly enhanced relative to those on PLA. In addition, the collagen I secreted from cells was increased and promoted cell attachment and cell cycle progression were depended on the PDA content. In osteogenesis assay, the ALP activity and osteocalcin of hADSCs cultured on PDA/PLA were significantly higher than seen in those cultured on pure PLA scaffolds. Moreover, hADSCs cultured on PDA/PLA showed up-regulation of the ang-1 and vWF proteins associated with angiogenic differentiation. Our results demonstrate that the bio-inspired coating synthetic PLA polymer can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to direct the specific responses of hADSCs. - Highlights: • A simple method of 3D printed poly(lactic acid) scaffold coated with PDA • Promoted proliferation of hADSCs on PDA/PLA scaffolds • Increased collagen I, cell cycle, and cell adhesion with a high PDA content • Up-regulation of angiogenic and osteogenic of hADSCs • A promising method for bioinspired surface modification on PLA using PDA.

Chemical hydrogels based on a hyaluronic acid-graft-α-elastin derivative as potential scaffolds for tissue engineering

International Nuclear Information System (INIS)

Palumbo, Fabio Salvatore; Pitarresi, Giovanna; Fiorica, Calogero; Rigogliuso, Salvatrice; Ghersi, Giulio; Giammona, Gaetano

2013-01-01

In this work hyaluronic acid (HA) functionalized with ethylenediamine (EDA) has been employed to graft α-elastin. In particular a HA-EDA derivative bearing 50 mol% of pendant amino groups has been successfully employed to produce the copolymer HA-EDA-g-α-elastin containing 32% w/w of protein. After grafting with α-elastin, remaining free amino groups reacted with ethylene glycol diglycidyl ether (EGDGE) for producing chemical hydrogels, proposed as scaffolds for tissue engineering. Swelling degree, resistance to chemical and enzymatic hydrolysis, as well as preliminary biological properties of HA-EDA-g-α-elastin/EGDGE scaffold have been evaluated and compared with a HA-EDA/EGDGE scaffold. The presence of α-elastin grafted to HA-EDA improves attachment, viability and proliferation of primary rat dermal fibroblasts and human umbilical artery smooth muscle cells. Biological performance of HA-EDA-g-α-elastin/EGDGE scaffold resulted comparable to that of a commercial collagen type I sponge (Antema®), chosen as a positive control. - Highlights: ► Hyaluronic acid (HA) has been functionalized with ethylenediamine (EDA). ► Amino groups of HA-EDA allow the reaction with α-elastin and ethylene glycol diglycidyl ether (EGDGE). ► Chemical scaffolds of HA-EDA-graft-α-elastin/EGDGE have been characterized. ► The presence of α-elastin affects porosity, swelling and enzymatic degradation of scaffolds. ► The presence of α-elastin improves attachment, viability and proliferation of fibroblasts and smooth muscle cells

Chemical hydrogels based on a hyaluronic acid-graft-α-elastin derivative as potential scaffolds for tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Palumbo, Fabio Salvatore [Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123, Palermo (Italy); Pitarresi, Giovanna, E-mail: giovanna.pitarresi@unipa.it [Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123, Palermo (Italy); Institute of Biophysics at Palermo, Italian National Research Council, Via Ugo La Malfa 153, 90146 Palermo (Italy); Fiorica, Calogero [Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123, Palermo (Italy); Rigogliuso, Salvatrice; Ghersi, Giulio [Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Biologia Cellulare, Università degli Studi di Palermo, Viale delle Scienze ed. 16, 90128, Palermo (Italy); Giammona, Gaetano [Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123, Palermo (Italy); IBIM-CNR, Via Ugo La Malfa 153, 90146 Palermo (Italy)

2013-07-01

In this work hyaluronic acid (HA) functionalized with ethylenediamine (EDA) has been employed to graft α-elastin. In particular a HA-EDA derivative bearing 50 mol% of pendant amino groups has been successfully employed to produce the copolymer HA-EDA-g-α-elastin containing 32% w/w of protein. After grafting with α-elastin, remaining free amino groups reacted with ethylene glycol diglycidyl ether (EGDGE) for producing chemical hydrogels, proposed as scaffolds for tissue engineering. Swelling degree, resistance to chemical and enzymatic hydrolysis, as well as preliminary biological properties of HA-EDA-g-α-elastin/EGDGE scaffold have been evaluated and compared with a HA-EDA/EGDGE scaffold. The presence of α-elastin grafted to HA-EDA improves attachment, viability and proliferation of primary rat dermal fibroblasts and human umbilical artery smooth muscle cells. Biological performance of HA-EDA-g-α-elastin/EGDGE scaffold resulted comparable to that of a commercial collagen type I sponge (Antema®), chosen as a positive control. - Highlights: ► Hyaluronic acid (HA) has been functionalized with ethylenediamine (EDA). ► Amino groups of HA-EDA allow the reaction with α-elastin and ethylene glycol diglycidyl ether (EGDGE). ► Chemical scaffolds of HA-EDA-graft-α-elastin/EGDGE have been characterized. ► The presence of α-elastin affects porosity, swelling and enzymatic degradation of scaffolds. ► The presence of α-elastin improves attachment, viability and proliferation of fibroblasts and smooth muscle cells.

Enhancement of skin wound healing with decellularized scaffolds loaded with hyaluronic acid and epidermal growth factor

Energy Technology Data Exchange (ETDEWEB)

Su, Zhongchun; Ma, Huan; Wu, Zhengzheng [Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Key Lab for Genetic Medicine of Guangdong Province, Jinan University, Guangzhou 510632 (China); Zeng, Huilan [Department of Hematology, The First Affiliated Hospital, Jinan University, Guangzhou 510632 (China); Li, Zhizhong [Department of Bone, The First Affiliated Hospital, Jinan University, Guangzhou 510632 (China); Wang, Yuechun; Liu, Gexiu [Department of Physiology, School of Medicine, Jinan University, Guangzhou 510632 (China); Xu, Bin; Lin, Yongliang; Zhang, Peng [Grandhope Biotech Co., Ltd., Building D, #408, Guangzhou International Business Incubator, Guangzhou Science Park, Guangzhou 510663, Guangdong (China); Wei, Xing, E-mail: wei70@hotmail.com [Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Key Lab for Genetic Medicine of Guangdong Province, Jinan University, Guangzhou 510632 (China)

2014-11-01

Current therapy for skin wound healing still relies on skin transplantation. Many studies were done to try to find out ways to replace skin transplantation, but there is still no effective alternative therapy. In this study, decellularized scaffolds were prepared from pig peritoneum by a series of physical and chemical treatments, and scaffolds loaded with hyaluronic acid (HA) and epidermal growth factor (EGF) were tested for their effect on wound healing. MTT assay showed that EGF increased NIH3T3 cell viability and confirmed that EGF used in this study was biologically active in vitro. Scanning electron microscope (SEM) showed that HA stably attached to scaffolds even after soaking in PBS for 48 h. ELISA assay showed that HA increased the adsorption of EGF to scaffolds and sustained the release of EGF from scaffolds. Animal study showed that the wounds covered with scaffolds containing HA and EGF recovered best among all 4 groups and had wound healing rates of 49.86%, 70.94% and 87.41% respectively for days 10, 15 and 20 post-surgery compared to scaffolds alone with wound healing rates of 29.26%, 42.80% and 70.14%. In addition, the wounds covered with scaffolds containing EGF alone were smaller than no EGF scaffolds on days 10, 15 and 20 post-surgery. Hematoxylin–Eosin (HE) staining confirmed these results by showing that on days 10, 15 and 20 post-surgery, the thicker epidermis and dermis layers were observed in the wounds covered with scaffolds containing HA and EGF than scaffolds alone. In addition, the thicker epidermis and dermis layers were also observed in the wounds covered with scaffolds containing EGF than scaffolds alone. Skin appendages were observed on day 20 only in the wound covered with scaffolds containing HA and EGF. These results demonstrate that the scaffolds containing HA and EGF can enhance wound healing. - Highlights: • HA can increase the adsorption of EGF to decellularized scaffolds. • HA can sustain the release of EGF from

Influence of layer-by-layer assembled electrospun poly (L-lactic acid) nanofiber mats on the bioactivity of endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Wu, Keke; Zhang, Xiazhi; Yang, Wufeng; Liu, Xiaoyan; Jiao, Yanpeng, E-mail: tjiaoyp@jnu.edu.cn; Zhou, Changren

2016-12-30

Highlights: • Layer-by-layer assembled PLLA nanofiber mats were successfully prepared. • The modified PLLA nanofiber mats enhanced the adhesion, proliferation of endothelial cells. • The modified PLLA nanofiber mats had inhibited the inflammatory response to some extent. - Abstract: Electrospun poly(L-lactic acid) (PLLA) nanofiber mats were successfully modified by deposition of multilayers with chitosan (CS), heparin (Hep) and graphene oxide (GO) through electrostatic layer-by-layer (LBL) self-assembly method. In this study, the surface properties of PLLA nanofiber mats before and after modification were investigated via scanning electron microscope (SEM), atomic force microscopy (AFM), attenuated total reflectance fourier transformation infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and water contact angle measurement. In addition, the cytocompatibility of the modified PLLA nanofiber mats were investigated by testing endothelial cells compatibility, including cell attachment, cell proliferation and cell cycle. The results revealed that the surfaces of modified PLLA nanofiber mats become much rougher, stifiness and the hydrophilicity of the LBL modified PLLA nanofiber mats were improved compared to original PLLA one. Moreover, the modified PLLA nanofiber mats had promoted the endothelial cells viability attachment significantly. Besides, we studied the PLLA nanofiber mats on the expression of necrosis factor (TNF-α), interleukine-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells. The results showed that modified PLLA nanofiber mats had inhibited the inflammatory response to some extent.

Biomimetic nanoclay scaffolds for bone tissue engineering

Science.gov (United States)

Ambre, Avinash Harishchandra

Tissue engineering offers a significant potential alternative to conventional methods for rectifying tissue defects by evoking natural regeneration process via interactions between cells and 3D porous scaffolds. Imparting adequate mechanical properties to biodegradable scaffolds for bone tissue engineering is an important challenge and extends from molecular to macroscale. This work focuses on the use of sodium montmorillonite (Na-MMT) to design polymer composite scaffolds having enhanced mechanical properties along with multiple interdependent properties. Materials design beginning at the molecular level was used in which Na-MMT clay was modified with three different unnatural amino acids and further characterized using Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD). Based on improved bicompatibility with human osteoblasts (bone cells) and intermediate increase in d-spacing of MMT clay (shown by XRD), 5-aminovaleric acid modified clay was further used to prepare biopolymer (chitosan-polygalacturonic acid complex) scaffolds. Osteoblast proliferation in biopolymer scaffolds containing 5-aminovaleric acid modified clay was similar to biopolymer scaffolds containing hydroxyapatite (HAP). A novel process based on biomineralization in bone was designed to prepare 5-aminovaleric acid modified clay capable of imparting multiple properties to the scaffolds. Bone-like apatite was mineralized in modified clay and a novel nanoclay-HAP hybrid (in situ HAPclay) was obtained. FTIR spectroscopy indicated a molecular level organic-inorganic association between the intercalated 5-aminovaleric acid and mineralized HAP. Osteoblasts formed clusters on biopolymer composite films prepared with different weight percent compositions of in situ HAPclay. Human MSCs formed mineralized nodules on composite films and mineralized extracellular matrix (ECM) in composite scaffolds without the use of osteogenic supplements. Polycaprolactone (PCL), a synthetic polymer, was

Cytocompatibility of Siloxane-Containing Vaterite/Poly(l-lactic acid) Composite Coatings on Metallic Magnesium.

Science.gov (United States)

Yamada, Shinya; Maeda, Hirotaka; Obata, Akiko; Lohbauer, Ulrich; Yamamoto, Akiko; Kasuga, Toshihiro

2013-12-12

Poly(l-lactic acid)-based films which include 60 wt % of vaterite (V) or siloxane-containing vaterite (SiV) were coated on a pure magnesium substrate, denoted by PLLA/V or PLLA/SiV, respectively, to suppress early corrosion and improve its cytocompatibility. Both coating films adhered to the Mg substrate with 2.3-2.8 MPa of tensile bonding strength. Soaking test for 7 days in α-modified minimum essential medium revealed that the morphological instability of the PLLA/V film caused a higher amount of Mg 2+ ion to be released from the coating sample. On the other hand, in the case of the coating with the PLLA/SiV film, no morphological change even after the soaking test was observed, owing to the suppression of the degradation rate. In cell culture tests, the proliferation of mouse osteoblast-like cell (MC3T3-E1) was significantly enhanced by both coatings, in comparison with the uncoated magnesium substrate. The cell morphology revealed that a few less-spread cells were observed on the PLLA/V film, while more elongated cells were done on the PLLA/SiV film. The cells on the PLLA/SiV film exhibited an extremely higher alkaline phosphatase activity after 21 days of incubation than that on the PLLA/V one. The PLLA/SiV film suppressed the early corrosion and enhanced cytocompatibility on metallic magnesium.

Cytocompatibility of Siloxane-Containing Vaterite/Poly(l-lactic acid Composite Coatings on Metallic Magnesium

Directory of Open Access Journals (Sweden)

Shinya Yamada

2013-12-01

Full Text Available Poly(l-lactic acid-based films which include 60 wt % of vaterite (V or siloxane-containing vaterite (SiV were coated on a pure magnesium substrate, denoted by PLLA/V or PLLA/SiV, respectively, to suppress early corrosion and improve its cytocompatibility. Both coating films adhered to the Mg substrate with 2.3–2.8 MPa of tensile bonding strength. Soaking test for 7 days in α-modified minimum essential medium revealed that the morphological instability of the PLLA/V film caused a higher amount of Mg2+ ion to be released from the coating sample. On the other hand, in the case of the coating with the PLLA/SiV film, no morphological change even after the soaking test was observed, owing to the suppression of the degradation rate. In cell culture tests, the proliferation of mouse osteoblast-like cell (MC3T3-E1 was significantly enhanced by both coatings, in comparison with the uncoated magnesium substrate. The cell morphology revealed that a few less-spread cells were observed on the PLLA/V film, while more elongated cells were done on the PLLA/SiV film. The cells on the PLLA/SiV film exhibited an extremely higher alkaline phosphatase activity after 21 days of incubation than that on the PLLA/V one. The PLLA/SiV film suppressed the early corrosion and enhanced cytocompatibility on metallic magnesium.

Biomimetic scaffolds based on hydroxyapatite nanorod/poly(D,L) lactic acid with their corresponding apatite-forming capability and biocompatibility for bone-tissue engineering.

Science.gov (United States)

Nga, Nguyen Kim; Hoai, Tran Thanh; Viet, Pham Hung

2015-04-01

This study presents a facile synthesis of biomimetic hydroxyapatite nanorod/poly(D,L) lactic acid (HAp/PDLLA) scaffolds with the use of solvent casting combined with a salt-leaching technique for bone-tissue engineering. Field emission scanning electron microscopy, Fourier transform infrared spectroscopy, and energy-dispersive X-ray spectroscopy were used to observe the morphologies, pore structures of synthesized scaffolds, interactions between hydroxyapatite nanorods and poly(D,L) lactic acid, as well as the compositions of the scaffolds, respectively. Porosity of the scaffolds was determined using the liquid substitution method. Moreover, the apatite-forming capability of the scaffolds was evaluated through simulated body fluid (SBF) incubation tests, whereas the viability, attachment, and distribution of human osteoblast cells (MG 63 cell line) on the scaffolds were determined through alamarBlue assay and confocal laser microscopy after nuclear staining with 4',6-diamidino-2-phenylindole and actin filaments of a cytoskeleton with Oregon Green 488 phalloidin. Results showed that hydroxyapatite nanorod/poly(D,L) lactic acid scaffolds that mimic the structure of natural bone were successfully produced. These scaffolds possessed macropore networks with high porosity (80-84%) and mean pore sizes ranging 117-183 μm. These scaffolds demonstrated excellent apatite-forming capabilities. The rapid formation of bone-like apatites with flower-like morphology was observed after 7 days of incubation in SBFs. The scaffolds that had a high percentage (30 wt.%) of hydroxyapatite demonstrated better cell adhesion, proliferation, and distribution than those with low percentages of hydroxyapatite as the days of culture increased. This work presented an efficient route for developing biomimetic composite scaffolds, which have potential applications in bone-tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity.

Science.gov (United States)

Entekhabi, Elahe; Haghbin Nazarpak, Masoumeh; Moztarzadeh, Fathollah; Sadeghi, Ali

2016-12-01

Given the large differences in nervous tissue and other tissues of the human body and its unique features, such as poor and/or lack of repair, there are many challenges in the repair process of this tissue. Tissue engineering is one of the most effective approaches to repair neural damages. Scaffolds made from electrospun fibers have special potential in cell adhesion, function and cell proliferation. This research attempted to design a high porous nanofibrous scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions for nerve regeneration by applying proper physicochemical and mechanical signals. Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds were measured by FTIR and tensile test. Morphology, swelling behavior, and biodegradability of the scaffolds were evaluated too. Porosity of various layers of scaffolds was measured by image analysis method. To assess the cell-scaffold interaction, SH-SY5Y human neuroblastoma cell line were cultured on the electrospun scaffolds. Taken together, these results suggest that the blended nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet all of the required specifications for neural cells and have potential application in neural tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

[Biological evaluation of three-dimensional printed co-poly lactic acid/glycolic acid/tri-calcium phosphate scaffold for bone reconstruction].

Science.gov (United States)

Li, S Y; Zhou, M; Lai, Y X; Geng, Y M; Cao, S S; Chen, X M

2016-11-09

Objective: To biologically evaluate the three-dimensional(3D) printed co-poly lactic acid/glycolic acid/tri-calcium phosphate(PLGA/TCP) scaffold which could be used for repairing oral and maxillofacial bone defects, and to provide experimental evidence for its further research and clinical application. Methods: PLGA/TCP scaffolds were fabricated using low temperature rapid prototyping technique. Micro-CT and scanning electron microscope(SEM) were used to characterize the surface morphology. MC3T3-E1 cells were seeded onto the scaffold and stained with the rhodamine phalloidin and calcein acetomethoxy. After that, confocal laser scanning microscope was exploited to observe the features and viability of the cells. Moreover, the cells were co-cultured with the extract of PLGA/TCP and complete medium, respectively. The proliferation capability of the cells was assessed by the cell counting kit-8 (CCK-8) on the 1st, 2nd, and 3rd day. The PLGA/TCP scaffolds incorporated with recombinant human bone morphogenetic protein-2(rhBMP-2) of 0, 30, 60 μg(i.e. blank control group, low-dose group and high-dose group) were implanted into the latissimus dorsi muscle of the rats, and 6 weeks later, the samples were harvested to estimate the volume and pattern of new bone. Results: The 3D printed PLGA/TCP scaffold possessed a regular and well-defined porous stereo-structure with porosity of (73±3)%. Micro-CT and SEM showed that pore size were (379±32) and (453±29) μm respectively, and distance between layers were (452± 24) and (415±25) μm, and cylinder diameter were (342±24) and (350±28) μm. It also exhibited excellent cell adhesion and growth ability on the exterior and inner surface through rhodamine phalloidin and calcein acetomethoxy staining. The CCK-8 test demonstrated that the absorbance value of extract group on the 1st and 2nd day(0.51±0.08 and 0.63±0.09) were significantly higher than those in the blank control group(0.39± 0.05 and 0.53±0.05)( P 0.05) on the 3

Synthesis and characterization of nanocrystalline forsterite coated poly(L-lactide-co-β-malic acid) scaffolds for bone tissue engineering applications.

Science.gov (United States)

Mozafari, M; Gholipourmalekabadi, M; Chauhan, N P S; Jalali, N; Asgari, S; Caicedoa, J C; Hamlekhan, A; Urbanska, A M

2015-05-01

In this research, after synthesizing poly(L-lactide-co-β-malic acid) (PLMA) copolymer, hybrid particles of ice and nanocrystalline forsterite (NF) as coating carriers were used to prepare NF-coated PLMA scaffolds. The porous NF-coated scaffolds were directly fabricated by a combined technique using porogen leaching and freeze-drying methods. The obtained results indicate that the scaffolds were structurally porous with NF particles on their surfaces. When compared to the uncoated scaffolds, the NF coating improved both mechanical properties as well as enhanced bioactivity of the scaffolds. In addition, in vitro biological response of the rat bone marrow stromal cells indicated that NF significantly increased the biocompatibility of NF-coated scaffolds compared with PLMA. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of layer-by-layer assembled electrospun poly (L-lactic acid) nanofiber mats on the bioactivity of endothelial cells

Science.gov (United States)

Wu, Keke; Zhang, Xiazhi; Yang, Wufeng; Liu, Xiaoyan; Jiao, Yanpeng; Zhou, Changren

2016-12-01

Electrospun poly(L-lactic acid) (PLLA) nanofiber mats were successfully modified by deposition of multilayers with chitosan (CS), heparin (Hep) and graphene oxide (GO) through electrostatic layer-by-layer (LBL) self-assembly method. In this study, the surface properties of PLLA nanofiber mats before and after modification were investigated via scanning electron microscope (SEM), atomic force microscopy (AFM), attenuated total reflectance fourier transformation infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and water contact angle measurement. In addition, the cytocompatibility of the modified PLLA nanofiber mats were investigated by testing endothelial cells compatibility, including cell attachment, cell proliferation and cell cycle. The results revealed that the surfaces of modified PLLA nanofiber mats become much rougher, stifiness and the hydrophilicity of the LBL modified PLLA nanofiber mats were improved compared to original PLLA one. Moreover, the modified PLLA nanofiber mats had promoted the endothelial cells viability attachment significantly. Besides, we studied the PLLA nanofiber mats on the expression of necrosis factor (TNF-α), interleukine-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells. The results showed that modified PLLA nanofiber mats had inhibited the inflammatory response to some extent.

Modification of physical properties of poly(L-lactic acid by addition of methyl-β-cyclodextrin

Directory of Open Access Journals (Sweden)

Toshiyuki Suzuki

2014-12-01

Full Text Available Poly(L-lactic acid (PLLA is a biodegradable plastic and one of the most famous plastics made from biobased materials. However, its physical strength is insufficient compared to general-purpose plastics. In this study, the effect of methylcyclodextrin (MeCD addition on the structure and physical properties, especially the drawing behavior, of PLLA was investigated. Through thermal analysis, it was found that MeCD addition lowers the crystallinity and enhances the mobility of PLLA. The sample containing approximately 17% MeCD was drawn to more than 1000% at 60 °C, although PLLA fractured at a strain of less than 100%. Differential scanning calorimetry (DSC-Raman in situ measurements also revealed decreases in the glass transition temperature (Tg, cold crystallization temperature (Tc, and melting point (Tm, and improvement in structural distribution with temperature. DSC-Raman measurements simultaneously supplied information about crystallinity and thermal properties. Thus, it was concluded that MeCD had high affinity for PLLA, and the addition of MeCD increased the amorphous component of PLLA and enhanced the drawability.

Optimization of protein cross-linking in bicomponent electrospun scaffolds for therapeutic use

Energy Technology Data Exchange (ETDEWEB)

Papa, Antonio [Institute for Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), V.le Kennedy 54, Naples 80125 (Italy); IMAST SCaRL, Piazza Bovio 22, 80133 Naples (Italy); Guarino, Vincenzo, E-mail: vincenzo.guarino@cnr.it; Cirillo, Valentina; Oliviero, Olimpia; Ambrosio, Luigi [Institute for Polymers, Composites and Biomaterials, National Research Council of Italy (IPCB-CNR), V.le Kennedy 54, Naples 80125 (Italy)

2015-12-17

Bio-instructive electrospun scaffolds based on the combination of synthetic polymers, such as PCL or PLLA, and natural polymers (e.g., collagen) have been extensively investigated as temporary extracellular matrix (ECM) analogues able to support cell proliferation and stem cell differentiation for the regeneration of several tissues. The growing use of natural polymers as carrier of bioactive molecules is introducing new ideas for the design of polymeric drug delivery systems based on electrospun fibers with improved bioavailability, therapeutic efficacy and programmed drug release. In particular, the release mechanism is driven by the use of water soluble proteins (i.e., collagen, gelatin) which fully degrade in in vitro microenvironment, thus delivering the active principles. However, these protein are generally rapidly digested by enzymes (i.e., collagenase) produced by many different cell types, both in vivo and in vitro with significant drawbacks in tissue engineering and controlled drug delivery. Here, we aim at investigating different chemical strategies to improve the in vitro stability and mechanical strength of scaffolds against enzymatic degradation, by modifying the biodegradation rates of proteins embedded in bicomponent fibers. By comparing scaffolds treated by different cross-linking agents (i.e., GC, EDC, BDDGE), we have provided an extensive morphological/chemical/physical characterization via SEM and TGA to identify the best conditions to control drug release via protein degradation from bicomponent fibers without compromising in vitro cell response.

Optimization of protein cross-linking in bicomponent electrospun scaffolds for therapeutic use

International Nuclear Information System (INIS)

Papa, Antonio; Guarino, Vincenzo; Cirillo, Valentina; Oliviero, Olimpia; Ambrosio, Luigi

2015-01-01

Bio-instructive electrospun scaffolds based on the combination of synthetic polymers, such as PCL or PLLA, and natural polymers (e.g., collagen) have been extensively investigated as temporary extracellular matrix (ECM) analogues able to support cell proliferation and stem cell differentiation for the regeneration of several tissues. The growing use of natural polymers as carrier of bioactive molecules is introducing new ideas for the design of polymeric drug delivery systems based on electrospun fibers with improved bioavailability, therapeutic efficacy and programmed drug release. In particular, the release mechanism is driven by the use of water soluble proteins (i.e., collagen, gelatin) which fully degrade in in vitro microenvironment, thus delivering the active principles. However, these protein are generally rapidly digested by enzymes (i.e., collagenase) produced by many different cell types, both in vivo and in vitro with significant drawbacks in tissue engineering and controlled drug delivery. Here, we aim at investigating different chemical strategies to improve the in vitro stability and mechanical strength of scaffolds against enzymatic degradation, by modifying the biodegradation rates of proteins embedded in bicomponent fibers. By comparing scaffolds treated by different cross-linking agents (i.e., GC, EDC, BDDGE), we have provided an extensive morphological/chemical/physical characterization via SEM and TGA to identify the best conditions to control drug release via protein degradation from bicomponent fibers without compromising in vitro cell response

Optimization of protein cross-linking in bicomponent electrospun scaffolds for therapeutic use

Science.gov (United States)

Papa, Antonio; Guarino, Vincenzo; Cirillo, Valentina; Oliviero, Olimpia; Ambrosio, Luigi

2015-12-01

Bio-instructive electrospun scaffolds based on the combination of synthetic polymers, such as PCL or PLLA, and natural polymers (e.g., collagen) have been extensively investigated as temporary extracellular matrix (ECM) analogues able to support cell proliferation and stem cell differentiation for the regeneration of several tissues. The growing use of natural polymers as carrier of bioactive molecules is introducing new ideas for the design of polymeric drug delivery systems based on electrospun fibers with improved bioavailability, therapeutic efficacy and programmed drug release. In particular, the release mechanism is driven by the use of water soluble proteins (i.e., collagen, gelatin) which fully degrade in in vitro microenvironment, thus delivering the active principles. However, these protein are generally rapidly digested by enzymes (i.e., collagenase) produced by many different cell types, both in vivo and in vitro with significant drawbacks in tissue engineering and controlled drug delivery. Here, we aim at investigating different chemical strategies to improve the in vitro stability and mechanical strength of scaffolds against enzymatic degradation, by modifying the biodegradation rates of proteins embedded in bicomponent fibers. By comparing scaffolds treated by different cross-linking agents (i.e., GC, EDC, BDDGE), we have provided an extensive morphological/chemical/physical characterization via SEM and TGA to identify the best conditions to control drug release via protein degradation from bicomponent fibers without compromising in vitro cell response.

Uniaxial drawing and mechanical properties of poly[(R)-3-hydroxybutyrate]/poly(L-lactic acid) blends.

Science.gov (United States)

Park, Jun Wuk; Doi, Yoshiharu; Iwata, Tadahisa

2004-01-01

Blends of poly(L-lactic acid) (PLLA) with two kinds of poly[(R)-3-hydroxybutyrate] (PHB) having different molecular weights, commercial-grade bacterial PHB (bacterial-PHB) and ultrahigh molecular weight PHB (UHMW-PHB), were prepared by the solvent-casting method and uniaxially drawn at two drawing temperatures, around PHB's T(g) (2 degrees C) for PHB-rich blends and around PLLA's T(g) (60 degrees C) for PLLA-rich blends. Differential scanning calorimetry analysis showed that this system was immiscible over the entire composition range. Mechanical properties of all of the samples were improved in proportion to the draw ratio. Although PLLA domains in bacterial-PHB-rich blends remained almost unstretched during cold drawing, a good interfacial adhesion between two polymers and the reinforcing role of PLLA components led to enhanced mechanical properties proportionally to the PLLA content at the same draw ratio. On the contrary, in the case of UHMW-PHB-rich blends, the minor component PLLA was found to be also oriented by cold drawing in ice water due to an increase in the interfacial entanglements caused by the very long chain length of the matrix polymer. As a result, their mechanical properties were considerably improved with increasing PLLA content compared with the bacterial-PHB system. Scanning electron microscopy observations on the surface and cross-section revealed that a layered structure with uniformly oriented microporous in the interior was obtained by selectively removal of PLLA component after simple alkaline treatment.

[Biocompatibility of poly-L-lactic acid/Bioglass-guided bone regeneration membranes processed with oxygen plasma].

Science.gov (United States)

Fang, Wei; Zeng, Shu-Guang; Gao, Wen-Feng

2015-04-01

To prepare and characterize a nano-scale fibrous hydrophilic poly-L-lactic acid/ Bioglass (PLLA/BG) composite membrane and evaluate its biocompatibility as a composite membrane for guiding bone regeneration (GBR). PLLA/BG-guided bone regeneration membrane was treated by oxygen plasma to improved its hydrophilicity. The growth of MG-63 osteoblasts on the membrane was observed using Hoechst fluorescence staining, and the biocompatibility of the membrane was evaluated by calculating the cells adhesion rate and proliferation rate. Osteogenesis of MG-63 cells was assessed by detecting alkaline phosphatase (ALP), and the formation of calcified nodules and cell morphology changes were observed using scanning electron microscope (SEM). The cell adhesion rates of PLLA/BG-guided bone regeneration membrane treated with oxygen plasma were (30.570±0.96)%, (47.27±0.78)%, and (66.78±0.69)% at 1, 3, and 6 h, respectively, significantly higher than those on PLLA membrane and untreated PLLA/BG membrane (Pmembranes increased with time, but highest on oxygen plasma-treated PLLA/BG membrane (Pplasma treatment of the PLLA/BG membrane promoted cell adhesion. The membranes with Bioglass promoted the matrix secretion of the osteoblasts. Under SEM, the formation of calcified nodules and spindle-shaped cell morphology were observed on oxygen plasma-treated PLLA/BG membrane. Oxygen plasma-treated PLLA/BG composite membrane has good biocompatibility and can promote adhesion, proliferation and osteogenesis of the osteoblasts.

Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding

International Nuclear Information System (INIS)

Mi, Hao-Yang; Salick, Max R.; Jing, Xin; Jacques, Brianna R.; Crone, Wendy C.; Peng, Xiang-Fang; Turng, Lih-Sheng

2013-01-01

Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of biocompatible and biodegradable polymers that can be used in biomedical applications. PLA has rigid mechanical properties while TPU possesses flexible mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different ratios for tunable properties were fabricated via twin screw extrusion and microcellular injection molding techniques for the first time. Multiple test methods were used to characterize these materials. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of the two components in the blends; differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy (SEM) images verified that, at the composition ratios studied, PLA was dispersed as spheres or islands inside the TPU matrix and that this phase morphology further influenced the scaffold's microstructure and surface roughness. The blends exhibited a large range of mechanical properties that covered several human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds supported cell proliferation and migration properly. Most importantly, this study demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds with tunable microstructures, surface roughnesses, and mechanical properties that have the potential to be used as artificial scaffolds in multiple tissue engineering applications. - Highlights: • Microcellular injection molding was used to fabricate tissue engineering scaffolds. • TPU/PLA tissue engineering scaffolds with tunable properties were fabricated. • Multiple test methods were used to characterize the scaffolds. • The biocompatibility of the scaffolds was confirmed by fibroblast cell culture. • Scaffolds produced have the potential to be used in multiple tissue applications

Biologically Safe Poly(l-lactic acid) Blends with Tunable Degradation Rate: Microstructure, Degradation Mechanism, and Mechanical Properties.

Science.gov (United States)

Oyama, Hideko T; Tanishima, Daisuke; Ogawa, Ryohei

2017-04-10

Although poly(l-lactic acid) (PLLA) is reputed to be biodegradable in the human body, its hydrophobic nature lets it persist for ca. 5.5 years. This study demonstrates that biologically safe lactide copolymers, poly(aspartic acid-co-l-lactide) (PAL) and poly(malic acid-co-l-lactide) (PML), dispersed in the PLLA function as detonators (triggers) for its hydrolytic degradation under physiological conditions. The copolymers significantly enhance hydrolysis, and consequently, the degradation rate of PLLA becomes easily tunable by controlling the amounts of PAL and PML. The present study elucidates the effects of uniaxial drawing on the structural development, mechanical properties, and hydrolytic degradation under physiological conditions of PLLA blend films. At initial degradation stages, the mass loss was not affected by uniaxial drawing; however, at late degradation stages, less developed crystals as well as amorphous chains were degradable at low draw ratio (DR), whereas not only highly developed crystals but also the oriented amorphous chains became insensitive to hydrolysis at high DR. Our work provides important molecular level results that demonstrate that biodegradable materials can have superb mechanical properties and also disappear in a required time under physiological conditions.

Study of Lysozyme-Loaded Poly-L-Lactide (PLLA Porous Microparticles in a Compressed CO2 Antisolvent Process

Directory of Open Access Journals (Sweden)

Xiao-Qian Su

2013-08-01

Full Text Available Lysozyme (LSZ-loaded poly-L-lactide (PLLA porous microparticles (PMs were successfully prepared by a compressed CO2 antisolvent process in combination with a water-in-oil emulsion process using LSZ as a drug model and ammonium bicarbonate as a porogen. The effects of different drug loads (5.0%, 7.5% and 10.0% on the surface morphology, particle size, porosity, tapped density and drug release profile of the harvested PMs were investigated. The results show that an increase in the amount of LSZ added led to an increase in drug load (DL but a decrease in encapsulation efficiency. The resulting LSZ-loaded PLLA PMs (LSZ-PLLA PMs exhibited a porous and uneven morphology, with a density less than 0.1 g·cm−3, a geometric mean diameter of 16.9–18.8 μm, an aerodynamic diameter less than 2.8 μm, a fine particle fraction (FPF of 59.2%–66.8%, and a porosity of 78.2%–86.3%. According to the results of differential scanning calorimetry, the addition of LSZ improved the thermal stability of PLLA. The Fourier transform infrared spectroscopy analysis and circular dichroism spectroscopy measurement reveal that no significant changes occurred in the molecular structures of LSZ during the fabrication process, which was further confirmed by the evaluation of enzyme activity of LSZ. It is demonstrated that the emulsion-combined precipitation with compressed antisolvent (PCA process could be a promising technology to develop biomacromolecular drug-loaded inhalable carrier for pulmonary drug delivery.

Design of a nanocomposite substrate inducing adult stem cell assembly and progression toward an Epiblast-like or Primitive Endoderm-like phenotype via mechanotransduction.

Science.gov (United States)

Morena, Francesco; Armentano, Ilaria; Montanucci, Pia; Argentati, Chiara; Fortunati, Elena; Montesano, Simona; Bicchi, Ilaria; Pescara, Teresa; Pennoni, Ilaria; Mattioli, Samantha; Torre, Luigi; Latterini, Loredana; Emiliani, Carla; Basta, Giuseppe; Calafiore, Riccardo; Kenny, Josè Maria; Martino, Sabata

2017-11-01

This work shows that the active interaction between human umbilical cord matrix stem cells and Poly (l-lactide)acid (PLLA) and PLLA/Multi Walled Carbon Nanotubes (MWCNTs) nanocomposite films results in the stem cell assembly as a spheroid conformation and affects the stem cell fate transition. We demonstrated that spheroids directly respond to a tunable surface and the bulk properties (electric, dielectric and thermal) of plain and nanocomposite PLLA films by triggering a mechanotransduction axis. This stepwise process starts from tethering of the cells' focal adhesion proteins to the surface, together with the adherens junctions between cells. Both complexes transmit traction forces to F-Actin stress fibres that link Filamin-A and Myosin-IIA proteins, generating a biological scaffold, with increased stiffening conformation from PLLA to PLLA/MWCNTs, and enable the nucleoskeleton proteins to boost chromatin reprogramming processes. Herein, the opposite expression of NANOG and GATA6 transcription factors, together with other lineage specification related proteins, steer spheroids toward an Epiblast-like or Primitive Endoderm-like lineage commitment, depending on the absence or presence of 1 wt% MWCNTs, respectively. This work represents a pioneering effort to create a stem cell/material interface that can model the stem cell fate transition under growth culture conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Miscibility, crystallization and mechanical properties of biodegradable blends of poly(L-lactic acid) and poly(butylene succinate-b-ethylene succinate) multiblock copolymer

International Nuclear Information System (INIS)

Jiao, Ling; Huang, Cai-Li; Zeng, Jian-Bing; Wang, Yu-Zhong; Wang, Xiu-Li

2012-01-01

Highlights: ► The blend of PLLA and PBES showed limited miscibility. ► The crystallization rate of PLLA was accelerated by blending with PBES. ► The crystal structures of PLLA and PBES did not change. - Abstract: Poly(L-lactic acid) (PLLA) is regarded as one of the most promising biobased and biodegradable polymers. However, its application was restricted due to the brittle nature. In the present study, PLLA was blended with a novel biodegradable flexible multiblock copolymer, poly(butylene succinate-b-ethylene succinate) (PBES) to produce new biodegradable materials. PLLA/PBES blends with different composition were prepared by solution blending and casting method with chloroform as a mutual solvent. Miscibility, crystallization behavior, and mechanical properties of the blends were investigated by differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and tensile tests. The results indicated that PLLA and PBES showed limited miscibility in the amorphous phase. The crystallization rate of PLLA was accelerated with the increase of PBES in the blends while the crystallization mechanism did not change. The results of tensile tests suggest that the blends showed longer elongation at break than neat PLLA. The elongation at break of PLLA was obtained to be 10%, and those of PLLA/PBES 80/20, 60/40, 40/60 and 20/80 were 29, 110, 442, and 455%, respectively.

Mechanical and biodegradable properties of porous titanium filled with poly-L-lactic acid by modified in situ polymerization technique.

Science.gov (United States)

Nakai, Masaaki; Niinomi, Mitsuo; Ishii, Daisuke

2011-10-01

Porous titanium (pTi) can possess a low Young's modulus equal to that of human bone, depending on its porosity. However, the mechanical strength of pTi deteriorates greatly with increasing porosity. On the other hand, certain medical polymers exhibit biofunctionalities, which are not possessed intrinsically by metallic materials. Therefore, a biodegradable medical polymer, poly-L-lactic acid (PLLA), was used to fill in the pTi pores using a modified in-situ polymerization technique. The mechanical and biodegradable properties of pTi filled with PLLA (pTi/PLLA) as fabricated by this technique and the effects of the PLLA filling were evaluated in this study. The pTi pores are almost completely filled with PLLA by the developed process (i.e., technique). The tensile strength and tensile Young's modulus of pTi barely changes with the PLLA filling. However, the PLLA filling improves the compressive 0.2% proof stress of pTi having any porosity and increases the compressive Young's modulus of pTi having relatively high porosity. This difference between the tensile and compressive properties of pTi/PLLA is considered to be caused by the differing resistances of PLLA in the pores to tensile and compressive deformations. The PLLA filled into the pTi pores degrades during immersion in Hanks' solution at 310 K. The weight loss due to PLLA degradation increases with increasing immersion time. However, the rate of weight loss of pTi/PLLA during immersion decreases with increasing immersion time. Hydroxyapatite formation is observed on the surface of pTi/PLLA after immersion for ≥8 weeks. The decrease in the weight-loss rate may be caused by weight gain due to hydroxyapatite formation and/or the decrease in contact area with Hanks' solution caused by its formation on the surface of pTi/PLLA. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bioevaluation study of {sup 32}P-CP-PLLA particle brachytherapy in a rabbit VX2 lung tumor model

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Xu Yuping [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi 214063 (China); Yang Min, E-mail: ymzfk@yahoo.com.hk [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi 214063 (China); Pan Donghui; Wang Lizhen [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, 20 Qianrong Road, Wuxi 214063 (China); Liu Lu; Huang Peilin [Nuclear Medicine Institute of Southeast University, Nanjing 210009 (China); Shao Guoqiang [Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing University, Nanjing 210006 (China)

2012-04-15

Objective: The purpose of this study was to investigate the therapy effects of intratumoral administration of {sup 32}P-CP-PLLA particles in a rabbit VX2 lung tumor model. Methods: 16 rabbits with tumors were randomly divided into 4 groups. 4 rabbits served as untreated controls, and others received intratumoral administration of {sup 32}P-CP-PLLA particles with CT guidance. The total radioactivities in treated groups were as follows: a low activity was 93 MBq (n=4) (group 1), a medium activity was 185 MBq (n=4) (group 2) and a high activity was 370 MBq (n=4) (group 3). Brachytherapy treated VX2 tumors underwent {sup 18}F-FDG PET/CT at 0 day, 3 day, 7 day and 14 day postinjection. In control group, {sup 18}F-FDG PET/CT images were acquired at the same time points but without any treatment. Bremsstrahlung SPECT images were performed at 14 days after intratumoral brachytherapy in treated groups. After Bremsstrahlung SPECT and last {sup 18}F-FDG PET/CT imagings, the rabbits were euthanized and the tumors were removed for histological examination. Results: Bremsstrahlung SPECT images study indicated that there was no leakage of {sup 32}P out of the injection site at 14 days after treatment. Compared with the control, the tumor volumes in treated groups significantly decreased, and {sup 32}P-CP-PLLA particle produced a reduction in maximum or mean SUV of VX2 tumor (p<0.05). The percentage changes in maximum and mean SUV gradually decreased in group 1 and group 2 from day 3 to day 14 (p<0.05). A transient increase in {sup 18}F-FDG accumulation at group 3 occurred due to the inflammatory reaction elements. Activity dependence was seen in HE and PCNA staining after 14 days treatment among three treated groups (p<0.05). Conclusions: Our data suggested that {sup 32}P-CP-PLLA particle localized on the injecting sites. This novel brachytherapy device efficiently suppressed the growth of the VX2 tumors implanted in the rabbit. - Highlights: Black-Right-Pointing-Pointer {sup 32

Chitosan/γ-poly(glutamic acid) scaffolds with surface-modified albumin, elastin and poly-l-lysine for cartilage tissue engineering.

Science.gov (United States)

Kuo, Yung-Chih; Ku, Hao-Fu; Rajesh, Rajendiran

2017-09-01

Cartilage has limited ability to self-repair due to the absence of blood vessels and nerves. The application of biomaterial scaffolds using biomimetic extracellular matrix (ECM)-related polymers has become an effective approach to production of engineered cartilage. Chitosan/γ-poly(glutamic acid) (γ-PGA) scaffolds with different mass ratios were prepared using genipin as a cross-linker and a freeze-drying method, and their surfaces were modified with elastin, human serum albumin (HSA) and poly-l-lysine (PLL). The scaffolds were formed through a complex between NH 3 + of chitosan and COO - of γ-PGA, confirmed by Fourier transform infrared spectroscopy, and exhibited an interconnected porous morphology in field emission scanning electron microscopy analysis. The prepared chitosan/γ-PGA scaffolds, at a 3:1 ratio, obtained the required porosity (90%), pore size (≥100μm), mechanical strength (compressive strength>4MPa, Young's modulus>4MPa) and biodegradation (30-60%) for articular cartilage tissue engineering applications. Surface modification of the scaffolds showed positive indications with improved activity toward cell proliferation (deoxyribonucleic acid), cell adhesion and ECM (glycoaminoglycans and type II collagen) secretion of bovine knee chondrocytes compared with unmodified scaffolds. In caspase-3 detection, elastin had a higher inhibitory effect on chondrocyte apoptosis in vitro, followed by HSA, and then PLL. We concluded that utilizing chitosan/γ-PGA scaffolds with surface active biomolecules, including elastin, HSA and PLL, can effectively promote the growth of chondrocytes, secrete ECM and improve the regenerative ability of cartilaginous tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of γ-rays irradiation on poly (L-lactic acid)

International Nuclear Information System (INIS)

Peng Chaorong; Chen Hao; Wang Jingxia; Wu Ling; Chen Zhuping; Deng Huachuan

2008-01-01

Poly (L-lactic acid) was irradiated by γ-rays. The effects of absorbed dose on viscosity average molecular weight, crystallization and thermal weight loss in irradiated condition under vacuum, nitrogen, air and oxygen were investigated, which were characterized by using ubbelohde viscometer, differential scamming calorimeter (DSC), polarized microscope and thermogravimetry analysis (TGA). Viscosity average molecular weight of PLLA decreases with increment of absorbed dose and viscosity average molecular weight of PLLA irradiated in vacuum is highest among the different irradiated condition at same absorbed dose. Both degree and rates of crystallization increase with increment of absorbed dose and TGA curves of PLLA irradiated under vacuum or nitrogen are shifted towards higher temperature compare with un-irradiated sample at the absorbed dose from 6-40kGy. The weight loss of PLLA irradiated under oxygen is lower than that under vacuum at absorbed dose of 6kGy. (authors)

Biosafety of the Novel Vancomycin-loaded Bone-like Hydroxyapatite/Poly-amino Acid Bony Scaffold

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Zhi-Dong Cao

2016-01-01

Full Text Available Background: Recently, local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration, and thereby effectively decrease any systemic toxicity and side effects. A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA, which was demonstrated to exhibit both porosity and perfect biodegradability. The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo. Methods: According to the ISO rules for medical implant biosafety, for in vitro tests, the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood, with simultaneous creation of positive control and negative control groups. The growth condition of L929 cells and hemolytic ratio were respectively evaluated after various incubation periods. For in vivo tests, a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established. After bacterial identification, the drug-loaded scaffold, drug-unloaded BHA/PAA, and poly (methyl methacrylate were implanted, and a blank control group was also set up. Subsequently, the in vivo blood drug concentrations were measured, and the kidney and liver functions were evaluated. Results: In the in vitro tests, the cytotoxicity grades of V-BHA/PAA and BHA/PAA-based on the relative growth rate were all below 1. The hemolysis ratios of V-BHA/PAA and BHA/PAA were 2.27% and 1.42%, respectively, both below 5%. In the in vivo tests, the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L, and the function and histomorphology of the liver and kidney were all normal. Conclusion: According to ISO standards, the V-BHA/PAA scaffold

Hyaluronic acid doped-poly(3,4-ethylenedioxythiophene)/chitosan/gelatin (PEDOT-HA/Cs/Gel) porous conductive scaffold for nerve regeneration

International Nuclear Information System (INIS)

Wang, Shuping; Guan, Shui; Zhu, Zhibo; Li, Wenfang; Liu, Tianqing; Ma, Xuehu

2017-01-01

Conducting polymer, as a “smart” biomaterial, has been increasingly used to construct tissue engineered scaffold for nerve tissue regeneration. In this study, a novel porous conductive scaffold was prepared by incorporating conductive hyaluronic acid (HA) doped-poly(3,4-ethylenedioxythiophene) (PEDOT-HA) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physicochemical characteristics of Cs/Gel scaffold with 0–10 wt% PEDOT-HA were analyzed and the results indicated that the incorporation of PEDOT-HA into scaffold increased the electrical and mechanical properties while decreasing the porosity and water absorption. Moreover, in vitro biodegradation of scaffold displayed a declining trend with the PEDOT-HA content increased. About the biocompatibility of conductive scaffold, neuron-like rat phaeochromocytoma (PC12) cells were cultured in scaffold to evaluate cell adhesion and growth. 8% PEDOT-HA/Cs/Gel scaffold had a higher cell adhesive efficiency and cell viability than the other conductive scaffolds. Furthermore, cells in the scaffold with 8 wt% PEDOT-HA expressed higher synapse growth gene of GAP43 and SYP compared with Cs/Gel control group. These results suggest that 8%PEDOT-HA/Cs/Gel scaffold is an attractive cell culture conductive substrate which could support cell adhesion, survival, proliferation, and synapse growth for the application in nerve tissue regeneration. - Highlights: • A porous conductive scaffold was prepared by freeze-drying method. • Conductive scaffold could support PC12 cells adhesion, survival, and proliferation. • Cells in conductive scaffold expressed high synapse growth gene of GAP43 and SYP.

Hyaluronic acid doped-poly(3,4-ethylenedioxythiophene)/chitosan/gelatin (PEDOT-HA/Cs/Gel) porous conductive scaffold for nerve regeneration

Energy Technology Data Exchange (ETDEWEB)

Wang, Shuping; Guan, Shui, E-mail: guanshui@dlut.edu.cn; Zhu, Zhibo; Li, Wenfang; Liu, Tianqing; Ma, Xuehu

2017-02-01

Conducting polymer, as a “smart” biomaterial, has been increasingly used to construct tissue engineered scaffold for nerve tissue regeneration. In this study, a novel porous conductive scaffold was prepared by incorporating conductive hyaluronic acid (HA) doped-poly(3,4-ethylenedioxythiophene) (PEDOT-HA) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physicochemical characteristics of Cs/Gel scaffold with 0–10 wt% PEDOT-HA were analyzed and the results indicated that the incorporation of PEDOT-HA into scaffold increased the electrical and mechanical properties while decreasing the porosity and water absorption. Moreover, in vitro biodegradation of scaffold displayed a declining trend with the PEDOT-HA content increased. About the biocompatibility of conductive scaffold, neuron-like rat phaeochromocytoma (PC12) cells were cultured in scaffold to evaluate cell adhesion and growth. 8% PEDOT-HA/Cs/Gel scaffold had a higher cell adhesive efficiency and cell viability than the other conductive scaffolds. Furthermore, cells in the scaffold with 8 wt% PEDOT-HA expressed higher synapse growth gene of GAP43 and SYP compared with Cs/Gel control group. These results suggest that 8%PEDOT-HA/Cs/Gel scaffold is an attractive cell culture conductive substrate which could support cell adhesion, survival, proliferation, and synapse growth for the application in nerve tissue regeneration. - Highlights: • A porous conductive scaffold was prepared by freeze-drying method. • Conductive scaffold could support PC12 cells adhesion, survival, and proliferation. • Cells in conductive scaffold expressed high synapse growth gene of GAP43 and SYP.

Surface Hydrophilicity of Poly(l-Lactide Acid Polymer Film Changes the Human Adult Adipose Stem Cell Architecture

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Chiara Argentati

2018-02-01

Full Text Available Current knowledge indicates that the molecular cross-talk between stem cells and biomaterials guides the stem cells’ fate within a tissue engineering system. In this work, we have explored the effects of the interaction between the poly(l-lactide acid (PLLA polymer film and human adult adipose stem cells (hASCs, focusing on the events correlating the materials’ surface characteristics and the cells’ plasma membrane. hASCs were seeded on films of pristine PLLA polymer and on a PLLA surface modified by the radiofrequency plasma method under oxygen flow (PLLA+O2. Comparative experiments were performed using human bone-marrow mesenchymal stem cells (hBM-MSCs and human umbilical matrix stem cells (hUCMSCs. After treatment with oxygen-plasma, the surface of PLLA films became hydrophilic, whereas the bulk properties were not affected. hASCs cultured on pristine PLLA polymer films acquired a spheroid conformation. On the contrary, hASCs seeded on PLLA+O2 film surface maintained the fibroblast-like morphology typically observed on tissue culture polystyrene. This suggests that the surface hydrophilicity is involved in the acquisition of the spheroid conformation. Noteworthy, the oxygen treatment had no effects on hBM-MSC and hUCMSC cultures and both stem cells maintained the same shape observed on PLLA films. This different behavior suggests that the biomaterial-interaction is stem cell specific.

Optimization of a biomimetic poly-(lactic acid) ligament scaffold

Science.gov (United States)

Uehlin, Andrew F.

The anterior cruciate ligament (ACL) is the most commonly injured ligament of the knee, often requiring orthopedic reconstruction using autograft or allograph tissue, both with significant disadvantages. As a result, tissue engineering an ACL replacement graft has been heavily investigated. The present study attempts to replicate the morphology and mechanical properties of the ACL using a nanomatrix composite of highly-aligned poly(lactic acid) (PLA) fibers with various surface and biochemical modifications. Additionally, this study attempts to recreate the natural mineralization gradient found at the ACL enthesis onto the scaffold, capable of inducing a favorable cellular response in vitro. Unidirectional electrospinning was used to create nanofibers of PLA, followed by an induced degradation of the nanofibers via 0.25M NaOH hydrolysis. The effects of the unidirectional electrospinning as well as the effects of NaOH hydrolysis on fiber alignment, fiber diameter, surface morphology, crystallinity, in vitro swelling, immobilization of fibrin, and mechanical properties were investigated, resulting in a modified morphology correlating to the microstructure of native ligament tissue with similar mechanical properties. Furthering the development of the PLA nanomatrix composite, a bioinkjet printer was used to immobilize nanoparticulate hydroxyapatite (HANP) on the surface of the scaffold. A series of 300pL droplets of HANP bioink were printed over a gradient pattern mimetic of (and spatially corresponding to) the mineralization gradient found over the microanatomy at the ACL enthesis. Proliferation and differentiation response of human mesenchymal stem cells (hMSCs) in vitro was assessed on a variety of conditions and combinations of the PLA nanofiber scaffold surface modifications (inclusive and exclusive of HANP, fibrin, and various time dependent NaOH treatments). It was found that a combinatory effect of the HANP gradient with fibrin on 20 minute NaOH treated PLA

Porous stable poly(lactic acid)/ethyl cellulose/hydroxyapatite composite scaffolds prepared by a combined method for bone regeneration.

Science.gov (United States)

Mao, Daoyong; Li, Qing; Bai, Ningning; Dong, Hongzhou; Li, Daikun

2018-01-15

A major challenge in bone tissue engineering is the development of biomimetic scaffolds which should simultaneously meet mechanical strength and pore structure requirements. Herein, we combined technologies of high concentration solvent casting, particulate leaching, and room temperature compression molding to prepare a novel poly(lactic acid)/ethyl cellulose/hydroxyapatite (PLA/EC/HA) scaffold. The functional, structural and mechanical properties of the obtained porous scaffolds were characterized. The results indicated that the PLA/EC/HA scaffolds at the 20wt% HA loading level showed optimal mechanical properties and desired porous structure. Its porosity, contact angle, compressive yield strength and weight loss after 56days were 84.28±7.04%, 45.13±2.40°, 1.57±0.09MPa and 4.77±0.32%, respectively, which could satisfy the physiological demands to guide bone regeneration. Thus, the developed scaffolds have potential to be used as a bone substitute material for bone tissue engineering application. Copyright © 2017. Published by Elsevier Ltd.

Quantitative analysis of mechanical and electrostatic properties of poly(lactic) acid fibers and poly(lactic) acid—carbon nanotube composites using atomic force microscopy

International Nuclear Information System (INIS)

Iqbal, Qais; Bernstein, Peter; Zhu, Yazhe; Rahamim, Joseph; Cebe, Peggy; Staii, Cristian

2015-01-01

We use atomic force microscopy (AFM) to perform a systematic quantitative characterization of the elastic modulus and dielectric constant of poly(L-lactic acid) electrospun nanofibers (PLLA), as well as composites of PLLA fibers with 1.0 wt% embedded multiwall carbon nanotubes (MWCNTs–PLLA). The elastic moduli are measured in the fiber skin region via AFM nanoindentation, and the dielectric constants are determined by measuring the phase shifts obtained via electrostatic force microscopy (EFM). We find that the average value for the elastic modulus for PLLA fibers is (9.8 ± 0.9) GPa, which is a factor of 2 larger than the measured average elastic modulus for MWCNT–PLLA composites (4.1 ± 0.7) GPa. We also use EFM to measure dielectric constants for both types of fibers. These measurements show that the dielectric constants of the MWCNT–PLLA fibers are significantly larger than the corresponding values obtained for PLLA fiber. This result is consistent with the higher polarizability of the MWCNT–PLLA composites. The measurement methods presented are general, and can be applied to determine the mechanical and electrical properties of other polymers and polymer nanocomposites. (paper)

Polyelectrolyte-complex nanostructured fibrous scaffolds for tissue engineering

International Nuclear Information System (INIS)

Verma, Devendra; Katti, Kalpana S.; Katti, Dinesh R.

2009-01-01

In the current work, polyelectrolyte complex (PEC) fibrous scaffolds for tissue engineering have been synthesized and a mechanism of their formation has been investigated. The scaffolds are synthesized using polygalacturonic acid and chitosan using the freeze drying methodology. Highly interconnected pores of sizes in the range of 5-20 μm are observed in the scaffolds. The thickness of the fibers was found to be in the range of 1-2 μm. Individual fibers have a nanogranular structure as observed using AFM imaging. In these scaffolds, PEC nanoparticles assemble together at the interface of ice crystals during freeze drying process. Further investigation shows that the freezing temperature and concentration have a remarkable effect on structure of scaffolds. Biocompatibility studies show that scaffold containing chitosan, polygalacturonic acid and hydroxyapatite promotes cell adhesion and proliferation. On the other hand, cells on scaffolds fabricated without hydroxyapatite nanoparticles showed poor adhesion.

Influence of fiber surface-treatment on interfacial property of poly(L-lactic acid)/ramie fabric biocomposites under UV-irradiation hydrothermal aging

Energy Technology Data Exchange (ETDEWEB)

Chen Dakai; Li Jing [Institute of Nano- and Bio-polymeric Materials, School of Material Science and Engineering, Tongji University, Shanghai 200092 (China); Ren Jie, E-mail: renjie6598@163.com [Institute of Nano- and Bio-polymeric Materials, School of Material Science and Engineering, Tongji University, Shanghai 200092 (China) and Key Laboratory of Advanced Civil Engineering Materials, Ministry of Education, Tongji University, Shanghai 200092 (China)

2011-04-15

Research highlights: {yields} Ramie fiber is used as reinforced material because it's lowest water absorption among sisal, jute, kenaf and ramie fiber. {yields} Fiber surface-treatment can cause an accelerated decline in mechanical properties of PLLA biocomposites after UV-irradiation hydrothermal aging. {yields} The swelling of ramie fibers reduce the interfacial adhesive strength in critical area of PLLA matrix-ramie fabric interface. - Abstract: The present study is devoted to the effect of fiber surface-treatment on the interfacial property of biocomposites based on poly(L-lactic acid) (PLLA) and ramie fabric. Ramie fiber is used as reinforced material because it's lowest water absorption among sisal, jute, kenaf and ramie fiber. Fiber surface-treatment can increase the water absorption of natural fibers. SEM images show that PLLA biocomposites with treated ramie fabric exhibit better interfacial adhesion character. DMA results show that the storage modulus of PLLA biocomposites with treated ramie increase compared to neat PLLA and PLLA biocomposites with untreated ramie. Unexpectedly, fiber surface-treatment can cause an accelerated decline in mechanical properties of PLLA biocomposites after UV-irradiation hydrothermal aging. Finally, GPC results show that there is no obvious decline in the molecular weight of PLLA. The main reason for this decline is the interfacial destructive effect induced by the water absorption of ramie fiber.

Non-isothermal Crystallization, Thermal Stability, and Mechanical Performance of Poly(L-lactic acid/Barium Phenylphosphonate Systems

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Cai Yan-Hua

2017-11-01

Full Text Available The introduction of a nucleating agent in semi-crystalline polymers is a frequently utilized way to improve the crystallization performance, and the use of a nucleating agent has a very great effect on the performance of the polymer in other areas including thermal stability and mechanical properties. In this investigation, barium phenylphosphonate (BaP was prepared as a crystallization accelerator for Poly(L-lactic acid (PLLA, and the non-isothermal crystallization behavior, thermal stability, and mechanical properties of PLLA modified by BaP were investigated using differential scanning calorimetry (DSC, X-ray diffraction (XRD, thermogravimetric analysis (TGA, and electronic tensile testing. Non-isothermal crystallization analysis showed that the BaP could significantly accelerate the crystallization of PLLA, and the non-isothermal crystallization peak shifted to a higher temperature with increasing concentration of BaP, however, the corresponding crystallization peak became wider. XRD results after non-isothermal crystallization confirmed the non-isothermal crystallization DSC results. Additionally, the addition of BaP did not change the crystal form of PLLA. A comparative study on thermal stability indicated that BaP decreased the onset decomposition temperature of PLLA, resulting from the formation of more tiny and imperfect crystals. Whereas the influence of BaP on the thermal decomposition profile of PLLA was negligible. In terms of mechanical properties, the tensile strength and elastic modulus of PLLA/BaP increased compared to the virgin PLLA, unfortunately, the elongation at break decreased.

Surface biofunctionalization of three-dimensional porous poly(lactic acid) scaffold using chitosan/OGP coating for bone tissue engineering.

Science.gov (United States)

Zeng, Sen; Ye, Jianhua; Cui, Zhixiang; Si, Junhui; Wang, Qianting; Wang, Xiaofeng; Peng, Kaiping; Chen, Wenzhe

2017-08-01

As one of the stimulators on bone formation, osteogenic growth peptide (OGP) improves both proliferation and differentiation of the bone cells in vitro and in vivo. The aim of this work was the preparation of three dimensional porous poly(lactic acid) (PLA) scaffold with high porosity from PLA-dioxane-water ternary system with the use of vacuum-assisted solvent casting, phase separation, solvent extraction and particle leaching methods. Then, by surface coating of PLA scaffold with chitosan (CS)/OGP solution, biofunctionalization of PLA scaffold had been completed for application in bone regeneration. The effects of frozen temperature (-20, -50, -80°C) and PLA solution concentration (10, 12, 14wt%) on the microstructure, water absorption, porosity, hydrophilicity, mechanical properties, and biocompatibility of PLA and CS/OGP/PLA scaffold were investigated. Results showed that both PLA and CS/OGP/PLA scaffolds have an interconnected network structure and a porosity of up to 96.1% and 91.5%, respectively. The CS/OGP/PLA scaffold exhibited better hydrophilicity and mechanical properties than that of uncoated PLA scaffold. Moreover, the results of cell culture test showed that CS/OGP coating could stimulate the proliferation and growth of osteoblast cells on CS/OGP/PLA scaffold. These finding suggested that the surface biofunctionalization by CS/OGP coating layer could be an effective method on enhancing cell adhesion to synthetic polymer-based scaffolds in tissue engineering application and the developed porous CS/OGP/PLA scaffold should be considered as alternative biomaterials for bone regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Immobilized Lentivirus Vector on Chondroitin Sulfate-Hyaluronate Acid-Silk Fibroin Hybrid Scaffold for Tissue-Engineered Ligament-Bone Junction

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Liguo Sun

2014-01-01

Full Text Available The lack of a fibrocartilage layer between graft and bone remains the leading cause of graft failure after anterior cruciate ligament (ACL reconstruction. The objective of this study was to develop a gene-modified silk cable-reinforced chondroitin sulfate-hyaluronate acid-silk fibroin (CHS hybrid scaffold for reconstructing the fibrocartilage layer. The scaffold was fabricated by lyophilizing the CHS mixture with braided silk cables. The scanning electronic microscopy (SEM showed that microporous CHS sponges were formed around silk cables. Each end of scaffold was modified with lentiviral-mediated transforming growth factor-β3 (TGF-β3 gene. The cells on scaffold were transfected by bonded lentivirus. In vitro culture demonstrated that mesenchymal stem cells (MSCs on scaffolds proliferated vigorously and produced abundant collagen. The transcription levels of cartilage-specific genes also increased with culture time. After 2 weeks, the MSCs were distributed uniformly throughout scaffold. Deposited collagen was also found to increase. The chondral differentiation of MSCs was verified by expressions of collagen II and TGF-β3 genes in mRNA and protein level. Histology also confirmed the production of cartilage extracellular matrix (ECM components. The results demonstrated that gene-modified silk cable-reinforced CHS scaffold was capable of supporting cell proliferation and differentiation to reconstruct the cartilage layer of interface.

Non-crystalline composite tissue engineering scaffolds using boron-containing bioactive glass and poly(d,l-lactic acid) coatings

International Nuclear Information System (INIS)

Mantsos, T; Chatzistavrou, X; Roether, J A; Boccaccini, A R; Hupa, L; Arstila, H

2009-01-01

The aim of this study was the fabrication of three-dimensional, highly porous, bioactive scaffolds using a recently developed bioactive glass powder, denominated '0106', with nominal composition (in wt%): 50 SiO 2 , 22.6 CaO, 5.9 Na 2 O, 4 P 2 O 5 , 12 K 2 O, 5.3 MgO and 0.2 B 2 O 3 . The optimum sintering conditions for the fabrication of scaffolds by the foam-replica method were identified (sintering temperature: 670 deg, C and dwell time: 5 h). Composite samples were also fabricated by applying a biopolymer coating of poly( D,L -lactic acid) (PDLLA) using a dip coating process. The average compressive strength values were 0.4 MPa for uncoated and 0.6 MPa for coated scaffolds. In vitro bioactivity studies in simulated body fluid (SBF) showed that a carbonate hydroxyapatite (HCAp) layer was deposited on uncoated and coated scaffolds after only 4 days of immersion in SBF, demonstrating the high in vitro bioactivity of the scaffolds. It was also confirmed that the scaffold structure remained amorphous (no crystallization) after the specific heat treatment used, with scaffolds exhibiting mechanical properties and bioactivity suitable for use in bone tissue engineering applications.

Non-crystalline composite tissue engineering scaffolds using boron-containing bioactive glass and poly(d,l-lactic acid) coatings

Energy Technology Data Exchange (ETDEWEB)

Mantsos, T; Chatzistavrou, X; Roether, J A; Boccaccini, A R [Department of Materials, Imperial College London, South Kensington Campus, London SW7 2AZ (United Kingdom); Hupa, L; Arstila, H, E-mail: a.boccaccini@imperial.ac.u [Process Chemistry Centre, Abo Akademi University, Piispankatu 8, FI-20500 Turku (Finland)

2009-10-15

The aim of this study was the fabrication of three-dimensional, highly porous, bioactive scaffolds using a recently developed bioactive glass powder, denominated '0106', with nominal composition (in wt%): 50 SiO{sub 2}, 22.6 CaO, 5.9 Na{sub 2}O, 4 P{sub 2}O{sub 5}, 12 K{sub 2}O, 5.3 MgO and 0.2 B{sub 2}O{sub 3}. The optimum sintering conditions for the fabrication of scaffolds by the foam-replica method were identified (sintering temperature: 670 deg, C and dwell time: 5 h). Composite samples were also fabricated by applying a biopolymer coating of poly({sub D,L}-lactic acid) (PDLLA) using a dip coating process. The average compressive strength values were 0.4 MPa for uncoated and 0.6 MPa for coated scaffolds. In vitro bioactivity studies in simulated body fluid (SBF) showed that a carbonate hydroxyapatite (HCAp) layer was deposited on uncoated and coated scaffolds after only 4 days of immersion in SBF, demonstrating the high in vitro bioactivity of the scaffolds. It was also confirmed that the scaffold structure remained amorphous (no crystallization) after the specific heat treatment used, with scaffolds exhibiting mechanical properties and bioactivity suitable for use in bone tissue engineering applications.

Micropore Geometry Manipulation by Macroscopic Deformation Based on Shape Memory Effect in Porous PLLA Membrane and its Enhanced Separation Performance.

Science.gov (United States)

Zhao, Jingxin; Yang, Qiucheng; Wang, Tao; Wang, Lian; You, Jichun; Li, Yongjin

2017-12-20

An effective strategy to tailor the microporous structures has been developed based on the shape memory effect in porous poly(l-lactic acid) membranes in which tiny crystals and amorphous matrix play the roles of shape-fixed phase and reversible-phase, respectively. Our results indicate that not only PLLA membranes but micropores exhibit shape memory properties. The proportional deformations on two scales have been achieved by uniaxial or biaxial tension, providing a facile way to manipulate continuously the size and the orientation degree of pores on microscale. The enhanced separation performance has been validated by taking polystyrene colloids with varying diameters as an example.

MRI study of bioabsorbable poly-L-lactic acid devices used for fixation of fracture and osteotomies

International Nuclear Information System (INIS)

Marumo, Keishi; Sato, Yasutomo; Suzuki, Hidehiko; Kurosaka, Daisaburo

2006-01-01

The overall clinical results of bioabsorbable fixation devices made of poly-L-lactic acid (PLLA) used for fixation of fractures, bone grafting, and osteotomies have been favorable. However, clinical studies demonstrated no sign of normal bony architecture restored after surgery, although implant channels had been filled with fibrous tissue. The purpose of the present retrospective study was to examine the extent of structural changes in PLLA devices (PLLA-Ds) for fixation of rotational acetabular osteotomies and displaced malleolar ankle fractures using magnetic resonance imaging (MRI). Altogether, 14 patients with osteoarthritis of hip joints and 15 with displaced malleolar ankle fractures were operated on using PLLA-D (NEOFIX). Of these patients, 22 were finally enrolled in the study, and the period from operation to the time of the study ranged from 17 to 78 months. The postoperative radiographic findings were evaluated for union, and changes around the implant holes were classified as sclerosis, resorption, or no change. MRI was carried out to estimate changes in the PLLA-Ds. Bone union was obtained in all cases; clinical complications such as infection, joint effusion, soft tissue irritation due to PLLA-D deviation, and motion pain in the joints were not observed. The MRI study suggested that water content in PLLA-D increased mainly due to biodegradation and that implants were not replaced by bony tissue. The PLLA-Ds were degraded but were not replaced by bony tissue during the observation period. Considering these findings and the assumption that in bony tissues mechanical strength of PLLA-D decreases with time, attention should be paid to mechanical insufficiency, which may occur when the cross-sectional area of a PLLA-D extends beyond the cross-sectional area of the osteosynthesis site. (author)

Enhancement of human mesenchymal stem cell infiltration into the electrospun poly(lactic-co-glycolic acid) scaffold by fluid shear stress.

Science.gov (United States)

Kim, Min Sung; Lee, Mi Hee; Kwon, Byeong-Ju; Koo, Min-Ah; Seon, Gyeung Mi; Park, Jong-Chul

The infiltration of the cells into the scaffolds is important phenomenon to give them good biocompatibility and even biodegradability. Fluid shear stress is one of the candidates for the infiltration of cells into scaffolds. Here we investigated the directional migration of human mesenchymal stem cells and infiltration into PLGA scaffold by fluid shear stress. The human mesenchymal stem cells showed directional migrations following the direction of the flow (8, 16 dyne/cm(2)). In the scaffold models, the fluid shear stress (8 dyne/cm(2)) enhanced the infiltration of cells but did not influence on the infiltration of Poly(lactic-co-glycolic acid) particles. Copyright © 2015 Elsevier Inc. All rights reserved.

Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model

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Ge Zigang; Tian Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo Jinfei; Cao Tong, E-mail: omscaot@nus.edu.s [Stem Cell Laboratory, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074 (Singapore)

2009-04-15

Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models. (communication)

Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model

International Nuclear Information System (INIS)

Ge Zigang; Tian Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo Jinfei; Cao Tong

2009-01-01

Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models. (communication)

Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid

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Sachiro eKakinoki

2014-07-01

Full Text Available We developed a microfibrous poly(L-lactic acid (PLLA nerve conduit with a three-layered structure to simultaneously enhance nerve regeneration and prevent adhesion of surrounding tissue. The inner layer was composed of PLLA microfiber containing 25% elastin-laminin mimetic protein (AG73-(VPGIG30 that promotes neurite outgrowth. The thickest middle layer was constructed of pure PLLA microfibers that impart the large mechanical stremgth to the conduit. A 10% poly(ethylene glycol was added to the outer layer to prevent the adhesion with the surrounding tissue. The AG73-(VPGIG30 composisting of an elastin-like repetitive sequence (VPGIG30 and a laminin-derived sequence (RKRLQVQLSIRT: AG73 was biosynthesized using Escherichia coli. The PLLA microfibrous conduits were fabricated using an electrospinning procedure. AG73-(VPGIG30 was successfully mixed in the PLLA microfibers, and the PLLA/AG73-(VPGIG30 microfibers were stable under physiological conditions. The PLLA/AG73-(VPGIG30 microfibers enhanced adhesion and neurite outgrowth of PC12 cells. The electrospun microfibrous conduit with a three-layered structure was implanted for bridging a 2.0-cm gap in the tibial nerve of a rabbit. Two months after implantation, no adhesion of surrounding tissue was observed, and the action potential was slightly improved in the nerve conduit with the PLLA/AG73-(VPGIG30 inner layer.

Three-layer microfibrous peripheral nerve guide conduit composed of elastin-laminin mimetic artificial protein and poly(L-lactic acid)

Science.gov (United States)

Kakinoki, Sachiro; Nakayama, Midori; Moritan, Toshiyuki; Yamaoka, Tetsuji

2014-07-01

We developed a microfibrous poly(L-lactic acid) (PLLA) nerve conduit with a three-layered structure to simultaneously enhance nerve regeneration and prevent adhesion of surrounding tissue. The inner layer was composed of PLLA microfiber containing 25% elastin-laminin mimetic protein (AG73-(VPGIG)30) that promotes neurite outgrowth. The thickest middle layer was constructed of pure PLLA microfibers that impart the large mechanical stremgth to the conduit. A 10% poly(ethylene glycol) was added to the outer layer to prevent the adhesion with the surrounding tissue. The AG73-(VPGIG)30 composisting of an elastin-like repetitive sequence (VPGIG)30 and a laminin-derived sequence (RKRLQVQLSIRT: AG73) was biosynthesized using Escherichia coli. The PLLA microfibrous conduits were fabricated using an electrospinning procedure. AG73-(VPGIG)30 was successfully mixed in the PLLA microfibers, and the PLLA/AG73-(VPGIG)30 microfibers were stable under physiological conditions. The PLLA/AG73-(VPGIG)30 microfibers enhanced adhesion and neurite outgrowth of PC12 cells. The electrospun microfibrous conduit with a three-layered structure was implanted for bridging a 2.0-cm gap in the tibial nerve of a rabbit. Two months after implantation, no adhesion of surrounding tissue was observed, and the action potential was slightly improved in the nerve conduit with the PLLA/AG73-(VPGIG)30 inner layer.

A Facile and Eco-friendly Route to Fabricate Poly(Lactic Acid) Scaffolds with Graded Pore Size.

Science.gov (United States)

Scaffaro, Roberto; Lopresti, Francesco; Botta, Luigi; Maio, Andrea; Sutera, Fiorenza; Mistretta, Maria Chiara; La Mantia, Francesco Paolo

2016-10-17

Over the recent years, functionally graded scaffolds (FGS) gaineda crucial role for manufacturing of devices for tissue engineering. The importance of this new field of biomaterials research is due to the necessity to develop implants capable of mimicking the complex functionality of the various tissues, including a continuous change from one structure or composition to another. In this latter context, one topic of main interest concerns the design of appropriate scaffolds for bone-cartilage interface tissue. In this study, three-layered scaffolds with graded pore size were achieved by melt mixing poly(lactic acid) (PLA), sodium chloride (NaCl) and polyethylene glycol (PEG). Pore size distributions were controlled by NaCl granulometry and PEG solvation. Scaffolds were characterized from a morphological and mechanical point of view. A correlation between the preparation method, the pore architecture and compressive mechanical behavior was found. The interface adhesion strength was quantitatively evaluated by using a custom-designed interfacial strength test. Furthermore, in order to imitate the human physiology, mechanical tests were also performed in phosphate buffered saline (PBS) solution at 37 °C. The method herein presented provides a high control of porosity, pore size distribution and mechanical performance, thus offering the possibility to fabricate three-layered scaffolds with tailored properties by following a simple and eco-friendly route.

Synthesis of antimicrobial Nisin-phosphorylated soybean protein isolate/poly(L-lactic acid)/ZrO2 membranes.

Science.gov (United States)

Jiang, Suwei; Wang, Hualin; Chu, Chenjiang; Ma, Xingkong; Sun, Min; Jiang, Shaotong

2015-01-01

Electrospinning technique was used to fabricate the model drug Nisin loaded phosphorylated soybean protein isolate/poly(l-lactic acid)/zirconium dioxide (Nisin-PSPI/PLLA/ZrO2) nanofibrous membranes. The average diameter of drug carrier PSPI/PLLA/ZrO2 nanofibers increased with the increase of content PSPI and some spindle-shape beads appeared when PSPI content reached 25 wt%. The loading dosage of Nisin caused no significant changes in the size and morphology of nanofibers when Nisin content was below 9 wt%. There existed hydrogen and Zr-O-C bonds among PSPI, PLLA and ZrO2 units, and the crystalline of PLLA matrix decreased owning to the introducing of PSPI and ZrO2 units. Moreover, the water absorption capability and degradation rate of PSPI/PLLA/ZrO2 nanofibrous membranes increased with increasing PSPI content. The antimicrobial activity and release experimental results showed that Nisin-PSPI/PLLA/ZrO2 nanofibrous membranes displayed well controlled release and better antimicrobial activity against Staphylococcus aureus (S. aureus), and the Nisin release from the medicated nanofibers could be described by Fickian diffusion model. The Nisin-PSPI/PLLA/ZrO2 nanofibrous membranes may have potential as a new nanofibrous membrane in drug delivery, food active packaging and wound dressing. Copyright © 2014 Elsevier B.V. All rights reserved.

Sequential crystallization and morphology of triple crystalline biodegradable PEO-b-PCL-b-PLLA triblock terpolymers

KAUST Repository

Palacios, Jordana; Mugica, Agurtzane; Zubitur, Manuela; Iturrospe, Amaia; Arbe, A.; Liu, Guoming; Wang, Dujin; Zhao, Junpeng; Hadjichristidis, Nikolaos; Muller, Alejandro

2016-01-01

The sequential crystallization of poly(ethylene oxide)-b-poly(e-caprolactone)-b-poly(L-lactide) (PEO-b-PCL-b-PLLA) triblock terpolymers, in which the three blocks are able to crystallize separately and sequentially from the melt, is presented. Two

[Mechanical properties of polylactic acid/beta-tricalcium phosphate composite scaffold with double channels based on three-dimensional printing technique].

Science.gov (United States)

Lian, Qin; Zhuang, Pei; Li, Changhai; Jin, Zhongmin; Li, Dichen

2014-03-01

To improve the poor mechanical strength of porous ceramic scaffold, an integrated method based on three-dimensional (3-D) printing technique is developed to incorporate the controlled double-channel porous structure into the polylactic acid/beta-tricalcium phosphate (PLA/beta-TCP) reinforced composite scaffolds (double-channel composite scaffold) to improve their tissue regeneration capability and the mechanical properties. The designed double-channel structure inside the ceramic scaffold consisted of both primary and secondary micropipes, which parallel but un-connected. The set of primary channels was used for cell ingrowth, while the set of secondary channels was used for the PLA perfusion. Integration technology of 3-D printing technique and gel-casting was firstly used to fabricate the double-channel ceramic scaffolds. PLA/beta-TCP composite scaffolds were obtained by the polymer gravity perfusion process to pour PLA solution into the double-channel ceramic scaffolds through the secondary channel set. Microscope, porosity, and mechanical experiments for the standard samples were used to evaluate the composite properties. The ceramic scaffold with only the primary channel (single-channel scaffold) was also prepared as a control. Morphology observation results showed that there was no PLA inside the primary channels of the double-channel composite scaffolds but a dense interface layer between PLA and beta-TCP obviously formed on the inner wall of the secondary channels by the PLA penetration during the perfusion process. Finite element simulation found that the compressive strength of the double-channel composite scaffold was less than that of the single-channel scaffold; however, mechanical tests found that the maximum compressive strength of the double-channel composite scaffold [(21.25 +/- 1.15) MPa] was higher than that of the single-channel scaffold[ (9.76 +/- 0.64) MPa]. The double-channel composite scaffolds fabricated by 3-D printing technique have

Influence of Poly(L-Lactic Acid Nanofibers and BMP-2–Containing Poly(L-Lactic Acid Nanofibers on Growth and Osteogenic Differentiation of Human Mesenchymal Stem Cells

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Markus D. Schofer

2008-01-01

Full Text Available The aim of this study was to characterize synthetic poly-(L-lactic acid (PLLA nanofibers concerning their ability to promote growth and osteogenic differentiation of stem cells in vitro, as well as to test their suitability as a carrier system for growth factors. Fiber matrices composed of PLLA or BMP-2–incorporated PLLA were seeded with human mesenchymal stem cells and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of alkaline phosphatase (ALP, osteocalcin (OC, and collagen I (COL-I. Furthermore, COL-I and OC deposition, as well as cell densities and proliferation, were analyzed using fluorescence microscopy. Although the presence of nanofibers diminished the dexamethasone-induced proliferation, there were no differences in cell densities or deposition of either COL-I or OC after 22 days of culture. The gene expression of ALP, OC, and COL-I decreased in the initial phase of cell cultivation on PLLA nanofibers as compared to cover slip control, but normalized during the course of cultivation. The initial down-regulation was not observed when BMP-2 was directly incorporated into PLLA nanofibers by electrospinning, indicating that growth factors like BMP-2 might survive the spinning process in a bioactive form.

Influence of Poly(L-Lactic Acid) Nanofibers and BMP-2–Containing Poly(L-Lactic Acid) Nanofibers on Growth and Osteogenic Differentiation of Human Mesenchymal Stem Cells

Science.gov (United States)

Schofer, Markus D.; Fuchs-Winkelmann, Susanne; Gräbedünkel, Christian; Wack, Christina; Dersch, Roland; Rudisile, Markus; Wendorff, Joachim H.; Greiner, Andreas; Paletta, Jürgen R. J.; Boudriot, Ulrich

2008-01-01

The aim of this study was to characterize synthetic poly-(L-lactic acid) (PLLA) nanofibers concerning their ability to promote growth and osteogenic differentiation of stem cells in vitro, as well as to test their suitability as a carrier system for growth factors. Fiber matrices composed of PLLA or BMP-2–incorporated PLLA were seeded with human mesenchymal stem cells and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and collagen I (COL-I). Furthermore, COL-I and OC deposition, as well as cell densities and proliferation, were analyzed using fluorescence microscopy. Although the presence of nanofibers diminished the dexamethasone-induced proliferation, there were no differences in cell densities or deposition of either COL-I or OC after 22 days of culture. The gene expression of ALP, OC, and COL-I decreased in the initial phase of cell cultivation on PLLA nanofibers as compared to cover slip control, but normalized during the course of cultivation. The initial down-regulation was not observed when BMP-2 was directly incorporated into PLLA nanofibers by electrospinning, indicating that growth factors like BMP-2 might survive the spinning process in a bioactive form. PMID:19112539

Increase the elongation at break of poly (lactic acid) composites for use in food packaging films

Science.gov (United States)

El-Hadi, Ahmed M.

2017-05-01

Poly (3-hydroxy butyrate) (PHB), cellulose nano crystal (CNC) and a plasticizer (TBC) are mixed together with PLLA with the aim to increase the elongation at break for use in the food packing sector. Spherical (CNC) and fibril nano crystal (CNF) were prepared by hydrolysis of microcrystalline cellulose (MCC) in distilled water, and then stirred using a magnetic stirrer for 15 days and ultrasonic treatment without using any acids as green method. The morphology, thermal, and mechanical properties were studied using POM, DSC, WAXD, SEM and tensile testing, respectively. DSC demonstrated that the addition of PHB, CNC and TBC to PLLA matrix lead to reduce Tg, TCC and Tm than pure PLLA. FT-IR verified that the carbonyl group C=O appeared broad and some peaks in the PLLA composites 5, 6 and 7 shifted from 3.98 × 108 to 4.07 × 108 Hz, at 3.54 × 108 to 3.44 × 108 Hz, at 3.19 × 108 to 3.13 × 108 Hz. Mechanical testing shows that pure PLLA is brittle, and the elongation at break of PLLA composites reaches up to 205%, making it suitable to use in food packaging.

Fundamental study on improvement of piezoelectricity of poly(ι-lactic acid) and its application to film actuators.

Science.gov (United States)

Tajitsu, Yoshiro

2013-08-01

We designed a new film actuator, whose driving force is generated by a surface wave, which induces rotational motion. Its performance is similar to that of a rotation motor even though the new film actuator has no complex mechanical parts. To realize the film actuator, we used a poly(l-lactic acid) (PLLA) film with improved piezoelectricity. First, we theoretically investigated the necessary conditions for a surface wave to be generated on the end face of a PLLA film by the fusion of its shear piezoelectricity and resonance, and then experimentally realized this. Using the actuator made using the PLLA film, we demonstrated that the clockwise and counterclockwise rotation of an object placed on the end face of the PLLA film actuator could be freely controlled by changing the frequency of the ac voltage applied to the actuator.

Chemical hydrogels based on a hyaluronic acid-graft-α-elastin derivative as potential scaffolds for tissue engineering.

Science.gov (United States)

Palumbo, Fabio Salvatore; Pitarresi, Giovanna; Fiorica, Calogero; Rigogliuso, Salvatrice; Ghersi, Giulio; Giammona, Gaetano

2013-07-01

In this work hyaluronic acid (HA) functionalized with ethylenediamine (EDA) has been employed to graft α-elastin. In particular a HA-EDA derivative bearing 50 mol% of pendant amino groups has been successfully employed to produce the copolymer HA-EDA-g-α-elastin containing 32% w/w of protein. After grafting with α-elastin, remaining free amino groups reacted with ethylene glycol diglycidyl ether (EGDGE) for producing chemical hydrogels, proposed as scaffolds for tissue engineering. Swelling degree, resistance to chemical and enzymatic hydrolysis, as well as preliminary biological properties of HA-EDA-g-α-elastin/EGDGE scaffold have been evaluated and compared with a HA-EDA/EGDGE scaffold. The presence of α-elastin grafted to HA-EDA improves attachment, viability and proliferation of primary rat dermal fibroblasts and human umbilical artery smooth muscle cells. Biological performance of HA-EDA-g-α-elastin/EGDGE scaffold resulted comparable to that of a commercial collagen type I sponge (Antema®), chosen as a positive control. Copyright © 2013 Elsevier B.V. All rights reserved.

Enzyme active site mimics based on TriAzaCyclophane (TAC)-scaffolded peptides and amino acid residues

NARCIS (Netherlands)

Albada, H.B.

2009-01-01

This thesis describes the scope and limitations of the application of TriAzaCyclophane (TAC)-scaffolded peptides or amino acid residues as enzyme active site mimics, as ligands in asymmetric catalysis and as hydrolysis catalysts attached to vancomycin. For the mimicry of functional group enzymes, of

Plasma surface modification of poly (L-lactic acid) and poly (lactic-co-glycolic acid) films for improvement of nerve cells adhesion

International Nuclear Information System (INIS)

Khorasani, M.T.; Mirzadeh, H.; Irani, S.

2008-01-01

Radio frequency (RF) plasma treatment in O 2 was applied to modify the surface of poly (L-lactic acid) (PLLA) and poly (D,L-lactic acid-coglycolic acid) (PLGA) as biodegradable polymers. The surface structure, morphology, wettability and surface chemistry of treated films were characterized by water drop contact angle measurement, scanning electron microscope (SEM), optical invert microscope, differential scanning calorimetry (DSC) and ATIR-FTIR spectroscopy. The cell affinity of the oxygen plasma treated film was evaluated by nervous tissue B65 cell culture in stationary conditions. The results showed that the hydrophilicity increased greatly after O 2 plasma treatment. The results showed that improved cell adhesion was attributed to the combination of surface chemistry and surface wettability during plasma treatment. Cell culture results showed that B65 nervous cell attachment and growth on the plasma treated PLLA was much higher than an unmodified sample and PLGA. Surface hydrophilicity and chemical functional groups with high polar component play an important role in enhancing cell attachment and growth

Mesoporous bioactive glass surface modified poly(lactic-co-glycolic acid electrospun fibrous scaffold for bone regeneration

Directory of Open Access Journals (Sweden)

Chen SJ

2015-06-01

Full Text Available Shijie Chen,1,* Zhiyuan Jian,2,* Linsheng Huang,2,* Wei Xu,3,* Shaohua Liu,4 Dajiang Song,3 Zongmiao Wan,3 Amanda Vaughn,5 Ruisen Zhan,1 Chaoyue Zhang,1 Song Wu,1 Minghua Hu,6 Jinsong Li1 1Department of Orthopaedics, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2The First General Surgery Department of Shiyan Taihe Hospital Affiliated to Hubei University of Medicine, Shiyan, People’s Republic of China; 3Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Molecular Biosciences, Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA; 6Department of Anthropotomy, Changsha Medical College, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Abstract: A mesoporous bioactive glass (MBG surface modified with poly(lactic-co-glycolic acid (PLGA electrospun fibrous scaffold for bone regeneration was prepared by dip-coating a PLGA electrospun fibrous scaffold into MBG precursor solution. Different surface structures and properties were acquired by different coating times. Surface morphology, chemical composition, microstructure, pore size distribution, and hydrophilicity of the PLGA-MBG scaffold were characterized. Results of scanning electron microscopy indicated that MBG surface coating made the scaffold rougher with the increase of MBG content. Scaffolds after MBG modification possessed mesoporous architecture on the surface. The measurements of the water contact angles suggested that the incorporation of MBG into the PLGA scaffold improved the surface hydrophilicity. An energy dispersive spectrometer evidenced that calcium-deficient carbonated hydroxyapatite formed on the PLGA-MBG scaffolds

Investigation of Localized Delivery of Diclofenac Sodium from Poly(D,L-Lactic Acid-co-Glycolic Acid)/Poly(Ethylene Glycol) Scaffolds Using an In Vitro Osteoblast Inflammation Model

Science.gov (United States)

Sidney, Laura E.; Heathman, Thomas R.J.; Britchford, Emily R.; Abed, Arif; Rahman, Cheryl V.

2015-01-01

Nonunion fractures and large bone defects are significant targets for osteochondral tissue engineering strategies. A major hurdle in the use of these therapies is the foreign body response of the host. Herein, we report the development of a bone tissue engineering scaffold with the ability to release anti-inflammatory drugs, in the hope of evading this response. Porous, sintered scaffolds composed of poly(D,L-lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) were prepared with and without the anti-inflammatory drug diclofenac sodium. Analysis of drug release over time demonstrated a profile suitable for the treatment of acute inflammation with ∼80% of drug released over the first 4 days and a subsequent release of around 0.2% per day. Effect of drug release was monitored using an in vitro osteoblast inflammation model, comprised of mouse primary calvarial osteoblasts stimulated with proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Levels of inflammation were monitored by cell viability and cellular production of nitric oxide (NO) and prostaglandin E2 (PGE2). The osteoblast inflammation model revealed that proinflammatory cytokine addition to the medium reduced cell viability to 33%, but the release of diclofenac sodium from scaffolds inhibited this effect with a final cell viability of ∼70%. However, releasing diclofenac sodium at high concentrations had a toxic effect on the cells. Proinflammatory cytokine addition led to increased NO and PGE2 production; diclofenac-sodium-releasing scaffolds inhibited NO release by ∼64% and PGE2 production by ∼52%, when the scaffold was loaded with the optimal concentration of drug. These observations demonstrate the potential use of PLGA/PEG scaffolds for localized delivery of anti-inflammatory drugs in bone tissue engineering applications. PMID:25104438

Tailoring the morphology and crystallinity of poly(L-lactide acid) electrospun membranes

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, Clarisse; Sencadas, Vitor; Costa, Carlos Miguel; Lanceros-Mendez, Senentxu [Centro/Departamento de Fisica da Universidade do Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Gomez Ribelles, Jose Luis, E-mail: lanceros@fisica.uminho.pt [Centro de Biomateriales e Ingenieria Tisular, Universidad Politecnica de Valencia, 46022 Valencia (Spain)

2011-02-15

Biodegradable poly(L-lactic acid) (PLLA) microfibers were prepared by electrospinning by varying the applied potential, solution flow rate and collector conditions. PLLA fibers with smoothly oriented and random morphologies were obtained and characterized by scanning electron microscopy. The optimum fiber orientation was obtained at 1000 rpm using a 20.3 cm diameter collecting drum, while for higher and lower drum rotation speeds, the rapid random motion of the jets resulted in a random fiber distribution. The deformation of the jet with rapid solidification during electrospinning often results in a metastable phase. PLLA electrospun fibers are amorphous but contain numerous crystal nuclei that rapidly grow when the sample is heated to 70-140 {sup 0}C. In this way, the degree of crystallinity of the fibers can be tailored between 0 and 50% by annealing. Infrared transmission spectra revealed that the processing conditions do not affect the PLLA samples at the molecular level and that the crystallinity of the samples is related to the presence of {alpha}-crystals.

Preparation and investigation of polylactic acid, calcium carbonate and polyvinylalcohol nanofibrous scaffolds for osteogenic differentiation of mesenchymal stem cells

Directory of Open Access Journals (Sweden)

A. Doustgani

2016-04-01

Full Text Available Objective(s: In this study, the effect of electrospun fiber orientation on proliferation and differentiation of mesenchymal stem cells (MSCs was evaluated. Materials and Methods: Aligned and random nanocomposite nanofibrous scaffolds were electrospun from polylactic acid (PLA, poly (vinyl alcohol (PVA and calcium carbonate nanoparticles (nCaP. The surface morphology of prepared nanofibrous scaffolds with and without cell was examined using scanning electron microscopy. Mechanical properties of electrospun nanofibrous scaffolds were determined with a  universal testing machine. The in vitro properties of fabricated scaffolds was also investigated by the MTT assay and alkaline phosphatase activity (ALP.Results: The average fiber diameter for aligned and random nanofibers were 82 ± 12 nm and 124 ± 25 nm, respectively. The mechanical testing indicated the higher tensile strength and elastic modulus of aligned nanofibers. MTT and ALP results showed that alignment of nanofiber increased the osteogenic differentiation of stem cells.Conclusion: Aligned nanofibrous nanocomposite scaffolds of PLA/nCaP/PVA could be an excellent substrate for MSCs and represents a potential bone-filling material.

A biomimetic multilayer nanofiber fabric fabricated by electrospinning and textile technology from polylactic acid and Tussah silk fibroin as a scaffold for bone tissue engineering

International Nuclear Information System (INIS)

Shao, Weili; He, Jianxin; Han, Qiming; Sang, Feng; Wang, Qian; Chen, Li; Cui, Shizhong

2016-01-01

To engineer bone tissue, a scaffold with good biological properties should be provided to approximate the hierarchical structure of collagen fibrils in natural bone. In this study, we fabricated a novel scaffold consisting of multilayer nanofiber fabrics (MLNFFs) by weaving nanofiber yarns of polylactic acid (PLA) and Tussah silk fibroin (TSF). The yarns were fabricated by electrospinning, and we found that spinnability, as well as the mechanical properties of the resulting scaffold, was determined by the ratio between polylactic acid and Tussah silk fibroin. In particular, a 9:1 mixture can be spun continuously into nanofiber yarns with narrow diameter distribution and good mechanical properties. Accordingly, woven scaffolds based on this mixture had excellent mechanical properties, with Young's modulus 417.65 MPa and tensile strength 180.36 MPa. For nonwoven scaffolds fabricated from the same materials, the Young's modulus and tensile strength were 2- and 4-fold lower, respectively. Woven scaffolds also supported adhesion and proliferation of mouse mesenchymal stem cells, and promoted biomineralization via alkaline phosphatase and mineral deposition. Finally, the scaffolds significantly enhanced the formation of new bone in damaged femoral condyle in rabbits. Thus, the scaffolds are potentially suitable for bone tissue engineering because of biomimetic architecture, excellent mechanical properties, and good biocompatibility. - Highlights: • A novel strategy to mimic the hierarchical collagen fibril in bone is proposed by electrospinning and conventional textile technology. • The tensile strength of the woven scaffold was nearly 4-fold larger than that of nonwoven mats. • The nanofiber woven scaffolds show excellent cytocompatibility and accelerate osteoblast differentiation. • The composite scaffold significantly enhanced formation of new bone in damaged condyles in rabbit femur.

A biomimetic multilayer nanofiber fabric fabricated by electrospinning and textile technology from polylactic acid and Tussah silk fibroin as a scaffold for bone tissue engineering

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Shao, Weili [Key Laboratory of Advanced Textile Composites, Ministry of Education, Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007 (China); He, Jianxin, E-mail: hejianxin771117@163.com [Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007 (China); Han, Qiming [Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007 (China); Sang, Feng [Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000 (China); Wang, Qian [Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007 (China); Chen, Li [Key Laboratory of Advanced Textile Composites, Ministry of Education, Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Cui, Shizhong [Key Laboratory of Advanced Textile Composites, Ministry of Education, Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Henan provincial key laboratory of functional textile materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Collaborative Innovation Center of Textile and Garment Industry, Henan Province, Zhengzhou 450007 (China); and others

2016-10-01

To engineer bone tissue, a scaffold with good biological properties should be provided to approximate the hierarchical structure of collagen fibrils in natural bone. In this study, we fabricated a novel scaffold consisting of multilayer nanofiber fabrics (MLNFFs) by weaving nanofiber yarns of polylactic acid (PLA) and Tussah silk fibroin (TSF). The yarns were fabricated by electrospinning, and we found that spinnability, as well as the mechanical properties of the resulting scaffold, was determined by the ratio between polylactic acid and Tussah silk fibroin. In particular, a 9:1 mixture can be spun continuously into nanofiber yarns with narrow diameter distribution and good mechanical properties. Accordingly, woven scaffolds based on this mixture had excellent mechanical properties, with Young's modulus 417.65 MPa and tensile strength 180.36 MPa. For nonwoven scaffolds fabricated from the same materials, the Young's modulus and tensile strength were 2- and 4-fold lower, respectively. Woven scaffolds also supported adhesion and proliferation of mouse mesenchymal stem cells, and promoted biomineralization via alkaline phosphatase and mineral deposition. Finally, the scaffolds significantly enhanced the formation of new bone in damaged femoral condyle in rabbits. Thus, the scaffolds are potentially suitable for bone tissue engineering because of biomimetic architecture, excellent mechanical properties, and good biocompatibility. - Highlights: • A novel strategy to mimic the hierarchical collagen fibril in bone is proposed by electrospinning and conventional textile technology. • The tensile strength of the woven scaffold was nearly 4-fold larger than that of nonwoven mats. • The nanofiber woven scaffolds show excellent cytocompatibility and accelerate osteoblast differentiation. • The composite scaffold significantly enhanced formation of new bone in damaged condyles in rabbit femur.

Experimental Investigation and Thermodynamic Assessment of Phase Equilibria in the PLLA/Dioxane/Water Ternary System for Applications in the Biomedical Field.

Science.gov (United States)

Ruggiero, Flavia; Netti, Paolo Antonio; Torino, Enza

2015-12-01

Fundamental understanding of thermodynamic of phase separation plays a key role in tuning the desired features of biomedical devices. In particular, phase separation of ternary solution is of remarkable interest in processes to obtain biodegradable and biocompatible architectures applied as artificial devices to repair, replace, or support damaged tissues or organs. In these perspectives, thermally induced phase separation (TIPS) is the most widely used technique to obtained porous morphologies and, in addition, among different ternary systems, polylactic acid (PLLA)/dioxane/water has given promising results and has been largely studied. However, to increase the control of TIPS-based processes and architectures, an investigation of the basic energetic phenomena occurring during phase separation is still required. Here we propose an experimental investigation of the selected ternary system by using isothermal titration calorimetric approach at different solvent/antisolvent ratio and a thermodynamic explanation related to the polymer-solvents interactions in terms of energetic contribution to the phase separation process. Furthermore, relevant information about the phase diagrams and interaction parameters of the studied systems are furnished in terms of liquid-liquid miscibility gap. Indeed, polymer-solvents interactions are responsible for the mechanism of the phase separation process and, therefore, of the final features of the morphologies; the knowledge of such data is fundamental to control processes for the production of membranes, scaffolds and several nanostructures. The behavior of the polymer at different solvent/nonsolvent ratios is discussed in terms of solvation mechanism and a preliminary contribution to the understanding of the role of the hydrogen bonding in the interface phenomena is also reported. It is the first time that thermodynamic data of a ternary system are collected by mean of nano-isothermal titration calorimetry (nano-ITC). Supporting

Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)-tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide.

Science.gov (United States)

Shao, Weili; He, Jianxin; Sang, Feng; Wang, Qian; Chen, Li; Cui, Shizhong; Ding, Bin

2016-05-01

To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Reinforcement of poly-l-lactic acid electrospun membranes with strontium borosilicate bioactive glasses for bone tissue engineering.

Science.gov (United States)

Fernandes, João S; Gentile, Piergiorgio; Martins, Margarida; Neves, Nuno M; Miller, Cheryl; Crawford, Aileen; Pires, Ricardo A; Hatton, Paul; Reis, Rui L

2016-10-15

Herein, for the first time, we combined poly-l-lactic acid (PLLA) with a strontium borosilicate bioactive glass (BBG-Sr) using electrospinning to fabricate a composite bioactive PLLA membrane loaded with 10% (w/w) of BBG-Sr glass particles (PLLA-BBG-Sr). The composites were characterised by scanning electron microscopy (SEM) and microcomputer tomography (μ-CT), and the results showed that we successfully fabricated smooth and uniform fibres (1-3μm in width) with a homogeneous distribution of BBG-Sr microparticles (bone marrow-derived mesenchymal stem cells (BM-MSCs) demonstrated that PLLA-BBG-Sr membranes promoted the osteogenic differentiation of the cells as demonstrated by increased alkaline phosphatase activity and up-regulated osteogenic gene expression (Alpl, Sp7 and Bglap) in relation to PLLA alone. These results strongly suggest that the composite PLLA membranes reinforced with the BBG-Sr glass particles have potential as an effective biomaterial capable of promoting bone regeneration. PLLA membranes were reinforced with 10% (w/w) of strontium-bioactive borosilicate glass microparticles, and their capacity to induce the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) was evaluated. These membranes presented an increased: degradability, water uptake, Young modulus and tensile strength. We also demonstrated that these membranes are non-cytotoxic and promote the attachment of BM-MSCs. The addition of the glass microparticles into the PLLA membranes promoted the increase of ALP activity (under osteogenic conditions), as well as the BM-MSCs osteogenic differentiation as shown by the upregulation of Alpl, Sp7 and Bglap gene expression. Overall, we demonstrated that the reinforcement of PLLA with glass microparticles results in a biomaterial with the appropriate properties for the regeneration of bone tissue. Copyright © 2016 Acta Materialia Inc. All rights reserved.

Nanosized Mesoporous Bioactive Glass/Poly(lactic-co-glycolic Acid Composite-Coated CaSiO3 Scaffolds with Multifunctional Properties for Bone Tissue Engineering

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Mengchao Shi

2014-01-01

Full Text Available It is of great importance to prepare multifunctional scaffolds combining good mechanical strength, bioactivity, and drug delivery ability for bone tissue engineering. In this study, nanosized mesoporous bioglass/poly(lactic-co-glycolic acid composite-coated calcium silicate scaffolds, named NMBG-PLGA/CS, were successfully prepared. The morphology and structure of the prepared scaffolds were characterized by scanning electron microscopy and X-ray diffraction. The effects of NMBG on the apatite mineralization activity and mechanical strength of the scaffolds and the attachment, proliferation, and alkaline phosphatase activity of MC3T3 cells as well as drug ibuprofen delivery properties were systematically studied. Compared to pure CS scaffolds and PLGA/CS scaffolds, the prepared NMBG-PLGA/CS scaffolds had greatly improved apatite mineralization activity in simulated body fluids, much higher mechanical property, and supported the attachment of MC3T3 cells and enhanced the cell proliferation and ALP activity. Furthermore, the prepared NMBG-PLGA/CS scaffolds could be used for delivering ibuprofen with a sustained release profile. Our study suggests that the prepared NMBG-PLGA/CS scaffolds have improved physicochemical, biological, and drug-delivery property as compared to conventional CS scaffolds, indicating that the multifunctional property of the prepared scaffolds for the potential application of bone tissue engineering.

Preparation and characterization of malonic acid cross-linked chitosan and collagen 3D scaffolds: an approach on non-covalent interactions.

Science.gov (United States)

Mitra, Tapas; Sailakshmi, G; Gnanamani, A; Mandal, A B

2012-05-01

The present study emphasizes the influence of non-covalent interactions on the mechanical and thermal properties of the scaffolds of chitosan/collagen origin. Malonic acid (MA), a bifuncitonal diacid was chosen to offer non-covalent cross-linking. Three dimensional scaffolds was prepared using chitosan at 1.0% (w/v) and MA at 0.2% (w/v), similarly collagen 0.5% (w/v) and MA 0.2% (w/v) and characterized. Results on FT-IR, TGA, DSC, SEM and mechanical properties (tensile strength, stiffness, Young's modulus, etc.) assessment demonstrated the existence of non-covalent interaction between MA and chitosan/collagen, which offered flexibility and high strength to the scaffolds suitable for tissue engineering research. Studies using NIH 3T3 fibroblast cells suggested biocompatibility nature of the scaffolds. Docking simulation study further supports the intermolecular hydrogen bonding interactions between MA and chitosan/collagen.

Surface modification of poly(D,L-lactic acid) scaffolds for orthopedic applications: a biocompatible, nondestructive route via diazonium chemistry.

Science.gov (United States)

Mahjoubi, Hesameddin; Kinsella, Joseph M; Murshed, Monzur; Cerruti, Marta

2014-07-09

Scaffolds made with synthetic polymers such as polyesters are commonly used in bone tissue engineering. However, their hydrophobicity and the lack of specific functionalities make their surface not ideal for cell adhesion and growth. Surface modification of these materials is thus crucial to enhance the scaffold's integration in the body. Different surface modification techniques have been developed to improve scaffold biocompatibility. Here we show that diazonium chemistry can be used to modify the outer and inner surfaces of three-dimensional poly(D,L-lactic acid) (PDLLA) scaffolds with phosphonate groups, using a simple two-step method. By changing reaction time and impregnation procedure, we were able to tune the concentration of phosphonate groups present on the scaffolds, without degrading the PDLLA matrix. To test the effectiveness of this modification, we immersed the scaffolds in simulated body fluid, and characterized them with scanning electron microscopy, X-ray photoelectron spectroscopy, Raman, and infrared spectroscopy. Our results showed that a layer of hydroxyapatite particles was formed on all scaffolds after 2 and 4 weeks of immersion; however, the precipitation was faster and in larger amounts on the phosphonate-modified than on the bare PDLLA scaffolds. Both osteogenic MC3T3-E1 and chondrogenic ATDC5 cell lines showed increased cell viability/metabolic activity when grown on a phosphonated PDLLA surface in comparison to a control PDLLA surface. Also, more calcium-containing minerals were deposited by cultures grown on phosphonated PDLLA, thus showing the pro-mineralization properties of the proposed modification. This work introduces diazonium chemistry as a simple and biocompatible technique to modify scaffold surfaces, allowing to covalently and homogeneously bind a number of functional groups without degrading the scaffold's polymeric matrix.

A novel akermanite/poly (lactic-co-glycolic acid) porous composite scaffold fabricated via a solvent casting-particulate leaching method improved by solvent self-proliferating process.

Science.gov (United States)

Deng, Yao; Zhang, Mengjiao; Chen, Xianchun; Pu, Ximing; Liao, Xiaoming; Huang, Zhongbing; Yin, Guangfu

2017-08-01

Desirable scaffolds for tissue engineering should be biodegradable carriers to supply suitable microenvironments mimicked the extracellular matrices for desired cellular interactions and to provide supports for the formation of new tissues. In this work, a kind of slightly soluble bioactive ceramic akermanite (AKT) powders were aboratively selected and introduced in the PLGA matrix, a novel l-lactide modified AKT/poly (lactic- co -glycolic acid) (m-AKT/PLGA) composite scaffold was fabricated via a solvent casting-particulate leaching method improved by solvent self-proliferating process. The effects of m-AKT contents on properties of composite scaffolds and on MC3T3-E1 cellular behaviors in vitro have been primarily investigated. The fabricated scaffolds exhibited three-dimensional porous networks, in which homogenously distributed cavities in size of 300-400 μm were interconnected by some smaller holes in a size of 100-200 μm. Meanwhile, the mechanical structure of scaffolds was reinforced by the introduction of m-AKT. Moreover, alkaline ionic products released by m-AKT could neutralize the acidic degradation products of PLGA, and the apatite-mineralization ability of scaffolds could be largely improved. More valuably, significant promotions on adhesion, proliferation, and differentiation of MC3T3-E1 have been observed, which implied the calcium, magnesium and especially silidous ions released sustainably from composite scaffolds could regulate the behaviors of osteogenesis-related cells.

Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury★

Science.gov (United States)

Wang, Dong; Fan, Yuhong; Zhang, Jianjun

2013-01-01

Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly(D,L-lactide-co-glycolic acid) has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly(D,L-lactide-co-glycolic acid) into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced cells plus the poly(D,L-lactide-co-glycolic acid) scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly(D,L-lactide-co-glycolic acid) scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury. PMID:25206713

Scaffolds for peripheral nerve repair and reconstruction.

Science.gov (United States)

Yi, Sheng; Xu, Lai; Gu, Xiaosong

2018-06-02

Trauma-associated peripheral nerve defect is a widespread clinical problem. Autologous nerve grafting, the current gold standard technique for the treatment of peripheral nerve injury, has many internal disadvantages. Emerging studies showed that tissue engineered nerve graft is an effective substitute to autologous nerves. Tissue engineered nerve graft is generally composed of neural scaffolds and incorporating cells and molecules. A variety of biomaterials have been used to construct neural scaffolds, the main component of tissue engineered nerve graft. Synthetic polymers (e.g. silicone, polyglycolic acid, and poly(lactic-co-glycolic acid)) and natural materials (e.g. chitosan, silk fibroin, and extracellular matrix components) are commonly used along or together to build neural scaffolds. Many other materials, including the extracellular matrix, glass fabrics, ceramics, and metallic materials, have also been used to construct neural scaffolds. These biomaterials are fabricated to create specific structures and surface features. Seeding supporting cells and/or incorporating neurotrophic factors to neural scaffolds further improve restoration effects. Preliminary studies demonstrate that clinical applications of these neural scaffolds achieve satisfactory functional recovery. Therefore, tissue engineered nerve graft provides a good alternative to autologous nerve graft and represents a promising frontier in neural tissue engineering. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of nanoparticles of hydroxyapatite and MWCNT’s in scaffolds of poly lactic acid

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Román-Doval, R.; Morales-Corona, J.; Olayo, R.; Escamilla-Rivera, V.; Uribe-Ramírez, M.; Ortega-López, M.

2016-12-01

In the tissue engineering, the cytotoxicity test is an important part of the biomaterials performance. This research reports the production and characterization of polylactic acid (PLA)-supported hydroxyapatite (HA) and multiwalled carbon nanotubes (MWCNT) scaffolds as a bone graft material. Samples containing different HA/MWCNT wt% ratios were prepared by electrospinning. The obtained samples displayed valuable characteristics for the cell adhesion because of their porous-spongy bone-like morphology. The Fourier transforms infrared and Raman analyses indicated no chemical interaction of HA and MWCNT with PLA molecules, but they appear to be only embedded into the PLA fibers. As indicated by x-ray diffraction, crystalline HA and MWCNT’s are supported in the amorphous PLA fibers. Under tensile stress, scaffolds display a Young’s Modulus about 86 MPa, whilst the scaffolds resistance increases with the HA-MWCNT’s ratio. However, the MTS in-vitro assays using the hFOB 1.19 (ATCC CRL-11372) cells, for cell exposure time of 24 and 48 h, revealed that viability reduces for HA-MWCNT’s ratio values over 25 wt%. Our results suggest that a maximum HA/MWCNT’s ratio of 19:1 could be acceptable for cell proliferation while maintaining HA at 200 mg.

Parallel fabrication of macroporous scaffolds.

Science.gov (United States)

Dobos, Andrew; Grandhi, Taraka Sai Pavan; Godeshala, Sudhakar; Meldrum, Deirdre R; Rege, Kaushal

2018-07-01

Scaffolds generated from naturally occurring and synthetic polymers have been investigated in several applications because of their biocompatibility and tunable chemo-mechanical properties. Existing methods for generation of 3D polymeric scaffolds typically cannot be parallelized, suffer from low throughputs, and do not allow for quick and easy removal of the fragile structures that are formed. Current molds used in hydrogel and scaffold fabrication using solvent casting and porogen leaching are often single-use and do not facilitate 3D scaffold formation in parallel. Here, we describe a simple device and related approaches for the parallel fabrication of macroporous scaffolds. This approach was employed for the generation of macroporous and non-macroporous materials in parallel, in higher throughput and allowed for easy retrieval of these 3D scaffolds once formed. In addition, macroporous scaffolds with interconnected as well as non-interconnected pores were generated, and the versatility of this approach was employed for the generation of 3D scaffolds from diverse materials including an aminoglycoside-derived cationic hydrogel ("Amikagel"), poly(lactic-co-glycolic acid) or PLGA, and collagen. Macroporous scaffolds generated using the device were investigated for plasmid DNA binding and cell loading, indicating the use of this approach for developing materials for different applications in biotechnology. Our results demonstrate that the device-based approach is a simple technology for generating scaffolds in parallel, which can enhance the toolbox of current fabrication techniques. © 2018 Wiley Periodicals, Inc.

Fabrication of Microfibrous and Nano-/Microfibrous Scaffolds: Melt and Hybrid Electrospinning and Surface Modification of Poly(L-lactic acid with Plasticizer

Directory of Open Access Journals (Sweden)

Young Il Yoon

2013-01-01

Full Text Available Biodegradable poly(L-lactic acid (PLA fibrous scaffolds were prepared by electrospinning from a PLA melt containing poly(ethylene glycol (PEG as a plasticizer to obtain thinner fibers. The effects of PEG on the melt electrospinning of PLA were examined in terms of the melt viscosity and fiber diameter. Among the parameters, the content of PEG had a more significant effect on the average fiber diameter and its distribution than those of the spinning temperature. Furthermore, nano-/microfibrous silk fibroin (SF/PLA and PLA/PLA composite scaffolds were fabricated by hybrid electrospinning, which involved a combination of solution electrospinning and melt electrospinning. The SF/PLA (20/80 scaffolds consisted of a randomly oriented structure of PLA microfibers (average fiber diameter = 8.9 µm and SF nanofibers (average fiber diameter = 820 nm. The PLA nano-/microfiber (20/80 scaffolds were found to have similar pore parameters to the PLA microfiber scaffolds. The PLA scaffolds were treated with plasma in the presence of either oxygen or ammonia gas to modify the surface of the fibers. This approach of controlling the surface properties and diameter of fibers could be useful in the design and tailoring of novel scaffolds for tissue engineering.

Innovative micro-textured hydroxyapatite and poly(l-lactic)-acid polymer composite film as a flexible, corrosion resistant, biocompatible, and bioactive coating for Mg implants.

Science.gov (United States)

Kim, Sae-Mi; Kang, Min-Ho; Kim, Hyoun-Ee; Lim, Ho-Kyung; Byun, Soo-Hwan; Lee, Jong-Ho; Lee, Sung-Mi

2017-12-01

The utility of a novel ceramic/polymer-composite coating with a micro-textured microstructure that would significantly enhance the functions of biodegradable Mg implants is demonstrated here. To accomplish this, bioactive hydroxyapatite (HA) micro-dots can be created by immersing a Mg implant with a micro-patterned photoresist surface in an aqueous solution containing calcium and phosphate ions. The HA micro-dots can then be surrounded by a flexible poly(l-lactic)-acid (PLLA) polymer using spin coating to form a HA/PLLA micro-textured coating layer. The HA/PLLA micro-textured coating layer showed an excellent corrosion resistance when it was immersed in a simulated body fluid (SBF) solution and good biocompatibility, which was assessed by in vitro cell tests. In addition, the HA/PLLA micro-textured coating layer had high deformation ability, where no apparent changes in the coating layer were observed even after a 5% elongation, which would be unobtainable using HA and PLLA coating layers; furthermore, this allowed the mechanically-strained Mg implant with the HA/PLLA micro-textured coating layer to preserve its excellent corrosion resistance and biocompatibility in vitro. Copyright © 2017 Elsevier B.V. All rights reserved.

The toxicity of rifampicin polylactic acid nanoparticles against Mycobacterium bovis BCG and human macrophage THP-1 cell line

International Nuclear Information System (INIS)

Erokhina, M; Rybalkina, E; Lepekha, L; Barsegyan, G; Onishchenko, G

2015-01-01

Tuberculosis is rapidly becoming a major health problem. The rise in tuberculosis incidence stimulates efforts to develop more effective delivery systems for the existing antituberculous drugs while decreasing the side effects. The nanotechnology may provide novel drug delivery tools allowing controlled drug release. Rifampicin is one of the main antituberculous drugs, characterized by high toxicity, and Poly (L-lactic acid) (PLLA) is a biodegradable polymer used for the preparation of encapsulated drugs. The aim of our work was to evaluate the toxicity of rifampicin-PLLA nanoparticles against Mycobacterium bovis BCG using human macrophage THP-1 cell line. Our data demonstrate that rifampicin-PLLA is effective against M. bovis BCG in the infected macrophages. The drug is inducing the dysfunction of mitochondria and apoptosis in the macrophages and is acting as a potential substrate of Pgp thereby modulating cell chemosensitivity. The severity of the toxic effects of the rifampicin-PLLA nanoparticles is increasing in a dose-dependent manner. We suggest that free rifampicin induces death of M. bovis BCG after PLLA degradation and diffusion from phago-lysosomes to cytoplasm causing mitochondria dysfunction and affecting the Pgp activity. (paper)

Poly(dopamine) coating of 3D printed poly(lactic acid) scaffolds for bone tissue engineering.

Science.gov (United States)

Kao, Chia-Tze; Lin, Chi-Chang; Chen, Yi-Wen; Yeh, Chia-Hung; Fang, Hsin-Yuan; Shie, Ming-You

2015-11-01

3D printing is a versatile technique to generate large quantities of a wide variety of shapes and sizes of polymer. The aim of this study is to develop functionalized 3D printed poly(lactic acid) (PLA) scaffolds and use a mussel-inspired surface coating to regulate cell adhesion, proliferation and differentiation of human adipose-derived stem cells (hADSCs). We prepared PLA 3D scaffolds coated with polydopamine (PDA). The chemical composition and surface properties of PDA/PLA were characterized by XPS. PDA/PLA modulated hADSCs' responses in several ways. Firstly, adhesion and proliferation, and cell cycle of hADSCs cultured on PDA/PLA were significantly enhanced relative to those on PLA. In addition, the collagen I secreted from cells was increased and promoted cell attachment and cell cycle progression were depended on the PDA content. In osteogenesis assay, the ALP activity and osteocalcin of hADSCs cultured on PDA/PLA were significantly higher than seen in those cultured on pure PLA scaffolds. Moreover, hADSCs cultured on PDA/PLA showed up-regulation of the ang-1 and vWF proteins associated with angiogenic differentiation. Our results demonstrate that the bio-inspired coating synthetic PLA polymer can be used as a simple technique to render the surfaces of synthetic scaffolds active, thus enabling them to direct the specific responses of hADSCs. Copyright © 2015 Elsevier B.V. All rights reserved.

Multi-material poly(lactic acid) scaffold fabricated via fused deposition modeling and direct hydroxyapatite injection as spacers in laminoplasty

Science.gov (United States)

Syuhada, Ghifari; Ramahdita, Ghiska; Rahyussalim, A. J.; Whulanza, Yudan

2018-02-01

Nowadays, additive manufacturing method has been used extensively to realize any product with specific attributes rather than the conventional subtractive manufacturing method. For instance, the additive manufacturing has enable us to construct a product layer-by-layer by successively depositing several materials in one session and one platform. This paper studied the properties of a 3D printed scaffold fabricated through Poly(Lactic-acid) (PLA) deposition modelling in combination with injectable hydroxyapatite (HA)/alginate as cell carrier. The scaffold was designed to serve as a spacer in cervical laminoplasty. Therefore, a series of test were conducted to elaborate the mechanical property, porosity and in-vitro toxicity testing. The results showed that the method is reliable to fabricate the scaffold as desired although the toxicity test needs more confirmation.

Poly(amino acid)-based fibrous scaffolds modified with surface-pendant peptides for cartilage tissue engineering

Czech Academy of Sciences Publication Activity Database

Svobodová, Jana; Proks, Vladimír; Karabiyik, Ö.; Calikoglu Koyuncu, A. C.; Köse, G. T.; Rypáček, František; Studenovská, Hana

2017-01-01

Roč. 11, č. 3 (2017), s. 831-842 ISSN 1932-6254 R&D Projects: GA ČR GAP108/12/1629; GA ČR GAP108/12/1538 Grant - others:AV ČR, TUBITAK(CZ) 111M031 Institutional support: RVO:61389013 Keywords : poly(amino acid) * fibrous scaffolds * adhesion peptide Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 3.989, year: 2016

A primer of statistical methods for correlating parameters and properties of electrospun poly( l -lactide) scaffolds for tissue engineering-PART 2: Regression

KAUST Repository

Seyedmahmoud, Rasoul

2014-04-07

This two-articles series presents an in-depth discussion of electrospun poly-l-lactide scaffolds for tissue engineering by means of statistical methodologies that can be used, in general, to gain a quantitative and systematic insight about effects and interactions between a handful of key scaffold properties (Ys) and a set of process parameters (Xs) in electrospinning. While Part-1 dealt with the DOE methods to unveil the interactions between Xs in determining the morphomechanical properties (ref. Y1-4), this Part-2 article continues and refocuses the discussion on the interdependence of scaffold properties investigated by standard regression methods. The discussion first explores the connection between mechanical properties (Y4) and morphological descriptors of the scaffolds (Y1-3) in 32 types of scaffolds, finding that the mean fiber diameter (Y1) plays a predominant role which is nonetheless and crucially modulated by the molecular weight (MW) of PLLA. The second part examines the biological performance (Y5) (i.e. the cell proliferation of seeded bone marrow-derived mesenchymal stromal cells) on a random subset of eight scaffolds vs. the mechanomorphological properties (Y1-4). In this case, the featured regression analysis on such an incomplete set was not conclusive, though, indirectly suggesting in quantitative terms that cell proliferation could not fully be explained as a function of considered mechanomorphological properties (Y1-4), but in the early stage seeding, and that a randomization effects occurs over time such that the differences in initial cell proliferation performance (at day 1) is smeared over time. The findings may be the cornerstone of a novel route to accrue sufficient understanding and establish design rules for scaffold biofunctional vs. architecture, mechanical properties, and process parameters.

Electrospun Poly(lactic acid-co-glycolic acid) Scaffolds for Skin Tissue Engineering

Science.gov (United States)

Kumbar, Sangamesh G.; Nukavarapu, Syam Prasad; James, Roshan; Nair, Lakshmi S.; Laurencin, Cato T.

2008-01-01

Electrospun fiber matrices composed of scaffolds of varying fiber diameters were investigated for potential application of severe skin loss. Few systematic studies have been performed to examine the effect of varying fiber diameter electrospun fiber matrices for skin regeneration. The present study reports the fabrication of poly[lactic acid-co-glycolic acid] (PLAGA) matrices with fiber diameters of 150–225, 200–300, 250–467, 500–900, 600–1200, 2500–3000 and 3250–6000 nm via electrospinning. All fiber matrices found to have a tensile modulus from 39.23 ± 8.15 to 79.21 ± 13.71 MPa which falls in the range for normal human skin. Further, the porous fiber matrices have porosity between 38–60 % and average pore diameters between 10–14µm. We evaluated the efficacy of these biodegradable fiber matrices as skin substitutes by seeding them with human skin fibroblasts (hSF). Human skin fibroblasts acquired a well spread morphology and showed significant progressive growth on fiber matrices in the 350–1100 nm diameter range. Collagen type III gene expression was significantly up-regulated in hSF seeded on matrices with fiber diameters in the range of 350–1100 nm. Based on the need, the proposed fiber skin substitutes can be successfully fabricated and optimized for skin fibroblast attachment and growth. PMID:18639927

Effect of lecithin content blend with poly (L-lactic acid) on viability and proliferation of mesenchymal stem cells

International Nuclear Information System (INIS)

Xu Zhonghua; Wu Qingyu

2009-01-01

Lecithin constitutes a natural mixture of phospholipids and neutral lipids and plays critical roles in cellular membrane structure and cellular signaling. In this study, lecithin was blended with poly (L-lactic acid) (PLLA) for modifying the surface of PLLA because it might obtain appropriate hydrophilicity and biocompatibility. The modified PLLA films were manufactured using conventional solvent-casting technique. The hydrophilicity clearly increased with an increase of lecithin content in the polymer blends, as determined by measuring the water contact angle (WCA). The cytocompatibility and any potential cytotoxic effects were studied over 7 days by seeding mesenchymal stem cells (MSCs) on the films of PLLA containing 0-15% lecithin (wt.%), in comparison with tissue culture plates (TCPs). Cell viability and proliferation were assessed using WST-8, lactate dehydrogenase (LDH) and cell morphology was studied by toluidine blue and propidium iodide staining. This results obtained above suggested that 5%lecithin-containing PLLA films could possess the optimal hydrophilicity, higher adhesion and proliferation of MSCs for a prolonged period and did not demonstrate any significant toxic effects to cells. The study showed that the hydrophilicity and biocompatibility of the modified PLLA were markedly improved by directly introducing lecithin into the polymer without the use of multiple synthetic steps. The information obtained should be useful for future research in vascular tissue engineering (VTE).

A combined strategy to reduce restenosis for vascular tissue engineering applications.

Science.gov (United States)

Patel, Hemang J; Su, Shih-Horng; Patterson, Cam; Nguyen, Kytai T

2006-01-01

Biodegradable polymers including poly(l-lactic acid) (PLLA) have been used to develop cardiovascular prostheses such as vascular grafts and stents. However, implant-associated thrombosis, inflammation, and restenosis are still major obstacles for the utility of these devices. The lack of an endothelial cell (EC) lining (endothelialization) on the implants and the responses of the immune systems toward the implants have been associated with these complications. In our research strategy, we have combined the drug delivery principle with the strategies of tissue engineering, the controlled release of anti-inflammation drugs and enhanced endothelialization, to reduce the implant-associated adverse responses. We first integrated curcumin, an anti-inflammatory drug and anti-smooth muscle cell (SMC) proliferative drug, with PLLA. This curcumin-loaded PLLA material was then modified using adsorptive coating of adhesive proteins such as fibronectin, collagen-I, vitronectin, laminin, and matrigel to improve the endothelial cell (EC) adhesion and proliferation, and ECs were seeded on top of these modified surfaces. Our results showed steady drug release kinetics over the period of 50 days from curcumin-loaded PLLA materials. Additionally, integration of curcumin in PLLA increased the roughness of the scaffold at the nanometric scale using an atomic force microscopic analysis. Moreover, coating with fibronectin on curcumin-loaded PLLA surfaces gave the highest EC adhesion and proliferation compared to other adhesive proteins using PicoGreen DNA assays. The ability of our strategy to release the curcumin for producing anti-inflammation and anti-proliferation responses and to improve EC adhesion and growth after EC seeding suggests this strategy may reduce implant-associated adverse responses and be a better approach for vascular tissue engineering applications.

Unusual large-pitch banding in poly(L-lactic acid): Effects of composition and geometry confinement

International Nuclear Information System (INIS)

Woo, Eamor M.; Lugito, Graecia; Hsieh, Ya-Ting; Nurkhamidah, Siti

2014-01-01

Lamellar patterns and orientations in blends of two crystalline polymers: poly(ethylene oxide) (PEO) and low-molecular-weight poly(L-lactic acid) (PLLA) were investigated using polarizing light optical microscopy (POM), and atomic and scanning electron microscopy (AFM, SEM). Specific etching off of PEO was used to reveal the complex earlier-grown PLLA lamellae patterns with various PEO content in blends. Banding of extremely long pitch (50 μm) in crystallized PLLA spherulites was induced by two kinetic factors: geometry confinement by top cover and introduction of diluent such as PEO. The mechanisms and correlation among the lamellar assembly, ring bands, and cracks are exemplified. Lamellar patterns and ring-band types in blends were found to vary with respect to not only blend compositions, but also confinement of top-cover

On Mineral Retrosynthesis of a Complex Biogenic Scaffold

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Ashit Rao

2017-03-01

Full Text Available Synergistic relations between organic molecules and mineral precursors regulate biogenic mineralization. Given the remarkable material properties of the egg shell as a biogenic ceramic, it serves as an important model to elucidate biomineral growth. With established roles of complex anionic biopolymers and a heterogeneous organic scaffold in egg shell mineralization, the present study explores the regulation over mineralization attained by applying synthetic polymeric counterparts (polyethylene glycol, poly(acrylic acid, poly(aspartic acid and poly(4-styrenesulfonic acid-co-maleic acid as additives during remineralization of decalcified eggshell membranes. By applying Mg2+ ions as a co-additive species, mineral retrosynthesis is achieved in a manner that modulates the polymorph and structure of mineral products. Notable features of the mineralization process include distinct local wettability of the biogenic organic scaffold by mineral precursors and mineralization-induced membrane actuation. Overall, the form, structure and polymorph of the mineralization products are synergistically affected by the additive and the content of Mg2+ ions. We also revisit the physicochemical nature of the biomineral scaffold and demonstrate the distinct spatial distribution of anionic biomolecules associated with the scaffold-mineral interface, as well as highlight the hydrogel-like properties of mammillae-associated macromolecules.

Collagen-grafted porous HDPE/PEAA scaffolds for bone reconstruction.

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Kim, Chang-Shik; Jung, Kyung-Hye; Kim, Hun; Kim, Chan-Bong; Kang, Inn-Kyu

2016-01-01

After tumor resection, bone reconstruction such as skull base reconstruction using interconnected porous structure is absolutely necessary. In this study, porous scaffolds for bone reconstruction were prepared using heat-pressing and salt-leaching methods. High-density polyethylene (HDPE) and poly(ethylene-co-acrylic acid) (PEAA) were chosen as the polymer composites for producing a porous scaffold of high mechanical strength and having high reactivity with biomaterials such as collagen, respectively. The porous structure was observed through surface images, and its intrusion volume and porosity were measured. Owing to the carboxylic acids on PEAA, collagen was successfully grafted onto the porous HDPE/PEAA scaffold, which was confirmed by FT-IR spectroscopy and electron spectroscopy for chemical analysis. Osteoblasts were cultured on the collagen-grafted porous scaffold, and their adhesion, proliferation, and differentiation were investigated. The high viability and growth of the osteoblasts suggest that the collagen-grafted porous HDPE/PEAA is a promising scaffold material for bone generation.

Three-dimensional wet-electrospun poly(lactic acid)/multi-wall carbon nanotubes scaffold induces differentiation of human menstrual blood-derived stem cells into germ-like cells.

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Eyni, Hossein; Ghorbani, Sadegh; Shirazi, Reza; Salari Asl, Leila; P Beiranvand, Shahram; Soleimani, Masoud

2017-09-01

Infertility caused by the disruption or absence of germ cells is a major and largely incurable medical problem. Germ cells (i.e., sperm or egg) play a key role in the transmission of genetic and epigenetic information across generations. Generation of gametes derived in vitro from stem cells hold promising prospects which could potentially help infertile men and women. Menstrual blood-derived stem cells are a unique stem cell source. Evidence suggests that menstrual blood-derived stem cells exhibit a multi-lineage potential and have attracted extensive attention in regenerative medicine. To maintain the three-dimensional structure of natural extra cellular matrices in vitro, scaffolds can do this favor and mimic a microenvironment for cell proliferation and differentiation. According to previous studies, poly(lactic acid) and multi-wall carbon nanotubes have been introduced as novel and promising biomaterials for the proliferation and differentiation of stem cells. Some cell types have been successfully grown on a matrix containing carbon nanotubes in tissue engineering but there is no report for this material to support stem cells differentiation into germ cells lineage. This study designed a 3D wet-electrospun poly(lactic acid) and poly(lactic acid)/multi-wall carbon nanotubes composite scaffold to compare infiltration, proliferation, and differentiation potential of menstrual blood-derived stem cells toward germ cell lineage with 2D culture. Our primary data revealed that the fabricated scaffold has mechanical and biological suitable qualities for supporting and attachments of stem cells. The differentiated menstrual blood-derived stem cells tracking in scaffolds using scanning electron microscopy confirmed cell attachment, aggregation, and distribution on the porous scaffold. Based on the differentiation assay by RT-PCR analysis, stem cells and germ-like cells markers were expressed in 3D groups as well as 2D one. It seems that poly(lactic acid

Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)–tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide

International Nuclear Information System (INIS)

Shao, Weili; He, Jianxin; Sang, Feng; Wang, Qian; Chen, Li; Cui, Shizhong; Ding, Bin

2016-01-01

To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering. - Highlights: • GO-doped PLGA–tussah silk fibroin ultrafine nanofibers with diameter of about 130 nm were fabricated by electrospinning. • Incorporation of 10 wt.% tussah silk to the PLGA nanofibers accelerates osteoblast differentiation and formation of new bone. • Mechanical properties of composite nanofiber mats had been significantly improved after embedding with GO nanosheets. • Nanostructured composite scaffolds effectively accelerate mesenchymal stem cells differentiation and formation of new bone.

Enhanced bone formation in electrospun poly(L-lactic-co-glycolic acid)–tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide

Energy Technology Data Exchange (ETDEWEB)

Shao, Weili [Key Laboratory of Advanced Textile Composites (Ministry of Education), Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); He, Jianxin, E-mail: hejianxin771117@163.com [Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Sang, Feng [Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000 (China); Wang, Qian [Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Chen, Li [Key Laboratory of Advanced Textile Composites (Ministry of Education), Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Cui, Shizhong [Key Laboratory of Advanced Textile Composites (Ministry of Education), Institute of Textile Composites, Tianjin Polytechnic University, Tianjin 300387 (China); Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); Ding, Bin [Henan Provincial Key Laboratory of Functional Textile Materials, Zhongyuan University of Technology, Zhengzhou 450007 (China); State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201600 (China)

2016-05-01

To engineer bone tissue, it is necessary to provide a biocompatible, mechanically robust scaffold. In this study, we fabricated an ultrafine nanofiber scaffold by electrospinning a blend of poly(L-lactic-co-glycolic acid), tussah silk fibroin, and graphene oxide (GO) and characterized its morphology, biocompatibility, mechanical properties, and biological activity. The data indicate that incorporation of 10 wt.% tussah silk and 1 wt.% graphene oxide into poly(L-lactic-co-glycolic acid) nanofibers significantly decreased the fiber diameter from 280 to 130 nm. Furthermore, tussah silk and graphene oxide boosted the Young's modulus and tensile strength by nearly 4-fold and 3-fold, respectively, and significantly enhanced adhesion, proliferation in mouse mesenchymal stem cells and functionally promoted biomineralization-relevant alkaline phosphatase (ALP) and mineral deposition. The results indicate that composite nanofibers could be excellent and versatile scaffolds for bone tissue engineering. - Highlights: • GO-doped PLGA–tussah silk fibroin ultrafine nanofibers with diameter of about 130 nm were fabricated by electrospinning. • Incorporation of 10 wt.% tussah silk to the PLGA nanofibers accelerates osteoblast differentiation and formation of new bone. • Mechanical properties of composite nanofiber mats had been significantly improved after embedding with GO nanosheets. • Nanostructured composite scaffolds effectively accelerate mesenchymal stem cells differentiation and formation of new bone.

In-situ birth of MSCs multicellular spheroids in poly(L-glutamic acid)/chitosan scaffold for hyaline-like cartilage regeneration.

Science.gov (United States)

Zhang, Kunxi; Yan, Shifeng; Li, Guifei; Cui, Lei; Yin, Jingbo

2015-12-01

The success of mesenchymal stem cells (MSCs) based articular cartilage tissue engineering is limited by the presence of fibrous tissue in generated cartilage, which is associated with the current scaffold strategy that promotes cellular adhesion and spreading. Here we design a non-fouling scaffold based on amide bonded poly(l-glutamic acid) (PLGA) and chitosan (CS) to drive adipose stem cells (ASCs) to aggregate to form multicellular spheroids with diameter of 80-110 μm in-situ. To illustrate the advantage of the present scaffolds, a cellular adhesive scaffold based on the same amide bonded PLGA and CS was created through a combination of air-drying and freeze-drying to limit the hydration effect while also achieving porous structure. Compared to ASCs spreading along the surface of pores within scaffold, the dense mass of aggregated ASCs in PLGA/CS scaffold exhibited enhanced chondrogenic differentiation capacity, as determined by up-regulated GAGs and COL II expression, and greatly decreased COL I deposition during in vitro chondrogenesis. Furthermore, after 12 weeks of implantation, neo-cartilages generated by ASCs adhered on scaffold significantly presented fibrous matrix which was characterized by high levels of COL I deposition. However, neo-cartilage at 12 weeks post-implantation generated by PLGA/CS scaffold carrying ASC spheroids possessed similar high level of GAGs and COL II and low level of COL I as that in normal cartilage. The in vitro and in vivo results indicated the present strategy could not only promote chondrogenesis of ASCs, but also facilitate hyaline-like cartilage regeneration with reduced fibrous tissue formation which may attenuate cartilage degradation in future long-term follow-up. Copyright © 2015 Elsevier Ltd. All rights reserved.

Shape memory nanocomposite of poly(L-lactic acid/graphene nanoplatelets triggered by infrared light and thermal heating

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S. Lashgari

2016-04-01

Full Text Available In this study, the effect of graphene nanoplatelets (GNPs on the shape memory properties of poly(L-lactic acid (PLLA was studied. In addition to thermal activation, the possibility of infrared actuating of thermo-responsive shape memory PLLA/GNPs nanocomposite was investigated. The incorporated GNPs were expected to absorb infrared wave’s energy and activate shape memory PLLA/GNPs. Different techniques such as differential scanning calorimetry (DSC, wide-angle X-ray diffraction (WAXD, field emission gun scanning electron microscope (FEG-SEM and dynamic mechanical thermal analysis (DMTA were used to characterize samples. DSC and WAXD results indicated that GNPs augmented crystallinity due to nucleating effect of graphene particles. GNPs improved both thermal and infrared activating shape memory properties along with faster response. Pure shape memory PLLA was slightly responsive to infrared light and its infrared actuated shape recovery ratio was 86% which increased to more than 95% with loading of GNPs. Drastic improvement in the crystallinity was obtained in nanocomposites with lower GNPs contents (0.5 and 1 wt% due to finer dispersion of graphene which resulted in more prominent mechanical and shape memory properties enhancement. Infrared activated shape memory PLLA/GNPs nanocomposites can be developed for wireless remote shape control of smart medical and bio-systems.

Patterning Multi-Nanostructured Poly(l-lactic acid) Fibrous Matrices to Manipulate Biomolecule Distribution and Functions.

Science.gov (United States)

Xiao, Wenwu; Li, Qingtao; He, Huimin; Li, Wenxiu; Cao, Xiaodong; Dong, Hua

2018-03-14

Precise manipulation of biomolecule distribution and functions via biomolecule-matrix interaction is very important and challenging for tissue engineering and regenerative medicine. As a well-known biomimetic matrix, electrospun fibers often lack the unique spatial complexity compared to their natural counterparts in vivo and thus cannot deliver fully the regulatory cues to biomolecules. In this paper, we report a facile and reliable method to fabricate micro- and nanostructured poly(l-lactic acid) (PLLA) fibrous matrices with spatial complexity by a combination of advanced electrospinning and agarose hydrogel stamp-based micropatterning. Specifically, advanced electrospinning is used to construct multi-nanostructures of fibrous matrices while solvent-loaded agarose hydrogel stamps are used to create microstructures. Compared with other methods, our method shows extreme simplicity and flexibility originated from the mono-/multi-spinneret conversion and limitless micropatterns of agarose hydrogel stamps. Three types of PLLA fibrous matrices including patterned nano-Ag/PLLA hybrid fibers, patterned bicompartment polyethylene terephthalate/PLLA fibers, and patterned hollow PLLA fibers are fabricated and their capability to manipulate biomolecule distribution and functions, that is, bacterial distribution and antibacterial performance, cell patterning and adhesion/spreading behaviors, and protein adsorption and delivery, is demonstrated in detail. The method described in our paper provides a powerful tool to restore spatial complexity in biomimetic matrices and would have promising applications in the field of biomedical engineering.

Development of macroporous calcium phosphate scaffold processed via microwave rapid drying

Energy Technology Data Exchange (ETDEWEB)

Jamuna-Thevi, K., E-mail: jamuna@sirim.my [Advanced Materials Research Centre (AMREC), SIRIM Berhad, Lot 34, Jalan Hi-Tech 2/3, Kulim Hi-Tech Park, 09000 Kulim, Kedah (Malaysia); Zakaria, F.A. [Advanced Materials Research Centre (AMREC), SIRIM Berhad, Lot 34, Jalan Hi-Tech 2/3, Kulim Hi-Tech Park, 09000 Kulim, Kedah (Malaysia); Othman, R. [Materials and Mineral Resources Engineering, Engineering Campus, Universiti Sains Malaysia, Seri Ampangan, 14300 Nibong Tebal, Penang (Malaysia); Muhamad, S. [Bioassay Unit, Herbal Medicine Research Centre (HMRC), Institute for Medical Research (IMR), Jalan Pahang, 50588 Kuala Lumpur (Malaysia)

2009-06-01

Porous hydroxyapatite (HA) scaffold has great potential in bone tissue engineering applications. A new method to fabricate macroporous calcium phosphate (CP) scaffold via microwave irradiation, followed by conventional sintering to form HA scaffold was developed. Incorporation of trisodium citrate dihydrate and citric acid in the CP mixture gave macroporous scaffolds upon microwave rapid drying. In this work, a mixture of {beta}-tricalcium phosphate ({beta}-TCP), calcium carbonate (CaCO{sub 3}), trisodium citrate dihydrate, citric acid and double distilled de-ionised water (DDI) was exposed to microwave radiation to form a macroporous structure. Based on gross eye examinations, addition of trisodium citrate at 30 and 40 wt.% in the CP mixture ({beta}-TCP and CaCO{sub 3}) without citric acid indicates increasing order of pore volume where the highest porosity yield was observed at 40 wt.% of trisodium citrate addition and the pore size was detected at several millimeters. Therefore, optimization of pore size was performed by adding 3-7 wt.% of citric acid in the CP mixture which was separately mixed with 30 and 40 wt.% of trisodium citrate for comparison purposes. Fabricated scaffolds were calcined at 600 deg. C and washed with DDI water to remove the sodium hydroxycarbonate and sintered at 1250 deg. C to form HA phase as confirmed in the X-ray diffraction (XRD) results. Based on Archimedes method, HA scaffolds prepared from 40 wt.% of trisodium citrate with 3-7 wt.% of citric acid added CP mixture have an open and interconnected porous structure ranging from 51 to 53 vol.% and observation using Scanning electron microscope (SEM) showed the pore size distribution between 100 and 500 {mu}m. The cytotoxicity tests revealed that the porous HA scaffolds have no cytotoxic potential on MG63 osteoblast-like cells which might allow for their use as biomaterials.

In vitro osteoclastogenesis on textile chitosan scaffold

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C Heinemann

2010-02-01

Full Text Available Textile chitosan fibre scaffolds were evaluated in terms of interaction with osteoclast-like cells, derived from human primary monocytes. Part of the scaffolds was further modified by coating with fibrillar collagen type I in order to make the surface biocompatible. Monocytes were cultured directly on the scaffolds in the presence of macrophage colony stimulating factor (M-CSF and receptor activator of nuclear factor kappaB ligand (RANKL for up to 18 days. Confocal laser scanning microscopy (CLSM as well as scanning electron microscopy (SEM revealed the formation of multinuclear osteoclast-like cells on both the raw chitosan fibres and the collagen-coated scaffolds. The modified surface supported the osteoclastogenesis. Differentiation towards the osteoclastic lineage was confirmed by the microscopic detection of cathepsin K, tartrate resistant acid phosphatase (TRAP, acidic compartments using 3-(2,4-dinitroanillino-3’-amino-N-methyldipropylamine (DAMP, immunological detection of TRAP isoform 5b, and analysis of gene expression of the osteoclastic markers TRAP, cathepsin K, vitronectin receptor, and calcitonin receptor using reverse transcription-polymerase chain reaction (RT-PCR. The feature of the collagen-coated but also of the raw chitosan fibre scaffolds to support attachment and differentiation of human monocytes facilitates cell-induced material resorption – one main requirement for successful bone tissue engineering.

Nature derived scaffolds for tissue engineering applications: Design and fabrication of a composite scaffold incorporating chitosan-g-d,l-lactic acid and cellulose nanocrystals from Lactuca sativa L. cv green leaf.

Science.gov (United States)

Ko, Sung Won; Soriano, Juan Paolo E; Lee, Ji Yeon; Unnithan, Afeesh Rajan; Park, Chan Hee; Kim, Cheol Sang

2018-04-15

Through exhaustive extraction via successive alkali and bleaching treatments cellulose was isolated from lettuce. The isolated cellulose was hydrolyzed using 64wt% H 2 SO 4 at 55°C under constant stirring for 1h to obtain cellulose nanocrystals (CNCs). Characterizations such as SEM, TEM, FTIR, TGA and XRD were done in order to determine differences in the physico-chemical characteristics of cellulose after each treatment step. The isolated CNCs have mean dimensions of 237±26, 33±12 and 32±7nm in length, thickness and height, respectively. These nanocrystals were incorporated to the formulations that were used to fabricate different chitosan-g-d,l-lactic acid (CgLA) scaffolds. Amide linkage formation between chitosan and lactic acid and further removal of water was facilitated by oven-drying under vacuum at 80°C. Results show that an increase in the concentration of CNCs added, increase in porosity, degradability, drug release property and cell viability were observed from the fabricated composite scaffolds. These results can provide information on how nanofillers such as CNCs can alter the properties of tissue scaffolds through the chemical properties and interactions they provide. Moreover, these characteristics can give new properties that are necessary for certain tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

[Strategies to choose scaffold materials for tissue engineering].

Science.gov (United States)

Gao, Qingdong; Zhu, Xulong; Xiang, Junxi; Lü, Yi; Li, Jianhui

2016-02-01

Current therapies of organ failure or a wide range of tissue defect are often not ideal. Transplantation is the only effective way for long time survival. But it is hard to meet huge patients demands because of donor shortage, immune rejection and other problems. Tissue engineering could be a potential option. Choosing a suitable scaffold material is an essential part of it. According to different sources, tissue engineering scaffold materials could be divided into three types which are natural and its modified materials, artificial and composite ones. The purpose of tissue engineering scaffold is to repair the tissues or organs damage, so could reach the ideal recovery in its function and structure aspect. Therefore, tissue engineering scaffold should even be as close as much to the original tissue or organs in function and structure. We call it "organic scaffold" and this strategy might be the drastic perfect substitute for the tissues or organs in concern. Optimized organization with each kind scaffold materials could make up for biomimetic structure and function of the tissue or organs. Scaffold material surface modification, optimized preparation procedure and cytosine sustained-release microsphere addition should be considered together. This strategy is expected to open new perspectives for tissue engineering. Multidisciplinary approach including material science, molecular biology, and engineering might find the most ideal tissue engineering scaffold. Using the strategy of drawing on each other strength and optimized organization with each kind scaffold material to prepare a multifunctional biomimetic tissue engineering scaffold might be a good method for choosing tissue engineering scaffold materials. Our research group had differentiated bone marrow mesenchymal stem cells into bile canaliculi like cells. We prepared poly(L-lactic acid)/poly(ε-caprolactone) biliary stent. The scaffold's internal played a part in the long-term release of cytokines which

Hyaluronic acid/poly(lactic-co-glycolic acid) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate as skin tissue engineering scaffolds.

Science.gov (United States)

Lee, Eun Ji; Lee, Jong Ho; Jin, Linhua; Jin, Oh Seong; Shin, Yong Cheol; Sang, Jin Oh; Lee, Jaebeom; Hyon, Suong-Hyu; Han, Dong-Wook

2014-11-01

In this study, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) for application to tissue engineering scaffolds for skin regeneration were prepared via coaxial electrospinning. Physicochemical properties of HA/PLGA-E core/shell fiber meshes were characterized by SEM, Raman spectroscopy, contact angle, EGCG release profiling and in vitro degradation. Biomechanical properties of HA/PLGA-E meshes were also investigated by a tensile strength test. SEM images showed that HA/PLGA-E fiber meshes had a three-dimensional interconnected pore structure with an average fiber diameter of about 1270 nm. Raman spectra revealed that EGCG was uniformly dispersed in the PLGA shell of meshes. HA/PLGA-E meshes showed sustained EGCG release patterns by controlled diffusion and PLGA degradation over 4 weeks. EGCG loading did not adversely affect the tensile strength and elastic modulus of HA/PLGA meshes, while increased their hydrophilicity and surface energy. Attachment of human dermal fibroblasts on HA/PLGA-E meshes was appreciably increased and their proliferation was steadily retained during the culture period. These results suggest that HA/PLGA-E core/shell fiber meshes can be potentially used as scaffolds supporting skin regeneration.

Reduction of inflammatory responses and enhancement of extracellular matrix formation by vanillin-incorporated poly(lactic-co-glycolic acid) scaffolds.

Science.gov (United States)

Lee, Yujung; Kwon, Jeongil; Khang, Gilson; Lee, Dongwon

2012-10-01

Vanillin is one of the major components of vanilla, a commonly used flavoring agent and preservative and is known to exert potent antioxidant and anti-inflammatory activities. In this work, vanillin-incorporated poly(lactic-co-glycolic acid) (PLGA) films and scaffolds were fabricated to evaluate the effects of vanillin on the inflammatory responses and extracellular matrix (ECM) formation in vitro and in vivo. The incorporation of vanillin to PLGA films induced hydrophilic nature, resulting in the higher cell attachment and proliferation than the pure PLGA film. Vanillin also reduced the generation of reactive oxygen species (ROS) in cells cultured on the pure PLGA film and significantly inhibited the PLGA-induced inflammatory responses in vivo, evidenced by the reduced accumulation of inflammatory cells and thinner fibrous capsules. The effects of vanillin on the ECM formation were evaluated using annulus fibrous (AF) cell-seeded porous PLGA/vanillin scaffolds. PLGA/vanillin scaffolds elicited the more production of glycosaminoglycan and collagen than the pure PLGA scaffold, in a concentration-dependent manner. Based on the low level of inflammatory responses and enhanced ECM formation, vanillin-incorporated PLGA constructs make them promising candidates in the future biomedical applications.

Reduction of Inflammatory Responses and Enhancement of Extracellular Matrix Formation by Vanillin-Incorporated Poly(Lactic-co-Glycolic Acid) Scaffolds

Science.gov (United States)

Lee, Yujung; Kwon, Jeongil; Khang, Gilson

2012-01-01

Vanillin is one of the major components of vanilla, a commonly used flavoring agent and preservative and is known to exert potent antioxidant and anti-inflammatory activities. In this work, vanillin-incorporated poly(lactic-co-glycolic acid) (PLGA) films and scaffolds were fabricated to evaluate the effects of vanillin on the inflammatory responses and extracellular matrix (ECM) formation in vitro and in vivo. The incorporation of vanillin to PLGA films induced hydrophilic nature, resulting in the higher cell attachment and proliferation than the pure PLGA film. Vanillin also reduced the generation of reactive oxygen species (ROS) in cells cultured on the pure PLGA film and significantly inhibited the PLGA-induced inflammatory responses in vivo, evidenced by the reduced accumulation of inflammatory cells and thinner fibrous capsules. The effects of vanillin on the ECM formation were evaluated using annulus fibrous (AF) cell-seeded porous PLGA/vanillin scaffolds. PLGA/vanillin scaffolds elicited the more production of glycosaminoglycan and collagen than the pure PLGA scaffold, in a concentration-dependent manner. Based on the low level of inflammatory responses and enhanced ECM formation, vanillin-incorporated PLGA constructs make them promising candidates in the future biomedical applications. PMID:22551555

A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering.

Science.gov (United States)

Boukari, Yamina; Qutachi, Omar; Scurr, David J; Morris, Andrew P; Doughty, Stephen W; Billa, Nashiru

2017-11-01

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.

Image-based characterization of foamed polymeric tissue scaffolds

International Nuclear Information System (INIS)

Mather, Melissa L; Morgan, Stephen P; Crowe, John A; White, Lisa J; Shakesheff, Kevin M; Tai, Hongyun; Howdle, Steven M; Kockenberger, Walter

2008-01-01

Tissue scaffolds are integral to many regenerative medicine therapies, providing suitable environments for tissue regeneration. In order to assess their suitability, methods to routinely and reproducibly characterize scaffolds are needed. Scaffold structures are typically complex, and thus their characterization is far from trivial. The work presented in this paper is centred on the application of the principles of scaffold characterization outlined in guidelines developed by ASTM International. Specifically, this work demonstrates the capabilities of different imaging modalities and analysis techniques used to characterize scaffolds fabricated from poly(lactic-co-glycolic acid) using supercritical carbon dioxide. Three structurally different scaffolds were used. The scaffolds were imaged using: scanning electron microscopy, micro x-ray computed tomography, magnetic resonance imaging and terahertz pulsed imaging. In each case two-dimensional images were obtained from which scaffold properties were determined using image processing. The findings of this work highlight how the chosen imaging modality and image-processing technique can influence the results of scaffold characterization. It is concluded that in order to obtain useful results from image-based scaffold characterization, an imaging methodology providing sufficient contrast and resolution must be used along with robust image segmentation methods to allow intercomparison of results

Culture on 3D Chitosan-Hyaluronic Acid Scaffolds Enhances Stem Cell Marker Expression and Drug Resistance in Human Glioblastoma Cancer Stem Cells.

Science.gov (United States)

Wang, Kui; Kievit, Forrest M; Erickson, Ariane E; Silber, John R; Ellenbogen, Richard G; Zhang, Miqin

2016-12-01

The lack of in vitro models that support the growth of glioblastoma (GBM) stem cells (GSCs) that underlie clinical aggressiveness hinders developing new, effective therapies for GBM. While orthotopic patient-derived xenograft models of GBM best reflect in vivo tumor behavior, establishing xenografts is a time consuming, costly, and frequently unsuccessful endeavor. To address these limitations, a 3D porous scaffold composed of chitosan and hyaluronic acid (CHA) is synthesized. Growth and expression of the cancer stem cell (CSC) phenotype of the GSC GBM6 taken directly from fresh xenogratfs grown on scaffolds or as adherent monolayers is compared. While 2D adherent cultures grow as monolayers of flat epitheliod cells, GBM6 cells proliferate within pores of CHA scaffolds as clusters of self-adherent ovoid cells. Growth on scaffolds is accompanied by greater expression of genes that mediate epithelial-mesenchymal transition and maintain a primitive, undifferentiated phenotype, hallmarks of CSCs. Scaffold-grown cells also display higher expression of genes that promote resistance to hypoxia-induced oxidative stress. In accord, scaffold-grown cells show markedly greater resistance to clinically utilized alkylating agents compared to adherent cells. These findings suggest that our CHA scaffolds better mimic in vivo biological and clinical behavior and provide insights for developing novel individualized treatments. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cold atmospheric plasma (CAP) surface nanomodified 3D printed polylactic acid (PLA) scaffolds for bone regeneration.

Science.gov (United States)

Wang, Mian; Favi, Pelagie; Cheng, Xiaoqian; Golshan, Negar H; Ziemer, Katherine S; Keidar, Michael; Webster, Thomas J

2016-12-01

Three-dimensional (3D) printing is a new fabrication method for tissue engineering which can precisely control scaffold architecture at the micron-scale. However, scaffolds not only need 3D biocompatible structures that mimic the micron structure of natural tissues, they also require mimicking of the nano-scale extracellular matrix properties of the tissue they intend to replace. In order to achieve this, the objective of the present in vitro study was to use cold atmospheric plasma (CAP) as a quick and inexpensive way to modify the nano-scale roughness and chemical composition of a 3D printed scaffold surface. Water contact angles of a normal 3D printed poly-lactic-acid (PLA) scaffold dramatically dropped after CAP treatment from 70±2° to 24±2°. In addition, the nano-scale surface roughness (Rq) of the untreated 3D PLA scaffolds drastically increased (up to 250%) after 1, 3, and 5min of CAP treatment from 1.20nm to 10.50nm, 22.90nm, and 27.60nm, respectively. X-ray photoelectron spectroscopy (XPS) analysis showed that the ratio of oxygen to carbon significantly increased after CAP treatment, which indicated that the CAP treatment of PLA not only changed nano-scale roughness but also chemistry. Both changes in hydrophilicity and nano-scale roughness demonstrated a very efficient plasma treatment, which in turn significantly promoted both osteoblast (bone forming cells) and mesenchymal stem cell attachment and proliferation. These promising results suggest that CAP surface modification may have potential applications for enhancing 3D printed PLA bone tissue engineering materials (and all 3D printed materials) in a quick and an inexpensive manner and, thus, should be further studied. Three-dimensional (3D) printing is a new fabrication method for tissue engineering which can precisely control scaffold architecture at the micron-scale. Although their success is related to their ability to exactly mimic the structure of natural tissues and control mechanical

Composite porous scaffold of PEG/PLA support improved bone matrix deposition in vitro compared to PLA-only scaffolds.

Science.gov (United States)

Bhaskar, Birru; Owen, Robert; Bahmaee, Hossein; Wally, Zena; Sreenivasa Rao, Parcha; Reilly, Gwendolen C

2018-05-01

Controllable pore size and architecture are essential properties for tissue-engineering scaffolds to support cell ingrowth colonization. To investigate the effect of polyethylene glycol (PEG) addition on porosity and bone-cell behavior, porous polylactic acid (PLA)-PEG scaffolds were developed with varied weight ratios of PLA-PEG (100/0, 90/10, 75/25) using solvent casting and porogen leaching. Sugar 200-300 µm in size was used as a porogen. To assess scaffold suitability for bone tissue engineering, MLO-A5 murine osteoblast cells were cultured and cell metabolic activity, alkaline phosphatase (ALP) activity and bone-matrix production determined using (alizarin red S staining for calcium and direct red 80 staining for collagen). It was found that metabolic activity was significantly higher over time on scaffolds containing PEG, ALP activity and mineralized matrix production were also significantly higher on scaffolds containing 25% PEG. Porous architecture and cell distribution and penetration into the scaffold were analyzed using SEM and confocal microscopy, revealing that inclusion of PEG increased pore interconnectivity and therefore cell ingrowth in comparison to pure PLA scaffolds. The results of this study confirmed that PLA-PEG porous scaffolds support mineralizing osteoblasts better than pure PLA scaffolds, indicating they have a high potential for use in bone tissue engineering applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1334-1340, 2018. © 2018 Wiley Periodicals, Inc.

Fabrication of novel high performance ductile poly(lactic acid) nanofiber scaffold coated with poly(vinyl alcohol) for tissue engineering applications

Energy Technology Data Exchange (ETDEWEB)

Abdal-hay, Abdalla, E-mail: abda_55@jbnu.ac.kr [Dept of Engineering Materials and Mechanical Design, Faculty of Engineering, South Valley of University, Qena 83523 (Egypt); Hussein, Kamal Hany [Stem Cell Institute and College of Veterinary Medicine, Kangwon National University, Chuncheon, Gangwon 200-701 (Korea, Republic of); Casettari, Luca [Department of Biomolecular Sciences, University of Urbino, Piazza Rinascimento, 6, Urbino, PU 61029 (Italy); Khalil, Khalil Abdelrazek [Dept. of Mechanical Engineering, College of Engineering, King Saud University, 800, Riyadh 11421 (Saudi Arabia); Dept. of Mechanical Engineering, Faculty of Energy Engineering, Aswan University, Aswan (Egypt); Hamdy, Abdel Salam [Dept. of Manufacturing and Industrial Engineering, College of Engineering and Computer Science, University of Texas Rio Grande Valley, 1201 West University Dr., Edinburg, TX 78541-2999 (United States)

2016-03-01

Poly(lactic acid) (PLA) nanofiber scaffold has received increasing interest as a promising material for potential application in the field of regenerative medicine. However, the low (hydrophilicity) and poor ductility restrict its practical application. Integration of hydrophilic elastic polymer onto the surface of the nanofiber scaffold may help to overcome the drawbacks of PLA material. Herein, we successfully optimized the parameters for in situ deposition of poly(vinyl alcohol), (PVA) onto post-electrospun PLA nanofibers using a simple hydrothermal approach. Our results showed that the average fiber diameter of coated nanofiber mat is about 1265 ± 222 nm, which is remarkably higher than its pristine counterpart (650 ± 180 nm). The hydrophilicity of PLA nanofiber scaffold coated with a PVA thin layer improved dramatically (36.11 ± 1.5°) compared to that of pristine PLA (119.7 ± 1.5°) scaffold. The mechanical testing showed that the PLA nanofiber scaffold could be converted from rigid to ductile with enhanced tensile strength, due to maximizing the hydrogen bond interaction during the heat treatment and in the presence of PVA. Cytocompatibility performance of the pristine and coated PLA fibers with PVA was observed through an in vitro experiment based on cell attachment and the MTT assay by EA.hy926 human endothelial cells. The cytocompatibility results showed that human cells induced more favorable attachment and proliferation behavior on hydrophilic PLA composite scaffold than that of pristine PLA. Hence, PVA coating resulted in an increase in initial human cell attachment and proliferation. We believe that the novel PVA-coated PLA nanofiber scaffold developed in this study, could be a promising high performance biomaterial in regeneration medicine. - Highlights: • Novel PVA-coated PLA nanofibers were prepared by a simple hydrothermal route. • This in situ treatment strategy for PLA fibers induced polymer chain conformation. • Bonding interaction

Fabrication of novel high performance ductile poly(lactic acid) nanofiber scaffold coated with poly(vinyl alcohol) for tissue engineering applications

International Nuclear Information System (INIS)

Abdal-hay, Abdalla; Hussein, Kamal Hany; Casettari, Luca; Khalil, Khalil Abdelrazek; Hamdy, Abdel Salam

2016-01-01

Poly(lactic acid) (PLA) nanofiber scaffold has received increasing interest as a promising material for potential application in the field of regenerative medicine. However, the low (hydrophilicity) and poor ductility restrict its practical application. Integration of hydrophilic elastic polymer onto the surface of the nanofiber scaffold may help to overcome the drawbacks of PLA material. Herein, we successfully optimized the parameters for in situ deposition of poly(vinyl alcohol), (PVA) onto post-electrospun PLA nanofibers using a simple hydrothermal approach. Our results showed that the average fiber diameter of coated nanofiber mat is about 1265 ± 222 nm, which is remarkably higher than its pristine counterpart (650 ± 180 nm). The hydrophilicity of PLA nanofiber scaffold coated with a PVA thin layer improved dramatically (36.11 ± 1.5°) compared to that of pristine PLA (119.7 ± 1.5°) scaffold. The mechanical testing showed that the PLA nanofiber scaffold could be converted from rigid to ductile with enhanced tensile strength, due to maximizing the hydrogen bond interaction during the heat treatment and in the presence of PVA. Cytocompatibility performance of the pristine and coated PLA fibers with PVA was observed through an in vitro experiment based on cell attachment and the MTT assay by EA.hy926 human endothelial cells. The cytocompatibility results showed that human cells induced more favorable attachment and proliferation behavior on hydrophilic PLA composite scaffold than that of pristine PLA. Hence, PVA coating resulted in an increase in initial human cell attachment and proliferation. We believe that the novel PVA-coated PLA nanofiber scaffold developed in this study, could be a promising high performance biomaterial in regeneration medicine. - Highlights: • Novel PVA-coated PLA nanofibers were prepared by a simple hydrothermal route. • This in situ treatment strategy for PLA fibers induced polymer chain conformation. • Bonding interaction

Novel biodegradable porous scaffold applied to skin regeneration.

Science.gov (United States)

Wang, Hui-Min; Chou, Yi-Ting; Wen, Zhi-Hong; Wang, Chau-Zen; Wang, Zhao-Ren; Chen, Chun-Hong; Ho, Mei-Ling

2013-01-01

Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5±8.4 µm measured from SEM images. With human skin cells growing for 7 days, the SEM images showed surface fractures on the scaffold due to enzymatic digestion, indicating the biodegradable properties of this scaffold. To simulate skin distribution, the human epidermal keratinocytes, melanocytes and dermal fibroblasts were seeded on the porous scaffold and the cross-section immunofluorescent staining demonstrated normal human skin layer distributions. The collagen amount was also quantified after skin cells seeding and presented an amount 50% higher than those seeded on culture wells. The in vivo histological results showed that the scaffold ameliorated wound healing, including decreasing neutrophil infiltrates and thickening newly generated skin compared to the group without treatments.

Novel biodegradable porous scaffold applied to skin regeneration.

Directory of Open Access Journals (Sweden)

Hui-Min Wang

Full Text Available Skin wound healing is an important lifesaving issue for massive lesions. A novel porous scaffold with collagen, hyaluronic acid and gelatin was developed for skin wound repair. The swelling ratio of this developed scaffold was assayed by water absorption capacity and showed a value of over 20 g water/g dried scaffold. The scaffold was then degraded in time- and dose-dependent manners by three enzymes: lysozyme, hyaluronidase and collagenase I. The average pore diameter of the scaffold was 132.5±8.4 µm measured from SEM images. With human skin cells growing for 7 days, the SEM images showed surface fractures on the scaffold due to enzymatic digestion, indicating the biodegradable properties of this scaffold. To simulate skin distribution, the human epidermal keratinocytes, melanocytes and dermal fibroblasts were seeded on the porous scaffold and the cross-section immunofluorescent staining demonstrated normal human skin layer distributions. The collagen amount was also quantified after skin cells seeding and presented an amount 50% higher than those seeded on culture wells. The in vivo histological results showed that the scaffold ameliorated wound healing, including decreasing neutrophil infiltrates and thickening newly generated skin compared to the group without treatments.

Porous titanium scaffolds with injectable hyaluronic acid-DBM gel for bone substitution in a rat critical-sized calvarial defect model.

Science.gov (United States)

van Houdt, C I A; Cardoso, D A; van Oirschot, B A J A; Ulrich, D J O; Jansen, J A; Leeuwenburgh, S C G; van den Beucken, J J J P

2017-09-01

Demineralized bone matrix (DBM) is an allograft bone substitute used for bone repair surgery to overcome drawbacks of autologous bone grafting, such as limited supply and donor-site comorbidities. In view of different demineralization treatments to obtain DBM, we examined the biological performance of two differently demineralized types of DBM, i.e. by acidic treatment using hydrochloric acid (HCl) or treatment with the chelating agent ethylene diamine tetra-acetate (EDTA). First, we evaluated the osteo-inductive properties of both DBMs by implanting the materials subcutaneously in rats. Second, we evaluated the effects on bone formation by incorporating DBM in a hyaluronic acid (HA) gel to fill a porous titanium scaffold for use in a critical-sized calvarial defect model in 36 male Wistar rats. These porous titanium scaffolds were implanted empty or filled with HA gel containing either DBM HCl or DBM EDTA. Ectopically implanted DBM HCl and DBM EDTA did not induce ectopic bone formation over the course of 12 weeks. For the calvarial defects, mean percentages of newly formed bone at 2 weeks were significantly higher for Ti-Empty compared to Ti-HA + DBM HCl , but not compared to Ti-HA + DBM EDTA. Significant temporal bone formation was observed for Ti-Empty and Ti-HA + DBM HCl, but not for Ti-HA + DBM EDTA. At 8 weeks there were no significant differences in values of bone formation between the three experimental constructs. In conclusion, these results showed that, under the current experimental conditions, neither DBM HCl nor DBM EDTA possess osteo-inductive properties. Additionally, in combination with an HA gel loaded in a porous titanium scaffold, DBM HCl and DBM EDTA showed similar amounts of new bone formation after 8 weeks, which were lower than using the empty porous titanium scaffold. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

In vitro evaluation of crosslinked electrospun fish gelatin scaffolds

International Nuclear Information System (INIS)

Gomes, S.R.; Rodrigues, G.; Martins, G.G.; Henriques, C.M.R.; Silva, J.C.

2013-01-01

Gelatin from cold water fish skin was electrospun, crosslinked and investigated as a substrate for the adhesion and proliferation of cells. Gelatin was first dissolved in either water or concentrated acetic acid and both solutions were successfully electrospun. Cross-linking was achieved via three different routes: glutaraldehyde vapor, genipin and dehydrothermal treatment. Solution's properties (surface tension, electrical conductivity and viscosity) and scaffold's properties (chemical bonds, weight loss and fiber diameters) were measured. Cellular viability was analyzed culturing 3T3 fibroblasts plated on the scaffolds and grown up to 7 days. The cells were fixed and observed with SEM or stained for DNA and F-actin and observed with confocal microscopy. In all scaffolds, the cells attached and spread with varying degrees. The evaluation of cell viability showed proliferation of cells until confluence in scaffolds crosslinked by glutaraldehyde and genipin; however the rate of growth in genipin crosslinked scaffolds was slow, recovering only by day five. The results using the dehydrothermal treatment were the less satisfactory. Our results show that glutaraldehyde treated fish gelatin is the most suitable substrate, of the three studied, for fibroblast adhesion and proliferation. - Highlights: ► Electrospinning of fish gelatin dissolved in both water or concentrated acetic acid ► Glutaraldehyde, genipin and dehydrothermal treatment effectively crosslink the fish gelatin fibers ► Fibroblasts effectively adhere to and propagate on all scaffolds ► Cell population is highest for glutaraldehyde crosslinked scaffolds ► Cells exhibit more filopodia and stress fibers on glutaraldehyde crosslinked scaffolds

In vitro evaluation of crosslinked electrospun fish gelatin scaffolds

Energy Technology Data Exchange (ETDEWEB)

Gomes, S.R. [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Rodrigues, G.; Martins, G.G. [Centro de Biologia Ambiental / Departamento de Biologia Animal, Faculdade de Ciências da Universidade de Lisboa, FCUL, 1749-016 Campo Grande, Lisboa (Portugal); Henriques, C.M.R. [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Silva, J.C., E-mail: jcs@fct.unl.pt [Centro de Física e Investigação Tecnológica / Departamento de Física, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

2013-04-01

Gelatin from cold water fish skin was electrospun, crosslinked and investigated as a substrate for the adhesion and proliferation of cells. Gelatin was first dissolved in either water or concentrated acetic acid and both solutions were successfully electrospun. Cross-linking was achieved via three different routes: glutaraldehyde vapor, genipin and dehydrothermal treatment. Solution's properties (surface tension, electrical conductivity and viscosity) and scaffold's properties (chemical bonds, weight loss and fiber diameters) were measured. Cellular viability was analyzed culturing 3T3 fibroblasts plated on the scaffolds and grown up to 7 days. The cells were fixed and observed with SEM or stained for DNA and F-actin and observed with confocal microscopy. In all scaffolds, the cells attached and spread with varying degrees. The evaluation of cell viability showed proliferation of cells until confluence in scaffolds crosslinked by glutaraldehyde and genipin; however the rate of growth in genipin crosslinked scaffolds was slow, recovering only by day five. The results using the dehydrothermal treatment were the less satisfactory. Our results show that glutaraldehyde treated fish gelatin is the most suitable substrate, of the three studied, for fibroblast adhesion and proliferation. - Highlights: ► Electrospinning of fish gelatin dissolved in both water or concentrated acetic acid ► Glutaraldehyde, genipin and dehydrothermal treatment effectively crosslink the fish gelatin fibers ► Fibroblasts effectively adhere to and propagate on all scaffolds ► Cell population is highest for glutaraldehyde crosslinked scaffolds ► Cells exhibit more filopodia and stress fibers on glutaraldehyde crosslinked scaffolds.

Electrospun poly(lactic acid) based conducting nanofibrous networks

International Nuclear Information System (INIS)

Patra, S N; Bhattacharyya, D; Ray, S; Easteal, A J

2009-01-01

Multi-functionalised micro/nanostructures of conducting polymers in neat or blended forms have received much attention because of their unique properties and technological applications in electrical, magnetic and biomedical devices. Biopolymer-based conducting fibrous mats are of special interest for tissue engineering because they not only physically support tissue growth but also are electrically conductive, and thus are able to stimulate specific cell functions or trigger cell responses. They are effective for carrying current in biological environments and can thus be considered for delivering local electrical stimuli at the site of damaged tissue to promote wound healing. Electrospinning is an established way to process polymer solutions or melts into continuous fibres with diameter often in the nanometre range. This process primarily depends on a number of parameters, including the type of polymer, solution viscosity, polarity and surface tension of the solvent, electric field strength and the distance between the spinneret and the collector. The present research has included polyaniline (PANi) as the conducting polymer and poly(L-lactic acid) (PLLA) as the biopolymer. Dodecylbenzene sulphonic acid (DBSA) doped PANi and PLLA have been dissolved in a common solvent (mixtures of chloroform and dimethyl formamide (DMF)), and the solutions successfully electrospun. DMF enhanced the dielectric constant of the solvent, and tetra butyl ammonium bromide (TBAB) was used as an additive to increase the conductivity of the solution. DBSA-doped PANi/PLLA mat exhibits an almost bead-free network of nanofibres that have extraordinarily smooth surface and diameters in the range 75 to 100 nm.

Fabrication of novel high performance ductile poly(lactic acid) nanofiber scaffold coated with poly(vinyl alcohol) for tissue engineering applications.

Science.gov (United States)

Abdal-Hay, Abdalla; Hussein, Kamal Hany; Casettari, Luca; Khalil, Khalil Abdelrazek; Hamdy, Abdel Salam

2016-03-01

Poly(lactic acid) (PLA) nanofiber scaffold has received increasing interest as a promising material for potential application in the field of regenerative medicine. However, the low hydrophilicity and poor ductility restrict its practical application. Integration of hydrophilic elastic polymer onto the surface of the nanofiber scaffold may help to overcome the drawbacks of PLA material. Herein, we successfully optimized the parameters for in situ deposition of poly(vinyl alcohol), (PVA) onto post-electrospun PLA nanofibers using a simple hydrothermal approach. Our results showed that the average fiber diameter of coated nanofiber mat is about 1265±222 nm, which is remarkably higher than its pristine counterpart (650±180 nm). The hydrophilicity of PLA nanofiber scaffold coated with a PVA thin layer improved dramatically (36.11±1.5°) compared to that of pristine PLA (119.7±1.5°) scaffold. The mechanical testing showed that the PLA nanofiber scaffold could be converted from rigid to ductile with enhanced tensile strength, due to maximizing the hydrogen bond interaction during the heat treatment and in the presence of PVA. Cytocompatibility performance of the pristine and coated PLA fibers with PVA was observed through an in vitro experiment based on cell attachment and the MTT assay by EA.hy926 human endothelial cells. The cytocompatibility results showed that human cells induced more favorable attachment and proliferation behavior on hydrophilic PLA composite scaffold than that of pristine PLA. Hence, PVA coating resulted in an increase in initial human cell attachment and proliferation. We believe that the novel PVA-coated PLA nanofiber scaffold developed in this study, could be a promising high performance biomaterial in regeneration medicine. Copyright © 2015. Published by Elsevier B.V.

Tough Blends of Polylactide and Castor Oil

Energy Technology Data Exchange (ETDEWEB)

Robertson, Megan L.; Paxton, Jessica M.; Hillmyer, Marc A. (UMM)

2012-10-10

Poly(l-lactide) (PLLA) is a renewable resource polymer derived from plant sugars with several commercial applications. Broader implementation of the material is limited due to its inherent brittleness. We show that the addition of 5 wt % castor oil to PLLA significantly enhances the overall tensile toughness with minimal reductions in the modulus and no plasticization of the PLLA matrix. In addition, we used poly(ricinoleic acid)-PLLA diblock copolymers, synthesized entirely from renewable resources, as compatibilizers for the PLLA/castor oil blends. Ricinoleic acid, the majority fatty acid comprising castor oil, was polymerized through a lipase-catalyzed condensation reaction. The resulting polymers contained a hydroxyl end-group that was subsequently used to initiate the ring-opening polymerization of L-lactide. The binary PLLA/castor oil blend exhibited a tensile toughness seven times greater than neat PLLA. The addition of block copolymer allowed for control over the morphology of the blends, and even further improvement in the tensile toughness was realized - an order of magnitude larger than that of neat PLLA.

Tough blends of polylactide and castor oil.

Science.gov (United States)

Robertson, Megan L; Paxton, Jessica M; Hillmyer, Marc A

2011-09-01

Poly(l-lactide) (PLLA) is a renewable resource polymer derived from plant sugars with several commercial applications. Broader implementation of the material is limited due to its inherent brittleness. We show that the addition of 5 wt % castor oil to PLLA significantly enhances the overall tensile toughness with minimal reductions in the modulus and no plasticization of the PLLA matrix. In addition, we used poly(ricinoleic acid)-PLLA diblock copolymers, synthesized entirely from renewable resources, as compatibilizers for the PLLA/castor oil blends. Ricinoleic acid, the majority fatty acid comprising castor oil, was polymerized through a lipase-catalyzed condensation reaction. The resulting polymers contained a hydroxyl end-group that was subsequently used to initiate the ring-opening polymerization of l-lactide. The binary PLLA/castor oil blend exhibited a tensile toughness seven times greater than neat PLLA. The addition of block copolymer allowed for control over the morphology of the blends, and even further improvement in the tensile toughness was realized-an order of magnitude larger than that of neat PLLA.

Carbon nanotube-coating accelerated cell adhesion and proliferation on poly (L-lactide)

International Nuclear Information System (INIS)

Hirata, Eri; Akasaka, Tsukasa; Uo, Motohiro; Takita, Hiroko; Watari, Fumio; Yokoyama, Atsuro

2012-01-01

Highlights: ► The surface of a polylactic acid (PLLA) was coated multiwalled carbon nanotubes (MWCNTs). ► MWCNT-coated PLLA showed remarkable higher wettability than uncoated PLLA. ► More Human osteosarcoma cell line (Saos2) adhered on the CNT-coated than those on uncoated PLLA at 2 h after seeding. ► MWCNT-coating on PLLA improved the surface wettability and initial cell attachment at early stage. - Abstract: The surface of a polylactic acid (PLLA) was coated multiwalled carbon nanotubes (MWCNTs) in order to improve the surface properties. In addition, its surface characteristics and cell culturing properties were examined. Whole surface of PLLA was homogeneously covered by MWCNTs maintained a unique tubular structure. MWCNT-coated PLLA showed remarkable higher wettability than uncoated PLLA. Human osteosarcoma cell line (Saos2) adhered well on the CNT-coated PLLA whereas there are few cells attached on the uncoated PLLA at 2 h after seeding. The number of the cells on uncoated PLLA was still smaller than on the MWCNT-coated PLLA at 1 and 3 days. Moreover, The DNA content in the cells attached to the MWCNT-coated PLLA was significantly higher than that on the uncoated PLLA (p 0.1). Therefore MWCNT-coating on PLLA improved the surface wettability and initial cell attachment at early stage.

Modification on ursodeoxycholic acid (UDCA) scaffold. discovery of bile acid derivatives as selective agonists of cell-surface G-protein coupled bile acid receptor 1 (GP-BAR1).

Science.gov (United States)

Sepe, Valentina; Renga, Barbara; Festa, Carmen; D'Amore, Claudio; Masullo, Dario; Cipriani, Sabrina; Di Leva, Francesco Saverio; Monti, Maria Chiara; Novellino, Ettore; Limongelli, Vittorio; Zampella, Angela; Fiorucci, Stefano

2014-09-25

Bile acids are signaling molecules interacting with the nuclear receptor FXR and the G-protein coupled receptor 1 (GP-BAR1/TGR5). GP-BAR1 is a promising pharmacological target for the treatment of steatohepatitis, type 2 diabetes, and obesity. Endogenous bile acids and currently available semisynthetic bile acids are poorly selective toward GP-BAR1 and FXR. Thus, in the present study we have investigated around the structure of UDCA, a clinically used bile acid devoid of FXR agonist activity, to develop a large family of side chain modified 3α,7β-dihydroxyl cholanoids that selectively activate GP-BAR1. In vivo and in vitro pharmacological evaluation demonstrated that administration of compound 16 selectively increases the expression of pro-glucagon 1, a GP-BAR1 target, in the small intestine, while it had no effect on FXR target genes in the liver. Further, compound 16 results in a significant reshaping of bile acid pool in a rodent model of cholestasis. These data demonstrate that UDCA is a useful scaffold to generate novel and selective steroidal ligands for GP-BAR1.

Fabrication of high conductivity dual multi-porous poly (L-lactic acid)/polypyrrole composite micro/nanofiber film

International Nuclear Information System (INIS)

Yu Qiaozhen; Dai Zhengwei; Lan Ping

2011-01-01

Highlights: → PLLA/H 2 SO 4 -doped PPy composite micro/nano fibers dual multi-pore membranes with high conductivity were fabricated by combining electrospinning with in situ polymerization.These composite fibers have a core-shell structure, the PPy is the core and the PLLA/PPy is the shell. → The size and shape of the pores in this PPy composite fiber membrane can be tuned by polymerization parameters. The largest size of the pores is about 250 μm. → The conductivity of this composite fiber membrane can be adjusted by polymerization parameters. The highest conductivity is 179.0 S cm -1 . The PLLA fibers act as the template in the pyrrole polymerization process and contributed to the increase of the conductivity. - Abstract: Dual multi-porous PLLA (poly(L-lactic acid))/H 2 SO 4 -doped PPy (polypyrrole) composite micro/nano fiber films were fabricated by combining electrospinning with in situ polymerization. The morphologies and structures of the resulting samples were analyzed by scanning electron microscopy (SEM). It was found that the composite micro/nano fibers exhibited a core-shell structure and the composite fiber film had a dual multi-pore structure composed of pores both in the fibers and among the fibers. Semiconductor parameter analyzer was used to characterize the electrical properties of the samples. It was interesting to find that all the PLLA/H 2 SO 4 -doped PPy composite micro/nano fiber films had higher conductivity than H 2 SO 4 -doped PPy particles when the polymerization time up to 180 min. Effects of the pyrrole synthesis conditions on the pore size and the conductivity of PLLA/PPy composite fiber film were assessed. By optimizing the polymerization conditions, the max conductivity of this composite fiber film was about 179.0 S cm -1 with a pore size of about 250 μm. The possible mechanism of PLLA/H 2 SO 4 -doped PPy composite micro/nano fiber films had much higher conductivity than H 2 SO 4 -doped PPy particles was discussed.

Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro.

Science.gov (United States)

Wu, Gui; Wu, Weigang; Zheng, Qixin; Li, Jingfeng; Zhou, Jianbo; Hu, Zhilei

2014-07-19

Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants' surfaces were observed with electron microscope. The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a "nest-shaped" way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day's release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was

Haste intramedular polimérica bioreabsorvível (PLLA/PHBV para uso na recuperação de fraturas ósseas Intramedullary bioresorbable polymeric pin (PLLA/PHBV for use in bone fracture recuperation

Directory of Open Access Journals (Sweden)

Betina M. P. Ferreira

2008-01-01

Full Text Available A crescente utilização de materiais poliméricos bioreabsorvíveis em medicina, tem estimulado pesquisadores na área ortopédica na busca de soluções mais biológicas, substituindo artefatos tais como fios, hastes e placas metálicas por polímeros bioreabsorvíveis no tratamento de fraturas. Para tanto, resolveu-se estudar implantes da blenda de PLLA/PHBV (dois polímeros bioreabsorvíveis moldados em uma mini-injetora. Esses implantes foram utilizados para recuperação de fraturas de fêmur de coelhos e avaliados em comparação ao fio de Steinmann (aço inox, usado comercialmente. Após eutanásia com 6, 12 e 24 semanas de implantação dos artefatos, os ossos foram estudados com radiografias, exame histológico e ensaio mecânico, enquanto os implantes poliméricos foram submetidos a microscopia eletrônica de varredura (SEM, ensaio mecânico e calorimetria diferencial de varredura modular (MDSC. As radiografias mostraram calos ósseos bem formados, tanto com o uso da haste de polímero como com o controle metálico. O estudo histológico mostrou ausência de reações inflamatórias ou osteólise. O ensaio mecânico mostrou que a consolidação óssea ocorreu nos dois grupos. Tanto no ensaio mecânico como na calorimetria observou-se que a haste polimérica apresentou sinais de degradação progressiva no tempo estudado. Com os dados obtidos neste estudo, podemos afirmar que o implante PLLA/PHBV demonstrou ser efetivo na reparação de fraturas do fêmur de coelhos quando comparado com o controle metálico.The growing interest in medicine with the use of bioreabsorbable polymeric materials has been stimulating researchers from orthopedic area to develop more biological solutions, substituting threads, stems and metallic plates for bioreabsorbable polymers in the treatment of fractures. So, we decided to study implants of the PLLA/PHBV blends (two bioreabsorbable polymers moulded in a mini-injector. Those implants were used for

Porosity characterization of biodegradable porous poly (L-lactic acid) electrospun nanofibers

Science.gov (United States)

Valipouri, Afsaneh; Gharehaghaji, Ali Akbar; Alirezazadeh, Azam; Ravandi, Seyed Abdolkarim Hosseini

2017-12-01

Poly-L lactic acid (PLLA) is one of the mostly used fibers in biomedical applications as a biodegradable and biocompatible material. Porosity and fiber diameter distribution are governing factors that determine the performance of nanofibers. Present work aims at investigating the process parameters that are affecting porosity and diameter distribution of PLLA nanofibers. PLLA nanofibers were fabricated through electrospinning method using the solution of PLLA polymer/dichloromethane (DCM). Nanofibers with various fiber diameter distribution and porosity were made by changing of process parameters such as spinning distance (5, 10 and 15 cm), voltage (11 and 15 kV), solution concentration (10, 11 and 12 wt%) and feeding rate (0.3, 0.4 and 0.7 ml h-1). Image processing techniques (with Matlab R2017), surface analysis (with Mountainsmap7) and diameter distribution analysis (with Measurement software) were used to examine surface morphology of samples. The results showed that the fiber diameter distribution becomes wider with increasing the applied voltage and reducing the spinning distance. In the other hand, coarse fibers possessed larger pores while having irregular and fewer pores in comparison to fine fibers. The most uniform nano-web with high porous nanofibers was attained by the choice of the process parameters at the voltage of 11 kV, spinning distance of 15 cm, feeding rate of 0.4 ml h-1 and solution concentration of 10 wt%.

Biocompatibility Assessment of Novel Collagen-Sericin Scaffolds Improved with Hyaluronic Acid and Chondroitin Sulfate for Cartilage Regeneration

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Sorina Dinescu

2013-01-01

Full Text Available Cartilage tissue engineering (CTE applications are focused towards the use of implantable biohybrids consisting of biodegradable scaffolds combined with in vitro cultured cells. Hyaluronic acid (HA and chondroitin sulfate (CS were identified as the most potent prochondrogenic factors used to design new biomaterials for CTE, while human adipose-derived stem cells (ASCs were proved to display high chondrogenic potential. In this context, our aim was not only to build novel 3D porous scaffolds based on natural compounds but also to evaluate their in vitro biological performances. Therefore, for prospective CTE, collagen-sericin (Coll-SS scaffolds improved with HA (5% or 10% and CS (5% or 10% were used as temporary physical supports for ASCs and were analyzed in terms of structural, thermal, morphological, and swelling properties and cytotoxic potential. To complete biocompatibility data, ASCs viability and proliferation potential were also assessed. Our studies revealed that Coll-SS hydrogels improved with 10% HA and 5% CS displayed the best biological performances in terms of cell viability, proliferation, morphology, and distribution. Thus, further work will address a novel 3D system including both HA 10% and CS 5% glycoproteins, which will probably be exposed to prochondrogenic conditions in order to assess its potential use in CTE applications.

Utilizing NaCl to increase the porosity of electrospun materials

International Nuclear Information System (INIS)

Wright, L.D.; Andric, T.; Freeman, J.W.

2011-01-01

Electrospinning has emerged as a popular method for creating scaffolding materials used in tissue engineering applications to repair or replace damaged tissues. To become a viable scaffold material, however, pore sizes in electrospun materials must be increased to improve cell infiltration. Deposition of NaCl crystals during electrospinning was utilized to help overcome this obstacle. The NaCl crystals are released above the rotating collection mandrel and become incorporated into the poly(L-lactide) electrospun material. The NaCl then leaches out of the electrospun material creating larger pores: average pore diameter of 48.7 μm for PLLA-NaCl electrospinning versus 5.5 μm for PLLA alone electrospinning. Electrospun PLLA scaffolds with NaCl pores have a lower elastic modulus (8.05 MPa) and yield stress (349 kPa) and a higher yield strain (0.04) compared to their traditional counterparts (40.36 MPa, 676 kPa, and 0.0188). Decreased elastic modulus and yield stress would be beneficial to tissue engineering of elastic tissues including skin. The presence of NaCl pores did not significantly affect the cellular proliferation of MC3T3 cells but did allow for cell infiltration into the electrospun material. Therefore, the creation of large pores through NaCl leaching can significantly improve the performance of electrospun materials for tissue engineering applications by improving cellular infiltration.

Bio-safe processing of polylactic-co-caprolactone and polylactic acid blends to fabricate fibrous porous scaffolds for in vitro mesenchymal stem cells adhesion and proliferation

Energy Technology Data Exchange (ETDEWEB)

Salerno, Aurelio, E-mail: asalerno@unina.it [Centre for Advanced Biomaterials for Health Care, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125 Napoli (Italy); Institute of Materials Science of Barcelona (ICMAB-CSIC), Campus de la UAB s/n, Bellaterra 08193 (Spain); Guarino, Vincenzo; Oliviero, Olimpia; Ambrosio, Luigi [Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, V.le Kennedy 54, Pad 20, Mostra d' Oltremare, 80125 Naples (Italy); Domingo, Concepción [Institute of Materials Science of Barcelona (ICMAB-CSIC), Campus de la UAB s/n, Bellaterra 08193 (Spain)

2016-06-01

In this study, the design and fabrication of porous scaffolds, made of blends of polylactic-co-caprolactone (PLC) and polylactic acid (PLA) polymers, for tissue engineering applications is reported. The scaffolds are prepared by means of a bio-safe thermally induced phase separation (TIPS) approach with or without the addition of NaCl particles used as particulate porogen. The scaffolds are characterized to assess their crystalline structure, morphology and mechanical properties, and the texture of the pores and the pore size distribution. Moreover, in vitro human mesenchymal stem cells (hMSCs) culture tests have been carried out to demonstrate the biocompatibility of the scaffolds. The results of this study demonstrate that all of the scaffold materials processed by means of TIPS process are semi-crystalline. Furthermore, the blend composition affected polymer crystallization and, in turn, the nano and macro-structural properties of the scaffolds. Indeed, neat PLC and neat PLA crystallize into globular and randomly arranged sub micro-size scale fibrous conformations, respectively. Concomitantly, the addition of NaCl particles during the fabrication route allows for the creation of an interconnected network of large pores inside the primary structure while resulted in a significant decrease of scaffolds mechanical response. Finally, the results of cell culture tests demonstrate that both the micro and macro-structure of the scaffold affect the in vitro hMSCs adhesion and proliferation. - Highlights: • Porous scaffolds are prepared by polymer blending, phase separation and NaCl leaching. • The process avoids the use of toxic solvents. • Blend composition dictates polymer crystallization and scaffold properties. • Scaffolds are provided of a sub micro-scale fibers structure and interconnected macropores. • Stem cells adhesion and proliferation depend on scaffolds composition and structure.

Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model

Science.gov (United States)

Zhang, Haifeng; Mao, Xiyuan; Du, Zijing; Jiang, Wenbo; Han, Xiuguo; Zhao, Danyang; Han, Dong; Li, Qingfeng

2016-01-01

We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 μm and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, β-tricalcium phosphate (β-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the biocompatibility, bone repairing capacity and degradation in three different bone substitute materials were estimated using a critical-size rat calvarial defect model in vivo. The defects were evaluated by micro-computed tomography and histological analysis at four and eight weeks after surgery, respectively. The results showed that each of the studied scaffolds had its own specific merits and drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good biocompatibility and stimulated BMSC cell proliferation and differentiation to osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds had good osteogenic capability and biodegradation activity with no difference in inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential applications in bone tissue engineering and may be used as graft substitutes in reconstructive surgery.

Estudo das células Neuro2A sobre os biomateriais PCL e PLLA

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Luiz Gabriel Maturana

2014-12-01

Full Text Available Os biomateriais poli L-ácido lático (PLLA e o poli caprolactona (PCL são os polímeros mais estudadas na área dos materiais bioreabsorvíveis. Dentre as suas principais características que contribuem para a interação celular, temos a especificidade química da superfície, elétrica, hidrofobicidade e topografia. Ainda, observa-se o tempo de degradação, porosidade, biocompatibilidade com o tecido biológico, bem como, a confecção com as mais variadas formas e dimensões. Já a prática da cultura celular, tem como objetivo estudar a adesão, migração, diferenciação e a proliferação celular utilizando-se um determinado material ou substância. Contudo, poucos trabalhos utilizando os biomateriais ora supracitados e a aplicação em células neuro2A foram realizados. Sabe-se que este tipo celular é derivado de células embrionárias da crista neural, as quais originam em neurônios simpáticos e apresentam como característica a imortalidade, portanto, são excelentes modelos em ensaios in vitro. Nesse sentido, o presente estudo avalia a adesão e a proliferação desta linhagem celular sobre os biopolímeros poli caprolactona (PCL e poli L-ácido lático (PLLA.

In Vitro Evaluation of Essential Mechanical Properties and Cell Behaviors of a Novel Polylactic-co-Glycolic Acid (PLGA-Based Tubular Scaffold for Small-Diameter Vascular Tissue Engineering

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Nuoxin Wang

2017-07-01

Full Text Available In this paper, we investigate essential mechanical properties and cell behaviors of the scaffolds fabricated by rolling polylactic-co-glycolic acid (PLGA electrospinning (ES films for small-diameter vascular grafts (inner diameter < 6 mm. The newly developed strategy can be used to fabricate small diameter vascular grafts with or without pre-seeded cells, which are two main branches for small diameter vascular engineering. We demonstrate that the mechanical properties of our rolling-based scaffolds can be tuned flexibly by the number of layers. For cell-free scaffolds, with the increase of layer number, burst pressure and suture retention increase, elastic tensile modulus maintains unchanged statistically, but compliance and liquid leakage decrease. For cell-containing scaffolds, seeding cells will significantly decrease the liquid leakage, but there are no statistical differences for other mechanical properties; moreover, cells live and proliferate well in the scaffold after a 6-day culture.

Optimized Diazo Scaffold for Protein Esterification

Science.gov (United States)

Mix, Kalie A.

2015-01-01

The O-alkylation of carboxylic acids with diazo compounds provides a means to esterify carboxylic acids in aqueous solution. A Hammett analysis of the reactivity of diazo compounds derived from phenylglycinamide revealed that the p-methylphenylglycinamide scaffold has an especially high reaction rate and ester:alcohol product ratio, and esterifies protein carboxyl groups more efficiently than does any known reagent. PMID:25938936

The metabolism of 32P-CP-PLLA seed implanted in the liver and its damage to the normal liver tissue: a study in the experimental dogs

International Nuclear Information System (INIS)

Tan Zhongbao; Liu Lu; Guo Jinhe; Zhu Guangyu; Wang Fuan; Nie Qi; Gao Hailin; Teng Gaojun

2010-01-01

Objective: To investigate the effects of intratumoral implantation of 32 P -CP-PLLA seeds on the normal canine liver tissue and to explore the metabolism of 32 P-CP-PLLA seeds implanted in the liver of experimental dogs. Methods: Twelve beagles were enrolled in this study. The dogs were randomly and equally divided into four groups: group A (185 MBq), group B (370 MBq), group C (740 MBq) and group D (0 MBq). By using laparotomy procedure 32 P-CP-PLLA seeds were implanted into dog's liver. CT scan was performed before operation as well as before the dog was sacrificed. All dogs were sacrificed three months after the implantation. Before the procedure and 1, 2, 4, 8 and 12 weeks after the procedure the blood tests and serum biochemical tests were conducted. One dog from group B and group C was selected respectively and was fed in a metabolic cage. Within one month after the procedure the cpm in feces and in urine was determined every 24 hours. One dog was picked out from each of the three groups and was punctured to get its liver tissue for pathologic exam each time at 1, 2, 4, 8 and 12 weeks after the implantation, and SPECT imaging was also performed at the same time. Pathologic study, both macroscopic and microscopic (including optical and electronic microscopy) was made to observe the liver damage after the dog was sacrificed. The statistical analysis was processed by using SPSS 13.0 software and the measuring data were expressed with mean ± standard deviation (x ± s). Results: Two months after the procedure, serological examination found that the serum alkaline phosphatase (BKP) in both group B and group C was significantly higher than that in other groups, the difference was statistically significant (P 32 P-CP-PLLA seeds was manifested as a spherical lesion which was encysted by a layer of fibrous tissue with an edematous zone peripherally. Conclusion: The implantation of 32 P-CP-PLLA seeds in dog's liver causes only localized hepatic damage with no general

Physical and degradation properties of PLGA scaffolds fabricated by salt fusion technique.

Science.gov (United States)

Mekala, Naveen Kumar; Baadhe, Rama Raju; Parcha, Sreenivasa Rao; Yalavarthy, Prameela Devi

2013-07-01

Tissue engineering scaffolds require a controlled pore size and interconnected pore structures to support the host tissue growth. In the present study, three dimensional (3D) hybrid scaffolds of poly lactic acid (PLA) and poly glycolic acid (PGA) were fabricated using solvent casting/particulate leaching. In this case, partially fused NaCl particles were used as porogen (200-300µ) to improve the overall porosity (≥90%) and internal texture of scaffolds. Differential scanning calorimeter (DSC) analysis of these porous scaffolds revealed a gradual reduction in glass transition temperature (Tg) (from 48°C to 42.5°C) with increase in hydrophilic PGA content. The potential applications of these scaffolds as implants were further tested for their biocompatibility and biodegradability in four simulated body fluid (SBF) types in vitro. Whereas, simulated body fluid (SBF) Type1 with the optimal amount of HCO3 (-) ions was found to be more appropriate and sensible for testing the bioactivity of scaffolds. Among three combinations of polymer scaffolds, sample B with a ratio of 75:25 of PLA: PGA showed greater stability in body fluids (pH 7.2) with an optimum degradation rate (9% to 12% approx). X-ray diffractogram also confirmed a thin layer of hydroxyapatite deposition over sample B with all SBF types in vitro.

Mechanical strength of ceramic scaffolds reinforced with biopolymers is comparable to that of human bone

DEFF Research Database (Denmark)

Henriksen, S S; Ding, M; Vinther Juhl, M

2011-01-01

Eight groups of calcium-phosphate scaffolds for bone implantation were prepared of which seven were reinforced with biopolymers, poly lactic acid (PLA) or hyaluronic acid in different concentrations in order to increase the mechanical strength, without significantly impairing the microarchitecture....... Controls were un-reinforced calcium-phosphate scaffolds. Microarchitectural properties were quantified using micro-CT scanning. Mechanical properties were evaluated by destructive compression testing. Results showed that adding 10 or 15% PLA to the scaffold significantly increased the mechanical strength...

Improving cytoactive of endothelial cell by introducing fibronectin to the surface of poly L-Lactic acid fiber mats via dopamine

Energy Technology Data Exchange (ETDEWEB)

Yang, Wufeng; Zhang, Xiazhi; Wu, Keke; Liu, Xiaoyan; Jiao, Yanpeng, E-mail: tjiaoyp@jnu.edu.cn; Zhou, Changren

2016-12-01

A simple but straightforward approach was reported to prepare fiber mats modified with fibronectin (Fn) protein for endothelial cells activity study. Based on the self-polymerization and strong adhesion feature of dopamine, poly L-Lactic acid (PLLA) fibers mat was modified via simply immersing them into dopamine solution for 16 h. Subsequently, Fn was immobilized onto the fiber mats surface by the coupling reactive polydopamine (PDA) layer and Fn. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) were used to determine the chemical compositions of fiber mats surface, which confirmed the successful immobilization of PDA and Fn molecules on the fiber surface. Scanning electronic microscopy (SEM) was used to observe the surface morphology changes after modification with PDA and Fn. The data of water contact angle showed that the hydrophilicity of the fiber mats was improved after surface modification. The data of in vitro cell culture proved that the PDA and Fn modified surface significantly enhanced the adhesion, proliferation and cell activity of endothelial cells on the fiber mats. And the release of tumor necrosis factor-α (TNF-α) by endothelial cells on the modified surface was suppressed compared to that on culture plate and PLLA film at 2 and 4 days, while the secretion of interleukin-1β (IL-1β) was increased compared to that on culture plate and PLLA film at 2 days. - Highlights: • Fibronectin (Fn) was grafted on PLLA fiber surface mediated by polydopamine coating. • Fn modified PLLA fiber enhanced the adhesion, proliferation of endothelial cells. • Fn and polydopamine modified PLLA fiber could adjust the release of inflammatory factor.

Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery.

Science.gov (United States)

Ceccarelli, Gabriele; Presta, Rossella; Benedetti, Laura; Cusella De Angelis, Maria Gabriella; Lupi, Saturnino Marco; Rodriguez Y Baena, Ruggero

2017-01-01

Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives) or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA), polylactic acid (PLA), and polycaprolactone). This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too.

Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery

Directory of Open Access Journals (Sweden)

Gabriele Ceccarelli

2017-01-01

Full Text Available Bone regeneration is currently one of the most important and challenging tissue engineering approaches in regenerative medicine. Bone regeneration is a promising approach in dentistry and is considered an ideal clinical strategy in treating diseases, injuries, and defects of the maxillofacial region. Advances in tissue engineering have resulted in the development of innovative scaffold designs, complemented by the progress made in cell-based therapies. In vitro bone regeneration can be achieved by the combination of stem cells, scaffolds, and bioactive factors. The biomimetic approach to create an ideal bone substitute provides strategies for developing combined scaffolds composed of adult stem cells with mesenchymal phenotype and different organic biomaterials (such as collagen and hyaluronic acid derivatives or inorganic biomaterials such as manufactured polymers (polyglycolic acid (PGA, polylactic acid (PLA, and polycaprolactone. This review focuses on different biomaterials currently used in dentistry as scaffolds for bone regeneration in treating bone defects or in surgical techniques, such as sinus lift, horizontal and vertical bone grafts, or socket preservation. Our review would be of particular interest to medical and surgical researchers at the interface of cell biology, materials science, and tissue engineering, as well as industry-related manufacturers and researchers in healthcare, prosthetics, and 3D printing, too.

Combining electrospinning and fused deposition modeling for the fabrication of a hybrid vascular graft

International Nuclear Information System (INIS)

Centola, M; Rainer, A; Trombetta, M; Spadaccio, C; Genovese, J A; De Porcellinis, S

2010-01-01

Tissue engineering of blood vessels is a promising strategy in regenerative medicine with a broad spectrum of potential applications. However, many hurdles for tissue-engineered vascular grafts, such as poor mechanical properties, thrombogenicity and cell over-growth inside the construct, need to be overcome prior to the clinical application. To surmount these shortcomings, we developed a poly-l-lactide (PLLA)/poly-ε-caprolactone (PCL) scaffold releasing heparin by a combination of electrospinning and fused deposition modeling technique. PLLA/heparin scaffolds were produced by electrospinning in tubular shape and then fused deposition modeling was used to armor the tube with a single coil of PCL on the outer layer to improve mechanical properties. Scaffolds were then seeded with human mesenchymal stem cells (hMSCs) and assayed in terms of morphology, mechanical tensile strength, cell viability and differentiation. This particular scaffold design allowed the generation of both a drug delivery system amenable to surmount thrombogenic issues and a microenvironment able to induce endothelial differentiation. At the same time, the PCL external coiling improved mechanical resistance of the microfibrous scaffold. By the combination of two notable techniques in biofabrication-electrospinning and FDM-and exploiting the biological effects of heparin, we developed an ad hoc differentiating device for hMSCs seeding, able to induce differentiation into vascular endothelium.

Combining electrospinning and fused deposition modeling for the fabrication of a hybrid vascular graft

Energy Technology Data Exchange (ETDEWEB)

Centola, M; Rainer, A; Trombetta, M [Laboratory of Chemistry and Biomaterials, CIR-Center of Integrated Research, University Campus Bio-Medico of Rome (Italy); Spadaccio, C; Genovese, J A [Area of Cardiovascular Surgery, CIR-Center of Integrated Research, University Campus Bio-Medico of Rome (Italy); De Porcellinis, S, E-mail: m.trombetta@unicampus.i [Complex Systems and Security Laboratory, CIR-Center of Integrated Research, University Campus Bio-Medico of Rome (Italy)

2010-03-15

Tissue engineering of blood vessels is a promising strategy in regenerative medicine with a broad spectrum of potential applications. However, many hurdles for tissue-engineered vascular grafts, such as poor mechanical properties, thrombogenicity and cell over-growth inside the construct, need to be overcome prior to the clinical application. To surmount these shortcomings, we developed a poly-l-lactide (PLLA)/poly-epsilon-caprolactone (PCL) scaffold releasing heparin by a combination of electrospinning and fused deposition modeling technique. PLLA/heparin scaffolds were produced by electrospinning in tubular shape and then fused deposition modeling was used to armor the tube with a single coil of PCL on the outer layer to improve mechanical properties. Scaffolds were then seeded with human mesenchymal stem cells (hMSCs) and assayed in terms of morphology, mechanical tensile strength, cell viability and differentiation. This particular scaffold design allowed the generation of both a drug delivery system amenable to surmount thrombogenic issues and a microenvironment able to induce endothelial differentiation. At the same time, the PCL external coiling improved mechanical resistance of the microfibrous scaffold. By the combination of two notable techniques in biofabrication-electrospinning and FDM-and exploiting the biological effects of heparin, we developed an ad hoc differentiating device for hMSCs seeding, able to induce differentiation into vascular endothelium.

Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

Science.gov (United States)

Thavornyutikarn, Boonlom; Chantarapanich, Nattapon; Sitthiseripratip, Kriskrai; Thouas, George A; Chen, Qizhi

Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

Tailoring the properties of mPEG-PLLA nanoparticles for better encapsulation and tuned release of the hydrophilic anticancer drug.

Science.gov (United States)

Surwase, Sachin S; Munot, Neha M; Idage, Bhaskar B; Idage, Susheela B

2017-06-01

Gemcitabine is used as a first-line drug for treating many solid tumours. However, it suffers from a major drawback of strong side effects and short plasma half-life because of degradation by enzyme when administered intravenously. Polyesters and copolyesters are the most widely used and preferred class of biodegradable polymer. In the present work, efforts have been made to prepare poly(ethylene glycol) monomethoxy ether-poly(L-lactide) (mPEG-PLLA), a biodegradable amphiphilic copolymer with a view to improve the entrapment and tuned release of hydrophilic drug gemcitabine. The different mPEG-PLLA copolymers were synthesized with the varying ratios of mPEG and characterized by different techniques namely FTIR and 1 H NMR spectroscopy, solution viscosity, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC). Gemcitabine-loaded nanoparticles were prepared using mPEG-PLLA copolymers by two methods i.e. nanoprecipitation and double emulsion solvent evaporation. The nanoprecipitation method showed very less entrapment and polymer solubility in the acetone-water mixture leading to uncontrolled polymer precipitation. The difficulties encountered in the nanoprecipitation method were overcome with the help of the double emulsion (w/o/w) solvent evaporation technique. It has been observed from the results that biodegradable copolymer nanoparticles protect the drug from degradation and also help in controlling the release of encapsulated drug. The properties of nanoparticles can be tailored by varying the composition of mPEG in order to get improved entrapment efficiency and desired drug release. The nanoparticles were assessed for their in vitro cytotoxicity (MTT and FACS) and cellular uptake (fluorescence microscopy) study which showed very promising results. Nanoparticles were also studied for their in vivo release after intravenous administration to Wistar albino rats, which successfully showed controlled drug release for more than 14 days.

Micro/Nano Multilayered Scaffolds of PLGA and Collagen by Alternately Electrospinning for Bone Tissue Engineering

Science.gov (United States)

Kwak, Sanghwa; Haider, Adnan; Gupta, Kailash Chandra; Kim, Sukyoung; Kang, Inn-Kyu

2016-07-01

The dual extrusion electrospinning technique was used to fabricate multilayered 3D scaffolds by stacking microfibrous meshes of poly(lactic acid-co-glycolic acid) (PLGA) in alternate fashion to micro/nano mixed fibrous meshes of PLGA and collagen. To fabricate the multilayered scaffold, 35 wt% solution of PLGA in THF-DMF binary solvent (3:1) and 5 wt% solution of collagen in hexafluoroisopropanol (HFIP) with and without hydroxyapatite nanorods (nHA) were used. The dual and individual electrospinning of PLGA and collagen were carried out at flow rates of 1.0 and 0.5 mL/h, respectively, at an applied voltage of 20 kV. The density of collagen fibers in multilayered scaffolds has controlled the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. The homogeneous dispersion of glutamic acid-modified hydroxyapatite nanorods (nHA-GA) in collagen solution has improved the osteogenic properties of fabricated multilayered scaffolds. The fabricated multilayered scaffolds were characterized using FT-IR, X-ray photoelectron spectroscopy, and transmission electron microscopy (TEM). The scanning electron microscopy (FE-SEM) was used to evaluate the adhesion and spreads of MC3T3-E1 cells on multilayered scaffolds. The activity of MC3T3-E1 cells on the multilayered scaffolds was evaluated by applying MTT, alkaline phosphatase, Alizarin Red, von Kossa, and cytoskeleton F-actin assaying protocols. The micro/nano fibrous PLGA-Col-HA scaffolds were found to be highly bioactive in comparison to pristine microfibrous PLGA and micro/nano mixed fibrous PLGA and Col scaffolds.

Injectable scaffold materials differ in their cell instructive effects on primary human myoblasts

DEFF Research Database (Denmark)

Hejbøl, Eva Kildall; Sellathurai, Jeeva; Nair, Prabha Damodaran

2017-01-01

Scaffolds are materials used for delivery of cells for regeneration of tissues. They support three-dimensional organization and improve cell survival. For the repair of small skeletal muscles, injections of small volumes of cells are attractive, and injectable scaffolds for delivery of cells offer...... a minimally invasive technique. In this study, we examined in vitro the cell instructive effects of three types of injectable scaffolds, fibrin, alginate, and poly(lactic-co-glycolic acid)-based microparticles on primary human myoblasts. The myoblast morphology and progression in the myogenic program differed......, depending on the type of scaffold material. In alginate gel, the cells obtained a round morphology, they ceased to proliferate, and entered quiescence. In the fibrin gels, differentiation was promoted, and myotubes were observed within a few days in culture, while poly(lactic-co-glycolic acid...

A poly(lactide) stereocomplex structure with modified magnesium oxide and its effects in enhancing the mechanical properties and suppressing inflammation.

Science.gov (United States)

Kum, Chang Hun; Cho, Youngjin; Seo, Seong Ho; Joung, Yoon Ki; Ahn, Dong June; Han, Dong Keun

2014-09-24

Biodegradable polymers such as poly(L-lactide) (PLLA) have been widely utilized as materials for biomedical applications. However, the relatively poor mechanical properties of PLLA and its acid-induced cell inflammation brought about by the acidic byproducts during biodegradation pose severe problems. In this study, these drawbacks of PLLA are addressed using a stereocomplex structure, where oligo-D-lactide-grafted magnesium hydroxide (MgO-ODLA) is synthesized by grafting d-lactide onto the surface of magnesium hydroxide, which is then blended with a PLLA film. The structure, morphology, pH change, thermal and mechanical properties, in-vitro cytotoxicity, and inflammation effect of the MgO-ODLAs and their PLLA composites are evaluated through various analyses. The PLLA/MgO70-ODLA30 (0-20 wt%) composite with a stereocomplex structure shows a 20% increase in its tensile strength and an improvement in the modulus compared to its oligo-L-lactide (PLLA/MgO70-OLLA30) counterpart. The interfacial interaction parameter of PLLA/MgO70-ODLA30 (5.459) has superior properties to those of PLLA/MgO70-OLLA30 (4.013) and PLLA/Mg(OH)2 (1.774). The cell cytotoxicity and acid-induced inflammatory response are suppressed by the neutralizing effect of the MgO-ODLAs. In addition, the inflammatory problem caused by the rapid acidification of the stereocomplex structure is also addressed. As a result, the stereocomplex structure of the MgO-ODLA/PLLA composite can be used to overcome the problems associated with the biomedical applications of PLLA films. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of the structure of poly (L-lactic acid) electrospun fibers on the bioactivity of endothelial cells: proliferation and inflammatory cytokines expression.

Science.gov (United States)

Liu, Xiaoyan; Zhang, Xiazhi; Wu, Keke; Yang, Wufeng; Jiao, Yanpeng; Zhou, Changren

2017-02-01

Electrospinning has been used to fabricate random and aligned poly (L-lactic acid) (PLLA) fibers with three kinds of diameter under optimal conditions. The main purpose of this paper was to investigate the influence of the diameter and orientation of fibers on the bioactivity of endothelial cells, especially on the inflammatory cytokines expression. The morphology of electrospun fibers and the cells on the fibers after 3 and 6 days culture were observed by scanning electron microscopy. Also the cell proliferation activity and cell cycle were tested and the results showed that the random fibers were more favorable for endothelial cells growth. The effect of PLLA film (served as a control) and six kinds of PLLA fibers mats on the inflammatory cytokines expression after cells incubated for 2 and 4 days were investigated. It was concluded that there was more intense inflammatory cytokines expression by cells on flat PLLA film than that on electrospun fiber mats. Also the fiber diameter has greater effect on the activity and inflammatory cytokines expression of endothelial cells than the fiber orientation, in which fibers with smaller size has weaker inflammatory reaction.

Development of nanofibrous scaffolds containing gum tragacanth/poly (ε-caprolactone) for application as skin scaffolds

Energy Technology Data Exchange (ETDEWEB)

Ranjbar-Mohammadi, Marziyeh [Textile Engineering Department, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Bahrami, S. Hajir, E-mail: hajirb@aut.ac.ir [Textile Engineering Department, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Center for excellence Modern Textile Characterization, Tehran (Iran, Islamic Republic of)

2015-03-01

Outstanding wound healing activity of gum tragacanth (GT) and higher mechanical strength of poly (ε-caprolactone) (PCL) may produce an excellent nanofibrous patch for either skin tissue engineering or wound dressing application. PCL/GT scaffold containing different concentrations of PCL with different blend ratios of GT/PCL was produced using 90% acetic acid as solvent. The results demonstrated that the PCL/GT (3:1.5) with PCL concentration of 20% (w/v) produced nanofibers with proper morphology. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were utilized to characterize the nanofibers. Surface wettability, functional groups analysis, porosity and tensile properties of nanofibers were evaluated. Morphological characterization showed that the addition of GT to PCL solution results in decreasing the average diameter of the PCL/GT nanofibers. However, the hydrophilicity increased in the PCL/GT nanofibers. Slight increase in melting peaks was observed due to the blending of PCL with GT nanofibers. PCL/GT nanofibers were used for in vitro cell culture of human fibroblast cell lines AGO and NIH 3T3 fibroblast cells. MTT assay and SEM results showed that the biocomposite PCL/GT mats enhanced the fibroblast adhesion and proliferation compared to PCL scaffolds. The antibacterial activity of PCL/GT and GT nanofibers against Staphylococcus aureus and Pseudomonas aeruginosa was also examined. - Highlights: • A new skin tissue engineering scaffold from poly (ε-caprolactone) (PCL) and gum tragacanth (GT) has been developed. • These scaffolds might be an effectual simulator of the structure and composition of native skin. • Very slight increase in melting peaks was observed due to the blending of PCL with GT nanofibers. • Biodegradation, water uptake and hydrophilicity properties of these scaffolds showed that produced scaffolds were adherent. • The electrospun PCL/GT scaffold can promote the skin regeneration of full

Development of nanofibrous scaffolds containing gum tragacanth/poly (ε-caprolactone) for application as skin scaffolds

International Nuclear Information System (INIS)

Ranjbar-Mohammadi, Marziyeh; Bahrami, S. Hajir

2015-01-01

Outstanding wound healing activity of gum tragacanth (GT) and higher mechanical strength of poly (ε-caprolactone) (PCL) may produce an excellent nanofibrous patch for either skin tissue engineering or wound dressing application. PCL/GT scaffold containing different concentrations of PCL with different blend ratios of GT/PCL was produced using 90% acetic acid as solvent. The results demonstrated that the PCL/GT (3:1.5) with PCL concentration of 20% (w/v) produced nanofibers with proper morphology. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were utilized to characterize the nanofibers. Surface wettability, functional groups analysis, porosity and tensile properties of nanofibers were evaluated. Morphological characterization showed that the addition of GT to PCL solution results in decreasing the average diameter of the PCL/GT nanofibers. However, the hydrophilicity increased in the PCL/GT nanofibers. Slight increase in melting peaks was observed due to the blending of PCL with GT nanofibers. PCL/GT nanofibers were used for in vitro cell culture of human fibroblast cell lines AGO and NIH 3T3 fibroblast cells. MTT assay and SEM results showed that the biocomposite PCL/GT mats enhanced the fibroblast adhesion and proliferation compared to PCL scaffolds. The antibacterial activity of PCL/GT and GT nanofibers against Staphylococcus aureus and Pseudomonas aeruginosa was also examined. - Highlights: • A new skin tissue engineering scaffold from poly (ε-caprolactone) (PCL) and gum tragacanth (GT) has been developed. • These scaffolds might be an effectual simulator of the structure and composition of native skin. • Very slight increase in melting peaks was observed due to the blending of PCL with GT nanofibers. • Biodegradation, water uptake and hydrophilicity properties of these scaffolds showed that produced scaffolds were adherent. • The electrospun PCL/GT scaffold can promote the skin regeneration of full

Healing of Osteochondral Defects Implanted with Biomimetic Scaffolds of Poly(ε-Caprolactone)/Hydroxyapatite and Glycidyl-Methacrylate-Modified Hyaluronic Acid in a Minipig.

Science.gov (United States)

Hsieh, Yi-Ho; Shen, Bo-Yuan; Wang, Yao-Horng; Lin, Bojain; Lee, Hung-Maan; Hsieh, Ming-Fa

2018-04-09

Articular cartilage is a structure lack of vascular distribution. Once the cartilage is injured or diseased, it is unable to regenerate by itself. Surgical treatments do not effectively heal defects in articular cartilage. Tissue engineering is the most potential solution to this problem. In this study, methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and hydroxyapatite at a weight ratio of 2:1 were mixed via fused deposition modeling (FDM) layer by layer to form a solid scaffold. The scaffolds were further infiltrated with glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of Transforming Growth Factor-β1 and photo cross-linked on top of the scaffolds. An in vivo test was performed on the knees of Lanyu miniature pigs for a period of 12 months. The healing process of the osteochondral defects was followed by computer tomography (CT). The defect was fully covered with regenerated tissues in the control pig, while different tissues were grown in the defect of knee of the experimental pig. In the gross anatomy of the cross section, the scaffold remained in the subchondral location, while surface cartilage was regenerated. The cross section of the knees of both the control and experimental pigs were subjected to hematoxylin and eosin staining. The cartilage of the knee in the experimental pig was partially matured, e.g., few chondrocyte cells were enclosed in the lacunae. In the knee of the control pig, the defect was fully grown with fibrocartilage. In another in vivo experiment in a rabbit and a pig, the composite of the TGF-β1-loaded hydrogel and scaffolds was found to regenerate hyaline cartilage. However, scaffolds that remain in the subchondral lesion potentially delay the healing process. Therefore, the structural design of the scaffold should be reconsidered to match the regeneration process of both cartilage and subchondral bone.

Healing of Osteochondral Defects Implanted with Biomimetic Scaffolds of Poly(ε-Caprolactone/Hydroxyapatite and Glycidyl-Methacrylate-Modified Hyaluronic Acid in a Minipig

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Yi-Ho Hsieh

2018-04-01

Full Text Available Articular cartilage is a structure lack of vascular distribution. Once the cartilage is injured or diseased, it is unable to regenerate by itself. Surgical treatments do not effectively heal defects in articular cartilage. Tissue engineering is the most potential solution to this problem. In this study, methoxy poly(ethylene glycol-block-poly(ε-caprolactone (mPEG-PCL and hydroxyapatite at a weight ratio of 2:1 were mixed via fused deposition modeling (FDM layer by layer to form a solid scaffold. The scaffolds were further infiltrated with glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of Transforming Growth Factor-β1 and photo cross-linked on top of the scaffolds. An in vivo test was performed on the knees of Lanyu miniature pigs for a period of 12 months. The healing process of the osteochondral defects was followed by computer tomography (CT. The defect was fully covered with regenerated tissues in the control pig, while different tissues were grown in the defect of knee of the experimental pig. In the gross anatomy of the cross section, the scaffold remained in the subchondral location, while surface cartilage was regenerated. The cross section of the knees of both the control and experimental pigs were subjected to hematoxylin and eosin staining. The cartilage of the knee in the experimental pig was partially matured, e.g., few chondrocyte cells were enclosed in the lacunae. In the knee of the control pig, the defect was fully grown with fibrocartilage. In another in vivo experiment in a rabbit and a pig, the composite of the TGF-β1-loaded hydrogel and scaffolds was found to regenerate hyaline cartilage. However, scaffolds that remain in the subchondral lesion potentially delay the healing process. Therefore, the structural design of the scaffold should be reconsidered to match the regeneration process of both cartilage and subchondral bone.

Pressure-activated microsyringe (PAM) fabrication of bioactive glass-poly(lactic-co-glycolic acid) composite scaffolds for bone tissue regeneration.

Science.gov (United States)

Mattioli-Belmonte, M; De Maria, C; Vitale-Brovarone, C; Baino, F; Dicarlo, M; Vozzi, G

2017-07-01

The aim of this work was the fabrication and characterization of bioactive glass-poly(lactic-co-glycolic acid) (PLGA) composite scaffolds mimicking the topological features of cancellous bone. Porous multilayer PLGA-CEL2 composite scaffolds were innovatively produced by a pressure-activated microsyringe (PAM) method, a CAD/CAM processing technique originally developed at the University of Pisa. In order to select the optimal formulations to be extruded by PAM, CEL2-PLGA composite films (CEL2 is an experimental bioactive SiO 2 -P 2 O 5 -CaO-MgO-Na 2 O-K 2 O glass developed at Politecnico di Torino) were produced and mechanically tested. The elastic modulus of the films increased from 30 to > 400 MPa, increasing the CEL2 amount (10-50 wt%) in the composite. The mixture containing 20 wt% CEL2 was used to fabricate 2D and 3D bone-like scaffolds composed by layers with different topologies (square, hexagonal and octagonal pores). It was observed that the increase of complexity of 2D topological structures led to an increment of the elastic modulus from 3 to 9 MPa in the composite porous monolayer. The elastic modulus of 3D multilayer scaffolds was intermediate (about 6.5 MPa) between the values of the monolayers with square and octagonal pores (corresponding to the lowest and highest complexity, respectively). MG63 osteoblast-like cells and periosteal-derived precursor cells (PDPCs) were used to assess the biocompatibility of the 3D bone-like scaffolds. A significant increase in cell proliferation between 48 h and 7 days of culture was observed for both cell phenotypes. Moreover, qRT-PCR analysis evidenced an induction of early genes of osteogenesis in PDPCs. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Implante de membranas de PLLA/Trietil-Citrato como alternativa no tratamento de feridas cutâneas

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Lenon Cardoso

2013-01-01

Full Text Available Polímeros sintéticos biorreabsorvíveis podem ser utilizados sob a forma de membranas para sustentar e guiar o crescimento celular, através do processo de reparação tecidual. Este trabalho avaliou membranas de poli(ácido lático, PLLA, com adição de 10% de trietil-citrato usadas como curativos de feridas cutâneas agudas em ratos Wistar. Inicialmente uma ferida de 2cm² foi provocada na região dorsal de 24 animais. Estes foram divididos em 2 grupos: tratamento, nos quais as feridas foram recobertas pela membrana polimérica e controle, com feridas permanecendo cruentas. Os resultados obtidos em 1, 3, 7 e 15 dias mostraram uma resposta inflamatória mais satisfatória nas feridas protegidas pelas membranas, com reparação precoce e colágeno mais organizado quando comparadas com as áreas incialmente mantidas sem proteção. Além do que, as áreas protegidas pelas membranas não mostraram alterações inflamatórias irritativas que pudessem ser imputadas ao uso da membrana polimérica. Diante disso, conclui-se que a membrana de PLLA/Trietil-citrato protegeu efetivamente as feridas, permitindo o processo de reparação e mostrando-se promissora como curativo cutâneo.

Enhancing the bioactivity of Poly(lactic-co-glycolic acid scaffold with a nano-hydroxyapatite coating for the treatment of segmental bone defect in a rabbit model

Directory of Open Access Journals (Sweden)

Wang DX

2013-05-01

Full Text Available De-Xin Wang,1,* Yao He,2,* Long Bi1,* Ze-Hua Qu,2 Ji-Wei Zou,1 Zhen Pan,2 Jun-Jun Fan,1 Liang Chen,2 Xin Dong,1 Xiang-Nan Liu,2 Guo-Xian Pei,1 Jian-Dong Ding,21Department of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, People's Republic of China; 2State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, People's Republic of China*These authors contributed equally to this workPurpose: Poly(lactic-co-glycolic acid (PLGA is excellent as a scaffolding matrix due to feasibility of processing and tunable biodegradability, yet the virgin scaffolds lack osteoconduction and osteoinduction. In this study, nano-hydroxyapatite (nHA was coated on the interior surfaces of PLGA scaffolds in order to facilitate in vivo bone defect restoration using biomimetic ceramics while keeping the polyester skeleton of the scaffolds.Methods: PLGA porous scaffolds were prepared and surface modification was carried out by incubation in modified simulated body fluids. The nHA coated PLGA scaffolds were compared to the virgin PLGA scaffolds both in vitro and in vivo. Viability and proliferation rate of bone marrow stromal cells of rabbits were examined. The constructs of scaffolds and autogenous bone marrow stromal cells were implanted into the segmental bone defect in the rabbit model, and the bone regeneration effects were observed.Results: In contrast to the relative smooth pore surface of the virgin PLGA scaffold, a biomimetic hierarchical nanostructure was found on the surface of the interior pores of the nHA coated PLGA scaffolds by scanning electron microscopy. Both the viability and proliferation rate of the cells seeded in nHA coated PLGA scaffolds were higher than those in PLGA scaffolds. For bone defect repairing, the radius defects had, after 12 weeks implantation of nHA coated PLGA scaffolds, completely recuperated with significantly better bone formation than in

Fibrin promotes proliferation and matrix production of intervertebral disc cells cultured in three-dimensional poly(lactic-co-glycolic acid) scaffold.

Science.gov (United States)

Sha'ban, Munirah; Yoon, Sun Jung; Ko, Youn Kyung; Ha, Hyun Jung; Kim, Soon Hee; So, Jung Won; Idrus, Ruszymah Bt Hj; Khang, Gilson

2008-01-01

Previously, we have proven that fibrin and poly(lactic-co-glycolic acid) (PLGA) scaffolds facilitate cell proliferation, matrix production and early chondrogenesis of rabbit articular chondrocytes in in vitro and in vivo experiments. In this study, we evaluated the potential of fibrin/PLGA scaffold for intervertebral disc (IVD) tissue engineering using annulus fibrosus (AF) and nucleus pulposus (NP) cells in relation to potential clinical application. PLGA scaffolds were soaked in cells-fibrin suspension and polymerized by dropping thrombin-sodium chloride (CaCl(2)) solution. A PLGA-cell complex without fibrin was used as control. Higher cellular proliferation activity was observed in fibrin/PLGA-seeded AF and NP cells at each time point of 3, 7, 14 and 7 days using the MTT assay. After 3 weeks in vitro incubation, fibrin/PLGA exhibited a firmer gross morphology than PLGA groups. A significant cartilaginous tissue formation was observed in fibrin/PLGA, as proven by the development of cells cluster of various sizes and three-dimensional (3D) cartilaginous histoarchitecture and the presence of proteoglycan-rich matrix and glycosaminoglycan (GAG). The sGAG production measured by 1,9-dimethylmethylene blue (DMMB) assay revealed greater sGAG production in fibrin/PLGA than PLGA group. Immunohistochemical analyses showed expressions of collagen type II, aggrecan core protein and collagen type I genes throughout in vitro culture in both fibrin/PLGA and PLGA. In conclusion, fibrin promotes cell proliferation, stable in vitro tissue morphology, superior cartilaginous tissue formation and sGAG production of AF and NP cells cultured in PLGA scaffold. The 3D porous PLGA scaffold-cell complexes using fibrin can provide a vehicle for delivery of cells to regenerate tissue-engineered IVD tissue.

Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis of splenocin and enterocin reveals a versatile way to introduce amino acids into polyketide carbon scaffolds.

Science.gov (United States)

Chang, Chenchen; Huang, Rong; Yan, Yan; Ma, Hongmin; Dai, Zheng; Zhang, Benying; Deng, Zixin; Liu, Wen; Qu, Xudong

2015-04-01

Selective modification of carbon scaffolds via biosynthetic engineering is important for polyketide structural diversification. Yet, this scope is currently restricted to simple aliphatic groups due to (1) limited variety of CoA-linked extender units, which lack aromatic structures and chemical reactivity, and (2) narrow acyltransferase (AT) specificity, which is limited to aliphatic CoA-linked extender units. In this report, we uncovered and characterized the first aromatic CoA-linked extender unit benzylmalonyl-CoA from the biosynthetic pathways of splenocin and enterocin in Streptomyces sp. CNQ431. Its synthesis employs a deamination/reductive carboxylation strategy to convert phenylalanine into benzylmalonyl-CoA, providing a link between amino acid and CoA-linked extender unit synthesis. By characterization of its selection, we further validated that AT domains of splenocin, and antimycin polyketide synthases are able to select this extender unit to introduce the phenyl group into their dilactone scaffolds. The biosynthetic machinery involved in the formation of this extender unit is highly versatile and can be potentially tailored for tyrosine, histidine and aspartic acid. The disclosed aromatic extender unit, amino acid-oriented synthetic pathway, and aromatic-selective AT domains provides a systematic breakthrough toward current knowledge of polyketide extender unit formation and selection, and also opens a route for further engineering of polyketide carbon scaffolds using amino acids.

The self-crosslinking smart hyaluronic acid hydrogels as injectable three-dimensional scaffolds for cells culture.

Science.gov (United States)

Bian, Shaoquan; He, Mengmeng; Sui, Junhui; Cai, Hanxu; Sun, Yong; Liang, Jie; Fan, Yujiang; Zhang, Xingdong

2016-04-01

Although the disulfide bond crosslinked hyaluronic acid hydrogels have been reported by many research groups, the major researches were focused on effectively forming hydrogels. However, few researchers paid attention to the potential significance of controlling the hydrogel formation and degradation, improving biocompatibility, reducing the toxicity of exogenous and providing convenience to the clinical operations later on. In this research, the novel controllable self-crosslinking smart hydrogels with in-situ gelation property was prepared by a single component, the thiolated hyaluronic acid derivative (HA-SH), and applied as a three-dimensional scaffold to mimic native extracellular matrix (ECM) for the culture of fibroblasts cells (L929) and chondrocytes. A series of HA-SH hydrogels were prepared depending on different degrees of thiol substitution (ranging from 10 to 60%) and molecule weights of HA (0.1, 0.3 and 1.0 MDa). The gelation time, swelling property and smart degradation behavior of HA-SH hydrogel were evaluated. The results showed that the gelation and degradation time of hydrogels could be controlled by adjusting the component of HA-SH polymers. The storage modulus of HA-SH hydrogels obtained by dynamic modulus analysis (DMA) could be up to 44.6 kPa. In addition, HA-SH hydrogels were investigated as a three-dimensional scaffold for the culture of fibroblasts cells (L929) and chondrocytes cells in vitro and as an injectable hydrogel for delivering chondrocytes cells in vivo. These results illustrated that HA-SH hydrogels with controllable gelation process, intelligent degradation behavior, excellent biocompatibility and convenient operational characteristics supplied potential clinical application capacity for tissue engineering and regenerative medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

Science.gov (United States)

Madden, Lauran R; Mortisen, Derek J; Sussman, Eric M; Dupras, Sarah K; Fugate, James A; Cuy, Janet L; Hauch, Kip D; Laflamme, Michael A; Murry, Charles E; Ratner, Buddy D

2010-08-24

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

Biomimetic multidirectional scaffolds for zonal osteochondral tissue engineering via a lyophilization bonding approach.

Science.gov (United States)

Clearfield, Drew; Nguyen, Andrew; Wei, Mei

2018-04-01

The zonal organization of osteochondral tissue underlies its long term function. Despite this, tissue engineering strategies targeted for osteochondral repair commonly rely on the use of isotropic biomaterials for tissue reconstruction. There exists a need for a new class of highly biomimetic, anisotropic scaffolds that may allow for the engineering of new tissue with zonal properties. To address this need, we report the facile production of monolithic multidirectional collagen-based scaffolds that recapitulate the zonal structure and composition of osteochondral tissue. First, superficial and osseous zone-mimicking scaffolds were fabricated by unidirectional freeze casting collagen-hyaluronic acid and collagen-hydroxyapatite-containing suspensions, respectively. Following their production, a lyophilization bonding process was used to conjoin these scaffolds with a distinct collagen-hyaluronic acid suspension mimicking the composition of the transition zone. Resulting matrices contained a thin, highly aligned superficial zone that interfaced with a cellular transition zone and vertically oriented calcified cartilage and osseous zones. Confocal microscopy confirmed a zone-specific localization of hyaluronic acid, reflecting the depth-dependent increase of glycosaminoglycans in the native tissue. Poorly crystalline, carbonated hydroxyapatite was localized to the calcified cartilage and osseous zones and bordered the transition zone. Compressive testing of hydrated scaffold zones confirmed an increase of stiffness with scaffold depth, where compressive moduli of chondral and osseous zones fell within or near ranges conducive for chondrogenesis or osteogenesis of mesenchymal stem cells. With the combination of these biomimetic architectural and compositional cues, these multidirectional scaffolds hold great promise for the engineering of zonal osteochondral tissue. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 948-958, 2018. © 2017 Wiley Periodicals

Novel elastomeric fibrous networks produced from poly(xylitol sebacate)2:5 by core/shell electrospinning: fabrication and mechanical properties.

Science.gov (United States)

Li, Yuan; Thouas, George A; Chen, Qizhi

2014-12-01

Fabrication of nonlinear elastic materials that resemble biological tissues remains a challenge in biomaterials research. Here, a new fabrication protocol to produce elastomeric fibrous scaffolds was established, using the core/shell electrospinning technique. A prepolymer of poly(xylitol sebacate) with a 2:5mol ratio of xylitol:sebacic acid (PXS2:5) was first formulated, then co-electrospun with polyvinyl alcohol (PVA - 95,000Mw). After cross-linking of core polymer PXS2:5, the PVA shells were rinsed off in water, leaving a porous elastomeric network of PXS2:5 fibres. Under aqueous conditions, the PXS2:5 fibrous scaffolds exhibited stable, nonlinear J-shaped stress-strain curves, with large average rupture elongation (76%) and Young׳s modulus (~1.0MPa), which were in the range of muscle tissue. Rupture elongation of PXS2:5 was also much higher when electrospun, compared to 2D solid sheets (45%). In direct contact with cell monolayers under physiological conditions, PXS2:5 scaffolds were as biocompatible as those made of poly-l-lactic acid (PLLA), with improvements over culture medium alone. In conclusion, the newly developed porous PXS2:5 scaffolds show tissue-like mechanical properties and excellent biocompatibility, making them very promising for bioengineering of soft tissues and organs. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electrospinning polymer blends for biomimetic scaffolds for ACL tissue engineering

Science.gov (United States)

Garcia, Vanessa Lizeth

The anterior cruciate ligament (ACL) rupture is one of the most common knee injuries. Current ACL reconstructive strategies consist of using an autograft or an allograft to replace the ligament. However, limitations have led researchers to create tissue engineered grafts, known as scaffolds, through electrospinning. Scaffolds made of natural and synthetic polymer blends have the potential to promote cell adhesion while having strong mechanical properties. However, enzymes found in the knee are known to degrade tissues and affect the healing of intra-articular injuries. Results suggest that the natural polymers used in this study modify the thermal properties and tensile strength of the synthetic polymers when blended. Scanning electron microscopy display bead-free and enzyme biodegradability of the fibers. Raman spectroscopy confirms the presence of the natural and synthetic polymers in the scaffolds while, amino acid analysis present the types of amino acids and their concentrations found in the natural polymers.

Plasma Surface Modification for Immobilization of Bone Morphogenic Protein-2 on Polycaprolactone Scaffolds

Science.gov (United States)

Kim, Byung Hoon; Myung, Sung Woon; Jung, Sang Chul; Ko, Yeong Mu

2013-11-01

The immobilization of recombinant human bone formation protein-2 (rhBMP-2) on polycaprolactone (PCL) scaffolds was performed by plasma polymerization. RhBMP-2, which induces osteoblast differentiation in various cell types, is a growth factor that plays an important role in bone formation and repair. The surface of the PCL scaffold was functionalized with the carboxyl groups of plasma-polymerized acrylic acid (PPAA) thin films. Plasma polymerization was carried out at a discharge power of 60 W at an acrylic acid flow rate of 7 sccm for 5 min. The PPAA thin film exhibited moderate hydrophilic properties and possessed a high density of carboxyl groups. Carboxyl groups and rhBMP-2 on the PCL scaffolds surface were identified by attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. The alkaline phosphatase activity assay showed that the rhBMP-2 immobilized PCL scaffold increased the level of MG-63 cell differentiation. Plasma surface modification for the preparation of biomaterials, such as biofunctionalized polymer scaffolds, can be used for the binding of bioactive molecules in tissue engineering.

A combinatorial approach towards the design of nanofibrous scaffolds for chondrogenesis

Science.gov (United States)

Ahmed, Maqsood; Ramos, Tiago André Da Silva; Damanik, Febriyani; Quang Le, Bach; Wieringa, Paul; Bennink, Martin; van Blitterswijk, Clemens; de Boer, Jan; Moroni, Lorenzo

2015-10-01

The extracellular matrix (ECM) is a three-dimensional (3D) structure composed of proteinaceous fibres that provide physical and biological cues to direct cell behaviour. Here, we build a library of hybrid collagen-polymer fibrous scaffolds with nanoscale dimensions and screen them for their ability to grow chondrocytes for cartilage repair. Poly(lactic acid) and poly (lactic-co-glycolic acid) at two different monomer ratios (85:15 and 50:50) were incrementally blended with collagen. Physical properties (wettability and stiffness) of the scaffolds were characterized and related to biological performance (proliferation, ECM production, and gene expression) and structure-function relationships were developed. We found that soft scaffolds with an intermediate wettability composed of the highly biodegradable PLGA50:50 and collagen, in two ratios (40:60 and 60:40), were optimal for chondrogenic differentiation of ATDC5 cells as determined by increased ECM production and enhanced cartilage specific gene expression. Long-term cultures indicated a stable phenotype with minimal de-differentiation or hypertrophy. The combinatorial methodology applied herein is a promising approach for the design and development of scaffolds for regenerative medicine.

Novel mechanically competent polysaccharide scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Kumbar, S G; Toti, U S; Deng, M; James, R; Laurencin, C T; Aravamudhan, A; Harmon, M; Ramos, D M

2011-01-01

The success of the scaffold-based bone regeneration approach critically depends on the biomaterial's mechanical and biological properties. Cellulose and its derivatives are inherently associated with exceptional strength and biocompatibility due to their β-glycosidic linkage and extensive hydrogen bonding. This polymer class has a long medical history as a dialysis membrane, wound care system and pharmaceutical excipient. Recently cellulose-based scaffolds have been developed and evaluated for a variety of tissue engineering applications. In general porous polysaccharide scaffolds in spite of many merits lack the necessary mechanical competence needed for load-bearing applications. The present study reports the fabrication and characterization of three-dimensional (3D) porous sintered microsphere scaffolds based on cellulose derivatives using a solvent/non-solvent sintering approach for load-bearing applications. These 3D scaffolds exhibited a compressive modulus and strength in the mid-range of human trabecular bone and underwent degradation resulting in a weight loss of 10–15% after 24 weeks. A typical stress–strain curve for these scaffolds showed an initial elastic region and a less-stiff post-yield region similar to that of native bone. Human osteoblasts cultured on these scaffolds showed progressive growth with time and maintained expression of osteoblast phenotype markers. Further, the elevated expression of alkaline phosphatase and mineralization at early time points as compared to heat-sintered poly(lactic acid–glycolic acid) control scaffolds with identical pore properties affirmed the advantages of polysaccharides and their potential for scaffold-based bone regeneration.

Osteogenic differentiation of MC3T3-E1 cells on poly(L-lactide)/Fe{sub 3}O{sub 4} nanofibers with static magnetic field exposure

Energy Technology Data Exchange (ETDEWEB)

Cai, Qing [State Key Laboratory of Organic–inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Shi, Yuzhou; Shan, Dingying; Jia, Wenkai; Duan, Shun [Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China); Deng, Xuliang [Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081 (China); Yang, Xiaoping, E-mail: yangxp@mail.buct.edu.cn [State Key Laboratory of Organic–inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 (China)

2015-10-01

Proliferation and differentiation of bone-related cells are modulated by many factors such as scaffold design, growth factor, dynamic culture system, and physical simulation. Nanofibrous structure and moderate-intensity (1 mT–1 T) static magnetic field (SMF) have been identified as capable of stimulating proliferation and differentiation of osteoblasts. Herein, magnetic nanofibers were prepared by electrospinning mixture solutions of poly(L-lactide) (PLLA) and ferromagnetic Fe{sub 3}O{sub 4} nanoparticles (NPs). The PLLA/Fe{sub 3}O{sub 4} composite nanofibers demonstrated homogeneous dispersion of Fe{sub 3}O{sub 4} NPs, and their magnetism depended on the contents of Fe{sub 3}O{sub 4} NPs. SMF of 100 mT was applied in the culture of MC3T3-E1 osteoblasts on pure PLLA and PLLA/Fe{sub 3}O{sub 4} composite nanofibers for the purpose of studying the effect of SMF on osteogenic differentiation of osteoblastic cells on magnetic nanofibrous scaffolds. On non-magnetic PLLA nanofibers, the application of external SMF could enhance the proliferation and osteogenic differentiation of MC3T3-E1 cells. In comparison with pure PLLA nanofibers, the incorporation of Fe{sub 3}O{sub 4} NPs could also promote the proliferation and osteogenic differentiation of MC3T3-E1 cells in the absence or presence of external SMF. The marriage of magnetic nanofibers and external SMF was found most effective in accelerating every aspect of biological behaviors of MC3T3-E1 osteoblasts. The findings demonstrated that the magnetic feature of substrate and microenvironment were applicable ways in regulating osteogenesis in bone tissue engineering. - Highlights: • Magnetic nanofibers containing well-dispersed Fe{sub 3}O{sub 4} nanoparticles were produced. • Static magnetic field (SMF) was applied to perform the culture of osteoblasts. • Osteogenic differentiation was enhanced on magnetic substrate with exposure to SMF.

Reduction of Inflammatory Responses and Enhancement of Extracellular Matrix Formation by Vanillin-Incorporated Poly(Lactic-co-Glycolic Acid) Scaffolds

OpenAIRE

Lee, Yujung; Kwon, Jeongil; Khang, Gilson; Lee, Dongwon

2012-01-01

Vanillin is one of the major components of vanilla, a commonly used flavoring agent and preservative and is known to exert potent antioxidant and anti-inflammatory activities. In this work, vanillin-incorporated poly(lactic-co-glycolic acid) (PLGA) films and scaffolds were fabricated to evaluate the effects of vanillin on the inflammatory responses and extracellular matrix (ECM) formation in vitro and in vivo. The incorporation of vanillin to PLGA films induced hydrophilic nature, resulting i...

Flexible tension sensor based on poly(l-lactic acid) film with coaxial structure

Science.gov (United States)

Yoshida, Mitsunobu; Onishi, Katsuki; Tanimoto, Kazuhiro; Nishikawa, Shigeo

2017-10-01

We have developed a tension sensor with a coaxial structure using a narrow slit ribbon made of a uniaxially stretched poly(l-lactic acid) (PLLA) film for application to a wearable device. The tension sensor is produced as follows. We used tinsel wire as the center conductor of the sensor. The tinsel wire consists of a yarn of synthetic fibers arranged at the center, with a spirally wound rolled copper foil ribbon on the side surface. Next, slit ribbons obtained from a uniaxially oriented film of PLLA are wound helically on the side surface of the center conductor in the direction of a left-handed screw, at an angle of 45° to the central axis. The rolled copper foil is used as an outer conductor and covers the yarn without a gap. The prototype of the fabricated tension sensor has good flexibility, since the sensor is in the form of a filament and consists of a highly flexible material. For the 1 mm tension sensor, it was found that for a tension of 1 N, a charge of 14 pC was output. It was also found that the sensor maintained its room-temperature sensitivity up to 60 °C. Compared with an existing coaxial line sensor using poly(vinylidene fluoride) (PVDF), the sensor using PLLA does not exhibit pyroelectricity, meaning that no undesirable voltage is generated when in contact with body heat, which is a significant advantage as wearable sensors. The result has demonstrated the potential application of the PLLA film to wearable devices for detecting heartbeat and respiration.

Influence of electrospun scaffolds prepared from distinct polymers on proliferation and viability of endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Matveeva, V. G., E-mail: matveeva-vg@mail.ru; Antonova, L. V., E-mail: antonova.la@mail.ru; Velikanova, E. A.; Sergeeva, E. A.; Krivkina, E. O.; Glushkova, T. V.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, 650002 (Russian Federation)

2015-10-27

We compared electrospun nonwoven scaffolds from polylactic acid (PLA), polycaprolactone (PCL), and polyhydroxybutyrate/valerate (PHBV)/polycaprolactone (PHBV/PCL). The surface of PHBV/PCL and PCL scaffolds was highly porous and consisted of randomly distributed fibers, whilst the surface of PLA scaffolds consisted of thin straight fibers, which located more sparsely, forming large pores. Culture of EA.hy 926 endothelial cells on these scaffolds during 7 days and further fluorescent microscopy demonstrated that the surface of PHBV/PCL scaffolds was most favorable for efficient adhesion, proliferation, and viability of endothelial cells. The lowest proliferation rate and cell viability were detected on PLA scaffolds. Therefore, PHBV/PCL electrospun nonwoven scaffolds demonstrated the best results regarding endothelial cell proliferation and viability as compared to PCL and PLA scaffolds.

Piezoelectricity of chiral polymeric fiber and its application in biomedical engineering.

Science.gov (United States)

Tajitsu, Y

2008-05-01

Poly-L-lactic acid (PLLA), which is a type of chiral polymer, exhibits a high shear piezoelectric constant. To realize a higher shear piezoelectric constant, we spun PLLA resin into fibers. We succeeded in controlling the piezoelectric motion of a PLLA fiber by applying a dc voltage and ac voltage, similar to the control of a piezoelectric actuator. On the basis of this experimental result, we designed a catheter using a PLLA fiber (PLLA fiber catheter) and tweezers using a pair of PLLA fibers (PLLA fiber tweezers), controlled by adjusting the applied voltage. Then, using the PLLA fiber tweezers or catheter, we successfully picked up and removed small samples, such as a thrombosis in a blood vessel.

Coating of hydrophobins on three-dimensional electrospun poly(lactic-co-glycolic acid) scaffolds for cell adhesion

Energy Technology Data Exchange (ETDEWEB)

Hou Sen; Li Xinxin; Li Xiaoyu; Feng Xizeng, E-mail: xzfeng@nankai.edu.c [College of Life Science, Nankai University, Weijin Road 94, Tianjin, 300071 (China)

2009-09-15

Surface modification with hydrophobins is very important for cell adhesion in its applications in biosensor fabrication. In this study, we modified the surface of three-dimensional electrospun poly(lactide-co-glycolide) (PLGA) scaffolds with hydrophobin HFBI and collagen, and investigated its applications for cell adhesion. We found that HFBI could not only improve the hydrophilicity of the three-dimensional electrospun PLGA scaffolds but also endow the electrospun PLGA scaffolds with water permeability. This permeability should be attributed to both the hydrophilicity of the modified PLGA surface and the large positive capillary effect induced by the microstructures. Further experiment indicated that HFBI modification could improve collagen immobilization on the electrospun PLGA scaffolds and the HFBI/collagen modified electrospun PLGA scaffolds showed higher efficiency in promoting cell adhesion than the native PLGA scaffolds. This finding should be of potential application in biosensor device fabrication.

Carbon nanotube-coating accelerated cell adhesion and proliferation on poly (L-lactide)

Science.gov (United States)

Hirata, Eri; Akasaka, Tsukasa; Uo, Motohiro; Takita, Hiroko; Watari, Fumio; Yokoyama, Atsuro

2012-12-01

The surface of a polylactic acid (PLLA) was coated multiwalled carbon nanotubes (MWCNTs) in order to improve the surface properties. In addition, its surface characteristics and cell culturing properties were examined. Whole surface of PLLA was homogeneously covered by MWCNTs maintained a unique tubular structure. MWCNT-coated PLLA showed remarkable higher wettability than uncoated PLLA. Human osteosarcoma cell line (Saos2) adhered well on the CNT-coated PLLA whereas there are few cells attached on the uncoated PLLA at 2 h after seeding. The number of the cells on uncoated PLLA was still smaller than on the MWCNT-coated PLLA at 1 and 3 days. Moreover, The DNA content in the cells attached to the MWCNT-coated PLLA was significantly higher than that on the uncoated PLLA (p 0.1). Therefore MWCNT-coating on PLLA improved the surface wettability and initial cell attachment at early stage.

Mechanical properties and dual drug delivery application of poly(lactic-co-glycolic acid) scaffolds fabricated with a poly(β-amino ester) porogen.

Science.gov (United States)

Clark, Amanda; Milbrandt, Todd A; Hilt, J Zach; Puleo, David A

2014-05-01

Polymeric scaffolds that are biocompatible and biodegradable are widely used for tissue engineering applications. Scaffolds can be further enhanced by enabling the release of one or more drugs to stimulate regeneration or for the treatment of a specific disease or condition. In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres were mixed with poly(β-amino ester) (PBAE) particles to create novel hybrid scaffolds capable of dual release of drug and growth factor. Fast-degrading PBAE particles loaded with the drug ketoprofen acted as porogens that provided a rapid 12h release. The PLGA microspheres were loaded with a growth factor, bone morphogenetic protein 2, and fused together around the porogens to create a slow-degrading matrix that provided sustained release lasting 70days. Drug release was further tailored by varying the amount of porogen added to the scaffold. Bioactivity measurements demonstrated that the scaffold fabrication technique did not damage the drug or protein. The compressive modulus was affected by the amount of porogen added, extending from 50 to 111MPa for loadings from 60 to 40% PBAE, and after 5days of degradation, it decreased to 0.6 to 1.1kPa when the porogen was gone. PLGA containing a quick-degrading porogen can be used to release two drugs while developing a porous microarchitecture for cell ingrowth with in a matrix capable of maintaining a compressive modulus applicable for soft tissue implants. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Injectable biomimetic liquid crystalline scaffolds enhance muscle stem cell transplantation

Science.gov (United States)

Sleep, Eduard; McClendon, Mark T.; Preslar, Adam T.; Chen, Charlotte H.; Sangji, M. Hussain; Pérez, Charles M. Rubert; Haynes, Russell D.; Meade, Thomas J.; Blau, Helen M.; Stupp, Samuel I.

2017-01-01

Muscle stem cells are a potent cell population dedicated to efficacious skeletal muscle regeneration, but their therapeutic utility is currently limited by mode of delivery. We developed a cell delivery strategy based on a supramolecular liquid crystal formed by peptide amphiphiles (PAs) that encapsulates cells and growth factors within a muscle-like unidirectionally ordered environment of nanofibers. The stiffness of the PA scaffolds, dependent on amino acid sequence, was found to determine the macroscopic degree of cell alignment templated by the nanofibers in vitro. Furthermore, these PA scaffolds support myogenic progenitor cell survival and proliferation and they can be optimized to induce cell differentiation and maturation. We engineered an in vivo delivery system to assemble scaffolds by injection of a PA solution that enabled coalignment of scaffold nanofibers with endogenous myofibers. These scaffolds locally retained growth factors, displayed degradation rates matching the time course of muscle tissue regeneration, and markedly enhanced the engraftment of muscle stem cells in injured and noninjured muscles in mice. PMID:28874575

The use of fibrin and poly(lactic-co-glycolic acid hybrid scaffold for articular cartilage tissue engineering: an in vivo analysis

Directory of Open Access Journals (Sweden)

S Munirah

2008-02-01

Full Text Available Our preliminary results indicated that fibrin and poly(lactic-co-glycolic acid (PLGA hybrid scaffold promoted early chondrogenesis of articular cartilage constructs in vitro. The aim of this study was to evaluate in vivo cartilaginous tissue formation by chondrocyte-seeded fibrin/PLGA hybrid scaffolds. PLGA scaffolds were soaked carefully, in chondrocyte-fibrin suspension, and polymerized by dropping thrombin-calcium chloride (CaCl2 solution. PLGA-seeded chondrocytes were used as a control. Resulting constructs were implanted subcutaneously, at the dorsum of nude mice, for 4 weeks. Macroscopic observation, histological evaluation, gene expression and sulphated-glycosaminoglycan (sGAG analyses were performed at each time point of 1, 2 and 4 weeks post-implantation. Cartilaginous tissue formation in fibrin/PLGA hybrid construct was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan and glycosaminoglycan (GAG in fibrin/PLGA hybrid constructs was confirmed by positive Safranin O and Alcian Blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene encoded cartilage-specific markers, collagen type II and aggrecan core protein. The sGAG production in fibrin/PLGA hybrid constructs was higher than in the PLGA group. In conclusion, fibrin/PLGA hybrid scaffold promotes cartilaginous tissue formation in vivo and may serve as a potential cell delivery vehicle and a structural basis for articular cartilage tissue-engineering.

Reconstruction of rat calvarial defects with human mesenchymal stem cells and osteoblast-like cells in poly-lactic-co-glycolic acid scaffolds

Directory of Open Access Journals (Sweden)

C Zong

2010-09-01

Full Text Available Human mesenchymal stem cells (hMSCs can be used for xenogenic transplantation due to their low immunogenicity, high proliferation rate, and multi-differentiation potentials. Therefore, hMSCs are an ideal seeding source for tissue engineering. The present study evaluates the reconstruction effects of hMSCs and osteoblast-like cells differentiated from hMSCs in poly-lactic-co-glycolic acid (PLGA scaffolds on the calvarial defect of rats. Two bilateral full-thickness defects (5mm in diameter were created in the calvarium of nonimmunosuppressed Sprague-Dawley rats. The defects were filled by PLGA scaffolds with hMSCs (hMSC Construct or with osteoblast-like cells differentiated from hMSCs (Osteoblast Construct. The defects without any graft (Blank Defect or filled with PLGA scaffold without any cells (Blank Scaffold were used as controls. Evaluation was performed using macroscopic view, histology and immunohistochemical analysis respectively at 10 and 20 weeks after transplantation. In addition, fluorescent carbocyanine CM-Dil was used to track the implanted cells in vivo during transplantation. The results showed that while both hMSC Construct and Osteoblast Construct led to an effective reconstruction of critical-size calvarial defects, the bone reconstruction potential of hMSC Construct was superior to that of Osteoblast Construct in non-autogenous applications. Our findings verify the feasibility of the use of xenogenic MSCs for tissue engineering and demonstrate that undifferentiated hMSCs are more suitable for bone reconstruction in xenotransplantation models.

In Vitro Testing of Scaffolds for Mesenchymal Stem Cell-Based Meniscus Tissue Engineering—Introducing a New Biocompatibility Scoring System

Directory of Open Access Journals (Sweden)

Felix P. Achatz

2016-04-01

Full Text Available A combination of mesenchymal stem cells (MSCs and scaffolds seems to be a promising approach for meniscus repair. To facilitate the search for an appropriate scaffold material a reliable and objective in vitro testing system is essential. This paper introduces a new scoring for this purpose and analyzes a hyaluronic acid (HA gelatin composite scaffold and a polyurethane scaffold in combination with MSCs for tissue engineering of meniscus. The pore quality and interconnectivity of pores of a HA gelatin composite scaffold and a polyurethane scaffold were analyzed by surface photography and Berliner-Blau-BSA-solution vacuum filling. Further the two scaffold materials were vacuum-filled with human MSCs and analyzed by histology and immunohistochemistry after 21 days in chondrogenic media to determine cell distribution and cell survival as well as proteoglycan production, collagen type I and II content. The polyurethane scaffold showed better results than the hyaluronic acid gelatin composite scaffold, with signs of central necrosis in the HA gelatin composite scaffolds. The polyurethane scaffold showed good porosity, excellent pore interconnectivity, good cell distribution and cell survival, as well as an extensive content of proteoglycans and collagen type II. The polyurethane scaffold seems to be a promising biomaterial for a mesenchymal stem cell-based tissue engineering approach for meniscal repair. The new score could be applied as a new standard for in vitro scaffold testing.

Development and characterization of coaxially electrospun gelatin coated poly (3-hydroxybutyric acid) thin films as potential scaffolds for skin regeneration

International Nuclear Information System (INIS)

Nagiah, Naveen; Madhavi, Lakshmi; Anitha, R.; Anandan, C.; Srinivasan, Natarajan Tirupattur; Sivagnanam, Uma Tirichurapalli

2013-01-01

The morphology of fibers synthesized through electrospinning has been found to mimic extracellular matrix. Coaxially electrospun fibers of gelatin (sheath) coated poly (3-hydroxybutyric acid) (PHB) (core) was developed using 2,2,2 trifluoroethanol(TFE) and 1,1,1,3,3,3 hexafluoro-2-propanol(HFIP) as solvents respectively. The coaxial structure and coating of gelatin with PHB fibers was confirmed through transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Thermal stability of the coaxially electrospun fibers was analyzed using thermogravimetric analysis(TGA), differential scanning calorimetry(DSC) and differential thermogravimetric analysis(DTA). Complete evaporation of solvent and gelatin grafting over PHB fibers was confirmed through attenuated total reflection-Fourier transformed infrared spectroscopy (ATR-FTIR). The coaxially electrospun fibers exhibited competent tensile properties for skin regeneration with high surface area and porosity. In vitro degradation studies proved the stability of fibers and its potential applications in tissue engineering. The fibers supported the growth of human dermal fibroblasts and keratinocytes with normal morphology indicating its potential as a scaffold for skin regeneration. - Highlights: • Coaxial electrospinning was employed to develop core-shell fibers of PHB and gelatin. • The scaffold has competent physicochemical properties. • Developed scaffold will have high impact as a dermal substitute in skin regeneration

Development and characterization of coaxially electrospun gelatin coated poly (3-hydroxybutyric acid) thin films as potential scaffolds for skin regeneration

Energy Technology Data Exchange (ETDEWEB)

Nagiah, Naveen [Bioproducts Lab, Central Leather Research Institute, Adyar, Chennai (India); Madhavi, Lakshmi; Anitha, R. [CavinKare Research Centre, Ekkattuthangal, Chennai (India); Anandan, C. [National Aerospace Laboratory, Banglore (India); Srinivasan, Natarajan Tirupattur, E-mail: naveen.nagiah@gmail.com [Conducting Polymers Lab, Department of Physics, Indian Institute of Technology Madras, Chennai (India); Sivagnanam, Uma Tirichurapalli, E-mail: suma67@gmail.com [Bioproducts Lab, Central Leather Research Institute, Adyar, Chennai (India)

2013-10-01

The morphology of fibers synthesized through electrospinning has been found to mimic extracellular matrix. Coaxially electrospun fibers of gelatin (sheath) coated poly (3-hydroxybutyric acid) (PHB) (core) was developed using 2,2,2 trifluoroethanol(TFE) and 1,1,1,3,3,3 hexafluoro-2-propanol(HFIP) as solvents respectively. The coaxial structure and coating of gelatin with PHB fibers was confirmed through transmission electron microscopy (TEM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). Thermal stability of the coaxially electrospun fibers was analyzed using thermogravimetric analysis(TGA), differential scanning calorimetry(DSC) and differential thermogravimetric analysis(DTA). Complete evaporation of solvent and gelatin grafting over PHB fibers was confirmed through attenuated total reflection-Fourier transformed infrared spectroscopy (ATR-FTIR). The coaxially electrospun fibers exhibited competent tensile properties for skin regeneration with high surface area and porosity. In vitro degradation studies proved the stability of fibers and its potential applications in tissue engineering. The fibers supported the growth of human dermal fibroblasts and keratinocytes with normal morphology indicating its potential as a scaffold for skin regeneration. - Highlights: • Coaxial electrospinning was employed to develop core-shell fibers of PHB and gelatin. • The scaffold has competent physicochemical properties. • Developed scaffold will have high impact as a dermal substitute in skin regeneration.

Comparison of Acute Thrombogenicity for Magnesium versus Stainless Steel Stents in a Porcine Arteriovenous Shunt Model.

Science.gov (United States)

Lipinski, Michael J; Acampado, Eduardo; Cheng, Qi; Adams, Lila; Torii, Sho; Gai, Jiaxiang; Torguson, Rebecca; Hellinga, David G; Joner, Michael; Harder, Claus; Zumstein, Philine; Finn, Aloke V; Kolodgie, Frank D; Virmani, Renu; Waksman, Ron

2018-05-08

Aims The aetiology for reduced thrombogenicity of the Magmaris resorbable magnesium scaffold (RMS) when compared with the Absorb bioresorbable vascular scaffold remains unclear. We therefore investigated whether the Magmaris RMS has platelet-repelling properties by comparing its acute thrombogenicity with an equivalent stainless steel stent in an arteriovenous shunt model. Methods and Results An ex vivo porcine carotid jugular arteriovenous shunt was established and connected to Sylgard tubing containing the Magmaris RMS with sirolimus-eluting PLLA coating and an equivalent 316L stainless steel stent with sirolimus-eluting PLLA coating. Six shunts (2 shunt runs per pig) were run comparing the 2 scaffolds (n=9) in alternating order. Nested generalised linear mixed models were employed to compare variables between scaffold groups. Confocal fluorescent microscopy costaining CD61/CD42b demonstrated that the 316L equivalent stent had significantly greater platelet coverage of the total scaffold compared with Magmaris (5.8% vs. 2.8%, Rate ratio 2.21 [1.41, 3.47], p=0.012). Scanning electron microscopy demonstrated significantly greater thrombus deposition on the 316L equivalent stent as a percentage of the total scaffold compared with Magmaris (8.0% vs. 5.3%, p=0.009). Magmaris also had significantly less CD14 positive monocyte deposition and a trend toward less PM-1 positive neutrophil compared with the 316L equivalent stent. Conclusion Despite having identical scaffold characteristics regarding geometrical design, Magmaris had significantly less thrombogenicity and inflammatory cell deposition compared with the equivalent 316L stainless steel stent in a porcine arteriovenous shunt model. These data suggest resorbable magnesium scaffolds may have inherent properties that reduce adhesion of platelets and inflammatory cells.

Poly(L-lactic acid) nanofibers containing Cissus quadrangularis induced osteogenic differentiation in vitro.

Science.gov (United States)

Parvathi, K; Krishnan, Amit G; Anitha, A; Jayakumar, R; Nair, Manitha B

2018-04-15

Cissus quadrangularis (CQ) is known as "bone setter" in Ayurvedic Medicine because of its ability to promote fracture healing. Polymers incorporated with CQ at lower concentration have shown to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. However, for the healing of clinically relevant critical sized bone defects, large amount of CQ would be required. Based on this perception, a herbal fibrous sheet containing high weight percentage of CQ [20,40 and 60wt/wt% in poly (L-lactic acid) (PLLA)] was fabricated through electrospinning. The solution concentration, flow rate, voltage and tip-target distance was optimized to obtain nanofibers. The hydrophobicity of PLLA fibers was reduced through CQ incorporation. There was considerable increase in the adhesion, proliferation and osteogenic differentiation of MSCs on herbal fibers than normal fibers, mainly on P-Q20 and P-CQ40. MSCs were differentiated into osteoblasts without providing any osteogenic supplements in the medium, indicating its osteoinductive capability. The herbal sheet also could promote mineralization when immersed in simulated body fluid for 14days. These studies specify that PLLA nanofibers loaded with 20 and 40wt% of CQ could serve as a potential candidate for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

PLDLA/PCL-T Scaffold for Meniscus Tissue Engineering.

Science.gov (United States)

Esposito, Andrea Rodrigues; Moda, Marlon; Cattani, Silvia Mara de Melo; de Santana, Gracy Mara; Barbieri, Juliana Abreu; Munhoz, Monique Moron; Cardoso, Túlio Pereira; Barbo, Maria Lourdes Peris; Russo, Teresa; D'Amora, Ugo; Gloria, Antonio; Ambrosio, Luigi; Duek, Eliana Aparecida de Rezende

2013-04-01

The inability of the avascular region of the meniscus to regenerate has led to the use of tissue engineering to treat meniscal injuries. The aim of this study was to evaluate the ability of fibrochondrocytes preseeded on PLDLA/PCL-T [poly(L-co-D,L-lactic acid)/poly(caprolactone-triol)] scaffolds to stimulate regeneration of the whole meniscus. Porous PLDLA/PCL-T (90/10) scaffolds were obtained by solvent casting and particulate leaching. Compressive modulus of 9.5±1.0 MPa and maximum stress of 4.7±0.9 MPa were evaluated. Fibrochondrocytes from rabbit menisci were isolated, seeded directly on the scaffolds, and cultured for 21 days. New Zealand rabbits underwent total meniscectomy, after which implants consisting of cell-free scaffolds or cell-seeded scaffolds were introduced into the medial knee meniscus; the negative control group consisted of rabbits that received no implant. Macroscopic and histological evaluations of the neomeniscus were performed 12 and 24 weeks after implantation. The polymer scaffold implants adapted well to surrounding tissues, without apparent rejection, infection, or chronic inflammatory response. Fibrocartilaginous tissue with mature collagen fibers was observed predominantly in implants with seeded scaffolds compared to cell-free implants after 24 weeks. Similar results were not observed in the control group. Articular cartilage was preserved in the polymeric implants and showed higher chondrocyte cell number than the control group. These findings show that the PLDLA/PCL-T 90/10 scaffold has potential for orthopedic applications since this material allowed the formation of fibrocartilaginous tissue, a structure of crucial importance for repairing injuries to joints, including replacement of the meniscus and the protection of articular cartilage from degeneration.

Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold.

Science.gov (United States)

Lv, Y M; Yu, Q S

2015-04-01

The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. The bone-cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid-hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56-64. ©2015 The British Editorial Society of Bone & Joint Surgery.

Post Processing and Biological Evaluation of the Titanium Scaffolds for Bone Tissue Engineering.

Science.gov (United States)

Wysocki, Bartłomiej; Idaszek, Joanna; Szlązak, Karol; Strzelczyk, Karolina; Brynk, Tomasz; Kurzydłowski, Krzysztof J; Święszkowski, Wojciech

2016-03-15

Nowadays, post-surgical or post-accidental bone loss can be substituted by custom-made scaffolds fabricated by additive manufacturing (AM) methods from metallic powders. However, the partially melted powder particles must be removed in a post-process chemical treatment. The aim of this study was to investigate the effect of the chemical polishing with various acid baths on novel scaffolds' morphology, porosity and mechanical properties. In the first stage, Magics software (Materialise NV, Leuven, Belgium) was used to design a porous scaffolds with pore size equal to (A) 200 µm, (B) 500 µm and (C) 200 + 500 µm, and diamond cell structure. The scaffolds were fabricated from commercially pure titanium powder (CP Ti) using a SLM50 3D printing machine (Realizer GmbH, Borchen, Germany). The selective laser melting (SLM) process was optimized and the laser beam energy density in range of 91-151 J/mm³ was applied to receive 3D structures with fully dense struts. To remove not fully melted titanium particles the scaffolds were chemically polished using various HF and HF-HNO₃ acid solutions. Based on scaffolds mass loss and scanning electron (SEM) observations, baths which provided most uniform surface cleaning were proposed for each porosity. The pore and strut size after chemical treatments was calculated based on the micro-computed tomography (µ-CT) and SEM images. The mechanical tests showed that the treated scaffolds had Young's modulus close to that of compact bone. Additionally, the effect of pore size of chemically polished scaffolds on cell retention, proliferation and differentiation was studied using human mesenchymal stem cells. Small pores yielded higher cell retention within the scaffolds, which then affected their growth. This shows that in vitro cell performance can be controlled to certain extent by varying pore sizes.

Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

Science.gov (United States)

Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

2017-02-01

Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering.

Science.gov (United States)

Chen, Chih-Hao; Kuo, Chang-Yi; Wang, Yan-Jie; Chen, Jyh-Ping

2016-11-23

Glucosamine (GlcN) fulfills many of the requirements as an ideal component in scaffolds used in cartilage tissue engineering. The incorporation of GlcN in a gelatin/hyaluronic acid (GH) cryogel scaffold could provide biological cues in maintaining the phenotype of chondrocytes. Nonetheless, substituting gelatin with GlcN may also decrease the crosslinking density and modulate the mechanical properties of the cryogel scaffold, which may be beneficial as physical cues for chondrocytes in the scaffold. Thus, we prepared cryogel scaffolds containing 9% GlcN (GH-GlcN9) and 16% GlcN (GH-GlcN16) by carbodiimide-mediated crosslinking reactions at -16 °C. The crosslinking density and the mechanical properties of the cryogel matrix could be tuned by adjusting the content of GlcN used during cryogel preparation. In general, incorporation of GlcN did not influence scaffold pore size and ultimate compressive strain but increased porosity. The GH-GlcN16 cryogel showed the highest swelling ratio and degradation rate in hyaluronidase and collagenase solutions. On the contrary, the Young's modulus, storage modulus, ultimate compressive stress, energy dissipation level, and rate of stress relaxation decreased by increasing the GlcN content in the cryogel. The release of GlcN from the scaffolds in the culture medium of chondrocytes could be sustained for 21 days for GH-GlcN16 in contrast to only 7 days for GH-GlcN9. In vitro cell culture experiments using rabbit articular chondrocytes revealed that GlcN incorporation affected cell proliferation, morphology, and maintenance of chondrogenic phenotype. Overall, GH-GlcN16 showed the best performance in maintaining chondrogenic phenotype with reduced cell proliferation rate but enhanced glycosaminoglycans (GAGs) and type II collagen (COL II) secretion. Quantitative real-time polymerase chain reaction also showed time-dependent up-regulation of cartilage-specific marker genes (COL II, aggrecan and Sox9) for GH-GlcN16. Implantation of

A new biocompatible delivery scaffold containing heparin and bone morphogenetic protein 2

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Thanyaphoo Suphannee

2016-09-01

Full Text Available Silicon-substituted calcium phosphate (Si-CaP was developed in our laboratory as a biomaterial for delivery in bone tissue engineering. It was fabricated as a 3D-construct of scaffolds using chitosan-trisodium polyphosphate (TPP cross-linked networks. In this study, heparin was covalently bonded to the residual -NH2 groups of chitosan on the scaffold applying carbodiimide chemistry. Bonded heparin was not leached away from scaffold surfaces upon vigorous washing or extended storage. Recombinant human bone morphogenetic protein 2 (rhBMP-2 was bound to conjugated scaffolds by ionic interactions between the negatively charged SO42- clusters of heparin and positively charged amino acids of rhBMP-2. The resulting scaffolds were inspected for bone regenerative capacity by subcutaneous implanting in rats. Histological observation and mineralization assay were performed after 4 weeks of implantation. Results from both in vitro and in vivo experiments suggest the potential of the developed scaffolds for bone tissue engineering applications in the future.

Annealing free, clean graphene transfer using alternative polymer scaffolds.

Science.gov (United States)

Wood, Joshua D; Doidge, Gregory P; Carrion, Enrique A; Koepke, Justin C; Kaitz, Joshua A; Datye, Isha; Behnam, Ashkan; Hewaparakrama, Jayan; Aruin, Basil; Chen, Yaofeng; Dong, Hefei; Haasch, Richard T; Lyding, Joseph W; Pop, Eric

2015-02-06

We examine the transfer of graphene grown by chemical vapor deposition (CVD) with polymer scaffolds of poly(methyl methacrylate) (PMMA), poly(lactic acid) (PLA), poly(phthalaldehyde) (PPA), and poly(bisphenol A carbonate) (PC). We find that optimally reactive PC scaffolds provide the cleanest graphene transfers without any annealing, after extensive comparison with optical microscopy, x-ray photoelectron spectroscopy, atomic force microscopy, and scanning tunneling microscopy. Comparatively, films transferred with PLA, PPA, PMMA/PC, and PMMA have a two-fold higher roughness and a five-fold higher chemical doping. Using PC scaffolds, we demonstrate the clean transfer of CVD multilayer graphene, fluorinated graphene, and hexagonal boron nitride. Our annealing free, PC transfers enable the use of atomically-clean nanomaterials in biomolecule encapsulation and flexible electronic applications.

Annealing free, clean graphene transfer using alternative polymer scaffolds

International Nuclear Information System (INIS)

Wood, Joshua D; Doidge, Gregory P; Carrion, Enrique A; Koepke, Justin C; Datye, Isha; Behnam, Ashkan; Hewaparakrama, Jayan; Aruin, Basil; Chen, Yaofeng; Lyding, Joseph W; Kaitz, Joshua A; Dong, Hefei; Haasch, Richard T; Pop, Eric

2015-01-01

We examine the transfer of graphene grown by chemical vapor deposition (CVD) with polymer scaffolds of poly(methyl methacrylate) (PMMA), poly(lactic acid) (PLA), poly(phthalaldehyde) (PPA), and poly(bisphenol A carbonate) (PC). We find that optimally reactive PC scaffolds provide the cleanest graphene transfers without any annealing, after extensive comparison with optical microscopy, x-ray photoelectron spectroscopy, atomic force microscopy, and scanning tunneling microscopy. Comparatively, films transferred with PLA, PPA, PMMA/PC, and PMMA have a two-fold higher roughness and a five-fold higher chemical doping. Using PC scaffolds, we demonstrate the clean transfer of CVD multilayer graphene, fluorinated graphene, and hexagonal boron nitride. Our annealing free, PC transfers enable the use of atomically-clean nanomaterials in biomolecule encapsulation and flexible electronic applications. (paper)

Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model

OpenAIRE

Zhang, Haifeng; Mao, Xiyuan; Du, Zijing; Jiang, Wenbo; Han, Xiuguo; Zhao, Danyang; Han, Dong; Li, Qingfeng

2016-01-01

Abstract We have explored the applicability of printed scaffold by comparing osteogenic ability and biodegradation property of three resorbable biomaterials. A polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500??m and 60% porosity was fabricated by three-dimensional printing. Three-dimensional printed PLA/HA, ?-tricalcium phosphate (?-TCP) and partially demineralized bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by cell adhesion, prolife...

Co-Deposition of a Hydrogel/Calcium Phosphate Hybrid Layer on 3D Printed Poly(Lactic Acid Scaffolds via Dip Coating: Towards Automated Biomaterials Fabrication

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Matthias Schneider

2018-03-01

Full Text Available The article describes the surface modification of 3D printed poly(lactic acid (PLA scaffolds with calcium phosphate (CP/gelatin and CP/chitosan hybrid coating layers. The presence of gelatin or chitosan significantly enhances CP co-deposition and adhesion of the mineral layer on the PLA scaffolds. The hydrogel/CP coating layers are fairly thick and the mineral is a mixture of brushite, octacalcium phosphate, and hydroxyapatite. Mineral formation is uniform throughout the printed architectures and all steps (printing, hydrogel deposition, and mineralization are in principle amenable to automatization. Overall, the process reported here therefore has a high application potential for the controlled synthesis of biomimetic coatings on polymeric biomaterials.

Tubular scaffolds of gelatin and poly(ε-caprolactone)-block-poly(γ-glutamic acid) blending hydrogel for the proliferation of the primary intestinal smooth muscle cells of rats

International Nuclear Information System (INIS)

Jwo, Shyh-Chuan; Chiu, Chu-Hua; Hsieh, Ming-Fa; Tang, Shye-Jye

2013-01-01

The proper regeneration of intestinal muscle for functional peristalsis is the most challenging aspect of current small intestine tissue engineering. This study aimed to fabricate a hydrogel scaffold for the proliferation of intestinal smooth muscle cells (ISMCs). Tubular porous scaffolds of 10–20 wt% gelatin and 0.05–0.1 wt% poly(ε-caprolactone)-block-poly(γ-glutamic acid) blending hydrogel were cross-linked by carbodiimide and succinimide in an annular space of a glass mold. The scaffolds with higher gelatin contents degraded slower in the phosphate buffer solution. In rheological measurements, the hydrated scaffolds were elastic (all tangent delta <0.45); they responded differentially to frequency, indicating a complete viscoelastic property that is beneficial for soft tissue regeneration. Isolated rat ISMCs, with the characteristic biomarkers α-SMA, calponin and myh11, were loaded into the scaffolds by using either static or centrifugal methods. The average cell density inside the scaffolds increased in a time-dependent manner in most scaffolds of both seeding groups, although at early time points (seven days) the centrifugal seeding method trapped cells more efficiently and yielded a higher cell density than the static seeding method. The static seeding method increased the cell density from 7.5-fold to 16.3-fold after 28 days, whereas the centrifugal procedure produced a maximum increase of only 2.4-fold in the same period. In vitro degradation data showed that 50–80% of the scaffold was degraded by the 14th day. However, the self-secreted extracellular matrix maintained the integrity of the scaffolds for cell proliferation and spreading for up to 28 days. Confocal microscopic images revealed cell–cell contacts with the formation of a 3D network, demonstrating that the fabricated scaffolds were highly biocompatible. Therefore, these polymeric biomaterials hold great promise for in vivo applications of intestinal tissue engineering. (paper)

Fabrication and characterization of novel multilayered structures by stereocomplexion of poly(D-lactic acid)/poly(L-lactic acid) and self-assembly of polyelectrolytes

Science.gov (United States)

Yang, Gesheng; Pastorino, Laura

2016-01-01

Summary The enantiomers poly(D-lactic acid) (PDLA) and poly(L-lactic acid) (PLLA) were alternately adsorbed directly on calcium carbonate (CaCO3) templates and on poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) multilayer precursors in order to fabricate a novel layer-by-layer (LBL) assembly. A single layer of poly(L-lysine) (PLL) was used as a linker between the (PDLA/PLLA)n stereocomplex and the cores with and without the polymeric (PSS/PAH)n/PLL multilayer precursor (PEM). Nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) were used to characterize the chemical composition and molecular weight of poly(lactic acid) polymers. Both multilayer structures, with and without polymeric precursor, were firstly fabricated and characterized on planar supports. A quartz crystal microbalance (QCM), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and ellipsometry were used to evaluate the thickness and mass of the multilayers. Then, hollow, spherical microcapsules were obtained by the removal of the CaCO3 sacrificial template. The chemical composition of the obtained microcapsules was confirmed by differential scanning calorimetry (DSC) and wide X-ray diffraction (WXRD) analyses. The microcapsule morphology was evaluated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) measurements. The experimental results confirm the successful fabrication of this innovative system, and its full biocompatibility makes it worthy of further characterization as a promising drug carrier for sustained release. PMID:26925356

In vivo guided vascular regeneration with a non-porous elastin-like polypeptide hydrogel tubular scaffold.

Science.gov (United States)

Mahara, Atsushi; Kiick, Kristi L; Yamaoka, Tetsuji

2017-06-01

Herein, we demonstrate a new approach for small-caliber vascular reconstruction using a non-porous elastin-like polypeptide hydrogel tubular scaffold, based on the concept of guided vascular regeneration (GVR). The scaffolds are composed of elastin-like polypeptide, (Val-Pro-Gly-Ile-Gly) n , for compliance matching and antithrombogenicity and an Arg-Gly-Asp (RGD) motif for connective tissue regeneration. When the polypeptide was mixed with an aqueous solution of β-[Tris(hydroxymethyl)phosphino]propionic acid at 37°C, the polypeptide hydrogel was rapidly formed. The elastic modulus of the hydrogel was 4.4 kPa. The hydrogel tubular scaffold was formed in a mold and reinforced with poly(lactic acid) nanofibers. When tubular scaffolds with an inner diameter of 1 mm and length of 5 mm were implanted into rat abdominal aortae, connective tissue grew along the scaffold luminal surface from the flanking native tissues, resulting in new blood vessel tissue with a thickness of 200 μm in 1 month. In contrast, rats implanted with control scaffolds without the RGD motif died. These results indicate that the non-porous hydrogel tubular scaffold containing the RGD motif effectively induced rapid tissue regeneration and that GVR is a promising strategy for the regeneration of small-diameter blood vessels. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1746-1755, 2017. © 2017 Wiley Periodicals, Inc.

In vitro evaluation of crosslinked electrospun fish gelatin scaffolds.

Science.gov (United States)

Gomes, S R; Rodrigues, G; Martins, G G; Henriques, C M R; Silva, J C

2013-04-01

Gelatin from cold water fish skin was electrospun, crosslinked and investigated as a substrate for the adhesion and proliferation of cells. Gelatin was first dissolved in either water or concentrated acetic acid and both solutions were successfully electrospun. Cross-linking was achieved via three different routes: glutaraldehyde vapor, genipin and dehydrothermal treatment. Solution's properties (surface tension, electrical conductivity and viscosity) and scaffold's properties (chemical bonds, weight loss and fiber diameters) were measured. Cellular viability was analyzed culturing 3T3 fibroblasts plated on the scaffolds and grown up to 7 days. The cells were fixed and observed with SEM or stained for DNA and F-actin and observed with confocal microscopy. In all scaffolds, the cells attached and spread with varying degrees. The evaluation of cell viability showed proliferation of cells until confluence in scaffolds crosslinked by glutaraldehyde and genipin; however the rate of growth in genipin crosslinked scaffolds was slow, recovering only by day five. The results using the dehydrothermal treatment were the less satisfactory. Our results show that glutaraldehyde treated fish gelatin is the most suitable substrate, of the three studied, for fibroblast adhesion and proliferation. Copyright © 2012 Elsevier B.V. All rights reserved.

Spontaneous Differentiation of Human Mesenchymal Stem Cells on Poly-Lactic-Co-Glycolic Acid Nano-Fiber Scaffold.

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Koshiro Sonomoto

Full Text Available Mesenchymal stem cells (MSCs have immunosuppressive activity and can differentiate into bone and cartilage; and thus seem ideal for treatment of rheumatoid arthritis (RA. Here, we investigated the osteogenesis and chondrogenesis potentials of MSCs seeded onto nano-fiber scaffolds (NFs in vitro and possible use for the repair of RA-affected joints.MSCs derived from healthy donors and patients with RA or osteoarthritis (OA were seeded on poly-lactic-glycolic acid (PLGA electrospun NFs and cultured in vitro.Healthy donor-derived MSCs seeded onto NFs stained positive with von Kossa at Day 14 post-stimulation for osteoblast differentiation. Similarly, MSCs stained positive with Safranin O at Day 14 post-stimulation for chondrocyte differentiation. Surprisingly, even cultured without any stimulation, MSCs expressed RUNX2 and SOX9 (master regulators of bone and cartilage differentiation at Day 7. Moreover, MSCs stained positive for osteocalcin, a bone marker, and simultaneously also with Safranin O at Day 14. On Day 28, the cell morphology changed from a spindle-like to an osteocyte-like appearance with processes, along with the expression of dentin matrix protein-1 (DMP-1 and matrix extracellular phosphoglycoprotein (MEPE, suggesting possible differentiation of MSCs into osteocytes. Calcification was observed on Day 56. Expression of osteoblast and chondrocyte differentiation markers was also noted in MSCs derived from RA or OA patients seeded on NFs. Lactic acid present in NFs potentially induced MSC differentiation into osteoblasts.Our PLGA scaffold NFs induced MSC differentiation into bone and cartilage. NFs induction process resembled the procedure of endochondral ossification. This finding indicates that the combination of MSCs and NFs is a promising therapeutic technique for the repair of RA or OA joints affected by bone and cartilage destruction.

In vitro cytotoxicity and antibacterial activity of silver-coated electrospun polycaprolactone/gelatine nanofibrous scaffolds

OpenAIRE

Lim, Mim Mim; Sultana, Naznin

2016-01-01

The development of nano-sized scaffolds with antibacterial properties that mimic the architecture of tissue is one of the challenges in tissue engineering. In this study, polycaprolactone (PCL) and PCL/gelatine (Ge) (70:30) nanofibrous scaffolds were fabricated using a less toxic and common solvent, formic acid and an electrospinning technique. Nanofibrous scaffolds were coated with silver (Ag) in different concentrations of silver nitrate (AgNO3) aqueous solution (1.25, 2.5, 5, and 10?%) by ...

Preparation, physicochemical properties and biocompatibility of PBLG/PLGA/bioglass composite scaffolds

Energy Technology Data Exchange (ETDEWEB)

Cui, Ning [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Qian, Junmin, E-mail: jmqian@mail.xjtu.edu.cn [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Wang, Jinlei [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Ji, Chuanlei [The Orthopaedic Department, XiJing Hospital Affiliated to the Fourth Military Medical University, Xi' an 710032 (China); Xu, Weijun; Wang, Hongjie [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China)

2017-02-01

In this study, novel poly(γ-benzyl L-glutamate)/poly(lactic-co-glycolic acid)/bioglass (PBLG/PLGA/BG) composite scaffolds with different weight ratios were fabricated using a negative NaCl-templating method. The morphology, compression modulus and degradation kinetics of the scaffolds were characterized. The results showed that the PBLG/PLGA/BG composite scaffolds with a weight ratio of 5:5:1, namely PBLG5PLGA5BG composite scaffolds, displayed a pore size range of 50–500 μm, high compressive modulus (566.6 ± 8.8 kPa), suitable glass transition temperature (46.8 ± 0.2 °C) and low degradation rate (> 8 weeks). The in vitro biocompatibility of the scaffolds was evaluated with MC3T3-E1 cells by live-dead staining, MTT and ALP activity assays. The obtained results indicated that the PBLG5PLGA5BG composite scaffolds were more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells than PBLG and PBLG/PLGA composite scaffolds. The in vivo biocompatibility of the scaffolds was evaluated in both SD rat subcutaneous model and rabbit tibia defect model. The results of H&E, Masson's trichrome and CD34 staining assays demonstrated that the PBLG5PLGA5BG composite scaffolds allowed the ingrowth of tissue and microvessels more effectively than PBLG/PLGA composite scaffolds. The results of digital radiography confirmed that the PBLG5PLGA5BG composite scaffolds significantly improved in vivo osteogenesis. Collectively, the PBLG5PLGA5BG composite scaffolds could be a promising candidate for tissue engineering applications. - Highlights: • Foamy PBLG/PLGA/bioglass composite scaffolds were fabricated by negative templating. • PBLG/PLGA/bioglass composite scaffolds displayed tunable physicochemical properties. • PBLG/PLGA/bioglass composite scaffolds had good biocompatibility in vitro and in vivo. • PBLG/PLGA/bioglass composite scaffolds could promote the healing of bone defects.

Multiscale fabrication of biomimetic scaffolds for tympanic membrane tissue engineering

International Nuclear Information System (INIS)

Mota, Carlos; Danti, Serena; D’Alessandro, Delfo; Trombi, Luisa; Ricci, Claudio; Berrettini, Stefano; Puppi, Dario; Dinucci, Dinuccio; Chiellini, Federica; Milazzo, Mario; Stefanini, Cesare; Moroni, Lorenzo

2015-01-01

The tympanic membrane (TM) is a thin tissue able to efficiently collect and transmit sound vibrations across the middle ear thanks to the particular orientation of its collagen fibers, radiate on one side and circular on the opposite side. Through the combination of advanced scaffolds and autologous cells, tissue engineering (TE) could offer valuable alternatives to autografting in major TM lesions. In this study, a multiscale approach based on electrospinning (ES) and additive manufacturing (AM) was investigated to fabricate scaffolds, based on FDA approved copolymers, resembling the anatomic features and collagen fiber arrangement of the human TM. A single scale TM scaffold was manufactured using a custom-made collector designed to confer a radial macro-arrangement to poly(lactic-co-glycolic acid) electrospun fibers during their deposition. Dual and triple scale scaffolds were fabricated combining conventional ES with AM to produce poly(ethylene oxide terephthalate)/poly(butylene terephthalate) block copolymer scaffolds with anatomic-like architecture. The processing parameters were optimized for each manufacturing method and copolymer. TM scaffolds were cultured in vitro with human mesenchymal stromal cells, which were viable, metabolically active and organized following the anisotropic character of the scaffolds. The highest viability, cell density and protein content were detected in dual and triple scale scaffolds. Our findings showed that these biomimetic micro-patterned substrates enabled cell disposal along architectural directions, thus appearing as promising substrates for developing functional TM replacements via TE. (paper)

Membrane-reinforced three-dimensional electrospun silk fibroin scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Yang, Sung Yeun; Hwang, Tae Heon; Ryu, WonHyoung; Che, Lihua; Oh, Jin Soo; Ha, Yoon

2015-01-01

Electrospun silk fibroin (SF) scaffolds have drawn much attention because of their resemblance to natural tissue architecture such as extracellular matrix, and the biocompatibility of SF as a candidate material to replace collagen. However, electrospun scaffolds lack the physical integrity of bone tissue scaffolds, which require resistance to mechanical loadings. In this work, we propose membrane-reinforced electrospun SF scaffolds by a serial process of electrospinning and freeze-drying of SF solutions in two different solvents: formic acid and water, respectively. After wet electrospinning followed by replacement of methanol with water, SF nanofibers dispersed in water were mixed with aqueous SF solution. Freeze-drying of the mixed solution resulted in 3D membrane-connected SF nanofibrous scaffolds (SF scaffolds) with a thickness of a few centimeters. We demonstrated that the SF concentration of aqueous SF solution controlled the degree of membrane reinforcement between nanofibers. It was also shown that both increase in degree of membrane reinforcement and inclusion of hydroxyapatite (HAP) nanoparticles resulted in higher resistance to compressive loadings of the SF scaffolds. Culture of human osteoblasts on collagen, SF, and SF-HAP scaffolds showed that both SF and SF-HAP scaffolds had biocompatibility and cell proliferation superior to that of the collagen scaffolds. SF-HAP scaffolds with and without BMP-2 were used for in vivo studies for 4 and 8 weeks, and they showed enhanced bone tissue formation in rat calvarial defect models. (paper)

Modifying the strength and strain concentration profile within collagen scaffolds using customizable arrays of poly-lactic acid fibers.

Science.gov (United States)

Mozdzen, Laura C; Vucetic, Alan; Harley, Brendan A C

2017-02-01

The tendon-to-bone junction is a highly specialized tissue which dissipates stress concentrations between mechanically dissimilar tendon and bone. Upon injury, the local heterogeneities across this insertion are not regenerated, leading to poor functional outcomes such as formation of scar tissue at the insertion and re-failure rates exceeding 90%. Although current tissue engineering methods are moving towards the development of spatially-graded biomaterials to begin to address these injuries, significant opportunities remain to engineer the often complex local mechanical behavior of such biomaterials to enhance their bioactivity. Here, we describe the use of three-dimensional printing techniques to create customizable arrays of poly-lactic acid (PLA) fibers that can be incorporated into a collagen scaffold under development for tendon bone junction repair. Notably, we use additive manufacturing concepts to generate arrays of spatially-graded fibers from biodegradable PLA that are incorporated into collagen scaffolds to create a collagen-PLA composite. We demonstrate the ability to tune the mechanical performance of the fiber-scaffold composite at the bulk scale. We also demonstrate the incorporation of spatially-heterogeneous fiber designs to establish non-uniform local mechanical performance of the composite biomaterial under tensile load, a critical element in the design of multi-compartment biomaterials for tendon-to-bone regeneration applications. Together, this work highlights the capacity to use multi-scale composite biomaterials to control local and bulk mechanical properties, and provides key insights into design elements under consideration for mechanically competent, multi-tissue regeneration platforms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Post Processing and Biological Evaluation of the Titanium Scaffolds for Bone Tissue Engineering

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Bartłomiej Wysocki

2016-03-01

Full Text Available Nowadays, post-surgical or post-accidental bone loss can be substituted by custom-made scaffolds fabricated by additive manufacturing (AM methods from metallic powders. However, the partially melted powder particles must be removed in a post-process chemical treatment. The aim of this study was to investigate the effect of the chemical polishing with various acid baths on novel scaffolds’ morphology, porosity and mechanical properties. In the first stage, Magics software (Materialise NV, Leuven, Belgium was used to design a porous scaffolds with pore size equal to (A 200 µm, (B 500 µm and (C 200 + 500 µm, and diamond cell structure. The scaffolds were fabricated from commercially pure titanium powder (CP Ti using a SLM50 3D printing machine (Realizer GmbH, Borchen, Germany. The selective laser melting (SLM process was optimized and the laser beam energy density in range of 91–151 J/mm3 was applied to receive 3D structures with fully dense struts. To remove not fully melted titanium particles the scaffolds were chemically polished using various HF and HF-HNO3 acid solutions. Based on scaffolds mass loss and scanning electron (SEM observations, baths which provided most uniform surface cleaning were proposed for each porosity. The pore and strut size after chemical treatments was calculated based on the micro-computed tomography (µ-CT and SEM images. The mechanical tests showed that the treated scaffolds had Young’s modulus close to that of compact bone. Additionally, the effect of pore size of chemically polished scaffolds on cell retention, proliferation and differentiation was studied using human mesenchymal stem cells. Small pores yielded higher cell retention within the scaffolds, which then affected their growth. This shows that in vitro cell performance can be controlled to certain extent by varying pore sizes.

Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair

Energy Technology Data Exchange (ETDEWEB)

Wang, Jianhua; Yang, Qiu; Cheng, Niangmei [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Tao, Xiaojun [Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, Hunan (China); Zhang, Zhihua; Sun, Xiaomin [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Zhang, Qiqing, E-mail: zhangqiq@126.com [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Key Laboratory of Biomedical Materials of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192 (China)

2016-04-01

For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration. - Highlights: • Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere proposed for cartilage repair was created. • In vivo, scaffold could enhance cartilage regeneration and integration between the repaired and surrounding cartilage. • In vitro, scaffold exhibits excellent characteristics, such as, improved porosity water absorption and good cell affinity.

Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Doğan, Ayşegül; Demirci, Selami [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey); Bayir, Yasin [Department of Biochemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Halici, Zekai [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karakus, Emre [Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum (Turkey); Aydin, Ali [Department of Orthopedics and Traumatology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Cadirci, Elif [Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Albayrak, Abdulmecit [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Demirci, Elif [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karaman, Adem [Department of Radiology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Ayan, Arif Kursat [Department of Nuclear Medicine, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Gundogdu, Cemal [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Şahin, Fikrettin, E-mail: fsahin@yeditepe.edu.tr [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey)

2014-11-01

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. - Highlights: • Boron containing PLGA scaffolds were developed for bone tissue engineering. • Boron incorporation increased cell viability and mineralization of stem cells. • Boron containing scaffolds increased bone-related protein expression in vivo. • Implantation of stem cells on boron containing scaffolds improved bone healing.

Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

Doğan, Ayşegül; Demirci, Selami; Bayir, Yasin; Halici, Zekai; Karakus, Emre; Aydin, Ali; Cadirci, Elif; Albayrak, Abdulmecit; Demirci, Elif; Karaman, Adem; Ayan, Arif Kursat; Gundogdu, Cemal; Şahin, Fikrettin

2014-01-01

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. - Highlights: • Boron containing PLGA scaffolds were developed for bone tissue engineering. • Boron incorporation increased cell viability and mineralization of stem cells. • Boron containing scaffolds increased bone-related protein expression in vivo. • Implantation of stem cells on boron containing scaffolds improved bone healing

Fabrication and loading of oral drug delivery microcontainers using hot punching

DEFF Research Database (Denmark)

Petersen, Ritika Singh; Borre, Mads T.; Keller, Stephan Sylvest

2015-01-01

In this paper, poly-l-lactic acid (PLLA) solution is spin coated to achieve a PLLA layer of 55 μm thickness. Hot punching with a Ni stamp is optimized to fabricate microcontainers in PLLA. Process optimization of thermal bonding of the microcontainers to a poly acrylic acid (PAA) layer is perform...... by modifying sample preparation and varying temperature. The fabricated microcontainers are loaded by hot punching in a spin coated drug polymer film of furosemide and poly-e-caprolactone (PCL)....

Fibrin and poly(lactic-co-glycolic acid) hybrid scaffold promotes early chondrogenesis of articular chondrocytes: an in vitro study.

Science.gov (United States)

Sha'ban, Munirah; Kim, Soon Hee; Idrus, Ruszymah Bh; Khang, Gilson

2008-04-25

Synthetic- and naturally derived- biodegradable polymers have been widely used to construct scaffolds for cartilage tissue engineering. Poly(lactic-co-glycolic acid) (PLGA) are bioresorbable and biocompatible, rendering them as a promising tool for clinical application. To minimize cells lost during the seeding procedure, we used the natural polymer fibrin to immobilize cells and to provide homogenous cells distribution in PLGA scaffolds. We evaluated in vitro chondrogenesis of rabbit articular chondrocytes in PLGA scaffolds using fibrin as cell transplantation matrix. PLGA scaffolds were soaked in chondrocytes-fibrin suspension (1 x 10(6) cells/scaffold) and polymerized by dropping thrombin-calcium chloride (CaCl2) solution. PLGA-seeded chondrocytes was used as control. All constructs were cultured for a maximum of 21 days. Cell proliferation activity was measured at 1, 3, 7, 14 and 21 days in vitro using 3-(4,5-dimethylthiazole-2-yl)-2-, 5-diphenyltetrazolium-bromide (MTT) assay. Morphological observation, histology, immunohistochemistry (IHC), gene expression and sulphated-glycosaminoglycan (sGAG) analyses were performed at each time point of 1, 2 and 3 weeks to elucidate in vitro cartilage development and deposition of cartilage-specific extracellular matrix (ECM). Cell proliferation activity was gradually increased from day-1 until day-14 and declined by day-21. A significant cartilaginous tissue formation was detected as early as 2-week in fibrin/PLGA hybrid construct as confirmed by the presence of cartilage-isolated cells and lacunae embedded within basophilic ECM. Cartilage formation was remarkably evidenced after 3 weeks. Presence of cartilage-specific proteoglycan and glycosaminoglycan (GAG) in fibrin/PLGA hybrid constructs were confirmed by positive Safranin O and Alcian Blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrix. Chondrogenic properties were further demonstrated by the expression of genes encoded for

Bony defect repair in rabbit using hybrid rapid prototyping polylactic co glycolic acid/β tricalciumphosphate collagen I/apatite scaffold and bone marrow mesenchymal stem cells

Directory of Open Access Journals (Sweden)

Long Pang

2013-01-01

Full Text Available Background: In bone tissue engineering, extracellular matrix exerts critical influence on cellular interaction with porous biomaterial and the apatite playing an important role in the bonding process of biomaterial to bone tissue. The aim of this study was to observe the therapeutic effects of hybrid rapid prototyping (RP scaffolds comprising polylactic-co-glycolic acid (PLGA, β-tricalciumphosphate (β-TCP, collagen I and apatite (PLGA/β-TCP-collagen I/apatite on segmental bone defects in conjunction with combination with bone marrow mesenchymal stem cells (BMSCs. Materials and Methods: BMSCs were seeded into the hybrid RP scaffolds to repair 15 mm defect in the radius of rabbits. Radiograph, microcomputed tomography and histology were used to evaluate new bone formation. Results: Radiographic analysis done from 12 to 36 weeks postoperative period demonstrated that new bone formed at the radial defect site and continues to increase until the medullary cavity is recanalized and remodelling is complete. The bone defect remained unconnected in the original RP scaffolds (PLGA/β-TCP during the whole study. Histological observations conformed to the radiographic images. In hybrid RP scaffold group, woven bone united the radial defect at 12 weeks and consecutively remodeled into lamellar bone 24 weeks postoperation and finally matured into cortical bone with normal marrow cavity after another 12 weeks. No bone formation but connective tissue has been detected in RP scaffold at the same time. Conclusion: Collagen I/apatite sponge composite coating could improve new bone formation in vivo. The hybrid RP scaffold of PLGA/β-TCP skeleton with collagen I/apatite sponge composite coating is a promising candidate for bone tissue engineering.

Fabrication and characterization of PCL/gelatin composite nanofibrous scaffold for tissue engineering applications by electrospinning method

International Nuclear Information System (INIS)

Gautam, Sneh; Dinda, Amit Kumar; Mishra, Narayan Chandra

2013-01-01

In the present study, composite nanofibrous tissue engineering-scaffold consisting of polycaprolactone and gelatin, was fabricated by electrospinning method, using a new cost-effective solvent mixture: chloroform/methanol for polycaprolactone (PCL) and acetic acid for gelatin. The morphology of the nanofibrous scaffold was investigated by using field emission scanning electron microscopy (FE-SEM) which clearly indicates that the morphology of nanofibers was influenced by the weight ratio of PCL to gelatin in the solution. Uniform fibers were produced only when the weight ratio of PCL/gelatin is sufficiently high (10:1). The scaffold was further characterized by Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric (TG) analysis, and X-ray diffraction (XRD). FT-IR and TG analysis indicated some interactions between PCL and gelatin molecules within the scaffold, while XRD results demonstrated crystalline nature of PCL/gelatin composite scaffold. Cytotoxicity effect of scaffold on L929 mouse fibroblast cells was evaluated by MTT assay and cell proliferation on the scaffold was confirmed by DNA quantification. Positive results of MTT assay and DNA quantification L929 mouse fibroblast cells indicated that the scaffold made from the combination of natural polymer (gelatin) and synthetic polymer (PCL) may serve as a good candidate for tissue engineering applications. - Highlights: ► PCL/Gelatin scaffold was successfully fabricated by electrospinning method. ► PCL in CHCl 3 /CH 3 OH and gelatin in acetic acid: a novel polymer-solvent system. ► The morphology of nanofibers was influenced by the weight ratio of PCL/gelatin. ► Chemical interactions between PCL and gelatin molecules enhanced cell growth. ► Cell culture studies indicate the suitability of scaffold for tissue regeneration