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Sample records for acid plla scaffolds

  1. Novel Antibacterial Nanofibrous PLLA Scaffolds

    PubMed Central

    Feng, Kai; Sun, Hongli; Bradley, Mark A.; Dupler, Ellen J.; Giannobile, William V.; Ma, Peter X.

    2010-01-01

    In order to achieve high local bioactivity and low systemic side effects of antibiotics in the treatment of dental, periodontal and bone infections, a localized and temporally controlled delivery system is crucial. In this study, a three-dimensional (3D) porous tissue engineering scaffold was developed with the ability to release antibiotics in a controlled fashion for long-term inhibition of bacterial growth. The highly soluble antibiotic drug, Doxycycline (DOXY), was successfully incorporated into PLGA nanospheres using a modified water-in-oil-in-oil (w/o/o) emulsion method. The PLGA nanospheres (NS) were then incorporated into prefabricated nanofibrous PLLA scaffolds with a well interconnected macroporous structure. The release kinetics of DOXY from four different PLGA NS formulations on a PLLA scaffold was investigated. DOXY could be released from the NS-scaffolds in a locally and temporally controlled manner. The DOXY release is controlled by DOXY diffusion out of the NS and is strongly dependent upon the physical and chemical properties of the PLGA. While PLGA50-6.5K, PLGA50-64K, and PLGA75-113K NS-scaffolds discharge DOXY rapidly with a high initial burst release, PLGA85-142K NS-scaffold can extend the release of DOXY to longer than 6 weeks with a low initial burst release. Compared to NS alone, the NS incorporated on a 3-D scaffold had significantly reduced the initial burst release. In vitro antibacterial tests of PLGA85 NS-scaffold demonstrated its ability to inhibit common bacterial growth (S.aureus and E.coli) for a prolonged duration. The successful incorporation of DOXY onto 3-D scaffolds and its controlled release from scaffolds extends the usage of nano-fibrous scaffolds from the delivery of large molecules such as growth factors to the delivery of small hydrophilic drugs, allowing for a broader application and a more complex tissue engineering strategy. PMID:20570700

  2. Effect of PEG-PLLA diblock copolymer on macroporous PLLA scaffolds by thermally induced phase separation.

    PubMed

    Kim, Hyun Do; Bae, Eun Hee; Kwon, Ick Chan; Pal, Ravindra Ramsurat; Nam, Jae Do; Lee, Doo Sung

    2004-05-01

    A regular and highly interconnected macroporous poly(L-lactic acid) (PLLA) scaffold was fabricated from a PLLA-dioxane-water ternary system with added polyethylene glycol (PEG)-PLLA diblock using thermally induced phase separation (TIPS). The morphology of the scaffold was investigated in detail by controlling the following TIPS parameters: quenching temperature, aging time, polymer concentration, molecular structure, and diblock concentration. The phase diagram was assessed visually on the basis of the turbidity. The cloud-point curve shifted to higher temperatures with increasing PEG content in the additives (PEG-PLLA diblocks), due to a stronger interaction between PEG and water in solution. The addition of diblock series (0.5 wt% in solution) stabilized interconnections of pores at a later stage without segregation or sedimentation. The pore size of the scaffold could be easily controlled in the range 50-300 microm. A macroporous PLLA scaffold was used to study an MC3T3-E1 cell (an osteoblast-like cell) culture. The cells successfully proliferated in the PLLA scaffold in the presence of added PEG-PLLA diblock for 4 weeks.

  3. Biomineral coating increases bone formation by ex vivo BMP-7 gene therapy in rapid prototyped poly(L-lactic acid) (PLLA) and poly(ε-caprolactone) (PCL) porous scaffolds.

    PubMed

    Saito, Eiji; Suarez-Gonzalez, Darilis; Murphy, William L; Hollister, Scott J

    2015-03-11

    Porousbiodegradable polymer scaffolds are widely utilized for bone tissue engineering, but are not osteoconductive like calcium phosphate scaffolds. We combine indirect solid freeform fabrication (SFF), ex vivo gene therapy, with biomineral coating to compare the effect of biomineral coating on bone regeneration for Poly (L-lactic acid) (PLLA) and Poly (ε-caprolactone) (PCL) scaffolds with the same porous architecture. Scanning electron microscope (SEM) and micro-computed tomography (μ-CT) demonstrate PLLA and PCL scaffolds have the same porous architecture and are completely coated. All scaffolds are seeded with human gingival fibroblasts (HGF) transduced with adenovirus encoded with either bone morphogenetic protein 7 (BMP-7) or green fluorescent protein (GFP), and implanted into mice subcutaneously for 3 and 10 weeks. Only scaffolds with BMP-7 transduced HGFs show mineralized tissue formation. At 3 weeks some blood vessel-like structures are observed in coated PLLA and PCL scaffolds, but there is no significant difference in bone ingrowth between the coated and uncoated scaffolds for either PLLA or PCL. At 10 weeks, however, coated scaffolds (both PLLA and PCL) have significantly more bone ingrowth than uncoated scaffolds, which have more fibrous tissue. Coated PLLA scaffolds have improved mechanical properties compared with uncoated PLLA scaffolds due to increased bone ingrowth.

  4. Synergistic interaction of platelet derived growth factor (PDGF) with the surface of PLLA/Col/HA and PLLA/HA scaffolds produces rapid osteogenic differentiation.

    PubMed

    Raghavendran, Hanumantha Rao Balaji; Mohan, Saktiswaren; Genasan, Krishnamurithy; Murali, Malliga Raman; Naveen, Sangeetha Vasudevaraj; Talebian, Sepehr; McKean, Robert; Kamarul, Tunku

    2016-03-01

    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering.

  5. Synergistic interaction of platelet derived growth factor (PDGF) with the surface of PLLA/Col/HA and PLLA/HA scaffolds produces rapid osteogenic differentiation.

    PubMed

    Raghavendran, Hanumantha Rao Balaji; Mohan, Saktiswaren; Genasan, Krishnamurithy; Murali, Malliga Raman; Naveen, Sangeetha Vasudevaraj; Talebian, Sepehr; McKean, Robert; Kamarul, Tunku

    2016-03-01

    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering. PMID:26700235

  6. Improved functionalization of electrospun PLLA/gelatin scaffold by alternate soaking method for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Jaiswal, Amit K.; Kadam, Sachin S.; Soni, Vivek P.; Bellare, Jayesh R.

    2013-03-01

    Biomimetic biomaterials are widely being explored as scaffold for bone regeneration. In this study, we prepared poly-L-lactic acid/hydroxyapatite (PLLA/HA) and poly-L-lactic acid/gelatin/hydroxyapatite (PLLA/Gel/HA) scaffold by electrospinning of poly-L-lactic acid (PLLA) and a blend of poly-L-lactic acid/gelatin (PLLA/Gel) followed by hydroxyapatite (HA) mineralization via alternate soaking in calcium and phosphate (Ca-P) solutions. HA growth on scaffold after each soaking cycle was confirmed by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The functional groups (COOsbnd and sbnd NH2) of gelatin in the PLLA/Gel scaffold facilitated the surface nucleation of HA as compared to the PLLA scaffold. Leaching study showed HA in PLLA/Gel/HA scaffold acts as binder of gelatin and eliminates use of toxic crosslinking agents. In vitro cell attachment on these scaffolds was assessed by using human osteosarcoma cells (MG-63). Cell proliferation on scaffolds was examined by MTT assay. MTT results clearly indicated that mineralized scaffolds did not inhibit the eventual cell proliferation. Alkaline phosphatase (ALP) activity of MG-63 cells was found to be the highest on PLLA/Gel/HA at day 7 compared to all other scaffolds. Complement activation study revealed minimum terminal complement complex (TCC) concentration for PLLA/Gel and PLLA/Gel/HA (617.33 and 654.13 ng/mL respectively). These results demonstrate the proficiency of PLLA/Gel/HA scaffold in better osteostimulation with lesser immune response, which attributed to synergistic role of gelatin and HA. Thus, by mimicking the natural microenvironment PLLA/Gel/HA scaffolds can become the choice of material in bone tissue engineering.

  7. PLLA-collagen and PLLA-gelatin hybrid scaffolds with funnel-like porous structure for skin tissue engineering

    NASA Astrophysics Data System (ADS)

    Lu, Hongxu; Oh, Hwan Hee; Kawazoe, Naoki; Yamagishi, Kozo; Chen, Guoping

    2012-12-01

    In skin tissue engineering, a three-dimensional porous scaffold is necessary to support cell adhesion and proliferation and to guide cells moving into the repair area in the wound healing process. Structurally, the porous scaffold should have an open and interconnected porous architecture to facilitate homogenous cell distribution. Moreover, the scaffolds should be mechanically strong to protect deformation during the formation of new skin. In this study, the hybrid scaffolds were prepared by forming funnel-like collagen or gelatin sponge on a woven poly(l-lactic acid) (PLLA) mesh. The hybrid scaffolds combined the advantages of both collagen or gelatin (good cell-interactions) and PLLA mesh (high mechanical strength). The hybrid scaffolds were used to culture dermal fibroblasts for dermal tissue engineering. The funnel-like porous structure promoted homogeneous cell distribution and extracellular matrix production. The PLLA mesh reinforced the scaffold to avoid deformation. Subcutaneous implantation showed that the PLLA-collagen and PLLA-gelatin scaffolds promoted the regeneration of dermal tissue and epidermis and reduced contraction during the formation of new tissue. These results indicate that funnel-like hybrid scaffolds can be used for skin tissue regeneration.

  8. Structure and properties of PLLA/β-TCP nanocomposite scaffolds for bone tissue engineering.

    PubMed

    Lou, Tao; Wang, Xuejun; Song, Guojun; Gu, Zheng; Yang, Zhen

    2015-01-01

    One of the key components of tissue engineering is a scaffold with suitable morphology, outstanding mechanical properties, and favorable biocompatibility. In this study, β-tricalcium phosphate (β-TCP) nanoparticles were synthesized and incorporated with poly(L-lactic acid) (PLLA) to fabricate nanocomposite scaffolds by the thermally induced phase separation method. The PLLA/β-TCP nanocomposite scaffolds showed a continuous nanofibrous PLLA matrix with strut diameters of 100-750 nm, interconnected micropores with pore diameters in the range of 0.5-10 μm, and high porosity (>92 %). β-TCP nanoparticles were homogeneously dispersed in the PLLA matrix, which significantly improved the compressive modulus and protein adsorption capacity. The prepared nanocomposite scaffolds provided a suitable microenvironment for osteoblast attachment and proliferation, demonstrating the potential of the PLLA/β-TCP nanocomposite scaffolds in bone tissue engineering applications.

  9. Fabrication of PLLA/β-TCP nanocomposite scaffolds with hierarchical porosity for bone tissue engineering.

    PubMed

    Lou, Tao; Wang, Xuejun; Song, Guojun; Gu, Zheng; Yang, Zhen

    2014-08-01

    Polymer and ceramic composite scaffolds play a crucial role in bone tissue engineering. In an attempt to mimic the architecture of natural extracellular matrix (ECM), poly(l-lactic acid)/β-tricalcium phosphate (PLLA/β-TCP) nanocomposite scaffolds with a hierarchical pore structure were fabricated by combining thermal induced phase separation and salt leaching techniques. The nanocomposite scaffold consisted of a nanofibrous PLLA matrix with a highly interconnected, high porosity (>93%) hierarchical pore structure with pore diameters ranging from 500nm to 300μm and a homogeneously distributed β-TCP nanoparticle phase. The nanofibrous PLLA matrix had a fiber diameter of 70-300nm. The nanocomposite scaffolds possess three levels of hierarchical structure: (1) porosity; (2) nanofibrous PLLA struts comprising the pore walls; and (3) β-TCP nanoparticle phase. The β-TCP nanoparticle phase improved the mechanical properties and bioactivity of the PLLA matrix. The nanocomposite scaffolds supported MG-63 osteoblast proliferation, penetration, and ECM deposition, indicating the potential of PLLA/β-TCP nanocomposite scaffolds with hierarchical porosity for bone tissue engineering applications.

  10. A Comparative Study on In Vitro Osteogenic Priming Potential of Electron Spun Scaffold PLLA/HA/Col, PLLA/HA, and PLLA/Col for Tissue Engineering Application

    PubMed Central

    Balaji Raghavendran, Hanumantha Rao; Puvaneswary, Subramaniam; Talebian, Sepehr; Raman Murali, Malliga; Vasudevaraj Naveen, Sangeetha; Krishnamurithy, G.; McKean, Robert; Kamarul, Tunku

    2014-01-01

    A comparative study on the in vitro osteogenic potential of electrospun poly-L-lactide/hydroxyapatite/collagen (PLLA/HA/Col, PLLA/HA, and PLLA/Col) scaffolds was conducted. The morphology, chemical composition, and surface roughness of the fibrous scaffolds were examined. Furthermore, cell attachment, distribution, morphology, mineralization, extracellular matrix protein localization, and gene expression of human mesenchymal stromal cells (hMSCs) differentiated on the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The electrospun scaffolds with a diameter of 200–950 nm demonstrated well-formed interconnected fibrous network structure, which supported the growth of hMSCs. When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds presented a higher density of viable cells and significant upregulation of genes associated with osteogenic lineage, which were achieved without the use of specific medium or growth factors. These results were supported by the elevated levels of calcium, osteocalcin, and mineralization (P<0.05) observed at different time points (0, 7, 14, and 21 days). Furthermore, electron microscopic observations and fibronectin localization revealed that PLLA/Col/HA scaffolds exhibited superior osteoinductivity, when compared with PLLA/Col or PLLA/HA scaffolds. These findings indicated that the fibrous structure and synergistic action of Col and nano-HA with high-molecular-weight PLLA played a vital role in inducing osteogenic differentiation of hMSCs. The data obtained in this study demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be supportive for stem cell based therapies for bone repair, when compared with the other two scaffolds. PMID:25140798

  11. A comparative study on in vitro osteogenic priming potential of electron spun scaffold PLLA/HA/Col, PLLA/HA, and PLLA/Col for tissue engineering application.

    PubMed

    Balaji Raghavendran, Hanumantha Rao; Puvaneswary, Subramaniam; Talebian, Sepehr; Murali, Malliga R; Raman Murali, Malliga; Naveen, Sangeetha V; Vasudevaraj Naveen, Sangeetha; Krishnamurithy, G; McKean, Robert; Kamarul, Tunku

    2014-01-01

    A comparative study on the in vitro osteogenic potential of electrospun poly-L-lactide/hydroxyapatite/collagen (PLLA/HA/Col, PLLA/HA, and PLLA/Col) scaffolds was conducted. The morphology, chemical composition, and surface roughness of the fibrous scaffolds were examined. Furthermore, cell attachment, distribution, morphology, mineralization, extracellular matrix protein localization, and gene expression of human mesenchymal stromal cells (hMSCs) differentiated on the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The electrospun scaffolds with a diameter of 200-950 nm demonstrated well-formed interconnected fibrous network structure, which supported the growth of hMSCs. When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds presented a higher density of viable cells and significant upregulation of genes associated with osteogenic lineage, which were achieved without the use of specific medium or growth factors. These results were supported by the elevated levels of calcium, osteocalcin, and mineralization (P<0.05) observed at different time points (0, 7, 14, and 21 days). Furthermore, electron microscopic observations and fibronectin localization revealed that PLLA/Col/HA scaffolds exhibited superior osteoinductivity, when compared with PLLA/Col or PLLA/HA scaffolds. These findings indicated that the fibrous structure and synergistic action of Col and nano-HA with high-molecular-weight PLLA played a vital role in inducing osteogenic differentiation of hMSCs. The data obtained in this study demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be supportive for stem cell based therapies for bone repair, when compared with the other two scaffolds. PMID:25140798

  12. A comparative study on in vitro osteogenic priming potential of electron spun scaffold PLLA/HA/Col, PLLA/HA, and PLLA/Col for tissue engineering application.

    PubMed

    Balaji Raghavendran, Hanumantha Rao; Puvaneswary, Subramaniam; Talebian, Sepehr; Murali, Malliga R; Raman Murali, Malliga; Naveen, Sangeetha V; Vasudevaraj Naveen, Sangeetha; Krishnamurithy, G; McKean, Robert; Kamarul, Tunku

    2014-01-01

    A comparative study on the in vitro osteogenic potential of electrospun poly-L-lactide/hydroxyapatite/collagen (PLLA/HA/Col, PLLA/HA, and PLLA/Col) scaffolds was conducted. The morphology, chemical composition, and surface roughness of the fibrous scaffolds were examined. Furthermore, cell attachment, distribution, morphology, mineralization, extracellular matrix protein localization, and gene expression of human mesenchymal stromal cells (hMSCs) differentiated on the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA were also analyzed. The electrospun scaffolds with a diameter of 200-950 nm demonstrated well-formed interconnected fibrous network structure, which supported the growth of hMSCs. When compared with PLLA/H%A and PLLA/Col scaffolds, PLLA/Col/HA scaffolds presented a higher density of viable cells and significant upregulation of genes associated with osteogenic lineage, which were achieved without the use of specific medium or growth factors. These results were supported by the elevated levels of calcium, osteocalcin, and mineralization (P<0.05) observed at different time points (0, 7, 14, and 21 days). Furthermore, electron microscopic observations and fibronectin localization revealed that PLLA/Col/HA scaffolds exhibited superior osteoinductivity, when compared with PLLA/Col or PLLA/HA scaffolds. These findings indicated that the fibrous structure and synergistic action of Col and nano-HA with high-molecular-weight PLLA played a vital role in inducing osteogenic differentiation of hMSCs. The data obtained in this study demonstrated that the developed fibrous PLLA/Col/HA biocomposite scaffold may be supportive for stem cell based therapies for bone repair, when compared with the other two scaffolds.

  13. Effects of designed PLLA and 50:50PLGA scaffold architectures on bone formation in vivo

    PubMed Central

    Saito, Eiji; Liao, Elly E.; Hu, Wei-Wen; Krebsbach, Paul H.; Hollister, Scott J.

    2015-01-01

    Biodegradable porous scaffolds have been investigated as an alternative approach to current metal, ceramic, and polymer bone graft substitutes for lost or damaged bone tissues. Although there have been many studies investigating the effects of scaffold architecture on bone formation, many of these scaffolds were fabricated using conventional methods, such as salt leaching and phase separation, and were constructed without designed architecture. To study the effects of both designed architecture and material on bone formation, we designed and fabricated three types of porous scaffold architecture from two biodegradable materials, poly (L-lactic acid) (PLLA) and 50:50Poly (lactic-co-glycolic acid) (PLGA) using image based design and indirect solid freeform fabrication techniques, seeded them with bone morphogenic protein-7 transduced human gingival fibroblasts and implanted them subcutaneously into mice for 4 and 8 weeks. Micro-computed tomography data confirmed that the fabricated porous scaffolds replicated the designed architectures. Histological analysis revealed that the 50:50PLGA scaffolds degraded and did not maintain their architecture after 4 weeks. The PLLA scaffolds maintained their architecture at both time points and showed improved bone ingrowth which followed the internal architecture of the scaffolds. Mechanical properties of both PLLA and 50:50PLGA scaffolds decreased, but PLLA scaffolds maintained greater mechanical properties than 50:50PLGA after implantation. The increase of mineralized tissue helped to support mechanical properties of bone tissue and scaffold constructs from 4 to 8 weeks. The results indicated the importance of choice of scaffold materials and computationally designed scaffolds to control tissue formation and mechanical properties for desired bone tissue regeneration. PMID:22162220

  14. In vitro degradation of porous PLLA/pearl powder composite scaffolds.

    PubMed

    Liu, Y S; Huang, Q L; Kienzle, A; Müller, W E G; Feng, Q L

    2014-05-01

    The in vitro degradation behavior of poly-L-lactide (PLLA), PLLA/aragonite pearl powder and PLLA/vaterite pearl powder scaffolds was investigated. The scaffolds were soaked in phosphate buffer solution (PBS) up to 200 days. Scanning electron microscopy (SEM), gel permeation chromatography (GPC), and differential scanning calorimetry (DSC) were used to observe any degradation of the scaffolds. Degradation behaviors such as changes in pH, porosity, bulk density, water absorption, weight loss and mechanical properties were discussed. The results show that a gradual increase of the pH in composite scaffolds can decrease the rate of hydrolysis of PLLA. PLLA/vaterite and PLLA/aragonite scaffolds have a similar degradation behavior but a slower rate of degradation than PLLA. PMID:24656373

  15. Heparinized PLLA/PLCL nanofibrous scaffold for potential engineering of small-diameter blood vessel: tunable elasticity and anticoagulation property.

    PubMed

    Wang, Weizhong; Hu, Jinwei; He, Chuanglong; Nie, Wei; Feng, Wei; Qiu, Kexin; Zhou, Xiaojun; Gao, Yu; Wang, Guoqing

    2015-05-01

    The success of tissue engineered vascular grafts depends greatly on the synthetic tubular scaffold, which can mimic the architecture, mechanical, and anticoagulation properties of native blood vessels. In this study, small-diameter tubular scaffolds were fabricated with different weight ratios of poly(l-lactic acid) (PLLA) and poly(l-lactide-co-ɛ-caprolactone) (PLCL) by means of thermally induced phase separation technique. To improve the anticoagulation property of materials, heparin was covalently linked to the tubular scaffolds by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide coupling chemistry. The as-prepared PLLA/PLCL scaffolds retained microporous nanofibrous structure as observed in the neat PLLA scaffolds, and their structural and mechanical properties can be fine-tuned by changing the ratio of two components. The scaffold containing 60% PLCL content was found to be the most promising scaffold for engineering small-diameter blood vessel in terms of elastic properties and structural integrity. The heparinized scaffolds showed higher hydrophilicity, lower protein adsorption ability, and better in vitro anticoagulation property than their untreated counterparts. Pig iliac endothelial cells seeded on the heparinized scaffold showed good cellular attachment, spreading, proliferation, and phenotypic maintenance. Furthermore, the heparinized scaffolds exhibited neovascularization after subcutaneous implantation into the New Zealand white rabbits for 1 and 2 months. Taken together, the heparinized PLLA/PLCL nanofibrous scaffolds have the great potential for vascular tissue engineering application.

  16. Research of osteoblastic induced rat bone marrow mesenchymal stem cells cultured on β-TCP/PLLA porous scaffold

    PubMed Central

    Yang, Yi; Wu, Jiang; Jin, Gele; Li, Liang; Li, Zhongwei; Li, Cao

    2015-01-01

    Background: Ceramic and polymer composite scaffolds are widely used in tissue engineering for bone tissue regeneration. Composite of β-tricalcium phosphate (β-TCP) and poly L-lactic acid (PLLA), due to its biocompatibility and biodegradability, is widely used in bioengineering. However, optimal ratio, porosity and pore size of this kind of scaffolds were not very clear yet. Materials and methods: We cultured osteoblastic induced rMSCs on β-TCP/PLLA scaffolds to investigate the optimum construction, which owned better properties for supporting cells growth, proliferation and differentiation. A total of 24 mice were divided into three groups: rMSCs + β-TCP/PLLA, osteoblastic rMSCs + β-TCP/PLLA and β-TCP/PLLA without cells. 8 rude mice were implanted with rMSCs + β-TCP/PLLA in the left thighs and β-TCP/PLLA without cells in the right thighs. 8 rude mice were implanted with osteoblastic rMSCs + β-TCP/PLLA in the left thighs and the same treatments in the right thighs as the above. After 8 and 12 weeks, the mice were sacrificed and implants with the surrounding tissues were harvested together. Paraffin sections were got and HE stain and Masson-Goldner stain were employed to observe the ectopic bone formation. Results: The scaffolds of β-TCP/PLLA = 2:1 significantly increased osteocalcin production of the cells. In addition, scaffolds with NaCl = 70 wt%, pore size 200~450 μm showed better compatibility to these seeding cells. A significantly larger area of bone formation in the osteoblastic rMSCs and β-TCP/PLLA composite than that in rMSCs/scaffold and in the scaffold without cells in vivo. Conclusion: compounds of osteoblastic induced rMSCs and the scaffold with β-TCP/PLLA = 2:1, NaCl = 70 wt%, pore size = 200-450 μm had good properties as a kind of bone substitute. PMID:26064209

  17. PHBV/PLLA-based composite scaffolds fabricated using an emulsion freezing/freeze-drying technique for bone tissue engineering: surface modification and in vitro biological evaluation.

    PubMed

    Sultana, Naznin; Wang, Min

    2012-03-01

    Tissue engineering combines living cells with biodegradable materials and/or bioactive components. Composite scaffolds containing biodegradable polymers and nanosized osteoconductive bioceramic with suitable properties are promising for bone tissue regeneration. In this paper, based on blending two biodegradable and biocompatible polymers, namely poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(L-lactic acid) (PLLA) with incorporated nano hydroxyapatite (HA), three-dimensional composite scaffolds with controlled microstructures and an interconnected porous structure, together with high porosity, were fabricated using an emulsion freezing/freeze-drying technique. The influence of various parameters involved in the emulsion freezing/freeze-drying technique was studied for the fabrication of good-quality polymer scaffolds based on PHBV polymers. The morphology, mechanical properties and crystallinity of PHBV/PLLA and HA in PHBV/PLLA composite scaffolds and PHBV polymer scaffolds were studied. The scaffolds were coated with collagen in order to improve wettability. During in vitro biological evaluation study, it was observed that SaOS-2 cells had high attachment on collagen-coated scaffolds. Significant improvement in cell proliferation and alkaline phosphatase activity for HA-incorporated composite scaffolds was observed due to the incorporation of HA. After 3 and 7 days of culture on all scaffolds, SaOS-2 cells also had normal morphology and growth. These results indicated that PHBV/PLLA-based scaffolds fabricated via an emulsion freezing/freeze-drying technique were favorable sites for osteoblastic cells and are promising for the applications of bone tissue engineering.

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

    PubMed

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

    2013-12-01

    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. PMID:24225196

  19. Gelatine/PLLA sponge-like scaffolds: morphological and biological characterization.

    PubMed

    Lazzeri, Luigi; Cascone, Maria Grazia; Danti, Serena; Serino, Lorenzo Pio; Moscato, Stefania; Bernardini, Nunzia

    2007-07-01

    Biodegradable synthetic polymers such as poly(lactic acid) (PLA) are widely used to prepare scaffolds for cell transplantation and tissue growth, using different techniques set up for the purpose. However the poor hydrophilicity of these polymers represents the main limitation to their use as scaffolds because it causes a low affinity for the cells. An effective way to solve this problem could be represented by the addition of biopolymers that are in general highly hydrophilic. The present work concerns porous biodegradable sponge-like systems based on poly(L-lactic acid) (PLLA) and gelatine. Morphology and porosity characteristics of the sponges were studied by scanning electron microscopy and mercury intrusion porosimetry respectively. Blood compatibility was investigated by bovine plasma fibrinogen (BPF) adsorption test and platelet adhesion test (PAT). The cell culture method was used in order to evaluate the ability of the matrices to work as scaffolds for tissue regeneration. The obtained results indicate that the sponges have interesting porous characteristics, good blood compatibility and above all good ability to support cell adhesion and growth. In fact viable and metabolically active animal cells were found inside the sponges after 8 weeks in culture. On this basis the systems produced seem to be good candidates as scaffolds for tissue regeneration.

  20. FEM modeling of the reinforcement mechanism of Hydroxyapatite in PLLA scaffolds produced by supercritical drying, for Tissue Engineering applications.

    PubMed

    Baldino, L; Naddeo, F; Cardea, S; Naddeo, A; Reverchon, E

    2015-11-01

    Scaffolds have been produced by supercritical CO2 drying of Poly-L-Lactid Acid (PLLA) gels loaded with micrometric fructose particles used as porogens. These structures show a microporous architecture generated by the voids left in the solid material by porogen leaching, while they maintain the nanostructure of the gel, consisting of a network of nanofilaments. These scaffolds have also been loaded with Hydroxyapatite (HA) nanoparticles, from 10 to 50% w/w with respect to the polymer, to improve the mechanical properties of the PLLA structure. Based on miscroscopic and mechanical considerations, we propose a parametric Finite Element Method (FEM) model of PLLA-HA composites that describes the microporous structure as a close-packing of equal spheres and the nanoscale structure as a space frame of isotropic curved fibers. The effect of HA on the mechanical properties of the scaffolds has been modeled on the basis of SEM images and by taking into consideration the formation of concentric cylinders of HA nanoparticles around PLLA nanofibers. Modeling analysis confirms that mechanical properties of these scaffolds depend on nanofibrous network connections and that bending is the major factor causing deformation of the network. The FEM model also takes into account the formation of HA multi-layer coating on some areas in the nanofiber network and its increase in thickness with HA percentage. The Young modulus tends to a plateau for HA percentages larger than 30% w/w and when the coverage of the nanofibers produced by HA nanoparticles reaches a loaded surface index of 0.14 in the FEM model.

  1. The use of flow perfusion culture and subcutaneous implantation with fibroblast-seeded PLLA-collagen 3D scaffolds for abdominal wall repair.

    PubMed

    Pu, Fanrong; Rhodes, Nicholas P; Bayon, Yves; Chen, Rui; Brans, Gerben; Benne, Remco; Hunt, John A

    2010-05-01

    Highly cellularised 3D-tissue constructs designed to repair large, complex abdominal wall defects were prepared using poly (lactic acid) (PLLA)-collagen scaffolds in vitro using a flow perfusion bioreactor. The PLLA-collagen scaffolds had a unique structure consisting of a collagen sponge formed within the pores of a mechanically stable knitted mesh of PLLA. The effect of the flow perfusion bioreactor culturing conditions was investigated in vitro for 0, 7, 14 and 28 days on scaffolds seeded with dermal fibroblasts. The cultured constructs were subsequently studied subcutaneously (SC) in an in vivo animal model. The results of in vitro studies demonstrated that the perfusion system facilitated increased cell proliferation and homogenous distribution in the PLLA-collagen scaffolds compared to static conditions. A highly cellularised 3D-tissue construct was formed by 7 days incubation under perfusion conditions, with increased cellularity by the 28 day time point. The in vivo model demonstrated that implanting constructs with high cellularity resulted in exceptional cell stabilisation, with the survival of implanted cells and expression of the phenotypically-relevant extracellular matrix proteins collagen types I and III, studied by fluorescence in situ hybridisation (FISH) and immunohistochemistry. The implantation of this porous PPLA-collagen scaffold seeded with dermal fibroblasts following in vitro maturation using a flow perfusion bioreactor system suggests a significant advance over current state-of-the-art procedures for the reconstruction of large, complex abdominal wall tissue defects. PMID:20219244

  2. Easy fabrication of aligned PLLA nanofibers-based 2D scaffolds suitable for cell contact guidance studies.

    PubMed

    Mohanraj, John; Puzzi, Luca; Capria, Ennio; Corvaglia, Stefania; Casalis, Loredana; Mestroni, Luisa; Sbaizero, Orfeo; Fraleoni-Morgera, Alessandro

    2016-05-01

    An easy, low-cost and fast wet processing-based method named ASB-SANS (Auxiliary Solvent-Based Sublimation-Aided NanoStructuring) has been used to fabricate poly(l-lactic acid) (PLLA) highly ordered and hierarchically organized 2D fibrillar patterns, with fiber widths between 40 and 500 nm and lengths exceeding tens of microns. A clear contact guidance effect of these nanofibrillar scaffolds with respect to HeLa and NIH-3T3 cells growth has been observed, on top of an overall good viability. For NIH-3T3 pronounced elongation of the cells was observed, as well as a remarkable ability of the patterns to guide the extension of pseudopodia. Moreover, SEM imaging revealed filopodia stemming from both sides of the pseudopodia and aligned with the secondary PLLA nanofibrous structures created by the ASB-SANS procedure. These results validate ASB-SANS as a technique capable to provide biocompatible 2D nanofibrillar patterns suitable for studying phenomena of contact guidance (and, more in general, the behavior of cells onto nanofibrous scaffolds), at very low costs and in an extremely easy way, accessible to virtually any laboratory. PMID:26952427

  3. Composite poly(l-lactic-acid)/silk fibroin scaffold prepared by electrospinning promotes chondrogenesis for cartilage tissue engineering.

    PubMed

    Li, Zhengqiang; Liu, Peng; Yang, Ting; Sun, Ying; You, Qi; Li, Jiale; Wang, Zilin; Han, Bing

    2016-05-01

    Nanofibrous materials produced by electrospinning have attracted considerable attention from researchers in regenerative medicine. A combination of nanofibrous scaffold and chondrocytes is considered promising for repair of cartilage defect or damage. In the present study, we fabricated a poly(l-lactic-acid) (PLLA)/silk fibroin (SF) nanofibrous scaffold by electrospinning and evaluated its chondrogenic potential. The PLLA/SF nanofibers were characterized for diameter, surface wettability, swelling ratio, and tensile strength. Throughin vitroexperiments, PLLA/SF scaffold-chondrocyte interactions were investigated relative to the unmodified PLLA scaffold with regard to cellular adhesion, spreading, and proliferation by scanning electron microscopy and confocal laser scanning microscopy, and through analyses of DNA, sulfated glycosaminoglycan, and collagen. In addition, hematoxylin-eosin and Alcian blue-nuclear fast red staining were used to observe growth of chondrocytes, and secretion and distribution of cartilage-specific extracellular matrices in the scaffolds. Expressions of cartilage-related genes (collagen II, aggrecan, sox9, collagen I, and collagen X) were detected by real-time quantitative PCR. The PLLA/SF scaffold had better hydrophilicity, and could support chondrocytes adhesion and spreading more effectively than the unmodified PLLA scaffold. Chondrocytes secreted more cartilage-specific extracellular matrices and maintained their phenotype on the PLLA/SF scaffold. So it is concluded that the PLLA/SF scaffold is more conducive toin vitroformation of cartilage-like new tissues than the unmodified PLLA scaffold, and may be a promising material in cartilage tissue engineering. PMID:27059497

  4. Composite poly(l-lactic-acid)/silk fibroin scaffold prepared by electrospinning promotes chondrogenesis for cartilage tissue engineering.

    PubMed

    Li, Zhengqiang; Liu, Peng; Yang, Ting; Sun, Ying; You, Qi; Li, Jiale; Wang, Zilin; Han, Bing

    2016-05-01

    Nanofibrous materials produced by electrospinning have attracted considerable attention from researchers in regenerative medicine. A combination of nanofibrous scaffold and chondrocytes is considered promising for repair of cartilage defect or damage. In the present study, we fabricated a poly(l-lactic-acid) (PLLA)/silk fibroin (SF) nanofibrous scaffold by electrospinning and evaluated its chondrogenic potential. The PLLA/SF nanofibers were characterized for diameter, surface wettability, swelling ratio, and tensile strength. Throughin vitroexperiments, PLLA/SF scaffold-chondrocyte interactions were investigated relative to the unmodified PLLA scaffold with regard to cellular adhesion, spreading, and proliferation by scanning electron microscopy and confocal laser scanning microscopy, and through analyses of DNA, sulfated glycosaminoglycan, and collagen. In addition, hematoxylin-eosin and Alcian blue-nuclear fast red staining were used to observe growth of chondrocytes, and secretion and distribution of cartilage-specific extracellular matrices in the scaffolds. Expressions of cartilage-related genes (collagen II, aggrecan, sox9, collagen I, and collagen X) were detected by real-time quantitative PCR. The PLLA/SF scaffold had better hydrophilicity, and could support chondrocytes adhesion and spreading more effectively than the unmodified PLLA scaffold. Chondrocytes secreted more cartilage-specific extracellular matrices and maintained their phenotype on the PLLA/SF scaffold. So it is concluded that the PLLA/SF scaffold is more conducive toin vitroformation of cartilage-like new tissues than the unmodified PLLA scaffold, and may be a promising material in cartilage tissue engineering.

  5. The effect of fiber size and pore size on cell proliferation and infiltration in PLLA scaffolds on bone tissue engineering.

    PubMed

    Wang, Xuejun; Lou, Tao; Zhao, Wenhua; Song, Guojun; Li, Chunyao; Cui, Guangpeng

    2016-05-01

    The scaffold microstructure has a great impact on cell functions in tissue engineering. Herein, the PLLA scaffolds with hierarchical fiber size and pore size were successfully fabricated by thermal-induced phase separation or combined thermal-induced phase separation and salt leaching methods. The PLLA scaffolds were fabricated as microfibrous scaffolds, microfibrous scaffolds with macropores (50-350 µm), nanofibrous scaffolds with micropores (100 nm to 10 µm), and nanofibrous scaffolds with both macropores and micropores by tailoring selective solvents for forming different fiber size and pre-sieved salts for creating controlled pore size. Among the four kinds of PLLA scaffolds, the nanofibrous scaffolds with both macropores and micropores provided a favorable microenvironment for protein adsorption, cell proliferation, and cell infiltration. The results further confirmed the significance of fiber size and pore size on the biological properties, and a scaffold with both micropores and macropores, and a nanofibrous matrix might have promising applications in bone tissue engineering.

  6. Bi-layer scaffold of chitosan/PCL-nanofibrous mat and PLLA-microporous disc for skin tissue engineering.

    PubMed

    Lou, Tao; Leung, Matthew; Wang, Xuejun; Chang, Julia Yu Fong; Tsao, Ching Ting; Sham, Jonathan Ghing Chi; Edmondson, Dennis; Zhang, Miqin

    2014-06-01

    Current treatments for severe skin damage involve the grafting of extremely limited autogenic skin or the use of synthetic skin grafts that do not fully recapitulate the biological properties of native skin. In this study we developed a novel bi-layer scaffold that provides the microenvironmental cues favorable to promoting skin healing and regeneration. The scaffold is composed of a superficial chitosan/PCL nanofibrous mat (CP-nano mat) and an underlying PLLA microporous disc (PLLA-micro disc). The porous structure of the scaffold permits the interaction of biomolecules released from two types of cells distributed, respectively, throughout the two layers of the scaffold, but the nanofibers prevent the direct intermingling of the cell types. The CP-nano mat and PLLA-micro disc were fabricated by electrospinning and thermally induced phase separation, respectively, and host keratinoctyes as an epidermal equivalent and fibroblasts as a dermal equivalent, respectively, present in the native skin. The potential of this bi-layer scaffold to serve as a skin equivalent was evaluated by co-culture of keratinocytes and fibroblasts and subsequent assessment of cell proliferation, cell morphology, gene transcription, and protein expression. The cell proliferation was found to be greatest in co-culture on bi-layer scaffolds. The gene and protein expression analyses further confirmed that the bi-layer scaffold provided a micro-environment similar to those present in the native extracellular matrix during initial wound healing. Our study suggested that the bi-layer scaffold has great potential to serve as a skin equivalent in tissue engineering. PMID:24749404

  7. Improvement of β-TCP/PLLA biodegradable material by surface modification with stearic acid.

    PubMed

    Ma, Fengcang; Chen, Sai; Liu, Ping; Geng, Fang; Li, Wei; Liu, Xinkuan; He, Daihua; Pan, Deng

    2016-05-01

    Poly-L-lactide (PLLA) is a biodegradable polymer and used widely. Incorporation of beta tricalcium phosphate (β-TCP) into PLLA can enhance its osteoinductive properties. But the interfacial layer between β-TCP particles with PLLA matrix is easy to be destroyed due to inferior interfacial compatibility of the organic/inorganic material. In this work, a method of β-TCP surface modification with stearic acid was investigated to improve the β-TCP/PLLA biomaterial. The effects of surface modification on the β-TCP were investigated by FTIR, XPS, TGA and CA. It was found that the stearic acid reacted with β-TCP and oxhydryl was formed during the surface modification. Hydrophilicity of untreated or modified β-TCP/PLLA composite was increased by the addition of 10 wt.% β-TCP, but it decreased as the addition amount increased from 10 wt.% to 20 wt.%. Two models were suggested to describe the effect of β-TCP concentration on CA of the composites. Mechanical properties of β-TCP/PLLA composites were tested by bending and tensile tests. Fractures of the composites after mechanical test were observed by SEM. It was found that surface modification with stearic acid improved bending and tensile strengths of the β-TCP/PLLA composites obviously. The SEM results indicated that surface modification decreased the probability of interface debonding between fillers and matrix under load.

  8. Osteogenic Properties of PBLG-g-HA/PLLA Nanocomposites

    PubMed Central

    Liao, Lan; Yang, Shuang; Miron, Richard J.; Wei, Junchao; Zhang, Yufeng; Zhang, Meng

    2014-01-01

    New development of biomaterial scaffolds remains a prominent issue for the regeneration of lost or fractured bone. Of these scaffolds, a number of bioactive polymers have been synthesized and fabricated for diverse biological roles. Although recent evidence has demonstrated that composite scaffolds such as HA/PLLA have improved properties when compared to either HA or PLLA alone, recent investigations have demonstrated that the phase compatibility between HA and PLLA layers is weak preventing optimal enhancement of the mechanical properties and making the composites prone to breakdown. In the present study, poly (γ-benzyl-L-glutamate) modified hydroxyapatite/(poly (L-lactic acid)) (PBLG-g-HA/PLLA) composite scaffolds were fabricated with improved phase compatibility and tested for their osteogenic properties in 18 Wistar female rats by analyzing new bone formation in 3 mm bilateral femur defects in vivo. At time points, 2, 4 and 8 weeks post surgery, bone formation was evaluated by µ-CT and histological analysis by comparing 4 treatment groups; 1) blank defect, 2) PLLA, 3) HA/PLLA and 4) PBLG-g-HA/PLLA scaffolds. The in vivo analysis demonstrated that new bone formation was much more prominent in HA/PLLA and PBLG-g-HA/PLLA groups as depicted by µ-CT, H&E staining and immunohistochemistry for collagen I. TRAP staining was also utilized to determine the influence of osteoclast cell number and staining intensity to the various scaffolds. No significant differences in either staining intensity or osteoclast numbers between all treatment modalities was observed, however blank defects did contain a higher number of osteoclast-like cells. The results from the present study illustrate the potential of PBLG-g-HA/PLLA scaffolds for bone tissue engineering applications by demonstrating favorable osteogenic properties. PMID:25184285

  9. Layered chitosan-collagen hydrogel/aligned PLLA nanofiber construct for flexor tendon regeneration.

    PubMed

    Deepthi, S; Nivedhitha Sundaram, M; Deepti Kadavan, J; Jayakumar, R

    2016-11-20

    The aim of our study was to develop a tendon construct of electrospun aligned poly (l-lactic acid) (PLLA) nanofibers, to mimic the aligned collagen fiber bundles and layering PLLA fibers with chitosan-collagen hydrogel, to mimic the glycosaminoglycans of sheath ECM for tendon regeneration. The hydrogel coated electrospun membrane was rolled and an outer coating of alginate gel was given to prevent peritendinous adhesion. The developed constructs were characterized by SEM, FT-IR and tensile testing. Protein adsorption studies showed lower protein adsorption on coated scaffolds compared to uncoated scaffolds. The samples were proven to be non-toxic to tenocytes. The chitosan-collagen/PLLA uncoated scaffolds and alginate gel coated chitosan-collagen/PLLA scaffolds showed good cell proliferation. The tenocytes showed good attachment and spreading on the scaffolds. This study indicated that the developed chitosan-collagen/PLLA/alginate scaffold would be suitable for flexor tendon regeneration. PMID:27561521

  10. Fabrication and biocompatibility of poly(l-lactic acid) and chitosan composite scaffolds with hierarchical microstructures.

    PubMed

    Lou, Tao; Wang, Xuejun; Yan, Xu; Miao, Yu; Long, Yun-Ze; Yin, Hai-Lei; Sun, Bin; Song, Guojun

    2016-07-01

    The scaffold microstructure is crucial to reconstruct tissue normal functions. In this article, poly(l-lactic acid) and chitosan fiber (PLLA/CTSF) composite scaffolds with hierarchical microstructures both in fiber and pore sizes were successfully fabricated by combining thermal induced phase separation and salt leaching techniques. The composite scaffolds consisted of a nanofibrous PLLA matrix with diameter of 50-500nm, and chitosan fibers with diameter of about 20μm were homogenously distributed in the PLLA matrix as a microsized reinforcer. The composite scaffolds also had high porosity (>94%) and hierarchical pore size, which were consisted of both micropores (50nm-10μm) and macropores (50-300μm). By tailoring the microstructure and chemical composition, the mechanical property, pH buffer and protein adsorption capacity of the composite scaffold were improved significantly compared with those of PLLA scaffold. Cell culture results also revealed that the PLLA/CTSF composite scaffolds supported MG-63 osteoblast proliferation and penetration. PMID:27127062

  11. Gelatine/PLLA sponge-like scaffolds: morphological and biological characterization.

    PubMed

    Lazzeri, Luigi; Cascone, Maria Grazia; Danti, Serena; Serino, Lorenzo Pio; Moscato, Stefania; Bernardini, Nunzia

    2006-12-01

    Biodegradable synthetic polymers such as poly(lactic acid) are widely used to prepare scaffolds for cell transplantation and tissue growth, using different techniques set up for the purpose. However the poor hydrophilicity of these polymers represents the main limitation to their use as scaffolds because it causes a low affinity for the cells. An effective way to solve this problem could be represented by the addition of biopolymers that are in general highly hydrophilic. The present work concerns porous biodegradable sponge-like systems based on poly(L-lactic acid) and gelatine. Morphology and porosity characteristics of the sponges were studied by scanning electron microscopy and mercury intrusion porosimetry respectively. Blood compatibility was investigated by bovine plasma fibrinogen adsorption test and platelet adhesion test. The cell culture method was used in order to evaluate the ability of the matrices to work as scaffolds for tissue regeneration. The obtained results indicate that the sponges have interesting porous characteristics, good blood compatibility and above all good ability to support cell adhesion and growth. In fact viable and metabolically active animal cells were found inside the sponges after 8 weeks in culture. On this basis the systems produced seem to be good candidates as scaffolds for tissue regeneration.

  12. Biomimetic poly(glycerol sebacate)/poly(l-lactic acid) blend scaffolds for adipose tissue engineering.

    PubMed

    Frydrych, Martin; Román, Sabiniano; MacNeil, Sheila; Chen, Biqiong

    2015-05-01

    Large three-dimensional poly(glycerol sebacate) (PGS)/poly(l-lactic acid) (PLLA) scaffolds with similar bulk mechanical properties to native low and high stress adapted adipose tissue were fabricated via a freeze-drying and a subsequent curing process. PGS/PLLA scaffolds containing 73vol.% PGS were prepared using two different organic solvents, resulting in highly interconnected open-pore structures with porosities and pore sizes in the range of 91-92% and 109-141μm, respectively. Scanning electron microscopic analysis indicated that the scaffolds featured different microstructure characteristics, depending on the organic solvent in use. The PGS/PLLA scaffolds had a tensile Young's modulus of 0.030MPa, tensile strength of 0.007MPa, elongation at the maximum stress of 25% and full shape recovery capability upon release of the compressive load. In vitro degradation tests presented mass losses of 11-16% and 54-55% without and with the presence of lipase enzyme in 31days, respectively. In vitro cell tests exhibited clear evidence that the PGS/PLLA scaffolds prepared with 1,4-dioxane as the solvent are suitable for culture of adipose derived stem cells. Compared to pristine PLLA scaffolds prepared with the same procedure, these scaffolds provided favourable porous microstructures, good hydrophilic characteristics, and appropriate mechanical properties for soft tissue applications, as well as enhanced scaffold cell penetration and tissue in-growth characteristics. This work demonstrates that the PGS/PLLA scaffolds have potential for applications in adipose tissue engineering. PMID:25769230

  13. Biomimetic poly(glycerol sebacate)/poly(l-lactic acid) blend scaffolds for adipose tissue engineering.

    PubMed

    Frydrych, Martin; Román, Sabiniano; MacNeil, Sheila; Chen, Biqiong

    2015-05-01

    Large three-dimensional poly(glycerol sebacate) (PGS)/poly(l-lactic acid) (PLLA) scaffolds with similar bulk mechanical properties to native low and high stress adapted adipose tissue were fabricated via a freeze-drying and a subsequent curing process. PGS/PLLA scaffolds containing 73vol.% PGS were prepared using two different organic solvents, resulting in highly interconnected open-pore structures with porosities and pore sizes in the range of 91-92% and 109-141μm, respectively. Scanning electron microscopic analysis indicated that the scaffolds featured different microstructure characteristics, depending on the organic solvent in use. The PGS/PLLA scaffolds had a tensile Young's modulus of 0.030MPa, tensile strength of 0.007MPa, elongation at the maximum stress of 25% and full shape recovery capability upon release of the compressive load. In vitro degradation tests presented mass losses of 11-16% and 54-55% without and with the presence of lipase enzyme in 31days, respectively. In vitro cell tests exhibited clear evidence that the PGS/PLLA scaffolds prepared with 1,4-dioxane as the solvent are suitable for culture of adipose derived stem cells. Compared to pristine PLLA scaffolds prepared with the same procedure, these scaffolds provided favourable porous microstructures, good hydrophilic characteristics, and appropriate mechanical properties for soft tissue applications, as well as enhanced scaffold cell penetration and tissue in-growth characteristics. This work demonstrates that the PGS/PLLA scaffolds have potential for applications in adipose tissue engineering.

  14. Delivery of rhBMP-2 Plasmid DNA Complexes via a PLLA/Collagen Electrospun Scaffold Induces Ectopic Bone Formation.

    PubMed

    Zhao, Xia; Komatsu, David E; Hadjiargyrou, Michael

    2016-06-01

    The development of effective strategies for gene delivery is a critical goal in DNA-based tissue engineering. Previously, our laboratory utilized the process of electrospinning to fabricate plasmid DNA-based polymeric scaffolds. Although there lease of DNA was robust, the in vitro transfection efficiency was low. In order to optimize these results, we recently modified our approach and utilized a strategy to adsorb plasmid DNA transfection complexes onto a PLLA/Collagen I electrospun scaffold for the delivery of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2). BMP-2 was selected since it is currently clinically used to stimulate osteogenesis. Initially, we tested this approach using β-gal plasmid DNA complexes adsorbed onto PLLA/Collagen I scaffolds and obtained a transfection efficiency of 41% of that of the positive control (over 90%, DNA complexes in solution). Next, we utilized the same approach using the rhBMP-2 plasmid DNA complexes with the pre-osteoblastic. cell line, MC3T3, and detected robust (13-fold) expression of rhBMP-2 mRNA following transfection. Lastly, a mouse muscle pouch model was used to evaluate in vivo gene delivery efficacy and ectopic bone inducing capability of the scaffold adsorbed rhBMP-2 transfection complexes. Results showed that both rhBMP-2mRNA and protein were expressed and stimulated some ectopic bone formation. As such, adsorption of plasmid DNA complexes can be an effective strategy for tissue engineering in vivo, but further research is required to optimize our approach and obtain a clinically meaningful tissue response. PMID:27319221

  15. Synthesis, characterization and foaming of PHEA-PLLA, a new graft copolymer for biomedical engineering.

    PubMed

    Carfì Pavia, Francesco; La Carrubba, Vincenzo; Brucato, Valerio; Palumbo, Fabio Salvatore; Giammona, Gaetano

    2014-08-01

    In this study a chemical grafting procedure was set up in order to link high molecular weight poly L-lactic acid (PLLA) chains to the hydrophilic α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) backbone. A graft copolymer named PHEA-g-PLLA (or simply PHEA-PLLA) was obtained bearing a degree of derivatization of 1.0 mol.% of PLLA as grafted chain. This new hybrid derivative offers both the opportune crystallinity necessary for the production of scaffolds trough a thermally induced phase separation (TIPS) technique and the proper chemical reactivity to perform further functionalizations with bio-effectors and drugs. PHEA-PLLA porous scaffolds for tissue engineering applications were successfully obtained via TIPS and characterized. Structures with an open porosity and a good level of interconnection were detected. As the applicability of the scaffold is mainly dependent on its pore size, preliminary studies about the mechanisms governing scaffold's pore diameter were carried out.

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

    PubMed

    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.

  17. Electrophoretic Deposition of Dexamethasone-Loaded Mesoporous Silica Nanoparticles onto Poly(L-Lactic Acid)/Poly(ε-Caprolactone) Composite Scaffold for Bone Tissue Engineering.

    PubMed

    Qiu, Kexin; Chen, Bo; Nie, Wei; Zhou, Xiaojun; Feng, Wei; Wang, Weizhong; Chen, Liang; Mo, Xiumei; Wei, Youzhen; He, Chuanglong

    2016-02-17

    The incorporation of microcarriers as drug delivery vehicles into polymeric scaffold for bone regeneration has aroused increasing interest. In this study, the aminated mesoporous silica nanoparticles (MSNs-NH2) were prepared and used as microcarriers for dexamethasone (DEX) loading. Poly(l-lactic acid)/poly(ε-caprolactone) (PLLA/PCL) nanofibrous scaffold was fabricated via thermally induced phase separation (TIPS) and served as template, onto which the drug-loaded MSNs-NH2 nanoparticles were deposited by electrophoretic deposition (EPD). The physicochemical and release properties of the prepared scaffolds (DEX@MSNs-NH2/PLLA/PCL) were examined, and their osteogenic activities were also evaluated through in vitro and in vivo studies. The release of DEX from the scaffolds revealed an initial rapid release followed by a slower and sustained one. The in vitro results indicated that the DEX@MSNs-NH2/PLLA/PCL scaffold exhibited good biocompatibility to rat bone marrow-derived mesenchymal stem cells (BMSCs). Also, BMSCs cultured on the DEX@MSNs-NH2/PLLA/PCL scaffold exhibited a higher degree of osteogenic differentiation than those cultured on PLLA/PCL and MSNs-NH2/PLLA/PCL scaffolds, in terms of alkaline phosphatase (ALP) activity, mineralized matrix formation, and osteocalcin (OCN) expression. Furthermore, the in vivo results in a calvarial defect model of Sprague-Dawley (SD) rats demonstrated that the DEX@MSNs-NH2/PLLA/PCL scaffold could significantly promote calvarial defect healing compared with the PLLA/PCL scaffold. Thus, the EPD technique provides a convenient way to incorporate osteogenic agents-containing microcarriers to polymer scaffold, and thus, prepared composite scaffold could be a potential candidate for bone tissue engineering application due to its capacity for delivery of osteogenic agents.

  18. Transfer molding processes for nanoscale patterning of poly-L-lactic acid (PLLA) films

    NASA Astrophysics Data System (ADS)

    Dhakal, Rabin; Peer, Akshit; Biswas, Rana; Kim, Jaeyoun

    2016-03-01

    Nanoscale patterned structures composed of biomaterials exhibit great potential for the fabrication of functional biostructures. In this paper, we report cost-effective, rapid, and highly reproducible soft lithographic transfer-molding techniques for creating periodic micro- and nano-scale textures on poly (L-lactic acid) (PLLA) surface. These artificial textures can increase the overall surface area and change the release dynamics of the therapeutic agents coated on it. Specifically, we use the double replication technique in which the master pattern is first transferred to the PDMS mold and the pattern on PDMS is then transferred to the PLLA films through drop-casting as well as nano-imprinting. The ensuing comparison studies reveal that the drop-cast PLLA allows pattern transfer at higher levels of fidelity, enabling the realization of nano-hole and nano-cone arrays with pitch down to ~700 nm. The nano-patterned PLLA film was then coated with rapamycin to make it drug-eluting.

  19. Preparation and in vitro characterization of scaffolds of poly(L-lactic acid) containing bioactive glass ceramic nanoparticles.

    PubMed

    Hong, Zhongkui; Reis, Rui L; Mano, João F

    2008-09-01

    Porous nanocomposite scaffolds of poly(l-lactic acid) (PLLA) containing different quantities of bioactive glass ceramic (BGC) nanoparticles (SiO(2):CaO:P(2)O(5) approximately 55:40:5 (mol)) were prepared by a thermally induced phase-separation method. Dioxane was used as the solvent for PLLA. Introduction of less than 20wt.% of BGC nanoparticles did not remarkably affect the porosity of PLLA foam. However, as the BGC content increased to 30wt.%, the porosity of the composite was observed to decrease rapidly. The compressive modulus of the scaffolds increased from 5.5 to 8.0MPa, while the compressive strength increased from 0.28 to 0.35MPa as the BGC content increased from 0 to 30wt.%. The in vitro bioactivity and biodegradability of nanocomposites were investigated by incubation in simulated body fluid (SBF) and phosphate-buffered saline, respectively. Scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy and X-ray diffraction were employed to monitor the surface variation of neat PLLA and PLLA/BGC porous scaffolds during incubation. PLLA/(20wt.%)BGC composite exhibited the best mineralization property in SBF, while the PLLA/(10wt.%)BGC composite showed the highest water absorption ability.

  20. Fabrication of Poly-l-lactic Acid/Dicalcium Phosphate Dihydrate Composite Scaffolds with High Mechanical Strength-Implications for Bone Tissue Engineering.

    PubMed

    Tanataweethum, Nida; Liu, Wai Ching; Goebel, W Scott; Li, Ding; Chu, Tien Min

    2015-11-04

    Scaffolds were fabricated from poly-l-lactic acid (PLLA)/dicalcium phosphate dihydrate (DCPD) composite by indirect casting. Sodium citrate and PLLA were used to improve the mechanical properties of the DCPD scaffolds. The resulting PLLA/DCPD composite scaffold had increased diametral tensile strength and fracture energy when compared to DCPD only scaffolds (1.05 vs. 2.70 MPa and 2.53 vs. 12.67 N-mm, respectively). Sodium citrate alone accelerated the degradation rate by 1.5 times independent of PLLA. Cytocompatibility of all samples were evaluated using proliferation and differentiation parameters of dog-bone marrow stromal cells (dog-BMSCs). The results showed that viable dog-BMSCs attached well on both DCPD and PLLA/DCPD composite surfaces. In both DCPD and PLLA/DCPD conditioned medium, dog-BMSCs proliferated well and expressed alkaline phosphatase (ALP) activity indicating cell differentiation. These findings indicate that incorporating both sodium citrate and PLLA could effectively improve mechanical strength and biocompatibility without increasing the degradation time of calcium phosphate cement scaffolds for bone tissue engineering purposes.

  1. Fabrication of Poly-l-lactic Acid/Dicalcium Phosphate Dihydrate Composite Scaffolds with High Mechanical Strength—Implications for Bone Tissue Engineering

    PubMed Central

    Tanataweethum, Nida; Liu, Wai Ching; Scott Goebel, W.; Li, Ding; Chu, Tien Min

    2015-01-01

    Scaffolds were fabricated from poly-l-lactic acid (PLLA)/dicalcium phosphate dihydrate (DCPD) composite by indirect casting. Sodium citrate and PLLA were used to improve the mechanical properties of the DCPD scaffolds. The resulting PLLA/DCPD composite scaffold had increased diametral tensile strength and fracture energy when compared to DCPD only scaffolds (1.05 vs. 2.70 MPa and 2.53 vs. 12.67 N-mm, respectively). Sodium citrate alone accelerated the degradation rate by 1.5 times independent of PLLA. Cytocompatibility of all samples were evaluated using proliferation and differentiation parameters of dog-bone marrow stromal cells (dog-BMSCs). The results showed that viable dog-BMSCs attached well on both DCPD and PLLA/DCPD composite surfaces. In both DCPD and PLLA/DCPD conditioned medium, dog-BMSCs proliferated well and expressed alkaline phosphatase (ALP) activity indicating cell differentiation. These findings indicate that incorporating both sodium citrate and PLLA could effectively improve mechanical strength and biocompatibility without increasing the degradation time of calcium phosphate cement scaffolds for bone tissue engineering purposes. PMID:26556380

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

    PubMed

    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. PMID:27550636

  3. Bionic electrospun ultrafine fibrous poly(L-lactic acid) scaffolds with a multi-scale structure.

    PubMed

    Zhang, Kai; Wang, Xuefen; Jing, Dazheng; Yang, Yin; Zhu, Meifang

    2009-06-01

    Poly(L-lactic acid) (PLLA) tissue engineering scaffolds with porous inner structures of individual fibers and controllable architectures were successfully fabricated from the homogeneous polymer-solvent-nonsolvent system (PLLA, CH(2)Cl(2) and DMF) by a single capillary electrospinning with certain conductive patterned templates as fiber collectors. PLLA was dissolved in dimethylformamide (DMF) and methylene chloride (CH(2)Cl(2)) mixed solvent with different ratios. Semi-hollow fiber with porous inner structure and compact shell wall was formed by controlling the content of DMF in the mixed solvents. It is believed that the phase separation should be the key origin for the formation of this microstructure. In order to mimic the natural extracellular matrix (ECM) with a specific structure, conductive patterned collectors were designed and employed to manufacture PLLA ultrafine fibrous scaffolds with three-dimensional architectures. We believe these kinds of multi-scale biodegradable fibrous scaffolds with specific microstructure and macro-architectures could make the electrospun fibrous scaffold better mimic the natural extracellular matrix to satisfy tissue engineering.

  4. A poly(L-lactic acid) nanofibre mesh scaffold for endothelial cells on vascular prostheses.

    PubMed

    François, Sébastien; Chakfé, Nabil; Durand, Bernard; Laroche, Gaétan

    2009-09-01

    The absence of neoendothelium covering the intimal surface of small-diameter PET vascular prostheses is known to be one cause of failure following implantation in humans. Protein coatings currently used to seal porous textile structures have not shown evidence of in vivo neoendothelium formation. In this study, we covered the inner wall of textile prostheses with a biodegradable synthetic scaffold made of poly(l-lactic) acid (PLLA) nanofibres obtained by an air-spinning process we developed that produces nanofibres by stretching a solution of polymer with a high-speed compressed air jet. The air spinning was designed to process a scaffold that would support good endothelial cell proliferation. Our innovative process enabled us to very rapidly cover textile samples with PLLA nanofibres to determine the influence of air pressure, polymer solution flow rate and polymer concentration on fibre quality. High air pressure was shown to induce a significant number of ruptures. High polymer flow rate stimulated the formation of polymer droplets, and the fibre diameter mean increased for the 4% and 7% polymer concentrations. The adherence and proliferation of bovine aortic endothelial cells was assessed to compare prosthesis samples with or without the PLLA nanofibre scaffold and PET film. The PLLA nanofibres displayed a significantly better proliferation rate, and enabled endothelial cells to proliferate in the monolayer. Our novel approach therefore opens the door to the development of partially degradable textile prostheses with a blood/textile interface that supports endothelial cell proliferation. PMID:19345622

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

    PubMed

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

    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. PMID:27612733

  6. A space network structure constructed by tetraneedlelike ZnO whiskers supporting boron nitride nanosheets to enhance comprehensive properties of poly(L-lacti acid) scaffolds.

    PubMed

    Feng, Pei; Peng, Shuping; Wu, Ping; Gao, Chengde; Huang, Wei; Deng, Youwen; Shuai, Cijun

    2016-01-01

    In this study, the mechanical strength and modulus of poly(L-lacti acid) (PLLA) scaffolds were enhanced with the mechanical properties of boron nitride nanosheets (BNNSs) and tetraneedlelike ZnO whiskers (T-ZnOw). The adhesion and proliferation of cells were improved as well as osteogenic differentiation of stem cells was increased. Their dispersion statues in PLLA matrix were improved through a space network structure constructed by three-dimensional T-ZnOw supporting two-dimensional BNNSs. The results showed that the compressive strength, modulus and Vickers hardness of the scaffolds with incorporation of 1 wt% BNNSs and 7 wt% T-ZnOw together were about 96.15%, 32.86% and 357.19% higher than that of the PLLA scaffolds, respectively. This might be due to the effect of the pull out and bridging of BNNSs and T-ZnOw as well as the crack deflection, facilitating the formation of effective stress transfer between the reinforcement phases and the matrix. Furthermore, incorporation of BNNSs and T-ZnOw together into PLLA scaffolds was beneficial for attachment and viability of MG-63 cells. More importantly, the scaffolds significantly increased proliferation and promoted osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The enhanced mechanical and biological properties provide the potentials of PLLA/BNNSs/T-ZnOw scaffolds for the application into bone tissue engineering. PMID:27629058

  7. A space network structure constructed by tetraneedlelike ZnO whiskers supporting boron nitride nanosheets to enhance comprehensive properties of poly(L-lacti acid) scaffolds

    PubMed Central

    Feng, Pei; Peng, Shuping; Wu, Ping; Gao, Chengde; Huang, Wei; Deng, Youwen; Shuai, Cijun

    2016-01-01

    In this study, the mechanical strength and modulus of poly(L-lacti acid) (PLLA) scaffolds were enhanced with the mechanical properties of boron nitride nanosheets (BNNSs) and tetraneedlelike ZnO whiskers (T-ZnOw). The adhesion and proliferation of cells were improved as well as osteogenic differentiation of stem cells was increased. Their dispersion statues in PLLA matrix were improved through a space network structure constructed by three-dimensional T-ZnOw supporting two-dimensional BNNSs. The results showed that the compressive strength, modulus and Vickers hardness of the scaffolds with incorporation of 1 wt% BNNSs and 7 wt% T-ZnOw together were about 96.15%, 32.86% and 357.19% higher than that of the PLLA scaffolds, respectively. This might be due to the effect of the pull out and bridging of BNNSs and T-ZnOw as well as the crack deflection, facilitating the formation of effective stress transfer between the reinforcement phases and the matrix. Furthermore, incorporation of BNNSs and T-ZnOw together into PLLA scaffolds was beneficial for attachment and viability of MG-63 cells. More importantly, the scaffolds significantly increased proliferation and promoted osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The enhanced mechanical and biological properties provide the potentials of PLLA/BNNSs/T-ZnOw scaffolds for the application into bone tissue engineering. PMID:27629058

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

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

    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 -NH2 (399.70 eV) was increased significantly and -N=CH (400.80 eV) and -NH3+ (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.

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

    SciTech Connect

    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

    2013-08-21

    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{sub 2} (399.70 eV) was increased significantly and –N=CH (400.80 eV) and –NH{sub 3}{sup +} (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.

  10. 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.

    PubMed

    Paletta, Juergen; Erffmeier, Karla; Theisen, Christina; Hussain, Daniel; Wendorff, Joachim H; Greiner, Andreas; Fuchs-Winkelmann, Susanne; Schofer, Markus D

    2009-12-16

    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.

  11. An electrically conductive 3D scaffold based on a nonwoven web of poly(L-lactic acid) and conductive poly(3,4-ethylenedioxythiophene).

    PubMed

    Niu, Xufeng; Rouabhia, Mahmoud; Chiffot, Nicolas; King, Martin W; Zhang, Ze

    2015-08-01

    This study was to demonstrate that an extremely thin coating of poly(3,4-ethylenedioxythiophene) (PEDOT) on nonwoven microfibrous poly(l-lactic acid) (PLLA) web is of sufficient electrical conductivity and stability in aqueous environment to sustain electrical stimulation (ES) to cultured human skin fibroblasts. The PEDOT imparted the web a surface resistivity of approximately 0.1 KΩ/square without altering the web morphology. X-ray photoelectron spectroscopy demonstrated that the surface chemistry of the PLLA/PEDOT is characteristic of both PLLA and PEDOT. The PEDOT-coated web also showed higher hydrophilicity, lower glass transition temperature and unchanged fiber crystallinity and thermal stability compared with the PLLA web. The addition of PEDOT to the web marginally increased the web's tensile strength and lowered the elongation. An electrical stability test showed that the PLLA/PEDOT structure was more stable than a polypyrrole treated PLLA fabric, showing only a slow deterioration in conductivity when exposed to culture medium. The cytotoxicity test showed that the PLLA/PEDOT scaffold was not cytotoxic and supported human dermal fibroblast adhesion, migration, and proliferation. Preliminary ES experiments have demonstrated that this conductive web mediated effective ES to fibroblasts. Therefore, this new conductive biodegradable scaffold may be used to electrically modulate cellular activity and tissue regeneration. PMID:25630631

  12. An electrically conductive 3D scaffold based on a nonwoven web of poly(L-lactic acid) and conductive poly(3,4-ethylenedioxythiophene).

    PubMed

    Niu, Xufeng; Rouabhia, Mahmoud; Chiffot, Nicolas; King, Martin W; Zhang, Ze

    2015-08-01

    This study was to demonstrate that an extremely thin coating of poly(3,4-ethylenedioxythiophene) (PEDOT) on nonwoven microfibrous poly(l-lactic acid) (PLLA) web is of sufficient electrical conductivity and stability in aqueous environment to sustain electrical stimulation (ES) to cultured human skin fibroblasts. The PEDOT imparted the web a surface resistivity of approximately 0.1 KΩ/square without altering the web morphology. X-ray photoelectron spectroscopy demonstrated that the surface chemistry of the PLLA/PEDOT is characteristic of both PLLA and PEDOT. The PEDOT-coated web also showed higher hydrophilicity, lower glass transition temperature and unchanged fiber crystallinity and thermal stability compared with the PLLA web. The addition of PEDOT to the web marginally increased the web's tensile strength and lowered the elongation. An electrical stability test showed that the PLLA/PEDOT structure was more stable than a polypyrrole treated PLLA fabric, showing only a slow deterioration in conductivity when exposed to culture medium. The cytotoxicity test showed that the PLLA/PEDOT scaffold was not cytotoxic and supported human dermal fibroblast adhesion, migration, and proliferation. Preliminary ES experiments have demonstrated that this conductive web mediated effective ES to fibroblasts. Therefore, this new conductive biodegradable scaffold may be used to electrically modulate cellular activity and tissue regeneration.

  13. Regulating inflammation using acid-responsive electrospun fibrous scaffolds for skin scarless healing.

    PubMed

    Yuan, Ziming; Zhao, Jingwen; Chen, Yigang; Yang, Zhili; Cui, Wenguo; Zheng, Qi

    2014-01-01

    Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the α-smooth muscle actin (α-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing. PMID:24795507

  14. Regulating inflammation using acid-responsive electrospun fibrous scaffolds for skin scarless healing.

    PubMed

    Yuan, Ziming; Zhao, Jingwen; Chen, Yigang; Yang, Zhili; Cui, Wenguo; Zheng, Qi

    2014-01-01

    Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the α-smooth muscle actin (α-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing.

  15. Regulating Inflammation Using Acid-Responsive Electrospun Fibrous Scaffolds for Skin Scarless Healing

    PubMed Central

    Yuan, Ziming; Zhao, Jingwen; Chen, Yigang; Yang, Zhili; Zheng, Qi

    2014-01-01

    Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the α-smooth muscle actin (α-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing. PMID:24795507

  16. Cytocompatibility of a conductive nanofibrous carbon nanotube/poly (L-Lactic acid) composite scaffold intended for nerve tissue engineering

    PubMed Central

    Kabiri, Mahboubeh; Oraee-Yazdani, Saeed; Dodel, Masumeh; Hanaee-Ahvaz, Hana; Soudi, Sara; Seyedjafari, Ehsan; Salehi, Mohammad; Soleimani, Masoud

    2015-01-01

    The purpose of this study was to fabricate a conductive aligned nanofibrous substrate and evaluate its suitability and cytocompatibility with neural cells for nerve tissue engineering purposes. In order to reach these goals, we first used electrospinning to fabricate single-walled carbon-nanotube (SWCNT) incorporated poly(L-lactic acid) (PLLA) nanofibrous scaffolds and then assessed its cytocompatibility with olfactory ensheathing glial cells (OEC). The plasma treated scaffolds were characterized using scanning electron microscopy and water contact angle. OECs were isolated from olfactory bulb of GFP Sprague-Dawley rats and characterized using OEC specific markers via immunocytochemistry and flow cytometery. The cytocompatibility of the conductive aligned nano-featured scaffold was assessed using microscopy and MTT assay. We indicate that doping of PLLA polymer with SWCNT can augment the aligned nanosized substrate with conductivity, making it favorable for nerve tissue engineering. Our results demonstrated that SWCNT/PLLA composite scaffold promote the adhesion, growth, survival and proliferation of OEC. Regarding the ideal physical, topographical and electrical properties of the scaffold and the neurotrophic and migratory features of the OECs, we suggest this scaffold and the cell/scaffold construct as a promising platform for cell delivery to neural defects in nerve tissue engineering approaches. PMID:26600751

  17. The impact of Fourier-Domain optical coherence tomography catheter induced motion artefacts on quantitative measurements of a PLLA-based bioresorbable scaffold.

    PubMed

    van Ditzhuijzen, N S; Karanasos, A; Bruining, N; van den Heuvel, M; Sorop, O; Ligthart, J; Witberg, K; Garcia-Garcia, H M; Zijlstra, F; Duncker, D J; van Beusekom, H M M; Regar, E

    2014-08-01

    Intracoronary Fourier-Domain optical coherence tomography (FD-OCT) enables imaging of the coronary artery within 2-4 seconds, a so far unparalleled speed. Despite such fast data acquisition, cardiac and respiratory motion can cause artefacts due to longitudinal displacement of the catheter within the artery. We studied the influence of longitudinal FD-OCT catheter displacement on serial global lumen and scaffold area measurements in coronary arteries of swine that received PLLA-based bioresorbable scaffolds. In 10 swine, 20 scaffolds (18 × 3.0 mm) were randomly implanted in two epicardial coronary arteries. Serial FD-OCT imaging was performed immediately after implantation (T1) and at 3 (T2) and 6 months (T3) follow-up. Two methods for the selection of OCT cross-sections were compared. Method A did not take into account longitudinal displacement of the FD-OCT catheter. Method B accounted for longitudinal displacement of the FD-OCT catheter. Fifty-one OCT pullbacks of 17 scaffolds were serially analyzed. The measured scaffold length differed between time points, up to one fourth of the total scaffold length, indicating the presence of longitudinal catheter displacement. Between method A and B, low error was demonstrated for mean area measurements. Correlations between measurements were high: R2 ranged from 0.91 to 0.99 for all mean area measurements at all time points. Considerable longitudinal displacement of the FD-OCT catheter was observed, diminishing the number of truly anatomically matching cross-sections in serial investigations. Global OCT dimensions such as mean lumen and scaffold area were not significantly affected by this displacement. Accurate co-registration of cross-sections, however, is mandatory when specific regions, e.g. jailed side branch ostia, are analyzed.

  18. 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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

    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.

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

    PubMed

    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.

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

    PubMed

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

    2015-12-01

    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. PMID:26551378

  1. A three-dimensional multiporous fibrous scaffold fabricated with regenerated spider silk protein/poly(l-lactic acid) for tissue engineering.

    PubMed

    Yu, Qiaozhen; Sun, Chengjun

    2015-02-01

    An axially aligned three-dimensional (3-D) fibrous scaffold was fabricated with regenerated spider silk protein (RSSP)/poly (l-lactic acid) (PLLA) through electrospinning and post treatment. The morphology, mechanical and degradation properties of the scaffold were controlled through the weight ratio of RSSP to PLLA, the thickness of the scaffold and the treatment time. The scaffold with a weight ratio of 2:3 (RSSP:PLLA) had a nanoleaves-on-nanofibers hierarchical nanostructure; the length and thickness of the nanoleaves were about 400 and 30 nm, respectively. The holes of the scaffolds ranged from hundreds of nanometers to several microns. The scaffold showed an ideal mechanical property that it was stiff when dry, but became soft once hydrated in the culture medium. Its degradation rate was very slow in the first 2 months, and then accelerated in the following 2 months. The pH values of the degradation mediums of all the samples remained in the range of 7.40-7.12 during degradation for 6 months. It had good biocompatibility with PC 12 cells. The aligned hierarchical nanostructure could guide the directions of the axon extension. This scaffold has a potential application in Tissue Engineering and controlled release. This study provides a method to produce synthetic or natural biodegradable polymer scaffold with tailored morphology, mechanical, and degradation properties. PMID:24825592

  2. A three-dimensional multiporous fibrous scaffold fabricated with regenerated spider silk protein/poly(l-lactic acid) for tissue engineering.

    PubMed

    Yu, Qiaozhen; Sun, Chengjun

    2015-02-01

    An axially aligned three-dimensional (3-D) fibrous scaffold was fabricated with regenerated spider silk protein (RSSP)/poly (l-lactic acid) (PLLA) through electrospinning and post treatment. The morphology, mechanical and degradation properties of the scaffold were controlled through the weight ratio of RSSP to PLLA, the thickness of the scaffold and the treatment time. The scaffold with a weight ratio of 2:3 (RSSP:PLLA) had a nanoleaves-on-nanofibers hierarchical nanostructure; the length and thickness of the nanoleaves were about 400 and 30 nm, respectively. The holes of the scaffolds ranged from hundreds of nanometers to several microns. The scaffold showed an ideal mechanical property that it was stiff when dry, but became soft once hydrated in the culture medium. Its degradation rate was very slow in the first 2 months, and then accelerated in the following 2 months. The pH values of the degradation mediums of all the samples remained in the range of 7.40-7.12 during degradation for 6 months. It had good biocompatibility with PC 12 cells. The aligned hierarchical nanostructure could guide the directions of the axon extension. This scaffold has a potential application in Tissue Engineering and controlled release. This study provides a method to produce synthetic or natural biodegradable polymer scaffold with tailored morphology, mechanical, and degradation properties.

  3. Mineralization and drug release of hydroxyapatite/poly(l-lactic acid) nanocomposite scaffolds prepared by Pickering emulsion templating.

    PubMed

    Hu, Yang; Zou, Shengwen; Chen, Weike; Tong, Zhen; Wang, Chaoyang

    2014-10-01

    Biodegradable and bioactive nanocomposite (NC) biomaterials with controlled microstructures and able to deliver special drugs have gained increasing attention in bone tissue engineering. In this study, the hydroxyapatite (HAp)/poly(l-lactic acid) (PLLA) NC scaffolds were facilely prepared using solvent evaporation from templating Pickering emulsions stabilized with PLLA-modified HAp (g-HAp) nanoparticles. Then, in vitro mineralization experiments were performed in a simulated body fluid (SBF) to evaluate the bioactivity of the NC scaffolds. Moreover, in vitro drug release of the NC scaffolds using anti-inflammatory drug (ibuprofen, IBU) as the model drug was also investigated. The results showed that the NC scaffolds possessed interconnected pore structures, which could be modulated by varying the g-HAp nanoparticle concentration. The NC scaffolds exhibited excellent bioactivity, since they induced the formation of calcium-sufficient, carbonated apatite nanoparticles on the scaffolds after mineralization in SBF for 3 days. The IBU loaded in the NC scaffolds showed a sustained release profile, and the release kinetic followed the Higuchi model with diffusion process. Thus, solvent evaporation based on Pickering emulsion droplets is a simple and effective method to prepare biodegradable and bioactive porous NC scaffolds for bone repair and replacement applications.

  4. Evaluation of the novel three-dimensional porous poly (L-lactic acid)/nano-hydroxyapatite composite scaffold.

    PubMed

    Huang, Jianghong; Xiong, Jianyi; Liu, Jianquan; Zhu, Weimin; Chen, Jielin; Duan, Li; Zhang, Jufeng; Wang, Daping

    2015-01-01

    To determine the optimal ratio of nano-hydroxyapatite (n-HA) to polylactic acid (PLLA) in the novel three-dimensional porous PLLA/n-HA composite scaffolds, low-temperature rapid prototyping technology was employed to fabricate the composite materials with different n-HA contents. Mechanical properties and degradation behaviors of the composites were examined, and the scaffold microstructure and n-HA dispersion were observed by scanning electron microscope (SEM). Mechanical tests demonstrated that the tensile strength of the composite material gradually decreased with an increase in n-HA content. When the n-HA content reached 20 wt%, the bending strength of the composite material peaked at 138.5 MPa. SEM images demonstrated that the optimal content of n-HA was 20 wt% as the largest interconnected pore size that can be seen, with a porosity as high as 80%. In vitro degradation experiments demonstrated that the pH value of the material containing solution gradually decreased in a time-dependent manner, with a simultaneous weakening of the mechanical properties. In vitro study using rat osteoblast cells showed that the composite scaffolds were biocompatible; the 20 wt% n-HA scaffold offered particular improvement to rat osteoblast cell adhesion and proliferation compared to other compositions. It was therefore concluded that 20 wt% n-HA is the optimal nano-hydroxyapatite (n-HA) to polylactic acid (PLLA) ratio, with promise for bone tissue engineering. PMID:26405972

  5. Evaluation of the novel three-dimensional porous poly (L-lactic acid)/nano-hydroxyapatite composite scaffold.

    PubMed

    Huang, Jianghong; Xiong, Jianyi; Liu, Jianquan; Zhu, Weimin; Chen, Jielin; Duan, Li; Zhang, Jufeng; Wang, Daping

    2015-01-01

    To determine the optimal ratio of nano-hydroxyapatite (n-HA) to polylactic acid (PLLA) in the novel three-dimensional porous PLLA/n-HA composite scaffolds, low-temperature rapid prototyping technology was employed to fabricate the composite materials with different n-HA contents. Mechanical properties and degradation behaviors of the composites were examined, and the scaffold microstructure and n-HA dispersion were observed by scanning electron microscope (SEM). Mechanical tests demonstrated that the tensile strength of the composite material gradually decreased with an increase in n-HA content. When the n-HA content reached 20 wt%, the bending strength of the composite material peaked at 138.5 MPa. SEM images demonstrated that the optimal content of n-HA was 20 wt% as the largest interconnected pore size that can be seen, with a porosity as high as 80%. In vitro degradation experiments demonstrated that the pH value of the material containing solution gradually decreased in a time-dependent manner, with a simultaneous weakening of the mechanical properties. In vitro study using rat osteoblast cells showed that the composite scaffolds were biocompatible; the 20 wt% n-HA scaffold offered particular improvement to rat osteoblast cell adhesion and proliferation compared to other compositions. It was therefore concluded that 20 wt% n-HA is the optimal nano-hydroxyapatite (n-HA) to polylactic acid (PLLA) ratio, with promise for bone tissue engineering.

  6. Additive and synergistic effects of bFGF and hypoxia on leporine meniscus cell-seeded PLLA scaffolds

    PubMed Central

    Gunja, Najmuddin J.; Athanasiou, Kyriacos A.

    2009-01-01

    Injuries to avascular regions of menisci do not heal and result in significant discomfort to patients. Current treatments, such as partial meniscectomy, alleviate these symptoms in the short-term, but lead to premature osteoarthritis as a result of compromised stability and changes in knee biomechanics. Thus, tissue engineering of the meniscus may provide an alternative treatment modality to overcome this problem. In this experiment, a scaffold-based tissue engineering approach was utilized to regenerate the meniscus. Meniscus cells were cultured on poly-l-lactic acid scaffolds in normoxic (~21% oxygen) or hypoxic (~2% oxygen) conditions in the presence or absence of the growth factor, basic fibroblast growth factor (bFGF). At t = 4 wks, histological sections of constructs showed presence of collagen and glycosaminoglycan (GAG) in all groups. Immunohistochemical staining showed presence of collagen I in all groups, and collagen II in groups cultured in hypoxic conditions. bFGF in the culture medium significantly increased cell number/construct by 25%, regardless of culturing condition. For GAG/construct, synergistic increases were observed in constructs cultured in hypoxic conditions and bFGF (2-fold) when compared to constructs cultured in normoxic conditions. Compressive tests showed synergistic increases in the relaxation modulus and coefficient of viscosity, and additive increases in the instantaneous modulus for constructs cultured in hypoxic conditions and bFGF when compared to constructs cultured in normoxic conditions. Overall, these results demonstrate that bFGF and hypoxia can significantly enhance the ability of meniscus cells to produce GAGs and improve the compressive properties of tissue engineered meniscus constructs in vitro. PMID:19937913

  7. In vitro hemocompatibility and cytocompatibility of a three-layered vascular scaffold fabricated by sequential electrospinning of PCL, collagen, and PLLA nanofibers.

    PubMed

    Haghjooy Javanmard, Shaghayegh; Anari, Jamal; Zargar Kharazi, Anousheh; Vatankhah, Elham

    2016-09-01

    Aiming to mimic a blood vessel structurally, morphologically, and mechanically, a sequential electrospinning technique using a small diameter mandrel collector was performed and a three-layered tubular scaffold composed of nanofibers of polycaprolactone, collagen, and poly(l-lactic acid) as inner, intermediate, and outer layers, respectively, was developed. Biological performances of the scaffold in terms of compatibility with blood and endothelial cells were assessed to get some insights into its potential use as a tissue engineered small-diameter vascular replacement compared to an expanded polytetrafluoroethylene vascular graft. Due to direct contact of the blood and endothelial cells with inner surface of the scaffold, polycaprolactone fibers were characterized using SEM, water contact angle measurement, and ATR-FTIR. Despite similar surface wettability of the electrospun scaffold and the expanded polytetrafluoroethylene graft, the three-layered scaffold significantly reduced platelet adhesion and hemolysis ratio compared to expanded polytetrafluoroethylene graft while comparable blood clotting profiles were observed for both electrospun scaffold and expanded polytetrafluoroethylene graft. However, inflammatory response to nanofibrous surface of the scaffold was reduced compared to expanded polytetrafluoroethylene graft. The electrospun scaffold also presented a significantly more supportive substrate for endothelialization than the expanded polytetrafluoroethylene graft. The results described herein suggested that the three-layered scaffold has superior biological properties compared to an expanded polytetrafluoroethylene graft for vascular tissue engineering. PMID:27247131

  8. In vitro hemocompatibility and cytocompatibility of a three-layered vascular scaffold fabricated by sequential electrospinning of PCL, collagen, and PLLA nanofibers.

    PubMed

    Haghjooy Javanmard, Shaghayegh; Anari, Jamal; Zargar Kharazi, Anousheh; Vatankhah, Elham

    2016-09-01

    Aiming to mimic a blood vessel structurally, morphologically, and mechanically, a sequential electrospinning technique using a small diameter mandrel collector was performed and a three-layered tubular scaffold composed of nanofibers of polycaprolactone, collagen, and poly(l-lactic acid) as inner, intermediate, and outer layers, respectively, was developed. Biological performances of the scaffold in terms of compatibility with blood and endothelial cells were assessed to get some insights into its potential use as a tissue engineered small-diameter vascular replacement compared to an expanded polytetrafluoroethylene vascular graft. Due to direct contact of the blood and endothelial cells with inner surface of the scaffold, polycaprolactone fibers were characterized using SEM, water contact angle measurement, and ATR-FTIR. Despite similar surface wettability of the electrospun scaffold and the expanded polytetrafluoroethylene graft, the three-layered scaffold significantly reduced platelet adhesion and hemolysis ratio compared to expanded polytetrafluoroethylene graft while comparable blood clotting profiles were observed for both electrospun scaffold and expanded polytetrafluoroethylene graft. However, inflammatory response to nanofibrous surface of the scaffold was reduced compared to expanded polytetrafluoroethylene graft. The electrospun scaffold also presented a significantly more supportive substrate for endothelialization than the expanded polytetrafluoroethylene graft. The results described herein suggested that the three-layered scaffold has superior biological properties compared to an expanded polytetrafluoroethylene graft for vascular tissue engineering.

  9. A Tissue-Specific Scaffold for Tissue Engineering-Based Ureteral Reconstruction

    PubMed Central

    Xu, Yongde; Fu, Weijun; Wang, Zhongxin; Li, Gang; Zhang, Xu

    2015-01-01

    Terminally differentiated somatic cells can rapidly change phenotypes when they are isolated from their native tissue and cultured in vitro. This problem may become a barrier to tissue engineering-based organ reconstruction, which utilizes somatic cells. The present study was designed to validate the feasibility of maintaining the urothelial cell phenotype in a tissue-specific ureteral scaffold. The tissue-specific scaffold was fabricated by blending poly (L-lactic acid) (PLLA) and ureteral extracellular matrix (UECM) using electrostatic spinning technology. PLLA was used to enhance the mechanical properties, and UECM was used to mimic the natural components of the ureter. Primary urothelial cells (UCs), derived from ureteral mucosa, were seeded onto the tissue-specific scaffold to assess cell adhesion, proliferation and phenotypes at designated time points. The results showed that UCs in the tissue-specific scaffold exhibited better proliferation compared to cells in pure PLLA or a PLLA-small intestinal submucosa (PLLA-SIS) scaffold (p<0.05). At different time points, the expression of a UC-specific marker (UroplakinⅢ) in the tissue-specific scaffold was significantly higher than its expression in pure PLLA or a PLLA-SIS scaffold (p<0.05). Therefore, the tissue-specific scaffold appears to be an ideal substrate for promoting UC survival and phenotype maintenance. PMID:25775033

  10. Electrospun nanofibrous scaffolds of segmented polyurethanes based on PEG, PLLA and PTMC blocks: Physico-chemical properties and morphology.

    PubMed

    Trinca, Rafael Bergamo; Abraham, Gustavo A; Felisberti, Maria Isabel

    2015-11-01

    Biocompatible polymeric scaffolds are crucial for successful tissue engineering. Biomedical segmented polyurethanes (SPUs) are an important and versatile class of polymers characterized by a broad spectrum of compositions, molecular architectures, properties and applications. Although SPUs are versatile materials that can be designed by different routes to cover a wide range of properties, they have been infrequently used for the preparation of electrospun nanofibrous scaffolds. This study reports the preparation of new electrospun polyurethane scaffolds. The segmented polyurethanes were synthesized using low molar masses macrodyols (poly(ethylene glycol), poly(l-lactide) and poly(trimethylene carbonate)) and 1,6-hexane diisocyanate and 1,4-butanodiol as isocyanate and chain extensor, respectively. Different electrospinning parameters such as solution properties and processing conditions were evaluated to achieve smooth, uniform bead-free fibers. Electrospun micro/nanofibrous structures with mean fiber diameters ranging from 600nm to 770nm were obtained by varying the processing conditions. They were characterized in terms of thermal and dynamical mechanical properties, swelling degree and morphology. The elastomeric polyurethane scaffolds exhibit interesting properties that could be appropriate as biomimetic matrices for soft tissue engineering applications. PMID:26249621

  11. Electrospun nanofibrous scaffolds of segmented polyurethanes based on PEG, PLLA and PTMC blocks: Physico-chemical properties and morphology.

    PubMed

    Trinca, Rafael Bergamo; Abraham, Gustavo A; Felisberti, Maria Isabel

    2015-11-01

    Biocompatible polymeric scaffolds are crucial for successful tissue engineering. Biomedical segmented polyurethanes (SPUs) are an important and versatile class of polymers characterized by a broad spectrum of compositions, molecular architectures, properties and applications. Although SPUs are versatile materials that can be designed by different routes to cover a wide range of properties, they have been infrequently used for the preparation of electrospun nanofibrous scaffolds. This study reports the preparation of new electrospun polyurethane scaffolds. The segmented polyurethanes were synthesized using low molar masses macrodyols (poly(ethylene glycol), poly(l-lactide) and poly(trimethylene carbonate)) and 1,6-hexane diisocyanate and 1,4-butanodiol as isocyanate and chain extensor, respectively. Different electrospinning parameters such as solution properties and processing conditions were evaluated to achieve smooth, uniform bead-free fibers. Electrospun micro/nanofibrous structures with mean fiber diameters ranging from 600nm to 770nm were obtained by varying the processing conditions. They were characterized in terms of thermal and dynamical mechanical properties, swelling degree and morphology. The elastomeric polyurethane scaffolds exhibit interesting properties that could be appropriate as biomimetic matrices for soft tissue engineering applications.

  12. PHEA-PLLA: A New Polymer Blend For Tissue Engineering Applications

    NASA Astrophysics Data System (ADS)

    Pavia, Francesco Carfi; La Carrubba, Vincenzo; Palumbo, Fabio; Giammona, Gaetano; Brucato, Valerio

    2011-05-01

    One of most important features that a material should have in order to be utilized for tissue engineering applications is its biocompatibility and its chemical surface. These properties are required for a high degree of cell adhesion on the scaffold. Poly-L-lactid acid (PLLA) is a biocompatible synthetic polymer approved by the Food and Drug Administration for human clinical applications. It has been largely employed, in the last years, as a constituent of surgical and implantable devices. PHEA is a biocompatible water-soluble synthetic polymer, with a protein-like structure, whose use as a drug carrier and as starting material for many other biomedical and pharmaceutical applications has been reported in the literature. In this work a copolymer (PHEA-PLLA) of the aforementioned polymers was synthesized and characterized the possibility to produce porous scaffolds with it was assessed. The results have shown that is possible to prepare scaffolds of PHEA-PLLA via Thermally Induced Phase Separation (TIPS). The scaffolds as-obtained present on theirs bulk an open porous structure with interconnected pores whose average pore size was ˜ 20 μm. Moreover a cloud point curve for the system PHEA-PLLA/Dioxane/water was built in order to find the more appropriate temperatures for the TIPS process.

  13. In Vivo Differentiation of Mesenchymal Stem Cells into Insulin Producing Cells on Electrospun Poly-L-Lactide Acid Scaffolds Coated with Matricaria chamomilla L. Oil

    PubMed Central

    Fazili, Afsaneh; Gholami, Soghra; Minaie Zangi, Bagher; Seyedjafari, Ehsan; Gholami, Mahdi

    2016-01-01

    Objective This study examined the in vivo differentiation of mesenchymal stem cells (MSCs) into insulin producing cells (IPCs) on electrospun poly-L-lactide acid (PLLA) scaffolds coated with Matricaria chammomila L. (chamomile) oil. Materials and Methods In this interventional, experimental study adipose MSCs (AMSCs) were isolated from 12 adult male New Zealand white rabbits and characterized by flow cytometry. AMSCs were subsequently differentiated into osteogenic and adipogenic lines. Cells were seeded onto either a PLLA scaffold (control) or PLLA scaffold coated with chamomile oil (experimental). A total of 24 scaffolds were inserted into the pancreatic area of each rabbit and placement was confirmed by ultrasound. After 21 days, immunohistochemistry analysis of insulin-producing like cells on protein levels confirmed insulin expression of insulin producing cells (IPSCs). Real-time polymerase chain reaction (PCR) determined the expressions of genes related to pancreatic endocrine development and function. Results Fourier transform infrared spectroscopy (FTIR) results confirmed the existence of oil on the surface of the PLLA scaffold. The results showed a new peak at 2854 cm-1 for the aliphatic CH2 bond. Pdx1 expression was 0.051 ± 0.007 in the experimental group and 0.009 ± 0.002 in the control group. There was significantly increased insulin expression in the scaffold coated with chamomile oil (0.09 ± 0.001) compared to control group (0.063 ± 0.009, P≤0.05). Both groups expressed Ngn3 and Pdx1 specific markers and pancreatic tissue was observed at 21 days post transplantation. Conclusion The pancreatic region is an optimal site for differentiation of AMSCs to IPCs. Chamomile oil (as an antioxidant agent) can affect cell adhesion to the scaffold and increase cell differentiation. In addition, the oil may lead to increased blood glucose uptake in pathways in the muscles, liver and fatty tissue of a diabetic animal model by some probable molecular mechanisms

  14. In Vivo Differentiation of Mesenchymal Stem Cells into Insulin Producing Cells on Electrospun Poly-L-Lactide Acid Scaffolds Coated with Matricaria chamomilla L. Oil

    PubMed Central

    Fazili, Afsaneh; Gholami, Soghra; Minaie Zangi, Bagher; Seyedjafari, Ehsan; Gholami, Mahdi

    2016-01-01

    Objective This study examined the in vivo differentiation of mesenchymal stem cells (MSCs) into insulin producing cells (IPCs) on electrospun poly-L-lactide acid (PLLA) scaffolds coated with Matricaria chammomila L. (chamomile) oil. Materials and Methods In this interventional, experimental study adipose MSCs (AMSCs) were isolated from 12 adult male New Zealand white rabbits and characterized by flow cytometry. AMSCs were subsequently differentiated into osteogenic and adipogenic lines. Cells were seeded onto either a PLLA scaffold (control) or PLLA scaffold coated with chamomile oil (experimental). A total of 24 scaffolds were inserted into the pancreatic area of each rabbit and placement was confirmed by ultrasound. After 21 days, immunohistochemistry analysis of insulin-producing like cells on protein levels confirmed insulin expression of insulin producing cells (IPSCs). Real-time polymerase chain reaction (PCR) determined the expressions of genes related to pancreatic endocrine development and function. Results Fourier transform infrared spectroscopy (FTIR) results confirmed the existence of oil on the surface of the PLLA scaffold. The results showed a new peak at 2854 cm-1 for the aliphatic CH2 bond. Pdx1 expression was 0.051 ± 0.007 in the experimental group and 0.009 ± 0.002 in the control group. There was significantly increased insulin expression in the scaffold coated with chamomile oil (0.09 ± 0.001) compared to control group (0.063 ± 0.009, P≤0.05). Both groups expressed Ngn3 and Pdx1 specific markers and pancreatic tissue was observed at 21 days post transplantation. Conclusion The pancreatic region is an optimal site for differentiation of AMSCs to IPCs. Chamomile oil (as an antioxidant agent) can affect cell adhesion to the scaffold and increase cell differentiation. In addition, the oil may lead to increased blood glucose uptake in pathways in the muscles, liver and fatty tissue of a diabetic animal model by some probable molecular mechanisms.

  15. The odontogenic differentiation of human dental pulp stem cells on nanofibrous poly(L-lactic acid) scaffolds in vitro and in vivo.

    PubMed

    Wang, Jing; Liu, Xiaohua; Jin, Xiaobing; Ma, Haiyun; Hu, Jiang; Ni, Longxing; Ma, Peter X

    2010-10-01

    The aim of this study was to investigate the odontogenic differentiation of human dental pulp stem cells (DPSCs) on nanofibrous (NF)-poly(l-lactic acid) (PLLA) scaffolds in vitro and in vivo. Highly porous NF-PLLA scaffolds which mimic the architecture of collagen type I fibers were fabricated by the combination of a phase-separation technique and a porogen-leaching method. The human DPSCs were then seeded onto the scaffolds and cultured in different media for odontogenic differentiation: "Control" medium without supplements; "DXM" medium containing 10(-8)M dexamethasone (DXM), 50 microgml(-1) ascorbic acid and 5mM beta-glycerophosphate; "BMP-7+DXM" medium containing 10(-8)M DXM, 50 microgml(-1) ascorbic acid, 5mM beta-glycerophosphate plus 50 ngml(-1) bone morphogenetic protein 7 (BMP-7). For odontogenic differentiation study in vitro, alkaline phosphatase activity quantification, reverse transcription polymerase chain reaction, scanning electron microscopy, von Kossa staining and calcium content quantification were carried out. While both "DXM" medium and "BMP-7+DXM" medium induced the DPSCs to odontoblast-like cells, the "BMP-7+DXM" medium had greater inducing capacity than the "DXM" medium. Consistent with the in vitro studies, the "BMP-7+DXM" group presented more extracellular matrix and hard tissue formation than the "DXM" group after 8 weeks of ectopic implantation in nude mice. Differentiation of DPSCs into odontoblast-like cells was identified by the positive immunohistochemical staining for dentin sialoprotein. In conclusion, odontogenic differentiation of DPSCs can be achieved on NF-PLLA scaffolds both in vitro and in vivo; the combination of BMP-7 and DXM induced the odontogenic differentiation more effectively than DXM alone. The NF-PLLA scaffold and the combined odontogenic inductive factors provide excellent environment for DPSCs to regenerate dental pulp and dentin. PMID:20406702

  16. Preparation of poly(L-lactic acid) nanofiber scaffolds with a rough surface by phase inversion using supercritical carbon dioxide.

    PubMed

    Yang, Ding-Zhu; Chen, Ai-Zheng; Wang, Shi-Bin; Li, Yi; Tang, Xiao-Lin; Wu, Yong-Jing

    2015-06-01

    Phase inversion using supercritical carbon dioxide (SC-CO2) has been widely used in the development of tissue engineering scaffolds, and particular attention has been given to obtaining desired morphology without additional post-treatments. However, the main challenge of this technique is the difficulty in generating a three-dimensional (3D) nanofiber structure with a rough surface in one step. Here, a poly(L-lactic acid) (PLLA) 3D nanofiber scaffold with a rough surface is obtained via phase inversion using SC-CO2 by carefully choosing fabrication conditions and porogens. It is found that this method can effectively modulate the structure morphology, promote the crystallization process of semicrystalline polymer, and induce the formation of rough structures on the surface of nanofibers. Meanwhile, the porogen of ammonium bicarbonate (AB) can produce a 3D structure with large pores, and porogen of menthol can improve the interconnectivity between the micropores of nanofibers. A significant increase in the fiber diameter is observed as the menthol content increases. Furthermore, the menthol may affect the mutual transition between the α' and α crystals of PLLA during the phase separation process. In addition, the results of protein adsorption, cell adhesion, and proliferation assays indicate that cells tend to have higher viability on the nanofiber scaffold. This process combines the characteristic properties of SC-CO2 and the solubility of menthol to tailor the morphology of polymeric scaffolds, which may have potential applications in tissue engineering. PMID:26107415

  17. Preparation of poly(L-lactic acid) nanofiber scaffolds with a rough surface by phase inversion using supercritical carbon dioxide.

    PubMed

    Yang, Ding-Zhu; Chen, Ai-Zheng; Wang, Shi-Bin; Li, Yi; Tang, Xiao-Lin; Wu, Yong-Jing

    2015-06-24

    Phase inversion using supercritical carbon dioxide (SC-CO2) has been widely used in the development of tissue engineering scaffolds, and particular attention has been given to obtaining desired morphology without additional post-treatments. However, the main challenge of this technique is the difficulty in generating a three-dimensional (3D) nanofiber structure with a rough surface in one step. Here, a poly(L-lactic acid) (PLLA) 3D nanofiber scaffold with a rough surface is obtained via phase inversion using SC-CO2 by carefully choosing fabrication conditions and porogens. It is found that this method can effectively modulate the structure morphology, promote the crystallization process of semicrystalline polymer, and induce the formation of rough structures on the surface of nanofibers. Meanwhile, the porogen of ammonium bicarbonate (AB) can produce a 3D structure with large pores, and porogen of menthol can improve the interconnectivity between the micropores of nanofibers. A significant increase in the fiber diameter is observed as the menthol content increases. Furthermore, the menthol may affect the mutual transition between the α' and α crystals of PLLA during the phase separation process. In addition, the results of protein adsorption, cell adhesion, and proliferation assays indicate that cells tend to have higher viability on the nanofiber scaffold. This process combines the characteristic properties of SC-CO2 and the solubility of menthol to tailor the morphology of polymeric scaffolds, which may have potential applications in tissue engineering.

  18. Poly(l-Lactic Acid)/Gelatin Fibrous Scaffold Loaded with Simvastatin/Beta-Cyclodextrin-Modified Hydroxyapatite Inclusion Complex for Bone Tissue Regeneration.

    PubMed

    Lee, Jung Bok; Kim, Ji Eun; Balikov, Daniel A; Bae, Min Soo; Heo, Dong Nyoung; Lee, Donghyun; Rim, Hyun Joon; Lee, Deok-Won; Sung, Hak-Joon; Kwon, Il Keun

    2016-07-01

    Recently, the application of nanostructured materials in the field of tissue engineering has garnered attention to mediate treatment and regeneration of bone defects. In this study, poly(l-lactic acid) (PLLA)/gelatin (PG) fibrous scaffolds are fabricated and β-cyclodextrin (βCD) grafted nano-hydroxyapatite (HAp) is coated onto the fibrous scaffold surface via an interaction between βCD and adamantane. Simvastatin (SIM), which is known to promote osteoblast viability and differentiation, is loaded into the remaining βCD. The specimen morphologies are characterized by scanning electron microscopy. The release profile of SIM from the drug loaded scaffold is also evaluated. In vitro proliferation and osteogenic differentiation of human adipose derived stem cells on SIM/HAp coated PG composite scaffolds is characterized by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and real time Polymerase chain reaction (PCR). The scaffolds are then implanted into rabbit calvarial defects and analyzed by microcomputed tomography for bone formation after four and eight weeks. These results demonstrate that SIM loaded PLLA/gelatin/HAp-(βCD) scaffolds promote significantly higher ALP activity, mineralization, osteogenic gene expression, and bone regeneration than control scaffolds. This suggests the potential application of this material toward bone tissue engineering. PMID:26996294

  19. Poly(l-Lactic Acid)/Gelatin Fibrous Scaffold Loaded with Simvastatin/Beta-Cyclodextrin-Modified Hydroxyapatite Inclusion Complex for Bone Tissue Regeneration.

    PubMed

    Lee, Jung Bok; Kim, Ji Eun; Balikov, Daniel A; Bae, Min Soo; Heo, Dong Nyoung; Lee, Donghyun; Rim, Hyun Joon; Lee, Deok-Won; Sung, Hak-Joon; Kwon, Il Keun

    2016-07-01

    Recently, the application of nanostructured materials in the field of tissue engineering has garnered attention to mediate treatment and regeneration of bone defects. In this study, poly(l-lactic acid) (PLLA)/gelatin (PG) fibrous scaffolds are fabricated and β-cyclodextrin (βCD) grafted nano-hydroxyapatite (HAp) is coated onto the fibrous scaffold surface via an interaction between βCD and adamantane. Simvastatin (SIM), which is known to promote osteoblast viability and differentiation, is loaded into the remaining βCD. The specimen morphologies are characterized by scanning electron microscopy. The release profile of SIM from the drug loaded scaffold is also evaluated. In vitro proliferation and osteogenic differentiation of human adipose derived stem cells on SIM/HAp coated PG composite scaffolds is characterized by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and real time Polymerase chain reaction (PCR). The scaffolds are then implanted into rabbit calvarial defects and analyzed by microcomputed tomography for bone formation after four and eight weeks. These results demonstrate that SIM loaded PLLA/gelatin/HAp-(βCD) scaffolds promote significantly higher ALP activity, mineralization, osteogenic gene expression, and bone regeneration than control scaffolds. This suggests the potential application of this material toward bone tissue engineering.

  20. The effect of scaffold architecture on odontogenic differentiation of human dental pulp stem cells.

    PubMed

    Wang, Jing; Ma, Haiyun; Jin, Xiaobing; Hu, Jiang; Liu, Xiaohua; Ni, Longxing; Ma, Peter X

    2011-11-01

    Previous studies have shown the superiority of nanofibrous (NF) poly(l-lactic acid) (PLLA) scaffolds in supporting the osteogenic differentiation of a few cell types and bone regeneration. The aim of the current study was to investigate whether NF-PLLA scaffolds are advantageous for the odontogenic differentiation and mineralization of human dental pulp stem cells (DPSCs) over solid-walled (SW) PLLA scaffolds. The in vitro studies demonstrated that, compared with SW scaffolds, NF scaffolds enhanced attachment and proliferation as well as odontogenic differentiation of human DPSCs. The alkaline phosphatase (ALP) activity and the expression of odontogenic genes of human DPSCs were increased on NF scaffolds compared with that on SW scaffolds. In addition, more mineral deposition was observed on the NF scaffolds, as demonstrated by von Kossa staining, calcium content measurement and scanning electron microscopy. Consistent with the in vitro studies, NF scaffolds promoted odontogenic differentiation and hard tissue formation compared with SW scaffolds after 8 weeks of ectopic transplantation in nude mice, as confirmed by von Kossa staining, Masson's trichrome staining and immunohistochemical staining for dentin sialoprotein. In conclusion, NF-PLLA scaffolds enhanced the odontogenic differentiation of human DPSCs and mineralization both in vitro and in vivo, and are promising scaffolds for dentin regeneration.

  1. Investigation of microstructure, mechanical properties and cellular viability of poly(L-lactic acid) tissue engineering scaffolds prepared by different thermally induced phase separation protocols.

    PubMed

    Molladavoodi, Sara; Gorbet, Maud; Medley, John; Kwon, Hyock Ju

    2013-01-01

    Two thermally induced phase separation (TIPS) methods have been used to fabricate biodegradable poly(L-lactic acid) (PLLA) tissue engineering scaffolds each with fibrous (F-TIPS) and porous (P-TIPS) microstructures. Three levels of PLLA concentration (3, 5 and 7 wt%) were employed in each fabrication method and both wet and dry specimens were studied. Simple compression testing revealed that an elastic-plastic representation of the mechanical behavior was possible for all specimens. Both elastic and plastic moduli were higher for the P-TIPS, for higher polymer concentration, and might be somewhat higher for dry as opposed to wet specimens. For F-TIPS specimens, permanent deformation occurred successively during cyclic deformation but a "memory effect" simplified the behavior. Although F-TIPS microstructure better resembled the natural extracellular matrix, human osteosarcoma fibroblast cells showed more consistent viability in the P-TIPS scaffolds under our unloaded test protocols. Biodegradation in cell culture medium resulted in a decreased elastic moduli for F-TIPS specimens. Information presented regarding the microstructure, mechanical properties and cell viability of these PLLA scaffolds that should help reduce the number of iterations involved in developing tissue engineering products.

  2. Use of Micro-Computed Tomography to Nondestructively Characterize Biomineral Coatings on Solid Freeform Fabricated Poly (L-Lactic Acid) and Poly (ɛ-Caprolactone) Scaffolds In Vitro and In Vivo

    PubMed Central

    Saito, Eiji; Suarez-Gonzalez, Darilis; Rao, Rameshwar R.; Stegemann, Jan P.; Murphy, William L.

    2013-01-01

    Biomineral coatings have been extensively used to enhance the osteoconductivity of polymeric scaffolds. Numerous porous scaffolds have previously been coated with a bone-like apatite mineral through incubation in simulated body fluid (SBF). However, characterization of the mineral layer formed on scaffolds, including the amount of mineral within the scaffolds, often requires destructive methods. We have developed a method using micro-computed tomography (μ-CT) scanning to nondestructively quantify the amount of mineral in vitro and in vivo on biodegradable scaffolds made of poly (L-lactic acid) (PLLA) and poly (ɛ-caprolactone) (PCL). PLLA and PCL scaffolds were fabricated using an indirect solid freeform fabrication (SFF) technique to achieve orthogonally interconnected pore architectures. Biomineral coatings were formed on the fabricated PLLA and PCL scaffolds after incubation in modified SBF (mSBF). Scanning electron microscopy and X-ray diffraction confirmed the formation of an apatite-like mineral. The scaffolds were implanted into mouse ectopic sites for 3 and 10 weeks. The presence of a biomineral coating within the porous scaffolds was confirmed through plastic embedding and μ-CT techniques. Tissue mineral content (TMC) and volume of mineral on the scaffold surfaces detected by μ-CT had a strong correlation with the amount of calcium measured by the orthocresolphthalein complex-one (OCPC) method before and after implantation. There was a strong correlation between OCPC pre- and postimplantation and μ-CT measured TMC (R2=0.96 preimplant; R2=0.90 postimplant) and mineral volume (R2=0.96 preimplant; R2=0.89 postimplant). The μ-CT technique showed increases in mineral following implantation, suggesting that μ-CT can be used to nondestructively determine the amount of calcium on coated scaffolds. PMID:23134479

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Synthesis of PDLLA/PLLA-bentonite nanocomposite through sonication

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

    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.

  5. Tubular perfusion system culture of human mesenchymal stem cells on poly-l-lactic acid scaffolds produced using a supercritical carbon dioxide-assisted process

    PubMed Central

    Pisanti, Paola; Yeatts, Andrew B.; Cardea, Stefano; Fisher, John P.; Reverchon, Ernesto

    2012-01-01

    In vitro human mesenchymal stem cell (hMSC) proliferation and differentiation is dependent on scaffold design parameters and specific culture conditions. In this study, we investigate how scaffold microstructure influences hMSC behavior in a perfusion bioreactor system. Poly-l-lactic acid (PLLA) scaffolds are fabricated using supercritical carbon dioxide (SC-CO2) gel drying. This production method results in scaffolds fabricated with nanostructure. To introduce a microporous structure, porogen leaching was used in addition to this technique to produce scaffolds of average pore size of 100, 250, and 500 µm. These scaffolds were then cultured in static culture in well plates or dynamic culture in the tubular perfusion system (TPS) bioreactor. Results indicated that hMSCs were able to attach and maintain viability on all scaffolds with higher proliferation in the 250 µm and 500 µm pore sizes of bioreactor cultured scaffolds and 100 µm pore size of statically cultured scaffolds. Osteoblastic differentiation was enhanced in TPS culture as compared to static culture with the highest alkaline phosphatase expression observed in the 250 µm pore size group. Bone morphogenetic protein-2 was also analyzed and expression levels were highest in the 250 µm and 500 µm pore size bioreactor cultured samples. These results demonstrate cellular response to pore size as well as the ability of dynamic culture to enhance these effects. PMID:22528808

  6. Composite Membranes of Recombinant Silkworm Antimicrobial Peptide and Poly (L-lactic Acid) (PLLA) for biomedical application.

    PubMed

    Li, Zhi; Liu, Xuan; Li, Yi; Lan, Xiqian; Leung, Polly Hangmei; Li, Jiashen; Li, Gang; Xie, Maobin; Han, Yanxia; Lin, Xiaofen

    2016-01-01

    Antimicrobial peptides, produced by innate immune system of hosts in response to invading pathogens, are capable of fighting against a spectrum of bacteria, viruses, fungi, parasites and cancer cells. Here, a recombinant silkworm AMP Bmattacin2 from heterologous expression is studied, indicating a broad spectrum of antibacterial activity and showing selective killing ability towards skin and colon cancer cells over their normal cell counterparts. For the purpose of biomedical application, the electrospinning fabrication technique is employed to load Bmattacin2 into PLLA nanofibrous membrane. In addition to a good compatibility with the normal cells, Bmattacin2 loaded nanofibrous membranes demonstrate instant antibacterial effects and sustained anticancer effects. The cancer cell and bacteria targeting dynamics of recombinant Bmattacin2 are investigated. With these characteristics, PLLA/Bmattacin2 composite membranes have a great potential for developing novel biomedical applications such as cancer therapies and wound healing treatments. PMID:27503270

  7. Composite Membranes of Recombinant Silkworm Antimicrobial Peptide and Poly (L-lactic Acid) (PLLA) for biomedical application

    PubMed Central

    Li, Zhi; Liu, Xuan; Li, Yi; Lan, Xiqian; Leung, Polly Hangmei; Li, Jiashen; Li, Gang; Xie, Maobin; Han, Yanxia; Lin, Xiaofen

    2016-01-01

    Antimicrobial peptides, produced by innate immune system of hosts in response to invading pathogens, are capable of fighting against a spectrum of bacteria, viruses, fungi, parasites and cancer cells. Here, a recombinant silkworm AMP Bmattacin2 from heterologous expression is studied, indicating a broad spectrum of antibacterial activity and showing selective killing ability towards skin and colon cancer cells over their normal cell counterparts. For the purpose of biomedical application, the electrospinning fabrication technique is employed to load Bmattacin2 into PLLA nanofibrous membrane. In addition to a good compatibility with the normal cells, Bmattacin2 loaded nanofibrous membranes demonstrate instant antibacterial effects and sustained anticancer effects. The cancer cell and bacteria targeting dynamics of recombinant Bmattacin2 are investigated. With these characteristics, PLLA/Bmattacin2 composite membranes have a great potential for developing novel biomedical applications such as cancer therapies and wound healing treatments. PMID:27503270

  8. Electrospinning of aniline pentamer-graft-gelatin/PLLA nanofibers for bone tissue engineering.

    PubMed

    Liu, Yadong; Cui, Haitao; Zhuang, Xiuli; Wei, Yen; Chen, Xuesi

    2014-12-01

    Blends of aniline pentamer-graft-gelatin (AP-g-GA) and poly(l-lactide) (PLLA) were electrospun to prepare uniform nanofibers as biomimetic scaffolds. The nanofibers exhibited good electroactivity, thermal stability and biodegradability. The biocompatibility of the nanofibers in vitro was evaluated by the adhesion and proliferation of mouse preosteoblastic MC3T3-E1 cells. The cellular elongation was significantly greater on electroactive AP-g-GA/PLLA nanofibers than on PLLA nanofibers. Moreover, the AP-g-GA/PLLA nanofibers stimulated by an electrical pulsed signal could promote the differentiation of MC3T3-E1 cells compared with pure PLLA nanofibers. Our results demonstrated that the biodegradable and electroactive AP-g-GA/PLLA nanofibers had potential application in vivo as bone repair scaffold materials in tissue engineering.

  9. Osteogenic/Odontogenic Bioengineering with co-Administration of Simvastatin and Hydroxyapatite on Poly Caprolactone Based Nanofibrous Scaffold

    PubMed Central

    Samiei, Mohammad; Aghazadeh, Marziyeh; Alizadeh, Effat; Aslaminabadi, Naser; Davaran, Soodabeh; Shirazi, Sajjad; Ashrafi, Farhad; Salehi, Roya

    2016-01-01

    Purpose: Statin is an effective factor for promoting osteogenesis. The aim of the present study was to evaluate the effect of simvastatin (SIM) and/or HA addition on changes in osteogenesis levels by human DPSCs transferred onto three-dimensional (3D) nanofibrous Poly (ε-caprolactone) (PCL)/Poly lactic acide (PLLA) polymeric scaffolds. Methods: For this purpose, a 3D nanofibrous composite scaffold of PCL/PLLA/HA was prepared by electrospinning method. SIM was added to scaffolds during DPSCs culturing step. Cell proliferation and osteogenic activity levels were assessed by using MTT assay and Alizarin Red assay methods. In addition, the expression of genes responsible for osteogenesis, including BMP2, Osteocalcin, DSPP and RUNX2, were determined before and 2 weeks after incorporation of SIM. Results: The MTT assay showed that PCL/PLLA/HA scaffolds seeded with DPSCs has significant (p<0.05) more proliferative effect than PCL/PLLA or DMEM cultured cells, additionally SIM administration improved this result over the PCL/PLLA/HA scaffolds without SIM treatment. SEM imaging revealed improved adhesion and probably osteogenic differentiation of DPSCs on PCL/PLLA/HA nanofibers treated with SIM, moreover the alizarin red assay ensured significant (p<0.05) higher mineralization of this group. Finally, real time PCR confirmed the positive regulation (P<0.05) of the expression of osteo/odontogenesis markers BMP2, Osteocalcin, DSPP and RUNX2 genes in PLLA-PCL-HA (0.1)-SIM group. Conclusion: As a result, addition of simvastatin with incorporation of hydroxyapatite in PCL-PLLA scaffolds might increase the expression of osteogenesis markers in the DPSCs, with a possible increase in cell differentiation and bone formation. PMID:27766219

  10. Developing bioactive composite scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    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

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

    PubMed Central

    Fox, Derek B.; Stoker, Aaron M.; Beatty, Mark; Cockrell, Mary; Janicek, John C.; Cook, James L.

    2014-01-01

    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 coating of PGA

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

    PubMed

    Shamaz, Bibi Halima; 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. Poly lactic acid based foams prepared via thermally induced phase separation (TIPS): A method to tune the crystallinity

    NASA Astrophysics Data System (ADS)

    Pavia, Francesco Carfı; La Carrubba, Vincenzo; Brucato, Valerio

    2012-07-01

    Blends of Poly-L-Lactic Acid (PLLA) with two Poly-Lactic Acid (PLA) in different proportions (90/10 and 70/30) were utilized in order to produce biodegradable and biocompatible scaffolds for soft tissue engineering applications. The scaffolds were produced via thermally induced phase separation (TIPS) starting from ternary systems where dioxane was the solvent and water the non-solvent. Morphology was evaluated by Scanning Electron Microscopy (average pore size and interconnection). Moreover a DSC analysis was carried out on the as-obtained scaffold in order to obtain information about theirs thermal properties (enthalpy of melt and crystallization). The results showed that is possible to prepare scaffolds of PLLA/PLA via TIPS. Moreover, the PLA seems to influences the TIPS process in terms of demixing temperatures. The data confirm that the morphology and the mechanical properties of the scaffold can be tuned, starting from PLLA blends and using PLA with different molecular weights.

  15. Fabrication of Aligned Conducting PPy-PLLA Fiber Films and Their Electrically Controlled Guidance and Orientation for Neurites.

    PubMed

    Zou, Yuanwen; Qin, Jiabang; Huang, Zhongbing; Yin, Guangfu; Pu, Ximing; He, Da

    2016-05-25

    Electrically conductive biomaterial scaffolds have great potential in neural tissue regeneration. In this work, an aligned conductive fibrous scaffold was prepared by electrospinning PLLA on rotating collector and chemical oxidation polymerization of pyrrole (PPy) codoped with poly(glutamic acid)/dodecyl benzenesulfonic acid sodium. The characterization results of composition, structure and mechanics of fiber films show that the existence of weak polar van der Waals' force between PPy coating and PLLA fibers. The resistivity of aligned rough PPy-PLLA fiber film (about 800 nm of fiber diameter) at the perpendicular and parallel directions is 0.971 and 0.874 Ω m, respectively. Aligned rough PPy-PLLA fiber film could guide the extension of 68% PC12 neurites along the direction of fiber axis. Under electrostimulation (ES) of 100, 200, and 400 mV/cm, median neurite lengths of differentiated PC12 on aligned fiber-films are 128, 149, and 141 μm, respectively. Furthermore, under ES of 100, 200, and 400 mV/cm, the alignment rate of neurite along the electropotential direction (angle between neurite and electropotential direction ≤10°) on random fibers film are 17, 23, and 28%, respectively, and the alignment rate of neurites along the fiber axis (angle between neurite and fiber axis ≤10°) on aligned fibers film reach to 76, 83, and 79%, respectively, indicating that the combination of ES and rough conducting aligned structure could adjust the alignment of cellular neurites along the direction of the fiber axis or electropotential. PMID:27172537

  16. Structure and Morphology of PEO-b-PLLA Diblock Copolymer Single Crystal

    NASA Astrophysics Data System (ADS)

    Li, Lingyu

    2005-03-01

    Poly (L-lactide) (PLLA) is an important biodegradable synthetic polymer of interest for medical applications such as controlled drug delivery, resorbable sutures, medical implants, and scaffolds for tissue engineering. Combining PLLA with Poly (ethylene oxide) (PEO) to form a block copolymer PEO-b-PLLA has attracted the interests of material scientists because modifications of physical and chemical properties lead to an accelerated biodegradability. Generally, the rate of degradation strongly depends on the solid state structure of the material therefore clear understanding of crystallization behavior of PEO-b-PLLA is important. Crystallization of PEO-b-PLLA primarily depends on crystallization temperature (Tc). Solution cast thin film crystallization method was used to obtain the PEO-b-PLLA single crystals. At temperatures above Tm of PEO and below that of PLLA, PLLA crystallizes and forms lozenge-shaped single crystal .When cooled to room temperature, PEO begins to crystallize and form fractal-like single crystal on the top of already formed PLLA crystals. However, at temperatures below Tm of PEO, only the fractal-like PEO single crystals were observed. Structure and morphology of this novel single crystal was explored using TEM and AFM.

  17. Electrospun poly(L-lactide)/poly(ε-caprolactone) blend nanofibrous scaffold: characterization and biocompatibility with human adipose-derived stem cells.

    PubMed

    Chen, Liang; Bai, Yi; Liao, Guiying; Peng, Ejun; Wu, Bolin; Wang, Yuxi; Zeng, Xiaoyong; Xie, Xiaolin

    2013-01-01

    The essence of tissue engineering is the fabrication of autologous cells or induced stem cells in naturally derived or synthetic scaffolds to form specific tissues. Polymer is thought as an appealing source of cell-seeded scaffold owing to the diversity of its physicochemical property and can be electrospun into nano-size to mimic natural structure. Poly (L-lactic acid) (PLLA) and poly (ε-caprolactone) (PCL) are both excellent aliphatic polyester with almost "opposite" characteristics. The controlling combination of PLLA and PCL provides varying properties and makes diverse applications. Compared with the copolymers of the same components, PLLA/PCL blend demonstrates its potential in regenerative medicine as a simple, efficient and scalable alternative. In this study, we electrospun PLLA/PCL blends of different weight ratios into nanofibrous scaffolds (NFS) and their properties were detected including morphology, porosity, degradation, ATR-FTIR analysis, stress-stain assay, and inflammatory reaction. To explore the biocompatibility of the NFS we synthesized, human adipose-derived stem cells (hASCs) were used to evaluate proliferation, attachment, viability and multi-lineage differentiation. In conclusion, the electrospun PLLA/PCL blend nanofibrous scaffold with the indicated weight ratios all supported hASCs well. However, the NFS of 1/1 weight ratio showed better properties and cellular responses in all assessments, implying it a biocompatible scaffold for tissue engineering. PMID:23990941

  18. Evaluation of the Effect of NT-3 and Biodegradable Poly-L-lactic Acid Nanofiber Scaffolds on Differentiation of Rat Hair Follicle Stem Cells into Neural Cells In Vitro.

    PubMed

    Ghoroghi, Fatemeh Moghani; Hejazian, Leila Beygom; Esmaielzade, Banafshe; Dodel, Masumeh; Roudbari, Masoud; Nobakht, Maliheh

    2013-08-20

    Recent improvement in neuroscience has led to new strategies in neural repair. Hair follicle stem cells are high promising source of accessible, active, and pluripotent adult stem cells. They have high affinity to differentiate to neurons. Aside from using cell-scaffold combinations for implantation, scaffolds can provide a suitable microenvironment for cell proliferation, migration, and differentiation. NT-3 is the most interesting neurotrophic factors being an important regulator of neural survival and differentiation. Since treatment duration in neural repair is very important, this study aims to evaluate the effect of NT-3 and poly-L-lactic acid (PLLA) on differentiation time of bulge stem cells of rat hair follicle to neural-like cells. HFSCs of rat whisker was isolated and cultured on PLLA and differentiated with 10 ng/mL NT-3. Biological features of cultured cells were evaluated with immunocytochemistry and flowcytometry methods by using CD34, nestin, and βІІІ-tubulin markers. For cell viability and morphological assessment, MTT assay and SEM were performed. Our results showed that bulge stem cells of hair follicle can express CD34 and Nestin before differentiation. By using NT-3 during differentiation process, the cells showed positive reaction to βІІІ-tubulin antibody. MTT results demonstrated that PLLA significantly increased cell viability. Finally, HFSCs adhesion was confirmed by SEM results. The results indicate that 10 ng/mL NT-3 and PLLA have significant effect on differentiation time of rat HFSCs to neural cells even in 10 days.

  19. Comparative Evaluation of Nanofibrous Scaffolding for Bone Regeneration in Critical-Size Calvarial Defects

    PubMed Central

    Woo, Kyung Mi; Chen, Victor J.; Jung, Hong-Moon; Kim, Tae-Il; Shin, Hong-In; Baek, Jeong-Hwa; Ryoo, Hyun-Mo

    2009-01-01

    In a previous study we found that nanofibrous poly(l-lactic acid) (PLLA) scaffolds mimicking collagen fibers in size were superior to solid-walled scaffolds in promoting osteoblast differentiation and bone formation in vitro. In this study we used an in vivo model to confirm the biological properties of nanofibrous PLLA scaffolds and to evaluate how effectively they support bone regeneration against solid-walled scaffolds. The scaffolds were implanted in critical-size defects made on rat calvarial bones. Compared with solid-walled scaffolds, nanofibrous scaffolds supported substantially more new bone tissue formation, which was confirmed by micro-computed tomography measurement and von Kossa staining. Goldner's trichrome staining showed abundant collagen deposition in nanofibrous scaffolds but not in the control solid-walled scaffolds. The cells in these scaffolds were immuno-stained strongly for Runx2 and bone sialoprotein (BSP). In contrast, solid-walled scaffolds implanted in the defects were stained weakly with trichrome, Runx2, and BSP. These in vivo results demonstrate that nanofibrous architecture enhances osteoblast differentiation and bone formation. PMID:19348597

  20. In Vivo Bioluminescence Imaging for Prolonged Survival of Transplanted Human Neural Stem Cells Using 3D Biocompatible Scaffold in Corticectomized Rat Model

    PubMed Central

    Lee, Do Hun; Kim, Han Young; Cho, Han Na; Chung, Hye Jin; Park, Yunwoong; Youn, Hyewon; Lee, Seung Jin; Lee, Hong J.; Kim, Seung U.; Wang, Kyu-Chang; Lee, Dong Soo

    2014-01-01

    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. PMID:25198726

  1. Hydrolytic degradation of electron beam irradiated high molecular weight and non-irradiated moderate molecular weight PLLA.

    PubMed

    Loo, Say Chye Joachim; Tan, Hui Tong; Ooi, Chui Ping; Boey, Yin Chiang Freddy

    2006-05-01

    The purpose of this study is to examine the hydrolytic degradation of electron beam irradiated ring-opening polymerized (ROP) poly(l-lactide) (PLLA-ir) and non-irradiated melt polycondensation polymerized poly(l-lactic acid) (PLLA-pc). It was observed that irradiation increases the hydrolytic degradation rate constant for ROP PLLA. This was due to a more hydrophilic PLLA-ir, as a result of irradiation. The degradation rate constants (k) of PLLA-ir samples were also found to be similar, regardless of the radiation dose, and an empirically formulated equation relating hydrolytic degradation time span to radiation dose was derived. The k value for PLLA-pc was observed to be lower than that for PLLA-ir, though the latter had a higher molecular weight. This was due to the difference in degradation mechanism, in which PLLA-ir undergoes end group scission, through a back- biting mechanism, during hydrolysis and thus a faster hydrolysis rate. Electron beam irradiation, though accelerates the degradation of PLLA, has been shown to be useful in accurately controlling the hydrolytic time span of PLLA. This method of controlling the hydrolytic degradation time was by far an easier task than through melt polycondensation polymerization. This would allow PLLA to be used for drug delivery purposes or as a temporary implant that requires a moderate time span (3-6 months). PMID:16701888

  2. Fabrication of poly(lactic-co-glycolic acid) scaffolds containing silk fibroin scaffolds for tissue engineering applications.

    PubMed

    Ju, Hyung Woo; Sheikh, Faheem A; Moon, Bo Mi; Park, Hyun Jung; Lee, Ok Joo; Kim, Jung Ho; Eun, Jang Ji; Khang, Gilson; Park, Chan Hum

    2014-08-01

    The present study deals with the fabrication of poly(lactic-co-glycolic acid) (PLGA) scaffolds modified with silk fibroin for biomedical application. The PLGA solutions were added with salt particles and pressed with high pressures; which were further subjected to salt leaching resulting in the creation of large sized pores in the PLGA scaffolds. To fill up these pores, 2%, 4%, and 8% of silk solutions were added, however, the addition created extra small sized pores. The scaffolds were characterized by various state of techniques; the scanning electronic microscopy revealed the large sized pores in the pristine scaffold can be tailored into smaller architecture by the addition of silk fibroin. The contact angle measurements confirmed the introduction of silk helped to change the hydrophobic nature of PLGA into hydrophilic, which is the main constrain for PLGA. The mechanical properties of scaffold can be easily improved by applying the higher amounts of silk into the scaffolds. The thermal gravimetric analyses and fourier transform infrared spectroscopy confirmed the presence of silk fibroin in scaffolds. The cell viability and cell attachment was checked by culturing the scaffolds with NIH 3T3 fibroblasts and chondrocytes. Furthermore, these results revealed that the introduction of silk had significant impact on the viability of fibroblast also had a good affinity for cell attachment and infiltration of human chondrocytes in scaffolds after culturing the cells for 2 and 5 weeks of time. PMID:24026912

  3. Cotton wool-like poly(lactic acid)/vaterite composite scaffolds releasing soluble silica for bone tissue engineering.

    PubMed

    Obata, Akiko; Ozasa, Hiroki; Kasuga, Toshihiro; Jones, Julian R

    2013-07-01

    Cotton wool-like poly(L-lactic acid) and siloxane-doped vaterite (SiV) composite scaffolds were prepared with a modified electrospinning system for bone tissue engineering applications. The effects of changing the SiV content in the materials from 10 to 30 wt% on elasticity and the ability to release calcium ions and soluble silica were evaluated. The elasticity of the cotton wool-like composites was almost the same as that of the PLLA from the results of compressibility and recovery tests. The materials released calcium ions for more than 56 days and soluble silica for 28-56 days in a tris buffer solution (pH 7.4). Mouse osteoblast-like cells (MC3T3-E1 cells) were cultured on/in the cotton wool-like materials or the fibremats out of the same composite materials as that used for the cotton wool-like materials. The cells penetrated into and proliferated inside the cotton wool-like materials, although they mainly adhered on the fibremat surface.

  4. Nebulized solvent ablation of aligned PLLA fibers for the study of neurite response to anisotropic-to-isotropic fiber/film transition (AFFT) boundaries in astrocyte–neuron co-cultures

    PubMed Central

    Zuidema, Jonathan M.; Desmond, Gregory P.; Rivet, Christopher J.; Kearns, Kathryn R.; Thompso, Deanna M.; Gilbert, Ryan J.

    2015-01-01

    Developing robust in vitro models of in vivo environments has the potential to reduce costs and bring new therapies from the bench top to the clinic more efficiently. This study aimed to develop a biomaterial platform capable of modeling isotropic-to-anisotropic cellular transitions observed in vivo, specifically focusing on changes in cellular organization following spinal cord injury. In order to accomplish this goal, nebulized solvent patterning of aligned, electrospun poly-l-lactic acid (PLLA) fiber substrates was developed. This method produced a clear topographic transitional boundary between aligned PLLA fibers and an isotropic PLLA film region. Astrocytes were then seeded on these scaffolds, and a shift between oriented and non-oriented astrocytes was created at the anisotropic-to-isotropic fiber/film transition (AFFT) boundary. Orientation of chondroitin sulfate proteoglycans (CSPGs) and fibronectin produced by these astrocytes was analyzed, and it was found that astrocytes growing on the aligned fibers produced aligned arrays of CSPGs and fibronectin, while astrocytes growing on the isotropic film region produced randomly-oriented CSPG and fibronectin arrays. Neurite extension from rat dissociated dorsal root ganglia (DRG) was studied on astrocytes cultured on anisotropic, aligned fibers, isotropic films, or from fibers to films. It was found that neurite extension was oriented and longer on PLLA fibers compared to PLLA films. When dissociated DRG were cultured on the astrocytes near the AFFT boundary, neurites showed directed orientation that was lost upon growth into the isotropic film region. The AFFT boundary also restricted neurite extension, limiting the extension of neurites once they grew from the fibers and into the isotropic film region. This study reveals the importance of anisotropic-to-isotropic transitions restricting neurite outgrowth by itself. Furthermore, we present this scaffold as an alternative culture system to analyze neurite

  5. Enhanced sintering ability of biphasic calcium phosphate by polymers used for bone scaffold fabrication.

    PubMed

    Gao, Chengde; Yang, Bo; Hu, Huanlong; Liu, Jinglin; Shuai, Cijun; Peng, Shuping

    2013-10-01

    Biphasic calcium phosphate (BCP), which is composed of hydroxyapatite [HAP, Ca10(PO4)6(OH)2] and β-tricalcium phosphate [β-TCP, β-Ca3(PO4)2], is usually difficult to densify into a solid state with selective laser sintering (SLS) due to the short sintering time. In this study, the sintering ability of BCP ceramics was significantly improved by adding a small amount of polymers, by which a liquid phase was introduced during the sintering process. The effects of the polymer content, laser power and HAP/β-TCP ratios on the microstructure, chemical composition and mechanical properties of the BCP scaffolds were investigated. The results showed that the BCP scaffolds became increasingly more compact with the increase of the poly(l-lactic acid) (PLLA) content (0-1 wt.%) and laser power (6-10 W). The fracture toughness and micro-hardness of the sintered scaffolds were also improved. Moreover, PLLA could be gradually decomposed in the late sintering stages and eliminated from the final BCP scaffolds if the PLLA content was below a certain value (approximately 1 wt.% in this case). The added PLLA could not be completely eliminated when its content was further increased to 1.5 wt.% or higher because an unexpected carbon phase was detected in the sintered scaffolds. Furthermore, many pores were observed due to the removal of PLLA. Micro-cracks and micro-pores occurred when the laser power was too high (12 W). These defects resulted in a deterioration of the mechanical properties. The hardness and fracture toughness reached maximum values of 490.3±10 HV and 1.72±0.10 MPa m(1/2), respectively, with a PLLA content of approximately 1 wt.% and laser power of approximately 10 W. Poly(l-lactic-co-glycolic acid) (PLGA) showed similar effects on the sintering process of BCP ceramics. Rectangular, porous BCP scaffolds were fabricated based on the optimum values of the polymer content and laser power. This work may provide an experimental basis for improving the mechanical

  6. Biocompatibility, degradability, bioactivity and osteogenesis of mesoporous/macroporous scaffolds of mesoporous diopside/poly(l-lactide) composite

    PubMed Central

    Liu, Zhulin; Ji, Jiajin; Tang, Songchao; Qian, Jun; Yan, Yonggang; Yu, Baoqing; Su, Jiacan; Wei, Jie

    2015-01-01

    Bioactive mesoporous diopside (m-DP) and poly(l-lactide) (PLLA) composite scaffolds with mesoporous/macroporous structure were prepared by the solution-casting and particulate-leaching method. The results demonstrated that the degradability and bioactivity of the mesoporous/macroporous scaffolds were significantly improved by incorporating m-DP into PLLA, and that the improvement was m-DP content-dependent. In addition, the scaffolds containing m-DP showed the ability to neutralize acidic degradation products and prevent the pH from dropping in the solution during the soaking period. Moreover, the scaffolds containing m-DP enhanced attachment, proliferation and alkaline phosphatase activity of MC3T3-E1 cells, which were also m-DP content-dependent. Furthermore, the histological and immunohistochemical analysis results showed that the scaffolds with m-DP significantly promoted new bone formation and improved the materials degraded in vivo, indicating good biocompatibility. The results suggested that the mesoporous/macroporous scaffolds of the m-DP/PLLA composite with osteogenesis had a potential for bone regeneration. PMID:26378120

  7. Preparation, in vitro degradability, cytotoxicity, and in vivo biocompatibility of porous hydroxyapatite whisker-reinforced poly(L-lactide) biocomposite scaffolds.

    PubMed

    Xie, Lu; Yu, Haiyang; Yang, Weizhong; Zhu, Zhuoli; Yue, Li

    2016-01-01

    Biodegradable and bioactive scaffolds with interconnected macroporous structures, suitable biodegradability, adequate mechanical property, and excellent biocompatibility have drawn increasing attention in bone tissue engineering. Hence, in this work, porous hydroxyapatite whisker-reinforced poly(L-lactide) (HA-w/PLLA) composite scaffolds with different ratios of HA and PLLA were successfully developed through compression molding and particle leaching. The microstructure, in vitro mineralization, cytocompatibility, hemocompatibility, and in vivo biocompatibility of the porous HA-w/PLLA were investigated for the first time. The SEM results revealed that these HA-w/PLLA scaffolds possessed interconnected pore structures. Compared with porous HA powder-reinforced PLLA (HA-p/PLLA) scaffolds, HA-w/PLLA scaffolds exhibited better mechanical property and in vitro bioactivity, as more formation of bone-like apatite layers were induced on these scaffolds after mineralization in SBF. Importantly, in vitro cytotoxicity displayed that porous HA-w/PLLA scaffold with HA/PLLA ratio of 1:1 (HA-w1/PLLA1) produced no deleterious effect on human mesenchymal stem cells (hMSCs), and cells performed elevated cell proliferation, indicating a good cytocompatibility. Simultaneously, well-behaved hemocompatibility and favorable in vivo biocompatibility determined from acute toxicity test and histological evaluation were also found in the porous HA-w1/PLLA1 scaffold. These findings may provide new prospects for utilizing the porous HA whisker-based biodegradable scaffolds in bone repair, replacement, and augmentation applications.

  8. Development and characterization of reinforced poly(L-lactide) scaffolds for bone tissue engineering.

    PubMed

    Park, Joo-Eon; Todo, Mitsugu

    2011-05-01

    Novel reinforced poly(L-lactic acid) (PLLA) scaffolds such as solid shell, porous shell, one beam and two beam reinforced scaffolds were developed to improve the mechanical properties of a standard PLLA scaffold. Experimental results clearly indicated that the compressive mechanical properties such as the strength and the modulus are effectively improved by introducing the reinforcement structures. A linear elastic model consisting of three phases, that is, the reinforcement, the porous matrix and the boundary layer was also introduced in order to predict the compressive moduli of the reinforced scaffolds. The comparative study clearly showed that the simple theoretical model can reasonably predict the moduli of the scaffolds with three phase structures. The failure mechanism of the solid shell and the porous shell reinforced scaffolds under compression were found to be buckling of the solid shell and localized buckling of the struts constructing the pores in the porous shell, respectively. For the beam reinforced scaffolds, on the contrary, the primary failure mechanism was understood to be micro-cracking within the beams and the subsequent formation of the main-crack due to the coalescence of the micro-racks. The biological study was exhibited that osteoblast-like cells, MC3T3-E1, were well adhered and proliferated on the surfaces of the scaffolds after 12 days culturing.

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

    PubMed

    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

  10. Electrospun nanostructured scaffolds for bone tissue engineering.

    PubMed

    Prabhakaran, Molamma P; Venugopal, J; Ramakrishna, S

    2009-10-01

    The current challenge in bone tissue engineering is to fabricate a bioartificial bone graft mimicking the extracellular matrix (ECM) with effective bone mineralization, resulting in the regeneration of fractured or diseased bones. Biocomposite polymeric nanofibers containing nanohydroxyapatite (HA) fabricated by electrospinning could be promising scaffolds for bone tissue engineering. Nanofibrous scaffolds of poly-l-lactide (PLLA, 860+/-110 nm), PLLA/HA (845+/-140 nm) and PLLA/collagen/HA (310+/-125 nm) were fabricated, and the morphology, chemical and mechanical characterization of the nanofibers were evaluated using scanning electron microscopy, Fourier transform infrared spectroscopy and tensile testing, respectively. The in vitro biocompatibility of different nanofibrous scaffolds was also assessed by growing human fetal osteoblasts (hFOB), and investigating the proliferation, alkaline phosphatase activity (ALP) and mineralization of cells on different nanofibrous scaffolds. Osteoblasts were found to adhere and grow actively on PLLA/collagen/HA nanofibers with enhanced mineral deposition of 57% higher than the PLLA/HA nanofibers. The synergistic effect of the presence of an ECM protein, collagen and HA in PLLA/collagen/HA nanofibers provided cell recognition sites together with apatite for cell proliferation and osteoconduction necessary for mineralization and bone formation. The results of our study showed that the biocomposite PLLA/collagen/HA nanofibrous scaffold could be a potential substrate for the proliferation and mineralization of osteoblasts, enhancing bone regeneration. PMID:19447211

  11. Efficient in vivo Vascularization of Tissue Engineering Scaffolds

    PubMed Central

    Hegen, Anja; Blois, Anna; Tiron, Crina E.; Hellesøy, Monica; Micklem, David R.; Nör, Jacques E.; Akslen, Lars A.; Lorens, James B.

    2010-01-01

    The success of tissue engineering depends on the rapid and efficient formation of a functional blood vasculature. Adult blood vessels comprise endothelial cells and peri-vascular mural cells that assemble into patent tubules ensheathed by a basement membrane during angiogenesis. Using individual vessel components, we characterized intra-scaffold microvessel self-assembly efficiency in a physiological in vivo tissue engineering implant context. Primary human microvascular endothelial- and vascular smooth muscle cells were seeded at different ratios in poly-L lactic acid (PLLA) scaffolds enriched with basement membrane proteins (Matrigel) and implanted subcutaneously into immunocompromised mice. Temporal intra-scaffold microvessel formation, anastomosis and perfusion were monitored by immunohistochemical, flow cytometric and in vivo multiphoton fluorescence microscopy analysis. Vascularization in the tissue engineering context was strongly enhanced in the implants seeded with a complete complement of blood vessel components: Human microvascular endothelial and vascular smooth muscle cells in vivo assembled a patent microvasculature within Matrigel-enriched PLLA scaffolds that anastomosed with the host circulation during the first week of implantation. Multiphoton fluorescence angiographic analysis of the intra-scaffold microcirculation showed a uniform, branched microvascular network. 3-D image reconstruction analysis of hPASMC distribution within vascularized implants was non-random and displayed a preferential peri-vascular localization. Hence, efficient microvessel self-assembly, anastomosis and establishment of a functional microvasculture in the native hypoxic in vivo tissue engineering context is promoted by providing a complete set of vascular components. PMID:20865694

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2013-09-13

    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.

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

    NASA Astrophysics Data System (ADS)

    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

  15. Migration of co-cultured endothelial cells and osteoblasts in composite hydroxyapatite/polylactic acid scaffolds.

    PubMed

    Shah, Amita R; Shah, Sarita R; Oh, Sunho; Ong, Joo L; Wenke, Joseph C; Agrawal, C Mauli

    2011-10-01

    Regeneration of bone in large segmental bone defects requires regeneration of both cortical bone and trabecular bone. A scaffold design consisting of a hydroxyapatite (HA) ring surrounding a polylactic acid (PLA) core simulates the structure of bone and provides an environment for indirect and direct co-culture conditions. In this experiment, human umbilical vein endothelial cells (EC) and normal human primary osteoblasts (OB) were co-cultured to evaluate cell migration and interactions within this biphasic composite scaffold. Both cell types were able to migrate between the different material phases of the scaffold. It was also observed that OB migration increased when they were co-cultured with ECs, whereas EC migration decreased in co-culture. The results show that co-culture of ECs and OBs in this composite biphasic scaffold allows for migration of cells throughout the scaffold and that pre-seeding a scaffold with ECs can increase OB infiltration into desired areas of the scaffold.

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

    PubMed

    Su, Zhongchun; Ma, Huan; Wu, Zhengzheng; Zeng, Huilan; Li, Zhizhong; Wang, Yuechun; Liu, Gexiu; Xu, Bin; Lin, Yongliang; Zhang, Peng; Wei, Xing

    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.

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

    PubMed

    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. PMID:19777575

  18. Supportive features of a new hybrid scaffold for urothelium engineering

    PubMed Central

    Naji, Mohammad; Rasouli, Javad; Shakhssalim, Nasser; Dehghan, Mohammad Mehdi

    2015-01-01

    Introduction Different clinical conditions can compromise the urinary bladder function and structure. Routine regenerative practices in urology for bladder augmentation have been associated with diverse side effects. The internal lining of the bladder, the urothelium, plays an integral role in normal bladder function. Tissue engineering has provided novel therapeutic strategies through scaffolding and cell transplantation. Nano-scale surface features of scaffolds are valuable parameters for enhancement of cell behavior and function. Material and methods We fabricated a new hybrid scaffold of poly ɛ-caprolactone (PCL) and poly-L-lactide acid (PLLA) using an electrospinning system to exploit each polymer's advantages at nano-scale in the same scaffold. Dog urothelial cells were isolated, characterized by immunocytochemistry, and expanded for loading on the scaffold. Cell viability and proliferation on the scaffold surface were assessed by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, cytoarchitecture, distribution and detailed morphology of cells, and expression of cell specific markers were examined using hematoxylin and eosin (H + E) staining, scanning electron microscopy (SEM), and immunohistochemistry, respectively. Results According to MTT results, the scaffold did not exert any cytotoxic effect, and also supported cell proliferation and viability for 14 days of culture, which led to a significant increase in the number of cells. Scanning electron microscopy images revealed evenly distributed and normal appearing colonies of urothelial cells. A well-defined layer of cells was observed using H + E staining, which preserved their markers (pan-cytokeratin and uroplakin III) while growing on the scaffold. Conclusions Our findings confirmed favorable properties of PCL/PLLA regarding biocompatibility and applicability for upcoming new methods of bladder augmentation and engineering. PMID:25995764

  19. Superabsorbent biphasic system based on poly(lactic acid) and poly(acrylic acid)

    NASA Astrophysics Data System (ADS)

    Sartore, Luciana; Pandini, Stefano; Baldi, Francesco; Bignotti, Fabio

    2016-05-01

    In this research work, biocomposites based on crosslinked particles of poly(acrylic acid), commonly used as superabsorbent polymer (SAP), and poly-L-lactic acid (PLLA) were developed to elucidate the role of the filler (i.e., polymeric crosslinked particles) on the overall physico-mechanical behavior and to obtain superabsorbent thermoplastic products. Samples prepared by melt-blending of components in different ratios showed a biphasic system with a regular distribution of particles, with diameter ranging from 5 to 10 μm, within the PLLA polymeric matrix. The polymeric biphasic system, coded PLASA i.e. superabsorbent poly(lactic acid), showed excellent swelling properties, demonstrating that cross-linked particles retain their superabsorbent ability, as in their free counterparts, even if distributed in a thermoplastic polymeric matrix. The thermal characteristics of the biocomposites evidence enhanced thermal stability in comparison with neat PLLA and also mechanical properties are markedly modified by addition of crosslinked particles which induce regular stiffening effect. Furthermore, in aqueous environments the particles swell and are leached from PLLA matrix generating very high porosity. These new open-pore PLLA foams, produced in absence of organic solvents and chemical foaming agents, with good physico-mechanical properties appear very promising for several applications, for instance in tissue engineering for scaffold production.

  20. Scaffolding along nucleic acid duplexes using 2'-amino-locked nucleic acids.

    PubMed

    Astakhova, I Kira; Wengel, Jesper

    2014-06-17

    CONSPECTUS: Incorporation of chemically modified nucleotide scaffolds into nucleic acids to form assemblies rich in function is an innovative area with great promise for nanotechnology and biomedical and material science applications. The intrinsic biorecognition potential of nucleic acids combined with advanced properties of the locked nucleic acids (LNAs) provide opportunities to develop new nanomaterials and devices like sensors, aptamers, and machines. In this Account, we describe recent research on preparation and investigation of the properties of LNA/DNA hybrids containing functionalized 2'-amino-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 depends on the chemical nature of the modification, its price, its availability, and applications of the product. One of the most useful applications of the product LNA/DNA scaffolds containing 2'-amino-LNA is to detect complementary DNA and RNA targets. Examples of these applications include sensing of clinically important single-nucleotide polymorphisms (SNPs) and imaging of nucleic acids in vitro, in cell culture, and in vivo. According to our studies, 2'-amino-LNA scaffolds are efficient within diagnostic probes for DNA and RNA targets and as therapeutics, whereas both 2'-amino- and isomeric 2'-α-l-amino-LNA scaffolds have promising properties for stabilization and detection of DNA nanostructures. Attachment of fluorescent groups to the 2'-amino group results in very high fluorescent quantum yields of the duplexes and remarkable sensitivity of the fluorescence signal to target binding. Notably, fluorescent LNA/DNA probes bind nucleic acid targets with advantages of high affinity and specificity. Thus, molecular motion of nanodevices and programmable

  1. Scaffolding along nucleic acid duplexes using 2'-amino-locked nucleic acids.

    PubMed

    Astakhova, I Kira; Wengel, Jesper

    2014-06-17

    CONSPECTUS: Incorporation of chemically modified nucleotide scaffolds into nucleic acids to form assemblies rich in function is an innovative area with great promise for nanotechnology and biomedical and material science applications. The intrinsic biorecognition potential of nucleic acids combined with advanced properties of the locked nucleic acids (LNAs) provide opportunities to develop new nanomaterials and devices like sensors, aptamers, and machines. In this Account, we describe recent research on preparation and investigation of the properties of LNA/DNA hybrids containing functionalized 2'-amino-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 depends on the chemical nature of the modification, its price, its availability, and applications of the product. One of the most useful applications of the product LNA/DNA scaffolds containing 2'-amino-LNA is to detect complementary DNA and RNA targets. Examples of these applications include sensing of clinically important single-nucleotide polymorphisms (SNPs) and imaging of nucleic acids in vitro, in cell culture, and in vivo. According to our studies, 2'-amino-LNA scaffolds are efficient within diagnostic probes for DNA and RNA targets and as therapeutics, whereas both 2'-amino- and isomeric 2'-α-l-amino-LNA scaffolds have promising properties for stabilization and detection of DNA nanostructures. Attachment of fluorescent groups to the 2'-amino group results in very high fluorescent quantum yields of the duplexes and remarkable sensitivity of the fluorescence signal to target binding. Notably, fluorescent LNA/DNA probes bind nucleic acid targets with advantages of high affinity and specificity. Thus, molecular motion of nanodevices and programmable

  2. Polyetheretherketone/poly (glycolic acid) blend scaffolds with biodegradable properties.

    PubMed

    Shuai, Chenying; Wu, Ping; Zhong, Yancheng; Feng, Pei; Gao, Chengde; Huang, Wei; Zhou, Zhiyang; Chen, Li; Shuai, Cijun

    2016-10-01

    Polyetheretherketone (PEEK) is widely applied in tissue engineering due to its good biocompatibility and mechanical properties. However, the slow degradation rate limits its further application. In this study, PEEK blended with plyglycolicacid (PGA) was used to fabricate porous scaffolds via selective laser sintering. The results demonstrated that the blend scaffolds could gradually degrade, and the degradation rate was able to regulate by tailoring the PGA content. Moreover, the scaffolds maintained good biocompatibility and suitable mechanical properties. These were explained as follows: PGA on the surface layer of the scaffolds might degrade first owing to its exposure to the ambient medium. The degraded PGA left much space, which could promote cell attachment and proliferation. Meanwhile, the slow degradation of PEEK was beneficial to sustaining the scaffolds' strength and stable structure. PMID:27398735

  3. ADSCs on PLLA/PCL Hybrid Nanoscaffold and Gelatin Modification: Cytocompatibility and Mechanical Properties

    PubMed Central

    Mashhadikhan, Maedeh; Soleimani, Masoud; Parivar, Kazem; Yaghmaei, Parichehr

    2015-01-01

    Background Development of tissue engineering and regenerative medicine has led to designing scaffolds and their modification to provide a better microenvironment which mimics the natural niche of the cells. Gelatin surface modification was applied to improve scaffold flexibility and cytocompatibility. Methods PLLA/PCL aligned fibrous scaffold was fabricated using electrospinning method. ADSCs were seeded after O2 plasma treatment and gelatin coating of the scaffolds. The morphological and mechanical properties of blends were assessed by Scanning Electron Microscopy (SEM), tensile test and ATR-FTIR. The cells proliferation was evaluated by MTT assay. Results Based on the results, it is supposed that gelatin coating is a brilliant method of surface modification which significantly increases the mechanical properties of scaffold without any changes on the construction or on the direction of nanofibers which conducts cell's elongation. MTT analysis exhibited that ADSCs attachment, viability and proliferation significantly (p < 0.05) increased after gelatin treatment. Conclusion Gelatin surface modification is a highly beneficial method to improve cytocompatibility, flexibility and mechanical features of the scaffolds which doesn't affect the nanofibers construction. Proliferation of Adipose Derived Stem Cells (ADSCs) as a remarkable source of stem cells was investigated for the first time on PLLA/PCL hybrid scaffold. PMID:25926950

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

    PubMed

    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. PMID:26538110

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

    PubMed

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

    2015-11-05

    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.

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

    PubMed

    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. PMID:27455643

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

    PubMed

    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.

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

    PubMed Central

    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

  9. Peracetic acid: a practical agent for sterilizing heat-labile polymeric tissue-engineering scaffolds.

    PubMed

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

    2014-09-01

    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

  10. Improved regeneration potential of fibroblasts using ascorbic acid-blended nanofibrous scaffolds.

    PubMed

    Sridhar, Sreepathy; Venugopal, Jayarama Reddy; Ramakrishna, Seeram

    2015-11-01

    Two-dimensional scaffolds, three-dimensional scaffolds, and dermal substitutes are extensively used for biomedical applications in skin tissue regeneration. Not much explored synthetic polymers, like poly(l-lactic acid)-co-poly-(ε-caprolactone) (PLACL), natural polymers, like silk fibroin (SF), and active inducing agents, such as ascorbic acid (AA) and tetracycline hydrochloride (TCH), represent a favorable matrix for fabricating dermal substitutes to engineer artificial skin for wound repair. The profligate nature of residing skin cells near the wound site is a paramount to survival and also regulating stem cells and other cellular networks and mechanical forces. PLACL/SF/TCH/AA nanofibrous scaffolds were fabricated by electrospinning and characterized for fiber morphology, membrane porosity, wettability, and significant subchains using Fourier transform infrared spectroscopy for culturing human-derived dermal fibroblasts. The PLACL, PLACL/SF, PLACL/SF/TCH, and PLACL/SF/TCH/AA scaffolds obtained diameters between 250 and 340 nm. The secretion of collagen by the laboratory-grown fibroblasts over the AA-blended scaffolds was found to be significantly higher compared with that of other scaffolds. The obtained results positively prove that introduction of naturally secreting compounds (AA) by the cells into the nanofibrous scaffolds will favor cell's microenvironment and eventually leads to complete tissue regeneration. PMID:25903719

  11. The Enhancement of Human Embryonic Stem Cell Osteogenic Differentiation with Nano-Fibrous Scaffolding

    PubMed Central

    Smith, Laura A.; Liu, Xiaohua; Hu, Jiang; Ma, Peter X.

    2010-01-01

    Human embryonic stem cells (hESC) hold great promise as a cell source for tissue engineering since they possess the ability to differentiate into any cell type within the body. However, much work must still be done to control the differentiation of the hESC to the desired lineage. In this study, we examined the effects of the nano-fibrous (NF) architecture in both two dimensional (2-D) poly(L-lactic acid) (PLLA) thin matrices and 3-D PLLA scaffolds in vitro to assess their affect on the osteogenic differentiation of hESC in vitro compared to more traditional solid films and solid-walled (SW) scaffolds. In 2-D culture, hESC on NF thin matrices were found to express collagen type 1, Runx2, and osteocalcin mRNA of higher levels than the hESC on the solid films after 1 week of culture and increased mineralization was observed on the NF matrices compared to the solid films after 3 weeks of culture. After 6 weeks of 3-D culture, the hESC on the NF scaffolds expressed signifcantly more osteocalcin mRNA compared to these on the SW scaffolds. The data indicates that the NF architecture enhances the osteogenic differentiation of the hESC compared to more traditional scaffolding architecture. PMID:20430439

  12. Incorporation of TGF-beta 3 within collagen-hyaluronic acid scaffolds improves their chondrogenic potential.

    PubMed

    Matsiko, Amos; Levingstone, Tanya J; Gleeson, John P; O'Brien, Fergal J

    2015-06-01

    Incorporation of therapeutics in the form of growth factors within biomaterials can enhance their biofunctionality. Two methods of incorporating transforming growth factor-beta 3 within collagen-hyaluronic acid scaffolds are described, markedly improving mesenchymal stem cell-mediated chondrogenic differentiation and matrix production. Such scaffolds offer control over the release of therapeutics, demonstrating their potential for repair of complex chondral defects requiring additional stimuli.

  13. Design of Cell-Matrix Interactions in Hyaluronic Acid Hydrogel Scaffolds

    PubMed Central

    Segura, Tatiana

    2013-01-01

    The design of hyaluronic acid-based hydrogel scaffolds to elicit highly controlled and tunable cell response and behavior is a major field of interest in developing tissue engineering and regenerative medicine applications. This review will begin with an overview of the biological context of hyaluronic acid, knowledge needed to better understand how to engineer cell-matrix interactions in the scaffolds via the incorporation of different types of signals in order to direct and control cell behavior. Specifically, recent methods of incorporating various bioactive, mechanical, and spatial signals are reviewed, as well as novel hyaluronic acid modifications and crosslinking schemes with a focus on specificity. PMID:23899481

  14. Effect of adipic dihydrazide modification on the performance of collagen/hyaluronic acid scaffold.

    PubMed

    Zhang, Ling; Xiao, Yumei; Jiang, Bo; Fan, Hongsong; Zhang, Xingdong

    2010-02-01

    Collagen and hydrazide-functionalized hyaluronic acid derivatives were hybridized by gelating and genipin crosslinking to form composite hydrogel. The study contributed to the understanding of the effects of adipic dihydrazide modification on the physicochemical and biological properties of the collagen/hyaluronic acid scaffold. The investigation included morphology observation, mechanical measurement, swelling evaluation, and collagenase degradation. The results revealed that the stability of composites was increased through adipic dihydrazide modification and genipin crosslinking. The improved biocompatibility and retention of hyaluronic acid made the composite material more favorable to chondrocytes growing, suggesting the prepared scaffold might be high potential for chondrogenesis. PMID:19810117

  15. Synthesis of novel trivalent amino acid glycoconjugates based on the cyclotriveratrylene ('CTV') scaffold.

    PubMed

    van Ameijde, Jeroen; Liskamp, Rob M J

    2003-08-01

    The convenient synthesis of novel trivalent amino acid glycoconjugates based on cyclotriveratrylene ('CTV') is described. These constructs consist of the CTV scaffold, three oligoethylene glycol spacers of variable length connected to a glyco amino acid residue which can also be varied. The resulting library of trivalent glycoconjugates can be used for studying multivalent interactions. PMID:12948190

  16. Osteogenic and osteoclastogenic differentiation of co-cultured cells in polylactic acid-nanohydroxyapatite fiber scaffolds.

    PubMed

    Morelli, Sabrina; Salerno, Simona; Holopainen, Jani; Ritala, Mikko; De Bartolo, Loredana

    2015-06-20

    The design of bone substitutes involves the creation of a microenvironment supporting molecular cross-talk between cells and scaffolds during tissue formation and remodelling. Bone remodelling process includes the cooperation of bone-building cells and bone-resorbing cells. In this paper we developed polylactic acid (PLA) and composite PLA-nanohydroxyapatite (nHA) scaffolds with 20 and 50wt.% of nHA by electrospinning technique to be used in bone tissue engineering. The developed scaffolds have different fiber diameter, porosity with interconnected pores and mechanical properties. Taking cues from the bone environment features we investigated the differentiation of human mesenchymal stem cells (hMSCs) from bone marrow in osteoblasts and the osteoclastogenesis in the developed scaffolds in homotypic and in co-culture up to 46 days. PLA and composite PLA-nHA scaffolds induced osteogenic and osteoclastogenic differentiation. Both osteoblasts and osteoclasts displayed high expression of specific markers (osteopontin, osteocalcin, RANK, RANKL) and functions such as secretion of ALP, cathepsin K and TRAP activity on composite scaffolds especially on PLA-nHA containing 20wt.% of nHA. The heterotypic interactions between osteoblasts and osteoclasts co-cultured in the developed scaffolds triggered their functional differentiation and activation.

  17. Silk fibroin/chondroitin sulfate/hyaluronic acid ternary scaffolds for dermal tissue reconstruction.

    PubMed

    Yan, Shuqin; Zhang, Qiang; Wang, Jiannan; Liu, Yu; Lu, Shenzhou; Li, Mingzhong; Kaplan, David L

    2013-06-01

    The fabrication of new dermal substitutes providing mechanical support and cellular cues is urgently needed in dermal reconstruction. Silk fibroin (SF)/chondroitin sulfate (CS)/hyaluronic acid (HA) ternary scaffolds (95-248μm in pore diameter, 88-93% in porosity) were prepared by freeze-drying. By the incorporation of CS and HA with the SF solution, the chemical potential and quantity of free water around ice crystals could be controlled to form smaller pores in the SF/CS/HA ternary scaffold main pores and improve scaffold equilibrium swelling. This feature offers benefits for cell adhesion, survival and proliferation. In vivo SF, SF/HA and SF/CS/HA (80/5/15) scaffolds as dermal equivalents were implanted onto dorsal full-thickness wounds of Sprague-Dawley rats to evaluate wound healing. Compared to SF and SF/HA scaffolds, the SF/CS/HA (80/5/15) scaffolds promoted dermis regeneration, related to improved angiogenesis and collagen deposition. Further, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) expression in the SF/CS/HA (80/5/15) groups were investigated by immunohistochemistry to assess the mechanisms involved in the stimulation of secretion of VEGF, PDGF and bFGF and accumulation of these growth factors related to accelerated wound process. These new three-dimensional ternary scaffolds offer potential for dermal tissue regeneration.

  18. Characterization of Mode I Fracture and Morphological Properties of PLLA Blends with Addition of Lysine Triisocyanate

    NASA Astrophysics Data System (ADS)

    Vannaladsaysy, Vilay; Todo, Mitsugu

    Poly(L-lactic acid) (PLLA) was toughened by blending with three different ductile biopolymers such as poly (ε-caprolactone) (PCL), poly(butylene succinate-co-e-caprolactone) (PBSC), poly (butylene succinate-co-L-lactate) (PBSL). The blend ratio was fixed to 50:50. Lysine triisocyanate (LTI) was added to the blends as a compatibilizer. Characterizations such as Fourier transform infra-red (FT-IR) spectroscopy, field-emission electron microscope (FE-SEM), and mode I fracture test were used to characterize the effectiveness of LTI on the mechanical and morphological properties of various PLLA blends. It was found that PLLA/PCL blend shows the highest toughness energy among the binary blends. On the other hand, addition of LTI in PLLA/PBSC blend exhibits the best toughness property. Based on the FE-SEM observation, fractured surfaces of PLLA blends with LTI indicate ductile fracture with dense elongated fibrils. The largest damage zone is generated in the vicinity of crack-trip, suggesting that high energy dissipation occurred in the crack-trip region. FT-IR analysis also suggested that the NCO groups of LTI were acted as a compatibilizer, as the results of interaction between the two phases of the polymer blends.

  19. PLLA nanofibrous paper-based plasmonic substrate with tailored hydrophilicity for focusing SERS detection.

    PubMed

    Shao, Jundong; Tong, Liping; Tang, Siying; Guo, Zhinan; Zhang, Han; Li, Penghui; Wang, Huaiyu; Du, Chang; Yu, Xue-Feng

    2015-03-11

    We report a new paper-based surface enhanced Raman scattering (SERS) substrate platform contributed by a poly(l-lactic acid) (PLLA) nanofibrous paper adsorbed with plasmonic nanostructures, which can circumvent many challenges of the existing SERS substrates. This PLLA nanofibrous paper has three-dimensional porous structure, extremely clean surface with good hydrophobicity (contact angle is as high as 133.4°), and negligible background interference under Raman laser excitation. Due to the strong electrostatic interaction between PLLA nanofiber and cetyltrimethylammonium bromide (CTAB) molecules, the CTAB-coated gold nanorods (GNRs) are efficiently immobilized onto the fibers. Such a hydrophobic paper substrate with locally hydrophilic SERS-active area can confine analyte molecules and prevent the random spreading of molecules. The confinement leads to focusing effect and the GNRs-PLLA SERS substrate is found to be highly sensitive (0.1 nM Rhodamine 6G and malachite green) and exhibit excellent reproducibility (∼8% relative standard deviation (RSD)) and long-term stability. Furthermore, it is also cost-efficient, with simple fabrication methodology, and demonstrates high sample collection efficiency. All of these benefits ensure that this GNRs-PLLA substrate is a really perfect choice for a variety of SERS applications. PMID:25697378

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

    PubMed

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

    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. PMID:27127042

  1. Polyester copolymer scaffolds enhance expression of bone markers in osteoblast-like cells.

    PubMed

    Idris, Shaza Bushra; Arvidson, Kristina; Plikk, Peter; Ibrahim, Salah; Finne-Wistrand, Anna; Albertsson, Ann-Christine; Bolstad, Anne Isine; Mustafa, Kamal

    2010-08-01

    In tissue engineering, the resorbable aliphatic polyester poly(L-lactide) (PLLA) is used as scaffolds in bone regeneration. Copolymers of poly(L-lactide)-co-(epsilon-caprolactone) [poly(LLA-co-CL)] and poly(L-lactide)-co-(1,5-dioxepan-2-one) [poly(LLA-co-DXO)], with superior mechanical properties to PLLA, have been developed to be used as scaffolds, but the influence on the osteogenic potential is unclear. This in vitro study of test scaffolds of poly(LLA-co-CL) and poly(LLA-co-DXO) using PLLA scaffolds as a control demonstrates the attachment and proliferation of human osteoblast-like cells (HOB) as measured by SEM and a methylthiazol tetrazolium (MTT) colorimetric assay, and the progression of HOB osteogenesis for up to 3 weeks; expressed as synthesis of the osteoblast differentiation markers: collagen type 1 (Col 1), alkaline phosphatase, bone sialoprotein, osteocalcin (OC), osteopontin and runt related gene 2 (Runx2). Surface analysis disclosed excellent surface attachment, spread and penetration of the cells into the pores of the test scaffolds compared to the PLLA. MTT results indicated that test scaffolds enhanced the proliferation of HOBs. Cells grown on the test scaffolds demonstrated higher synthesis of Col 1 and OC and also increased bone markers mRNA expression. Compared to scaffolds of PLLA, the poly(LLA-co-CL) and poly(LLA-co-DXO) scaffolds enhanced attachment, proliferation, and expression of osteogenic markers by HOBs in vitro. Therefore, these scaffolds might be appropriate carriers for bone engineering.

  2. Biocompatibility and bone-repairing effects: comparison between porous poly-lactic-co-glycolic acid and nano-hydroxyapatite/poly(lactic acid) scaffolds.

    PubMed

    Zong, Chen; Qian, Xiaodan; Tang, Zihua; Hu, Qinghong; Chen, Jiarong; Gao, Changyou; Tang, Ruikang; Tong, Xiangmin; Wang, Jinfu

    2014-06-01

    Copolymer composite scaffolds and bioceramic/polymer composite scaffolds are two representative forms of composite scaffolds used for bone tissue engineering. Studies to compare biocompatibility and bone-repairing effects between these two scaffolds are significant for selecting or improving the scaffold for clinical application. We prepared two porous scaffolds comprising poly-lactic-acid/poly-glycolic-acid (PLGA) and poly-lactic-acid/nano-hydroxyapatite (nHAP/PLA) respectively, and examined their biocompatibility with human bone marrow-derived mesenchymal stem cells (hMSCs) through evaluating adhesion, proliferation and osteogenic differentiation potentials of hMSCs in the scaffold. Then, the PLGA scaffold with hMSCs (PM construct) and the nHAP/PLA scaffold with hMSCs (HPM construct) were transplanted into the rat calvarial defect areas to compare their effects on the bone reconstruction. The results showed that the nHAP/PLA scaffold was in favor of adhesion, matrix deposition and osteogenic differentiation of hMSCs. For in vivo transplantation, both HPM and PM constructs led to mineralization and osteogenesis in the defect area of rat. However, the area grafted with PM construct showed a better formation of mature bone than that with HPM construct. In addition, the evaluation of in vitro and in vivo degradation indicated that the degradation rate of nHAP/PLA scaffold was much lower than that of PLGA scaffold. It is inferred that the lower degradation of nHAP/PLA scaffold should result in its inferior bone reconstruction in rat calvaria. Therefore, the preparation of an ideal composite scaffold for bone tissue engineering should be taken into account of the balance between its biocompatibility, degradation rate, osteoconductivity and mechanical property.

  3. Functionalisation and surface modification of electrospun polylactic acid scaffold for tissue engineering.

    PubMed

    Hoveizi, Elham; Nabiuni, Mohammad; Parivar, Kazem; Rajabi-Zeleti, Sareh; Tavakol, Shima

    2014-01-01

    Repair or replacement of damaged tissues using tissue engineering technology is considered to be a fine solution for enhanced treatment of different diseases such as skin diseases. Although the nanofibers made of synthetic degradable polymers, such as polylactic acid (PLA), have been widely used in the medical field, they do not favour cellular adhesion and proliferation. To enhance cell adherence on scaffold and improve biocompatibility, the surface of PLA scaffold was modified by gelatin in our experiments. For electrospinning, PLA and gelatin were dissolved in hexafluoroisopropanol (HFIP) solvent at varying compositions (PLA:gelatin at 3:7 and 7:3). The properties of the blending nanofiber scaffold were investigated by Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Modified PLA/gelatin 7/3 scaffold is more suitable for fibroblasts attachment and viability than the PLA or gelatin nanofiber alone. Thus fibroblast cultured on PLA/gelatin scaffold could be an alternative way to improve skin wound healing. PMID:24030862

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

    PubMed Central

    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

  5. Culturing primary human osteoblasts on electrospun poly(lactic-co-glycolic acid) and poly(lactic-co-glycolic acid)/nanohydroxyapatite scaffolds for bone tissue engineering.

    PubMed

    Li, Mengmeng; Liu, Wenwen; Sun, Jiashu; Xianyu, Yunlei; Wang, Jidong; Zhang, Wei; Zheng, Wenfu; Huang, Deyong; Di, Shiyu; Long, Yun-Ze; Jiang, Xingyu

    2013-07-10

    In this work, we fabricated polymeric fibrous scaffolds for bone tissue engineering using primary human osteoblasts (HOB) as the model cell. By employing one simple approach, electrospinning, we produced poly(lactic-co-glycolic acid) (PLGA) scaffolds with different topographies including microspheres, beaded fibers, and uniform fibers, as well as the PLGA/nanohydroxyapatite (nano-HA) composite scaffold. The bone-bonding ability of electrospun scaffolds was investigated by using simulated body fluid (SBF) solution, and the nano-HA in PLGA/nano-HA composite scaffold can significantly enhance the formation of the bonelike apatites. Furthermore, we carried out in vitro experiments to test the performance of electrospun scaffolds by utilizing both mouse preosteoblast cell line (MC 3T3 E1) and HOB. Results including cell viability, alkaline phosphatase (ALP) activity, and osteocalcin concentration demonstrated that the PLGA/nano-HA fibers can promote the proliferation of HOB efficiently, indicating that it is a promising scaffold for human bone repair.

  6. Optimization of poly(L-lactic acid)/segmented polyurethane electrospinning process for the production of bilayered small-diameter nanofibrous tubular structures.

    PubMed

    Montini Ballarin, F; Caracciolo, P C; Blotta, E; Ballarin, V L; Abraham, G A

    2014-09-01

    The present study is focused on the electrospinning process as a versatile technique to obtain nanofibrous tubular structures for potential applications in vascular tissue engineering. A bilayered scaffolding structure composed of poly(L-lactic acid) (PLLA)/bioresorbable segmented polyurethane (SPEU) blends for small-diameter (5mm) vascular bypass grafts was obtained by multilayering electrospinning. Polymer blend ratios were chosen to mimic the media and adventitia layers. The influence of the different electrospinning parameters into the fiber formation, fiber morphology and fiber mean diameter for PLLA, SPEU and two PLLA/SPEU blends were studied. Flat and two-parallel plate collectors were used to analyze the effect of the electrostatic field on the PLLA nanofiber alignment in the rotating mandrel. Membrane topography resulted in random or aligned nanofibrous structures depending on the auxiliary collector setup used. Finally, composition, surface hydrophilicity, thermal properties and morphology of nanofibrous scaffolds were characterized and discussed. Since the development of tissue engineered microvascular prostheses is still a challenge, the prepared scaffolding tubular structures are promising candidates for vascular tissue engineering.

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

    PubMed Central

    Chen, Shijie; Jian, Zhiyuan; Huang, Linsheng; Xu, Wei; Liu, Shaohua; Song, Dajiang; Wan, Zongmiao; Vaughn, Amanda; Zhan, Ruisen; Zhang, Chaoyue; Wu, Song; Hu, Minghua; Li, Jinsong

    2015-01-01

    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 after a 7-day immersion in simulated body fluid. In vitro studies showed that the incorporation of MBG favored cell proliferation and osteogenic differentiation of human mesenchymal stem cells on the PLGA scaffolds. Moreover, the MBG surface-modified PLGA (PLGA-MBG) scaffolds were shown to be capable of providing the improved adsorption/release behaviors of bone morphogenetic protein-2 (BMP-2). It is very significant that PLGA-MBG scaffolds could be effective for BMP-2 delivery and bone regeneration. PMID:26082632

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

    PubMed

    Chen, Shijie; Jian, Zhiyuan; Huang, Linsheng; Xu, Wei; Liu, Shaohua; Song, Dajiang; Wan, Zongmiao; Vaughn, Amanda; Zhan, Ruisen; Zhang, Chaoyue; Wu, Song; Hu, Minghua; Li, Jinsong

    2015-01-01

    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 after a 7-day immersion in simulated body fluid. In vitro studies showed that the incorporation of MBG favored cell proliferation and osteogenic differentiation of human mesenchymal stem cells on the PLGA scaffolds. Moreover, the MBG surface-modified PLGA (PLGA-MBG) scaffolds were shown to be capable of providing the improved adsorption/release behaviors of bone morphogenetic protein-2 (BMP-2). It is very significant that PLGA-MBG scaffolds could be effective for BMP-2 delivery and bone regeneration. PMID:26082632

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

    PubMed

    Chen, Shijie; Jian, Zhiyuan; Huang, Linsheng; Xu, Wei; Liu, Shaohua; Song, Dajiang; Wan, Zongmiao; Vaughn, Amanda; Zhan, Ruisen; Zhang, Chaoyue; Wu, Song; Hu, Minghua; Li, Jinsong

    2015-01-01

    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 after a 7-day immersion in simulated body fluid. In vitro studies showed that the incorporation of MBG favored cell proliferation and osteogenic differentiation of human mesenchymal stem cells on the PLGA scaffolds. Moreover, the MBG surface-modified PLGA (PLGA-MBG) scaffolds were shown to be capable of providing the improved adsorption/release behaviors of bone morphogenetic protein-2 (BMP-2). It is very significant that PLGA-MBG scaffolds could be effective for BMP-2 delivery and bone regeneration.

  10. Fast degradable citrate-based bone scaffold promotes spinal fusion

    PubMed Central

    Tang, Jiajun; Guo, Jinshan; Li, Zhen; Yang, Cheng; Xie, Denghui; Chen, Jian; Li, Shengfa; Li, Shaolin; Kim, Gloria B.; Bai, Xiaochun; Zhang, Zhongmin; Yang, Jian

    2015-01-01

    It is well known that high rates of fusion failure and pseudoarthrosis development (5~35%) are concomitant in spinal fusion surgery, which was ascribed to the shortage of suitable materials for bone regeneration. Citrate was recently recognized to play an indispensable role in enhancing osteconductivity and osteoinductivity, and promoting bone formation. To address the material challenges in spinal fusion surgery, we have synthesized mechanically robust and fast degrading citrate-based polymers by incorporating N-methyldiethanolamine (MDEA) into clickable poly(1, 8-octanediol citrates) (POC-click), referred to as POC-M-click. The obtained POC-M-click were fabricated into POC-M-click-HA matchstick scaffolds by compositing with hydroxyapatite (HA) for interbody spinal fusion in a rabbit model. Spinal fusion was analyzed by radiography, manual palpation, biomechanical testing, and histological evaluation. At 4 and 8 weeks post surgery, POC-M-click-HA scaffolds presented optimal degradation rates that facilitated faster new bone formation and higher spinal fusion rates (11.2±3.7, 80±4.5 at week 4 and 8, respectively) than the poly(L-lactic acid)-HA (PLLA-HA) control group (9.3±2.4 and 71.1±4.4) (p<0.05). The POC-M-click-HA scaffold-fused vertebrates possessed a maximum load and stiffness of 880.8±14.5 N and 843.2±22.4 N/mm, respectively, which were also much higher than those of the PLLA-HA group (maximum: 712.0±37.5 N, stiffness: 622.5±28.4 N/mm, p<0.05). Overall, the results suggest that POC-M-click-HA scaffolds could potentially serve as promising bone grafts for spinal fusion applications. PMID:26213625

  11. Betidamino acids: versatile and constrained scaffolds for drug discovery.

    PubMed Central

    Rivier, J E; Jiang, G; Koerber, S C; Porter, J; Simon, L; Craig, A G; Hoeger, C A

    1996-01-01

    Betidamino acids (a contraction of "beta" position and "amide") are N'-monoacylated (optionally, N'-monoacylated and N-mono- or N,N'-dialkylated) aminoglycine derivatives in which each N'acyl/alkyl group may mimic naturally occurring amino acid side chains or introduce novel functionalities. Betidamino acids are most conveniently generated on solid supports used for the synthesis of peptides by selective acylation of one of the two amino functions of orthogonally protected aminoglycine(s) to generate the side chain either prior to or after the elongation of the main chain. We have used unresolved Nalpha-tert-butyloxycarbonyl-N'alpha-fluorenylmethoxycarbonyl++ + aminoglycine, and Nalpha-(Nalpha-methyl)-tert-butyloxycarbonyl-N'alpha-fluo renylmethoxycarbonyl aminoglycine as the templates for the introduction of betidamino acids in Acyline [Ac-D2Nal-D4Cpa-D3Pal-Ser-4Aph(Ac)-D4Aph(A c)-Leu-Ilys-Pro-DAla-NH2, where 2Nal is 2-naphthylalanine, 4Cpa is 4-chlorophenylalanine, 3Pal is 3-pyridylalanine, Aph is 4-aminophenylalanine, and Ilys is Nepsilon-isopropyllysine], a potent gonadotropin-releasing hormone antagonist, in order to test biocompatibility of these derivatives. Diasteremneric peptides could be separated in most cases by reverse-phase HPLC. Biological results indicated small differences in relative potencies (<5-fold) between the D and L nonalkylated betidamino acid-containing Acyline derivatives. Importantly, most betide diastereomers were equipotent with Acyline. In an attempt to correlate structure and observed potency, Ramachandran-type plots were calculated for a series of betidamino acids and their methylated homologs. According to these calculations, betidamino acids have access to a more limited and distinct number of conformational states (including those associated with alpha-helices, beta-sheets, or turn structures), with deeper minima than those observed for natural amino acids. PMID:8700880

  12. Switchable mechanical DNA ``arms'' operating on nucleic acid scaffolds associated with electrodes or semiconductor quantum dots

    NASA Astrophysics Data System (ADS)

    Pelossof, Gilad; Tel-Vered, Ran; Liu, Xiaoqing; Willner, Itamar

    2013-09-01

    Functional footholds linked to DNA scaffolds associated with surfaces provide nano-engineered assemblies acting as switching devices. By the assembly of a β-cyclodextrin receptor on one foothold, and a ferrocene-modified nucleic acid on a second foothold, the switchable and reversible, fuel-driven activation of ``molecular arms'' proceeds, transduced by electrochemical or optical signals.Functional footholds linked to DNA scaffolds associated with surfaces provide nano-engineered assemblies acting as switching devices. By the assembly of a β-cyclodextrin receptor on one foothold, and a ferrocene-modified nucleic acid on a second foothold, the switchable and reversible, fuel-driven activation of ``molecular arms'' proceeds, transduced by electrochemical or optical signals. Electronic supplementary information (ESI) available: Experimental procedures, time-dependent deactivation of a DNA ``arm'' using a DNA anti-fuel, and control experiments, excluding β-cyclodextrin from the systems. See DOI: 10.1039/c3nr02653a

  13. Development and molecular characterization of polymeric micro-nanofibrous scaffold of a defined 3-D niche for in vitro chemosensitivity analysis against acute myeloid leukemia cells

    PubMed Central

    Nair, Maya S; Mony, Ullas; Menon, Deepthy; Koyakutty, Manzoor; Sidharthan, Neeraj; Pavithran, Keechilat; Nair, Shantikumar V; Menon, Krishnakumar N

    2015-01-01

    Standard in vitro drug testing employs 2-D tissue culture plate systems to test anti-leukemic drugs against cell adhesion-mediated drug-resistant leukemic cells that harbor in 3-D bone marrow microenvironments. This drawback necessitates the fabrication of 3-D scaffolds that have cell adhesion-mediated drug-resistant properties similar to in vivo niches. We therefore aimed at exploiting the known property of polyurethane (PU)/poly-l-lactic acid (PLLA) in forming a micro-nanofibrous structure to fabricate unique, not presented before, as far as we are aware, 3-D micro-nanofibrous scaffold composites using a thermally induced phase separation technique. Among the different combinations of PU/PLLA composites generated, the unique PU/PLLA 60:40 composite displayed micro-nanofibrous morphology similar to decellularized bone marrow with increased protein and fibronectin adsorption. Culturing of acute myeloid leukemia (AML) KG1a cells in FN-coated PU/PLLA 60:40 shows increased cell adhesion and cell adhesion-mediated drug resistance to the drugs cytarabine and daunorubicin without changing the original CD34+/CD38−/CD33− phenotype for 168 hours compared to fibronectin tissue culture plate systems. Molecularly, as seen in vivo, increased chemoresistance is associated with the upregulation of anti-apoptotic Bcl2 and the cell cycle regulatory protein p27Kip1 leading to cell growth arrest. Abrogation of Bcl2 activity by the Bcl2-specific inhibitor ABT 737 led to cell death in the presence of both cytarabine and daunorubicin, demonstrating that the cell adhesion-mediated drug resistance induced by Bcl2 and p27Kip1 in the scaffold was similar to that seen in vivo. These results thus show the utility of a platform technology, wherein drug testing can be performed before administering to patients without the necessity for stromal cells. PMID:26028971

  14. Activated carbon fibers/poly(lactic-co-glycolic) acid composite scaffolds: preparation and characterizations.

    PubMed

    Shi, Yanni; Han, Hao; Quan, Haiyu; Zang, Yongju; Wang, Ning; Ren, Guizhi; Xing, Melcolm; Wu, Qilin

    2014-10-01

    The present work is a first trial to introduce activated carbon fibers (ACF) with high adsorption capacity into poly(lactic-co-glycolic) acid (PLGA), resulting in a novel kind of scaffolds for tissue engineering applications. ACF, prepared via high-temperature processing of carbon fibers, are considered to possess bioactivity and biocompatibility. The ACF/PLGA composite scaffolds are prepared by solvent casting/particulate leaching method. Increments in both pore quantity and quality over the surface of ACF as well as a robust combination between ACF and PLGA matrix are observed via scanning electron microscopy (SEM). The high adsorption capacity of ACF is confirmed by methylene blue solution absorbency test. The surfaces of ACF are affiliated with many hydrophilic groups and characterized by Fourier transform infrared spectroscopy. Furthermore, the SEM images show that cells possess a favorable spreading morphology on the ACF/PLGA scaffolds. Besides, vivo experiments are also carried out to evaluate the histocompatibility of the composite scaffolds. The results show that ACF have the potential to become one of the most promising materials in biological fields.

  15. Activated carbon fibers/poly(lactic-co-glycolic) acid composite scaffolds: preparation and characterizations.

    PubMed

    Shi, Yanni; Han, Hao; Quan, Haiyu; Zang, Yongju; Wang, Ning; Ren, Guizhi; Xing, Melcolm; Wu, Qilin

    2014-10-01

    The present work is a first trial to introduce activated carbon fibers (ACF) with high adsorption capacity into poly(lactic-co-glycolic) acid (PLGA), resulting in a novel kind of scaffolds for tissue engineering applications. ACF, prepared via high-temperature processing of carbon fibers, are considered to possess bioactivity and biocompatibility. The ACF/PLGA composite scaffolds are prepared by solvent casting/particulate leaching method. Increments in both pore quantity and quality over the surface of ACF as well as a robust combination between ACF and PLGA matrix are observed via scanning electron microscopy (SEM). The high adsorption capacity of ACF is confirmed by methylene blue solution absorbency test. The surfaces of ACF are affiliated with many hydrophilic groups and characterized by Fourier transform infrared spectroscopy. Furthermore, the SEM images show that cells possess a favorable spreading morphology on the ACF/PLGA scaffolds. Besides, vivo experiments are also carried out to evaluate the histocompatibility of the composite scaffolds. The results show that ACF have the potential to become one of the most promising materials in biological fields. PMID:25175194

  16. PLLA/ZnO nanocomposites: Dynamic surfaces to harness cell differentiation.

    PubMed

    Trujillo, Sara; Lizundia, Erlantz; Vilas, José Luis; Salmeron-Sanchez, Manuel

    2016-08-01

    This work investigates the effect of the sequential availability of ZnO nanoparticles, (nanorods of ∼40nm) loaded within a degradable poly(lactic acid) (PLLA) matrix, in cell differentiation. The system constitutes a dynamic surface, in which nanoparticles are exposed as the polymer matrix degrades. ZnO nanoparticles were loaded into PLLA and the system was measured at different time points to characterise the time evolution of the physicochemical properties, including wettability and thermal properties. The micro and nanostructure were also investigated using AFM, SEM and TEM images. Cellular experiments with C2C12 myoblasts show that cell differentiation was significantly enhanced on ZnO nanoparticles-loaded PLLA, as the polymer degrades and the availability of nanoparticles become more apparent, whereas the release of zinc within the culture medium was negligible. Our results suggest PLLA/ZnO nanocomposites can be used as a dynamic system where nanoparticles are exposed during degradation, activating the material surface and driving cell differentiation. PMID:27085047

  17. Effect of Hydrolysis on Mechanical Behavior of TCP/PLLA Composites

    NASA Astrophysics Data System (ADS)

    Kobayashi, Satoshi; Yamaji, Shusaku

    2014-03-01

    Bioactive ceramics/poly-L-lactic acid (PLLA) composites have been expected as a material for the bone fracture fixations which have more biocompatibility than monolithic PLLA. In this study, hydrolysis behavior of tricalcium phosphate (TCP)/PLLA composites containing three different TCP contents (5, 10, 15 wt%) in simulated body environment were characterized. These specimens were immersed in phosphate buffered solution. Tensile tests were conducted on the specimen after immersion in various strain rates. In order to predict stress-strain behavior after immersion, damage micromechanical analysis proposed by the authors were conducted. In this model, nonlinear behavior in stress strain relationship were simulated considering interfacial debonding between TCP particle and PLLA matrix. For the purpose of deciding the interfacial strength, such as critical energy release rate, curve fitting was conducted on the result of 15wt% composites under three types of strain rates. Theoretical results using the interfacial strength obtained on 5wt% and 10wt% composites were in good agreement with experimental results. This result indicated that interfacial strength was dependent only on strain rate and was independent from TCP fraction.

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

    PubMed

    Smiga-Matuszowicz, Monika; Janicki, Bartosz; Jaszcz, Katarzyna; Łukaszczyk, Jan; Kaczmarek, Marcin; Lesiak, Marta; Sieroń, Aleksander L; Simka, Wojciech; Mierzwiński, Maciej; Kusz, Damian

    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 3h 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. PMID:25491802

  19. In vitro chondrocyte behavior on porous biodegradable poly(e-caprolactone)/polyglycolic acid scaffolds for articular chondrocyte adhesion and proliferation.

    PubMed

    Jonnalagadda, John B; Rivero, Iris V; Dertien, Janet S

    2015-01-01

    In this study, poly(e-caprolactone)/polyglycolic acid (PCL/PGA) scaffolds for repairing articular cartilage were fabricated via solid-state cryomilling along with compression molding and porogen leaching. Four distinct scaffolds were fabricated using this approach by four independent cryomilling times. These scaffolds were assessed for their suitability to promote articular cartilage regeneration with in vitro chondrocyte cell culture studies. The scaffolds were characterized for pore size, porosity, swelling ratio, compressive, and thermal properties. Cryomilling time proved to significantly affect the physical, mechanical, and morphological properties of the scaffolds. In vitro bovine chondrocyte culture was performed dynamically for 1, 7, 14, 28, and 35 days. Chondrocyte viability and adhesion were tested using MTT assay and scanning electron microscopy micrographs. Glycosaminoglycan (GAG) and DNA assays were performed to investigate the extracellular matrix (ECM) formation and cell proliferation, respectively. PCL/PGA scaffolds demonstrated high porosity for all scaffold types. Morphological analysis and poly(ethylene oxide) continuity demonstrated the existence of a co-continuous network of interconnected pores with pore sizes appropriate for tissue engineering and chondrocyte ingrowth. While mean pore size decreased, water uptake and compressive properties increased with increasing cryomilling times. Compressive modulus of 12, 30, and 60 min scaffolds matched the compressive modulus of human articular cartilage. Viable cells increased besides increase in cell proliferation and ECM formation with progress in culture period. Chondrocytes exhibited spherical morphology on all scaffold types. The pore size of the scaffold affected chondrocyte adhesion, proliferation, and GAG secretion. The results indicated that the 12 min scaffolds delivered promising results for applications in articular cartilage repair.

  20. Tissue anti-adhesion potential of ibuprofen-loaded PLLA-PEG diblock copolymer films.

    PubMed

    Lee, Jin Ho; Go, Ae Kyung; Oh, Se Heang; Lee, Ka Eul; Yuk, Soon Hong

    2005-02-01

    This study was designed to evaluate the effect of polyethylene glycol (PEG) and nonsteroidal anti-inflammatory drug (ibuprofen) on the prevention of postsurgical tissue adhesion. For this, poly(L-lactic acid) (PLLA)-PEG diblock copolymers were synthesized by ring opening polymerization of L-lactide and methoxy polyethylene glycol (Mw 5000) of different compositions. The synthesized copolymers were characterized by gel permeation chromatography and 1H-nuclear magnetic resonance spectroscopy. PLLA-PEG copolymer films were prepared by solvent casting. The prepared copolymer films were more flexible and hydrophilic than the control PLLA film, as investigated by the measurements of glass transition temperature, water absorption content, and water contact angle. The drug release behavior from the ibuprofen (10 wt%)-loaded copolymer films was examined by high performance liquid chromatography. It was observed that the drug was released gradually up to about 40% of total loading amount after 20 days, depending on PEG composition; more drug release from the films with higher PEG compositions. In vitro cell adhesions on the copolymer films with/without drug were compared by the culture of NIH/3T3 mouse embryo fibroblasts on the surfaces. For in vivo evaluation of tissue anti-adhesion potential, the copolymer films with/without drug were implanted between the cecum and peritoneal wall defects of rats and their tissue adhesion extents were compared. It was observed that the ibuprofen-containing PLLA-PEG films with high PEG composition (particularly PLLA113-PEG113 film with PEG composition, 50 mol%) were very effective in preventing cell or tissue adhesion on the film surfaces, probably owing to the synergistic effects of highly mobile, hydrophilic PEG and anti-inflammatory drug, ibuprofen.

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

    PubMed

    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.

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

    PubMed

    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. PMID:27612726

  3. Multiplicity of morphologies in poly (l-lactide) bioresorbable vascular scaffolds

    PubMed Central

    Ailianou, Artemis; Ramachandran, Karthik; Kossuth, Mary Beth; Oberhauser, James Paul; Kornfield, Julia A.

    2016-01-01

    Poly(l-lactide) (PLLA) is the structural material of the first clinically approved bioresorbable vascular scaffold (BVS), a promising alternative to permanent metal stents for treatment of coronary heart disease. BVSs are transient implants that support the occluded artery for 6 mo and are completely resorbed in 2 y. Clinical trials of BVSs report restoration of arterial vasomotion and elimination of serious complications such as late stent thrombosis. It is remarkable that a scaffold made from PLLA, known as a brittle polymer, does not fracture when crimped onto a balloon catheter or during deployment in the artery. We used X-ray microdiffraction to discover how PLLA acquired ductile character and found that the crimping process creates localized regions of extreme anisotropy; PLLA chains in the scaffold change orientation from the hoop direction to the radial direction on micrometer-scale distances. This multiplicity of morphologies in the crimped scaffold works in tandem to enable a low-stress response during deployment, which avoids fracture of the PLLA hoops and leaves them with the strength needed to support the artery. Thus, the transformations of the semicrystalline PLLA microstructure during crimping explain the unexpected strength and ductility of the current BVS and point the way to thinner resorbable scaffolds in the future. PMID:27671659

  4. Compositional and in Vitro Evaluation of Nonwoven Type I Collagen/Poly-dl-lactic Acid Scaffolds for Bone Regeneration

    PubMed Central

    Qiao, Xiangchen; Russell, Stephen J.; Yang, Xuebin; Tronci, Giuseppe; Wood, David J.

    2015-01-01

    Poly-dl-lactic acid (PDLLA) was blended with type I collagen to attempt to overcome the instantaneous gelation of electrospun collagen scaffolds in biological environments. Scaffolds based on blends of type I collagen and PDLLA were investigated for material stability in cell culture conditions (37 °C; 5% CO2) in which post-electrospinning glutaraldehyde crosslinking was also applied. The resulting wet-stable webs were cultured with bone marrow stromal cells (HBMSC) for five weeks. Scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), Fourier transform infra-red spectroscopy (FTIR) and biochemical assays were used to characterise the scaffolds and the consequent cell-scaffold constructs. To investigate any electrospinning-induced denaturation of collagen, identical PDLLA/collagen and PDLLA/gelatine blends were electrospun and their potential to promote osteogenic differentiation investigated. PDLLA/collagen blends with w/w ratios of 40/60, 60/40 and 80/20 resulted in satisfactory wet stabilities in a humid environment, although chemical crosslinking was essential to ensure long term material cell culture. Scaffolds of PDLLA/collagen at a 60:40 weight ratio provided the greatest stability over a five-week culture period. The PDLLA/collagen scaffolds promoted greater cell proliferation and osteogenic differentiation compared to HMBSCs seeded on the corresponding PDLLA/gelatine scaffolds, suggesting that any electrospinning-induced collagen denaturation did not affect material biofunctionality within 5 weeks in vitro. PMID:26251924

  5. Gelatin-poly(lactic-co-glycolic acid) scaffolds with oriented pore channel architecture - From in vitro to in vivo testing.

    PubMed

    Thiem, A; Bagheri, M; Große-Siestrup, C; Zehbe, R

    2016-05-01

    A gelatin-poly(lactic-co-glycolic acid), PLGA, composite scaffold, featuring a highly oriented pore channel structure, was developed as a template for articular cartilage regeneration. As a design principle the composite scaffold was optimized to contain only medical grade educts and accordingly no chemical cross linking agents or other toxicological relevant substances or methods were used. Scaffolds were synthesized using a freeze structuring method combined with an electrochemical process followed by freeze-drying. Finally, cross linking was performed using dehydrothermal treatment, which was simultaneously used for sterilization purposes. These composite scaffolds were analyzed in regard to structural and biomechanical properties, and to their degradation behavior. Furthermore, cell culture performance was tested using chondrocytes originated from joint articular cartilage tissue from 6 to 10 months old domestic pigs. Finally, the scaffolds were tested for tissue biocompatibility and their ability for tissue integration in a rat model. The scaffolds showed both excellent functional performance and high biocompatibility in vitro and in vivo. We expect that these gelatin-PLGA scaffolds can effectively support chondrogenesis in vivo demonstrating great potential for the use in cartilage defect treatment. PMID:26952462

  6. Cell adhesive and growth behavior on electrospun nanofibrous scaffolds by designed multifunctional composites.

    PubMed

    Cao, Ding; Wu, Yi-Pan; Fu, Zhi-Feng; Tian, Yuan; Li, Cong-Ju; Gao, Chun-Ying; Chen, Zhong-Liang; Feng, Xi-Zeng

    2011-05-01

    Nanostructured biocomposite scaffolds of poly(l-lactide) (PLLA) blended with collagen (coll) or hydroxyapatite (HA), or both for tissue engineering application, were fabricated by electrospinning. The electrospun scaffolds were characterized for the morphology, chemical and tensile properties by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), water contact angle (WCA), Fourier transform infrared (FTIR) measurement, and tensile testing. Electrospun biocomposite scaffolds of PLLA and collagen or (and) HA in the diameter range of 200-700 nm mimic the nanoscale structure of the extracellular matrix (ECM) with a well-interconnection pore network structure. The presence of collagen in the scaffolds increased their hydrophility, and enhanced cell attachment and proliferation, while HA improved the tensile properties of the scaffolds. The biocompatibility of the electrospun scaffolds and the viability of contacting cells were evaluated by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) nuclear staining and by fluorescein diacetate (FDA) and propidium iodide (PI) double staining methods. The results support the conclusion that 293T cells grew well on composite scaffolds. Compared with pure PLLA scaffolds a greater density of viable cells was seen on the composites, especially the PLLA/HA/collagen scaffolds. PMID:21227659

  7. Regulating surface wettability of PEO/PLLA composite electrospun nanofibrous membrane for liquid phase filtration

    NASA Astrophysics Data System (ADS)

    Poonsit, Lalada; Sunthornvarabhas, Jackapon; Akira, Ito; Lertworasirikul, Amornrat

    2014-06-01

    The PEO/PLLA composite nanofibrous membranes were prepared by electrospinning technique for liquid phase filtration application. In this experiment, PLLA homopolymer and PLLA-PEG copolymer were added into PEO solution to increase hydrophobicity of nanofibrous membrane surface. PLLA content was fixed at 30% by weight of total solid. Morphology and fiber diameter were characterized from scanning electron microscope (SEM) images. Fiber diameters of PEO/PLLA homopolymer and PEO/PLLA-PEG copolymer are 582+/-78 nm and 657+/-167 nm, respectively. Surface wettability property of PEO/PLLA composite nanofibrous membranes were measured by apparent water contact angle. The apparent water contact angle value of PEO/PLLA is 120°+/-2°, while PEO/PEG-b-PLLA is 99°+/-7°. The surface wettability of PEO/PLLA composite nanofibrous membranes can be modified by varying type of polymer.

  8. Potential of Hydrogels Based on Poly(Ethylene Glycol) and Sebacic Acid as Orthopedic Tissue Engineering Scaffolds

    PubMed Central

    Kim, Jinku; Hefferan, Theresa E.; Yaszemski, Michael J.

    2009-01-01

    In this study, the bioactive effects of poly(ethylene glycol) (PEG) sebacic acid diacrylate (PEGSDA) hydrogels with or without RGD peptide modification on osteogenic differentiation and mineralization of marrow stromal cells (MSCs) were examined. In a separate experiment, the ability of PEGSDA hydrogel to serve as a delivery vehicle for bone morphogenetic protein 2 (BMP-2) was also investigated. As a scaffold, the attachment and proliferation of MSCs on PEGSDA hydrogel scaffolds with and without RGD peptide modification was similar to the control, tissue culture polystyrene. In contrast, cells were barely seen on unmodified PEG diacrylate (PEGDA) hydrogel throughout the culture period for up to 21 days. Osteogenic phenotypic expression such as alkaline phosphatase (ALP) of MSCs as well as mineralized calcium content were significantly higher on PEGSDA-based hydrogels than those on the control or PEGDA hydrogels. Potential use of PEGSDA scaffold as a delivery vehicle of osteogenic molecules such as BMP-2 was also evaluated. Initial burst release of BMP-2 from PEGSDA hydrogel scaffold (14.7%) was significantly reduced compared to PEGDA hydrogel scaffold (84.2%) during the first 3 days of a 21-day release period. ALP activity of an osteoblast was significantly higher in the presence of BMP-2 released from PEGSDA hydrogel scaffolds compared to that in the presence of BMP-2 released from PEGDA scaffolds, especially after 6 days of release. Overall, PEGSDA hydrogel scaffolds without further modification may be useful as orthopedic tissue engineering scaffolds as well as local drug carriers for prolonged sustained release of osteoinductive molecules. PMID:19292677

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

    NASA Astrophysics Data System (ADS)

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

    2010-09-01

    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 (Δ H∗) 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 Δ H∗ 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.

  10. Epicardial delivery of VEGF and cardiac stem cells guided by 3-dimensional PLLA mat enhancing cardiac regeneration and angiogenesis in acute myocardial infarction.

    PubMed

    Chung, Hye-Jin; Kim, Jong-Tae; Kim, Hee-Jung; Kyung, Hei-Won; Katila, Pramila; Lee, Jeong-Han; Yang, Tae-Hyun; Yang, Young-Il; Lee, Seung-Jin

    2015-05-10

    Congestive heart failure is mostly resulted in a consequence of the limited myocardial regeneration capacity after acute myocardial infarction. Targeted delivery of proangiogenic factors and/or stem cells to the ischemic myocardium is a promising strategy for enhancing their local and sustained therapeutic effects. Herein, we designed an epicardial delivery system of vascular endothelial growth factor (VEGF) and cardiac stem cells (CSCs) using poly(l-lactic acid) (PLLA) mat applied to the acutely infarcted myocardium. The fibrous VEGF-loaded PLLA mat was fabricated by an electrospinning method using PLLA solution emulsified VEGF. This mat not only allowed for sustained release of VEGF for 4weeks but boosted migration and proliferation of both endothelial cells and CSCs in vitro. Furthermore, sustained release of VEGF showed a positive effect on in vitro capillary-like network formation of endothelial cells compared with bolus treatment of VEGF. PLLA mat provided a permissive 3-dimensional (3D) substratum that led to spontaneous cardiomyogenic differentiation of CSCs in vitro. Notably, sustained stimulation by VEGF-loaded PLLA mat resulted in a substantial increase in the expression of proangiogenic mRNAs of CSCs in vitro. The epicardially implanted VEGF-loaded PLLA mat showed modest effects on angiogenesis and cardiomyogenesis in the acutely infarcted hearts. However, co-implantation of VEGF and CSCs using the PLLA mat showed meaningful therapeutic effects on angiogenesis and cardiomyogenesis compared with controls, leading to reduced cardiac remodeling and enhanced global cardiac function. Collectively, the PLLA mat allowed a smart cargo that enabled the sustained release of VEGF and the delivery of CSCs, thereby synergistically inducing angiogenesis and cardiomyogenesis in acute myocardial infarction.

  11. Triazolo-β-aza-ε-amino acid and its aromatic analogue as novel scaffolds for β-turn peptidomimetics.

    PubMed

    Bag, Subhendu Sekhar; Jana, Subhashis; Yashmeen, Afsana; De, Suranjan

    2015-03-28

    Triazolo-β-aza-ε-amino acid and its aromatic analogue ((Al)TAA/(Ar)TAA) in the peptide backbone mark a novel class of conformationally constrained molecular scaffolds to induce β-turn conformations. This was demonstrated for (Al)TAA in a Leu-enkephalin analogue and in a designed pentapeptide wherein the FRET process was established. Restricted rotation induced chirality and turn conformation into the achiral aromatic amino acid scaffold, (Ar)TAA, which in a short tripeptide backbone acted as a β-turn mimic as a β-sheet folding nucleator.

  12. Electrospun homogeneous silk fibroin/poly (ɛ-caprolactone) nanofibrous scaffolds by addition of acetic acid for tissue engineering.

    PubMed

    Zhu, Jiang; Luo, Jingjing; Zhao, Xingyan; Gao, Junjiu; Xiong, Jie

    2016-09-01

    In this study, we investigated the phase separation phenomenon of silk fibroin/poly (ɛ-caprolactone) electrospinning solution to improve the performance of silk fibroin/poly (ɛ-caprolactone) electrospun nanofibers. It showed that phase separation does occur in just a few hours in the silk fibroin/poly (ɛ-caprolactone)/formic acid mixture solution. Acetic acid, small molecule nonsolvent for silk fibroin, was first introduced to silk fibroin/poly (ɛ-caprolactone)/formic acid solution, a homogeneous solution without separation for over several days was achieved after mixing for 5 h. The morphology and composition of the silk fibroin/poly (ɛ-caprolactone) and acetic acid-modified silk fibroin/poly (ɛ-caprolactone) fibrous scaffolds were examined by scanning electron microscopy, Fourier transform infrared spectroscopy and thermal gravimetric analyzer. Attachment and proliferation of mouse osteoblast MC3T3-E1 cells were tested by scanning electron microscopy and cytotoxity assay. The results indicated that the phase separation of silk fibroin/poly (ɛ-caprolactone) solution might led to inhomogeneous morphology and composition of the composite scaffolds, and the inhomogeneity of the silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid as solvent had a remarkable difference on cell adhesion and proliferation. In contrast, there was no significant difference among the silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid/acetic acid as solvent because of their good consistency in fiber morphology and composition. These obtained silk fibroin/poly (ɛ-caprolactone) nanofibers had small average diameter of 190 ± 40 nm. The obtained results proved that this study provided a facile and effective approach to achieve compositionally homogeneous silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid as solvent for effective applications. PMID:27422715

  13. Delivering Nucleic-Acid Based Nanomedicines on Biomaterial Scaffolds for Orthopedic Tissue Repair: Challenges, Progress and Future Perspectives.

    PubMed

    Raftery, Rosanne M; Walsh, David P; Castaño, Irene Mencía; Heise, Andreas; Duffy, Garry P; Cryan, Sally-Ann; O'Brien, Fergal J

    2016-07-01

    As well as acting to fill defects and allow for cell infiltration and proliferation in regenerative medicine, biomaterial scaffolds can also act as carriers for therapeutics, further enhancing their efficacy. Drug and protein delivery on scaffolds have shown potential, however, supraphysiological quantities of therapeutic are often released at the defect site, causing off-target side effects and cytotoxicity. Gene therapy involves the introduction of foreign genes into a cell in order to exert an effect; either replacing a missing gene or modulating expression of a protein. State of the art gene therapy also encompasses manipulation of the transcriptome by harnessing RNA interference (RNAi) therapy. The delivery of nucleic acid nanomedicines on biomaterial scaffolds - gene-activated scaffolds -has shown potential for use in a variety of tissue engineering applications, but as of yet, have not reached clinical use. The current state of the art in terms of biomaterial scaffolds and delivery vector materials for gene therapy is reviewed, and the limitations of current procedures discussed. Future directions in the clinical translation of gene-activated scaffolds are also considered, with a particular focus on bone and cartilage tissue regeneration.

  14. Delivering Nucleic-Acid Based Nanomedicines on Biomaterial Scaffolds for Orthopedic Tissue Repair: Challenges, Progress and Future Perspectives.

    PubMed

    Raftery, Rosanne M; Walsh, David P; Castaño, Irene Mencía; Heise, Andreas; Duffy, Garry P; Cryan, Sally-Ann; O'Brien, Fergal J

    2016-07-01

    As well as acting to fill defects and allow for cell infiltration and proliferation in regenerative medicine, biomaterial scaffolds can also act as carriers for therapeutics, further enhancing their efficacy. Drug and protein delivery on scaffolds have shown potential, however, supraphysiological quantities of therapeutic are often released at the defect site, causing off-target side effects and cytotoxicity. Gene therapy involves the introduction of foreign genes into a cell in order to exert an effect; either replacing a missing gene or modulating expression of a protein. State of the art gene therapy also encompasses manipulation of the transcriptome by harnessing RNA interference (RNAi) therapy. The delivery of nucleic acid nanomedicines on biomaterial scaffolds - gene-activated scaffolds -has shown potential for use in a variety of tissue engineering applications, but as of yet, have not reached clinical use. The current state of the art in terms of biomaterial scaffolds and delivery vector materials for gene therapy is reviewed, and the limitations of current procedures discussed. Future directions in the clinical translation of gene-activated scaffolds are also considered, with a particular focus on bone and cartilage tissue regeneration. PMID:26840618

  15. Degradation and osteogenic potential of a novel poly(lactic acid)/nano-sized β-tricalcium phosphate scaffold

    PubMed Central

    Cao, Lu; Duan, Ping-Guo; Wang, Hui-Ren; Li, Xi-Lei; Yuan, Feng-Lai; Fan, Zhong-Yong; Li, Su-Ming; Dong, Jian

    2012-01-01

    The purpose of this study was to investigate the influence of nano-sized β-tricalcium phosphate (β-TCP) on the biological performance of poly (lactic acid) (PLA) composite scaffolds by using in vitro degradation and an in vivo model of heterotopic bone formation. Nano-sized β-TCP (nβ-TCP) was prepared with a wet grinding method from micro-sized β-TCP (mβ-TCP), and composite scaffolds containing 0, 10, 30, or 50 wt% nβ-TCP or 30 wt% mβ-TCP were generated using a freeze-drying method. Degradation was assessed by monitoring changes in microstructure, pH, weight, and compressive strength over a 26-week period of hydrolysis. Composite scaffolds were processed into blocks, and implanted into muscular pockets of rabbits after loading with recombinant human bone morphogenetic protein-2 (rhBMP-2). New bone formation was evaluated based on histological and immunohistochemical analysis 2, 4, and 8 weeks after implantation. The in vitro results indicated that the buffering effect of nβ-TCP was stronger than mβ-TCP, which was positively correlated with the content of nβ-TCP. The in vivo findings demonstrated that nβ-TCP enhanced the osteoconductivity of the scaffolds. Although composite scaffolds containing 30% nβ-TCP exhibited similar osteoconductivity to 50% nβ-TCP, they had better mechanical properties than the 50% nβ-TCP scaffolds. This study supports the potential application of a composite scaffold containing 30% nβ-TCP as a promising scaffold for bone regeneration. PMID:23226019

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

    NASA Astrophysics Data System (ADS)

    Jung, Kyung-Hye; Ferraris, John P.

    2016-10-01

    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.

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

    PubMed

    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. PMID:27632072

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

    PubMed

    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.

  19. Tough and elastic hydrogel of hyaluronic acid and chondroitin sulfate as potential cell scaffold materials.

    PubMed

    Ni, Yilu; Tang, Zhurong; Cao, Wanxu; Lin, Hai; Fan, Yujiang; Guo, Likun; Zhang, Xingdong

    2015-03-01

    Natural polysaccharides are extensively investigated as cell scaffold materials for cellular adhesion, proliferation, and differentiation due to their excellent biocompatibility, biodegradability, and biofunctions. However, their application is often severely limited by their mechanical behavior. In this study, a tough and elastic hydrogel scaffold was prepared with hyaluronic acid (HA) and chondroitin sulfate (CS). HA and CS were conjugated with tyramine (TA) and the degree of substitution (DS) was 10.7% and 11.3%, respectively, as calculated by (1)H NMR spectra. The hydrogel was prepared by mixing HA-TA and CS-TA in presence of H2O2 and HRP. The sectional morphology of hydrogels was observed by SEM, static and dynamic mechanical properties were analyzed by Shimadzu electromechanical testing machine and dynamic mechanical thermal analyzer Q800. All samples showed good ability to recover their appearances after deformation, the storage modulus (E') of hydrogels became higher as the testing frequency went up. Hydrogels also showed fatigue resistance to cyclic compression. Mesenchymal stem cells encapsulated in hydrogels showed good cell viability as detected by CLSM. This study suggests that the hydrogels have both good mechanical properties and biocompatibility, and may serve as model systems to explore mechanisms of deformation and energy dissipation or find some applications in tissue engineering. PMID:25445680

  20. Dendrigraft polylysine coated-poly(glycolic acid) fibrous scaffolds for hippocampal neurons.

    PubMed

    Kojima, Chie; Fusaoka-Nishioka, Eri; Imai, Toshio; Nakahira, Atsushi; Onodera, Hiroshi

    2016-11-01

    Poly(glycolic acid) (PGA) fibers are a good candidate material for nerve cell scaffolds, which is applicable to the treatment of peripheral nerve injuries. Polylysine is widely used as a coating material for cell substrates to promote nerve cell adhesion. In this study, linear and dendrigraft polylysines were used to coat PGA fibers. The association of large dendrigraft polylysines with PGA fibers was lower and unstable, compared with linear polylysine. However, more hippocampal neurons adhered to PGA fibers coated with large dendrigraft polylysine than linear polylysine. Enhanced cell adhesion was observed, even when the dendrigraft polylysine was coated on the PGA fibers at a low concentration (0.05 μg/mL) or when it was coated in water instead of alkaline buffer. Differences in cell adhesion properties were seen between the dendrigraft polylysine coating and a laminin coating. Thus, large dendrigraft polylysines are a useful coating material for nerve cell scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2744-2750, 2016.

  1. Dendrigraft polylysine coated-poly(glycolic acid) fibrous scaffolds for hippocampal neurons.

    PubMed

    Kojima, Chie; Fusaoka-Nishioka, Eri; Imai, Toshio; Nakahira, Atsushi; Onodera, Hiroshi

    2016-11-01

    Poly(glycolic acid) (PGA) fibers are a good candidate material for nerve cell scaffolds, which is applicable to the treatment of peripheral nerve injuries. Polylysine is widely used as a coating material for cell substrates to promote nerve cell adhesion. In this study, linear and dendrigraft polylysines were used to coat PGA fibers. The association of large dendrigraft polylysines with PGA fibers was lower and unstable, compared with linear polylysine. However, more hippocampal neurons adhered to PGA fibers coated with large dendrigraft polylysine than linear polylysine. Enhanced cell adhesion was observed, even when the dendrigraft polylysine was coated on the PGA fibers at a low concentration (0.05 μg/mL) or when it was coated in water instead of alkaline buffer. Differences in cell adhesion properties were seen between the dendrigraft polylysine coating and a laminin coating. Thus, large dendrigraft polylysines are a useful coating material for nerve cell scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2744-2750, 2016. PMID:27324925

  2. Use of Decellularized Scaffolds Combined with Hyaluronic Acid and Basic Fibroblast Growth Factor for Skin Tissue Engineering

    PubMed Central

    Wu, Zhengzheng; Fan, Lina; Xu, Bin; Lin, Yongliang; Zhang, Peng

    2015-01-01

    Skin damage is one of the common clinical skin diseases, and the main cure is the use of skin graft, especially for large area of skin injury or deep-skin damage. However, skin graft demand is far greater than that currently available. In this study, xenogeneic decellularized scaffold was prepared with pig peritoneum by a series of biochemical treatments to retain normal three-dimensional tissue scaffold and remove cells and antigenic components from the tissue. Scaffold was combined with hyaluronic acid (HA) plus two different concentrations of basic fibroblast growth factor (bFGF) and tested for its use for the repair of skin wounds. HA enhanced bFGF to adsorb to the decellularized scaffolds and slowed the release of bFGF from the scaffolds in vitro. A total of 20 rabbits were sacrificed on day 3, 6, 11, or 14 postsurgery. The wound healing rate and the thickness of dermis layer of each wound were determined for analyzing the wound repair. Statistical analysis was performed by the two-tailed Student's t-test. Wounds covered with scaffolds containing 1 μg/mL bFGF had higher wound healing rates of 47.24%, 74.69%, and 87.54%, respectively, for days 6, 11, and 14 postsurgery than scaffolds alone with wound healing rates of 28.17%, 50.31%, and 61.36% and vaseline oil gauze with wound healing rates of 24.84%, 42.75%, and 57.62%. Wounds covered with scaffolds containing 1 μg/mL bFGF showed more dermis regeneration than the other wounds and had dermis layer of 210.60, 374.40, and 774.20 μm, respectively, for days 6, 11, and 14 postsurgery compared with scaffolds alone with dermis layer of 116.60, 200.00, and 455.40 μm and vaseline oil gauze with dermis layer of 82.60, 186.20, and 384.40 μm. There was no significant difference in wound healing rates and thickness of dermis layer between wounds covered with scaffolds containing 1 and 3 μg/mL bFGF on days 3, 6, 11, and 14 postsurgery. The decellularized scaffolds combined with HA and bFGF can be further

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

    PubMed

    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.

  4. Optimal Viscosity and Particle Shape of Hyaluronic Acid Filler as a Scaffold for Human Fibroblasts.

    PubMed

    Kim, Deok-Yeol; Namgoong, Sik; Han, Seung-Kyu; Won, Chang-Hoon; Jeong, Seong-Ho; Dhong, Eun-Sang; Kim, Woo-Kyung

    2015-07-01

    The authors previously reported that cultured human fibroblasts suspended in a hyaluronic acid filler can produce human dermal matrices with extended in vivo stability in animal and clinical studies. The present study was undertaken to determine the optimal viscosity and particle shape of hyaluronic acid filler as a scaffold for cultured human dermal fibroblasts to enhance the maximal viability of injected cells. The fibroblasts were suspended in either 1 of 3 hyaluronic acid viscosities at 2 different particle shapes. The viscosities used in this study were low (600,000-800,000 centipoises), moderate (2,000,000-4,000,000 centipoises), and high (8,000,000-12,000,000 centipoises). The particle shape was evaluated by testing round and irregular shapes. The fibroblast mixed bioimplants were injected into the back of individual athymic nude mice. The levels of type I collagen were measured using fluorescent-activated cell sorting (FACS) and immunohistochemical staining at 16 weeks after the injections. Results of FACS demonstrated that the mean cell ratio with human collagens in the moderate viscosity group was greater than those of control, low, and high viscosity groups. An immunohistochemical study showed similar results. The moderate viscosity group demonstrated the highest positive staining of human collagens. However, there were no significant differences between groups of irregular and round shape particles. A hyaluronic acid bioimplant with moderate viscosity is superior to that with low or high viscosity in the viability for human fibroblasts. However, the particle shape does not influence the viability of the fibroblasts.

  5. Sterilization of auto-crosslinked hyaluronic acid scaffolds structured in microparticles and sponges.

    PubMed

    Shimojo, Andréa Arruda Martins; de Souza Brissac, Isabela Cambraia; Pina, Lucas Martins; Lambert, Carlos Salles; Santana, Maria Helena Andrade

    2015-01-01

    This work evaluated the effects of UV irradiation, plasma radiation, steam and 70% ethanol treatments on the sterilization and integrity of auto-crosslinked hyaluronic acid (HA-ACP) scaffolds structured in microparticles and sponges aiming in vivo applications for regenerative medicine of bone tissue. The integrity of the microparticles was characterized by rheological behavior, while for the sponges, it was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. The effectiveness of the sterilization treatment was verified by the number of microorganism colonies in the samples after the treatments. In conclusion, plasma radiation was the best treatment for the sponges, while steam sterilization in the autoclave at 126°C (1.5 kgf/cm2) for 5 min was the best treatment for the microparticles. PMID:26684890

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

    PubMed Central

    Zhai, Dong; Zhao, Lang

    2014-01-01

    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. PMID:24724080

  7. Nanosized mesoporous bioactive glass/poly(lactic-co-glycolic acid) composite-coated CaSiO3 scaffolds with multifunctional properties for bone tissue engineering.

    PubMed

    Shi, Mengchao; Zhai, Dong; Zhao, Lang; Wu, Chengtie; Chang, Jiang

    2014-01-01

    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.

  8. Polymeric vs hydroxyapatite-based scaffolds on dental pulp stem cell proliferation and differentiation

    PubMed Central

    Khojasteh, Arash; Motamedian, Saeed Reza; Rad, Maryam Rezai; Shahriari, Mehrnoosh Hasan; Nadjmi, Nasser

    2015-01-01

    AIM: To evaluate adhesion, proliferation and differentiation of human dental pulp stem cells (hDPSCs) on four commercially available scaffold biomaterials. METHODS: hDPSCs were isolated from human dental pulp tissues of extracted wisdom teeth and established in stem cell growth medium. hDPSCs at passage 3-5 were seeded on four commercially available scaffold biomaterials, SureOss (Allograft), Cerabone (Xenograft), PLLA (Synthetic), and OSTEON II Collagen (Composite), for 7 and 14 d in osteogenic medium. Cell adhesion and morphology to the scaffolds were evaluated by scanning electron microscopy (SEM). Cell proliferation and differentiation into osteogenic lineage were evaluated using DNA counting and alkaline phosphatase (ALP) activity assay, respectively. RESULTS: All scaffold biomaterials except SureOss (Allograft) supported hDPSC adhesion, proliferation and differentiation. hDPSCs seeded on PLLA (Synthetic) scaffold showed the highest cell proliferation and attachment as indicated with both SEM and DNA counting assay. Evaluating the osteogenic differentiation capability of hDPSCs on different scaffold biomaterials with ALP activity assay showed high level of ALP activity on cells cultured on PLLA (Synthetic) and OSTEON II Collagen (Composite) scaffolds. SEM micrographs also showed that in the presence of Cerabone (Xenograft) and OSTEON II Collagen (Composite) scaffolds, the hDPSCs demonstrated the fibroblastic phenotype with several cytoplasmic extension, while the cells on PLLA scaffold showed the osteoblastic-like morphology, round-like shape. CONCLUSION: PLLA scaffold supports adhesion, proliferation and osteogenic differentiation of hDPSCs. Hence, it may be useful in combination with hDPSCs for cell-based reconstructive therapy. PMID:26640621

  9. Borax-Loaded PLLA for Promotion of Myogenic Differentiation.

    PubMed

    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. PMID:26239605

  10. Borax-Loaded PLLA for Promotion of Myogenic Differentiation.

    PubMed

    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.

  11. Enhanced GLT-1 mediated glutamate uptake and migration of primary astrocytes directed by fibronectin-coated electrospun poly-L-lactic acid fibers

    PubMed Central

    Zuidema, Jonathan M.; Hyzinski-García, María C.; Vlasselaer, Kristien Van; Zaccor, Nicholas; Plopper, George E.; Mongin, Alexander A.; Gilbert, Ryan J.

    2014-01-01

    Bioengineered fiber substrates are increasingly studied as a means to promote regeneration and remodeling in the injured central nervous system (CNS). Previous reports largely focused on the ability of oriented scaffolds to bridge injured regions and direct outgrowth of axonal projections. In the present work, we explored the effects of electrospun microfibers on the migration and physiological properties of brain astroglial cells. Primary rat astrocytes were cultured on either fibronectin-coated poly-l-lactic acid (PLLA) films, fibronectin-coated randomly oriented PLLA electrospun fibers, or fibronectin-coated aligned PLLA electrospun fibers. Aligned PLLA fibers strongly altered astrocytic morphology, orienting cell processes, actin microfilaments, and microtubules along the length of the fibers. On aligned fibers, astrocytes also significantly increased their migration rates in the direction of fiber orientation. We further investigated if fiber topography modifies astrocytic neuroprotective properties, namely glutamate and glutamine transport and metabolism. This was done by quantifying changes in mRNA expression (qRT-PCR) and protein levels (Western blotting) for a battery of relevant biomolecules. Interestingly, we found that cells grown on random and/or aligned fibers increased the expression levels of two glutamate transporters, GLAST and GLT-1, and an important metabolic enzyme, glutamine synthetase, as compared to the fibronectin-coated films. Functional assays revealed increases in glutamate transport rates due to GLT-1 mediated uptake, which was largely determined by the dihydrokainate-sensitive GLT-1. Overall, this study suggests that aligned PLLA fibers can promote directed astrocytic migration, and, of most importance, our in vitro results indicate for the first time that electrospun PLLA fibers can positively modify neuroprotective properties of glial cells by increasing rates of glutamate uptake. PMID:24246642

  12. Sugar amino acid based scaffolds--novel peptidomimetics and their potential in combinatorial synthesis.

    PubMed

    Chakraborty, Tushar K; Jayaprakash, Sarva; Ghosh, Subhash

    2002-08-01

    To meet the growing demands for the development of new molecular entities for discovering new drugs and materials, organic chemists have started looking for new concepts to supplement traditional approaches. In one such approach, the expertise gained over the years in the area of organic synthesis and the rational drug-design concepts are combined together to create "nature-like" and yet unnatural organic molecules that are expected to provide leads in discovering new molecules. Emulating the basic principles followed by nature to build its vast repertoire of biomolecules, organic chemists are developing many novel multifunctional building blocks. Sugar amino acids constitute an important class of such polyfunctional scaffolds where the carboxyl, amino and hydroxyl groups provide an excellent opportunity for organic chemists to create structural diversities akin to nature's molecular arsenal. Recent advances in the area of combinatorial chemistry give unprecedented technological support for rapid compilations of sugar amino acid-based libraries exploiting the diversities of carbohydrate molecules and well-developed solid-phase peptide synthesis methods. This review chronicles the development of sugar amino acids as a novel class of peptidomimetic building blocks and their applications in generating desired secondary structures in peptides as well as in creating mimics of natural biopolymers. PMID:12180903

  13. Electrospun Poly(l-lactide)/Poly(ethylene glycol) Scaffolds Seeded with Human Amniotic Mesenchymal Stem Cells for Urethral Epithelium Repair.

    PubMed

    Lv, Xiaokui; Guo, Qianping; Han, Fengxuan; Chen, Chunyang; Ling, Christopher; Chen, Weiguo; Li, Bin

    2016-01-01

    Tissue engineering-based urethral replacement holds potential for repairing large segmental urethral defects, which remains a great challenge at present. This study aims to explore the potential of combining biodegradable poly(l-lactide) (PLLA)/poly(ethylene glycol) (PEG) scaffolds and human amniotic mesenchymal cells (hAMSCs) for repairing urethral defects. PLLA/PEG fibrous scaffolds with various PEG fractions were fabricated via electrospinning. The scaffolds were then seeded with hAMSCs prior to implantation in New Zealand male rabbits that had 2.0 cm-long defects in the urethras. The rabbits were randomly divided into three groups. In group A, hAMSCs were grown on PLLA/PEG scaffolds for two days and then implanted to the urethral defects. In group B, only the PLLA/PEG scaffolds were used to rebuild the rabbit urethral defect. In group C, the urethral defect was reconstructed using a regular urethral reparation technique. The repair efficacy was compared among the three groups by examining the urethral morphology, tissue reconstruction, luminal patency, and complication incidence (including calculus formation, urinary fistula, and urethral stricture) using histological evaluation and urethral radiography methods. Findings from this study indicate that hAMSCs-loaded PLLA/PEG scaffolds resulted in the best urethral defect repair in rabbits, which predicts the promising application of a tissue engineering approach for urethral repair. PMID:27517902

  14. Electrospun Poly(l-lactide)/Poly(ethylene glycol) Scaffolds Seeded with Human Amniotic Mesenchymal Stem Cells for Urethral Epithelium Repair.

    PubMed

    Lv, Xiaokui; Guo, Qianping; Han, Fengxuan; Chen, Chunyang; Ling, Christopher; Chen, Weiguo; Li, Bin

    2016-01-01

    Tissue engineering-based urethral replacement holds potential for repairing large segmental urethral defects, which remains a great challenge at present. This study aims to explore the potential of combining biodegradable poly(l-lactide) (PLLA)/poly(ethylene glycol) (PEG) scaffolds and human amniotic mesenchymal cells (hAMSCs) for repairing urethral defects. PLLA/PEG fibrous scaffolds with various PEG fractions were fabricated via electrospinning. The scaffolds were then seeded with hAMSCs prior to implantation in New Zealand male rabbits that had 2.0 cm-long defects in the urethras. The rabbits were randomly divided into three groups. In group A, hAMSCs were grown on PLLA/PEG scaffolds for two days and then implanted to the urethral defects. In group B, only the PLLA/PEG scaffolds were used to rebuild the rabbit urethral defect. In group C, the urethral defect was reconstructed using a regular urethral reparation technique. The repair efficacy was compared among the three groups by examining the urethral morphology, tissue reconstruction, luminal patency, and complication incidence (including calculus formation, urinary fistula, and urethral stricture) using histological evaluation and urethral radiography methods. Findings from this study indicate that hAMSCs-loaded PLLA/PEG scaffolds resulted in the best urethral defect repair in rabbits, which predicts the promising application of a tissue engineering approach for urethral repair.

  15. Electrospun Poly(l-lactide)/Poly(ethylene glycol) Scaffolds Seeded with Human Amniotic Mesenchymal Stem Cells for Urethral Epithelium Repair

    PubMed Central

    Lv, Xiaokui; Guo, Qianping; Han, Fengxuan; Chen, Chunyang; Ling, Christopher; Chen, Weiguo; Li, Bin

    2016-01-01

    Tissue engineering-based urethral replacement holds potential for repairing large segmental urethral defects, which remains a great challenge at present. This study aims to explore the potential of combining biodegradable poly(l-lactide) (PLLA)/poly(ethylene glycol) (PEG) scaffolds and human amniotic mesenchymal cells (hAMSCs) for repairing urethral defects. PLLA/PEG fibrous scaffolds with various PEG fractions were fabricated via electrospinning. The scaffolds were then seeded with hAMSCs prior to implantation in New Zealand male rabbits that had 2.0 cm-long defects in the urethras. The rabbits were randomly divided into three groups. In group A, hAMSCs were grown on PLLA/PEG scaffolds for two days and then implanted to the urethral defects. In group B, only the PLLA/PEG scaffolds were used to rebuild the rabbit urethral defect. In group C, the urethral defect was reconstructed using a regular urethral reparation technique. The repair efficacy was compared among the three groups by examining the urethral morphology, tissue reconstruction, luminal patency, and complication incidence (including calculus formation, urinary fistula, and urethral stricture) using histological evaluation and urethral radiography methods. Findings from this study indicate that hAMSCs-loaded PLLA/PEG scaffolds resulted in the best urethral defect repair in rabbits, which predicts the promising application of a tissue engineering approach for urethral repair. PMID:27517902

  16. In-vitro degradation characteristics of poly(e-caprolactone)/poly(glycolic acid) scaffolds fabricated via solid-state cryomilling.

    PubMed

    Jonnalagadda, John B; Rivero, Iris V; Warzywoda, Juliusz

    2015-10-01

    Poly(e-caprolactone) (PCL)/poly(glycolic acid) (PGA) scaffolds were fabricated via solid-state cryomilling along with compression molding and porogen leaching techniques. Four types of scaffolds were produced using four distinct cryomilling times. These scaffolds were evaluated for their in-vitro degradation behavior hydrolytically in phosphate buffer saline (PBS). The degradation profiles were investigated over a period of 60 days. The percentage of weight loss, percentage of water absorption, morphology, compressive, thermal, and material properties were studied as a function of degradation time. Weight loss and water absorption demonstrated a high correlation, which showed an increasing behavior with increase in cryomilling time and degradation time. Morphology of the scaffolds analyzed through scanning electron microscopy (SEM) revealed micro-cracks on the surface of the cylindrical struts due to hydrolytic attack and dissolution of hydrophilic PGA. Changes in compressive modulus and crystallinity over the degradation period and material properties were analyzed using X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. DSC and XRD results indicated that hydrolytic attack had taken place during degradation, resulting in moments of increased and decreased percent crystallinity. This study successfully brought forth the differences in resultant properties of the PCL/PGA scaffolds as a function of degradation time.

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

    PubMed

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

    2013-12-01

    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.

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

    PubMed

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

    2013-12-01

    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. PMID:24094186

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

    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 (Mw) 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 Mw 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-NO3--N·g-MLSS·h-1 by changing the Mw 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.

  20. Microporous Poly(L-Lactic Acid) Membranes Fabricated by Polyethylene Glycol Solvent-Cast/Particulate Leaching Technique

    PubMed Central

    Selvam, Shivaram; Chang, Wenji V.; Nakamura, Tamako; Samant, Deedar M.; Thomas, Padmaja B.; Trousdale, Melvin D.; Mircheff, Austin K.; Schechter, Joel E.

    2009-01-01

    With the eventual goal of developing a tissue-engineered tear secretory system, we found that primary lacrimal gland acinar cells grown on solid poly(L-lactic acid) (PLLA) supports expressed the best histiotypic morphology. However, to be able to perform vectorial transport functions, epithelia must be supported by a permeable substratum. In the present study, we describe the use of a solvent-cast/particulate leaching technique to fabricate microporous PLLA membranes (mpPLLAm) from PLLA/polyethylene glycol blends. Scanning electron microscopy revealed pores on both the air-cured (∼4 μm) and glass-cured sides (<2 μm) of the mpPLLAm. Diffusion studies were performed with mpPLLAm fabricated from 57.1% PLLA/42.9% polyethylene glycol blends to confirm the presence of channelized pores. The data reveal that glucose, L-tryptophan, and dextran (a high molecular weight glucose polymer) readily permeate mpPLLAm. Diffusion of the immunoglobulin G through the mpPLLAm decreased with time, suggesting the possible adsorption and occlusion of the pores. Cells cultured on the mpPLLAm (57.1/42.9 wt%) grew to subconfluent monolayers but retained histiotypic morphological and physiological characteristics of lacrimal acinar cells in vivo. Our results suggest that mpPLLAm fabricated using this technique may be useful as a scaffold for a bioartificial lacrimal gland device. PMID:19260769

  1. Importance of Poly(lactic-co-glycolic acid) in Scaffolds for Guided Bone Regeneration: A Focused Review.

    PubMed

    Castillo-Dalí, Gabriel; Velázquez-Cayón, Rocío; Serrera-Figallo, M Angeles; Rodríguez-González-Elipe, Agustín; Gutierrez-Pérez, José-Luis; Torres-Lagares, Daniel

    2015-08-01

    Total or partial tissue damage and loss of function in an organ are two of the most serious and costly issues in human health. Initially, these problems were approached through organ and allogenic tissue transplantation, but this option is limited by the scarce availability of donors. In this manner, new bone for restoring or replacing lost and damaged bone tissue is an important health and socioeconomic necessity. Tissue engineering has been used as a strategy during the 21st century for mitigating this need through the development of guided bone regeneration scaffold and composites. In this manner, compared with other traditional methods, bone tissue engineering offers a new and interesting approach to bone repair. The poly-α-hydroxy acids, which include the copolymers of lactic acid and glycolic acid, have been used commonly in the fabrication of these scaffolds. The objective of our article was to review the characteristics and functions of scaffold with biomedical applications, with special interest in scaffold construction using poly(lactic-co-glycolic acid) polymers, in order to update the current methods used for fabrication and to improve the quality of these scaffolds, integrating this information into the context of advancements made in tissue engineering based on these structures. In the future, research into bone regeneration should be oriented toward a fruitful exchange between disciplines involved in tissue engineering, which is coming very close to filling the gaps in our ability to provide implants and restoration of functionality in bone tissue. Overcoming this challenge will provide benefits to a major portion of the population and facilitate substantial improvements to quality of life.

  2. Improvement of Distribution and Osteogenic Differentiation of Human Mesenchymal Stem Cells by Hyaluronic Acid and β-Tricalcium Phosphate-Coated Polymeric Scaffold In Vitro

    PubMed Central

    Chen, Muwan; Le, Dang Q.S.; Kjems, Jørgen; Bünger, Cody; Lysdahl, Helle

    2015-01-01

    Abstract Bone tissue engineering requires a well-designed scaffold that can be biodegradable, biocompatible, and support the stem cells to osteogenic differentiation. Porous polycaprolactone (PCL) scaffold prepared by fused deposition modeling is an attractive biomaterial that has been used in clinic. However, PCL scaffolds lack biological function and osteoinductivity. In this study, we functionalized the PCL scaffolds by embedding them with a matrix of hyaluronic acid/β-tricalcium phosphate (HA/TCP). Human mesenchymal stem cells (MSCs) were cultured on scaffolds with and without coating to investigate proliferation and osteogenic differentiation. The DNA amount was significantly higher in the HA/TCP-coated scaffold on day 21. At the gene expression level, HA/TCP coating significantly increased the expression of ALP and COLI on day 4. These data correlated with the ALP activity peaking on day 7 in the HA/TCP-coated scaffold. Scanning electron microscope and histological analysis revealed that the cell matrix and calcium deposition were distributed more uniformly in the coated scaffolds compared to scaffolds without coating. In conclusion, the HA/TCP coating improved cellular proliferation, osteogenic differentiation, and uniform distribution of the cellular matrix in vitro. The HA/TCP-PCL scaffold holds great promise to accommodate human bone marrow-derived MSCs for bone reconstruction purposes, which warrants future in vivo studies. PMID:26487981

  3. Biological and Tribological Assessment of Poly(Ethylene Oxide Terephthalate)/Poly(Butylene Terephthalate), Polycaprolactone, and Poly (L\\DL) Lactic Acid Plotted Scaffolds for Skeletal Tissue Regeneration.

    PubMed

    Hendrikson, Wilhelmus J; Zeng, Xiangqiong; Rouwkema, Jeroen; van Blitterswijk, Clemens A; van der Heide, Emile; Moroni, Lorenzo

    2016-01-21

    Additive manufactured scaffolds are fabricated from three commonly used biomaterials, polycaprolactone (PCL), poly (L\\DL) lactic acid (P(L\\DL)LA), and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT). Scaffolds are compared biologically and tribologically. Cell-seeded PEOT/PBT scaffolds cultured in osteogenic and chondrogenic differentiation media show statistical significantly higher alkaline phosphatase (ALP) activity/DNA and glycosaminoglycans (GAG)/DNA ratios, followed by PCL and P(L\\DL)LA scaffolds, respectively. The tribological performance is assessed by determining the friction coefficients of the scaffolds at different loads and sliding velocities. With increasing load or decreasing sliding velocity, the friction coefficient value decreases. PEOT/PBT show to have the lowest friction coefficient value, followed by PCL and P(L\\DL)LA. The influence of the scaffold architecture is further determined with PEOT/PBT. Reducing of the fiber spacing results in a lower friction coefficient value. The best and the worst performing scaffold architecture are chosen to investigate the effect of cell culture on the friction coefficient. Matrix deposition is low in the cell-seeded scaffolds and the effect is, therefore, undetermined. Taken together, our studies show that PEOT/PBT scaffolds support better skeletal differentiation of seeded stromal cells and lower friction coefficient compared to PCL and P(L/DL)A scaffolds.

  4. Biological and Tribological Assessment of Poly(Ethylene Oxide Terephthalate)/Poly(Butylene Terephthalate), Polycaprolactone, and Poly (L\\DL) Lactic Acid Plotted Scaffolds for Skeletal Tissue Regeneration.

    PubMed

    Hendrikson, Wilhelmus J; Zeng, Xiangqiong; Rouwkema, Jeroen; van Blitterswijk, Clemens A; van der Heide, Emile; Moroni, Lorenzo

    2016-01-21

    Additive manufactured scaffolds are fabricated from three commonly used biomaterials, polycaprolactone (PCL), poly (L\\DL) lactic acid (P(L\\DL)LA), and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT). Scaffolds are compared biologically and tribologically. Cell-seeded PEOT/PBT scaffolds cultured in osteogenic and chondrogenic differentiation media show statistical significantly higher alkaline phosphatase (ALP) activity/DNA and glycosaminoglycans (GAG)/DNA ratios, followed by PCL and P(L\\DL)LA scaffolds, respectively. The tribological performance is assessed by determining the friction coefficients of the scaffolds at different loads and sliding velocities. With increasing load or decreasing sliding velocity, the friction coefficient value decreases. PEOT/PBT show to have the lowest friction coefficient value, followed by PCL and P(L\\DL)LA. The influence of the scaffold architecture is further determined with PEOT/PBT. Reducing of the fiber spacing results in a lower friction coefficient value. The best and the worst performing scaffold architecture are chosen to investigate the effect of cell culture on the friction coefficient. Matrix deposition is low in the cell-seeded scaffolds and the effect is, therefore, undetermined. Taken together, our studies show that PEOT/PBT scaffolds support better skeletal differentiation of seeded stromal cells and lower friction coefficient compared to PCL and P(L/DL)A scaffolds. PMID:26775915

  5. Synthesis and Characterization of Poly(lactic-co-glycolic) Acid Nanoparticles-Loaded Chitosan/Bioactive Glass Scaffolds as a Localized Delivery System in the Bone Defects

    PubMed Central

    Nazemi, K.; Moztarzadeh, F.; Jalali, N.; Asgari, S.; Mozafari, M.

    2014-01-01

    The functionality of tissue engineering scaffolds can be enhanced by localized delivery of appropriate biological macromolecules incorporated within biodegradable nanoparticles. In this research, chitosan/58S-bioactive glass (58S-BG) containing poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been prepared and then characterized. The effects of further addition of 58S-BG on the structure of scaffolds have been investigated to optimize the characteristics of the scaffolds for bone tissue engineering applications. The results showed that the scaffolds had high porosity with open pores. It was also shown that the porosity decreased with increasing 58S-BG content. Furthermore, the PLGA nanoparticles were homogenously distributed within the scaffolds. According to the obtained results, the nanocomposites could be considered as highly bioactive bone tissue engineering scaffolds with the potential of localized delivery of biological macromolecules. PMID:24949477

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

    PubMed

    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.

  7. Compressive and Tensile Behaviours of PLLA Matrix Composites Reinforced with Randomly Dispersed Flax Fibres

    NASA Astrophysics Data System (ADS)

    Roussière, Fabrice; Baley, Christophe; Godard, Grégory; Burr, Dominique

    2012-04-01

    Nowadays, the ecological footprint of a material is becoming tremendously important. The Poly l-Lactide Acid (PLLA) matrix composites reinforced by randomly scattered flax fibres have mechanical properties similar to polyester/glass composites [1], lower environmental impacts and can be compost at the end of their lives. In this study, the mechanical characterization of biocomposites has been pushed further with the determination of the compressive and tensile properties. Furthermore, the mechanical properties of single flax fibres have been measured and implemented in a micro-mechanical estimation of the composite elastic modulus. Tensile and compressive stiffness determined by the mechanical analyses show very good correlations with the mathematical estimation.

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

    PubMed

    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.

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

    PubMed

    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. PMID:25791418

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

    PubMed

    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.

  11. Effects of hesperidin loaded poly(lactic-co-glycolic acid) scaffolds on growth behavior of costal cartilage cells in vitro and in vivo.

    PubMed

    Cho, Sun Ah; Cha, Se Rom; Park, Sang Mi; Kim, Kyoung Hee; Lee, Hyun Gu; Kim, Eun Young; Lee, Dongwon; Khang, Gilson

    2014-01-01

    It has been widely accepted that costal cartilage cells (CCs) have more excellent initial proliferation capacity than articular cartilage cells. Biodegradable synthetic polymer poly(lactic-co-glycolic acid) (PLGA) was approved by Food and Drug Administration. Hesperidin has antifungal, antiviral, antioxidant, anti-inflammatory, and anticarcinogenic properties. Hesperidin loaded (0, 3, 5, and 10 wt.%) PLGA scaffolds were prepared and in vitro and in vivo properties were characterized. Scaffolds were seeded with CCs isolated from rabbit, which were kept in culture to harvest for histological analysis. Hesperidin/PLGA scaffolds were also implanted in nude mice for 7 and 28 days. Assays of 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfo-phenyl)-2H-tetrazolium, monosodium salt (WST), and scanning electron microscope were carried out to evaluate attachment and proliferation of CCs in hesperidin/PLGA scaffolds. Glycosaminoglycan assay was performed to confirm the effects of hesperidin on extracellular matrix formation. Reverse-transcriptase polymerase chain reaction was carried out to confirm the expression of the specific genes for CCs. In these results, we demonstrated that cell attachment and proliferation on hesperidin/PLGA scaffolds were more excellent compared with on PLGA scaffold. Specially, 5 wt.% hesperidin/PLGA scaffold represented the best results among other scaffolds. Thus, 5 wt.% hesperidin/PLGA scaffold will be applicable to tissue engineering cartilage. PMID:24588773

  12. Effect of cryomilling times on the resultant properties of porous biodegradable poly(e-caprolactone)/poly(glycolic acid) scaffolds for articular cartilage tissue engineering.

    PubMed

    Jonnalagadda, John B; Rivero, Iris V

    2014-12-01

    The aim of this research is to develop a parametric investigation of the fabrication of poly(e-caprolactone) (PCL)/poly(glycolic acid) (PGA) scaffolds to decipher the influence of cryomilling time on the scaffolds' resultant physical, morphological and mechanical characteristics. Scaffolds were fabricated via solid-state cryomilling to prepare a homogeneous blend along with conventional compression molding and porogen leaching yielding interconnected porous scaffolds. PCL/PGA scaffolds fabricated through this technique demonstrated high porosity at all cryomilling times. Morphological analysis revealed a co-continuous interconnected pore network. While mean pore size decreased, water uptake and compressive properties increased with increasing cryomilling times. Porous scaffolds cryomilled for 12min exhibited a mean pore size within the optimal range for tissue engineering and chondrocyte ingrowth. And the compressive modulus of scaffolds cryomilled for 12, 30 and 60min matched the compressive modulus of human articular cartilage. In addition, scaffolds exhibited water uptake, a key requirement in tissue engineering. A 60 day in vitro degradation study revealed mass loss starting from day 10 and increasing through day 60, while notable reduction in compressive properties was observed. The results indicated that cryomilling times affected the resultant properties of PCL/PGA scaffolds and will be interesting candidates for articular cartilage tissue engineering.

  13. A Combination of Biphasic Calcium Phosphate Scaffold with Hyaluronic Acid-Gelatin Hydrogel as a New Tool for Bone Regeneration

    PubMed Central

    Nguyen, Thuy Ba Linh

    2014-01-01

    A novel bone substitute was fabricated to enhance bone healing by combining ceramic and polymer materials. In this study, Hyaluronic acid (HyA)–Gelatin (Gel) hydrogel was loaded into a biphasic calcium phosphate (BCP) ceramic, and the resulting scaffold, with unique micro- and macroporous orientation, was evaluated for bone regeneration applications. The fabricated scaffold showed high interconnected porosity, with an average compressive strength of 2.8±0.15 MPa, which is usually recommended for cancellous bone substitution. In vitro cytocompatibility studies were conducted using bone marrow mesenchymal stem cells. The HyA-Gel–loaded BCP scaffold resulted in a significant increase in cell proliferation at 3 (p<0.05) and 7 days (p<0.001) and high alkaline phosphatase activities at 14 and 21 days. Furthermore, the in vivo studies showed that the implanted HyA-Gel–loaded BCP scaffold begins to degrade within 3 months after implantation. Histological sections also confirmed a rapid new bone formation and a high rate of collagen mineralization. A bone matrix formation was confirmed by positive immunohistochemistry staining of osteopontin, osteocalcin, and collagen type I. In vivo expression of extracellular matrix proteins demonstrated that this novel bone substitute holds great promise for use in stimulating new bone regeneration. PMID:24517159

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

    PubMed

    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.

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

    PubMed

    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.

  16. Polylactic acid-phosphate glass composite foams as scaffolds for bone tissue engineering.

    PubMed

    Georgiou, G; Mathieu, L; Pioletti, D P; Bourban, P-E; Månson, J-A E; Knowles, J C; Nazhat, S N

    2007-02-01

    Phosphate glass (PG) of the composition 0.46(CaO)-0.04(Na(2)O)-0.5(P(2)O(5)) was used as filler in poly-L-lactic acid (PLA) foams developed as degradable scaffolds for bone tissue engineering. The effect of PG on PLA was assessed both in bulk and porous composite foams. Composites with various PG content (0, 5, 10, and 20 wt %) were melt-extruded, and either compression-molded or foamed through supercritical CO(2). Dynamic mechanical analysis on the bulk composites showed that incorporating 20 wt % PG resulted in a significant increase in storage modulus. Aging studies in deionized water in terms of weight loss, pH change, and ion release inferred that the degradation was due to PG dissolution, and dependent on the amount of glass in the composites. Foaming was only possible for composites containing 5 and 10 wt % PG, as an increase in PG increased the foam densities; however, the level of porosity was maintained above 75%. PLA-T(g) in the foams was higher than those obtained for the bulk. Compressive moduli showed no significant reinforcement with glass incorporation in either expansion direction, indicating no anisotropy. Biocompatibility showed that proliferation of human fetal bone cells was more rapid for PLA compared to PLA-PG foams. However, the proliferation rate of PLA-PG foams were similar to those obtained for foams of PLA with either hydroxyapatite or beta-tricalcium phosphate.

  17. 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.

    PubMed

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

    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 417.65MPa and tensile strength 180.36MPa. 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.

  18. 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.

    PubMed

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

    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 417.65MPa and tensile strength 180.36MPa. 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. PMID:27287159

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

    PubMed

    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.

  20. Functionalization of Polycaprolactone Scaffolds with Hyaluronic Acid and β-TCP Facilitates Migration and Osteogenic Differentiation of Human Dental Pulp Stem Cells In Vitro

    PubMed Central

    Kraft, David Christian Evar; Lysdahl, Helle; Foldager, Casper Bindzus; Chen, Muwan; Kristiansen, Asger Albæk; Rölfing, Jan Hendrik Duedal; Bünger, Cody Eric

    2015-01-01

    In this study, we sought to assess the osteogenic potential of human dental pulp stem cells (DPSCs) on three different polycaprolactone (PCL) scaffolds. The backbone structure of the scaffolds was manufactured by fused deposition modeling (PCL scaffold). The composition and morphology was functionalized in two of the scaffolds. The first underwent thermal induced phase separation of PCL infused into the pores of the PCL scaffold. This procedure resulted in a highly variable micro- and nanostructured porous (NSP), interconnected, and isotropic tubular morphology (NSP-PCL scaffold). The second scaffold type was functionalized by dip-coating the PCL scaffold with a mixture of hyaluronic acid and β-TCP (HT-PCL scaffold). The scaffolds were cylindrical and measured 5 mm in height and 10 mm in diameter. They were seeded with 1×106 human DPSCs, a cell type known to express bone-related markers, differentiate into osteoblasts-like cells, and to produce a mineralized bone-like extracellular matrix. DPSCs were phenotypically characterized by flow cytometry for CD90+, CD73+, CD105+, and CD14−. DNA, ALP, and Ca2+ assays and real-time quantitative polymerase chain reaction for genes involved in osteogenic differentiation were analyzed on day 1, 7, 14, and 21. Cell viability and distribution were assessed on day 1, 7, 14, and 21 by fluorescent-, scanning electron-, and confocal microscopy. The results revealed that the DPSCs expressed relevant gene expression consistent with osteogenic differentiation. The NSP-PCL and HT-PCL scaffolds promoted osteogenic differentiation and Ca2+ deposition after 21 days of cultivation. Different gene expressions associated with mature osteoblasts were upregulated in these two scaffold types, suggesting that the methods in which the scaffolds promote osteogenic differentiation, depends on functionalization approaches. However, only the HT-PCL scaffold was also able to support cell proliferation and cell migration resulting in even cell

  1. Influence of micro-patterned PLLA membranes on outgrowth and orientation of hippocampal neurites.

    PubMed

    Morelli, Sabrina; Salerno, Simona; Piscioneri, Antonella; Papenburg, Bernke J; Di Vito, Anna; Giusi, Giuseppina; Canonaco, Marcello; Stamatialis, Dimitrios; Drioli, Enrico; De Bartolo, Loredana

    2010-09-01

    In neuronal tissue engineering many efforts are focused on creating biomaterials with physical and chemical pathways for controlling cellular proliferation and orientation. Neurons have the ability to respond to topographical features in their microenvironment causing among others, axons to proliferate along surface features such as substrate grooves in micro-and nanoscales. As a consequence these neuronal elements are able to correctly adhere, migrate and orient within their new environment during growth. Here we explored the polarization and orientation of hippocampal neuronal cells on nonpatterned and micro-patterned biodegradable poly(l-lactic acid) (PLLA) membranes with highly selective permeable properties. Dense and porous nonpatterned and micro-patterned membranes were prepared from PLLA by Phase Separation Micromolding. The micro-patterned membranes have a three-dimensional structure consisting of channels and ridges and of bricks of different widths. Nonpatterned and patterned membranes were used for hippocampal neuronal cultures isolated from postnatal days 1-3 hamsters and the neurite length, orientation and specific functions of cells were investigated up to 12 days of culture. Neurite outgrowth, length plus orientation tightly overlapped the pattern of the membrane surface. Cell distribution occurred only in correspondence to membrane grooves characterized by continuous channels whereas on membranes with interconnected channels, cells not only adhered to and elongated their cellular processes in the grooves but also in the breaking points. High orientation degrees of cells were determined particularly on the patterned porous membranes with channel width of 20 mum and ridges of 17 mum whereas on dense nonpatterned membranes as well as on polystyrene culture dish (PSCD) controls, a larger number of primary developed neurites were distributed. Based on these results, PLLA patterned membranes may directly improve the guidance of neurite extension and

  2. Raman and infrared study of electrospun PLLA/PCL nanofiber blends for use in tissue engineering

    NASA Astrophysics Data System (ADS)

    Enriquez Carrejo, Jose Luis

    Recently, the biomedical engineering field has developed at a very fast pace as improved techniques and materials become available to promote its growth. Consequently, the research in polymeric biomaterials has been highly stimulated by this trend. The goal of the current research is to demonstrate the usefulness of the Raman scattering, Raman mapping, and infrared absorption spectroscopies to tissue engineering, by spectroscopically characterizing blends of PLLA and PCL polymers, which were prepared by electrospinning with and without cell addition. The proposed use of these blends is as primary biomaterials in biodegradable scaffolds used in tissue engineering. Both Raman and infrared absorption spectra showed a direct relation between the relative intensities of the characteristic molecular vibrations of the individual polymers with their concentrations in each blend. The confocal Raman mapping of the samples that were prepared by co-electrospinning allowed direct visualization of different polymeric fibers. These images not only reveal the microstructural characteristics of each polymer, but they are also in good agreement with the Raman scattering results. Furthermore, by performing Raman mapping inside a single fiber, the homogeneity of the polymeric mixture can be visualized. These results demonstrate the existence of sub-domains of non-interacting polymers. The broadening of the cell characteristic peak at 1661 cm -1 observed in the Raman spectra of the blends seeded with C2C12 myoblasts, could be an indication of cell attachment onto the scaffolds.

  3. Preparation of PLLA/bpV(pic) microspheres and their effect on nerve cells.

    PubMed

    Lin, Qiang; Chen, Hai-yun; Li, Hao-shen; Cai, Yang-ting

    2014-02-01

    In this study, we prepared PLLA/bpV(pic) microspheres, a bpV(pic) controlled release system and examined their ability to protect nerve cells and promote axonal growth. PLLA microspheres were prepared by employing the o/w single emulsification-evaporation technique. Neural stem cells and dorsal root ganglia were divided into 3 groups in terms of the treatment they received: a routine medium group (cultured in DMEM), a PLLA microsphere group (DMEM containing PLLA microspheres alone) and a PLLA/bpV(pic) group [DMEM containing PLLA/bpV(pic) microspheres]. The effects of PLLA/bpV(pic) microspheres were evaluated by the live-dead test and measurement of axonal length. Our results showed that PLLA/bpV(pic) granulation rate was (88.2±5.6)%; particle size was (16.8±3.1)%, drug loading was (4.05±0.3)%; encapsulation efficiency was (48.5±1.8)%. The release time lasted for 30 days. In PLLA/bpV(pic) microsphere group, the cell survival rate was (95.2 ±4.77)%, and the length of dorsal root ganglion (DRG) was 718±95 μm, which were all significantly greater than those in ordinary routine medium group and PLLA microsphere group. This preliminary test results showed the PLLA/bpV(pic) microspheres were successfully prepared and they could promote the survival and growth of neural cells in DRG.

  4. Applying Electrospun Gelatin/Poly(lactic acid-co-glycolic acid) Bilayered Nanofibers to Fabrication of Meniscal Tissue Engineering Scaffold.

    PubMed

    Li, Peng; Zhang, Weiguo; Yu, Hongquan; Zheng, Lianjie; Yang, Liang; Liu, Gang; Sheng, Chenchen; Gui, Haoran; Ni, Shuo; Li, Pengsheng; Shi, Feng

    2016-05-01

    The menisci are fibrocartilaginous tissues composed primarily of an interlacing network of collagen fibers with nanoscale diameter. Electrospinning is a suitable process of producing nanoscale fibers that mimic collagen fibers. In this study, a bilayered scaffold (group B), which consists of a gelatin nanofiber mesh and a PLGA nanofiber mesh, has been fabricated through an electrospinning method. At the same time, we electrospun pure PLGA fibrous mesh (group A) and gelatin/PLGA composite fibrous mesh (group C) as control groups. In order to compare all scaffold morphologies, the scaffolds were imaged by SEM and some parameters were measured and analyzed as following: Diameters of fibrils are from the smallest of less than average 0.14 μm for group C to the biggest of nearly average 0.38 μm for group B. The scaffolds pore diameters are from average 4.9 μm for group A to average 11.2 μm for group B. Porosity rates show that the group B has the highest porosity rate at about 91%. The scaffolds' properties were compared and analyzed, including hydrophilicity property (water contact angle) and mechanical properties (tensile strength). The results of water contact angle showed the group B is the most hydrophil among the groups. The results of tensile strength showed the tensile strength of group C is the weakest among the groups. All the results showed significant differences between the groups. Finally, in vitro, the meniscal cells derived from New Zealand white rabbits menisci were seeded in the scaffolds. We observed the cells proliferation behavior in the scaffolds. All above demonstrates that a bi-layered gelatin/PLGA scaffold reveals not only concurrent effects of mechanics and cytocompatibility in a fibrous context, but also a promising scaffold for future meniscal repair strategies. PMID:27483813

  5. Magnetic NGF-releasing PLLA/iron oxide nanoparticles direct extending neurites and preferentially guide neurites along aligned electrospun microfibers.

    PubMed

    Zuidema, Jonathan M; Provenza, Christina; Caliendo, Tyler; Dutz, Silvio; Gilbert, Ryan J

    2015-11-18

    Nerve growth factor releasing composite nanoparticles (NGF-cNPs) were developed to direct the extension of neurite outgrowth from dorsal root ganglia (DRG). Iron oxide magnetic nanoparticles were incorporated into poly-l-lactic acid (PLLA) nanoparticles in order to position the NGF-cNPs in a culture dish. Neurites growing from DRG extended toward the NGF released from the NGF-cNPs. DRG were then cultured on aligned PLLA microfibers in the presence of NGF-cNPs, and these biomaterials combined to align DRG neurite extension along one axis and preferentially toward the NGF-cNPs. This combinatorial biomaterial approach shows promise as a strategy to direct the extension of regenerating neurites. PMID:26322376

  6. Fabrication of cell penetration enhanced poly (l-lactic acid-co-ɛ-caprolactone)/silk vascular scaffolds utilizing air-impedance electrospinning.

    PubMed

    Yin, Anlin; Li, Jiukai; Bowlin, Gary L; Li, Dawei; Rodriguez, Isaac A; Wang, Jing; Wu, Tong; Ei-Hamshary, Hany A; Al-Deyab, Salem S; Mo, Xiumei

    2014-08-01

    In the vascular prosthetic field, the prevailing thought is that for clinical, long-term success, especially bioresorbable grafts, cellular migration and penetration into the prosthetic structure is required to promote neointima formation and vascular wall development. In this study, we fabricated poly (l-lactic acid-co-ɛ-caprolactone) P(LLA-CL)/silk fibroin (SF) vascular scaffolds through electrospinning using both perforated mandrel subjected to various intraluminal air pressures (0-300kPa), and solid mandrel. The scaffolds were evaluated the cellular infiltration in vitro and mechanical properties. Vascular scaffolds were seeded with smooth muscle cells (SMCs) to evaluate cellular infiltration at 1, 7, and 14 days. The results revealed that air-impedance scaffolds allowed significantly more cell infiltration as compared to the scaffolds fabricated with solid mandrel. Meanwhile, results showed that both mandrel model and applied air pressure determined the interfiber distance and the alignment of fibers in the enhanced porosity regions of the structure which influenced cell infiltration. Uniaxial tensile testing indicated that the air-impedance scaffolds have sufficient ultimate strength, suture retention strength, and burst pressure as well as compliance approximating a native artery. In conclusion, the air-impedance scaffolds improved cellular infiltration without compromising overall biomechanical properties. These results support the scaffold's potential for vascular grafting and in situ regeneration.

  7. 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.

    PubMed

    Salerno, Aurelio; Guarino, Vincenzo; Oliviero, Olimpia; Ambrosio, Luigi; Domingo, Concepción

    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.

  8. ERK Signals: Scaffolding Scaffolds?

    PubMed Central

    Casar, Berta; Crespo, Piero

    2016-01-01

    ERK1/2 MAP Kinases become activated in response to multiple intra- and extra-cellular stimuli through a signaling module composed of sequential tiers of cytoplasmic kinases. Scaffold proteins regulate ERK signals by connecting the different components of the module into a multi-enzymatic complex by which signal amplitude and duration are fine-tuned, and also provide signal fidelity by isolating this complex from external interferences. In addition, scaffold proteins play a central role as spatial regulators of ERKs signals. In this respect, depending on the subcellular localization from which the activating signals emanate, defined scaffolds specify which substrates are amenable to be phosphorylated. Recent evidence has unveiled direct interactions among different scaffold protein species. These scaffold-scaffold macro-complexes could constitute an additional level of regulation for ERK signals and may serve as nodes for the integration of incoming signals and the subsequent diversification of the outgoing signals with respect to substrate engagement. PMID:27303664

  9. Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury.

    PubMed

    Kushchayev, Sergiy V; Giers, Morgan B; Hom Eng, Doris; Martirosyan, Nikolay L; Eschbacher, Jennifer M; Mortazavi, Martin M; Theodore, Nicholas; Panitch, Alyssa; Preul, Mark C

    2016-07-01

    OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel-treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel-treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel-treated group. There was a decreased presence of inflammatory cells in the HA hydrogel-treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a

  10. Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury.

    PubMed

    Kushchayev, Sergiy V; Giers, Morgan B; Hom Eng, Doris; Martirosyan, Nikolay L; Eschbacher, Jennifer M; Mortazavi, Martin M; Theodore, Nicholas; Panitch, Alyssa; Preul, Mark C

    2016-07-01

    OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel-treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel-treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel-treated group. There was a decreased presence of inflammatory cells in the HA hydrogel-treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a

  11. Echogenicity as a surrogate for bioresorbable everolimus-eluting scaffold degradation: analysis at 1-, 3-, 6-, 12- 18, 24-, 30-, 36- and 42-month follow-up in a porcine model.

    PubMed

    Campos, Carlos M; Ishibashi, Yuki; Eggermont, Jeroen; Nakatani, Shimpei; Cho, Yun Kyeong; Dijkstra, Jouke; Reiber, Johan H C; Sheehy, Alexander; Lane, Jennifer; Kamberi, Marika; Rapoza, Richard; Perkins, Laura; Garcia-Garcia, Hector M; Onuma, Yoshinobu; Serruys, Patrick W

    2015-03-01

    The objective of the study is to validate intravascular quantitative echogenicity as a surrogate for molecular weight assessment of poly-l-lactide-acid (PLLA) bioresorbable scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California). We analyzed at 9 time points (from 1- to 42-month follow-up) a population of 40 pigs that received 97 Absorb scaffolds. The treated regions were analyzed by echogenicity using adventitia as reference, and were categorized as more (hyperechogenic or upperechogenic) or less bright (hypoechogenic) than the reference. The volumes of echogenicity categories were correlated with the measurements of molecular weight (Mw) by gel permeation chromatography. Scaffold struts appeared as high echogenic structures. The quantification of grey level intensity in the scaffold-vessel compartment had strong correlation with the scaffold Mw: hyperechogenicity (correlation coefficient = 0.75; P < 0.01), upperechogenicity (correlation coefficient = 0.63; P < 0.01) and hyper + upperechogenicity (correlation coefficient = 0.78; P < 0.01). In the linear regression, the R(2) for high echogenicity and Mw was 0.57 for the combination of hyper and upper echogenicity. IVUS high intensity grey level quantification is correlated to Absorb BVS residual molecular weight and can be used as a surrogate for the monitoring of the degradation of semi-crystalline polymers scaffolds. PMID:25627777

  12. Evaluation of electrospun PLLA/PEGDMA polymer coatings for vascular stent material.

    PubMed

    Boodagh, Parnaz; Guo, Dong-Jie; Nagiah, Naveen; Tan, Wei

    2016-08-01

    The field of percutaneous coronary intervention has seen a plethora of advances over the past few decades, which have allowed for its development into safe and effective treatments for patients suffering from cardiovascular diseases. However, stent thrombosis and in-stent restenosis remain clinically significant problems. Herein, we describe the synthesis and characterization of fibrous polymer coatings on stent material nitinol, in the hopes of developing a more suitable stent surface to enhance re-endothelialization. Electrospinning technique was used to fabricate polyethylene glycol dimethacrylate/poly l-lactide acid (PEGDMA/PLLA) blend fiber substrate with tunable elasticity and hydrophilicity for use as coatings. Attachment of platelets and arterial smooth muscle cells (SMC) onto the coatings as well as the secretory effect of mesenchymal stem cells cultured on the coatings on the proliferation and migration of arterial endothelial cells and SMCs were assessed. It was demonstrated that electrospun PEGDMA/PLLA coating with 1:1 ratio of the components on the nitinol stent-reduced platelet and SMC attachment and increased stem cell secretory factors that enhance endothelial proliferation. We therefore postulate that the fibrous coating surface would possess enhanced biological compatibility of nitinol stents and hold the potential in preventing stent failure through restenosis and thrombosis. PMID:27137629

  13. Biocompatibility assessment of novel collagen-sericin scaffolds improved with hyaluronic Acid and chondroitin sulfate for cartilage regeneration.

    PubMed

    Dinescu, Sorina; Gălăţeanu, Bianca; Albu, Mădălina; Lungu, Adriana; Radu, Eugen; Hermenean, Anca; Costache, Marieta

    2013-01-01

    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. PMID:24308001

  14. Improved hemocompatibility and endothelialization of vascular grafts by covalent immobilization of sulfated silk fibroin on poly(lactic-co-glycolic acid) scaffolds.

    PubMed

    Liu, Haifeng; Li, Xiaoming; Niu, Xufeng; Zhou, Gang; Li, Ping; Fan, Yubo

    2011-08-01

    Endothelialization of vascular grafts prior to implantation has been investigated widely to enhance biocompatibility and antithrombogenicity. Thrombosis of artificial vessels is typically caused by platelet adhesion and agglomeration following endothelial cells detachment when exposed to the shear stress of blood circulation. The present study thus aimed at preventing platelet adhesion and aggregation onto biomaterials before the endothelial confluence is fully achieved. We report this modification of poly(lactic-co-glycolic acid) (PLGA) scaffolds, both to impart hemocompatibility to prevent platelet adhesion and aggregation before the endothelial confluence is fully achieved and to support EC growth to accelerate endothelialization. The modification was achieved by covalent immobilization of sulfated silk fibroin on PLGA scaffolds using γ irradiation. Using phosphate-buffered saline (PBS) as an aging medium, it was demonstrated that the scaffolds prepared by γ irradiation had a good retention of sulfated silk fibroin. The systematic in vitro hemocompatibility evaluation revealed that sulfated silk fibroin covalently immobilized PLGA (S-PLGA) scaffolds-reduced platelet adhesion and activation, prolonged whole blood clotting time, activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). To evaluate further in vitro cytocompatibility of the scaffolds, we seeded vascular ECs on the scaffolds and cultured them for 2 weeks. The ECs were seen to attach and proliferate well on S-PLGA scaffolds, forming cell aggregates that gradually increased in size and fused with adjacent cell aggregates to form a monolayer covering the scaffold surface. Moreover, it was demonstrated through the gene transcript levels and the protein expressions of EC-specific markers that the cell functions of ECs on S-PLGA scaffolds were better preserved than those on PLGA scaffolds. Therefore, this study has described the generation of a vascular graft that

  15. Fabrication and mechanical properties of PLLA/PCL/HA composites via a biomimetic, dip coating, and hot compression procedure.

    PubMed

    Charles, L F; Shaw, M T; Olson, J R; Wei, M

    2010-06-01

    Currently, the bone-repair biomaterials market is dominated by high modulus metals and their alloys. The problem of stress-shielding, which results from elastic modulus mismatch between these metallic materials and natural bone, has stimulated increasing research into the development of polymer-ceramic composite materials that can more closely match the modulus of bone. In this study, we prepared poly(L: -lactic acid)/hydroxyapatite/poly(epsilon-caprolactone) (PLLA/HA/PCL) composites via a four-step process, which includes surface etching of the fiber, the deposition of the HA coating onto the PLLA fibers through immersion in simulated body fluid (SBF), PCL coating through a dip-coating process, and hot compression molding. The initial HA-coated PLLA fiber had a homogeneous and continuous coating with a gradient structure. The effects of HA: PCL ratio and molding temperature on flexural mechanical properties were studied and both were shown to be important to mechanical properties. Mechanical results showed that at low molding temperatures and up to an HA: PCL volume ratio of 1, the flexural strain decreased while the flexural modulus and strength increased. At higher mold temperatures with a lower viscosity of the PCL a HA: PCL ratio of 1.6 gave similar properties. The process successfully produced composites with flexural moduli near the lower range of bone. Such composites may have clinical use for load bearing bone fixation.

  16. Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

    NASA Astrophysics Data System (ADS)

    di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

    2015-11-01

    Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation.

  17. Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

    PubMed Central

    Di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

    2015-01-01

    Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation. PMID:26567894

  18. Immobilized lentivirus vector on chondroitin sulfate-hyaluronate acid-silk fibroin hybrid scaffold for tissue-engineered ligament-bone junction.

    PubMed

    Sun, Liguo; Li, Hongguo; Qu, Ling; Zhu, Rui; Fan, Xiangli; Xue, Yingsen; Xie, Zhenghong; Fan, Hongbin

    2014-01-01

    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- β 3 (TGF- β 3) 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- β 3 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.

  19. Modelling the degradation and elastic properties of poly(lactic-co-glycolic acid) films and regular open-cell tissue engineering scaffolds.

    PubMed

    Shirazi, Reyhaneh Neghabat; Ronan, William; Rochev, Yury; McHugh, Peter

    2016-02-01

    Scaffolding plays a critical rule in tissue engineering and an appropriate degradation rate and sufficient mechanical integrity are required during degradation and healing of tissue. This paper presents a computational investigation of the molecular weight degradation and the mechanical performance of poly(lactic-co-glycolic acid) (PLGA) films and tissue engineering scaffolds. A reaction-diffusion model which predicts the degradation behaviour is coupled with an entropy-based mechanical model which relates Young׳s modulus and the molecular weight. The model parameters are determined based on experimental data for in-vitro degradation of a PLGA film. Microstructural models of three different scaffold architectures are used to investigate the degradation and mechanical behaviour of each scaffold. Although the architecture of the scaffold does not have a significant influence on the degradation rate, it determines the initial stiffness of the scaffold. It is revealed that the size of the scaffold strut controls the degradation rate and the mechanical collapse. A critical length scale due to competition between diffusion of degradation products and autocatalytic degradation is determined to be in the range 2-100μm. Below this range, slower homogenous degradation occurs; however, for larger samples monomers are trapped inside the sample and faster autocatalytic degradation occurs.

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

    PubMed Central

    Yoon, Young Il; Park, Ko Eun; Lee, Seung Jin; Park, Won Ho

    2013-01-01

    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. PMID:24381937

  1. Fabrication of microfibrous and nano-/microfibrous scaffolds: melt and hybrid electrospinning and surface modification of poly(L-lactic acid) with plasticizer.

    PubMed

    Yoon, Young Il; Park, Ko Eun; Lee, Seung Jin; Park, Won Ho

    2013-01-01

    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.

  2. Production of gamma-aminobutyric acid from glucose by introduction of synthetic scaffolds between isocitrate dehydrogenase, glutamate synthase and glutamate decarboxylase in recombinant Escherichia coli.

    PubMed

    Pham, Van Dung; Lee, Seung Hwan; Park, Si Jae; Hong, Soon Ho

    2015-08-10

    Escherichia coli were engineered for the direct production of gamma-aminobutyric acid from glucose by introduction of synthetic protein scaffold. In this study, three enzymes consisting GABA pathway (isocitrate dehydrogenase, glutamate synthase and glutamate decarboxylase) were connected via synthetic protein scaffold. By introduction of scaffold, 0.92g/L of GABA was produced from 10g/L of glucose while no GABA was produced in wild type E. coli. The optimum pH and temperature for GABA production were 4.5 and 30°C, respectively. When competing metabolic network was inactivated by knockout mutation, maximum GABA concentration of 1.3g/L was obtained from 10g/L glucose. The recombinant E. coli strain which produces GABA directly from glucose was successfully constructed by introduction of protein scaffold.

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

    PubMed

    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

  4. Impact of polymer structure and composition on fully resorbable endovascular scaffold performance

    PubMed Central

    Ferdous, Jahid; Kolachalama, Vijaya B.; Shazly, Tarek

    2014-01-01

    Fully erodible endovascular scaffolds are being increasingly considered for the treatment of obstructive arterial disease owing to their potential to mitigate long-term risks associated with permanent alternatives. While complete scaffold erosion facilitates vessel healing, generation and release of material degradation by-products from candidate materials such as poly-l-lactide (PLLA) may elicit local inflammatory responses that limit implant efficacy. We developed a computational framework to quantify how the compositional and structural parameters of PLLA-based fully erodible endovascular scaffolds affect degradation kinetics, erosion kinetics and the transient accumulation of material by-products within the arterial wall. Parametric studies reveal that, while some material properties have similar effects on these critical processes, others induce qualitatively opposing responses. For example, scaffold degradation is only mildly responsive to changes in either PLLA polydispersity or the initial degree of crystallinity, while the erosion kinetics is comparatively sensitive to crystallinity. Moreover, lactide doping can effectively tune both scaffold degradation and erosion, but a concomitant increase in local byproduct accumulation raises concerns about implant safety. Optimized erodible endovascular scaffolds must precisely balance therapeutic function and biological response over the implant lifetime, where compositional and structural parameters will have differential effects on implant performance. PMID:23261926

  5. Fabrication of three-dimensional nano, micro and micro/nano scaffolds of porous poly(lactic acid) by electrospinning and comparison of cell infiltration by Z-stacking/three-dimensional projection technique.

    PubMed

    Shalumon, K T; Chennazhi, K P; Tamura, H; Kawahara, K; Nair, S V; Jayakumar, R

    2012-03-01

    The use of electrospun extracellular matrix (ECM)-mimicking nanofibrous scaffolds for tissue engineering is limited by poor cellular infiltration. The authors hypothesised that cell penetration could be enhanced in scaffolds by using a hierarchical structure where nano fibres are combined with micron-scale fibres while preserving the overall scaffold architecture. To assess this, we fabricated electrospun porous poly(lactic acid) (PLA) scaffolds having nanoscale, microscale and combined micro/nano architecture and evaluated the structural characteristics and biological response in detail. Although the bioactivity was intermediate to that for nanofibre and microfibre scaffold, a unique result of this study was that the micro/nano combined fibrous scaffold showed improved cell infiltration and distribution than the nanofibrous scaffold. Although the cells were found to be lining the scaffold periphery in the case of nanofibrous scaffold, micro/nano scaffolds had cells dispersed throughout the scaffold. Further, as expected, the addition of nanoparticles of hydroxyapatite (nHAp) improved the bioactivity, although it did not play a significant role in cell penetration. Thus, this strategy of creating a three-dimensional (3D) micro/nano architecture that would increase the porosity of the fibrous scaffold and thereby improving the cell penetration, can be utilised for the generation of functional tissue engineered constructs in vitro.

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

    PubMed

    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. PMID:26952489

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

    PubMed

    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.

  8. Implantation of preadipocyte-loaded hyaluronic acid-based scaffolds into nude mice to evaluate potential for soft tissue engineering.

    PubMed

    Hemmrich, Karsten; von Heimburg, Dennis; Rendchen, Raoul; Di Bartolo, Chiara; Milella, Eva; Pallua, Norbert

    2005-12-01

    The reconstruction of soft tissue defects following extensive deep burns or tumor resections remains an unresolved problem in plastic and reconstructive surgery since adequate implant materials are still not available. Preadipocytes, immature precursor cells found between mature adipocytes in adipose tissue, are a potential material for soft tissue engineering since they can proliferate and differentiate into adipose tissue after transplantation. In previous studies, we identified hyaluronan benzyl ester (HYAFF 11) sponges to be promising carrier matrices. This study now evaluates, in vitro and in vivo, a new sponge architecture with pores of 400 microm either made of plain HYAFF 11 or HYAFF 11 coated with the extracellular matrix glycosaminoglycan hyaluronic acid. Human preadipocytes were isolated, seeded onto carriers and implanted into nude athymic mice. Explants harvested after 3, 8, and 12 weeks were examined for macroscopical appearance, thickness, weight, pore structure, histology, and immunohistochemistry. Compared to previous studies, we found better penetration of cells into both types of scaffolds, with more extensive formation of new vessels throughout the construct but with only minor adipose tissue. Our encouraging results contribute towards a better seeded and vascularised scaffold but also show that the enhancement of adipogenic conversion of preadipocytes remains a major task for further in vivo experiments.

  9. Coating of ß-tricalcium phosphate scaffolds-a comparison between graphene oxide and poly-lactic-co-glycolic acid.

    PubMed

    Ardjomandi, N; Henrich, A; Huth, J; Klein, C; Schweizer, E; Scheideler, L; Rupp, F; Reinert, S; Alexander, D

    2015-08-04

    Bone regeneration in critical size defects is a major challenge in oral and maxillofacial surgery, and the gold standard for bone reconstruction still requires the use of autologous tissue. To overcome the need for a second intervention and to minimize morbidity, the development of new biomaterials with osteoinductive features is the focus of current research. As a scaffolding material, ß-tricalcium phosphate (ß-TCP) is suitable for bone regeneration purposes, although it does not carry any functional groups for the covalent immobilization of molecules. The aim of the present study was to establish effective coating variants for ß-TCP constructs to enable the biofunctionalization of anorganic blocks with different osteogenic molecules in future studies. We established working protocols for thin surface coatings consisting of polylactic-co-glycolic acid (PLGA) and graphene oxide (GO) by varying parameters. Surface properties such as the angularity and topography of the developed scaffolds were analyzed. To examine biological functionality, the adhesion and proliferation behavior of jaw periosteal cells (JPCs) were tested on the coated constructs. Our results suggest that PLGA is the superior material for surface coating of ß-TCP matrices, leading to higher JPC proliferation rates and providing a more suitable basis for further biofunctionalization in the field of bone tissue engineering.

  10. Self-reinforced composites of hydroxyapatite-coated PLLA fibers: fabrication and mechanical characterization.

    PubMed

    Charles, Lyndon F; Kramer, Erica R; Shaw, Montgomery T; Olson, James R; Wei, Mei

    2013-01-01

    Self-reinforced composites (SRCs) are materials where both the matrix and fiber-reinforcing phase are made up of the same polymer. Improved bonding can be achieved with self-reinforced composites compared to traditional dual-polymer, fiber-reinforced composites owing to the identical chemistry of the components in SRCs. Bonding between the fiber and matrix phase is an important factor in applications where mechanical stability is required, such as in the field of bone repair. In this study, we prepared bioabsorbable poly(L-lactic acid)/hydroxyapatite (PLLA/HA) self-reinforced composites via a three-step process that includes surface etching of the fiber, the deposition of the HA coating onto the PLLA fibers through immersion in simulated body fluid (SBF), and hot compaction molding. Although coated with a layer of HA, self-reinforced composites were successfully generated by hot compaction. The effects of compaction time (15 and 30 min), compaction temperature (140, 150, 155, 160, 165, and 170 °C), and HA wt% (0, 5, 10, and 15 wt%) on flexural mechanical properties were studied. Mechanical test results indicated that in unfilled (no HA) PLLA SRCs, compaction time and temperature increased the flexural modulus of the composites tested. Based on the results obtained for unfilled composites, a single compaction time and temperature condition of 15 min and 170 °C were selected to study the effect of HA loading on the composite mechanical properties. HA was successfully loaded onto the fibers at 0, 5, 10, and 15 wt% before hot compaction and was found to significantly increase flexural modulus (P=0.0001). Modulus values ranged from 8.3 GPa±0.5 (0 wt% HA) to 9.7 GPa±0.6 (15 wt% HA). Microscopy results suggest that the HA in these composites forms a nodular-like structure along the fibers, which allows polymer-polymer contact yet prevents longitudinal shear. The procedure used successfully generated composites with flexural moduli near the lower range of bone that may

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

    PubMed

    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. PMID:25958546

  12. Novel genipin-collagen immobilization of polylactic acid (PLA) fibers for use as tissue engineering scaffolds.

    PubMed

    Tambe, Nisarg; Di, Jin; Zhang, Ze; Bernacki, Susan; El-Shafei, Ahmed; King, Martin W

    2015-08-01

    The material surface plays an important role in the case of biomaterials used as tissue engineering scaffolds. On exposure to a biological environment, extra cellular matrix (ECM) proteins are adsorbed non-specifically onto the surface and cells interact indirectly with the surface through the adsorbed proteins. Most synthetic polymeric biomaterials lack the desirable surface properties for cells as well as have poor cellular adhesion due to their hydrophobic nature. The main objective of this study was to harness surface functionalization technologies to fabricate scaffolds that would be biocompatible and support the adhesion and proliferation of fibroblast cells. The collagen was immobilized on the surface of functionalized PLA via a novel natural cross-linking molecule genipin which resulted in improved cell proliferation of human dermal fibroblasts as compared to the PLA surface coated with collagen without genipin. It is believed that genipin helps reduce steric problems between the functional groups and large protein molecules, and enables immobilized peptide to move more freely in a biological environment.

  13. A 45-amino acid scaffold mined from the Protein Data Bank for high affinity ligand engineering

    PubMed Central

    Kruziki, Max A.; Bhatnagar, Sumit; Woldring, Daniel R.; Duong, Vandon T.; Hackel, Benjamin J.

    2015-01-01

    Summary Small protein ligands can provide superior physiological distribution versus antibodies and improved stability, production, and specific conjugation. Systematic evaluation of the Protein Data Bank identified a scaffold to push the limits of small size and robust evolution of stable, high-affinity ligands: 45-residue T7 phage gene 2 protein (Gp2) contains an α-helix opposite a β-sheet with two adjacent loops amenable to mutation. De novo ligand discovery from 108 mutants and directed evolution towards four targets yielded target-specific binders with affinities as strong as 200 ±100 pM, Tm’s from 65 ±3 °C to 80 ±1 °C, and retained activity after thermal denaturation. For cancer targeting, a Gp2 domain for epidermal growth factor receptor was evolved with 18 ±8 nM affinity, receptor-specific binding, and high thermal stability with refolding. The efficiency of evolving new binding function and the size, affinity, specificity, and stability of evolved domains render Gp2 a uniquely effective ligand scaffold. PMID:26165154

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

    NASA Astrophysics Data System (ADS)

    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

  15. Spontaneous Differentiation of Human Mesenchymal Stem Cells on Poly-Lactic-Co-Glycolic Acid Nano-Fiber Scaffold

    PubMed Central

    Sonomoto, Koshiro; Yamaoka, Kunihiro; Kaneko, Hiroaki; Yamagata, Kaoru; Sakata, Kei; Zhang, Xiangmei; Kondo, Masahiro; Zenke, Yukichi; Sabanai, Ken; Nakayamada, Shingo; Sakai, Akinori; Tanaka, Yoshiya

    2016-01-01

    Introduction 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. Methods 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. Results 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. Conclusions 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. PMID:27055270

  16. In vivo evaluation of nerve guidance channels of PTMC/PLLA porous biomaterial

    PubMed Central

    Adamus, Agnieszka; Kowalska-Ludwicka, Karolina; Grobelski, Bartlomiej; Cala, Jaroslaw; Rosiak, Janusz M.; Pasieka, Zbigniew

    2013-01-01

    Introduction Peripheral nerve disruptions, frequently occurring during limb injuries, give rise to serious complications of patients recovery resulting from limitations in neural tissue regeneration capabilities. To overcome this problem bridging techniques utilizing guidance channels gain their importance. Biodegradable polymeric tubes seem to be more prospective then non-degradable materials – no necessity of implant removal and possibilities of release of incorporated drugs or biologically active agents that may support nerve regeneration process are the main advantages. Material and methods Polymer blend of commercial poly(L-lactic acid) (PLLA) and in-house synthesized poly(trimethylene carbonate) (PTMC) were processed in an organic solvent – phase inversion process on a supporting rod – to form a guidance porous tube of 1.1 mm inner diameter. In vivo experiments on rat's cut femoral nerve by using either the tubes or end-to-end suturing (control group) involved 22 and 19 rats, respectively. Motor recovery of operated limbs, neuroma occurrence and histopathology of explanted nerves were evaluated after 30, 60 and 90 days of implantation. Results Motor recovery of the limbs was of similar rate for the two animal groups. The neuroma formation was evident in over 90% control specimens, while for the bridging group it was less than 40% of all evaluable samples (p = 0.0022). Biocompatibility of applied materials was affirmed by moderate tissue response. Conclusions Application of the biodegradable PLLA/PTMC polymeric tubes effectively supports regeneration of discontinued nerves. The applied material prevents neuroma formation, by reducing the scar tissue formation time and, thus, accelerating the process of neural tissue restoration. PMID:25861309

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

    SciTech Connect

    Matsuda, Yasuhiro; Fukatsu, Akinobu; Wang, Yangyang; Miyamoto, Kazuaki; Mays, Jimmy; Tasaka, Shigeru

    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.

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

    PubMed

    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. PMID:26706517

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

    PubMed

    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.

  20. Ligand-induced substrate steering and reshaping of [Ag2(H)](+) scaffold for selective CO2 extrusion from formic acid.

    PubMed

    Zavras, Athanasios; Khairallah, George N; Krstić, Marjan; Girod, Marion; Daly, Steven; Antoine, Rodolphe; Maitre, Philippe; Mulder, Roger J; Alexander, Stefanie-Ann; Bonačić-Koutecký, Vlasta; Dugourd, Philippe; O'Hair, Richard A J

    2016-01-01

    Metalloenzymes preorganize the reaction environment to steer substrate(s) along the required reaction coordinate. Here, we show that phosphine ligands selectively facilitate protonation of binuclear silver hydride cations, [LAg2(H)](+) by optimizing the geometry of the active site. This is a key step in the selective, catalysed extrusion of carbon dioxide from formic acid, HO2CH, with important applications (for example, hydrogen storage). Gas-phase ion-molecule reactions, collision-induced dissociation (CID), infrared and ultraviolet action spectroscopy and computational chemistry link structure to reactivity and mechanism. [Ag2(H)](+) and [Ph3PAg2(H)](+) react with formic acid yielding Lewis adducts, while [(Ph3P)2Ag2(H)](+) is unreactive. Using bis(diphenylphosphino)methane (dppm) reshapes the geometry of the binuclear Ag2(H)(+) scaffold, triggering reactivity towards formic acid, to produce [dppmAg2(O2CH)](+) and H2. Decarboxylation of [dppmAg2(O2CH)](+) via CID regenerates [dppmAg2(H)](+). These gas-phase insights inspired variable temperature NMR studies that show CO2 and H2 production at 70 °C from solutions containing dppm, AgBF4, NaO2CH and HO2CH. PMID:27265868

  1. Ligand-induced substrate steering and reshaping of [Ag2(H)]+ scaffold for selective CO2 extrusion from formic acid

    PubMed Central

    Zavras, Athanasios; Khairallah, George N.; Krstić, Marjan; Girod, Marion; Daly, Steven; Antoine, Rodolphe; Maitre, Philippe; Mulder, Roger J.; Alexander, Stefanie-Ann; Bonačić-Koutecký, Vlasta; Dugourd, Philippe; O'Hair, Richard A. J.

    2016-01-01

    Metalloenzymes preorganize the reaction environment to steer substrate(s) along the required reaction coordinate. Here, we show that phosphine ligands selectively facilitate protonation of binuclear silver hydride cations, [LAg2(H)]+ by optimizing the geometry of the active site. This is a key step in the selective, catalysed extrusion of carbon dioxide from formic acid, HO2CH, with important applications (for example, hydrogen storage). Gas-phase ion-molecule reactions, collision-induced dissociation (CID), infrared and ultraviolet action spectroscopy and computational chemistry link structure to reactivity and mechanism. [Ag2(H)]+ and [Ph3PAg2(H)]+ react with formic acid yielding Lewis adducts, while [(Ph3P)2Ag2(H)]+ is unreactive. Using bis(diphenylphosphino)methane (dppm) reshapes the geometry of the binuclear Ag2(H)+ scaffold, triggering reactivity towards formic acid, to produce [dppmAg2(O2CH)]+ and H2. Decarboxylation of [dppmAg2(O2CH)]+ via CID regenerates [dppmAg2(H)]+. These gas-phase insights inspired variable temperature NMR studies that show CO2 and H2 production at 70 °C from solutions containing dppm, AgBF4, NaO2CH and HO2CH. PMID:27265868

  2. Poly-L-lactic acid: a perspective from my practice.

    PubMed

    Sadick, Neil S

    2008-03-01

    Lipoatrophic sagging in the periorbital and cheek areas is a characteristic feature of the aging face. Soft tissue regeneration in these areas using a volumizer such as poly-l-lactic acid (PLLA) can help reduce the impact of these features. PLLA generates semipermanent correction, lasting for 2 years, and is a resorbable biocompatible device with a history of successful use in many clinical applications. This practice has administered many treatments of PLLA over the past 2 years with excellent results and with minimal complications. Minimization of adverse events and optimal cosmetic results are achieved when PLLA is diluted appropriately, injected in the proper plane and with posttreatment massage. The physician can fine-tune tissue volume correction with PLLA by spacing treatment sessions at least 4 to 6 weeks apart. Although approved for the correction of facial lipoatrophy in patients with human immunodeficiency virus, approval for the use of PLLA for cosmetic indications is currently pending.

  3. Fabrication of long-acting drug release property of hierarchical porous bioglasses/polylactic acid fibre scaffolds for bone tissue engineering.

    PubMed

    Wang, Dan; Lin, Huiming; Jiang, Jingjie; Jin, Qumei; Li, Lei; Dong, Yan; Qu, Fengyu

    2015-04-01

    Hierarchical porous fibre scaffolds with mesoporous bioglasses (MBGs) and polylactic acid (PLA) were successfully fabricated by the electrospinning method. These compound scaffolds possess macropores with sizes of about 100 nm because of the solvent evaporation from the fibre and the mesoporous structure ( ∼4.0 nm) originated from MBGs. The biomineralisation ability was investigated in simulated body fluid. The fibre structure is beneficial for inducing the growth of hydroxyapatite. In addition, compared with pure MBGs, the materials (MP-1 and MP-2) exhibit a long-acting drug release process up to 140 h and the drug release process corresponds with the Fickian diffusion mechanism. With the special fibre morphology and the hierarchical porous structure, the MBGs/PLA fibre scaffolds are expected to have potential application for bone tissue repair and regeneration.

  4. Preparation of hydrophilic poly(lactic acid) tissue engineering scaffold via (PLA)-(PLA-b-PEG)-(PEG) solution casting and thermal-induced surface structural transformation.

    PubMed

    Zhu, Xiaomin; Zhong, Tian; Huang, Ran; Wan, Ajun

    2015-01-01

    Porous poly(lactic acid) (PLA) tissue engineering scaffolds with a hydrophilic surface assembled by polyethylene glycol aggregations were prepared by the solvent casting/particulate leaching method from (PLA)-(PLA-b-PEG)-(PEG) blend solution, where the PLA-b-PEG block polymer serves as an amphiphilic glue between two phases. A thermal recrystallization process was inserted before leaching to induce a phase separation, which subsequently squeezes out PEG to form a hydrophilic shell. Characterizations of XRD and DSC indicated the composition and mixing states of materials. The water contact angle test qualitatively presented the excellent hydrophilicity compared to the pure PLA or PLA-PEG simple blend scaffold. The scanning electron microscope results confirmed the formation of porous structure of [Formula: see text] pore size, with an observable phase separation on the surface. The scaffold was degraded in PBS at [Formula: see text], and the degradation exhibits a three-stage behavior, which evidenced the amphiphilically glued phase separations.

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

    PubMed

    Wang, Zongliang; Xu, Yang; Wang, Yu; Ito, Yoshihiro; Zhang, Peibiao; Chen, Xuesi

    2016-03-14

    Nanocomposite of hydroxyapatite (HA) surface grafted with L-lactic acid oligomer (LAc oligomer) (op-HA) showed improved interface compatibility, mechanical property, and biocompatibility in our previous study. In this paper, composite scaffolds of op-HA with controlled grafting different amounts of LAc oligomer (1.1, 5.2, and 9.1 wt %) were fabricated and implanted to repair rabbit radius defects. The dispersion of op-HA nanoparticles was more uniform than n-HA in chloroform and nanocomposites scaffold. Calcium and phosphorus exposure, in vitro biomineralization ability, and cell proliferation were much higher in the op-HA1.1 wt %/PLGA scaffolds than the other groups. The osteodifferentiation and bone fusion in animal tests were significantly enhanced for op-HA5.2 wt %/PLGA scaffolds. The results indicated that the grafted LAc oligomer of 5.2 or 9.1 wt %, which formed a barrier layer on the HA surface, prevented the exposure of nucleation sites. The shielded nucleation sites of op-HA particles (5.2 wt %) might be easily exposed as the grafted LAc oligomer was decomposed easily by enzyme systems in vivo. Findings from this study have revealed that grafting 1.1 wt % amount of LAc oligomer on hydroxyapatite could improve in vitro mineralization, and 5.2 wt % could promote in vivo osteogenesis capacity of composite scaffolds. PMID:26821731

  6. Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells.

    PubMed

    Caires, Hugo R; Esteves, Tiago; Quelhas, Pedro; Barbosa, Mário A; Navarro, Melba; Almeida, Catarina R

    2016-09-01

    Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment.

  7. Macrophage interactions with polylactic acid and chitosan scaffolds lead to improved recruitment of human mesenchymal stem/stromal cells: a comprehensive study with different immune cells.

    PubMed

    Caires, Hugo R; Esteves, Tiago; Quelhas, Pedro; Barbosa, Mário A; Navarro, Melba; Almeida, Catarina R

    2016-09-01

    Despite the importance of immune cell-biomaterial interactions for the regenerative outcome, few studies have investigated how distinct three-dimensional biomaterials modulate the immune cell-mediated mesenchymal stem/stromal cells (MSC) recruitment and function. Thus, this work compares the response of varied primary human immune cell populations triggered by different model scaffolds and describes its functional consequence on recruitment and motility of bone marrow MSC. It was found that polylactic acid (PLA) and chitosan scaffolds lead to an increase in the metabolic activity of macrophages but not of peripheral blood mononuclear cells (PBMC), natural killer (NK) cells or monocytes. PBMC and NK cells increase their cell number in PLA scaffolds and express a secretion profile that does not promote MSC recruitment. Importantly, chitosan increases IL-8, MIP-1, MCP-1 and RANTES secretion by macrophages while PLA stimulates IL-6, IL-8 and MCP-1 production, all chemokines that can lead to MSC recruitment. This secretion profile of macrophages in contact with biomaterials correlates with the highest MSC invasion. Furthermore, macrophages enhance stem cell motility within chitosan scaffolds by 44% but not in PLA scaffolds. Thus, macrophages are the cells that in contact with engineered biomaterials become activated to secrete bioactive molecules that stimulate MSC recruitment. PMID:27628173

  8. Engineering vascular tissue with functional smooth muscle cells derived from human iPS cells and nanofibrous scaffolds.

    PubMed

    Wang, Yongyu; Hu, Jiang; Jiao, Jiao; Liu, Zhongning; Zhou, Zhou; Zhao, Chao; Chang, Lung-Ji; Chen, Y Eugene; Ma, Peter X; Yang, Bo

    2014-10-01

    Tissue-engineered blood vessels (TEBVs) are promising in the replacement of diseased vascular tissues. However, it remains a great challenge to obtain a sufficient number of functional smooth muscle cells (SMCs) in a clinical setting to construct patient-specific TEBVs. In addition, it is critical to develop a scaffold to accommodate these cells and retain their functional phenotype for the regeneration of TEBVs. In this study, human induced pluripotent stem cells (iPSCs) were established from primary human aortic fibroblasts, and characterized with the pluripotency markers expression and cells' capabilities to differentiate into all three germ layer cells. A highly efficient method was then developed to induce these human iPSCs into proliferative SMCs. After multiple times of expansion, the expanded SMCs retained the potential to be induced into the functional contractile phenotype of mature SMCs, which was characterized by the contractile response to carbachol treatment, up-regulation of specific collagen genes under transforming growth factor β1 treatment, and up-regulation of specific matrix metalloproteinase genes under cytokine stimulation. We also developed an advanced macroporous and nanofibrous (NF) poly(l-lactic acid) (PLLA) scaffold with suitable pore size and interpore connectivity to seed these human iPSC-derived SMCs and maintain their differentiated phenotype. Subcutaneous implantation of the SMC-scaffold construct in nude mice demonstrated vascular tissue formation, with robust collagenous matrix deposition inside the scaffold and the maintenance of differentiated SMC phenotype. Taken together, this study established an exciting approach towards the construction of patient-specific TEBVs. We established patient-specific human iPSCs, derived proliferative SMCs for expansion, turned on their mature contractile SMC phenotype, and developed an advanced scaffold for these cells to regenerate vascular tissue in vivo.

  9. Effect of interfacial serum proteins on melanoma cell adhesion to biodegradable poly(l-lactic acid) microspheres coated with hydroxyapatite.

    PubMed

    Shinto, Hiroyuki; Hirata, Takuya; Fukasawa, Tomonori; Fujii, Syuji; Maeda, Hayata; Okada, Masahiro; Nakamura, Yoshinobu; Furuzono, Tsutomu

    2013-08-01

    We have measured the interaction forces between a murine melanoma cell and a poly(l-lactic acid) (PLLA) microsphere coated with/without hydroxyapatite (HAp) nanoparticles (i.e., an HAp/PLLA or a bare PLLA microsphere) in a serum-free culture medium, using atomic force microscopy (AFM) with colloid probe technique, in order to investigate how the HAp-nanoparticle coating as well as interfacial serum proteins influence the cell-microsphere adhesion. The cell adhesion force of the HAp/PLLA microspheres was 1.4-fold stronger than that of the bare PLLA microspheres. When the microspheres were pretreated with a culture medium supplemented with 10% fetal bovine serum, the cell adhesion force of the HAp/PLLA microspheres was increased by a factor of 2.1; in contrast, no change was observed in the cell adhesion force of the bare PLLA microspheres before/after the pretreatment. Indeed, the cell adhesion force of the HAp/PLLA was 2.8-fold larger than that of the bare PLLA after the pretreatment. Additionally, we have investigated the effect of interfacial serum proteins on the zeta potentials of these microspheres. On the basis of the obtained results, possible mechanism of cell adhesion to the HAp/PLLA and bare PLLA microspheres in the presence/absence of the interfacial serum proteins is discussed.

  10. Effect of interfacial serum proteins on melanoma cell adhesion to biodegradable poly(l-lactic acid) microspheres coated with hydroxyapatite.

    PubMed

    Shinto, Hiroyuki; Hirata, Takuya; Fukasawa, Tomonori; Fujii, Syuji; Maeda, Hayata; Okada, Masahiro; Nakamura, Yoshinobu; Furuzono, Tsutomu

    2013-08-01

    We have measured the interaction forces between a murine melanoma cell and a poly(l-lactic acid) (PLLA) microsphere coated with/without hydroxyapatite (HAp) nanoparticles (i.e., an HAp/PLLA or a bare PLLA microsphere) in a serum-free culture medium, using atomic force microscopy (AFM) with colloid probe technique, in order to investigate how the HAp-nanoparticle coating as well as interfacial serum proteins influence the cell-microsphere adhesion. The cell adhesion force of the HAp/PLLA microspheres was 1.4-fold stronger than that of the bare PLLA microspheres. When the microspheres were pretreated with a culture medium supplemented with 10% fetal bovine serum, the cell adhesion force of the HAp/PLLA microspheres was increased by a factor of 2.1; in contrast, no change was observed in the cell adhesion force of the bare PLLA microspheres before/after the pretreatment. Indeed, the cell adhesion force of the HAp/PLLA was 2.8-fold larger than that of the bare PLLA after the pretreatment. Additionally, we have investigated the effect of interfacial serum proteins on the zeta potentials of these microspheres. On the basis of the obtained results, possible mechanism of cell adhesion to the HAp/PLLA and bare PLLA microspheres in the presence/absence of the interfacial serum proteins is discussed. PMID:23524077

  11. 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.

    PubMed

    Wang, Dong; Fan, Yuhong; Zhang, Jianjun

    2013-03-15

    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.

  12. Calcium phosphate deposition rate, structure and osteoconductivity on electrospun poly(l-lactic acid) matrix using electrodeposition or simulated body fluid incubation.

    PubMed

    He, Chuanglong; Jin, Xiaobing; Ma, Peter X

    2014-01-01

    Mineralized nanofibrous scaffolds have been proposed as promising scaffolds for bone regeneration due to their ability to mimic both nanoscale architecture and chemical composition of natural bone extracellular matrix. In this study, a novel electrodeposition method was compared with an extensively explored simulated body fluid (SBF) incubation method in terms of the deposition rate, chemical composition and morphology of calcium phosphate formed on electrospun fibrous thin matrices with a fiber diameter in the range ~200-1400 nm prepared using 6, 8, 10 and 12 wt.% poly(l-lactic acid) (PLLA) solutions in a mixture of dichloromethane and acetone (2:1 in volume). The effects of the surface modification using the two mineralization techniques on osteoblastic cell (MC3T3-E1) proliferation and differentiation were also examined. It was found that electrodeposition was two to three orders of magnitude faster than the SBF method in mineralizing the fibrous matrices, reducing the mineralization time from ~2 weeks to 1h to achieve the same amounts of mineralization. The mineralization rate also varied with the fiber diameter but in opposite directions between the two mineralization methods. As a general trend, the increase of fiber diameter resulted in a faster mineralization rate for the electrodeposition method but a slower mineralization rate for the SBF incubation method. Using the electrodeposition method, one can control the chemical composition and morphology of the calcium phosphate by varying the electric deposition potential and electrolyte temperature to tune the mixture of dicalcium phosphate dihydrate and hydroxyapatite (HAp). Using the SBF method, one can only obtain a low crystallinity HAp. The mineralized electrospun PLLA fibrous matrices from either method similarly facilitate the proliferation and osteogenic differentiation of preosteoblastic MC3T3-E1 cells as compared to neat PLLA matrices. Therefore, the electrodeposition method can be utilized as a fast

  13. Calcium phosphate deposition rate, structure and osteoconductivity on electrospun poly(l-lactic acid) matrix using electrodeposition or simulated body fluid incubation

    PubMed Central

    He, Chuanglong; Jin, Xiaobing; Ma, Peter X.

    2013-01-01

    Mineralized nanofibrous scaffolds have been proposed as promising scaffolds for bone regeneration due to their ability to mimic both nanoscale architecture and chemical composition of natural bone extracellular matrix (ECM). In this study, a novel electrodeposition method was compared with an extensively explored simulated body fluid (SBF) incubation method in terms of the deposition rate, chemical composition, and morphology of calcium phosphate formed on electrospun fibrous thin matrices with a fiber diameter in the range from about 200 nm to about 1400 nm prepared using 6, 8, 10 and 12 wt% poly(l-lactic acid) (PLLA) solutions in a mixture of dichloromethane and acetone (2:1 in volume). The effects of the surface modification using the two mineralization techniques on osteoblastic cell (MC3T3-E1) proliferation and differentiation were also examined. It was found that electrodeposition was two to three orders of magnitude faster than the SBF method in mineralizing the fibrous matrices, reducing the mineralization time from about two weeks to an hour to achieve the same amounts of mineralization. The mineralization rate also varied with the fiber diameter but in opposite directions between the two mineralization methods. As a general trend, the increase of fiber diameter resulted in a faster mineralization rate for the electrodeposition method but a slower mineralization rate for the SBF incubation method. Using the electrodeposition method, one can control the chemical composition and morphology of the calcium phosphate by varying the electric deposition potential and electrolyte temperature to tune the mixture of dicalcium phosphate dihydrate (DCPD) and hydroxy apatite (HAp). Using the SBF method, one can only obtain a low crystallinity HAp. The mineralized electrospun PLLA fibrous matrices from either method similarly facilitate the proliferation and osteogenic differentiation of preosteoblastic MC3T3-E1 cells as compared to neat PLLA matrices. Therefore, the

  14. Hemocompatibility and selective cell fate of polydopamine-assisted heparinized PEO/PLLA composite coating on biodegradable AZ31 alloy.

    PubMed

    Wei, Zhongling; Tian, Peng; Liu, Xuanyong; Zhou, Bangxin

    2014-09-01

    Biodegradable magnesium and its alloys have attracted much attention, as they have been used as cardiovascular stents recently because of their biodegradation after implantation. However, their corrosion resistance, hemocompatibility and surface biocompatibility are needed for practical applications. In this work, heparinization of the plasma electrolytic oxidation/poly(l-lactic acid) (PEO/PLLA) composite coating on biodegradable AZ31 alloy was achieved by the strong adhesion of mussel-inspired polydopamine (PDAM). The corrosion resistance of the coated substrates was evaluated in simulated body fluid. In particular, the hemolysis ratio and platelet adhesion tests were conducted to evaluate the hemocompatibility of the composite coatings. The in vitro cytotoxicity of the composite coatings was evaluated with human umbilical vein endothelial cells (HUVECs). The adhesion and proliferation of HUVECs and human umbilical artery smooth muscle cells (HUASMCs) directly incubated on the composite coatings were also investigated. The results showed that although PDAM modification and further heparinization reduced the corrosion resistance of the PEO/PLLA composite coating, the protection of the coating for the substrate was mainly maintained. Moreover, PDAM modification and further heparinization significantly suppressed the adhesion of platelets and had little influence on sustaining a low hemolysis ratio thus resulting in good surface hemocompatibility of the composite coating. The in vitro cell test demonstrated that none of the composite coatings presented obvious cytotoxicity. Significantly, after surface heparinization, the composite coating became more suitable for HUVEC growth and simultaneously inhibited HUASMC growth. The results show that further modification of the PEO/PLLA composite coating on biodegradable magnesium alloy is a promising method to obtain good surface hemocompatibility for anticoagulation and to regulate the cell fate for fast re

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

    PubMed

    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. PMID:26917380

  16. Enhancement of osteoinduction by continual simvastatin release from poly(lactic-co-glycolic acid)-hydroxyapatite-simvastatin nano-fibrous scaffold.

    PubMed

    Jiang, Liming; Sun, Haizhu; Yuan, Anliang; Zhang, Kai; Li, Daowei; Li, Chen; Shi, Ce; Li, Xiangwei; Gao, Kai; Zheng, Changyu; Yang, Bai; Sun, Hongchen

    2013-11-01

    Simvastatin is considered as a stimulator for bone formation. However, the half-life for simvastatin is generally 2 hours, which means, it is difficult to maintain biologically active simvastatin in vivo. To overcome this limitation, we created a system to slowly release simvastatin in vitro and in vivo. We constructed a poly(lactic-co-glycolic acid)/hydroxyapatite nano-fibrous scaffold to carry simvastatin. Releasing assays showed that simvastatin was released from poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin quickly within - 15 days, and small amounts continued to be released through day 56 (experiments terminated). MTT assays demonstrated that both poly(lactic-co-glycolic acid)/hydroxyapatite and poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin promoted MC3T3-E1 cell proliferation. However, Alkaline phosphatase assays showed that only poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold significantly promoted the osteogenic differentiation of MC3T3-E1 cells in vitro on day 14. To further test in vivo, we created calvaria bone defect models and implanted either poly(lactic-co-glycolic acid)/hydroxyapatite or poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin. After 4 or 8 weeks post-implantation, the results indicated that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin scaffold induced bone formation more efficiently than poly(lactic-co-glycolic acid)/hydroxyapatite alone. Our data demonstrates that poly(lactic-co-glycolic acid)/hydroxyapatite/simvastatin has the potential to aid in healing bone defects and promoting bone regeneration in the future although we still need to optimize this complex to efficiently promote bone regeneration.

  17. Differentiation of neuronal stem cells into motor neurons using electrospun poly-L-lactic acid/gelatin scaffold.

    PubMed

    Binan, Loïc; Tendey, Charlène; De Crescenzo, Gregory; El Ayoubi, Rouwayda; Ajji, Abdellah; Jolicoeur, Mario

    2014-01-01

    Neural stem cells (NSCs) provide promising therapeutic potential for cell replacement therapy in spinal cord injury (SCI). However, high increases of cell viability and poor control of cell differentiation remain major obstacles. In this study, we have developed a non-woven material made of co-electrospun fibers of poly L-lactic acid and gelatin with a degradation rate and mechanical properties similar to peripheral nerve tissue and investigated their effect on cell survival and differentiation into motor neuronal lineages through the controlled release of retinoic acid (RA) and purmorphamine. Engineered Neural Stem-Like Cells (NSLCs) seeded on these fibers, with and without the instructive cues, differentiated into β-III-tubulin, HB-9, Islet-1, and choactase-positive motor neurons by immunostaining, in response to the release of the biomolecules. In addition, the bioactive material not only enhanced the differentiation into motor neuronal lineages but also promoted neurite outgrowth. This study elucidated that a combination of electrospun fiber scaffolds, neural stem cells, and controlled delivery of instructive cues could lead to the development of a better strategy for peripheral nerve injury repair. PMID:24161168

  18. Effect of stilbene and chalcone scaffolds incorporation in clofibric acid on PPARα agonistic activity.

    PubMed

    Giampietro, Letizia; D'Angelo, Alessandra; Giancristofaro, Antonella; Ammazzalorso, Alessandra; De Filippis, Barbara; Di Matteo, Mauro; Fantacuzzi, Marialuigia; Linciano, Pasquale; Maccallini, Cristina; Amoroso, Rosa

    2014-01-01

    In an effort to develop safe and efficacious compounds for the treatment of metabolic disorders, new compounds based on a combination of clofibric acid, the active metabolite of clofibrate, and trans-stilbene, chalcone, and other lipophilic groups were synthesized. They were evaluated for PPARα transactivation activity; all branched derivatives showed an increase of the transcriptional activity of receptor compared to the linear ones. Noteworthy, stilbene and benzophenone branched derivatives activated the PPARα better than clofibric acid. PMID:23432317

  19. Fabrication and surface modification of macroporous poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds for human skin fibroblast cell culture.

    PubMed

    Yang, Jian; Shi, Guixin; Bei, Jianzhong; Wang, Shenguo; Cao, Yilin; Shang, Qingxin; Yang, Guanghui; Wang, Wenjing

    2002-12-01

    The fabrication and surface modification of a porous cell scaffold are very important in tissue engineering. Of most concern are high-density cell seeding, nutrient and oxygen supply, and cell affinity. In the present study, poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds with different pore structures were fabricated. An improved method based on Archimedes' Principle for measuring the porosity of scaffolds, using a density bottle, was developed. Anhydrous ammonia plasma treatment was used to modify surface properties to improve the cell affinity of the scaffolds. The results show that hydrophilicity and surface energy were improved. The polar N-containing groups and positive charged groups also were incorporated into the sample surface. A low-temperature treatment was used to maintain the plasma-modified surface properties effectively. It would do help to the further application of plasma treatment technique. Cell culture results showed that pores smaller than 160 microm are suitable for human skin fibroblast cell growth. Cell seeding efficiency was maintained at above 99%, which is better than the efficiency achieved with the common method of prewetting by ethanol. The plasma-treatment method also helped to resolve the problem of cell loss during cell seeding, and the negative effects of the ethanol trace on cell culture were avoided. The results suggest that anhydrous ammonia plasma treatment enhances the cell affinity of porous scaffolds. Mass transport issues also have been considered. PMID:12209930

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

    PubMed

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

    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 (8wt.% 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. PMID:27612778

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

    PubMed

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

    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 (8wt.% 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.

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

    PubMed

    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.

  3. First Chemical Feature Based Pharmacophore Modeling of Potent Retinoidal Retinoic Acid Metabolism Blocking Agents (RAMBAs): Identification of Novel RAMBA Scaffolds

    PubMed Central

    Purushottamachar, Puranik; Patel, Jyoti B.; Gediya, Lalji K; Clement, Omoshile O.; Njar, Vincent C. O.

    2011-01-01

    The first three-dimensional (3D) pharmacophore model was developed for potent retinoidal retinoic acid metabolism blocking agents (RAMBAs) with IC50 values ranging from 0.0009 to 5.84 nM. The seven common chemical features in these RAMBAs as deduced by the Catalyst/HipHop program include five hydrophobic groups (hydrophobes), one hydrogen bond acceptor (HBA) and one ring aromatic group. Using the pharmacophore model as a 3D search query against NCI and Maybridge conformational Catalyst formatted databases; we retrieved several compounds with different structures (scaffolds) as hits. Twenty one retrieved hits were tested for RAMBA activity at 100 nM concentration. The most potent of these compounds, NCI10308597 and HTS01914 showed inhibitory potencies less (54.7% and 53.2%, respectively, at 100 nM) than those of our best previously reported RAMBAs VN/12-1 and VN/14-1 (90% and 86%, respectively, at 100 nM). Docking studies using a CYP26A1 homology model revealed that our most potent RAMBAs showed similar binding to the one observed for a series of RAMBAs reported previously by others. Our data shows the potential of our pharmacophore model in identifying structurally diverse and potent RAMBAs. Further refinement of the model and searches of other robust databases is currently in progress with a view to identifying and optimizing new leads. PMID:22130607

  4. Rational discovery and development of a mitochondria-targeted antioxidant based on cinnamic acid scaffold.

    PubMed

    Teixeira, José; Soares, Pedro; Benfeito, Sofia; Gaspar, Alexandra; Garrido, Jorge; Murphy, Michael P; Borges, Fernanda

    2012-05-01

    A novel mitochondria-targeted antioxidant (TPP-OH) was synthesized by attaching the natural hydrophilic antioxidant caffeic acid to an aliphatic lipophilic carbon chain containing a triphenylphosphonium (TPP) cation. This compound has similar antioxidant activity to caffeic acid as demonstrated by measurement of DPPH/ABTS radical quenching and redox potentials, but is significantly more hydrophobic than its precursor as indicated by the relative partition coefficients. The antioxidant activity of both compounds was intrinsic related to the ortho-catechol system, as the methoxylation of the phenolic functions, namely in TPP-OCH(3) and dimethoxycinnamic acid, gave compounds with negligible antioxidant action. The incorporation of the lipophilic TPP cation to form TTP-OH and TPP-OCH(3) allowed the cinnamic derivatives to accumulate within mitochondria in a process driven by the membrane potential. However, only TPP-OH was an effective antioxidant: TPP-OH protected cells against H(2)O(2) and linoleic acid hydroperoxide-induced oxidative stress. As mitochondrial oxidative damage is associated with a number of clinical disorders, TPP-OH may be a useful lead that could be added to the family of mitochondria-targeted antioxidants that can decrease mitochondrial oxidative damage.

  5. Polyglycolic acid-polylactic acid scaffold response to different progenitor cell in vitro cultures: a demonstrative and comparative X-ray synchrotron radiation phase-contrast microtomography study.

    PubMed

    Giuliani, Alessandra; Moroncini, Francesca; Mazzoni, Serena; Belicchi, Marzia Laura Chiara; Villa, Chiara; Erratico, Silvia; Colombo, Elena; Calcaterra, Francesca; Brambilla, Lucia; Torrente, Yvan; Albertini, Gianni; Della Bella, Silvia

    2014-04-01

    Spatiotemporal interactions play important roles in tissue development and function, especially in stem cell-seeded bioscaffolds. Cells interact with the surface of bioscaffold polymers and influence material-driven control of cell differentiation. In vitro cultures of different human progenitor cells, that is, endothelial colony-forming cells (ECFCs) from a healthy control and a patient with Kaposi sarcoma (an angioproliferative disease) and human CD133+ muscle-derived stem cells (MSH 133+ cells), were seeded onto polyglycolic acid-polylactic acid scaffolds. Three-dimensional (3D) images were obtained by X-ray phase-contrast microtomography (micro-CT) and processed with the Modified Bronnikov Algorithm. The method enabled high spatial resolution detection of the 3D structural organization of cells on the bioscaffold and evaluation of the way and rate at which cells modified the construct at different time points from seeding. The different cell types displayed significant differences in the proliferation rate. In conclusion, X-ray synchrotron radiation phase-contrast micro-CT analysis proved to be a useful and sensitive tool to investigate the spatiotemporal pattern of progenitor cell organization on a bioscaffold.

  6. Polymorphic Crystallization and Crystalline Reorganization of Poly(l-lactic acid)/Poly(d-lactic acid) Racemic Mixture Influenced by Blending with Poly(vinylidene fluoride).

    PubMed

    Yu, Chengtao; Han, Lili; Bao, Jianna; Shan, Guorong; Bao, Yongzhong; Pan, Pengju

    2016-08-18

    The effects of poly(vinylidene fluoride) (PVDF) on the crystallization kinetics, competing formations of homocrystallites (HCs) and stereocomplexes (SCs), polymorphic crystalline structure, and HC-to-SC crystalline reorganization of the poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic mixture were investigated. Even though the PLLA/PDLA/PVDF blends are immiscible, blending with PVDF enhances the crystallization rate and SC formation of PLLA/PDLA components at different temperatures that are higher or lower than the melting temperature of the PVDF component; it also facilitates the HC-to-SC melt reorganization upon heating. The crystallization rate and degree of SC crystallinity (Xc,SC) of PLLA/PDLA components in nonisothermal crystallization increase after immiscible blending with PVDF. At different isothermal crystallization temperatures, the crystallization half-time of PLLA/PDLA components decreases; its spherulitic growth rate and Xc,SC increase as the mass fraction of PVDF increases from 0 to 0.5 in the presence of either a solidified or a molten PVDF phase. The HCs formed in primary crystallization of PLLA/PDLA components melt and recrystallize into SCs upon heating; the HC-to-SC melt reorganization is promoted after blending with PVDF. We proposed that the PVDF-promoted crystallization, SC formation, and HC-to-SC melt reorganization of PLLA/PDLA components in PLLA/PDLA/PVDF blends stem from the enhanced diffusion ability of PLLA and PDLA chains. PMID:27414064

  7. In Vitro and in Vivo Studies of Novel Poly(D,L-lactic acid), Superhydrophilic Carbon Nanotubes, and Nanohydroxyapatite Scaffolds for Bone Regeneration.

    PubMed

    Siqueira, Idalia A W B; Corat, Marcus Alexandre F; Cavalcanti, Bruno das Neves; Ribeiro Neto, Wilson Alves; Martin, Airton Abrahao; Bretas, Rosario Elida Suman; Marciano, Fernanda Roberta; Lobo, Anderson Oliveira

    2015-05-13

    Poly(D,L-lactide acid, PDLLA) has been researched for scaffolds in bone regeneration. However, its hydrophobocity and smooth surface impedes its interaction with biological fluid and cell adhesion. To alter the surface characteristics, different surface modification techniques have been developed to facilitate biological application. The present study compared two different routes to produce PDLLA/superhydrophilic vertically aligned carbon nanotubes:nanohydroxyapatite (PDLLA/VACNT-O:nHAp) scaffolds. For this, we used electrodeposition and immersion in simulated body fluid (SBF). Characterization by goniometry, scanning electron microscopy, X-ray diffraction, and infrared spectroscopy confirmed the polymer modifications, the in vitro bioactivity, and biomineralization. Differential scanning calorimetry and thermal gravimetric analyses showed that the inclusion of VACNT-O:nHA probably acts as a nucleating agent increasing the crystallization rate in the neat PDLLA without structural alteration. Our results showed the formation of a dense nHAp layer on all scaffolds after 14 days of immersion in SBF solution; the most intense carbonated nHAp peaks observed in the PDLLA/VACNT-O:nHAp samples suggest higher calcium precipitation compared to the PDLLA control. Both cell viability and alkaline phosphatase assays showed favorable results, because no cytotoxic effects were present and all produced scaffolds were able to induce detectable mineralization. Bone defects were used to evaluate the bone regeneration; the confocal Raman and histological results confirmed high potential for bone applications. In vivo study showed that the PDLLA/VACNT-O:nHAp scaffolds mimicked the immature bone and induced bone remodeling. These findings indicate surface improvement and the applicability of this new nanobiomaterial for bone regenerative medicine. PMID:25899398

  8. In Vitro and in Vivo Studies of Novel Poly(D,L-lactic acid), Superhydrophilic Carbon Nanotubes, and Nanohydroxyapatite Scaffolds for Bone Regeneration.

    PubMed

    Siqueira, Idalia A W B; Corat, Marcus Alexandre F; Cavalcanti, Bruno das Neves; Ribeiro Neto, Wilson Alves; Martin, Airton Abrahao; Bretas, Rosario Elida Suman; Marciano, Fernanda Roberta; Lobo, Anderson Oliveira

    2015-05-13

    Poly(D,L-lactide acid, PDLLA) has been researched for scaffolds in bone regeneration. However, its hydrophobocity and smooth surface impedes its interaction with biological fluid and cell adhesion. To alter the surface characteristics, different surface modification techniques have been developed to facilitate biological application. The present study compared two different routes to produce PDLLA/superhydrophilic vertically aligned carbon nanotubes:nanohydroxyapatite (PDLLA/VACNT-O:nHAp) scaffolds. For this, we used electrodeposition and immersion in simulated body fluid (SBF). Characterization by goniometry, scanning electron microscopy, X-ray diffraction, and infrared spectroscopy confirmed the polymer modifications, the in vitro bioactivity, and biomineralization. Differential scanning calorimetry and thermal gravimetric analyses showed that the inclusion of VACNT-O:nHA probably acts as a nucleating agent increasing the crystallization rate in the neat PDLLA without structural alteration. Our results showed the formation of a dense nHAp layer on all scaffolds after 14 days of immersion in SBF solution; the most intense carbonated nHAp peaks observed in the PDLLA/VACNT-O:nHAp samples suggest higher calcium precipitation compared to the PDLLA control. Both cell viability and alkaline phosphatase assays showed favorable results, because no cytotoxic effects were present and all produced scaffolds were able to induce detectable mineralization. Bone defects were used to evaluate the bone regeneration; the confocal Raman and histological results confirmed high potential for bone applications. In vivo study showed that the PDLLA/VACNT-O:nHAp scaffolds mimicked the immature bone and induced bone remodeling. These findings indicate surface improvement and the applicability of this new nanobiomaterial for bone regenerative medicine.

  9. Synthesis of oxacyclic scaffolds via dual ruthenium hydride/Brønsted acid-catalyzed isomerization/cyclization of allylic ethers.

    PubMed

    Ascic, Erhad; Ohm, Ragnhild G; Petersen, Rico; Hansen, Mette R; Hansen, Casper L; Madsen, Daniel; Tanner, David; Nielsen, Thomas E

    2014-03-17

    A ruthenium hydride/Brønsted acid-catalyzed tandem sequence is reported for the synthesis of 1,3,4,9-tetrahydropyrano[3,4-b]indoles (THPIs) and related oxacyclic scaffolds. The process was designed on the premise that readily available allylic ethers would undergo sequential isomerization, first to enol ethers (Ru catalysis), then to oxocarbenium ions (Brønsted acid catalysis) amenable to endo cyclization with tethered nucleophiles. This methodology provides not only an attractive alternative to the traditional oxa-Pictet-Spengler reaction for the synthesis of THPIs, but also convenient access to THPI congeners and other important oxacycles such as acetals. PMID:24616060

  10. Hyaluronic acid hydrogel scaffolds with a triple degradation behavior for bone tissue engineering.

    PubMed

    Cui, Ning; Qian, Junmin; Liu, Ting; Zhao, Na; Wang, Hongjie

    2015-08-01

    In this study, in order to better mimick the nature of bone extracellular matrix, hyaluronic acid (HA) hydrogels having a triple degradation behavior were synthesized from 3,3'-dithiodipropionate hydrazide-modified HA (DTPH-HA) and polyethylene glycol dilevulinate (LEV-PEG-LEV) via the reaction of the ketone carbonyl groups of LEV-PEG-LEV with the hydrazide groups of DTPH-HA. The HA hydrogels were characterized by solid state (13)C NMR, FT-IR, SEM, and rheological, swelling and degradation tests. The results showed that the HA hydrogels exhibited a highly porous morphology and had pore diameters ranging from 20 to 200 μm. The equilibrium swelling ratio of the HA hydrogels was no less than 37.5. The HA hydrogels could be degraded by hyaluronidase and reducing substances or at acidic pH values. The biocompatibility of the HA hydrogels was evaluated using osteoblast-like MC3T3-E1 cells by live/dead staining and MTT assays. The results revealed that the HA hydrogels had good biocompatibility and could support the attachment and proliferation of MC3T3-E1 cells. All the results indicated that the HA hydrogels synthesized by hydrazone bond crosslinking might have great potential to be used in bone tissue engineering. PMID:25933539

  11. Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease.

    PubMed

    de Menezes, Dayanne da Rocha; Calvet, Claudia Magalhães; Rodrigues, Giseli Capaci; de Souza Pereira, Mirian Claudia; Almeida, Igor Rodrigues; de Aguiar, Alcino Palermo; Supuran, Claudiu T; Vermelho, Alane Beatriz

    2016-12-01

    This work describes the antitrypanocidal activity of two hydroxamic acid derivatives containing o-ethoxy (HAD1) and p-ethoxy (HAD2) as substituent in the aromatic ring linked to the isoxazoline ring. HAD1 and HAD2 induced a significant reduction in the number of intracellular parasites and consequently showed activity on the multiplication of the parasite. Treatment of cardiomyocytes and macrophages with the compounds revealed no significant loss in cell viability. Ultrastructural alterations after treatment of cardiomyocytes or macrophages infected by Trypanosoma cruzi with the IC50 value of HAD1 revealed alterations to amastigotes, showing initial damage seen as swelling of the kinetoplast. This gave a good indication of the ability of the drug to permeate through the host cell membrane as well as its selectivity to the parasite target. Both compounds HAD1 and 2 were able to reduce the cysteine peptidases and decrease the activity of metallopeptidases.

  12. Redirection of Metabolic Flux into Novel Gamma-Aminobutyric Acid Production Pathway by Introduction of Synthetic Scaffolds Strategy in Escherichia Coli.

    PubMed

    Pham, Van Dung; Somasundaram, Sivachandiran; Lee, Seung Hwan; Park, Si Jae; Hong, Soon Ho

    2016-04-01

    In general, gamma-aminobutyric acid (GABA) pathway involves the decarboxylation of glutamate, which is produced from sugar by Corynebacterium fermentation. GABA can be used for the production of pharmaceuticals and functional foods. Due to the increasing demand of GABA, it is essential to create an effective alternative pathway for the GABA production. In this study, Escherichia coli were engineered to produce GABA from glucose via GABA shunt, which consists of succinate dehydrogenase, succinate-semialdehyde dehydrogenase, and GABA aminotransferase. The three enzymes were physically attached to each other through a synthetic scaffold, and the Krebs cycle flux was redirected to the GABA pathway. By introduction of synthetic scaffold, 0.75 g/l of GABA was produced from 10 g/l of glucose at 30 °C and pH 6.5. The inactivation of competing metabolic pathways provided 15.4 % increase in the final GABA concentration. PMID:26667817

  13. Processing and quantitative analysis of biodegradable polymers (PLLA and PCL) thermal bonding

    NASA Astrophysics Data System (ADS)

    Boutry, C. M.; Kiran, R.; Umbrecht, F.; Hierold, C.

    2010-08-01

    A quantitative analysis of the bond strength and microstructure integrity achieved when bonding the biodegradable polymers poly(L-lactide) (PLLA) and poly(ɛ-caprolactone) (PCL) has been performed using the response surface methodology. The respective influence of the bonding parameters (temperature, pressure, duration) on the bond strength and microchannel integrity was investigated. PLLA and PCL were identified as suitable candidates for packaging materials for bioelectronic circuits of conductive biodegradable polymers. For a future packaging application, the bonding parameters were adapted to optimize the bond strength; the estimated values for the bond strength and channel integrity that were predicted by the surface plots were 2.32 ± 0.26 MPa and 33.7 ± 12.9% for PLLA, and 0.81 ± 0.11 MPa and 50.9 ± 5.7% for PCL. These values were in good agreement with the experimentally determined bond strength of 2.00 ± 1.10 MPa (PLLA) and 0.67 ± 0.22 MPa (PCL) and deformation of 31.4 ± 7.0% (PLLA) and 52.9 ± 4.1% (PCL). Microchannels with an aspect ratio of 1:12.5 were successfully fabricated. The impact of the fabrication process on the PLLA and PCL chemical properties was also investigated through differential scanning calorimetry and gel permeation chromatography measurements. It was observed that the weight average molecular weight Mw decreases after each fabrication step, as much as 68% for PLLA and 59% for PCL. The strongest reduction was observed after the compression molding (above the melting temperature) which should be kept as short as possible. An annealing step allowed increasing the crystallinity and improved the overall polymer stiffness.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    Ma, Haiyun; Xue, Li

    2015-01-16

    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.

  16. Poly-L-lactide/sodium alginate/chitosan microsphere hybrid scaffolds made with braiding manufacture and adhesion technique: Solution to the incongruence between porosity and compressive strength.

    PubMed

    Lin, Jia-Horng; Chen, Chih-Kuang; Wen, Shih-Peng; Lou, Ching-Wen

    2015-01-01

    Bone scaffolds require a three-dimensional structure, high porosity, interconnected pores, adequate mechanical strengths, and non-toxicity. A high porosity is incongruent with mechanical strengths. Therefore, this study combines a braiding method and microsphere solution to create bone scaffolds with a high porosity and sufficient mechanical strengths. First, poly-L-lactide (PLLA) plied yarns are braided into 5-, 10-, 15-, 20-, and 25-layer hollow braids, and then thermally treated at 165 °C for various durations. Next, sodium alginate (SA) microspheres, cross-linked with CaCl2 solution with various concentrations, are combined with PLLA porous braided bone scaffolds to form PLLA/SA/CS microsphere hybrid scaffolds, which are then observed for surface observation, and tested for porosity, water contact angle, compressive strength, MTT assay, bioactivity, alkaline phosphatase (ALP) assay, cell attachment, and statistical analyses. The test results show that the layer amount of the bone scaffold is proportional to the compressive strength. With the same number of layers, the compressive strength is inversely proportional to the concentration of the CaCl2 solution. The results of surface observation, porosity, and water contact angle tests show that PLLA/SA/CS microsphere hybrid scaffolds possess a high porosity and good hydrophilicity; as a result, the braiding manufacture and the bonding technique effectively solve the confliction between porosity and mechanical strength. The concentration of CaCl2 does not pertain to cell activity and ALP results, exemplified by good cell attachment on bone scaffolds for each specification. PMID:25953547

  17. Preparation of hydrophilic poly(lactic acid) tissue engineering scaffold via (PLA)-(PLA-b-PEG)-(PEG) solution casting and thermal-induced surface structural transformation.

    PubMed

    Zhu, Xiaomin; Zhong, Tian; Huang, Ran; Wan, Ajun

    2015-01-01

    Porous poly(lactic acid) (PLA) tissue engineering scaffolds with a hydrophilic surface assembled by polyethylene glycol aggregations were prepared by the solvent casting/particulate leaching method from (PLA)-(PLA-b-PEG)-(PEG) blend solution, where the PLA-b-PEG block polymer serves as an amphiphilic glue between two phases. A thermal recrystallization process was inserted before leaching to induce a phase separation, which subsequently squeezes out PEG to form a hydrophilic shell. Characterizations of XRD and DSC indicated the composition and mixing states of materials. The water contact angle test qualitatively presented the excellent hydrophilicity compared to the pure PLA or PLA-PEG simple blend scaffold. The scanning electron microscope results confirmed the formation of porous structure of [Formula: see text] pore size, with an observable phase separation on the surface. The scaffold was degraded in PBS at [Formula: see text], and the degradation exhibits a three-stage behavior, which evidenced the amphiphilically glued phase separations. PMID:26324121

  18. Bone scaffolds loaded with siRNA-Semaphorin4d for the treatment of osteoporosis related bone defects

    PubMed Central

    Zhang, Yufeng; Wei, Lingfei; Miron, Richard J.; Shi, Bin; Bian, Zhuan

    2016-01-01

    Osteoporosis is a prominent disorder affecting over 200 million people worldwide. Recently, semaphorins have been implicated in the cell-cell communication between osteoclasts and osteoblasts and have been associated with the progression of osteoporosis. Previously, we demonstrated that knockdown of semaphorin4d (Sema4d) using siRNA delivered with a bone-targeting system prevented bone loss in an osteoporotic animal model. Here, we used this bone-specific technology containing siRNA-Sema4d and fabricated a PLLA scaffold capable of enhancing bone repair following fracture. We investigated the ability of the implant to release siRNA-Sema4d into the surrounding tissues over time and to influence new bone formation in a 3 mm femur osteoporotic defect model in ovariectomized rats. Delivery of the bone-targeting system released from PLLA scaffolds began 2 hours post-implantation, peaked at 1 day, and was sustained over a 21 day period. μCT analysis demonstrated a significantly higher bone volume/total volume bone mineral density and number of osteoblasts in the rats that were transplanted with scaffolds loaded with siRNA-Sema4d. These results confirm the specific role of Sema4d in bone remodeling and demonstrate that significant increases in the speed and quality of new bone formation occur when siRNA-Sema4d is delivered via a PLLA scaffold. PMID:27254469

  19. Electrospun Poly(acrylic acid)/Silica Hydrogel Nanofibers Scaffold for Highly Efficient Adsorption of Lanthanide Ions and Its Photoluminescence Performance.

    PubMed

    Wang, Min; Li, Xiong; Hua, Weikang; Shen, Lingdi; Yu, Xufeng; Wang, Xuefen

    2016-09-14

    Combined with the features of electrospun nanofibers and the nature of hydrogel, a novel choreographed poly(acrylic acid)-silica hydrogel nanofibers (PAA-S HNFs) scaffold with excellent rare earth elements (REEs) recovery performance was fabricated by a facile route consisting of colloid-electrospinning of PAA/SiO2 precursor solution, moderate thermal cross-linking of PAA-S nanofiber matrix, and full swelling in water. The resultant PAA-S HNFs with a loose and spongy porous network structure exhibited a remarkable adsorption capacity of lanthanide ions (Ln(3+)) triggered by the penetration of Ln(3+) from the nanofiber surface to interior through the abundant water channels, which took full advantage of the internal adsorption sites of nanofibers. The effects of initial solution pH, concentration, and contact time on adsorption of Ln(3+) have been investigated comprehensively. The maximum equilibrium adsorption capacities for La(3+), Eu(3+), and Tb(3+) were 232.6, 268.8, and 250.0 mg/g, respectively, at pH 6, and the adsorption data were well-fitted to the Langmuir isotherm and pseudo-second-order models. The resultant PAA-S HNFs scaffolds could be regenerated successfully. Furthermore, the proposed adsorption mechanism of Ln(3+) on PAA-S HNFs scaffolds was the formation of bidentate carboxylates between carboxyl groups and Ln(3+) confirmed by FT-IR and XPS analysis. The well-designed PAA-S HNFs scaffold can be used as a promising alternative for effective REEs recovery. Moreover, benefiting from the unique features of Ln(3+), the Ln-PAA-S HNFs simultaneously exhibited versatile advantages including good photoluminescent performance, tunable emission color, and excellent flexibility and processability, which also hold great potential for applications in luminescent patterning, underwater fluorescent devices, sensors, and biomaterials, among others. PMID:27537710

  20. Scaffolding and Metacognition

    ERIC Educational Resources Information Center

    Holton, Derek; Clarke, David

    2006-01-01

    This paper proposes an expanded conception of scaffolding with four key elements: (1) scaffolding agency--expert, reciprocal, and self-scaffolding; (2) scaffolding domain--conceptual and heuristic scaffolding; (3) the identification of self-scaffolding with metacognition; and (4) the identification of six zones of scaffolding activity; each zone…

  1. Optimizing poly-L-lactic acid use.

    PubMed

    Lowe, Nick J

    2008-03-01

    Injectable devices are less invasive than surgical interventions for restoring youthful contours. Sculptra (Dermik Laboratories, Bridgewater, NJ, USA, a business of sanofi aventis U.S. LLC) contains poly-l-lactic acid (PLLA), which is thought to elicit in vivo collagen production around the injected implant, producing new volume gradually over time, and with effects lasting up to 2 years. Correct reconstitution and preparation of PLLA, as well as injection technique, are essential to ensure optimal outcomes and reduce adverse events. This article provides an overview of injectable devices, specifically focusing on PLLA in cosmetic application and optimal administration techniques to maximize efficacy and duration of effect.

  2. Assessment of multicomponent hydrogel scaffolds of poly(acrylic acid-2-hydroxy ethyl methacrylate)/gelatin for tissue engineering applications.

    PubMed

    Jaiswal, Maneesh; Koul, Veena

    2013-03-01

    The article describes the design of the multicomponent hydrogel system of poly(acrylic acid-HEMA)/gelatin for tissue engineering application. Derivative of polycaprolactone-diol (polycaprolactone diacrylate (PCL-DAr)) was used to cross-link acrylate monomers whereas gelatin was kept free for cell proliferation. Epigallocatechin gallate (EGCG), an anti-oxidant phytochemical, was loaded by diffusion method. Its in vitro release study in PBS (pH 6.5) at 37 ± 0.2°C (75 rpm) revealed a sustained release profile upto 20 days. Fitting of drug release data in Korsmeyer-Peppas model equation revealed probable release mechanism through the value of release coefficient (n), which was found to depend on formulations composition. Drug-polymer interaction, thermal behavior, and surface morphology were investigated by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, thermogravimetric analysis (TGA), and scanning electron microscopic (SEM). Swelling behavior of hydrogel in PBS (pH 6.5 and 7.4, 0.2 M) and in distilled water was found to increase with increasing AAc/HEMA ratio. Compression modulus decreased from 203 ± 3.7 KPa to 11.6 ± 1.1KPa, at 30% strain, whereas displacement values significantly increased from 3.2 ± 0.2 to 4.7 ± 0.6 mm at 20 N force (p < 0.05), with increasing AAc/HEMA ratio. Percentage cell viability was analyzed using indirect 3-[4, 5-dimethylthiazolyl-2]-2,5-diphenyltetrazo-liumbromide (MTT) assay with fibroblast L929 cells; showed ≥92.3% cell viability after 24 h incubation. Cell proliferation on the scaffold surface was found to increase with incorporation of HEMA in P(AAc)/G cross-linked hydrogel matrix upto a certain extent. These biocompatible, elastic, and swellable hydrogels can serve as a matrix for drug delivery and tissue engineering applications.

  3. Preparation of Porous Core-Shell Poly L-Lactic Acid/Polyethylene Glycol Superfine Fibres Containing Drug.

    PubMed

    Yang, Wenjing; He, Nongyue; Fu, Juan; Li, Zhiyang; Ji, Xuyuan

    2015-12-01

    In this paper, poly L-lactic acid (PLLA) blended with polyethylene glycol (PEG) was dissolved in methylene dichloride solution as the shell solution, and rapamycin (RAPA), was encapsulated inside the core of PLLA micro/nano fibres as a model drug. The effects of the blending ratio of PLLA to PEG, the concentration of the electrospinning solution, the voltage, the flow rate, and the encapsulation efficiency were studied. Uniform and porous RAPA-Loading PLLA fibres were obtained when the ratio of PLLA to PEG was 7/3, the concentration of PLLA was 3%, the applied voltage was 7.5 kV, and the pump speed was V(core) = 0.1 mL/h, V(shell) = 1 mL/h, repectively. The average diameter of PLLA fibres increased with the gradual increase in PLLA concentration. FTIR results showed that RAPA was successfully encapsulated into the core-co-shell PLLA fibres. Meanwhile, the RAPA-loading of coaxial electrospun PLLA fibres was significantly higher than that of the blending electrospun fibres. It was also found that the porous core-shell PLLA/PEG blending superfine fibres could regulate the appearance of pore on the surface of superfine fibres by adjusting the electrospinning parameters. The porous PLLA/PEG blending fibres can be used as drug carriers and, to improve the single way of drug release depending on the degradation of shell material to meet different need. It will be a remarkable breakthrough in the area for sustained and controlled release drug delivery system. PMID:26682434

  4. Preparation of Porous Core-Shell Poly L-Lactic Acid/Polyethylene Glycol Superfine Fibres Containing Drug.

    PubMed

    Yang, Wenjing; He, Nongyue; Fu, Juan; Li, Zhiyang; Ji, Xuyuan

    2015-12-01

    In this paper, poly L-lactic acid (PLLA) blended with polyethylene glycol (PEG) was dissolved in methylene dichloride solution as the shell solution, and rapamycin (RAPA), was encapsulated inside the core of PLLA micro/nano fibres as a model drug. The effects of the blending ratio of PLLA to PEG, the concentration of the electrospinning solution, the voltage, the flow rate, and the encapsulation efficiency were studied. Uniform and porous RAPA-Loading PLLA fibres were obtained when the ratio of PLLA to PEG was 7/3, the concentration of PLLA was 3%, the applied voltage was 7.5 kV, and the pump speed was V(core) = 0.1 mL/h, V(shell) = 1 mL/h, repectively. The average diameter of PLLA fibres increased with the gradual increase in PLLA concentration. FTIR results showed that RAPA was successfully encapsulated into the core-co-shell PLLA fibres. Meanwhile, the RAPA-loading of coaxial electrospun PLLA fibres was significantly higher than that of the blending electrospun fibres. It was also found that the porous core-shell PLLA/PEG blending superfine fibres could regulate the appearance of pore on the surface of superfine fibres by adjusting the electrospinning parameters. The porous PLLA/PEG blending fibres can be used as drug carriers and, to improve the single way of drug release depending on the degradation of shell material to meet different need. It will be a remarkable breakthrough in the area for sustained and controlled release drug delivery system.

  5. Scaffolded biology.

    PubMed

    Minelli, Alessandro

    2016-09-01

    Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology. PMID:27287514

  6. Scaffolded biology.

    PubMed

    Minelli, Alessandro

    2016-09-01

    Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

  7. Re-engineering nalidixic acid's chemical scaffold: A step towards the development of novel anti-tubercular and anti-bacterial leads for resistant pathogens.

    PubMed

    Peraman, Ramalingam; Varma, Raghu Veer; Reddy, Y Padmanabha

    2015-10-01

    Occurrence of antibacterial and antimycobacterial resistance stimulated a thrust to discover new drugs for infectious diseases. Herein we report the work on re-engineering nalidixic acid's chemical scaffold for newer leads. Stepwise clubbing of quinoxaline, 1,2,4-triazole/1,3,4-oxadiazole with nalidixic acid yielded better compounds. Compounds were screened against ciprofloxacin resistant bacteria and Mycobacterium tuberculosis H37Rv species. Results were obtained as minimum inhibitory concentration, it was evident that molecule with quinoxaline linked azide as side chain served as antitubercular lead (<6.25 μg/ml) whilst molecule with oxadiazole or triazole linked quinoxaline side chain served as anti-bacterial lead. Few compounds were significantly active against Escherichia coli and Proteus vulgaris with MIC less than 0.06 μg/ml and relatively potent than ciprofloxacin. No true compound was potentially active against Salmonella species as compared to amoxicillin.

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

    PubMed

    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.

  9. Consistent quasistatic and acoustic elasticity determination of poly-L-lactide-based rapid-prototyped tissue engineering scaffolds.

    PubMed

    Luczynski, Krzysztof W; Brynk, Tomasz; Ostrowska, Barbara; Swieszkowski, Wojciech; Reihsner, Roland; Hellmich, Christian

    2013-01-01

    This paper is concerned with reliable and physically sound elasticity determination of rapid-prototyped tissue engineering scaffolds made of poly-L-lactide (PLLA), with and without small portions of tricalcium phosphate (TCP) inclusions. At the level of overall scaffolds, that is, that of several millimeters, multiple uniaxial loading-unloading (quasistatic) tests were performed, giving access to the scaffolds' Young's moduli, through stress-strain characteristics during unloading. In addition, acoustic tests with 0.05 MHz frequency delivered an independent access to elastic properties, in terms of the normal components of the scaffolds' stiffness tensors. The latter strongly correlate, in a linear fashion, with the Young's moduli from the unloading tests, revealing porosity independence of Poisson's ratio. The magnitude of the latter is in full agreement with literature data on polymers. Both of these facts underline that both ultrasound tests and quasistatic unloading tests reliably provide the elastic properties of tissue engineering scaffolds.

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

    PubMed

    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. PMID:27561528

  11. Enhanced stereocomplex formation of poly(L-lactic acid) and poly(D-lactic acid) in the presence of stereoblock poly(lactic acid).

    PubMed

    Fukushima, Kazuki; Chang, Yoon-Hee; Kimura, Yoshiharu

    2007-06-01

    Stereoblock poly(lactic acid) (sb-PLA) is incorporated into a 1:1 polymer blend system of poly(L-lactic acid) (PLLA) and poly(D-lactic acid) (PDLA) that has a high molecular weight to study its addition effect on the stereocomplex (sc) formation of PLLA and PDLA. The ternary polymer blend films are first prepared by casting polymer solutions of sb-PLA, PLLA, and PDLA with different compositions. Upon increasing the content of sb-PLA in the blend films the sc crystallization is driven to a higher degree, while the formation of homo-chiral (hc) crystals is decreased. Lowering the molecular weight of the incorporated sb-PLA effectively increases the sc formation. Consequently, it is revealed that sb-PLA can work as a compatibilizer to improve the poor sc formation in the polymer blend of PLLA and PDLA. PMID:17541929

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

    PubMed

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

    2015-03-13

    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. PMID:25683087

  13. Safety Evaluation of a Bioglass–Polylactic Acid Composite Scaffold Seeded with Progenitor Cells in a Rat Skull Critical-Size Bone Defect

    PubMed Central

    El-Kady, Abeer M.; Arbid, Mahmoud S.; Abd El-Hady, Bothaina M.; Marzi, Ingo; Seebach, Caroline

    2014-01-01

    Treating large bone defects represents a major challenge in traumatic and orthopedic surgery. Bone tissue engineering provides a promising therapeutic option to improve the local bone healing response. In the present study tissue biocompatibility, systemic toxicity and tumorigenicity of a newly developed composite material consisting of polylactic acid (PLA) and 20% or 40% bioglass (BG20 and BG40), respectively, were analyzed. These materials were seeded with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) and tested in a rat calvarial critical size defect model for 3 months and compared to a scaffold consisting only of PLA. Serum was analyzed for organ damage markers such as GOT and creatinine. Leukocyte count, temperature and free radical indicators were measured to determine the degree of systemic inflammation. Possible tumor occurrence was assessed macroscopically and histologically in slides of liver, kidney and spleen. Furthermore, the concentrations of serum malondialdehyde (MDA) and sodium oxide dismutase (SOD) were assessed as indicators of tumor progression. Qualitative tissue response towards the implants and new bone mass formation was histologically investigated. BG20 and BG40, with or without progenitor cells, did not cause organ damage, long-term systemic inflammatory reactions or tumor formation. BG20 and BG40 supported bone formation, which was further enhanced in the presence of EPCs and MSCs. This investigation reflects good biocompatibility of the biomaterials BG20 and BG40 and provides evidence that additionally seeding EPCs and MSCs onto the scaffold does not induce tumor formation. PMID:24498345

  14. [(18)F]Fluorobenzoyllysinepentanedioic Acid Carbamates: New Scaffolds for Positron Emission Tomography (PET) Imaging of Prostate-Specific Membrane Antigen (PSMA).

    PubMed

    Yang, Xing; Mease, Ronnie C; Pullambhatla, Mrudula; Lisok, Ala; Chen, Ying; Foss, Catherine A; Wang, Yuchuan; Shallal, Hassan; Edelman, Hannah; Hoye, Adam T; Attardo, Giorgio; Nimmagadda, Sridhar; Pomper, Martin G

    2016-01-14

    Radiolabeled urea-based low-molecular weight inhibitors of the prostate-specific membrane antigen (PSMA) are under intense investigation as imaging and therapeutic agents for prostate and other cancers. In an effort to provide agents with less nontarget organ uptake than the ureas, we synthesized four (18)F-labeled inhibitors of PSMA based on carbamate scaffolds. 4-Bromo-2-[(18)F]fluorobenzoyllysineoxypentanedioic acid (OPA) carbamate [(18)F]23 and 4-iodo-2-[(18)F]fluorobenzoyllysine OPA carbamate [(18)F]24 in particular exhibited high target-selective uptake in PSMA+ PC3 PIP tumor xenografts, with tumor-to-kidney ratios of >1 by 4 h postinjection, an important benchmark. Because of its high tumor uptake (90% injected dose per gram of tissue at 2 h postinjection) and high tumor-to-organ ratios, [(18)F]23 is promising for clinical translation. Prolonged tumor-specific uptake demonstrated by [(18)F]24, which did not reach equilibrium during the 4 h study period, suggests carbamates as alternative scaffolds for mitigating dose to nontarget tissues. PMID:26629713

  15. Designs for the self-assembly of open and closed macromolecular structures and a molecular switch using DNA methyltransferases to order proteins on nucleic acid scaffolds

    NASA Astrophysics Data System (ADS)

    Smith, Steven S.

    2002-06-01

    The methyltransferase-directed addressing of fusion proteins to DNA scaffolds offers an approach to the construction of protein/nucleic acid biostructures with potential in a variety of applications. The technology is currently only limited by the yield of high occupancy structures. However, current evidence shows that DNA scaffolds that contain three or four targeted proteins can be reliably constructed. This permits a variety of macromolecular designs, several of which are given in this paper. Designs for open and closed two-dimensional and three-dimensional assemblies and a design for a molecular switch are discussed. The closed two-dimensional assembly takes the form of a square, and could find application as a component of other systems including a macromolecular rotaxane. The closed three-dimensional system takes the form of a trigonal bipyramid and could find application as a macromolecular carcerand. The molecular switch could find application as a peptide biosensor. Guidelines for the construction and structural verification of these designs are reported.

  16. Meniscal scaffolds.

    PubMed

    Myers, Kevin R; Sgaglione, Nicholas A; Goodwillie, Andrew D

    2014-12-01

    There are two scaffold products designed for meniscal reconstruction or substitution of partial meniscal defects that are currently available in the Europe: the collagen meniscal implant (CMI; Ivy Sports Medicine, Gräfelfing, Germany) and the polymer scaffold (PS; Actifit, Orteq Bioengineering, London, United Kingdom). The CMI has demonstrated improved clinical outcomes compared with baseline in patients with chronic postmeniscectomy symptoms with follow-up ranging from 5 to more than 10 years. There are also several comparative studies that report improved clinical scores in patients with chronic medial meniscus symptoms treated with CMI versus repeat partial meniscectomy, and a lower reoperation rate. Recently, PS insertion was shown to result in improved clinical outcomes in patients with chronic postmeniscectomy symptoms of the medial or lateral meniscus at short-term follow-up. However, there is currently no medium- or long-term data available for the PS. The use of meniscal scaffolds in the acute setting has not been found to result in improved outcomes in most studies. The authors' surgical indications for meniscal scaffold implantation, preferred surgical technique, and postoperative rehabilitation protocol are described. PMID:25172967

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Treatment of the aged hand with injectable poly-l-lactic acid.

    PubMed

    Rendon, Marta I; Cardona, Lina M; Pinzon-Plazas, Mariana

    2010-12-01

    We report the use of injectable poly-l-lactic acid (PLLA) for volume restoration in a 45-year-old white female who was concerned about the appearance of her hands. The patient expressed a desire for long-term restoration, and selected injectable PLLA because of its known 2-year duration of effect, although she was informed that injectable PLLA is not FDA-approved for use in the hands. After reconstitution with 8 ml of diluent plus lidocaine, 0.1-0.2-ml aliquots of injectable PLLA were injected into selected sites, up to 5 ml per hand. The patient underwent three identical treatments, followed by postinjection use of moisturizing cream and massage; improvement in appearance was noted by the patient between the second and third treatments. Correction was maintained for at least 18 months, with no adverse events. We have also briefly reviewed the literature on the use of injectable PLLA for volume restoration in the hand.

  19. In vitro degradation, hemolysis, and cytocompatibility of PEO/PLLA composite coating on biodegradable AZ31 alloy.

    PubMed

    Wei, Zhongling; Tian, Peng; Liu, Xuanyong; Zhou, Bangxin

    2015-02-01

    Magnesium and its alloys have large potential as degradable and absorbable biomaterials because of their mechanical properties and biocompatibility. However, their corrosion resistance is usually inadequate especially in physiological environment, which limits their broad applications in biomedical areas. In this work, plasma electrolytic oxidized/poly(l-lactide) (PEO/PLLA) composite coating was successfully fabricated on biodegradable AZ31 alloy by combing PEO process and sealing with PLLA. The microstructure, elemental composition, and phase composition of the PEO/PLLA composite coating were investigated. The in vitro degradation of the PEO/PLLA composite coating in simulated body fluid (SBF) was also systematically evaluated. The results revealed that the PEO/PLLA composite coating improved the corrosion resistance of AZ31 alloy significantly. The corrosion potential shifted from -1.663V to more positive position -1.317 V and the corrosion current density was reduced with six-order of magnitude. The Mg(2+) ions, hydrogen release, and pH value change of solution caused by degradation were all decreased significantly. Moreover, the PEO process played a critical role in sustaining the integrity of the implant in long-term service. The result of hemolysis test showed that the PEO/PLLA composite coating vested AZ31 alloy a low hemolysis ratio (0.806 ± 0.771)%, which is much lower than the safe value of 5% according to ISO 10993-4. For the cytocompatibility test, compared with bare AZ31 alloy and PEO coating, MC3T3-E1 cells showed much better adhesion and proliferation on the PEO/PLLA composite coating with nearly 4-fold increase of cells after 7-day cultivation, indicating that the PEO/PLLA composite coating has good biocompatibility for biomedical applications.

  20. Effects of Nano-hydroxyapatite/Poly(DL-lactic-co-glycolic acid) Microsphere-Based Composite Scaffolds on Repair of Bone Defects: Evaluating the Role of Nano-hydroxyapatite Content.

    PubMed

    He, Shu; Lin, Kai-Feng; Sun, Zhen; Song, Yue; Zhao, Yi-Nan; Wang, Zheng; Bi, Long; Liu, Jian

    2016-07-01

    The aim of the current study was to prepare microsphere-based composite scaffolds made of nano-hydroxyapatite (nHA)/poly (DL-lactic-co-glycolic acid) (PLGA) at different ratios and evaluate the effects of nHA on the characteristics of scaffolds for tissue engineering application. First, microsphere-based composite scaffolds made of two ratios of nHA/PLGA (nHA/PLGA = 20/80 and nHA/PLGA = 50/50) were prepared. Then, the effects of nHA on the wettability, mechanical strength, and degradation of scaffolds were investigated. Second, the biocompatibility and osteoinductivity were evaluated and compared by co-culture of scaffolds with bone marrow stromal stem cells (BMSCs). The results showed that the adhesion, proliferation, and osteogenic differentiation of BMSCs with nHA/PLGA (50/50) were better than those with nHA/PLGA (20/80). Finally, we implanted the scaffolds into femur bone defects in a rabbit model, then the capacity of guiding bone regeneration as well as the in vivo degradation were observed by micro-CT and histological examinations. After 4 weeks' implantation, there was no significant difference on the repair of bone defects. However, after 8 and 12 weeks' implantation, the nHA/PLGA (20/80) exhibited better bone formation than nHA/PLGA (50/50). These results suggested that a proper concentration of nHA in the nHA/PLGA composite should be taken into account when the composite scaffolds were prepared, which plays an important role in the biocompatibility, degradation rate and osteoconductivity.

  1. Organometallic Enantiomeric Scaffolding: General Access to 2-Substituted Oxa- and Azabicyclo[3.2.1]octenes via a Brønsted Acid-catalyzed [5+2] Cycloaddition Reaction

    PubMed Central

    Garnier, Ethel C.; Liebeskind, Lanny S.

    2009-01-01

    6-Substituted TpMo(CO)2(η-2,3,4-pyranyl)- and TpMo(CO)2(η-2,3,4-pyridinyl) scaffolds (Tp = hydridotrispyrazolylborato) function as reaction partners in an efficient regio- and stereocontrolled synthesis of functionalized oxa- and azabicyclo[3.2.1]octenes through a novel Brønsted acid-catalyzed [5+2] cycloaddition reaction. Excellent exo-selectivities are obtained and the reaction gives products with complete retention of enantiomeric purity when carried out with chiral, non-racemic scaffolds. The substituent at C-6 of the η3-coordinated heterocyclic scaffold not only influences [5+2] reactivity but also plays a critical role in the demetalation step directing the reaction to only one of two possible products. PMID:18479131

  2. Star-shaped PCL/PLLA blended fiber membrane via electrospinning.

    PubMed

    Li, Haotian; Qiao, Tiankui; Song, Ping; Guo, HuiLing; Song, Xiaofeng; Zhang, Baochang; Chen, Xuesi

    2015-01-01

    Electrospun fiber mesh has been a candidate for guided bone regeneration membrane. However, its poor mechanics property has been limited in clinical application. In this study, various star-shaped poly(ε-caprolactones) (PCLs) are successfully synthesized by ring-opening polymerization and mixed with poly(l-lactide) (PLLA) to be made into blended membranes through electrospinning. Their corresponding properties are evaluated including morphology, thermodynamics, mechanics, and cytotoxicity. The blended fibers show smooth surface and well-distributed structure, which have slight differences in morphology with the change of arm number of star-shaped PCL. Crystallization of the fibrous membrane is influenced by star-shaped PCLs. Glass temperature drops from 64.23 °C for pure PLLA membrane to 53.62-49 °C for the blended membranes. The membranous tensile strength is depended strongly on star-shaped PCLs. The tensile strength goes up with arm number increasing; on the contrary, at the same arm number, the mechanics strength decreases with molecular weight increasing. And the fibrous membrane containing 20 wt.% star-shaped PCL shows better mechanics property compared to the other membranes. The star-shaped PCL/PLLA fiber membrane is not cytotoxicity.

  3. Modification of polylactic acid surface using RF plasma discharge with sputter deposition of a hydroxyapatite target for increased biocompatibility

    NASA Astrophysics Data System (ADS)

    Tverdokhlebov, S. I.; Bolbasov, E. N.; Shesterikov, E. V.; Antonova, L. V.; Golovkin, A. S.; Matveeva, V. G.; Petlin, D. G.; Anissimov, Y. G.

    2015-02-01

    Surface modification of polylactic acid (PLLA) by plasma of radio-frequency magnetron discharge with hydroxyapatite target sputtering was investigated. Increased biocompatibility was demonstrated using studies with bone marrow multipotent mesenchymal stromal cells. Atomic force microscopy demonstrates that the plasma treatment modifies the surface morphology of PLLA to produce rougher surface. Infrared spectroscopy and X-ray diffraction revealed that changes in the surface morphology are caused by the processes of PLLA crystallization. Fluorescent X-ray spectroscopy showed that the plasma treatment also changes the chemical composition of PLLA, enriching it with ions of the sputtered target: calcium, phosphorus and oxygen. It is hypothesized that these surface modifications increase biocompatibility of PLLA without increasing toxicity.

  4. Bacterial adherence to titanium, poly-L-lactic acid, and composite hydroxyapatite and poly-L-lactic acid interference screws.

    PubMed

    Masini, Brendan D; Stinner, Daniel J; Waterman, Scott M; Wenke, Joseph C; Gerlinger, Tad L

    2012-01-01

    This study investigates a potential site of bacterial adherence, the implant surface, comparing titanium, poly-L-lactic acid (PLLA), and composite hydroxyapatite and poly-L-lactic acid (PLLA-HA) interference screws using a bioluminescent in vitro model. Interference screws of three materials, titanium (Arthrex, Naples, FL), bioabsorbable poly-L-lactic acid (BIORCI, Smith & Nephew, Andover, MA), and bioabsorbable composite hydroxyapatite and poly-L-lactic acid (BIORCI-HA, Smith & Nephew, Andover, MA) were immersed in a broth of bioluminescent Staphylococcus aureus. The screws were irrigated and then imaged with a photon-capturing camera system yielding a total photon count correlating with residual adherent bacteria. The titanium screws had the lowest mean total bacterial counts followed by the PLLA-HA screws and with the PLLA screws having the highest mean total counts. The difference in means between the titanium group and the PLLA group was statistically significant (p < .001). Titanium interference screws have less bacterial adherence than comparable bioabsorbable PLLA screws.

  5. The surface grafting of graphene oxide with poly(ethylene glycol) as a reinforcement for poly(lactic acid) nanocomposite scaffolds for potential tissue engineering applications.

    PubMed

    Zhang, Chunmei; Wang, Liwei; Zhai, Tianliang; Wang, Xinchao; Dan, Yi; Turng, Lih-Sheng

    2016-01-01

    Graphene oxide (GO) was incorporated into poly(lactic acid) (PLA) as a reinforcing nanofiller to produce composite nanofibrous scaffolds using the electrospinning technique. To improve the dispersion of GO in PLA and the interfacial adhesion between the filler and matrix, GO was surface-grafted with poly(ethylene glycol) (PEG). Morphological, thermal, mechanical, and wettability properties, as well as preliminary cytocompatibility with Swiss mouse NIH 3T3 cells of PLA, PLA/GO, and PLA/GO-g-PEG electrospun nanofibers, were characterized. Results showed that the average diameter of PLA/GO-g-PEG electrospun nanofibers decreased with filler content. Both GO and GO-g-PEG improved the thermal stability of PLA, but GO-g-PEG was more effective. The water contact angle test of the nanofiber mats showed that the addition of GO in PLA did not change the surface wettability of the materials, but PLA/GO-g-PEG samples exhibited improved wettability with lower water contact angles. The tensile strength of the composite nanofiber mats was improved with the addition of GO, and it was further enhanced when GO was surface grafted with PEG. This suggested that improved interfacial adhesion between GO and PLA was achieved by grafting PEG onto the GO. The cell viability and proliferation results showed that the cytocompatibility of PLA was not compromised with the addition of GO and GO-g-PEG. With enhanced mechanical properties as well as good wettability and cytocompatibility, PLA/GO-g-PEG composite nanofibers have the potential to be used as scaffolds in tissue engineering. PMID:26409231

  6. The surface grafting of graphene oxide with poly(ethylene glycol) as a reinforcement for poly(lactic acid) nanocomposite scaffolds for potential tissue engineering applications.

    PubMed

    Zhang, Chunmei; Wang, Liwei; Zhai, Tianliang; Wang, Xinchao; Dan, Yi; Turng, Lih-Sheng

    2016-01-01

    Graphene oxide (GO) was incorporated into poly(lactic acid) (PLA) as a reinforcing nanofiller to produce composite nanofibrous scaffolds using the electrospinning technique. To improve the dispersion of GO in PLA and the interfacial adhesion between the filler and matrix, GO was surface-grafted with poly(ethylene glycol) (PEG). Morphological, thermal, mechanical, and wettability properties, as well as preliminary cytocompatibility with Swiss mouse NIH 3T3 cells of PLA, PLA/GO, and PLA/GO-g-PEG electrospun nanofibers, were characterized. Results showed that the average diameter of PLA/GO-g-PEG electrospun nanofibers decreased with filler content. Both GO and GO-g-PEG improved the thermal stability of PLA, but GO-g-PEG was more effective. The water contact angle test of the nanofiber mats showed that the addition of GO in PLA did not change the surface wettability of the materials, but PLA/GO-g-PEG samples exhibited improved wettability with lower water contact angles. The tensile strength of the composite nanofiber mats was improved with the addition of GO, and it was further enhanced when GO was surface grafted with PEG. This suggested that improved interfacial adhesion between GO and PLA was achieved by grafting PEG onto the GO. The cell viability and proliferation results showed that the cytocompatibility of PLA was not compromised with the addition of GO and GO-g-PEG. With enhanced mechanical properties as well as good wettability and cytocompatibility, PLA/GO-g-PEG composite nanofibers have the potential to be used as scaffolds in tissue engineering.

  7. Characterization of Electrospun Nanofibrous Scaffolds for Nanobiomedical Applications

    NASA Astrophysics Data System (ADS)

    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.

  8. A computer-designed scaffold for bone regeneration within cranial defect using human dental pulp stem cells

    PubMed Central

    Yeon Kwon, Doo; Seon Kwon, Jin; Hun Park, Seung; Hun Park, Ji; Hee Jang, So; Yun Yin, Xiang; Yun, Jeong-Ho; Ho Kim, Jae; Hyun Min, Byoung; Hee Lee, Jun; Kim, Wan-Doo; Suk Kim, Moon

    2015-01-01

    A computer-designed, solvent-free scaffold offer several potential advantages such as ease of customized manufacture and in vivo safety. In this work, we firstly used a computer-designed, solvent-free scaffold and human dental pulp stem cells (hDPSCs) to regenerate neo-bone within cranial bone defects. The hDPSCs expressed mesenchymal stem cell markers and served as an abundant source of stem cells with a high proliferation rate. In addition, hDPSCs showed a phenotype of differentiated osteoblasts in the presence of osteogenic factors (OF). We used solid freeform fabrication (SFF) with biodegradable polyesters (MPEG-(PLLA-co-PGA-co-PCL) (PLGC)) to fabricate a computer-designed scaffold. The SFF technology gave quick and reproducible results. To assess bone tissue engineering in vivo, the computer-designed, circular PLGC scaffold was implanted into a full-thickness cranial bone defect and monitored by micro-computed tomography (CT) and histology of the in vivo tissue-engineered bone. Neo-bone formation of more than 50% in both micro-CT and histology tests was observed at only PLGC scaffold with hDPSCs/OF. Furthermore, the PLGC scaffold gradually degraded, as evidenced by the fluorescent-labeled PLGC scaffold, which provides information to tract biodegradation of implanted PLGC scaffold. In conclusion, we confirmed neo-bone formation within a cranial bone defect using hDPSCs and a computer-designed PLGC scaffold. PMID:26234712

  9. A computer-designed scaffold for bone regeneration within cranial defect using human dental pulp stem cells.

    PubMed

    Kwon, Doo Yeon; Kwon, Jin Seon; Park, Seung Hun; Park, Ji Hun; Jang, So Hee; Yin, Xiang Yun; Yun, Jeong-Ho; Kim, Jae Ho; Min, Byoung Hyun; Lee, Jun Hee; Kim, Wan-Doo; Kim, Moon Suk

    2015-08-03

    A computer-designed, solvent-free scaffold offer several potential advantages such as ease of customized manufacture and in vivo safety. In this work, we firstly used a computer-designed, solvent-free scaffold and human dental pulp stem cells (hDPSCs) to regenerate neo-bone within cranial bone defects. The hDPSCs expressed mesenchymal stem cell markers and served as an abundant source of stem cells with a high proliferation rate. In addition, hDPSCs showed a phenotype of differentiated osteoblasts in the presence of osteogenic factors (OF). We used solid freeform fabrication (SFF) with biodegradable polyesters (MPEG-(PLLA-co-PGA-co-PCL) (PLGC)) to fabricate a computer-designed scaffold. The SFF technology gave quick and reproducible results. To assess bone tissue engineering in vivo, the computer-designed, circular PLGC scaffold was implanted into a full-thickness cranial bone defect and monitored by micro-computed tomography (CT) and histology of the in vivo tissue-engineered bone. Neo-bone formation of more than 50% in both micro-CT and histology tests was observed at only PLGC scaffold with hDPSCs/OF. Furthermore, the PLGC scaffold gradually degraded, as evidenced by the fluorescent-labeled PLGC scaffold, which provides information to tract biodegradation of implanted PLGC scaffold. In conclusion, we confirmed neo-bone formation within a cranial bone defect using hDPSCs and a computer-designed PLGC scaffold.

  10. Modification of poly(L-lactic acid) electrospun fibers and films with poly(propylene imine) dendrimer

    NASA Astrophysics Data System (ADS)

    Khaliliazar, Sh.; Akbari, S.; Kish, M. H.

    2016-02-01

    Poly(L-lactic acid) (PLLA) electrospun fibers and films were modified with the second generation of poly(propylene imine) dendrimer (PPI-G2) by three different approaches, namely, sodium hydroxide hydrolysis, plasma treatment and direct application of PPI-G2. For the first and the second approaches, PLLA was modified by sodium hydroxide hydrolysis or plasma treatment to produce carboxylic acid groups. Then, the carboxylic acid groups were activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) and N,N‧-dicyclohexyl carbodiimide (DCC) as a hetero bi-functional cross-linker. The cross-linkers promoted the grafting of carboxylic acid groups on the modified PLLA with NH2 groups of PPI-G2. In the third approach, the PPI-G2 dendrimer was directly used as an aminolysis agent for the functionalization of PLLA in a one step process. FTIR analysis confirmed the presence of sbnd NH2 groups of PPI-G2 on the modified PLLA samples, resulting from each one of the three modification methods. Studies by SEM shows bead free electrospun fibers. Also, FE-SEM shows nano-cracks on the surface of films after modification. Contact angle, drug release tests, antibacterial effects and the dying results confirmed that these functionalization methods increased hydrophilicity and reactive side-chains of PLLA in the wet chemical process resulted in providing host-guest properties on the PLLA surface for adsorbing various kinds of guest molecules.

  11. Discovery and Evaluation of Novel Inhibitors of Mycobacterium Protein Tyrosine Phosphatase B from the 6-Hydroxy-Benzofuran-5-Carboxylic Acid Scaffold

    PubMed Central

    He, Yantao; Xu, Jie; Yu, Zhi-hong; Gunawan, Andrea M.; Wu, Li; Wang, Lina; Zhang, Zhong-Yin

    2013-01-01

    Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatase B (mPTPB) is a virulence factor secreted by the pathogen and mediates mycobacterial survival in macrophages by targeting host cell immune responses. Consequently, mPTPB represents an exciting new target to combat TB infection. We describe a medicinal chemistry-oriented approach that transforms a benzofuran salicylic acid scaffold into a highly potent (IC50 = 38 nM) and selective mPTPB inhibitor (>50 fold against a large panel of PTPs). Importantly, the inhibitor is capable of reversing the altered host immune responses induced by the bacterial phosphatase and restoring the macrophage’s full capacity to secrete IL-6 and undergo apoptosis in response to IFN-γ stimulation, validating the concept that chemical inhibition of mPTPB may be therapeutically useful for novel TB treatment. The study further demonstrates that bicyclic salicylic acid pharmacophores can be used to deliver PTP inhibitors with high potency, selectivity, and cellular efficacy. PMID:23305444

  12. Repair of mandibular defects using MSCs-seeded biodegradable polyester porous scaffolds.

    PubMed

    Ren, Jie; Ren, Tianbin; Zhao, Peng; Huang, Yanxia; Pan, Kefeng

    2007-01-01

    PLLA, PLA-PEG and PLGA porous scaffolds with pore size ranging from 100 to 250 microm and porosity over 85% were fabricated by a solution-casting/salt-leaching method. The porous structure and porosity of the scaffold were mainly dependent on volume fraction and size of the porogens of NaCl particles. The effects of the polymeric materials on the cell culture behavior and bone formation in vitro in their scaffolds were studied. In vitro cell culture in the scaffolds of the three polymers demonstrated that mesenchymal stem cells (MSCs) had a good adhesion and spread. The composite matrixes cultured for several days possessed preliminary functions of tissue-engineering bone, with signs of the calcium knur formation and the expression of osteocalcin and collagen I in mRNA, especially that of PLA-PEG and PLGA. These cell-loaded porous scaffolds showed effective repair of mandibular defect of rabbits in vivo. Contrastive experiments demonstrated that the MSCs/PLGA scaffold owned better ability facilitating for the MSCs proliferation, differentiation and defect repair. These composite scaffolds can be a potential effective tool for treating mandibular and other bone defects. PMID:17550655

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

    PubMed

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

    2010-10-01

    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.

  14. A Novel Electrostimulated Drug Delivery System Based on PLLA Composites Exploiting the Multiple Functions of Graphite Nanoplatelets

    PubMed Central

    2016-01-01

    A novel drug delivery system based on poly(l-lactide) (PLLA), graphite, and porphyrin was developed. In particular, 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (THPP) was chosen because, besides its potential as codispersing agent of graphite, it is a pharmacologically active molecule. Graphite nanoplatelets, homogeneously dispersed in both the neat PLLA and the PLLA/porphyrin films, which were prepared by solution casting, turned out to improve the crystallinity of the polymer. Moreover, IR measurements demonstrated that unlike PLLA/porphyrin film, where the porphyrin was prone to aggregate causing variable concentration throughout the sample, the system containing also GNP was characterized by a homogeneous dispersion of the above molecule. The effect of graphite nanoplatelets on the thermal stabilization, electrical conductivity, and improvement of mechanical properties of the polymer resulted to be increased by the addition of the porphyrin to the system, thus demonstrating the role of the molecule in ameliorating the filler dispersion in PLLA. The porphyrin release from the composite film, occurring both naturally and with the application of an electrical field, was measured using an UV–vis spectrophotometer. Indeed, voltage application turned out to improve significantly the kinetic of drug release. The biocompatibility of the polymer matrix as well as the mechanical and thermal properties of the composite together with its electrical response makes the developed material extremely promising in biological applications, particularly in the drug delivery field. PMID:27581486

  15. Degradation of poly(lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLLA) by electron beam radiation.

    PubMed

    Loo, J S C; Ooi, C P; Boey, F Y C

    2005-04-01

    This paper seeks to examine the effects of electron beam (e-beam) radiation on biodegradable polymers (PLGA and PLLA), and to understand their radiation-induced degradation mechanisms. PLGA (80:20) and PLLA polymer films were e-beam irradiated at doses from 2.5 to 50 Mrad and the degradation of these films were studied by measuring the changes in their molecular weights, FTIR spectra, thermal and morphological properties. The dominant effect of e-beam irradiation on both PLGA and PLLA is chain scission. Chain scission occurs first through scission of the polymer main chain, followed by hydrogen abstraction. Chain scission, though responsible for the reduction in the average molecular weight, Tc, Tg and Tm of both polymers, encourages crystallization in PLGA. PLLA also undergoes chain scission upon irradiation but to a lesser degree compared to PLGA. The higher crystallinity of PLLA is the key factor in its greater stability to e-beam radiation compared to PLGA. A linear relationship is also established between the decrease in molecular weight with respect to radiation dose. PMID:15482823

  16. A Novel Electrostimulated Drug Delivery System Based on PLLA Composites Exploiting the Multiple Functions of Graphite Nanoplatelets.

    PubMed

    Gardella, Lorenza; Colonna, Samuele; Fina, Alberto; Monticelli, Orietta

    2016-09-21

    A novel drug delivery system based on poly(l-lactide) (PLLA), graphite, and porphyrin was developed. In particular, 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (THPP) was chosen because, besides its potential as codispersing agent of graphite, it is a pharmacologically active molecule. Graphite nanoplatelets, homogeneously dispersed in both the neat PLLA and the PLLA/porphyrin films, which were prepared by solution casting, turned out to improve the crystallinity of the polymer. Moreover, IR measurements demonstrated that unlike PLLA/porphyrin film, where the porphyrin was prone to aggregate causing variable concentration throughout the sample, the system containing also GNP was characterized by a homogeneous dispersion of the above molecule. The effect of graphite nanoplatelets on the thermal stabilization, electrical conductivity, and improvement of mechanical properties of the polymer resulted to be increased by the addition of the porphyrin to the system, thus demonstrating the role of the molecule in ameliorating the filler dispersion in PLLA. The porphyrin release from the composite film, occurring both naturally and with the application of an electrical field, was measured using an UV-vis spectrophotometer. Indeed, voltage application turned out to improve significantly the kinetic of drug release. The biocompatibility of the polymer matrix as well as the mechanical and thermal properties of the composite together with its electrical response makes the developed material extremely promising in biological applications, particularly in the drug delivery field. PMID:27581486

  17. Nanoscale patterning of poly (L-lactic acid) films with nanoimprinting methods

    NASA Astrophysics Data System (ADS)

    Peer, Akshit; Dhakal, Rabin; Biswas, Rana; Kim, Jaeyoun

    2015-08-01

    Biological applications can benefit from nanoscale texturing of materials for biomedical functions. Texturing of biomaterials can increase the available surface area so that they can be coated with larger doses of therapeutic agents. We demonstrate nano-texturing of poly (L-lactic acid) (PLLA) - a prototypical material commonly used for drug-eluting coronary stents and as a template for cell growth. A master pattern consisting of a periodic array was transferred to a PDMS mold. Drop-casting PLLA achieves the best transfer of patterns, with nanoarrays of holes with pitch ~700 nm. Nanoimprinting the PLLA films results in shallower and less resolved features.

  18. Poly-L-lactic acid facial rejuvenation: an alternative to autologous fat?

    PubMed

    Buckingham, Edward D

    2013-05-01

    Facial volume loss is an important component of facial aging and tends to present at an earlier age than other aspects of aging. Several surgical and nonsurgical products and techniques are available to replace volume loss associated with aging. One surgical technique uses a patient's fat cells to replace or augment volume deficiency. Poly-L-lactic acid (PLLA) injection is a nonsurgical option. This article compares these 2 volume augmentation procedures and discusses characteristics of facial aging, the consultation process involved in assessing individual volume loss, procedure details of autologous fat grafting and PLLA injection, the decision of PLLA versus autologous fat, and patient outcomes.

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2014-01-01

    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 strength 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 compositing 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. PMID:25101261

  2. Evidence for catalytic intermediates involved in generating the chromopyrrolic acid scaffold of rebeccamycin by RebO and RebD.

    PubMed

    Spolitak, Tatyana; Ballou, David P

    2015-05-01

    We provide the first experimental evidence for intermediates being involved in catalysis by RebD in generating the chromopyrrolic acid (CPA) scaffold of rebeccamycin. In the presence of its substrates (indole pyruvate imine - IPAI - and H2O2 both produced by the flavoprotein oxidase RebO that oxidizes tryptophan), RebD reacts as a peroxidase forming two IPAI radicals that recombine as a C-C bond in the CPA. When catalase is included to remove H2O2, CPA can still be formed because the IPAI rapidly reduces RebD, which reacts with O2, utilizing oxidase-peroxidase chemistry to produce CPA. Reduced RebD can also react with H2O2 forming Cpd II directly, which can oxidize IPAI. Stopped-flow spectrophotometric studies demonstrated that during the reaction of RebO and RebD with Trp and oxygen, a species with a red-shifted Soret band at 424.5 nm appeared. This species can react with either guaiacol or ABTS to form ferric RebD, suggesting that it is Cpd II of RebD involved in the formation of CPA. In summary, the studies reveal new and unusual aspects peroxidase and peroxygenase chemistry used by RebD in catalyzing carbon-carbon oxidative coupling reactions that are involved in biosynthesis of indolocarbazoles. PMID:25837855

  3. Fumaric acid monoethyl ester-functionalized poly(D,L-lactide)/N-vinyl-2-pyrrolidone resins for the preparation of tissue engineering scaffolds by stereolithography.

    PubMed

    Jansen, Janine; Melchels, Ferry P W; Grijpma, Dirk W; Feijen, Jan

    2009-02-01

    Polymer networks were prepared by photocross-linking fumaric acid monoethyl ester (FAME) functionalized, three-armed poly(D,L-lactide) oligomers using N-vinyl-2-pyrrolidone (NVP) as diluent and comonomer. The use of NVP together with FAME-functionalized oligomers resulted in copolymerization at high rates, and networks with gel contents in excess of 90% were obtained. The hydrophilicity of the poly(D,L-lactide) networks increases with increasing amounts of NVP, networks containing 50 wt % of NVP absorbed 40% of water. As the amount of NVP was increased from 30 to 50 wt %, the Young's modulus after equilibration in water decreased from 0.8 to 0.2 GPa, as opposed to an increase from 1.5 to 2.1 GPa in the dry state. Mouse preosteoblasts readily adhered and spread onto all prepared networks. Using stereolithography, porous structures with a well-defined gyroid architecture were prepared from these novel materials. This allows the preparation of tissue engineering scaffolds with optimized pore architecture and tunable material properties.

  4. Polyglycolic Acid–Polylactic Acid Scaffold Response to Different Progenitor Cell In Vitro Cultures: A Demonstrative and Comparative X-Ray Synchrotron Radiation Phase-Contrast Microtomography Study

    PubMed Central

    Moroncini, Francesca; Mazzoni, Serena; Belicchi, Marzia Laura Chiara; Villa, Chiara; Erratico, Silvia; Colombo, Elena; Calcaterra, Francesca; Brambilla, Lucia; Torrente, Yvan; Albertini, Gianni; Della Bella, Silvia

    2014-01-01

    Spatiotemporal interactions play important roles in tissue development and function, especially in stem cell-seeded bioscaffolds. Cells interact with the surface of bioscaffold polymers and influence material-driven control of cell differentiation. In vitro cultures of different human progenitor cells, that is, endothelial colony-forming cells (ECFCs) from a healthy control and a patient with Kaposi sarcoma (an angioproliferative disease) and human CD133+ muscle-derived stem cells (MSH 133+ cells), were seeded onto polyglycolic acid–polylactic acid scaffolds. Three-dimensional (3D) images were obtained by X-ray phase-contrast microtomography (micro-CT) and processed with the Modified Bronnikov Algorithm. The method enabled high spatial resolution detection of the 3D structural organization of cells on the bioscaffold and evaluation of the way and rate at which cells modified the construct at different time points from seeding. The different cell types displayed significant differences in the proliferation rate. In conclusion, X-ray synchrotron radiation phase-contrast micro-CT analysis proved to be a useful and sensitive tool to investigate the spatiotemporal pattern of progenitor cell organization on a bioscaffold. PMID:23879738

  5. First chemical feature-based pharmacophore modeling of potent retinoidal retinoic acid metabolism blocking agents (RAMBAs): identification of novel RAMBA scaffolds.

    PubMed

    Purushottamachar, Puranik; Patel, Jyoti B; Gediya, Lalji K; Clement, Omoshile O; Njar, Vincent C O

    2012-01-01

    The first three-dimensional (3D) pharmacophore model was developed for potent retinoidal retinoic acid metabolism blocking agents (RAMBAs) with IC(50) values ranging from 0.0009 to 5.84nM. The seven common chemical features in these RAMBAs as deduced by the Catalyst/HipHop program include five hydrophobic groups (hydrophobes), and two hydrogen bond acceptors. Using the pharmacophore model as a 3D search query against NCI and Maybridge conformational Catalyst formatted databases; we retrieved several compounds with different structures (scaffolds) as hits. Twenty-one retrieved hits were tested for RAMBA activity at 100nM concentration. The most potent of these compounds, NCI10308597 and HTS01914 showed inhibitory potencies less (54.7% and 53.2%, respectively, at 100nM) than those of our best previously reported RAMBAs VN/12-1 and VN/14-1 (90% and 86%, respectively, at 100nM). Docking studies using a CYP26A1 homology model revealed that our most potent RAMBAs showed similar binding to the one observed for a series of RAMBAs reported previously by others. Our data shows the potential of our pharmacophore model in identifying structurally diverse and potent RAMBAs. Further refinement of the model and searches of other robust databases is currently in progress with a view to identifying and optimizing new leads. PMID:22130607

  6. First chemical feature-based pharmacophore modeling of potent retinoidal retinoic acid metabolism blocking agents (RAMBAs): identification of novel RAMBA scaffolds.

    PubMed

    Purushottamachar, Puranik; Patel, Jyoti B; Gediya, Lalji K; Clement, Omoshile O; Njar, Vincent C O

    2012-01-01

    The first three-dimensional (3D) pharmacophore model was developed for potent retinoidal retinoic acid metabolism blocking agents (RAMBAs) with IC(50) values ranging from 0.0009 to 5.84nM. The seven common chemical features in these RAMBAs as deduced by the Catalyst/HipHop program include five hydrophobic groups (hydrophobes), and two hydrogen bond acceptors. Using the pharmacophore model as a 3D search query against NCI and Maybridge conformational Catalyst formatted databases; we retrieved several compounds with different structures (scaffolds) as hits. Twenty-one retrieved hits were tested for RAMBA activity at 100nM concentration. The most potent of these compounds, NCI10308597 and HTS01914 showed inhibitory potencies less (54.7% and 53.2%, respectively, at 100nM) than those of our best previously reported RAMBAs VN/12-1 and VN/14-1 (90% and 86%, respectively, at 100nM). Docking studies using a CYP26A1 homology model revealed that our most potent RAMBAs showed similar binding to the one observed for a series of RAMBAs reported previously by others. Our data shows the potential of our pharmacophore model in identifying structurally diverse and potent RAMBAs. Further refinement of the model and searches of other robust databases is currently in progress with a view to identifying and optimizing new leads.

  7. Bio-inspired dicalcium phosphate anhydrate/poly(lactic acid) nanocomposite fibrous scaffolds for hard tissue regeneration: in situ synthesis and electrospinning.

    PubMed

    Chae, Taesik; Yang, Heejae; Ko, Frank; Troczynski, Tom

    2014-02-01

    The fundamental building blocks of hierarchically structured bone tissue are mineralized collagen fibrils with calcium phosphate nanocrystals that are biologically "engineered" through biomineralization. In this study, we demonstrate an original invention of dicalcium phosphate anhydrate (DCPA)/poly(lactic acid) (PLA) composite nanofibers, which mimics the mineralized collagen fibrils via biomimetic in situ synthesis and electrospinning for hard tissue regenerative medicines. The interaction of the Ca(2+) ions and the carbonyl groups in the PLA provides nucleation sites for DCPA during the in situ synthesis process. This resulted in the improved dispersion of DCPA nanocrystallites in the intrananoporous PLA nanofibers through electrospinning, compared to the severely agglomerated clusters of DCPA nanoparticles fabricated by conventional mechanical blending/electrospinning methods. The addition of poly(ethylene glycol), as a copolymer source, generated more stable and efficient electrospun jets and aided in the electrospinability of the PLA nanofibers incorporating the nanocrystallites. It is expected that the uniformly distributed DCPA nanocrystallites and its unique nanocomposite fibrous topography will enhance the biological performance and the structural stability of the scaffolds used for hard tissue reconstruction and regeneration.

  8. Poly(L-lactic acid)/poly(glycolic acid) microfibrillar polymer-polymer composites: Preparation and viscoelastic properties

    NASA Astrophysics Data System (ADS)

    Kimble, L. D.; Fakirov, S.; Bhattacharyya, D.

    2015-05-01

    Microfibrillar composites (MFCs) from petrochemical-derived polymers have been investigated for several years and the technique can result in significant improvements in mechanical properties when compared with the neat matrix material of the respective composite. The current work applies the technique to biodegradable, biocompatible polymers for potential applications in bioabsorbable medical devices. MFCs were prepared from melt blended poly(L-lactic acid) (PLLA) and poly(glycolic acid) (PGA) via cold drawing then compression molding of extruded yarn. These MFCs were shown to have higher Young's moduli than that of neat PLLA but for load-bearing applications the creep characteristics are of interest. The MFC sheets resulting from compression molding were subjected to tensile relaxation tests at 37°C in the fiber orientation direction. Specimens were also tested via dynamic mechanical thermal analysis (DMTA). Neat PLLA specimens were subjected to the same tests for comparison. Results indicate that at 37°C PLLA/PGA MFCs exhibit lower creep resistance than that of neat PLLA due to the more rapid relaxation of stress observed. DMTA results elucidate the loss modulus changes in PLLA/PGA MFCs which occur as the material approaches the glass transition temperature of PGA (˜45°C).

  9. Global gene expression profile of osteoblast-like cells grown on polyester copolymer scaffolds.

    PubMed

    Idris, Shaza B; Bolstad, Anne Isine; Ibrahim, Salah O; Dånmark, Staffan; Finne-Wistrand, Anna; Albertsson, Ann-Christine; Arvidson, Kristina; Mustafa, Kamal

    2011-11-01

    One of the principal goals in tissue engineering is to produce scaffold materials that will guide cells to differentiate and regenerate functional replacement tissue at the site of injury. Poly(l-lactide-co-1,5-dioxepan-2-one) [Poly(LLA-co-DXO)], a potential scaffolding material for bone tissue engineering, has high hydrophilicity. Previous in vitro studies using human osteoblast-like cells (HOBs) demonstrated greater cytocompatibility and enhanced osteogenic differentiation when HOBs were seeded onto Poly(LLA-co-DXO) compared to Poly(l-lactide) [P(LLA)] scaffolds. The aim of the study was to identify the gene expression profiles of HOBs obtained from alveolar bone and grown on Poly(LLA-co-DXO) biodegradable polymer scaffolds compared to P(LLA) one. Illumina HumanWG-6 v3.0 Expression BeadChips were used for the gene expression analysis. Several genes were found as differentially expressed at 24 h and at 21 days. Expression of genes related to cell adhesion, cytoskeleton, antiapoptosis, proliferation, and bone mineralization was influenced by adding the monomer 1,5-dioxepan-2-one to the L-lactide. Genes related to three biological pathways involving Integrin, Notch, and Ras were found to be upregulated. For selected genes, results were confirmed by quantitative reverse transcriptase-polymerase chain reaction. Further, calcium content analysis revealed a significant enhancement of calcium deposition on both tested scaffolds. This observation was confirmed by Von Kossa and Alizarin Red S staining. Findings of this study are relevant to a better understanding of the molecular mechanisms underlying the behavior of HOBs in bone regenerative procedure.

  10. Amino acidic scaffolds bearing unnatural side chains: an old idea generates new and versatile tools for the life sciences.

    PubMed

    Stevenazzi, Andrea; Marchini, Mattia; Sandrone, Giovanni; Vergani, Barbara; Lattanzio, Maria

    2014-12-01

    The unnatural amino acids (UAAs) are members of a class of molecules with relevant impacts in the life sciences. Due to the role of these molecules in the modulation of the chemical and physical properties of biological and inorganic materials, UAAs have attracted increasing interest in recent years. The aim of this review is to highlight (i) the most recent and innovative synthetic routes for the preparation of UAAs, (ii) the recently marketed UAA-based drugs, and (iii) the most promising technological applications involving novel UAA-containing molecular entities.

  11. Bioresorbable vascular scaffolds-what does the future bring?

    PubMed

    Bil, Jacek; Gil, Robert J

    2016-08-01

    Bioresorbable vascular scaffolds (BVS) have emerged as an interesting alternative since the presence of the prosthesis in the coronary artery is transient. This technology enables to restore the normal vasomotor tone and allows positive remodeling, simultaneously reducing the trigger for persistent inflammation and facilitating further interventions by percutaneous or surgical means. Absorb BVS(®) is the first generation everolimus-eluting poly-L-lactide (PLLA) bioresorbable scaffold. In recent meta-analyses Absorb BVS(®) was definitely proved to be safe and effective device in the treatment of symptomatic coronary artery disease. This was recently confirmed by FDA advisory panel of experts who recommended approval of the device based on an analysis of its risks and rewards. Nevertheless, still there are some concerns regarding stent thrombosis, and the real vessel functionality restoration at long-term observation. Worth mentioning is the fact that apart from stable coronary disease Absorb BVS(®) is used successfully in a series of off-label clinical settings such as acute coronary syndromes including STEMI, in-stent restenosis, coronary bifurcations, left main stenting or chronic total occlusions. Moreover, new bioresorbable scaffolds are under development with DEsolve(®) and DREAM 2G(®), which are the most advanced. PMID:27619478

  12. Bioresorbable scaffolds: a new paradigm in percutaneous coronary intervention.

    PubMed

    Tenekecioglu, Erhan; Farooq, Vasim; Bourantas, Christos V; Silva, Rafael Cavalcante; Onuma, Yoshinobu; Yılmaz, Mustafa; Serruys, Patrick W

    2016-01-01

    Numerous advances and innovative therapies have been introduced in interventional cardiology over the recent years, since the first introduction of balloon angioplasty, but bioresorbable scaffold is certainly one of the most exciting and attracting one. Despite the fact that the metallic drug-eluting stents have significantly diminished the re-stenosis ratio, they have considerable limitations including the hypersensitivity reaction to the polymer that can cause local inflammation, the risk of neo-atherosclerotic lesion formation which can lead to late stent failure as well as the fact that they may preclude surgical revascularization and distort vessel physiology. Bioresorbable scaffolds overcome these limitations as they have the ability to dissolve after providing temporary scaffolding which safeguards vessel patency. In this article we review the recent developments in the field and provide an overview of the devices and the evidence that support their efficacy in the treatment of CAD. Currently 3 devices are CE marked and in clinical use. Additional 24 companies are developing these kind of coronary devices. Most frequently used material is PLLA followed by magnesium. PMID:26868826

  13. Amniotic epithelial stem cell biocompatibility for electrospun poly(lactide-co-glycolide), poly(ε-caprolactone), poly(lactic acid) scaffolds.

    PubMed

    Russo, Valentina; Tammaro, Loredana; Di Marcantonio, Lisa; Sorrentino, Andrea; Ancora, Massimo; Valbonetti, Luca; Turriani, Maura; Martelli, Alessandra; Cammà, Cesare; Barboni, Barbara

    2016-12-01

    Three biodegradable thermoplastic polymers, poly(ε-caprolactone) (PCL), poly(l-lactide-co-d,l-lactide) (PLA) and poly(l-lactide-co-glycolide) (PLGA), have been used to produce nonwovens scaffolds with uniform micrometer fibres. Scaffolds' physical and morphological characterization was performed by X-ray diffraction, Scanning Electron Microscopy and Contact-Angle test. Morphological investigations revealed that all produced fibres were randomly orientated with interconnected pores ranging between 5 and 12μm in diameter. An average fibre diameter of 1.5, 0.75 and 1.2μm was found for PCL, PLA and PLGA, respectively. Moreover, experiments were designed to verify whether the fabricated electrospun substrates were biocompatible for ovine amniotic epithelial stem cells (oAECs) under in vitro conditions. Cell adhesion, survival, spatial organization on fibres, proliferation index, and DNA quantification after 48h culture, showed an enhanced adhesion and proliferation, especially for PLGA scaffolds. The favourable interaction between oAECs and the fibrous scaffolds was attributed to the greatly improved porosity and pore size distribution of the electrospun scaffolds. In addition, AECs can be considered ideal for tissue engineering especially when using biocompatible and opportunely produced scaffolds. PMID:27612719

  14. Amniotic epithelial stem cell biocompatibility for electrospun poly(lactide-co-glycolide), poly(ε-caprolactone), poly(lactic acid) scaffolds.

    PubMed

    Russo, Valentina; Tammaro, Loredana; Di Marcantonio, Lisa; Sorrentino, Andrea; Ancora, Massimo; Valbonetti, Luca; Turriani, Maura; Martelli, Alessandra; Cammà, Cesare; Barboni, Barbara

    2016-12-01

    Three biodegradable thermoplastic polymers, poly(ε-caprolactone) (PCL), poly(l-lactide-co-d,l-lactide) (PLA) and poly(l-lactide-co-glycolide) (PLGA), have been used to produce nonwovens scaffolds with uniform micrometer fibres. Scaffolds' physical and morphological characterization was performed by X-ray diffraction, Scanning Electron Microscopy and Contact-Angle test. Morphological investigations revealed that all produced fibres were randomly orientated with interconnected pores ranging between 5 and 12μm in diameter. An average fibre diameter of 1.5, 0.75 and 1.2μm was found for PCL, PLA and PLGA, respectively. Moreover, experiments were designed to verify whether the fabricated electrospun substrates were biocompatible for ovine amniotic epithelial stem cells (oAECs) under in vitro conditions. Cell adhesion, survival, spatial organization on fibres, proliferation index, and DNA quantification after 48h culture, showed an enhanced adhesion and proliferation, especially for PLGA scaffolds. The favourable interaction between oAECs and the fibrous scaffolds was attributed to the greatly improved porosity and pore size distribution of the electrospun scaffolds. In addition, AECs can be considered ideal for tissue engineering especially when using biocompatible and opportunely produced scaffolds.

  15. Long-term toxicity of holmium-loaded poly(L-lactic acid) microspheres in rats.

    PubMed

    Zielhuis, Sander W; Nijsen, J Frank W; Seppenwoolde, Jan-Henry; Bakker, Chris J G; Krijger, Gerard C; Dullens, Hub F J; Zonnenberg, Bernard A; van Rijk, Peter P; Hennink, Wim E; van het Schip, Alfred D

    2007-11-01

    The aim of this study was to get insight into the toxic effects of holmium-166-loaded poly(L-lactic acid) microspheres (Ho-PLLA-MS) which have very interesting features for treatment of liver malignancies. Acute, mid- and long-term effects were studied in healthy Wistar rats by evaluating clinical, biochemical and tissue response. Rats were divided into four treatment groups: sham, decayed neutron-irradiated Ho-PLLA-MS, non-irradiated Ho-PLLA-MS and PLLA-MS. After implantation of the microspheres into the liver of the rats, the animals were monitored (body weight, temperature and liver enzymes) for a period of 14-18 months. Some of the rats that received previously neutron-irradiated Ho-PLLA-MS were periodically scanned with magnetic resonance imaging (MRI) to see if holmium was released from the microspheres. After sacrifice, the liver tissue was histologically evaluated. Bone tissue was subjected to neutron-activation analysis in order to examine whether accumulation of released holmium in the bone had occurred. No measurable clinical and biochemical toxic effects were observed in any of the treatment groups. Furthermore, histological analyses of liver tissue samples only showed signs of a slight chronic inflammation and no significant differences in the tissue reaction between rats of the different treatment groups could be observed. The non-irradiated PLLA-MS and Ho-PLLA-MS stayed intact during the study. In contrast, 14 months after administration, the neutron-irradiated Ho-PLLA-MS was not completely spherical anymore, indicating that degradation had started. However, the holmium loading had not been released as was illustrated with MRI and affirmed by neutron-activation analysis of bone tissue. In conclusion, neutron-irradiated Ho-PLLA-MS does not provoke any toxic reaction and can be applied safely in vivo.

  16. Fine tuning and measurement of mechanical properties of crosslinked hyaluronic acid hydrogels as biomimetic scaffold coating in regenerative medicine.

    PubMed

    Credi, Caterina; Biella, Serena; De Marco, Carmela; Levi, Marinella; Suriano, Raffaella; Turri, Stefano

    2014-01-01

    Chemically crosslinked hyaluronic acid hydrogels are synthesized with a homogeneous crosslinking process using divinyl sulfone (DVS) as crosslinking agent. Testing different conditions, in terms of both DVS content and curing time, we aim to keep control over the crosslinking process in order to prepare biocompatible hydrogels with mechanical properties closely approximating those of extracellular matrix (ECM) of natural stem cells niches (0.1÷50kPa). The hydrogels properties are evaluated through a reliable methodology based on three independent techniques: dynamic rheological analysis, used as benchmark method; swelling experiments following the Flory-Rehner theory and atomic force microscope (AFM) nanoindentation experiments. Our results demonstrate that controlling crosslinking parameters it is possible to design hydrogels with desired elastic moduli values. HA hydrogels can be ideal coating materials to be implemented in regenerative medicine and particularly in the engineering of ECM niches in vitro.

  17. The Catalytic Scaffold fo the Haloalkanoic Acid Dehalogenase Enzyme Superfamily Acts as a Mold for the Trigonal Bipyramidal Transition State

    SciTech Connect

    Lu,Z.; Dunaway-Mariano, D.; Allen, K.

    2008-01-01

    The evolution of new catalytic activities and specificities within an enzyme superfamily requires the exploration of sequence space for adaptation to a new substrate with retention of those elements required to stabilize key intermediates/transition states. Here, we propose that core residues in the large enzyme family, the haloalkanoic acid dehalogenase enzyme superfamily (HADSF) form a 'mold' in which the trigonal bipyramidal transition states formed during phosphoryl transfer are stabilized by electrostatic forces. The vanadate complex of the hexose phosphate phosphatase BT4131 from Bacteroides thetaiotaomicron VPI-5482 (HPP) determined at 1.00 Angstroms resolution via X-ray crystallography assumes a trigonal bipyramidal coordination geometry with the nucleophilic Asp-8 and one oxygen ligand at the apical position. Remarkably, the tungstate in the complex determined to 1.03 Angstroms resolution assumes the same coordination geometry. The contribution of the general acid/base residue Asp-10 in the stabilization of the trigonal bipyramidal species via hydrogen-bond formation with the apical oxygen atom is evidenced by the 1.52 Angstroms structure of the D10A mutant bound to vanadate. This structure shows a collapse of the trigonal bipyramidal geometry with displacement of the water molecule formerly occupying the apical position. Furthermore, the 1.07 Angstroms resolution structure of the D10A mutant complexed with tungstate shows the tungstate to be in a typical 'phosphate-like' tetrahedral configuration. The analysis of 12 liganded HADSF structures deposited in the protein data bank (PDB) identified stringently conserved elements that stabilize the trigonal bipyramidal transition states by engaging in favorable electrostatic interactions with the axial and equatorial atoms of the transferring phosphoryl group.

  18. Biomimetic nanoclay scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    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

  19. Poly(D,L-lactic acid) coated 45S5 Bioglass-based scaffolds: processing and characterization.

    PubMed

    Chen, Q Z; Boccaccini, A R

    2006-06-01

    A comparative investigation has been carried out on the mechanical properties and bioactivity of Bioglass-based foams, before and after applying a poly(D,L-lactic acid) (PDLLA) coating layer on the foam struts. It was found that the bioactivity of foams upon immersion in simulated body fluid (SBF) was maintained in the PDLLA-coated foams; however, the transformation kinetics in SBF of the crystalline phase (Na(2)Ca(2)Si(3)O(9)) in the foam struts to an amorphous calcium phosphate phase was retarded by PDLLA coating. The compressive and three-point bending strengths of the Bioglass-based foams were slightly improved by the PDLLA-coating, and the work-of-fracture of the foams was considerably enhanced, as indicated by stress-strain curves. Immersion in SBF for 4 weeks led to a large decrease of the mechanical strength of as-sintered foams decreased (from 0.3 to 0.03 MPa), because of the transformation of the crystalline phase to an amorphous calcium phosphate. On the other hand, the mechanical strength was well-maintained in PDLLA-coated foams after immersion in SBF for 8 weeks. This behavior was attributed to the in-situ formation of a nanocomposite PDLLA/calcium phosphate film on the strut surfaces upon immersion in SBF.

  20. Effect of osteoblastic culture conditions on the structure of poly(DL-lactic-co-glycolic acid) foam scaffolds

    NASA Technical Reports Server (NTRS)

    Goldstein, A. S.; Zhu, G.; Morris, G. E.; Meszlenyi, R. K.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1999-01-01

    Poly(DL-lactic-co-glycolic acid) (PLGA) foams are an osteoconductive support that holds promise for the development of bone tissue in vitro and implantation into orthopedic defects. Because it is desirable that foams maintain their shape and size, we examined a variety of foams cultured in vitro with osteoblastic cells. Foams were prepared with different porosities and pore sizes by the method of solvent casting/porogen leaching using 80, 85, and 90 wt% NaCl sieved with particle sizes of 150-300 and 300-500 microm and characterized by mercury intrusion porosimetry. Foams seeded with cells were found to have volumes after 7 days in static culture that decreased with increasing porosity: the least porous exhibited no change in volume while the most porous foams decreased by 39 +/- 10%. In addition, a correlation was observed between decreasing foam volume after 7 days in culture and decreasing internal surface area of the foams prior to seeding. Furthermore, foams prepared with the 300-500 microm porogen had lower porosities, greater mean wall thicknesses between adjacent pores, and larger volumes after 7 days in culture than those prepared with the smaller porogen. Two culture conditions for maintaining cells, static and agitated (in a rotary vessel), were found to have similar influences on foam size, cell density, and osteoblastic function for 7 and 14 days in culture. Finally, we examined unseeded foams in aqueous solutions of pH 3.0, 5.0, and 7.4 and found no significant decrease in foam size with degradation. This study demonstrates that adherent osteoblastic cells may collapse very porous PLGA foams prepared by solvent casting/particulate leaching: a potentially undesirable property for repair of orthopedic defects.

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

    PubMed

    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. PMID:25193100

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

    PubMed

    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.

  3. Optimizing injectable poly-L-lactic acid administration for soft tissue augmentation: The rationale for three treatment sessions

    PubMed Central

    Bauer, Ute; Graivier, Miles H

    2011-01-01

    BACKGROUND: The availability and variety of different injectable modalities has led to a dramatic increase in soft tissue augmentation procedures in recent years. Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable polymer device approved in the United States for use in immunocompetent patients as a single regimen of up to four treatment sessions for correction of shallow to deep nasolabial fold contour deficiencies and other facial wrinkles. Injectable PLLA is also approved for restoration and/or correction of signs of facial fat loss (lipoatrophy) in individuals with HIV. METHODS: The present article provides an overview of previous studies with injectable PLLA, and specifically focuses on the number of recommended treatment sessions and intervals between treatment sessions. The authors also provide two case studies to support their recommendations for an average of three treatment sessions. RESULTS: Although the specific mechanisms remain hypothetical, injections of PLLA are believed to cause a cascade of cellular events that lead to collagen repair and subsequent restoration of facial volume. Because the development of a response to injectable PLLA is gradual and its duration of effect is long lasting, sufficient time between treatment sessions should be allocated to avoid overcorrection. CONCLUSION: Studies of injectable PLLA support the hypothesized mode of operation, and the experience and clinical recommendations of the authors that suggest that three treatment sessions are an optimal regimen for use of injectable PLLA in the majority of patients. PMID:22942665

  4. Influence of purified multiwalled carbon nanotubes on the mechanical and morphological behavior in poly (L-lactic acid) matrix.

    PubMed

    Leal, C V; Martinez, D S T; Más, B A; Alves, O L; Duek, E A R

    2016-06-01

    Poly (L-latic acid) (PLLA) is a bioresorbable polymer widely used as a biomaterial, but its fragility can limit its use. An alternative is to produce polymer nanocomposites, which can enhance the mechanical properties of polymeric matrix, resulting in a material with differentiated properties. In this work, PLLA based nanocomposites containing 0.25, 0.5 and 1.0wt% of purified multiwalled carbon nanotubes (p-MWCNTs) were prepared by the solvent casting method. The morphology and mechanical properties results show an improvement in strain at break for 0.25 and 0.5wt% p-MWCNTs and an increase in stiffness and elastic modulus for all compositions. Nanocomposites presented a p-MWCNTs agglomeration; however, there was a good stress transfer between PLLA and p-MWCNTs, which was confirmed by the increase in the hardness and elastic modulus. Atomic force microscopy analysis indicated an increase in roughness after nanotube addition. The in vitro biological study showed that PLLA/p-MWCNTs nanocomposites are cytocompatible with osteoblasts cells. The capacity of PLLA nanocomposites to stimulate osteogenesis was investigated by alkaline phosphatase (ALP) activity assay. Higher ALP activity was found on osteoblasts cultured on nanocomposites with 0.25 and 0.5wt% p-MWCNT compared to neat PLLA, confirming that PLLA cytocompatibility was improved on these compositions. Finally, our results showed that by a simple and inexpensive solvent casting method, it is possible to manufacture biofunctional nanocomposites devices with potential for orthopedic applications. PMID:27038896

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

    PubMed Central

    Burks, T.; Akthar, F.; Saleemi, M.; Avila, M.; Kiros, Y.

    2015-01-01

    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. PMID:26681961

  6. The influence of the initial preparation and crystallinity on the free radical evolution in gamma irradiated PLLA

    NASA Astrophysics Data System (ADS)

    Milicevic, D.; Milivojevic, D.; Suljovrujic, E.

    2012-09-01

    Poly-L-lactide (PLLA) is a well-known biodegradable and biocompatible semi-crystalline polymer, used in a wide variety of applications, from implantable medical devices and drug release matrices to environmentally friendly packaging materials; diversity in the initial preparation, morphology and crystallinity plays a significant role in most of these applications. On the other hand, gamma radiation, as a processing tool, has often been used for the sterilisation of sensitive polymeric materials. This study presents the influence of the initial preparation and crystallinity on the gamma radiation-induced evolution of free radicals in PLLA. For this purpose, PLLA samples with a large variation in crystallinity (below 20% and over 70%), prepared by two different procedures, were exposed to gamma radiation in air to absorbed doses of 25, 50 and 100 kGy. The annealing treatment was applied to part of the samples, too. The presence and evolution of free radicals were followed using electron spin resonance (ESR) spectroscopy for three weeks. Further characterisation was performed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD) measurements. Presented results show that depending on the initial preparation conditions, the radiation-induced changes in structure and properties of PLLA, as well as the evolution of free radicals, can differ significantly. Furthermore, the annealing treatment substantially reduces the concentration of long-lived free radicals, but can also introduce significant crystallisation.

  7. ZnO-PLLA nanofiber nanocomposite for continuous flow mode purification of water from Cr(VI).

    PubMed

    Burks, T; Akthar, F; Saleemi, M; Avila, M; Kiros, Y

    2015-01-01

    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. PMID:26681961

  8. Biomimetic magnetic silk scaffolds.

    PubMed

    Samal, Sangram K; Dash, Mamoni; Shelyakova, Tatiana; Declercq, Heidi A; Uhlarz, Marc; Bañobre-López, Manuel; Dubruel, Peter; Cornelissen, Maria; Herrmannsdörfer, Thomas; Rivas, Jose; Padeletti, Giuseppina; De Smedt, Stefaan; Braeckmans, Kevin; Kaplan, David L; Dediu, V Alek

    2015-03-25

    Magnetic silk fibroin protein (SFP) scaffolds integrating magnetic materials and featuring magnetic gradients were prepared for potential utility in magnetic-field assisted tissue engineering. Magnetic nanoparticles (MNPs) were introduced into SFP scaffolds via dip-coating methods, resulting in magnetic SFP scaffolds with different strengths of magnetization. Magnetic SFP scaffolds showed excellent hyperthermia properties achieving temperature increases up to 8 °C in about 100 s. The scaffolds were not toxic to osteogenic cells and improved cell adhesion and proliferation. These findings suggest that tailored magnetized silk-based biomaterials can be engineered with interesting features for biomaterials and tissue-engineering applications.

  9. Versatile modular scaffolds

    NASA Technical Reports Server (NTRS)

    Kerley, J.

    1981-01-01

    Movable and fixed modular scaffolds can be tailored to most scaffolding needs by interconnecting only 4 basic structural elements: platforms, rails, vertical-support angles, and stiffener. Standard nuts and bolts are used to join elements, simplifying construction, and reducing costs. Scaffolds are rigid and can be made any length. They are stable on unlevel ground and can extend to well over 50 feet in height. Scaffolds allow for internal elevators and for wheels and air mounts so that same elements can be used for standing or movable scaffold.

  10. Preparation of methotrexate-loaded, large, highly-porous PLLA microspheres by a high-voltage electrostatic antisolvent process.

    PubMed

    Chen, Ai-Zheng; Yang, Yue-Mei; Wang, Shi-Bin; Wang, Guang-Ya; Liu, Yuan-Gang; Sun, Qing-Qing

    2013-08-01

    A high-voltage (10 kV) electrostatic antisolvent process was used to prepare methotrexate (MTX)-loaded, large, highly-porous poly-L-lactide (PLLA) microspheres. MTX solution in dimethyl sulfoxide (DMSO) and PLLA solution in dichloromethane (DCM) were homogeneously mixed, and then ammonium bicarbonate (AB) aqueous solution was added. The mixed solution was emulsified by ultrasonication with Pluronic F127 (PF127) as an emulsion stabilizer. The emulsion was electrosprayed by the specific high-voltage apparatus and dropped into a 100 mL of ethanol, which acted as an antisolvent for the solute and extracted DMSO and DCM, causing the co-precipitation of PLLA and MTX, thus forming microspheres with AB aqueous micro-droplets uniformly inlaid. The obtained MTX-PLLA microspheres were subsequently lyophilized to obtain large, highly-porous MTX-PLLA microspheres, which exhibited an identifiable spherical shape and a rough surface furnished with open pores, with a mean particle size of 25.0 μm, mass median aerodynamic diameter of 3.1 ± 0.2 μm, fine-particle fraction of 57.1 ± 1.6 %, and porosity of 81.8 %; furthermore, they offered a sustained release of MTX. X-ray diffraction and Fourier transform-infrared spectra revealed that no crystallinity or alteration of chemical structure occurred during the high-voltage electrostatic antisolvent process, which in this study was proved to have great potential for preparing highly-porous drug-loaded polymer microspheres for use in pulmonary drug delivery.

  11. Satisfying patient expectations with poly-L-lactic acid soft tissue augmentation.

    PubMed

    Vleggaar, Danny; Fitzgerald, Rebecca; Lorenc, Z Paul

    2014-04-01

    Patient interest and physician use of soft tissue augmentation have increased significantly in recent years, especially among younger patients. A recent consumer survey conducted on behalf of the American Society of Plastic Surgeons found that the majority of respondents would rather have a facial injectable treatment than a surgical treatment. In another recent survey, consumers gave the highest overall satisfaction ratings to injectable filler treatments (92%), including poly-L-lactic acid (PLLA), and injectable wrinkle relaxers (92%), with injectable fillers receiving the highest "extremely satisfied" rating (45%). Long-lasting benefit is a desirable attribute in soft tissue augmentation, making PLLA a favorable alternative for many patients. When considering the use of PLLA, clinicians should ensure that their patients understand its benefit profile, and that these benefits are consistent with the patients' cosmetic goals. The implementation of the latest recommendations on methodological approaches in the use of PLLA will minimize the occurrence of adverse events, further enhancing patient satisfaction. PMID:24719077

  12. Porous three-dimensional carbon nanotube scaffolds for tissue engineering.

    PubMed

    Lalwani, Gaurav; Gopalan, Anu; D'Agati, Michael; Sankaran, Jeyantt Srinivas; Judex, Stefan; Qin, Yi-Xian; Sitharaman, Balaji

    2015-10-01

    Assembly of carbon nanomaterials into three-dimensional (3D) architectures is necessary to harness their unique physiochemical properties for tissue engineering and regenerative medicine applications. Herein, we report the fabrication and comprehensive cytocompatibility assessment of 3D chemically crosslinked macrosized (5-8 mm height and 4-6 mm diameter) porous carbon nanotube (CNT) scaffolds. Scaffolds prepared via radical initiated thermal crosslinking of single- or multiwalled CNTs (SWCNTs and MWCNTs) possess high porosity (>80%), and nano-, micro-, and macroscale interconnected pores. MC3T3 preosteoblast cells on MWCNT and SWCNT scaffolds showed good cell viability comparable to poly(lactic-co-glycolic) acid (PLGA) scaffolds after 5 days. Confocal live cell and immunofluorescence imaging showed that MC3T3 cells were metabolically active and could attach, proliferate, and infiltrate MWCNT and SWCNT scaffolds. SEM imaging corroborated cell attachment and spreading and suggested that cell morphology is governed by scaffold surface roughness. MC3T3 cells were elongated on scaffolds with high surface roughness (MWCNTs) and rounded on scaffolds with low surface roughness (SWCNTs). The surface roughness of scaffolds may be exploited to control cellular morphology and, in turn, govern cell fate. These results indicate that crosslinked MWCNTs and SWCNTs scaffolds are cytocompatible, and open avenues toward development of multifunctional all-carbon scaffolds for tissue engineering applications.

  13. PLLA/Flax Mat/Balsa Bio-Sandwich Manufacture and Mechanical Properties

    NASA Astrophysics Data System (ADS)

    Le Duigou, Antoine; Deux, Jean-Marc; Davies, Peter; Baley, Christophe

    2011-10-01

    This paper describes the manufacture and mechanical characterization of a sandwich material which is 100% bio-sourced. The flax mat/PLLA facings and balsa core can also be composted at end of service life. Manufacture is by vacuum bag moulding. The optimum moulding time and temperature are a compromise between ensuring good impregnation and avoiding degradation, and holding for 60 min at 180°C was found to be satisfactory. The mechanical properties of the bio-sandwich obtained are compared to those of a traditional glass reinforced polyester balsa sandwich. The flexural strength is 30% lower, as predicted based on the facing properties. Skin/core adhesion is also measured using debonding tests. Crack propagation occurs at the skin/core interface in the traditional sandwich but within the facing in the bio-sandwich. The impregnation of the core in the two materials is examined using X-ray micro-tomography.

  14. Various Cyclization Scaffolds by a truly Ugi 4-CR

    PubMed Central

    Sinha, Mantosh K.; Khoury, Kareem; Herdtweck, Eberhardt; Dömling, Alexander

    2013-01-01

    Efficient access to a large chemical space based on new scaffolds with defined 3D conformations and highly variable in the side chains is needed to find novel functional materials. Four heterocyclic scaffolds based on a four component Ugi reaction of α-amino acids, oxo components, isocyanides and primary or secondary amines suitably functionalized are described. A handful of examples are described for each scaffold. PMID:23760036

  15. Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats

    NASA Astrophysics Data System (ADS)

    Luo, Binhua; Wang, Siqi; Rao, Rong; Liu, Xuhan; Xu, Haibo; Wu, Yun; Yang, Xiangliang; Liu, Wei

    2016-04-01

    The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T 2 relaxation rate ( r 2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM-1 s-1. In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian blue staining of the section clearly

  16. Conjugation Magnetic PAEEP-PLLA Nanoparticles with Lactoferrin as a Specific Targeting MRI Contrast Agent for Detection of Brain Glioma in Rats.

    PubMed

    Luo, Binhua; Wang, Siqi; Rao, Rong; Liu, Xuhan; Xu, Haibo; Wu, Yun; Yang, Xiangliang; Liu, Wei

    2016-12-01

    The diagnosis of malignant brain gliomas is largely based on magnetic resonance imaging (MRI) with contrast agents. In recent years, nano-sized contrast agents have been developed for improved MRI diagnosis. In this study, oleylamine-coated Fe3O4 magnetic nanoparticles (OAM-MNPs) were synthesized with thermal decomposition method and encapsulated in novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer nanoparticles. The OAM-MNP-loaded PAEEP-PLLA nanoparticles (M-PAEEP-PLLA-NPs) were further conjugated with lactoferrin (Lf) for glioma tumor targeting. The Lf-conjugated M-PAEEP-PLLA-NPs (Lf-M-PAEEP-PLLA-NPs) were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The average size of OAM-MNPs, M-PAEEP-PLLA-NPs, and Lf-M-PAEEP-PLLA-NPs were 8.6 ± 0.3, 165.7 ± 0.6, and 218.2 ± 0.4 nm, with polydispersity index (PDI) of 0.185 ± 0.023, 0.192 ± 0.021, and 0.224 ± 0.036, respectively. TEM imaging showed that OAM-MNPs were monodisperse and encapsulated in Lf-M-PAEEP-PLLA-NPs. TGA analysis showed that the content of iron oxide nanoparticles was 92.8 % in OAM-MNPs and 45.2 % in Lf-M-PAEEP-PLLA-NPs. VSM results indicated that both OAM-MNPs and Lf-M-PAEEP-PLLA-NPs were superparamagnetic, and the saturated magnetic intensity were 77.1 and 74.8 emu/g Fe. Lf-M-PAEEP-PLLA-NPs exhibited good biocompatibility in cytotoxicity assay. The high cellular uptake of Lf-M-PAEEP-PLLA-NPs in C6 cells indicated that Lf provided effective targeting for the brain tumor cells. The T 2 relaxation rate (r 2) of M-PAEEP-PLLA-NPs and Lf-M-PAEEP-PLLA-NPs were calculated to be 167.2 and 151.3 mM(-1) s(-1). In MRI on Wistar rat-bearing glioma tumor, significant contrast enhancement could clearly appear at 4 h after injection and last 48 h. Prussian

  17. Fiber-reinforced hydrogel scaffolds for heart valve tissue engineering.

    PubMed

    Eslami, Maryam; Vrana, Nihal Engin; Zorlutuna, Pinar; Sant, Shilpa; Jung, Sungmi; Masoumi, Nafiseh; Khavari-Nejad, Ramazan Ali; Javadi, Gholamreza; Khademhosseini, Ali

    2014-09-01

    Heart valve-related disorders are among the major causes of death worldwide. Although prosthetic valves are widely used to treat this pathology, current prosthetic grafts cannot grow with the patient while maintaining normal valve mechanical and hemodynamic properties. Tissue engineering may provide a possible solution to this issue through using biodegradable scaffolds and patients' own cells. Despite their similarity to heart valve tissue, most hydrogel scaffolds are not mechanically suitable for the dynamic stresses of the heart valve microenvironment. In this study, we integrated electrospun poly(glycerol sebacate) (PGS)-poly(ɛ-caprolactone) (PCL) microfiber scaffolds, which possess enhanced mechanical properties for heart valve engineering, within a hybrid hydrogel made from methacrylated hyaluronic acid and methacrylated gelatin. Sheep mitral valvular interstitial cells were encapsulated in the hydrogel and evaluated in hydrogel-only, PGS-PCL scaffold-only, and composite scaffold conditions. Although the cellular viability and metabolic activity were similar among all scaffold types, the presence of the hydrogel improved the three-dimensional distribution of mitral valvular interstitial cells. As seen by similar values in both the Young's modulus and the ultimate tensile strength between the PGS-PCL scaffolds and the composites, microfibrous scaffolds preserved their mechanical properties in the presence of the hydrogels. Compared to electrospun or hydrogel scaffolds alone, this combined system may provide a more suitable three-dimensional structure for generating scaffolds for heart valve tissue engineering.

  18. Phase-separation-induced single-crystal morphology in poly(L-lactic acid) blended with poly(1,4-butylene adipate) at specific composition.

    PubMed

    Nurkhamidah, Siti; Woo, E M

    2011-11-17

    The single-crystal morphology of poly(L-lactic acid) (PLLA) in blending with poly(butylene adipate) (PBA) in PLLA/PBA blends was for the first time reported in melt crystallization. At crystallization temperature (T(c)) = 110 °C, by adding 30 wt % PBA into PLLA, the lamellae exhibit six-stalk dendrites with single-crystal packing. Phase separation and crystallization took place simultaneously at T(c) = 110 °C in PLLA/PBA (70/30) blend, leading to discrete PBA domains and continuous PLLA domains. For PLLA/PBA (70/30) blend, all PBA were rejected from the growth front of PLLA crystals, expelled, and crystallized at ambient temperature as ring-banded PBA spherulites inside the discrete domains only, resulting in a favorable environment for formation of PLLA single crystals in the continuous domain. Atomic force microscopy (AFM) observation on individual crystallites reveals that lozenge-shaped single crystals were packed with a clockwise spiral pattern, stacked in 1-3 layers, and these lozenge-shaped crystals are aligned six hexasected directions into hexastalk dendrites with occasional side branches that are also aligned at 60° to main branches. The monolamellar thickness of lozenge-shaped single crystals was measured to be about 13-34 nm, and the dimension is about 0.8-3 μm along the short axis and 1.6-5 μm along the long axis. Typically, three layers of single crystals are stacked one on another; the lozenge crystals on the bottom layer are about twice as large as those on the top layer, forming a pyramid shape in the depth direction. Formation mechanisms of single crystals in melt-crystallized PLLA/PBA blend from 700 nm film thickness are discussed in correlation with exact phase separation at 30 wt % PBA. PMID:21962158

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

    NASA Astrophysics Data System (ADS)

    Kantoǧlu, Ömer; Güven, Olgun

    2002-12-01

    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 ( Tg) 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.

  20. Optimizing facial rejuvenation outcomes by combining poly-L-lactic acid, hyaluronic acid, calcium hydroxylapatite, and neurotoxins: two case studies.

    PubMed

    Lorenc, Z Paul; Daro-Kaftan, Elizabeth

    2014-02-01

    Reversal of the visible signs of facial aging with the use of injectable products as an alternative to surgery has become more popular, with nearly 5 million procedures performed in the United States in 2012. Volume augmentation products, such as hyaluronic acid (HA), calcium hydroxylapatite (CaHA), and poly-L-lactic acid (PLLA), are often used in combination with one another and with neurotoxins for facial rejuvenation because of the complementary modes of action. This article presents 2 case reports involving patientspecific combinations of 2 different HA products, injectable PLLA, and CaHA with incobotulinumtoxinA or abobotulinumtoxinA. The combination of HA, CaHA, PLLA, and neurotoxins has resulted in outstanding outcomes for many patients, with no clinical evidence of increased adverse events secondary to combination therapy. PMID:24509971

  1. Optimizing facial rejuvenation outcomes by combining poly-L-lactic acid, hyaluronic acid, calcium hydroxylapatite, and neurotoxins: two case studies.

    PubMed

    Lorenc, Z Paul; Daro-Kaftan, Elizabeth

    2014-02-01

    Reversal of the visible signs of facial aging with the use of injectable products as an alternative to surgery has become more popular, with nearly 5 million procedures performed in the United States in 2012. Volume augmentation products, such as hyaluronic acid (HA), calcium hydroxylapatite (CaHA), and poly-L-lactic acid (PLLA), are often used in combination with one another and with neurotoxins for facial rejuvenation because of the complementary modes of action. This article presents 2 case reports involving patientspecific combinations of 2 different HA products, injectable PLLA, and CaHA with incobotulinumtoxinA or abobotulinumtoxinA. The combination of HA, CaHA, PLLA, and neurotoxins has resulted in outstanding outcomes for many patients, with no clinical evidence of increased adverse events secondary to combination therapy.

  2. Flow perfusion improves seeding of tissue engineering scaffolds with different architectures.

    PubMed

    Alvarez-Barreto, Jose F; Linehan, Shawna M; Shambaugh, Robert L; Sikavitsas, Vassilios I

    2007-03-01

    Engineered bone grafts have been generated in static and dynamic systems by seeding and culturing osteoblastic cells on 3-D scaffolds. Seeding determines initial cellularity and cell spatial distribution throughout the scaffold, and affects cell-matrix interactions. Static seeding often yields low seeding efficiencies and poor cell distributions; thus creating a need for techniques that can improve these parameters. We have evaluated the effect of oscillating flow perfusion on seeding efficiency and spatial distribution of MC3T3-E1 pre-osteoblastic cells in fibrous polystyrene matrices (20, 35 and 50-microm fibers) and foams prepared by salt leaching, using as controls statically seeded scaffolds. An additional control was investigated where static seeding was followed by unidirectional perfusion. Oscillating perfusion resulted in the most efficient technique by yielding higher seeding efficiencies, more homogeneous distribution and stronger cell-matrix interactions. Cell surface density increased with inoculation cell number and then reached a maximum, but significant detachment occurred at greater flow rates. Oxygen plasma treatment of the fibers greatly improved seeding efficiency. Having similar porosity and dimensions, fibrous matrices yielded higher cell surface densities than foams. Fluorescence microscopy and histological analyses in polystyrene and PLLA scaffolds demonstrated that perfusion seeding produced more homogeneous cell distribution, with fibrous matrices presenting greater uniformity than the foams.

  3. Polylactic-co-glycolic acid mesh coated with fibrin or collagen and biological adhesive substance as a prefabricated, degradable, biocompatible, and functional scaffold for regeneration of the urinary bladder wall.

    PubMed

    Salem, Salah Abood; Hwei, Ng Min; Bin Saim, Aminuddin; Ho, Christopher C K; Sagap, Ismail; Singh, Rajesh; Yusof, Mohd Reusmaazran; Md Zainuddin, Zulkifili; Idrus, Ruszymah Bt Hj

    2013-08-01

    The chief obstacle for reconstructing the bladder is the absence of a biomaterial, either permanent or biodegradable, that will function as a suitable scaffold for the natural process of regeneration. In this study, polylactic-co-glycolic acid (PLGA) plus collagen or fibrin was evaluated for its suitability as a scaffold for urinary bladder construct. Human adipose-derived stem cells (HADSCs) were cultured, followed by incubation in smooth muscle cells differentiation media. Differentiated HADSCs were then seeded onto PLGA mesh supported with collagen or fibrin. Evaluation of cell-seeded PLGA composite immersed in culture medium was performed under a light and scanning microscope. To determine if the composite is compatible with the urodynamic properties of urinary bladder, porosity and leaking test was performed. The PLGA samples were subjected to tensile testing was pulled until PLGA fibers break. The results showed that the PLGA composite is biocompatible to differentiated HADSCs. PLGA-collagen mesh appeared to be optimal as a cell carrier while the three-layered PLGA-fibrin composite is better in relation to its leaking/ porosity property. A biomechanical test was also performed for three-layered PLGA with biological adhesive and three-layered PLGA alone. The tensile stress at failure was 30.82 ± 3.80 (MPa) and 34.36 ± 2.57 (MPa), respectively. Maximum tensile strain at failure was 19.42 ± 2.24 (mm) and 23.06 ± 2.47 (mm), respectively. Young's modulus was 0.035 ± 0.0083 and 0.043 ± 0.012, respectively. The maximum load at break was 58.55 ± 7.90 (N) and 65.29 ± 4.89 (N), respectively. In conclusion, PLGA-Fibrin fulfils the criteria as a scaffold for urinary bladder reconstruction.

  4. Bioactive Nano-Fibrous Scaffolds for Bone and Cartilage Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Feng, Kai

    Scaffolds that can mimic the structural features of natural extracellular matrix and can deliver biomolecules in a controlled fashion may provide cells with a favorable microenvironment to facilitate tissue regeneration. Biodegradable nanofibrous scaffolds with interconnected pore network have previously been developed in our laboratory to mimic collagen matrix and advantageously support both bone and cartilage regeneration. This dissertation project aims to expand both the structural complexity and the biomolecule delivery capacity of such biomimetic scaffolds for tissue engineering. We first developed a nanofibrous scaffold that can release an antibiotic (doxycycline) with a tunable release rate and a tunable dosage, which was demonstrated to be able to inhibit bacterial growth over a prolonged time period. We then developed a nanofibrous tissue-engineciing scaffold that can release basic fibroblast growth factor (bFGF) in a spatially and temporally controlled fashion. In a mouse subcutaneous implantation model, the bFGF-releasing scaffold was shown to enhance cell penetration, tissue ingrowth and angiogenesis. It was also found that both the dose and the release rate of bFGF play roles in the biologic function of the scaffold. After that, we developed a nanofibrous PLLA scaffold that can release both bone morphogenetic protein 7 (BMP-7) and platelet-derived growth factor (PDGF) with distinct dosages and release kinetics. It was demonstrated that BMP-7 and PDGF could synergistically enhance bone regeneration using a mouse ectopic bone formation model and a rat periodontal fenestration defect regeneration model. The regeneration outcome was dependent on the dosage, the ratio and the release kinetics of the two growth factors. Last, we developed an anisotropic composite scaffold with an upper layer mimicking the superficial zone of cartilage and a lower layer mimicking the middle zone of cartilage. The thin superficial layer was fabricated using an electrospinning

  5. Hydroxyapatite surface modified by L-lactic acid and its subsequent grafting polymerization of L-lactide.

    PubMed

    Qiu, Xueyu; Hong, Zhongkui; Hu, Junli; Chen, Li; Chen, Xuesi; Jing, Xiabin

    2005-01-01

    A new method of surface modification of hydroxyapatite nanoparticles (n-HA) by surface grafting reaction of l-lactic acid and ring-opening polymerization of l-lactide (LLA) was developed. Two modified HA nanoparticles were obtained: HA modified by l-lactic acid (l-HA) and HA grafting with poly(l-lactide) (PLLA; p-HA). The modified surface of n-HA was attested by Fourier transformation infrared, (31)P MAS NMR, and thermal gravimetric analysis. The results showed that l-lactic acid could be easily grafted onto the n-HA surface by forming a Ca carboxylate bond and initiated by the hydroxyl group of the grafted l-lactic acid and LLA could be graft-polymerized onto the n-HA surface in the presence of stannous octanoate. The highest grafting amounts of l-lactic acid and PLLA were about 33 and 22 wt %, respectively. The modified HA/PLLA composites showed good mechanical properties and uniform microstructure. The tensile strength and modulus of the p-HA/PLLA composite containing 15 wt % of p-HA were 67 MPa and 2.1 GPa, respectively, while those of the n-HA/PLLA composites were 45 MPa and 1.7 GPa, respectively. The elongation at the break of the l-HA/PLLA composite containing 15 wt % l-HA could reach 44%, in comparison with 6.5% of the n-HA/PLLA composites containing 15 wt % n-HA. PMID:15877333

  6. Laser microstructured biodegradable scaffolds.

    PubMed

    Koroleva, Anastasia; Kufelt, Olga; Schlie-Wolter, Sabrina; Hinze, Ulf; Chichkov, Boris

    2013-10-01

    The two-photon polymerization technique (2PP) uses non-linear absorption of femtosecond laser pulses to selectively polymerize photosensitive materials. 2PP has the ability to fabricate structures with a resolution from tens of micrometers down to hundreds of nanometers. Three-dimensional microstructuring by the 2PP technique provides many interesting possibilities for biomedical applications. This microstructuring technique is suitable with many biocompatible polymeric materials, such as polyethylene glycol, polylactic acid, polycaprolactone, gelatin, zirconium-based hybrids, and others. The process of fabrication does not require clean room conditions and does not use hazard chemicals or high temperatures. The most beneficial property of 2PP is that it is capable of producing especially complex three-dimensional (3-D) structures, including devices with overhangs, without using any supportive structure. The flexibility in controlling geometries and feature sizes and the possibility to fabricate structures without the addition of new material layers makes this technique particularly appealing for fabrication of 3-D scaffolds for tissue engineering. PMID:23729598

  7. [Strategies to choose scaffold materials for tissue engineering].

    PubMed

    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

  8. [Strategies to choose scaffold materials for tissue engineering].

    PubMed

    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

  9. The history behind the use of injectable poly-L-lactic acid for facial and nonfacial volumization: the positive impact of evolving methodology.

    PubMed

    Vleggaar, Danny; Fitzgerald, Rebecca; Lorenc, Z Paul

    2014-04-01

    Poly-L-lactic acid (PLLA) was first approved for soft tissue augmentation in Europe in 1999 for the cosmetic correction of scars and wrinkles. Due, in part, to inadequate usage recommendations that included those related to product reconstitution and hydration, injection sites, techniques, and timing, and patient selection, PLLA use was initially associated with suboptimal cosmetic benefit and a high rate of specific adverse events, such as the formation of nodules. As clinical experience with PLLA has increased, the implementation of specific methodological changes has allowed greater, more consistent cosmetic effects to be achieved, with a low rate of adverse events. This enhanced PLLA methodology, coupled with an evolving understanding of the interplay between structures in the aging face, now allows predictably favorable results across a broad range of patient types. PMID:24719075

  10. Production and characterization of 166Ho polylactic acid microspheres.

    PubMed

    Yavari, Kamal; Yeganeh, Ehsan; Abolghasemi, Hossein

    2016-01-01

    Microsphere and particle technology with selective transport of radiation represents a new generation of therapeutics. Poly-L-lactic acid (PLLA) microspheres loaded with holmium-166 acetylacetonate ((166)Ho-PLLA-MS) are novel microdevices. In this research, (165)HoAcAc-PLLA microparticles were prepared by the solvent evaporation technique. Microspheres were irradiated at Tehran Research Reactor. The diameter and surface morphologies were characterized by particle sizer and scanning electron microscopy before and after irradiation. The complex stability, radiochemical purity, and in vivo biodistribiotion were checked in the final solution up to 3 days. In this study, (166)Ho-PLLA spherical particles with a smooth surface and diameter of 20-40 µm were obtained, which were stable in vitro and in vivo studies. Neutron irradiation did not damage the particles. The ease with which the PLLA spheres could be made in the optimal size range for later irradiation and their ability to retain the (166)Ho provided good evidence for their potential use in radioembolization.

  11. Hierarchically designed electrospun tubular scaffolds for cardiovascular applications.

    PubMed

    Shalumon, K T; Sreerekha, P R; Sathish, D; Tamura, H; Nair, S V; Chennazhi, K P; Jayakumar, R

    2011-10-01

    Hierarchically designed tubular scaffolds with bi-layer and multi-layer structures are expected to mimic native vessels in its structural geometry. A new approach for the fabrication of hierarchically designed tubular scaffold with suitable morphology was introduced through electrospinning technique. Among these scaffolds, bi-layer scaffold had a single inner and outer layer whereas multilayer scaffold had more number of inner layers. The inner layer/layers of the scaffolds were made up of aligned poly (lactic acid) (PLA) fibers for EC adhesion where as outer layers were composed of random fibers of poly (caprolactone) (PCL) and PLA providing larger pores for SMC penetration. The fabricated scaffolds were characterized by FTIR spectroscopy and Differential Thermal Analysis (DTA) and examined by evaluating cellular interactions. Human Umbilical Vein Endothelial Cells (HUVECs) seeded on aligned PLA fibers showed enhanced cellular orientation and cytoskeletal organization. In addition, the PCL-PLA composite random fibers supported SMC adhesion and proliferation sufficiently. The functionality of the endothelial cells grown on the PLA-aligned scaffold was also found to be satisfactory. Lining the constructs with a luminal monolayer of well-organized ECs along with homogenously distributed SMCs surrounding them might result in vascular conduits suitable for in vivo applications. Since this hierarchically designed tubular scaffold closely mimics the morphology of native vessel, this could be a better candidate for vascular tissue engineering. PMID:22195478

  12. Novel biodegradable porous scaffold applied to skin regeneration.

    PubMed

    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.

  13. Optimized Diazo Scaffold for Protein Esterification

    PubMed Central

    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

  14. Influence of electrospun scaffolds prepared from distinct polymers on proliferation and viability of endothelial cells

    SciTech Connect

    Matveeva, V. G. Antonova, L. V. Velikanova, E. A.; Sergeeva, E. A.; Krivkina, E. O.; Glushkova, T. V.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S.

    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.

  15. Influence of electrospun scaffolds prepared from distinct polymers on proliferation and viability of endothelial cells

    NASA Astrophysics Data System (ADS)

    Matveeva, V. G.; Antonova, L. V.; Velikanova, E. A.; Sergeeva, E. A.; Krivkina, E. O.; Glushkova, T. V.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S.

    2015-10-01

    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.

  16. Exact approaches for scaffolding

    PubMed Central

    2015-01-01

    This paper presents new structural and algorithmic results around the scaffolding problem, which occurs prominently in next generation sequencing. The problem can be formalized as an optimization problem on a special graph, the "scaffold graph". We prove that the problem is polynomial if this graph is a tree by providing a dynamic programming algorithm for this case. This algorithm serves as a basis to deduce an exact algorithm for general graphs using a tree decomposition of the input. We explore other structural parameters, proving a linear-size problem kernel with respect to the size of a feedback-edge set on a restricted version of Scaffolding. Finally, we examine some parameters of scaffold graphs, which are based on real-world genomes, revealing that the feedback edge set is significantly smaller than the input size. PMID:26451725

  17. Human flexor tendon tissue engineering: revitalization of biostatic allograft scaffolds.

    PubMed

    Woon, Colin Y L; Farnebo, Simon; Schmitt, Taliah; Kraus, Armin; Megerle, Kai; Pham, Hung; Yan, Xinrui; Gambhir, Sanjiv S; Chang, James

    2012-12-01

    Cadaveric tendon allografts form a readily available and underutilized source of graft material. Because of their material properties, allografts are biomechanically and biologically superior to synthetic scaffolds. However, before clinical use, allografts must undergo decellularization to reduce immunogenicity and oxidation to increase porosity, leaving a nonvital biostatic scaffold. Ex vivo seeding, or revitalization, is thought to hasten graft incorporation and stimulate intrinsic tendon healing, permitting early mobilization and return to function. In this study, we examined physical and biochemical augmentation methods, including scaffold surface scoring (physical) and rehydration of lyophilized scaffolds in serum (biochemical). Scaffolds were divided into four groups: (1) scored scaffolds, (2) lyophilized scaffolds rehydrated in fetal calf serum (FCS), (3) scaffolds both scored and rehydrated in FCS, and (4) control scaffolds. Scaffolds were reseeded with adipose-derived stem cells (ADSCs). Reseeding efficacy was quantified by a live cell and total cell assays and qualified histologically with hematoxylin and eosin, live/dead and SYTO green nucleic acid stains, TUNEL apoptosis stains, procollagen stains, and transmission electron microscopy. Scaffold-seeded cell viability at up to 2 weeks in vitro and up to 4 weeks in vivo was demonstrated with bioluminescent imaging of scaffolds seeded with luciferase-positive ADSCs. The effect of seeding on scaffold biomechanical properties was demonstrated with evaluation of ultimate tensile stress (UTS) and an elastic modulus (EM). We found that scaffold surface scoring led to an increase in live and total cell attachment and penetration (MTS assay, p<0.001 and DNA assay, p=0.003, respectively). Histology confirmed greater total cell number in both construct core and surface in scored compared with unscored constructs. Cells reseeded on scored constructs displayed reduced apoptosis, persistent procollagen production, and

  18. Neurite Outgrowth On Electrospun PLLA Fibers Is Enhanced By Exogenous Electrical Stimulation

    PubMed Central

    Koppes, A. N.; Zaccor, N. W.; Rivet, C. J.; Williams, L. A.; Piselli, J. M.; Gilbert, R. J.; Thompson, D. M.

    2014-01-01

    Objective Both electrical stimuli (endogenous and exogenous) and topographical cues are instructive to axonal extension. This report, for the first time, investigated the relative dominance of directional topographical guidance cues and directional electrical cues to enhance and/or direct primary neurite extension. We hypothesized the combination of electrical stimulation with electrospun fiber topography would induce longer neurite extension from DRG neurons than the presence of electrical stimulation or aligned topography alone. Approach To test the hypothesis, neurite outgrowth was examined on laminin-coated poly-L-lactide (PLLA) films or electrospun fibers (2 μm in diameter) in the presence or absence of electrical stimulation. Immunostained neurons were semi-automatically traced using Neurolucida software and morphology was evaluated. Results Neurite extension increased 74% on the aligned fibers compared to film controls. Stimulation alone increased outgrowth by 32% on films or fibers relative to unstimulated film controls. The co-presentation of topographical (fibers) with biophysical (electrical stimulation) cues resulted in a synergistic 126% increase in outgrowth relative to unstimulated film controls. Field polarity had no influence on the directionality of neurite, indicating topographical cues are responsible to guide neurite extension. Significance Both cues (electrical stimulation and fiber geometry) are modular in nature and can be synergistically applied in conjunction with other common methods in regenerative medicine such as controlled release of growth factors to further influence axonal growth in vivo. The combined application of electrical and aligned fiber topographical guidance cues described herein, if translated in vivo, could provide a more supportive environment for directed and robust axonal regeneration following peripheral nerve injury. PMID:24891494

  19. Influence of Poly(L-Lactic Acid) Aligned Nanofibers on PC12 Differentiation.

    PubMed

    Yu, Yadong; Lü, Xiaoying; Ding, Fei

    2015-05-01

    The aim of this study was to unveil the mechanism by which aligned nanofibers influence neuronal differentiation. PC12 cells were seeded on three different poly(L-lactic acid) (PLLA) substrates (PLLA films (control), electrospun PLLA random nanofibers (RF) and electrospun PLLA aligned nanofibers (AF)). Subsequently, cellular experiments, cDNA microarrays and molecular biological approaches were employed to investigate the impacts of the different PLLA substrates on PC12 cell differentiation. Scanning electron microscope observation revealed that neurite outgrowth in the AF group was parallel to the direction of nanofiber alignment and that the filopodias at the neurite tips spread along the aligned nanofiber axis. Meanwhile, both neurite length and the expression of GAP43 (a neuronal differentiation marker gene) were higher in the AF group than those in the control and RF groups. These results suggested that the PLLA aligned nanofibers enhanced PC12 cell differentiation. cDNA microarray experiment revealed that 876 and 1937 genes had significantly changed expression in the RF and AF groups, respectively. Based on gene ontology analysis, 493 and 1193 differentially expressed genes involved in neuronal differentiation were found in the RF and AF groups, respectively. Pathway analysis showed that the PLLA aligned nanofibers mainly mediated their effects via integrin-mediated pathways. qRT-PCR and western blotting assays further confirmed that gene and protein expression levels in the integrin-mediated FAK-MEK-ERK pathway (e.g., Tln1, Mapk6, phosphorylated-ERK1/2) were enhanced by the PLLA aligned nanofibers. Both PC12 cell differentiation and the expressions of genes and proteins in the integrin-mediated FAK-MEK-ERK pathway were inhibited when integrins were blocked by the pentapeptide GRGDS. In addition, the Pafah1b-1 gene was found to be involved in PLLA aligned nanofibers' promotion of PC12 cell differentiation. Taken together, the results suggested that PLLA

  20. Multimodal Ultrasound-Photoacoustic Imaging of Tissue Engineering Scaffolds and Blood Oxygen Saturation In and Around the Scaffolds

    PubMed Central

    Talukdar, Yahfi; Avti, Pramod; Sun, John

    2014-01-01

    Preclinical, noninvasive imaging of tissue engineering polymeric scaffold structure and/or the physiological processes such as blood oxygenation remains a challenge. In vitro or ex vivo, the widely used scaffold characterization modalities such as porosimetry, electron or optical microscopy, and X-ray microcomputed tomography have limitations or disadvantages—some are invasive or destructive, others have limited tissue penetration (few hundred micrometers) and/or show poor contrast under physiological conditions. Postmortem histological analysis, the most robust technique for the evaluation of neovascularization is obviously not appropriate for acquiring physiological or longitudinal data. In this study, we have explored the potential of ultrasound (US)-coregistered photoacoustic (PA) imaging as a noninvasive multimodal imaging modality to overcome some of the above challenges and/or provide complementary information. US-PA imaging was employed to characterize poly(lactic-co-glycolic acid) (PLGA) polymer scaffolds or single-walled carbon nanotube (SWCNT)-incorporated PLGA (SWCNT-PLGA) polymer scaffolds as well as blood oxygen saturation within and around the scaffolds. Ex vivo, PLGA and SWCNT-PLGA scaffolds were placed at 0.5, 2, and 6 mm depths in chicken breast tissues. PLGA scaffolds could be localized with US imaging, but generate no PA signal (excitation wavelengths 680 and 780 nm). SWCNT-PLGA scaffolds generated strong PA signals at both wavelengths due to the presence of the SWCNTs and could be localized with both US and PA imaging depths between 0.5–6 mm (lateral resolution=90 μm, axial resolution=40 μm). In vivo, PLGA and SWCNT-PLGA scaffolds were implanted in subcutaneous pockets at 2 mm depth in rats, and imaged at 7 and 14 days postsurgery. The anatomical position of both the scaffolds could be determined from the US images. Only SWCNT-PLGA scaffolds could be easily detected in the US-PA images. SWCNT-PLGA scaffolds had significant

  1. Multimodal ultrasound-photoacoustic imaging of tissue engineering scaffolds and blood oxygen saturation in and around the scaffolds.

    PubMed

    Talukdar, Yahfi; Avti, Pramod; Sun, John; Sitharaman, Balaji

    2014-05-01

    Preclinical, noninvasive imaging of tissue engineering polymeric scaffold structure and/or the physiological processes such as blood oxygenation remains a challenge. In vitro or ex vivo, the widely used scaffold characterization modalities such as porosimetry, electron or optical microscopy, and X-ray microcomputed tomography have limitations or disadvantages-some are invasive or destructive, others have limited tissue penetration (few hundred micrometers) and/or show poor contrast under physiological conditions. Postmortem histological analysis, the most robust technique for the evaluation of neovascularization is obviously not appropriate for acquiring physiological or longitudinal data. In this study, we have explored the potential of ultrasound (US)-coregistered photoacoustic (PA) imaging as a noninvasive multimodal imaging modality to overcome some of the above challenges and/or provide complementary information. US-PA imaging was employed to characterize poly(lactic-co-glycolic acid) (PLGA) polymer scaffolds or single-walled carbon nanotube (SWCNT)-incorporated PLGA (SWCNT-PLGA) polymer scaffolds as well as blood oxygen saturation within and around the scaffolds. Ex vivo, PLGA and SWCNT-PLGA scaffolds were placed at 0.5, 2, and 6 mm depths in chicken breast tissues. PLGA scaffolds could be localized with US imaging, but generate no PA signal (excitation wavelengths 680 and 780 nm). SWCNT-PLGA scaffolds generated strong PA signals at both wavelengths due to the presence of the SWCNTs and could be localized with both US and PA imaging depths between 0.5-6 mm (lateral resolution = 90 μm, axial resolution = 40 μm). In vivo, PLGA and SWCNT-PLGA scaffolds were implanted in subcutaneous pockets at 2 mm depth in rats, and imaged at 7 and 14 days postsurgery. The anatomical position of both the scaffolds could be determined from the US images. Only SWCNT-PLGA scaffolds could be easily detected in the US-PA images. SWCNT-PLGA scaffolds had significant four times

  2. Holmium-loaded PLLA nanoparticles for intratumoral radiotherapy via the TMT technique: preparation, characterization, and stability evaluation after neutron irradiation.

    PubMed

    Hamoudeh, Misara; Fessi, Hatem; Salim, Hani; Barbos, Dumitru

    2008-08-01

    This article describes the preparation of biocompatible radioactive holmium-loaded particles with appropriate nanoscale size for radionuclide intratumoral administration by the targeted multitherapy (TMT) technique. For this objective, holmium acetylacetonate has been encapsulated in poly-L-lactide (PLLA)-based nanoparticles (NP) by oil-in-water emulsion-solvent evaporation method. NP sizes ranged between 100 and 1,100 m being suitable for the TMT administration method. Elemental holmium loading was found to be around 18% wt/wt and the holmium acetylacetonate trihydrate (HoAcAc) encapsulation efficacy was about 90%. Different experiments demonstrated an amorphous state of HoAcAc after incorporation in NPs. The NPs were irradiated in a nuclear reactor with a neutron flux of 1.1 x 10(13) n/cm(2)/s for 1 h, which yielded a specific activity of about 27.4 GBq/g of NPs being sufficient for our desired application. Microscopic analysis of irradiated NPs showed some alteration after neutron irradiation as some NPs looked partially coagglomerated and a few pores appeared at their surface because of the locally released heat in the irradiation vials. Furthermore, differential scanning calorimetry (DSC) results indicated a clear decrease in PLLA melting point and melting enthalpy reflecting a decrease in polymer crystallinity. This was accompanied by a clear decrease in polymer molecular weights, which can be ascribed to a radiation-induced chain scission mechanism. However, interestingly, other experiments confirmed the chemical identity retention of both HoAcAc and PLLA in irradiated NPs despite this detected decrease in the polymer crystallinity and molecular weight. Although neutron irradiation has induced some NPs damage, these NPs kept out their overall chemical composition, and their size distribution remained suitable for the TMT administration technique. Coupled with the TMT technique, these NPs may represent a novel potential radiopharmaceutical agent for

  3. Scaffolds in Tendon Tissue Engineering

    PubMed Central

    Longo, Umile Giuseppe; Lamberti, Alfredo; Petrillo, Stefano; Maffulli, Nicola; Denaro, Vincenzo

    2012-01-01

    Tissue engineering techniques using novel scaffold materials offer potential alternatives for managing tendon disorders. Tissue engineering strategies to improve tendon repair healing include the use of scaffolds, growth factors, cell seeding, or a combination of these approaches. Scaffolds have been the most common strategy investigated to date. Available scaffolds for tendon repair include both biological scaffolds, obtained from mammalian tissues, and synthetic scaffolds, manufactured from chemical compounds. Preliminary studies support the idea that scaffolds can provide an alternative for tendon augmentation with an enormous therapeutic potential. However, available data are lacking to allow definitive conclusion on the use of scaffolds for tendon augmentation. We review the current basic science and clinical understanding in the field of scaffolds and tissue engineering for tendon repair. PMID:22190961

  4. The role of scaffold architecture and composition on the bone formation by adipose-derived stem cells.

    PubMed

    Declercq, Heidi A; Desmet, Tim; Dubruel, Peter; Cornelissen, Maria J

    2014-01-01

    Scaffold architecture and composition are crucial parameters determining the initial cell spatial distribution and consequently bone tissue formation. Three-dimensional poly-ε-caprolactone (PCL) scaffolds with a 0/90° lay-down pattern were plotted and subjected to (1) an oxygen plasma (PCL O) or (2) a postargon plasma modification with gelatin and fibronectin (PCL Fn). These scaffolds with an open pore structure were compared with more compact scaffolds fabricated by conventional processing techniques: oxidized polylactic acid (LA O) and collagen (COL) scaffolds. Human adipose tissue-derived stem cell/scaffold interactions were studied. The study revealed that the biomimetic surface modification of plotted scaffolds did not increase the seeding efficiency. The proliferation and colonization was superior for PCL Fn in comparison with PCL O. The plotted PCL Fn was completely colonized throughout the scaffold, whereas conventional scaffolds only at the edge. Protein-based scaffolds (PCL Fn and COL) enhanced the differentiation, although plotted scaffolds showed a delay in their differentiation compared with compact scaffolds. In conclusion, protein modification of plotted PCL scaffolds enhances uniform tissue formation, but shows a delayed differentiation in comparison with compact scaffolds. The present study demonstrates that biomimetic PCL scaffolds could serve as a guiding template to obtain a uniform bone tissue formation in vivo.

  5. Polylactide stereocomplexation leads to higher hydrolytic stability but more acidic hydrolysis product pattern.

    PubMed

    Andersson, Sofia Regnell; Hakkarainen, Minna; Inkinen, Saara; Södergård, Anders; Albertsson, Ann-Christine

    2010-04-12

    Poly-l-lactide/poly-d-lactide (PLLA/PDLA) stereocomplex had much higher hydrolytic stability compared to plain PLLA, but at the same time shorter and more acidic degradation products were formed. Both materials were subjected to hydrolytic degradation in water and in phosphate buffer at 37 and 60 degrees C, and the degradation processes were monitored by following mass loss, water uptake, thermal properties, surface changes, and pH of the aging medium. The degradation product patterns were determined by electrospray ionization-mass spectrometry (ESI-MS). The high crystallinity and strong secondary interactions in the stereocomplex prevented water uptake and resulted in lower mass loss and degradation rate. However, somewhat surprisingly, the pH of the aging medium decreased much faster in the case of PLLA/PDLA stereocomplex. In accordance, the ESI-MS results showed that hydrolysis of PLLA/PDLA resulted in shorter and more acidic degradation products. This could be explained by the increased intermolecular crystallization due to stereocomplexation, which results in an increased number of tie chains. Because mainly these short tie chains are susceptible to hydrolysis this leads to formation of shorter oligomers compared to hydrolysis of regular PLLA.

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

    SciTech Connect

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

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Multiscale fabrication of biomimetic scaffolds for tympanic membrane tissue engineering.

    PubMed

    Mota, Carlos; Danti, Serena; D'Alessandro, Delfo; Trombi, Luisa; Ricci, Claudio; Puppi, Dario; Dinucci, Dinuccio; Milazzo, Mario; Stefanini, Cesare; Chiellini, Federica; Moroni, Lorenzo; Berrettini, Stefano

    2015-06-01

    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. PMID:25947357

  9. The in vitro and in vivo anti-tumor effects of MTX-Fe3O 4-PLLA-PEG-PLLA microspheres prepared by suspension-enhanced dispersion by supercritical CO2.

    PubMed

    Chen, AiZheng; Dang, TingTing; Wang, ShiBin; Tang, Na; Liu, YuanGang; Wu, WenGuo

    2014-07-01

    The in vitro and in vivo anti-tumor efficacy of methotrexate-loaded Fe3O4-poly-L-lactide-poly(ethylene glycol)-poly-L-lactide magnetic composite microspheres (MTX-Fe3O4-PLLA-PEG-PLLA MCMs, MMCMs), which were produced by co-precipitation (C) and microencapsulation (M) in a supercritical process, was evaluated at various levels: cellular, molecular, and integrated. The results at the cellular level indicate that MMCMs (M) show a better anti-proliferation activity than raw MTX and could induce morphological changes of cells undergoing apoptosis. At the molecular level, MMCMs (M) lead to a significantly higher relative mRNA expression of bax/bcl-2 and caspase-3 than MMCMs (C) at 10 μg mL(-1) (P<0.01); and the pro-caspase-3 protein expression measured by Western blot analysis also demonstrates that MMCMs (M) can effectively activate pro-caspase-3. At the integrated level, mice bearing a sarcoma-180 tumor are used; in vivo anti-tumor activity tests reveal that MMCMs (M) with magnetic induction display a much higher tumor suppression rate and lower toxicity than raw MTX. Pharmacokinetic studies show that MMCMs (M) with magnetic induction significantly increase the accumulation of MTX in the tumor tissue compared with the other treatments. These results suggest that the MMCMs (M) prepared by the SpEDS process have great potential to play a positive role in the magnetic targeted therapy field. PMID:24935781

  10. Development of polycaprolactone/chitosan blend porous scaffolds.

    PubMed

    Wan, Ying; Xiao, Bo; Dalai, Siqin; Cao, Xiaoying; Wu, Quan

    2009-03-01

    Polycaprolactone (PCL) and chitosan were blended to fabricate porous scaffolds for tissue-engineering applications by employing a concentrated acetic acid solution as solvent and salt particles as porogen. These scaffolds showed well-controlled and interconnected porous structures. The pore size and porosity of the scaffolds could be effectively modulated by selecting appropriate amounts and sizes of porogen. The results obtained from compressive mechanical measurements indicated that PCL/chitosan could basically retain their strength in their dry state compared to individual components. In a hydrated state, their compressive stress and modulus could be still well maintained even though the weight ratio of chitosan reached around 50 wt%. PMID:18987952

  11. Strength retention behavior of oriented PLLA, 96L/4D PLA, and 80L/20D,L PLA

    PubMed Central

    Huttunen, Mikko; Kellomäki, Minna

    2013-01-01

    The strength retention characteristics of oriented semicrystalline polylactides were monitored during hydrolytic degradation in vitro. The effects of the polymer type, the material’s initial inherent viscosity (iv), the sample diameter and the residual monomer content on strength retention were analyzed. The analyzed polylactides had similar, but not identical, strength retention characteristics. It was concluded that a higher degree of initial crystallinity was a major variable determining the earlier and more profound strength loss of PLLA than 96L/4D PLA and 80L/20 D,L PLA. Samples with a higher initial iv were found to have a longer strength retention time than lower iv samples. Size-dependency was observed, as the strength retention time was shorter for the smaller diameter samples. This size-dependency was caused by faster iv decay. The amount of residual monomer content had a remarkable impact on strength retention. Neither the sample diameter, initial iv or residual monomer content were found to have an effect on the iv range in which there was a rapid decline in strength properties. Therefore, it was concluded that the inherent viscosity and/or molecular weight of oriented PLLA, 96L/4D PLA and 80L/20 D,L PLA is a major variable determining the strength retention of these materials. PMID:24025528

  12. Cell-seeding and in vitro biocompatibility evaluation of polymeric matrices of PEO/PBT copolymers and PLLA.

    PubMed

    Beumer, G J; van Blitterswijk, C A; Bakker, D; Ponec, M

    1993-07-01

    A bilayered matrix has been evaluated in vitro as a carrier for autografts of cultured epidermal keratinocytes and dermal fibroblasts, to be used as a skin substitute in deep dermal skin defects. A poly-L-lactide (PLLA) and an elastomeric and biodegradable poly(ethyleneoxide)-poly(butyleneterephthalate)(PEO-PBT++ +)copolymer, called Polyactive, were chosen as the constituents of the matrix. The substrate properties of the bilayers for human and rat epidermal keratinocytes and dermal fibroblasts were assessed. Keratinocytes attached and expanded into confluent sheets on both the routine cell culture plastic (TCPS) and the experimental substrates. Morphology of the cells cultured on the biomaterials was found to be comparable with the morphology of those grown on TCPS. In contrast to dense films, porous PEO:PBT copolymer and PLLA appeared poor substrates for fibroblasts. Long-term (in vivo) degradation of the biomaterials was mimicked in vitro to screen the biomaterials for any release of toxic substances. Culturing keratinocytes and fibroblasts in media based on the artificially aged biomaterials did not result in any negative effects on proliferative activity or morphological appearance of the cells.

  13. Preferential Stereocomplex Crystallization in Enantiomeric Blends of Cellulose Acetate-g-Poly(lactic acid)s with Comblike Topology.

    PubMed

    Bao, Jianna; Han, Lili; Shan, Guorong; Bao, Yongzhong; Pan, Pengju

    2015-10-01

    Although stereocomplex (sc) crystallization is highly effective for improving the thermal resistance of poly(lactic acid) (PLA), it is much less predominant than homocrystallization in high-molecular-weight (HMW) poly(l-lactic acid)/ poly(d-lactic acid) (PLLA/PDLA) racemic blends. In this contribution, the sc crystallization of HMW PLLA/PDLA racemic blends was facilitated by using comblike PLAs with cellulose acetate as the backbone. Competing crystallization kinetics, polymorphic crystalline structure, and structural transition of comblike PLLA/PDLA blends with a wide range of MWs were investigated and compared with the corresponding linear/comblike and linear blends. The HMW comblike blend is preferentially crystallized in sc polymorphs and exhibits a faster crystallization rate than does the corresponding linear blend. The sc crystallites are predominantly formed in nonisothermal cold crystallization and isothermal crystallization at temperatures above 120 °C for the comblike blends. Except for the facilitated sc formation in primary crystallization, synchrotron radiation WAXD analysis indicates that the presence of a comblike component also facilitates the transition or recrystallization from homocrystallite (hc) to sc crystallite upon heating. Preferential sc formation of comblike blends is probably attributable to the favorable interdigitation between enantiomeric branches and the increased mobility of polymer segments. After crystallization under the same temperature, the comblike blends, which mainly contain sc crystallites, show smaller long periods and thinner crystalline lamellae than do the corresponding PLLA with homocrystalline structures.

  14. Biomimetic Scaffolds for Osteogenesis

    PubMed Central

    Yuan, Nance; Rezzadeh, Kameron S.; Lee, Justine C.

    2015-01-01

    Skeletal regenerative medicine emerged as a field of investigation to address large osseous deficiencies secondary to congenital, traumatic, and post-oncologic conditions. Although autologous bone grafts have been the gold standard for reconstruction of skeletal defects, donor site morbidity remains a significant limitation. To address these limitations, contemporary bone tissue engineering research aims to target delivery of osteogenic cells and growth factors in a defined three dimensional space using scaffolding material. Using bone as a template, biomimetic strategies in scaffold engineering unite organic and inorganic components in an optimal configuration to both support osteoinduction as well as osteoconduction. This article reviews the various structural and functional considerations behind the development of effective biomimetic scaffolds for osteogenesis and highlights strategies for enhancing osteogenesis. PMID:26413557

  15. Potency of Fish Collagen as a Scaffold for Regenerative Medicine

    PubMed Central

    Yamamoto, Kohei; Yanagiguchi, Kajiro

    2014-01-01

    Cells, growth factors, and scaffold are the crucial factors for tissue engineering. Recently, scaffolds consisting of natural polymers, such as collagen and gelatin, bioabsorbable synthetic polymers, such as polylactic acid and polyglycolic acid, and inorganic materials, such as hydroxyapatite, as well as composite materials have been rapidly developed. In particular, collagen is the most promising material for tissue engineering due to its biocompatibility and biodegradability. Collagen contains specific cell adhesion domains, including the arginine-glycine-aspartic acid (RGD) motif. After the integrin receptor on the cell surface binds to the RGD motif on the collagen molecule, cell adhesion is actively induced. This interaction contributes to the promotion of cell growth and differentiation and the regulation of various cell functions. However, it is difficult to use a pure collagen scaffold as a tissue engineering material due to its low mechanical strength. In order to make up for this disadvantage, collagen scaffolds are often modified using a cross-linker, such as gamma irradiation and carbodiimide. Taking into account the possibility of zoonosis, a variety of recent reports have been documented using fish collagen scaffolds. We herein review the potency of fish collagen scaffolds as well as associated problems to be addressed for use in regenerative medicine. PMID:24982861

  16. Nano/macro porous bioactive glass scaffold

    NASA Astrophysics Data System (ADS)

    Wang, Shaojie

    Bioactive glass (BG) and ceramics have been widely studied and developed as implants to replace hard tissues of the musculo-skeletal system, such as bones and teeth. Recently, instead of using bulk materials, which usually do not degrade rapidly enough and may remain in the human body for a long time, the idea of bioscaffold for tissue regeneration has generated much interest. An ideal bioscaffold is a porous material that would not only provide a three-dimensional structure for the regeneration of natural tissue, but also degrade gradually and, eventually be replaced by the natural tissue completely. Among various material choices the nano-macro dual porous BG appears as the most promising candidate for bioscaffold applications. Here macropores facilitate tissue growth while nanopores control degradation and enhance cell response. The surface area, which controls the degradation of scaffold can also be tuned by changing the nanopore size. However, fabrication of such 3D structure with desirable nano and macro pores has remained challenging. In this dissertation, sol-gel process combined with spinodal decomposition or polymer sponge replication method has been developed to fabricate the nano-macro porous BG scaffolds. Macropores up to 100microm are created by freezing polymer induced spinodal structure through sol-gel transition, while larger macropores (>200um) of predetermined size are obtained by the polymer sponge replication technique. The size of nanopores, which are inherent to the sol-gel method of glass fabrication, has been tailored using several approaches: Before gel point, small nanopores are generated using acid catalyst that leads to weakly-branched polymer-like network. On the other hand, larger nanopores are created with the base-catalyzed gel with highly-branched cluster-like structure. After the gel point, the nanostructure can be further modified by manipulating the sintering temperature and/or the ammonia concentration used in the solvent

  17. L_RNA_scaffolder: scaffolding genomes with transcripts

    PubMed Central

    2013-01-01

    Background Generation of large mate-pair libraries is necessary for de novo genome assembly but the procedure is complex and time-consuming. Furthermore, in some complex genomes, it is hard to increase the N50 length even with large mate-pair libraries, which leads to low transcript coverage. Thus, it is necessary to develop other simple scaffolding approaches, to at least solve the elongation of transcribed fragments. Results We describe L_RNA_scaffolder, a novel genome scaffolding method that uses long transcriptome reads to order, orient and combine genomic fragments into larger sequences. To demonstrate the accuracy of the method, the zebrafish genome was scaffolded. With expanded human transcriptome data, the N50 of human genome was doubled and L_RNA_scaffolder out-performed most scaffolding results by existing scaffolders which employ mate-pair libraries. In these two examples, the transcript coverage was almost complete, especially for long transcripts. We applied L_RNA_scaffolder to the highly polymorphic pearl oyster draft genome and the gene model length significantly increased. Conclusions The simplicity and high-throughput of RNA-seq data makes this approach suitable for genome scaffolding. L_RNA_scaffolder is available at http://www.fishbrowser.org/software/L_RNA_scaffolder. PMID:24010822

  18. Treatment of the aged hand with injectable poly-l-lactic acid.

    PubMed

    Rendon, Marta I; Cardona, Lina M; Pinzon-Plazas, Mariana

    2010-12-01

    We report the use of injectable poly-l-lactic acid (PLLA) for volume restoration in a 45-year-old white female who was concerned about the appearance of her hands. The patient expressed a desire for long-term restoration, and selected injectable PLLA because of its known 2-year duration of effect, although she was informed that injectable PLLA is not FDA-approved for use in the hands. After reconstitution with 8 ml of diluent plus lidocaine, 0.1-0.2-ml aliquots of injectable PLLA were injected into selected sites, up to 5 ml per hand. The patient underwent three identical treatments, followed by postinjection use of moisturizing cream and massage; improvement in appearance was noted by the patient between the second and third treatments. Correction was maintained for at least 18 months, with no adverse events. We have also briefly reviewed the literature on the use of injectable PLLA for volume restoration in the hand. PMID:21142738

  19. Superhydrophobic poly(L-lactic acid) surface as potential bacterial colonization substrate

    PubMed Central

    2011-01-01

    Hydrophobicity is a very important surface property and there is a growing interest in the production and characterization of superhydrophobic surfaces. Accordingly, it was recently shown how to obtain a superhydrophobic surface using a simple and cost-effective method on a polymer named poly(L-lactic acid) (PLLA). To evaluate the ability of such material as a substrate for bacterial colonization, this work assessed the capability of different bacteria to colonize a biomimetic rough superhydrophobic (SH) PLLA surface and also a smooth hydrophobic (H) one. The interaction between these surfaces and bacteria with different morphologies and cell walls was studied using one strain of Staphylococcus aureus and one of Pseudomonas aeruginosa. Results showed that both bacterial strains colonized the surfaces tested, although significantly higher numbers of S. aureus cells were found on SH surfaces comparing to H ones. Moreover, scanning electron microscopy images showed an extracellular matrix produced by P. aeruginosa on SH PLLA surfaces, indicating that this bacterium is able to form a biofilm on such substratum. Bacterial removal through lotus leaf effect was also tested, being more efficient on H coupons than on SH PLLA ones. Overall, the results showed that SH PLLA surfaces can be used as a substrate for bacterial colonization and, thus, have an exceptional potential for biotechnology applications. PMID:22018163

  20. The Interactions Between Aligned Poly(L-Lactic Acid) Nanofibers and SH-SY5Y Cells In Vitro.

    PubMed

    Yu, Yadong; Meng, Dianhuai; Man, Lili; Wang, Xin

    2016-06-01

    Aligned nanofibers have been regarded as promising nanomaterials in facilitating nerve regeneration. Investigating the interactions between aligned nanofibers and neuronal cells will be critically important for the design and application of aligned nanofibers in nerve tissue engineering. In this study, we explored the effects of electrospun Poly(L-Lactic Acid) (PLLA) aligned nanofibers on SH-SY5Y cells (a type of human neuroblastoma cell line) and specifically focused on the role of integrin in the PLLA aligned nanofiber-SH-SY5Y cell interaction. We found that PLLA aligned nanofibers could significantly guide the neurite outgrowth of SH-SY5Y cell, and promote the viability, proliferation, glucose and lactic acid metabolism of SH-SY5Y cell. This promotion effect could be alleviated when the functions of integrins on the SH-SY5Y cell membrane were hampered by pentapeptide GRGDS. Moreover, we found that PLLA aligned nanofibers could enhance the expression of phosphorylated-ERK1/2 (p-ERK1/2) in the SH-SY5Y cells and blocking the integrins would decrease p-ERK1/2 expression. These results suggested that PLLA aligned nanofibers might affect many cellular behaviors of SH-SY5Y cells via integrin mediated ERK pathway. Our findings provided more insights for understanding the interaction between aligned nanofibers and neuronal cells. PMID:27427727

  1. The Interactions Between Aligned Poly(L-Lactic Acid) Nanofibers and SH-SY5Y Cells In Vitro.

    PubMed

    Yu, Yadong; Meng, Dianhuai; Man, Lili; Wang, Xin

    2016-06-01

    Aligned nanofibers have been regarded as promising nanomaterials in facilitating nerve regeneration. Investigating the interactions between aligned nanofibers and neuronal cells will be critically important for the design and application of aligned nanofibers in nerve tissue engineering. In this study, we explored the effects of electrospun Poly(L-Lactic Acid) (PLLA) aligned nanofibers on SH-SY5Y cells (a type of human neuroblastoma cell line) and specifically focused on the role of integrin in the PLLA aligned nanofiber-SH-SY5Y cell interaction. We found that PLLA aligned nanofibers could significantly guide the neurite outgrowth of SH-SY5Y cell, and promote the viability, proliferation, glucose and lactic acid metabolism of SH-SY5Y cell. This promotion effect could be alleviated when the functions of integrins on the SH-SY5Y cell membrane were hampered by pentapeptide GRGDS. Moreover, we found that PLLA aligned nanofibers could enhance the expression of phosphorylated-ERK1/2 (p-ERK1/2) in the SH-SY5Y cells and blocking the integrins would decrease p-ERK1/2 expression. These results suggested that PLLA aligned nanofibers might affect many cellular behaviors of SH-SY5Y cells via integrin mediated ERK pathway. Our findings provided more insights for understanding the interaction between aligned nanofibers and neuronal cells.

  2. Mathematical Abstraction through Scaffolding

    ERIC Educational Resources Information Center

    Ozmantar, Mehmet Fatih; Roper, Tom

    2004-01-01

    This paper examines the role of scaffolding in the process of abstraction. An activity-theoretic approach to abstraction in context is taken. This examination is carried out with reference to verbal protocols of two 17 year-old students working together on a task connected to sketching the graph of |f|x|)|. Examination of the data suggests that…

  3. Comparative Study of Degradation Behavior of Bioresorbable Cardiovascular Scaffolds.

    PubMed

    Luo, Qiyi; Huang, Chubo; Wang, Shuai; Meng, Juan; Li, Zhonghua; Chang, Zhaohua; Zhu, Yufang; Hua, Zezhao

    2015-03-01

    This comparative study investigated the biodegradation behavior and mechanism of bioresorbable cardiovascular scaffolds using bench testing under physiological conditions and in vivo experiment. The results show that the molecular weight of the scaffold decreased with respect to time after implantation in both in vivo and in vitro tests. It was found that the molecular weights of the implanted scaffolds in the in vivo and in vitro models decreased to 61.8 and 68.5% respectively 6 months after implantation, but the thermodynamic properties of the scaffold material were not significantly affected by the 6-month degradation. Moreover, the study indicated that in spite of the 6-month degradation, the scaffold maintained sufficient radial strength and mechanical integrity. Furthermore, it was noted that the changes in the trends of the mechanical properties and degradation behavior of the scaffolds in the in vitro model were coherent with the results of the in vivo study, which means the in vitro study of the degradation behavior of polylactic acid (PLA) scaffold could offer clinical relevant data and physical insights to predict the in vivo performance.

  4. Membrane-reinforced three-dimensional electrospun silk fibroin scaffolds for bone tissue engineering.

    PubMed

    Yang, Sung Yeun; Hwang, Tae Heon; Che, Lihua; Oh, Jin Soo; Ha, Yoon; Ryu, WonHyoung

    2015-06-01

    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. PMID:26106926

  5. Considerations for the use of injectable poly-L-lactic acid in people of color.

    PubMed

    Hamilton, Tiffani K; Burgess, Cheryl M

    2010-05-01

    With demand for minimally invasive cosmetic procedures rising in patients of color, it is becoming increasingly important for clinical dermatologists to be aware of specific needs of these patients. This article therefore reviews considerations for using cosmetic procedures on skin of color, and reports the authors' clinical experience with the use of injectable poly-L-lactic acid (PLLA, Sculptra, Dermik Laboratories, a business of sanofi-aventis U.S. LLC) in this patient population. The authors' experience indicates that patients with skin of color may require an increased interval between treatments; however, with proper attention to patient selection and administration technique, injectable PLLA can be used effectively in this patient group. Controlled clinical studies that include more patients of color are needed to fully assess the benefits and risks of cosmetic products, such as injectable PLLA, in these populations.

  6. Micro/nanofabrication of poly(L-lactic acid) using focused ion beam direct etching

    NASA Astrophysics Data System (ADS)

    Oyama, Tomoko Gowa; Hinata, Toru; Nagasawa, Naotsugu; Oshima, Akihiro; Washio, Masakazu; Tagawa, Seiichi; Taguchi, Mitsumasa

    2013-10-01

    Micro/nanofabrication of biocompatible and biodegradable poly(L-lactic acid) (PLLA) using focused Ga ion beam direct etching was evaluated for future bio-device applications. The fabrication performance was determined with different ion fluences and fluxes (beam currents), and it was found that the etching speed and fabrication accuracy were affected by irradiation-induced heat. Focused ion beam (FIB)-irradiated surfaces were analyzed using micro-area X-ray photoelectron spectroscopy. Owing to reactions such as the physical sputtering of atoms and radiation-induced decomposition, PLLA was gradually carbonized with increasing C=C bonds. Controlled micro/nanostructures of PLLA were fabricated with C=C bond-rich surfaces expected to have good cell attachment properties.

  7. Poly(propylene fumarate) and poly(DL-lactic-co-glycolic acid) as scaffold materials for solid and foam-coated composite tissue-engineered constructs for cranial reconstruction.

    PubMed

    Dean, David; Topham, Neal S; Meneghetti, S Cristina; Wolfe, Michael S; Jepsen, Karl; He, Shulin; Chen, Jeffrey E-K; Fisher, John P; Cooke, Malcolm; Rimnac, Clare; Mikos, Antonios G

    2003-06-01

    This pilot study investigates the osseointegration of four types of critical-size (1.5-cm diameter) rabbit cranial defect (n = 35) bone graft scaffolds. The first is a solid poly(propylene fumarate)/beta-tricalcium phosphate(PPF/beta-TCP) disk; the three remaining constructs contain a PPF/beta-TCP core coated with a 1-mm resorptive porous foam layer of PPF or PLGA [poly(DL-lactic-co-glycolic acid)], and bone marrow. Animals were killed at 6, 12, and 20 weeks. There was no evidence of a foreign body inflammatory response at any time during the study. Histomorphometric analyses of new bone formation sorted lineal and areal measures of new bone into three cranial layers (i.e., external, middle, and internal). Statistical analyses revealed significantly more bone in the PLGA foam-coated constructs than in the PPF foam-coated constructs (p < 0.03). No implant fixation was used; there is no strength at time 0. Twenty percent of all explants were tested for incorporation strength with a one-point "push-in" test, and failure ranged from 8.3 to 34.7 lb. The results of this study support the use of PPF as a biocompatible material that provides both a structural and osteogenic substrate for the repair of cranial defects.

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

    NASA Astrophysics Data System (ADS)

    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 < 0.05) at 1 and 3 days. There was no significant difference between the scaffolds for ALP activity normalized by DNA content at both term (p > 0.1). Therefore MWCNT-coating on PLLA improved the surface wettability and initial cell attachment at early stage.

  9. PD98059-Impregnated Functional PLGA Scaffold for Direct Tissue Engineering Promotes Chondrogenesis and Prevents Hypertrophy from Mesenchymal Stem Cells

    PubMed Central

    Lee, Jong Min; Kim, Jong Dae; Oh, Eun Jo; Oh, Se Heang; Lee, Jin Ho

    2014-01-01

    In cartilage tissue engineering from mesenchymal stem cells, it is important to suppress hypertrophy to produce a neocartilage with stable phenotypes of hyaline articular cartilage (AC). The aim of this study was to develop and test the usefulness of functional chondrogenic scaffolds that serve the purpose of hypertrophy suppression. PD98059-impregnated poly(lactic-co-glycolic acid) (PLGA) scaffold is fabricated and compared with transforming growth factor (TGF)-β2-immobilized scaffold. The PD98059 is continuously released from the scaffolds over 140 days in contrast to the rapid release in TGF-β2-immobilized scaffold. The in vitro culture results show that the PD98059-impregated scaffold is more effective in suppressing hypertrophy than the TGF-β2-immobilized scaffold while both scaffolds enhance chondrogenesis from human mesenchymal stem cells. After 10 weeks of in vivo implantation in rabbits, the osteochondral defects is successfully repaired in both PD98059-impregnated and TGF-β2-immobilized scaffold seeded with rabbit mesenchymal stem cells when evaluated grossly and microscopically. However, type X collagen is not observed from regenerated cartilage in PD98059-impregnated scaffold, whereas it is detected around chondrocytes in the TGF-β2-impregnated scaffolds. In addition, the PD98059-impregnated scaffold has better reconstitution of the subchondral plate. These results suggest that the use of the PD98059-impregnated scaffold leads to AC regeneration of better quality and prevents hypertrophy when implanted in the osteochondral defects. PMID:24188591

  10. Development of channeled nanofibrous scaffolds for oriented tissue engineering

    PubMed Central

    Sun, Chenghui; Jin, Xiaobing; Holzwarth, Jeremy M.; Liu, Xiaohua; Hu, Jiang; Gupte, Melanie J.; Zhao, Yaoming; Ma, Peter X

    2013-01-01

    A tissue-engineering scaffold resembling the characteristic structure of the natural extracellular matrix can often facilitate tissue regeneration. Nerve and tendon are oriented micro-scale sheathed tissue bundles. In this study, a method combining injection molding and thermally induced phase separation techniques was developed to create single- and multiple-channeled nanofibrous (NF) poly(L-lactic acid) scaffolds. The overall shape, the number and arrangement of channels, and the channel wall matrix architecture of the scaffolds were tailored by altering the configuration of the mold assembly and the phase separation conditions. The porosity and mechanical properties of the scaffolds were tailored by varying the concentration of the polymer solution used. The porous NF channel wall matrix provided a beneficial luminal microenvironment that increased protein adsorption and promoted the attachment of PC12 rat neuronal cells and rabbit patellar tendon fibroblast cells, showing potential for neural and tendon tissue regeneration. PMID:22508530

  11. Encapsulated boron as an osteoinductive agent for bone scaffolds.

    PubMed

    Gümüşderelioğlu, Menemşe; Tunçay, Ekin Ö; Kaynak, Gökçe; Demirtaş, Tolga T; Aydın, Seda Tığlı; Hakkı, Sema S

    2015-01-01

    The aim of this study was to develop boron (B)-releasing polymeric scaffold to promote regeneration of bone tissue. Boric acid-doped chitosan nanoparticles with a diameter of approx. 175 nm were produced by tripolyphosphate (TPP)-initiated ionic gelation process. The nanoparticles strongly attached via electrostatic interactions into chitosan scaffolds produced by freeze-drying with approx. 100 μm pore diameter. According to the ICP-OES results, following first 5h initial burst release, fast release of B from scaffolds was observed for 24h incubation period in conditioned medium. Then, slow release of B was performed over 120 h. The results of the cell culture studies proved that the encapsulated boron within the scaffolds can be used as an osteoinductive agent by showing its positive effects on the proliferation and differentiation of MC3T3-E1 preosteoblastic cells.

  12. 3-Fluoroazetidinecarboxylic Acids and trans,trans-3,4-Difluoroproline as Peptide Scaffolds: Inhibition of Pancreatic Cancer Cell Growth by a Fluoroazetidine Iminosugar.

    PubMed

    Liu, Zilei; Jenkinson, Sarah F; Vermaas, Tom; Adachi, Isao; Wormald, Mark R; Hata, Yukako; Kurashima, Yukiko; Kaji, Akira; Yu, Chu-Yi; Kato, Atsushi; Fleet, George W J

    2015-05-01

    Reverse aldol opening renders amides of 3-hydroxyazetidinecarboxylic acids (3-OH-Aze) unstable above pH 8. Aze, found in sugar beet, is mis-incorporated for proline in peptides in humans and is associated with multiple sclerosis and teratogenesis. Aze-containing peptides may be oxygenated by prolyl hydroxylases resulting in potential damage of the protein by a reverse aldol of the hydroxyazetidine; this, rather than changes in conformation, may account for the deleterious effects of Aze. This paper describes the synthesis of 3-fluoro-Aze amino acids as hydroxy-Aze analogues which are not susceptible to aldol cleavage. 4-(Azidomethyl)-3-fluoro-Aze and 3,4-difluoroproline are new peptide building blocks. trans,trans-2,4-Dihydroxy-3-fluoroazetidine, an iminosugar, inhibits the growth of pancreatic cancer cells to a similar degree as gemcitabine.

  13. Oxidative Stress Induced by Pt(IV) Pro-drugs Based on the Cisplatin Scaffold and Indole Carboxylic Acids in Axial Position

    PubMed Central

    Tolan, Dina; Gandin, Valentina; Morrison, Liam; El-Nahas, Ahmed; Marzano, Cristina; Montagner, Diego; Erxleben, Andrea

    2016-01-01

    The use of Pt(IV) complexes as pro-drugs that are activated by intracellular reduction is a widely investigated approach to overcome the limitations of Pt(II) anticancer agents. A series of ten mono- and bis-carboxylated Pt(IV) complexes with axial indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) ligands were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, 1H and 195Pt NMR spectroscopy. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. All the complexes are able to overcome cisplatin-resistance and the most potent complex, cis,cis,trans-[Pt(NH3)2Cl2(IPA)(OH)] was on average three times more active than cisplatin. Mechanistic studies revealed that the trend in cytotoxicity of the Pt(IV) complexes is primarily consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which in turn results in the loss of mitochondrial membrane potential and apoptosis induction. The role of the indole acid ligand as a redox modulator is discussed. PMID:27404565

  14. Oxidative Stress Induced by Pt(IV) Pro-drugs Based on the Cisplatin Scaffold and Indole Carboxylic Acids in Axial Position.

    PubMed

    Tolan, Dina; Gandin, Valentina; Morrison, Liam; El-Nahas, Ahmed; Marzano, Cristina; Montagner, Diego; Erxleben, Andrea

    2016-01-01

    The use of Pt(IV) complexes as pro-drugs that are activated by intracellular reduction is a widely investigated approach to overcome the limitations of Pt(II) anticancer agents. A series of ten mono- and bis-carboxylated Pt(IV) complexes with axial indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) ligands were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, (1)H and (195)Pt NMR spectroscopy. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. All the complexes are able to overcome cisplatin-resistance and the most potent complex, cis,cis,trans-[Pt(NH3)2Cl2(IPA)(OH)] was on average three times more active than cisplatin. Mechanistic studies revealed that the trend in cytotoxicity of the Pt(IV) complexes is primarily consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which in turn results in the loss of mitochondrial membrane potential and apoptosis induction. The role of the indole acid ligand as a redox modulator is discussed. PMID:27404565

  15. Oxidative Stress Induced by Pt(IV) Pro-drugs Based on the Cisplatin Scaffold and Indole Carboxylic Acids in Axial Position

    NASA Astrophysics Data System (ADS)

    Tolan, Dina; Gandin, Valentina; Morrison, Liam; El-Nahas, Ahmed; Marzano, Cristina; Montagner, Diego; Erxleben, Andrea

    2016-07-01

    The use of Pt(IV) complexes as pro-drugs that are activated by intracellular reduction is a widely investigated approach to overcome the limitations of Pt(II) anticancer agents. A series of ten mono- and bis-carboxylated Pt(IV) complexes with axial indole-3-acetic acid (IAA) and indole-3-propionic acid (IPA) ligands were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, 1H and 195Pt NMR spectroscopy. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. All the complexes are able to overcome cisplatin-resistance and the most potent complex, cis,cis,trans-[Pt(NH3)2Cl2(IPA)(OH)] was on average three times more active than cisplatin. Mechanistic studies revealed that the trend in cytotoxicity of the Pt(IV) complexes is primarily consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which in turn results in the loss of mitochondrial membrane potential and apoptosis induction. The role of the indole acid ligand as a redox modulator is discussed.

  16. Biodegradable HA-PLA 3-D porous scaffolds: effect of nano-sized filler content on scaffold properties.

    PubMed

    Kothapalli, Chandrasekhar R; Shaw, Montgomery T; Wei, Mei

    2005-11-01

    Scaffolds comprising poly(lactic acid) and nano-hydroxyapatite (HA) were prepared using the solvent-casting/salt-leaching technique. NaCl was used as the leaching agent. Nano-sized HA was synthesized by a hydrothermal method at 170 degrees C and autogenous pressure. High-resolution TEM imaging revealed that the HA particles were ellipsoidal-shaped with needle-like morphologies. The particles had an average size of approximately 25 nm in width and 150 nm in length with aspect ratios ranging from 6 to 8. As the HA content increased in the scaffold from 0 to 50 wt%, the compression modulus of the scaffolds increased from 4.72+/-1.2 to 9.87+/-1.8 MPa, while the yield strength from 0.29+/-0.03 to 0.44+/-0.01 MPa. Such polymeric scaffolds should be suitable materials for non-load sharing tissue-engineering applications. PMID:16701846

  17. Scaffolding Student Participation in Mathematical Practices

    ERIC Educational Resources Information Center

    Moschkovich, Judit N.

    2015-01-01

    The concept of scaffolding can be used to describe various types of adult guidance, in multiple settings, across different time scales. This article clarifies what we mean by scaffolding, considering several questions specifically for scaffolding in mathematics: What theoretical assumptions are framing scaffolding? What is being scaffolded? At…

  18. 49 CFR 214.109 - Scaffolding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... requirements: (1) Each scaffold and scaffold component, except suspension ropes and guardrail systems, but... least four times the maximum intended load applied or transmitted to that scaffold or scaffold component... guardrail system and the walking/working level. (b) Scaffolds shall not be altered or moved while they...

  19. 49 CFR 214.109 - Scaffolding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... requirements: (1) Each scaffold and scaffold component, except suspension ropes and guardrail systems, but... least four times the maximum intended load applied or transmitted to that scaffold or scaffold component... guardrail system and the walking/working level. (b) Scaffolds shall not be altered or moved while they...

  20. 49 CFR 214.109 - Scaffolding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... requirements: (1) Each scaffold and scaffold component, except suspension ropes and guardrail systems, but... least four times the maximum intended load applied or transmitted to that scaffold or scaffold component... guardrail system and the walking/working level. (b) Scaffolds shall not be altered or moved while they...

  1. 49 CFR 214.109 - Scaffolding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... requirements: (1) Each scaffold and scaffold component, except suspension ropes and guardrail systems, but... least four times the maximum intended load applied or transmitted to that scaffold or scaffold component... guardrail system and the walking/working level. (b) Scaffolds shall not be altered or moved while they...

  2. 49 CFR 214.109 - Scaffolding.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... requirements: (1) Each scaffold and scaffold component, except suspension ropes and guardrail systems, but... least four times the maximum intended load applied or transmitted to that scaffold or scaffold component... guardrail system and the walking/working level. (b) Scaffolds shall not be altered or moved while they...

  3. Bioresorbable Scaffolds for Atheroregression: Understanding of Transient Scaffolding.

    PubMed

    Kharlamov, Alexander N

    2016-01-01

    This review focuses on the clinical and biological features of the bioresorbable scaffolds in interventional cardiology highlighting scientific achievements and challenges of the transient scaffolding with Absorb BVS. Special attention is granted to the vascular biology pathways which, involved in the resorption of scaffold, artery remodeling and mechanisms of Glagovian atheroregression setting the stage for subsequent clinical applications. Twenty five years ago Glagov described the phenomenon of limited external elastic membrane enlargement in response to an increase in plaque burden. We believe this threshold becomes the target for development of strategies that reverse atherosclerosis, and particularly transient scaffolding has a potential to be a tool to ultimately conquer atherosclerosis. PMID:26818488

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

    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.

  5. Injectable poly-L: -lactic acid: a novel sculpting agent for the treatment of dermal fat atrophy after severe acne.

    PubMed

    Sadove, Richard

    2009-01-01

    Acne vulgaris affects up to 80% of people 11 to 30 years of age, and scarring can occur for up to 95% of these patients. Scarring may be pitted or hypertrophic in nature, although in most cases it is atrophic. Atrophic acne scarring follows dermal collagen and fat loss after moderate to severe acne infection. Injectable poly-L-acid (PLLA) is a biocompatible, biodegradable, synthetic polymer device that is hypothesized to enhance dermal volume via the endogenous production of fibroblasts and, subsequently, collagen. The gradual improvements in cutaneous volume observed after treatment with injectable