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Sample records for scaffold degradation elevates

  1. Polymer scaffold degradation control via chemical control

    DOEpatents

    Hedberg-Dirk, Elizabeth L.; Dirk, Shawn; Cicotte, Kirsten

    2016-01-05

    A variety of polymers and copolymers suitable for use as biologically compatible constructs and, as a non-limiting specific example, in the formation of degradable tissue scaffolds as well methods for synthesizing these polymers and copolymers are described. The polymers and copolymers have degradation rates that are substantially faster than those of previously described polymers suitable for the same uses. Copolymers having a synthesis route which enables one to fine tune the degradation rate by selecting the specific stoichiometry of the monomers in the resulting copolymer are also described. The disclosure also provides a novel synthesis route for maleoyl chloride which yields monomers suitable for use in the copolymer synthesis methods described herein.

  2. Control of scaffold degradation in tissue engineering: a review.

    PubMed

    Zhang, Hongbo; Zhou, Li; Zhang, Wenjun

    2014-10-01

    Tissue engineering has shown a great promise as a solution to the high demand for tissue and organ transplantations. Biomaterial scaffolds serve to house and direct cells to grow, exposing them to an adequate perfusion of nutrients, oxygen, metabolic products, and appropriate growth factors to enhance their differentiation and function. The degradation of biomaterial scaffolds is a key factor to successful tissue regeneration. In this article, the existing degradation control approaches in the context of scaffold tissue engineering were reviewed and a new paradigm of thinking called active control of scaffold degradation, proposed elsewhere by us, was also revisited and discussed in light of its benefit and requirement of this new technology.

  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. A Semi-Degradable Composite Scaffold for Articular Cartilage Defects

    PubMed Central

    Scholten, Paul M.; Ng, Kenneth W.; Joh, Kiwon; Serino, Lorenzo P.; Warren, Russell F.; Torzilli, Peter A.; Maher, Suzanne A.

    2010-01-01

    Few options exist to replace or repair damaged articular cartilage. The optimal solution that has been suggested is a scaffold that can carry load and integrate with surrounding tissues; but such a construct has thus far been elusive. The objectives of this study were to manufacture and characterize a non-degradable hydrated scaffold. Our hypothesis was that the polymer content of the scaffold can be used to control its mechanical properties, while an internal porous network augmented with biological agents can facilitate integration with the host tissue. Using a two-step water-in-oil emulsion process a porous poly-vinyl alcohol (PVA) hydrogel scaffold combined with alginate microspheres was manufactured. The scaffold had a porosity of 11–30% with pore diameters of 107–187 μm, which readily allowed for movement of cells through the scaffold. Alginate microparticles were evenly distributed through the scaffold and allowed for the slow release of biological factors. The elastic modulus (Es) and Poisson’s ratio (υ), Aggregate modulus (Ha) and dynamic modulus (ED) of the scaffold were significantly affected by % PVA, as it varied from 10% to 20% wt/vol. Es and υ were similar to that of articular cartilage for both polymer concentrations, while Ha and ED were similar to that of cartilage only at 20% PVA. The ability to control scaffold mechanical properties, while facilitating cellular migration suggest that this scaffold is a potentially viable candidate for the functional replacement of cartilage defects. PMID:21308980

  5. Highly charged cyanine fluorophores for trafficking scaffold degradation

    PubMed Central

    Owens, Eric A; Hyun, Hoon; Kim, Soon Hee; Lee, Jeong Heon; Park, GwangLi; Ashitate, Yoshitomo; Choi, Jungmun; Hong, Gloria H; Alyabyev, Sergey; Lee, Sang Jin

    2013-01-01

    Biodegradable scaffolds have been extensively used in the field of tissue engineering and regenerative medicine. However, noninvasive monitoring of in vivo scaffold degradation is still lacking. In order to develop a real-time trafficking technique, a series of meso-brominated near-infrared (NIR) fluorophores were synthesized and conjugated to biodegradable gelatin scaffolds. Since the pentamethine cyanine core is highly lipophilic, the side chain of each fluorophore was modified with either quaternary ammonium salts or sulfonate groups. The physicochemical properties such as lipophilicity and net charge of fluorophores played a key role in the fate of NIR-conjugated scaffolds in vivo after biodegradation. The positively charged fluorophore-conjugated scaffold fragments were found in salivary glands, lymph nodes, and most of the hepatobiliary excretion route. However, halogenated fluorophores intensively accumulated into lymph nodes and the liver. Interestingly, balanced-charged gelatin scaffolds were degraded into urine in a short period of time. These results demonstrate that the noninvasive optical imaging using NIR fluorophores can be useful for the translation of biodegradable scaffolds into the clinic. PMID:23353870

  6. Evaluating changes in structure and cytotoxicity during in vitro degradation of three-dimensional printed scaffolds.

    PubMed

    Wang, Martha O; Piard, Charlotte M; Melchiorri, Anthony; Dreher, Maureen L; Fisher, John P

    2015-05-01

    This study evaluated the structural, mechanical, and cytocompatibility changes of three-dimensional (3D) printed porous polymer scaffolds during degradation. Three porous scaffold designs were fabricated from a poly(propylene fumarate) (PPF) resin. PPF is a hydrolytically degradable polymer that has been well characterized for applications in bone tissue engineering. Over a 224 day period, scaffolds were hydrolytically degraded and changes in scaffold parameters, such as porosity and pore size, were measured nondestructively using micro-computed tomography. In addition, changes in scaffold mechanical properties were also measured during degradation. Scaffold degradation was verified through decreasing pH and increasing mass loss as well as the formation of micropores and surface channels. Current methods to evaluate polymer cytotoxicity have been well established; however, the ability to evaluate toxicity of an absorbable polymer as it degrades has not been well explored. This study, therefore, also proposes a novel method to evaluate the cytotoxicity of the absorbable scaffolds using a combination of degradation extract, phosphate-buffered saline, and cell culture media. Fibroblasts were incubated with this combination media, and cytotoxicity was evaluated using XTT assay and fluorescence imaging. Cell culture testing demonstrated that the 3D-printed scaffold extracts did not induce significant cell death. In addition, results showed that over a 224 day time period, porous PPF scaffolds provided mechanical stability while degrading. Overall, these results show that degradable, 3D-printed PPF scaffolds are suitable for bone tissue engineering through the use of a novel toxicity during degradation assay.

  7. 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

  8. Effects of degradation and porosity on the load bearing properties of model hydroxyapatite bone scaffolds.

    SciTech Connect

    Dellinger, Jennifer Gwynne; Cesarano, Joseph, III; Jamison, Russell D.; Wojtowicz, Abigail M.

    2005-06-01

    Degradation of three types of model hydroxyapatite (HA) scaffolds was studied after in vitro degradation in a sodium acetate buffer (pH 4). Degradation was evaluated using compression testing, scanning electron microscopy (SEM), inductively coupled plasma (ICP) analysis, and weight measurements. Scaffolds were fabricated with a solid freeform fabrication (SFF) technique based on the robotic deposition of colloidal pastes. Scaffolds had a macrostructure resembling a lattice of rods. Scaffolds contained either macropores (270 or 680 m in the x-y direction and 280 m in the z-direction) and micropores (1-30-m pores and pores <1 m) or only macropores pores (270 m in the x-y direction and 280 m in the z-direction). A computer-aided design (CAD) program controlled the size and distribution of macropores; micropores were created by polymethylmethacrylate (PMMA) microsphere porogens (1-30-m pore diameter) and controlled sintering (pores <1 m). Percent weight loss of the scaffolds and calcium and phosphorus ion concentrations in solution increased as the degradation period increased for all scaffold types. After degradation, compressive strength and compressive modulus decreased significantly for those scaffolds with microporosity. For scaffolds without microporosity, the changes in strength and modulus after degradation were not statistically significant. The compressive strength of scaffolds without microporosity was significantly greater than the scaffolds with microporosity.

  9. In vitro degradation and mechanical properties of PLA-PCL copolymer unit cell scaffolds generated by two-photon polymerization.

    PubMed

    Felfel, R M; Poocza, Leander; Gimeno-Fabra, Miquel; Milde, Tobias; Hildebrand, Gerhard; Ahmed, Ifty; Scotchford, Colin; Sottile, Virginie; Grant, David M; Liefeith, Klaus

    2016-02-01

    The manufacture of 3D scaffolds with specific controlled porous architecture, defined microstructure and an adjustable degradation profile was achieved using two-photon polymerization (TPP) with a size of 2  ×  4  ×  2 mm(3). Scaffolds made from poly(D,L-lactide-co-ɛ-caprolactone) copolymer with varying lactic acid (LA) and ɛ -caprolactone (CL) ratios (LC16:4, 18:2 and 9:1) were generated via ring-opening-polymerization and photoactivation. The reactivity was quantified using photo-DSC, yielding a double bond conversion ranging from 70% to 90%. The pore sizes for all LC scaffolds were see 300 μm and throat sizes varied from 152 to 177 μm. In vitro degradation was conducted at different temperatures; 37, 50 and 65 °C. Change in compressive properties immersed at 37 °C over time was also measured. Variations in thermal, degradation and mechanical properties of the LC scaffolds were related to the LA/CL ratio. Scaffold LC16:4 showed significantly lower glass transition temperature (T g) (4.8 °C) in comparison with the LC 18:2 and 9:1 (see 32 °C). Rates of mass loss for the LC16:4 scaffolds at all temperatures were significantly lower than that for LC18:2 and 9:1. The degradation activation energies for scaffold materials ranged from 82.7 to 94.9 kJ mol(-1). A prediction for degradation time was applied through a correlation between long-term degradation studies at 37 °C and short-term studies at elevated temperatures (50 and 65 °C) using the half-life of mass loss (Time (M1/2)) parameter. However, the initial compressive moduli for LC18:2 and 9:1 scaffolds were 7 to 14 times higher than LC16:4 (see 0.27) which was suggested to be due to its higher CL content (20%). All scaffolds showed a gradual loss in their compressive strength and modulus over time as a result of progressive mass loss over time. The manufacturing process utilized and the scaffolds produced have potential for use in tissue engineering and regenerative medicine

  10. A Porous Tissue Engineering Scaffold Selectively Degraded by Cell-Generated Reactive Oxygen Species

    PubMed Central

    Martin, John R.; Gupta, Mukesh K.; Page, Jonathan M.; Yu, Fang; Davidson, Jeffrey M.; Guelcher, Scott A.

    2014-01-01

    Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic breakdown products that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are key mediators of cell function in both health and disease, especially at sites of inflammation and tissue healing, and induction of inflammation and ROS are natural components of the in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating tissue engineering scaffolds with better matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds were synthesized that degrade specifically by an ROS-dependent mechanism. PTK-UR scaffolds had significantly higher compressive moduli than analogous poly(ester urethane) (PEUR) scaffolds formed from hydrolytically-degradable ester-based diols (p < 0.05). Unlike PEUR scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS, indicating that their biodegradation would be exclusively cell-mediated. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p < 0.05), and correlated to ROS concentration. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that ROS-degradable PTK-UR tissue engineering scaffolds have significant advantages over analogous

  11. A porous tissue engineering scaffold selectively degraded by cell-generated reactive oxygen species.

    PubMed

    Martin, John R; Gupta, Mukesh K; Page, Jonathan M; Yu, Fang; Davidson, Jeffrey M; Guelcher, Scott A; Duvall, Craig L

    2014-04-01

    Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic breakdown products that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are key mediators of cell function in both health and disease, especially at sites of inflammation and tissue healing, and induction of inflammation and ROS are natural components of the in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating tissue engineering scaffolds with better matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds were synthesized that degrade specifically by an ROS-dependent mechanism. PTK-UR scaffolds had significantly higher compressive moduli than analogous poly(ester urethane) (PEUR) scaffolds formed from hydrolytically-degradable ester-based diols (p < 0.05). Unlike PEUR scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS, indicating that their biodegradation would be exclusively cell-mediated. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p < 0.05), and correlated to ROS concentration. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that ROS-degradable PTK-UR tissue engineering scaffolds have significant advantages over

  12. Biocompatibility and degradation of tendon-derived scaffolds

    PubMed Central

    Alberti, Kyle A.; Xu, Qiaobing

    2016-01-01

    Decellularized extracellular matrix has often been used as a biomaterial for tissue engineering applications. Its function, once implanted can be crucial to determining whether a tissue engineered construct will be successful, both in terms of how the material breaks down, and how the body reacts to the material’s presence in the first place. Collagen is one of the primary components of extracellular matrix and has been used for a number of biomedical applications. Scaffolds comprised of highly aligned collagen fibrils can be fabricated directly from decellularized tendon using a slicing, stacking, and rolling technique, to create two- and three-dimensional constructs. Here, the degradation characteristics of the material are evaluated in vitro, showing that chemical crosslinking can reduce degradation while maintaining fiber structure. In vivo, non-crosslinked and crosslinked samples are implanted, and their biological response and degradation evaluated through histological sectioning, trichrome staining, and immunohistochemical staining for macrophages. Non-crosslinked samples are rapidly degraded and lose fiber morphology while crosslinked samples retain both macroscopic structure as well as fiber orientation. The cellular response of both materials is also investigated. The in vivo response demonstrates that the decellularized tendon material is biocompatible, biodegradable and can be crosslinked to maintain surface features for extended periods of time in vivo. This study provides material characteristics for the use of decellularized tendon as biomaterial for tissue engineering. PMID:26816651

  13. Modeling material-degradation-induced elastic property of tissue engineering scaffolds.

    PubMed

    Bawolin, N K; Li, M G; Chen, X B; Zhang, W J

    2010-11-01

    The mechanical properties of tissue engineering scaffolds play a critical role in the success of repairing damaged tissues/organs. Determining the mechanical properties has proven to be a challenging task as these properties are not constant but depend upon time as the scaffold degrades. In this study, the modeling of the time-dependent mechanical properties of a scaffold is performed based on the concept of finite element model updating. This modeling approach contains three steps: (1) development of a finite element model for the effective mechanical properties of the scaffold, (2) parametrizing the finite element model by selecting parameters associated with the scaffold microstructure and/or material properties, which vary with scaffold degradation, and (3) identifying selected parameters as functions of time based on measurements from the tests on the scaffold mechanical properties as they degrade. To validate the developed model, scaffolds were made from the biocompatible polymer polycaprolactone (PCL) mixed with hydroxylapatite (HA) nanoparticles and their mechanical properties were examined in terms of the Young modulus. Based on the bulk degradation exhibited by the PCL/HA scaffold, the molecular weight was selected for model updating. With the identified molecular weight, the finite element model developed was effective for predicting the time-dependent mechanical properties of PCL/HA scaffolds during degradation.

  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. Evaluating Changes in Structure and Cytotoxicity During In Vitro Degradation of Three-Dimensional Printed Scaffolds

    PubMed Central

    Wang, Martha O.; Piard, Charlotte M.; Melchiorri, Anthony; Dreher, Maureen L.

    2015-01-01

    This study evaluated the structural, mechanical, and cytocompatibility changes of three-dimensional (3D) printed porous polymer scaffolds during degradation. Three porous scaffold designs were fabricated from a poly(propylene fumarate) (PPF) resin. PPF is a hydrolytically degradable polymer that has been well characterized for applications in bone tissue engineering. Over a 224 day period, scaffolds were hydrolytically degraded and changes in scaffold parameters, such as porosity and pore size, were measured nondestructively using micro-computed tomography. In addition, changes in scaffold mechanical properties were also measured during degradation. Scaffold degradation was verified through decreasing pH and increasing mass loss as well as the formation of micropores and surface channels. Current methods to evaluate polymer cytotoxicity have been well established; however, the ability to evaluate toxicity of an absorbable polymer as it degrades has not been well explored. This study, therefore, also proposes a novel method to evaluate the cytotoxicity of the absorbable scaffolds using a combination of degradation extract, phosphate-buffered saline, and cell culture media. Fibroblasts were incubated with this combination media, and cytotoxicity was evaluated using XTT assay and fluorescence imaging. Cell culture testing demonstrated that the 3D-printed scaffold extracts did not induce significant cell death. In addition, results showed that over a 224 day time period, porous PPF scaffolds provided mechanical stability while degrading. Overall, these results show that degradable, 3D-printed PPF scaffolds are suitable for bone tissue engineering through the use of a novel toxicity during degradation assay. PMID:25627168

  16. Characterization of the degradation mechanisms of lysine-derived aliphatic poly(ester urethane) scaffolds.

    PubMed

    Hafeman, Andrea E; Zienkiewicz, Katarzyna J; Zachman, Angela L; Sung, Hak-Joon; Nanney, Lillian B; Davidson, Jeffrey M; Guelcher, Scott A

    2011-01-01

    Characterization of the degradation mechanism of polymeric scaffolds and delivery systems for regenerative medicine is essential to assess their clinical applicability. Key performance criteria include induction of a minimal, transient inflammatory response and controlled degradation to soluble non-cytotoxic breakdown products that are cleared from the body by physiological processes. Scaffolds fabricated from biodegradable poly(ester urethane)s (PEURs) undergo controlled degradation to non-cytotoxic breakdown products and support the ingrowth of new tissue in preclinical models of tissue regeneration. While previous studies have shown that PEUR scaffolds prepared from lysine-derived polyisocyanates degrade faster under in vivo compared to in vitro conditions, the degradation mechanism is not well understood. In this study, we have shown that PEUR scaffolds prepared from lysine triisocyanate (LTI) or a trimer of hexamethylene diisocyanate (HDIt) undergo hydrolytic, esterolytic, and oxidative degradation. Hydrolysis of ester bonds to yield α-hydroxy acids is the dominant mechanism in buffer, and esterolytic media modestly increase the degradation rate. While HDIt scaffolds show a modest (<20%) increase in degradation rate in oxidative medium, LTI scaffolds degrade six times faster in oxidative medium. Furthermore, the in vitro rate of degradation of LTI scaffolds in oxidative medium approximates the in vivo rate in rat excisional wounds, and histological sections show macrophages expressing myeloperoxidase at the material surface. While recent preclinical studies have underscored the potential of injectable PEUR scaffolds and delivery systems for tissue regeneration, this promising class of biomaterials has a limited regulatory history. Elucidation of the macrophage-mediated oxidative mechanism by which LTI scaffolds degrade in vivo provides key insights into the ultimate fate of these materials when injected into the body. PMID:20864156

  17. Characterization of the Degradation Mechanisms of Lysine-derived Aliphatic Poly(ester urethane) Scaffolds

    PubMed Central

    Hafeman, Andrea E.; Zienkiewicz, Katarzyna J.; Zachman, Angela L.; Sung, Hak-Joon; Nanney, Lillian B.; Davidson, Jeffrey M.; Guelcher, Scott A.

    2010-01-01

    Characterization of the degradation mechanism of polymeric scaffolds and delivery systems for regenerative medicine is essential to assess their clinical applicability. Key performance criteria include induction of a minimal, transient inflammatory response and controlled degradation to soluble non-cytotoxic breakdown products that are cleared from the body by physiological processes. Scaffolds fabricated from biodegradable poly(ester urethane)s (PEURs) undergo controlled degradation to non-cytotoxic breakdown products and support the ingrowth of new tissue in preclinical models of tissue regeneration. While previous studies have shown that PEUR scaffolds prepared from lysine-derived polyisocyanates degrade faster under in vivo compared to in vitro conditions, the degradation mechanism is not well understood. In this study, we have shown that PEUR scaffolds prepared from lysine triisocyanate (LTI) or a trimer of hexamethylene diisocyanate (HDIt) undergo hydrolytic, esterolytic, and oxidative degradation. Hydrolysis of ester bonds to yield α-hydroxy acids is the dominant mechanism in buffer, and esterolytic media modestly increase the degradation rate. While HDIt scaffolds show a modest (<20%) increase in degradation rate in oxidative medium, LTI scaffolds degrade six times faster in oxidative medium. Furthermore, the in vitro rate of degradation of LTI scaffolds in oxidative medium approximates the in vivo rate in rat excisional wounds, and histological sections show macrophages expressing myeloperoxidase at the material surface. While recent preclinical studies have underscored the potential of injectable PEUR scaffolds and delivery systems for tissue regeneration, this promising class of biomaterials has a limited regulatory history. Elucidation of the macrophage-mediated oxidative mechanism by which LTI scaffolds degrade in vivo provides key insights into the ultimate fate of these materials when injected into the body. PMID:20864156

  18. Degradability, bioactivity, and osteogenesis of biocomposite scaffolds of lithium-containing mesoporous bioglass and mPEG-PLGA-b-PLL copolymer

    PubMed Central

    Cai, Yanrong; Guo, Lieping; Shen, Hongxing; An, Xiaofei; Jiang, Hong; Ji, Fang; Niu, Yunfei

    2015-01-01

    Biocomposite scaffolds of lithium (Li)-containing mesoporous bioglass and monomethoxy poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine) (mPEG-PLGA-b-PLL) copolymer were fabricated in this study. The results showed that the water absorption and degradability of Li-containing mesoporous bioglass/mPEG-PLGA-b-PLL composite (l-MBPC) scaffolds were obviously higher than Li-containing bioglass/mPEG-PLGA-b-PLL composite (l-BPC) scaffolds. Moreover, the apatite-formation ability of l-MBPC scaffolds was markedly enhanced as compared with l-BPC scaffolds, indicating that l-MBPC scaffolds containing mesoporous bioglass exhibited good bioactivity. The cell experimental results showed that cell attachment, proliferation, and alkaline phosphatase activity of MC3T3-E1 cells on l-MBPC scaffolds were remarkably improved as compared to l-BPC scaffolds. In animal experiments, the histological elevation results revealed that l-MBPC scaffolds significantly promoted new bone formation, indicating good osteogenesis. l-MBPC scaffolds with improved properties would be an excellent candidate for bone tissue repair. PMID:26150718

  19. Degradability, bioactivity, and osteogenesis of biocomposite scaffolds of lithium-containing mesoporous bioglass and mPEG-PLGA-b-PLL copolymer.

    PubMed

    Cai, Yanrong; Guo, Lieping; Shen, Hongxing; An, Xiaofei; Jiang, Hong; Ji, Fang; Niu, Yunfei

    2015-01-01

    Biocomposite scaffolds of lithium (Li)-containing mesoporous bioglass and monomethoxy poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine) (mPEG-PLGA-b-PLL) copolymer were fabricated in this study. The results showed that the water absorption and degradability of Li-containing mesoporous bioglass/mPEG-PLGA-b-PLL composite (l-MBPC) scaffolds were obviously higher than Li-containing bioglass/mPEG-PLGA-b-PLL composite (l-BPC) scaffolds. Moreover, the apatite-formation ability of l-MBPC scaffolds was markedly enhanced as compared with l-BPC scaffolds, indicating that l-MBPC scaffolds containing mesoporous bioglass exhibited good bioactivity. The cell experimental results showed that cell attachment, proliferation, and alkaline phosphatase activity of MC3T3-E1 cells on l-MBPC scaffolds were remarkably improved as compared to l-BPC scaffolds. In animal experiments, the histological elevation results revealed that l-MBPC scaffolds significantly promoted new bone formation, indicating good osteogenesis. l-MBPC scaffolds with improved properties would be an excellent candidate for bone tissue repair.

  20. Synchrotron-Based in Situ Characterization of the Scaffold Mass Loss from Erosion Degradation

    PubMed Central

    Bawolin, Nahshon K.; Chen, Xiongbaio

    2016-01-01

    The mass loss behavior of degradable tissue scaffolds is critical to their lifespan and other degradation-related properties including mechanical strength and mass transport characteristics. This paper presents a novel method based on synchrotron imaging to characterize the scaffold mass loss from erosion degradation in situ, or without the need of extracting scaffolds once implanted. Specifically, the surface-eroding degradation of scaffolds in a degrading medium was monitored in situ by synchrotron-based imaging; and the time-dependent geometry of scaffolds captured by images was then employed to estimate their mass loss with time, based on the mathematical model that was adopted from the literature of surface erosion with the experimentally-identified model parameters. Acceptable agreement between experimental results and model predictions was observed for scaffolds in a cylindrical shape, made from poly(lactic-co-glycolic) acid (PLGA) and polycaprolactone (PCL). This study illustrates that geometry evaluation by synchrotron-based imaging is an effective means to in situ characterize the scaffold mass loss as well as possibly other degradation-related properties. PMID:27399789

  1. Synchrotron-Based in Situ Characterization of the Scaffold Mass Loss from Erosion Degradation.

    PubMed

    Bawolin, Nahshon K; Chen, Xiongbaio

    2016-01-01

    The mass loss behavior of degradable tissue scaffolds is critical to their lifespan and other degradation-related properties including mechanical strength and mass transport characteristics. This paper presents a novel method based on synchrotron imaging to characterize the scaffold mass loss from erosion degradation in situ, or without the need of extracting scaffolds once implanted. Specifically, the surface-eroding degradation of scaffolds in a degrading medium was monitored in situ by synchrotron-based imaging; and the time-dependent geometry of scaffolds captured by images was then employed to estimate their mass loss with time, based on the mathematical model that was adopted from the literature of surface erosion with the experimentally-identified model parameters. Acceptable agreement between experimental results and model predictions was observed for scaffolds in a cylindrical shape, made from poly(lactic-co-glycolic) acid (PLGA) and polycaprolactone (PCL). This study illustrates that geometry evaluation by synchrotron-based imaging is an effective means to in situ characterize the scaffold mass loss as well as possibly other degradation-related properties. PMID:27399789

  2. Superior Tissue Evolution in Slow-Degrading Scaffolds for Valvular Tissue Engineering.

    PubMed

    Brugmans, Marieke M C P; Soekhradj-Soechit, R Sarita; van Geemen, Daphne; Cox, Martijn; Bouten, Carlijn V C; Baaijens, Frank P T; Driessen-Mol, Anita

    2016-01-01

    Synthetic polymers are widely used to fabricate porous scaffolds for the regeneration of cardiovascular tissues. To ensure mechanical integrity, a balance between the rate of scaffold absorption and tissue formation is of high importance. A higher rate of tissue formation is expected in fast-degrading materials than in slow-degrading materials. This could be a result of synthetic cells, which aim to compensate for the fast loss of mechanical integrity of the scaffold by deposition of collagen fibers. Here, we studied the effect of fast-degrading polyglycolic acid scaffolds coated with poly-4-hydroxybutyrate (PGA-P4HB) and slow-degrading poly-ɛ-caprolactone (PCL) scaffolds on amount of tissue, composition, and mechanical characteristics in time, and compared these engineered values with values for native human heart valves. Electrospun PGA-P4HB and PCL scaffolds were either kept unseeded in culture or were seeded with human vascular-derived cells. Tissue formation, extracellular matrix (ECM) composition, remaining scaffold weight, tissue-to-scaffold weight ratio, and mechanical properties were analyzed every week up to 6 weeks. Mass of unseeded PCL scaffolds remained stable during culture, whereas PGA-P4HB scaffolds degraded rapidly. When seeded with cells, both scaffold types demonstrated increasing amounts of tissue with time, which was more pronounced for PGA-P4HB-based tissues during the first 2 weeks; however, PCL-based tissues resulted in the highest amount of tissue after 6 weeks. This study is the first to provide insight into the tissue-to-scaffold weight ratio, therewith allowing for a fair comparison between engineered tissues cultured on scaffolds as well as between native heart valve tissues. Although the absolute amount of ECM components differed between the engineered tissues, the ratio between ECM components was similar after 6 weeks. PCL-based tissues maintained their shape, whereas the PGA-P4HB-based tissues deformed during culture. After 6 weeks

  3. Macroporous photocrosslinked elastomer scaffolds containing microposity: preparation and in vitro degradation properties.

    PubMed

    Ilagan, Bernadette G; Amsden, Brian G

    2010-04-01

    The engineering of soft tissue would benefit from the development of effective biodegradable scaffolds capable of dynamic, elastic loading. For this purpose, highly porous, elastomeric scaffolds containing microporous struts were prepared using a dual porogen approach and a photocrosslinkable elastomer. The combination of paraffin microbeads distributed through a water-in-[star-poly(lactide-co-epsilon-caprolactone) triacrylate dissolved in ethyl acetate] emulsion followed by photocrosslinking generated a macroporous foam scaffold of average porosities between 90% to 93%, with an average pore diameter of 104 +/- 31 microm with struts containing micropores of 3.1 +/- 2 microm average diameter. The mechanical properties of the scaffolds were readily manipulatable by altering the molecular weight of the star-poly(lactide-co-epsilon-caprolactone) triacrylate prepolymer used. The elastomer scaffolds degraded at the same rate as nonporous polymer samples of the same molecular weight, and exhibited similar changes in mass loss, mechanical properties, and sol fraction during in vitro degradation as found with the nonporous scaffolds. The modulus and stress at break of the scaffolds decreased continuously during degradation while the strain at break remained constant. These scaffolds show potential for use in the engineering of soft tissues. PMID:19544482

  4. Relating pore size variation of poly (ɛ-caprolactone) scaffolds to molecular weight of porogen and evaluation of scaffold properties after degradation.

    PubMed

    Columbus, Soumya; Krishnan, Lissy K; Kalliyana Krishnan, V

    2014-05-01

    The major challenge in designing a scaffold for fabricating tissue engineered blood vessels is optimization of its microstructure for supporting uniform cellular in-growth with good mechanical integrity and degradation kinetics suitable for long-term implantation. In this study, we have investigated the feasibility of varying the pore size of poly(ɛ-caprolactone) (PCL) scaffold by altering the molecular weight of porogen and studied the effect of degradation on morphological characteristics and mechanical properties of scaffolds by correlating to the extent of degradation. Scaffolds with two different pore sizes were prepared by solvent casting and particulate leaching where poly(ethylene glycol) (PEG) porogens having two molecular weights (3400 and 8000) were used and subjected to in vitro degradation in phosphate buffered saline (PBS) upto six months. Microcomputed tomography studies of scaffolds revealed narrower pore size distribution when PEG-3400 was used as porogen and had 78% pores in the 12-24 µ range, whereas incorporation of PEG-8000 resulted in broader distribution with only 65% pores in the same range. Degradation resulted in scaffolds with narrower pore size distribution to have better retention of morphological and mechanical characteristics compared to scaffolds with broader distribution. Gravimetric and molecular weight studies also showed that scaffold degradation in both cases was only in initial stages after 6 months and PCL scaffolds had potential to be recommended for vascular tissue engineering applications.

  5. Physiologically-Relevant Oxidative Degradation of Oligo(proline)-Crosslinked Polymeric Scaffolds

    PubMed Central

    Yu, Shann S.; Koblin, Rachel L.; Zachman, Angela L.; Perrien, Daniel S.; Hofmeister, Lucas H.; Giorgio, Todd D.; Sung, Hak-Joon

    2011-01-01

    Chronic inflammation-mediated oxidative stress is a common mechanism of implant rejection and failure. Therefore, polymer scaffolds that can degrade slowly in response to this environment may provide a viable platform for implant site-specific, sustained release of immunomodulatory agents over a long time period. In this work, proline oligomers of varying lengths (Pn) were synthesized and exposed to oxidative environments, and their accelerated degradation under oxidative conditions was verified via high performance liquid chromatography and gel permeation chromatography. Next, diblock copolymers of poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) were carboxylated to form 100 kDa terpolymers of 4%PEG-86%PCL-10%cPCL (cPCL = poly(carboxyl-ε-caprolactone); i% indicates molar ratio). The polymers were then crosslinked with bi-aminated PEG-Pn-PEG chains—where Pn indicates the length of the proline oligomer flanked by PEG chains. Salt-leaching of the polymeric matrices created scaffolds of macroporous and microporous architecture as observed by scanning electron microscopy. The degradation of scaffolds was accelerated under oxidative conditions, as evidenced by mass loss and differential scanning calorimetry measurements. Immortalized murine bone marrow-derived macrophages were then seeded on the scaffolds, and activated through the addition of γ-interferon and lipopolysaccharide throughout the 9-day study period. This treatment promoted the release of H2O2 by the macrophages, and the degradation of proline-containing scaffolds compared to the control scaffolds. The accelerated degradation was evidenced by increased scaffold porosity, as visualized through scanning electron microscoopy and X-ray microtomography imaging. The current study provides insight into the development of scaffolds that respond to oxidative environments through gradual degradation, for the controlled release of therapeutics targeted to diseases that feature chronic inflammation and

  6. Physiologically relevant oxidative degradation of oligo(proline) cross-linked polymeric scaffolds.

    PubMed

    Yu, Shann S; Koblin, Rachel L; Zachman, Angela L; Perrien, Daniel S; Hofmeister, Lucas H; Giorgio, Todd D; Sung, Hak-Joon

    2011-12-12

    Chronic inflammation-mediated oxidative stress is a common mechanism of implant rejection and failure. Therefore, polymer scaffolds that can degrade slowly in response to this environment may provide a viable platform for implant site-specific, sustained release of immunomodulatory agents over a long time period. In this work, proline oligomers of varying lengths (P(n)) were synthesized and exposed to oxidative environments, and their accelerated degradation under oxidative conditions was verified via high performance liquid chromatography and gel permeation chromatography. Next, diblock copolymers of poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) were carboxylated to form 100 kDa terpolymers of 4%PEG-86%PCL-10%cPCL (cPCL = poly(carboxyl-ε-caprolactone); i% indicates molar ratio). The polymers were then cross-linked with biaminated PEG-P(n)-PEG chains, where P(n) indicates the length of the proline oligomer flanked by PEG chains. Salt-leaching of the polymeric matrices created scaffolds of macroporous and microporous architecture, as observed by scanning electron microscopy. The degradation of scaffolds was accelerated under oxidative conditions, as evidenced by mass loss and differential scanning calorimetry measurements. Immortalized murine bone-marrow-derived macrophages were then seeded on the scaffolds and activated through the addition of γ-interferon and lipopolysaccharide throughout the 9-day study period. This treatment promoted the release of H(2)O(2) by the macrophages and the degradation of proline-containing scaffolds compared to the control scaffolds. The accelerated degradation was evidenced by increased scaffold porosity, as visualized through scanning electron microscopy and X-ray microtomography imaging. The current study provides insight into the development of scaffolds that respond to oxidative environments through gradual degradation for the controlled release of therapeutics targeted to diseases that feature chronic

  7. An animal experimental study of porous magnesium scaffold degradation and osteogenesis.

    PubMed

    Liu, Y J; Yang, Z Y; Tan, L L; Li, H; Zhang, Y Z

    2014-08-01

    Our objective was to observe the biodegradable and osteogenic properties of magnesium scaffolding under in vivo conditions. Twelve 6-month-old male New Zealand white rabbits were randomly divided into two groups. The chosen operation site was the femoral condyle on the right side. The experimental group was implanted with porous magnesium scaffolds, while the control group was implanted with hydroxyapatite scaffolds. X-ray and blood tests, which included serum magnesium, alanine aminotransferase (ALT), creatinine (CREA), and blood urea nitrogen (BUN) were performed serially at 1, 2, and 3 weeks, and 1, 2, and 3 months. All rabbits were killed 3 months postoperatively, and the heart, kidney, spleen, and liver were analyzed with hematoxylin and eosin (HE) staining. The bone samples were subjected to microcomputed tomography scanning (micro-CT) and hard tissue biopsy. SPSS 13.0 (USA) was used for data analysis, and values of P<0.05 were considered to be significant. Bubbles appeared in the X-ray of the experimental group after 2 weeks, whereas there was no gas in the control group. There were no statistical differences for the serum magnesium concentrations, ALT, BUN, and CREA between the two groups (P>0.05). All HE-stained slices were normal, which suggested good biocompatibility of the scaffold. Micro-CT showed that magnesium scaffolds degraded mainly from the outside to inside, and new bone was ingrown following the degradation of magnesium scaffolds. The hydroxyapatite scaffold was not degraded and had fewer osteoblasts scattered on its surface. There was a significant difference in the new bone formation and scaffold bioabsorption between the two groups (9.29 ± 1.27 vs 1.40 ± 0.49 and 7.80 ± 0.50 vs 0.00 ± 0.00 mm3, respectively; P<0.05). The magnesium scaffold performed well in degradation and osteogenesis, and is a promising material for orthopedics.

  8. An animal experimental study of porous magnesium scaffold degradation and osteogenesis

    PubMed Central

    Liu, Y.J.; Yang, Z.Y.; Tan, L.L.; Li, H.; Zhang, Y.Z.

    2014-01-01

    Our objective was to observe the biodegradable and osteogenic properties of magnesium scaffolding under in vivo conditions. Twelve 6-month-old male New Zealand white rabbits were randomly divided into two groups. The chosen operation site was the femoral condyle on the right side. The experimental group was implanted with porous magnesium scaffolds, while the control group was implanted with hydroxyapatite scaffolds. X-ray and blood tests, which included serum magnesium, alanine aminotransferase (ALT), creatinine (CREA), and blood urea nitrogen (BUN) were performed serially at 1, 2, and 3 weeks, and 1, 2, and 3 months. All rabbits were killed 3 months postoperatively, and the heart, kidney, spleen, and liver were analyzed with hematoxylin and eosin (HE) staining. The bone samples were subjected to microcomputed tomography scanning (micro-CT) and hard tissue biopsy. SPSS 13.0 (USA) was used for data analysis, and values of P<0.05 were considered to be significant. Bubbles appeared in the X-ray of the experimental group after 2 weeks, whereas there was no gas in the control group. There were no statistical differences for the serum magnesium concentrations, ALT, BUN, and CREA between the two groups (P>0.05). All HE-stained slices were normal, which suggested good biocompatibility of the scaffold. Micro-CT showed that magnesium scaffolds degraded mainly from the outside to inside, and new bone was ingrown following the degradation of magnesium scaffolds. The hydroxyapatite scaffold was not degraded and had fewer osteoblasts scattered on its surface. There was a significant difference in the new bone formation and scaffold bioabsorption between the two groups (9.29±1.27 vs 1.40±0.49 and 7.80±0.50 vs 0.00±0.00 mm3, respectively; P<0.05). The magnesium scaffold performed well in degradation and osteogenesis, and is a promising material for orthopedics. PMID:25098717

  9. Viscoelastic, physical, and bio-degradable properties of dermal scaffolds and related cell behaviour.

    PubMed

    Sharma, Vaibhav; Patel, Nimesha; Kohli, Nupur; Ravindran, Nivedita; Hook, Lilian; Mason, Chris; García-Gareta, Elena

    2016-01-01

    Dermal scaffolds promote healing of debilitating skin injuries caused by burns and chronic skin conditions. Currently available products present disadvantages and therefore, there is still a clinical need for developing new dermal substitutes. This study aimed at comparing the viscoelastic, physical and bio-degradable properties of two dermal scaffolds, the collagen-based and clinically well established Integra(®) and a novel fibrin-based dermal scaffold developed at our laboratory called Smart Matrix(®), to further evaluate our previous published findings that suggested a higher influx of cells, reduced wound contraction and less scarring for Smart Matrix(®) when used in vivo. Rheological results showed that Integra(®) (G'  =  313.74 kPa) is mechanically stronger than Smart Matrix(®) (G'  =  8.26 kPa), due to the presence of the silicone backing layer in Integra(®). Micro-pores were observed on both dermal scaffolds, although nano-pores as well as densely packed nano-fibres were only observed for Smart Matrix(®). Average surface roughness was higher for Smart Matrix(®) (Sa  =  114.776 nm) than for Integra(®) (Sa  =  75.565 nm). Both scaffolds possess a highly porous structure (80-90%) and display a range of pore micro-sizes that represent the actual in vivo scenario. In vitro proteolytic bio-degradation suggested that Smart Matrix(®) would degrade faster upon implantation in vivo than Integra(®). For both scaffolds, the enzymatic digestion occurs via bulk degradation. These observed differences could affect cell behaviour on both scaffolds. Our results suggest that fine-tuning of scaffolds' viscoelastic, physical and bio-degradable properties can maximise cell behaviour in terms of attachment, proliferation and infiltration, which are essential for tissue repair. PMID:27586397

  10. Degradability, cytocompatibility, and osteogenesis of porous scaffolds of nanobredigite and PCL–PEG–PCL composite

    PubMed Central

    Hou, Jun; Fan, Donghui; Zhao, Lingming; Yu, Baoqin; Su, Jiacan; Wei, Jie; Shin, Jung-Woog

    2016-01-01

    Biocomposite scaffolds were fabricated by incorporation of nanobredigite (n-BD) into the polymer of poly(ε-caprolactone)–poly(ethyleneglycol)–poly(ε-caprolactone) (PCL–PEG–PCL). The results revealed that the addition of n-BD into PCL–PEG–PCL significantly improved water absorption, compressive strength, and degradability of the scaffolds of n-BD/PCL–PEG–PCL composite (n-BPC) compared with PCL–PEG–PCL scaffolds alone. In addition, the proliferation and alkaline phosphatase activity of MG63 cells cultured on n-BPC scaffolds were obviously higher than that cultured on PCL–PEG–PCL scaffolds. Moreover, the results of the histological evaluation from the animal model revealed that the n-BPC scaffolds significantly improved new bone formation compared with the PCL–PEG–PCL scaffolds, indicating good osteogenesis. The n-BPC scaffolds with good biocompatibility could stimulate cell proliferation, differentiation, and bone tissue regeneration and would be an excellent candidate for bone defect repair. PMID:27555774

  11. Degradability, cytocompatibility, and osteogenesis of porous scaffolds of nanobredigite and PCL-PEG-PCL composite.

    PubMed

    Hou, Jun; Fan, Donghui; Zhao, Lingming; Yu, Baoqin; Su, Jiacan; Wei, Jie; Shin, Jung-Woog

    2016-01-01

    Biocomposite scaffolds were fabricated by incorporation of nanobredigite (n-BD) into the polymer of poly(ε-caprolactone)-poly(ethyleneglycol)-poly(ε-caprolactone) (PCL-PEG-PCL). The results revealed that the addition of n-BD into PCL-PEG-PCL significantly improved water absorption, compressive strength, and degradability of the scaffolds of n-BD/PCL-PEG-PCL composite (n-BPC) compared with PCL-PEG-PCL scaffolds alone. In addition, the proliferation and alkaline phosphatase activity of MG63 cells cultured on n-BPC scaffolds were obviously higher than that cultured on PCL-PEG-PCL scaffolds. Moreover, the results of the histological evaluation from the animal model revealed that the n-BPC scaffolds significantly improved new bone formation compared with the PCL-PEG-PCL scaffolds, indicating good osteogenesis. The n-BPC scaffolds with good biocompatibility could stimulate cell proliferation, differentiation, and bone tissue regeneration and would be an excellent candidate for bone defect repair. PMID:27555774

  12. Data for accelerated degradation of calcium phosphate surface-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds.

    PubMed

    Poh, Patrina S P; Hutmacher, Dietmar W; Holzapfel, Boris M; Solanki, Anu K; Woodruff, Maria A

    2016-06-01

    Polycaprolactone (PCL)-based composite scaffolds containing 50 wt% of 45S5 bioactive glass (45S5) or strontium-substituted bioactive glass (SrBG) particles were fabricated into scaffolds using melt-extrusion based additive manufacturing technique. Additionally, the PCL scaffolds were surface coated with a layer of calcium phosphate (CaP). For a comparison of the scaffold degradation, the scaffolds were then subjected to in vitro accelerated degradation by immersion in 5 M sodium hydroxide (NaOH) solution for up to 7 days. The scaffold׳s morphology was observed by means of SEM imaging and scaffold mass loss was recorded over the experimental period. PMID:27081669

  13. Data for accelerated degradation of calcium phosphate surface-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds.

    PubMed

    Poh, Patrina S P; Hutmacher, Dietmar W; Holzapfel, Boris M; Solanki, Anu K; Woodruff, Maria A

    2016-06-01

    Polycaprolactone (PCL)-based composite scaffolds containing 50 wt% of 45S5 bioactive glass (45S5) or strontium-substituted bioactive glass (SrBG) particles were fabricated into scaffolds using melt-extrusion based additive manufacturing technique. Additionally, the PCL scaffolds were surface coated with a layer of calcium phosphate (CaP). For a comparison of the scaffold degradation, the scaffolds were then subjected to in vitro accelerated degradation by immersion in 5 M sodium hydroxide (NaOH) solution for up to 7 days. The scaffold׳s morphology was observed by means of SEM imaging and scaffold mass loss was recorded over the experimental period.

  14. Data for accelerated degradation of calcium phosphate surface-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds

    PubMed Central

    Poh, Patrina S.P.; Hutmacher, Dietmar W.; Holzapfel, Boris M.; Solanki, Anu K.; Woodruff, Maria A.

    2016-01-01

    Polycaprolactone (PCL)-based composite scaffolds containing 50 wt% of 45S5 bioactive glass (45S5) or strontium-substituted bioactive glass (SrBG) particles were fabricated into scaffolds using melt-extrusion based additive manufacturing technique. Additionally, the PCL scaffolds were surface coated with a layer of calcium phosphate (CaP). For a comparison of the scaffold degradation, the scaffolds were then subjected to in vitro accelerated degradation by immersion in 5 M sodium hydroxide (NaOH) solution for up to 7 days. The scaffold׳s morphology was observed by means of SEM imaging and scaffold mass loss was recorded over the experimental period. PMID:27081669

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

    PubMed Central

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

    2013-01-01

    Tissue engineering scaffolds require a controlled pore size and interconnected pore structures to support the host tissue growth. In the present study, three dimensional (3D) hybrid scaffolds of poly lactic acid (PLA) and poly glycolic acid (PGA) were fabricated using solvent casting/particulate leaching. In this case, partially fused NaCl particles were used as porogen (200-300µ) to improve the overall porosity (≥90%) and internal texture of scaffolds. Differential scanning calorimeter (DSC) analysis of these porous scaffolds revealed a gradual reduction in glass transition temperature (Tg) (from 48°C to 42.5°C) with increase in hydrophilic PGA content. The potential applications of these scaffolds as implants were further tested for their biocompatibility and biodegradability in four simulated body fluid (SBF) types in vitro. Whereas, simulated body fluid (SBF) Type1 with the optimal amount of HCO3− ions was found to be more appropriate and sensible for testing the bioactivity of scaffolds. Among three combinations of polymer scaffolds, sample B with a ratio of 75:25 of PLA: PGA showed greater stability in body fluids (pH 7.2) with an optimum degradation rate (9% to 12% approx). X-ray diffractogram also confirmed a thin layer of hydroxyapatite deposition over sample B with all SBF types in vitro. PMID:23885272

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

    PubMed

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

    2013-07-01

    Tissue engineering scaffolds require a controlled pore size and interconnected pore structures to support the host tissue growth. In the present study, three dimensional (3D) hybrid scaffolds of poly lactic acid (PLA) and poly glycolic acid (PGA) were fabricated using solvent casting/particulate leaching. In this case, partially fused NaCl particles were used as porogen (200-300µ) to improve the overall porosity (≥90%) and internal texture of scaffolds. Differential scanning calorimeter (DSC) analysis of these porous scaffolds revealed a gradual reduction in glass transition temperature (Tg) (from 48°C to 42.5°C) with increase in hydrophilic PGA content. The potential applications of these scaffolds as implants were further tested for their biocompatibility and biodegradability in four simulated body fluid (SBF) types in vitro. Whereas, simulated body fluid (SBF) Type1 with the optimal amount of HCO3 (-) ions was found to be more appropriate and sensible for testing the bioactivity of scaffolds. Among three combinations of polymer scaffolds, sample B with a ratio of 75:25 of PLA: PGA showed greater stability in body fluids (pH 7.2) with an optimum degradation rate (9% to 12% approx). X-ray diffractogram also confirmed a thin layer of hydroxyapatite deposition over sample B with all SBF types in vitro. PMID:23885272

  17. Degradation and biocompatibility of porous nano-hydroxyapatite/polyurethane composite scaffold for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Dong, Zhihong; Li, Yubao; Zou, Qin

    2009-04-01

    Porous scaffold containing 30 wt% nano-hydroxyapatite (n-HA) and 70 wt% polyurethane (PU) from castor oil was prepared by a foaming method and investigated by X-ray diffraction (XRD), Fourier transform infrared absorption (FTIR), scanning electron microscopy (SEM) techniques. The results show that n-HA particles disperse homogeneously in the PU matrix. The porous scaffold has not only macropores of 100-800 μm in size but also a lot of micropores on the walls of macropores. The porosity and compressive strength of scaffold are 80% and 271 kPa, respectively. After soaking in simulated body fluid (SBF), hydrolysis and deposition partly occur on the scaffold. The biological evaluation in vitro and in vivo shows that the n-HA/PU scaffold is non-cytotoxic and degradable. The porous structure provides a good microenvironment for cell adherence, growth and proliferation. The n-HA/PU composite scaffold can be satisfied with the basic requirement for tissue engineering, and has the potential to be applied in repair and substitute of human menisci of the knee-joint and articular cartilage.

  18. Synthesis and fabrication of a degradable poly(N-isopropyl acrylamide) scaffold for tissue engineering applications

    PubMed Central

    Galperin, Anna; Long, Thomas J.; Garty, Shai; Ratner, Buddy D.

    2013-01-01

    Biodegradable poly(N-isopropyl acrylamide) (poly-NIPAM) hydrogels with controlled molecular weight of the parent polymer and its degradation products were synthesized by atom transfer radical polymerization in the presence of a polycaprolactone-based di-chlorinated macroinitiator and polycaprolactone dimethacrylate. The phase transition temperature, swelling, hydrolytic degradability, and mechanical properties at 25 and 37°C were explored. A cytocompatibility study showed good NIH3T3 cell response over 5 days culture on the surface of the hydrogels, demonstrated by a consistent increase in cell proliferation detected by an Alamar Blue assay. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide] results suggested that the hydrogels and their degradation products in the concentration range of 1–25 mg/ mL were not cytotoxic to NIH3T3 cells. A sphere-templating technique was utilized to fabricate biodegradable polyNIPAM scaffolds with monodisperse, pore size. Scaffolds with pore diameter of 48 ± 6 μm were loaded with A-10 smooth muscle cells and then warmed to 37°C entrapping cells in pores approximately 40 μm in diameter, a size we have found to be optimal for angiogenesis and biointegration. Due to their degradable nature, tunable molecular weight, highly interconnected morphology, thermally controlled monodisperse pore size, and temperature-induced volume expansion–contraction, the polyNIPAM-based scaffolds developed in this work will be valuable in tissue engineering. PMID:22961921

  19. Culture & differentiation of mesenchymal stem cell into osteoblast on degradable biomedical composite scaffold: In vitro study

    PubMed Central

    Jain, Krishan G.; Mohanty, Sujata; Ray, Alok R.; Malhotra, Rajesh; Airan, Balram

    2015-01-01

    degradable 3D composite may have great potential to be used as scaffold in bone tissue engineering. PMID:26831424

  20. Poly(ε-caprolactone)/nano fluoridated hydroxyapatite scaffolds for bone tissue engineering: in vitro degradation and biocompatibility study.

    PubMed

    Johari, N; Fathi, M H; Golozar, M A; Erfani, E; Samadikuchaksaraei, A

    2012-03-01

    In this study, biodegradation and biocompatibility of novel poly(ε-caparolactone)/nano fluoridated hydroxyapatite (PCL-FHA) scaffolds were investigated. The FHA nanopowders were prepared via mechanical alloying method and had a chemical composition of Ca(10)(PO(4))(6)OH(2-x )F(x) (where x values were selected equal to 0.5 and 2.0). In order to fabricate PCL-FHA scaffolds, 10, 20, 30 and 40 wt% of the FHA were added to the PCL. The PCL-FHA scaffolds were produced by the solvent casting/particulate leaching using sodium chloride particles (with diameters of 300-500 μm) as the porogen. The phase structure, microstructure and morphology of the scaffolds were evaluated using X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy techniques. Porosity of the scaffolds was measured using the Archimedes' Principle. In vitro degradation of PCL-FHA scaffolds was studied by incubating the samples in phosphate buffered saline at 37°C and pH 7.4 for 30 days. Moreover, biocompatibility was evaluated by MTT assay after seeding and culture of osteoblast-like cells on the scaffolds. Results showed that the osteoblast-like cells attached to and proliferated on PCL-FHA and increasing the porosity of the scaffolds increased the cell viability. Also, degradation rate of scaffolds were increased with increasing the fluorine content in scaffolds composition. PMID:22190197

  1. Surfactant tuning of hydrophilicity of porous degradable copolymer scaffolds promotes cellular proliferation and enhances bone formation.

    PubMed

    Yassin, Mohammed A; Leknes, Knut N; Sun, Yang; Lie, Stein A; Finne-Wistrand, Anna; Mustafa, Kamal

    2016-08-01

    Poly(l-lactide-co-ɛ-caprolactone) (poly(LLA-co-CL)) has been blended with Tween 80 to tune the material properties and optimize cell-material interactions. Accordingly, the aims of this study were fourfold: to evaluate the effect of low concentrations of Tween 80 on the surface microstructure of 3D poly(LLA-co-CL) porous scaffolds: to determine the effect of different concentrations of Tween 80 on proliferation of bone marrow stromal cells (BMSCs) in vitro under dynamic cell culture at 7 and 21 days; to assess the influence of Tween 80 on the degradation rate of poly(LLA-co-CL) at 7 and 21 days; and in a subcutaneous rat model, to evaluate the effect on bone formation of porous scaffolds modified with 3% Tween 80 at 2 and 8 weeks. Blending 3% (w/w) Tween 80 with poly(LLA-co-CL) improves the surface wettability (p < 0.001). Poly(LLA-co-CL)/3% Tween 80 shows significantly increased cellular proliferation at days 7 and 21 (p < 0.001). Moreover, the presence of Tween 80 facilitates the degradation of poly(LLA-co-CL). Two weeks post-implantation, the poly(LLA-co-CL)/3% Tween 80 scaffolds exhibit significant mRNA expression of Runx2 (p = 0.004). After 8 weeks, poly(LLA-co-CL)/3% Tween 80 scaffolds show significantly increased de novo bone formation, demonstrated by μ-CT (p = 0.0133) and confirmed histologically. It can be concluded that blending 3% (w/w) Tween 80 with poly (LLA-co-CL) improves the hydrophilicity and osteogenic potential of the scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2049-2059, 2016.

  2. Shape-memory properties and degradation behavior of multifunctional electro-spun scaffolds.

    PubMed

    Kratz, Karl; Habermann, Ronny; Becker, Tino; Richau, Klaus; Lendlein, Andreas

    2011-02-01

    Multifunctional polymer-based biomaterials, which combine degradability and shape-memory capability, are promising candidate materials for the realization of active self-anchoring implants. In this work we explored the shape-memory capability as well as the hydrolytic and enzymatic in vitro degradation behavior of electro-spun scaffolds prepared from a multiblock copolymer, containing hydrolytically degradable poly(p-dioxanone) (PPDO) and poly(e-caprolactone) (PCL) segments, which we have named PDC. Electro-spun PDC scaffolds with an average deposit thickness of 80 ± 20 µm and a porosity in the range from 70% to 80% were prepared, where the single fiber diameter was around 3 µm. Excellent shape-memory properties were achieved with high recovery rate (Rr) values in the range of Rr = 92% to 98% and a recovery stress of smax = 4.6 MPa to 5.0 MPa. The switching temperature (Tsw) and the characteristic temperature obtained under constant strain recovery conditions (Ts,max) were found in the range from 32 °C to 35 °C, which was close to the melting temperature (Tm,PCL) associated to the poly(e-caprolactone) domains. A linear mass loss was observed in both hydrolytic and enzymatic degradation experiments. The mass loss was substantially accelerated, in enzymatic degradation when Pseudomonas cepacia lipase was added, which was reported to accelerate the degradation of PCL. During hydrolytic degradation a continuous decrease in elongation at break (eB) from eB = 800% to 15% was observed in a time period of 92 days, while in enzymatic degradation experiments a complete mechanical failure was obtained after 4 days.

  3. Investigating the morphological, mechanical and degradation properties of scaffolds comprising collagen, gelatin and elastin for use in soft tissue engineering.

    PubMed

    Grover, Chloe N; Cameron, Ruth E; Best, Serena M

    2012-06-01

    Collagen-based scaffolds can be used to mimic the extracellular matrix (ECM) of soft tissues and provide support during tissue regeneration. To better match the native ECM composition and mechanical properties as well as tailor the degradation resistance and available cell binding motifs, other proteins or different collagen types may be added. The present study has explored the use of components such as gelatin or elastin and investigated their effect on the bulk physical properties of the resulting scaffolds compared to those made from pure collagen type I. The effect of altering the composition and crosslinking was evaluated in terms of the scaffold structure, mechanical properties, swelling, degradation and cell attachment. Results demonstrate that scaffolds based on gelatin had reduced tensile stiffness and degradation time compared with collagen. The addition of elastin reduced the overall strength and stiffness of the scaffolds, with electron microscopy results suggesting that insoluble elastin interacts best with collagen and soluble elastin interacts best with gelatin. Carbodiimide crosslinking was essential for structural stability, strength and degradation resistance for scaffolds of all compositions. In addition, preliminary cell adhesion studies showed these highly porous structures (pore size 130-160 μm) to be able to support HT1080 cell infiltration and growth. Therefore, this study suggests that the use of gelatin in place of collagen, with additions of elastin, can tailor the physical properties of scaffolds and could be a design strategy for reducing the overall material costs. PMID:22520419

  4. 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.

  5. Hydrolytically degradable poly(ethylene glycol) hydrogel scaffolds with tunable degradation and mechanical properties

    PubMed Central

    Zustiak, Silviya P.

    2011-01-01

    The objective of this work was to create three-dimensional (3D) hydrogel matrices with defined mechanical properties, as well as tunable degradability for use in applications involving protein delivery and cell encapsulation. Thus, we report the synthesis and characterization of a novel hydrolytically degradable poly(ethylene glycol) (PEG) hydrogel composed of PEG vinyl sulfone (PEG-VS) cross-linked with PEG-diester-dithiol. Unlike previously reported degradable PEG-based hydrogels, these materials are homogeneous in structure, fully hydrophilic and have highly specific cross-linking chemistry. We characterized hydrogel degradation and associated trends in mechanical properties, i.e., storage modulus (G′), swelling ratio (QM), and mesh size (ξ). Degradation time and the monitored mechanical properties of the hydrogel correlated with cross-linker molecular weight, cross-linker functionality, and total polymer density; these properties changed predictably as degradation proceeded (G′ decreased, whereas QM and ξ increased) until the gels reached complete degradation. Balb/3T3 fibroblast adhesion and proliferation within the 3D hydrogel matrices were also verified. In sum, these unique properties indicate that the reported degradable PEG hydrogels are well poised for specific applications in protein and cell delivery to repair soft tissue. PMID:20355705

  6. Comparison of the in vitro and in vivo degradations of silk fibroin scaffolds from mulberry and nonmulberry silkworms.

    PubMed

    You, Renchuan; Xu, Yamei; Liu, Yi; Li, Xiufang; Li, Mingzhong

    2015-02-01

    Degradation behavior is very important in the field of silk-based biomaterials. Mulberry and nonmulberry silk fibroins are structurally and functionally distinguishable; however, no studies have examined the differences in the degradation behaviors of silk materials from various silkworm species. In this study, Ca(NO3)2 was used as a uniform solvent to obtain regenerated mulberry and nonmulberry (Antheraea pernyi and Antheraea yamamai) silk fibroin (SF) solutions, and the degradation behaviors of various SF scaffolds were examined. In vitro and in vivo results demonstrated that regenerated mulberry SF scaffolds exhibited significantly higher mass loss and free amino acid content release than did nonmulberry SF scaffolds. The differences in the primary structures and condensed structures between mulberry and nonmulberry SF contributed to the significant difference in degradation rates, in which the characteristic (-Ala-)n repeats, compact crystal structure and high α-helix and β-sheet contents make nonmulberry SF more resistant than mulberry SF to enzymatic degradation. Moreover, the Antheraea pernyi and Antheraea yamamai SFs possess similar primary structures and condensed structures, although a slight difference in degradation was observed; this difference might depend on the differences in molecular weight following the regeneration process. The results indicate that the original sources of SF significantly influence the degradation rates of SF-based materials; therefore, the original sources of SF should be fully considered for preparing tissue engineering scaffolds with matched degradation rates.

  7. Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. I. Preparation and in vitro degradation.

    PubMed

    Fu, Qiang; Rahaman, Mohamed N; Fu, Hailuo; Liu, Xin

    2010-10-01

    Bioactive glass scaffolds with a microstructure similar to that of dry human trabecular bone but with three different compositions were evaluated for potential applications in bone repair. The preparation of the scaffolds and the effect of the glass composition on the degradation and conversion of the scaffolds to a hydroxyapatite (HA)-type material in a simulated body fluid (SBF) are reported here (Part I). The in vitro response of osteogenic cells to the scaffolds and the in vivo evaluation of the scaffolds in a rat subcutaneous implantation model are described in Part II. Scaffolds (porosity = 78-82%; pore size = 100-500 microm) were prepared using a polymer foam replication technique. The glasses consisted of a silicate (13-93) composition, a borosilicate composition (designated 13-93B1), and a borate composition (13-93B3), in which one-third or all of the SiO2 content of 13-93 was replaced by B2O3, respectively. The conversion rate of the scaffolds to HA in the SBF increased markedly with the B2O3 content of the glass. Concurrently, the pH of the SBF also increased with the B2O3 content of the scaffolds. The compressive strengths of the as-prepared scaffolds (5-11 MPa) were in the upper range of values reported for trabecular bone, but they decreased markedly with immersion time in the SBF and with increasing B2O3 content of the glass. The results show that scaffolds with a wide range of bioactivity and degradation rate can be achieved by replacing varying amounts of SiO(2) in silicate bioactive glass with B2O3.

  8. Factors Controlling Elevated Temperature Strength Degradation of Silicon Carbide Composites

    NASA Technical Reports Server (NTRS)

    2005-01-01

    For 5 years, the cooperative agreement NCC3-763 has focused on the development and understanding of Sic-based composites. Most of the work was performed in the area of SiC fiber-reinforced composites for UEET and NGLT and in collaboration with Goodrich Corporation under a partially reimbursable Space Act Agreement. A smaller amount of work was performed on C fiber-reinforced SiC matrix composites for NGLT. Major accomplishments during this agreement included: Improvements to the interphase used in melt-infiltrated (MI) SiC/SiC composites which increases the life under stressed-oxidation at intermediate temperatures referred to as "outside-debonding". This concept is currently in the patent process and received a Space Act Award. Mechanistic-based models of intermediate temperature degradation for MI SiC/SiC Quantification and relatively robust relationships for matrix crack evolution under stress in SiC/SiC composites which serve as the basis for stress-strain and elevated temperature life models The furthering of acoustic emission as a useful tool in composite damage evolution and the extension of the technique to other composite systems Development of hybrid C-SiC fiber-reinforced SiC matrix composites Numerous presentations at conferences, industry partners, and government centers and publications in recognized proceedings and journals. Other recognition of the author's accomplishments by NASA with a TGIR award (2004), NASA's Medal for Public Service (2004), and The American Ceramic Society s Richard M. Fulrath Award (2005). The following will briefly describe the work of the past five years in the three areas of interest: SiC/SiC composite development, mechanistic understanding and modeling of SiC/SiC composites, and environmental durability of C/SiC composites. More detail can be found in the publications cited at the end of this report.

  9. 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

  10. 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.

  11. Rapid fabrication of poly(DL-lactide) nanofiber scaffolds with tunable degradation for tissue engineering applications by air-brushing

    PubMed Central

    Behrens, Adam M; Kim, Jeffrey; Hotaling, Nathan; Seppala, Jonathan E; Kofinas, Peter; Tutak, Wojtek

    2016-01-01

    Polymer nanofiber based materials have been widely investigated for use as tissue engineering scaffolds. While promising, these materials are typically fabricated through techniques that require significant time or cost. Here we report a rapid and cost effective air-brushing method for fabricating nanofiber scaffolds using a simple handheld apparatus, compressed air, and a polymer solution. Air-brushing also facilities control over the scaffold degradation rate without adversely impacting architecture. This was accomplished through a one step blending process of high (Mw ≈ 100 000 g mol−1) and low (Mw ≈ 25 000 g mol−1) molecular weight poly(DL-lactide) (PDLLA) polymers at various ratios (100:0, 70:30 and 50:50). Through this approach, we were able to control fiber scaffold degradation rate while maintaining similar fiber morphology, scaffold porosity, and bulk mechanical properties across all of the tested compositions. The impact of altered degradation rates was biologically evaluated in human bone marrow stromal cell (hBMSC) cultures for up to 16 days and demonstrated degradation rate dependence of both total DNA concentration and gene regulation. PMID:27121660

  12. Rapid fabrication of poly(DL-lactide) nanofiber scaffolds with tunable degradation for tissue engineering applications by air-brushing.

    PubMed

    Behrens, Adam M; Kim, Jeffrey; Hotaling, Nathan; Seppala, Jonathan E; Kofinas, Peter; Tutak, Wojtek

    2016-01-01

    Polymer nanofiber based materials have been widely investigated for use as tissue engineering scaffolds. While promising, these materials are typically fabricated through techniques that require significant time or cost. Here we report a rapid and cost effective air-brushing method for fabricating nanofiber scaffolds using a simple handheld apparatus, compressed air, and a polymer solution. Air-brushing also facilities control over the scaffold degradation rate without adversely impacting architecture. This was accomplished through a one step blending process of high (M w  ≈  100 000 g mol(-1)) and low (M w  ≈  25 000 g mol(-1)) molecular weight poly(DL-lactide) (PDLLA) polymers at various ratios (100:0, 70:30 and 50:50). Through this approach, we were able to control fiber scaffold degradation rate while maintaining similar fiber morphology, scaffold porosity, and bulk mechanical properties across all of the tested compositions. The impact of altered degradation rates was biologically evaluated in human bone marrow stromal cell (hBMSC) cultures for up to 16 days and demonstrated degradation rate dependence of both total DNA concentration and gene regulation. PMID:27121660

  13. 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

  14. PLA-poloxamer/poloxamine copolymers for ligament tissue engineering: sound macromolecular design for degradable scaffolds and MSC differentiation.

    PubMed

    Leroy, Adrien; Nottelet, Benjamin; Bony, Claire; Pinese, Coline; Charlot, Benoît; Garric, Xavier; Noël, Danièle; Coudane, Jean

    2015-04-01

    The treatment of anterior cruciate ligament (ACL) failures remains a current clinical challenge. The present study aims at providing suitable degradable scaffolds for ligament tissue engineering. First, we focus on the design and the evaluation of poly(lactide)/poloxamer or poly(lactide)/poloxamine multiblock copolymers selected and developed to have suitable degradation and mechanical properties to match ACL repair. In the second part, it is shown that the copolymers can be processed in the form of microfibers and scaffolds consisting of a combination of twisted/braided fibers to further modulate the mechanical properties and prepare scaffold prototypes suitable for ligament application. Finally, after assessment of their cytocompatibility, the polymer scaffolds are associated with mesenchymal stem cells (MSCs). MSC differentiation toward a ligament fibroblast phenotype is promoted by a dual stimulation including an inductive culture medium and cyclic mechanical loads. RT-qPCR analyses confirm the potential of our scaffolds and MSCs for ACL regeneration with upregulation of some differentiation markers including Scleraxis, Tenascin-C and Tenomodulin.

  15. Resilin-PEG Hybrid Hydrogels Yield Degradable Elastomeric Scaffolds with Heterogeneous Microstructure.

    PubMed

    McGann, Christopher L; Akins, Robert E; Kiick, Kristi L

    2016-01-11

    Hydrogels derived from resilin-like polypeptides (RLPs) have shown outstanding mechanical resilience and cytocompatibility; expanding the versatility of RLP-based materials via conjugation with other polypeptides and polymers would offer great promise in the design of a range of materials. Here, we present an investigation of the biochemical and mechanical properties of hybrid hydrogels composed of a recombinant RLP and a multiarm PEG macromer. These hybrid hydrogels can be rapidly cross-linked through a Michael-type addition reaction between the thiols of cysteine residues on the RLP and vinyl sulfone groups on the multiarm PEG. Oscillatory rheology and tensile testing confirmed the formation of elastomeric hydrogels with mechanical resilience comparable to aortic elastin; hydrogel stiffness was easily modulated through the cross-linking ratio. Macromolecular phase separation of the RLP-PEG hydrogels offers the unique advantage of imparting a heterogeneous microstructure, which can be used to localize cells, through simple mixing and cross-linking. Assessment of degradation of the RLP by matrix metalloproteinases (MMPs) illustrated the specific proteolysis of the polypeptide in both its soluble form and when cross-linked into hydrogels. Finally, the successful encapsulation and viable three-dimensional culture of human mesenchymal stem cells (hMSCs) demonstrated the cytocompatibility of the RLP-PEG gels. Overall, the cytocompatibility, elastomeric mechanical properties, microheterogeneity, and degradability of the RLP-PEG hybrid hydrogels offer a suite of promising properties for the development of cell-instructive, structured tissue engineering scaffolds.

  16. Resilin-PEG Hybrid Hydrogels Yield Degradable Elastomeric Scaffolds with Heterogeneous Microstructure.

    PubMed

    McGann, Christopher L; Akins, Robert E; Kiick, Kristi L

    2016-01-11

    Hydrogels derived from resilin-like polypeptides (RLPs) have shown outstanding mechanical resilience and cytocompatibility; expanding the versatility of RLP-based materials via conjugation with other polypeptides and polymers would offer great promise in the design of a range of materials. Here, we present an investigation of the biochemical and mechanical properties of hybrid hydrogels composed of a recombinant RLP and a multiarm PEG macromer. These hybrid hydrogels can be rapidly cross-linked through a Michael-type addition reaction between the thiols of cysteine residues on the RLP and vinyl sulfone groups on the multiarm PEG. Oscillatory rheology and tensile testing confirmed the formation of elastomeric hydrogels with mechanical resilience comparable to aortic elastin; hydrogel stiffness was easily modulated through the cross-linking ratio. Macromolecular phase separation of the RLP-PEG hydrogels offers the unique advantage of imparting a heterogeneous microstructure, which can be used to localize cells, through simple mixing and cross-linking. Assessment of degradation of the RLP by matrix metalloproteinases (MMPs) illustrated the specific proteolysis of the polypeptide in both its soluble form and when cross-linked into hydrogels. Finally, the successful encapsulation and viable three-dimensional culture of human mesenchymal stem cells (hMSCs) demonstrated the cytocompatibility of the RLP-PEG gels. Overall, the cytocompatibility, elastomeric mechanical properties, microheterogeneity, and degradability of the RLP-PEG hybrid hydrogels offer a suite of promising properties for the development of cell-instructive, structured tissue engineering scaffolds. PMID:26646060

  17. Metabolomics reveals elevated macromolecular degradation in periodontal disease.

    PubMed

    Barnes, V M; Ciancio, S G; Shibly, O; Xu, T; Devizio, W; Trivedi, H M; Guo, L; Jönsson, T J

    2011-11-01

    Periodontitis is a chronic inflammatory disease characterized by tissue destruction. In the diseased oral environment, saliva has primarily been considered to act as a protectant by lubricating the tissue, mineralizing the bones, neutralizing the pH, and combating microbes. To understand the metabolic role that saliva plays in the diseased state, we performed untargeted metabolomic profiling of saliva from healthy and periodontitic individuals. Several classes of biochemicals, including dipeptide, amino acid, carbohydrate, lipids, and nucleotide metabolites, were altered, consistent with increased macromolecular degradation of proteins, triacylglycerol, glycerolphospholipids, polysaccharides, and polynucleotides in the individuals with periodontal disease. These changes partially reflected the enhanced host-bacterial interactions in the diseased state as supported by increased levels of bacterially modified amino acids and creatine metabolite. More importantly, the increased lipase, protease, and glycosidase activities associated with periodontitis generated a more favorable energy environment for oral bacteria, potentially exacerbating the disease state. PMID:21856966

  18. Metabolomics reveals elevated macromolecular degradation in periodontal disease.

    PubMed

    Barnes, V M; Ciancio, S G; Shibly, O; Xu, T; Devizio, W; Trivedi, H M; Guo, L; Jönsson, T J

    2011-11-01

    Periodontitis is a chronic inflammatory disease characterized by tissue destruction. In the diseased oral environment, saliva has primarily been considered to act as a protectant by lubricating the tissue, mineralizing the bones, neutralizing the pH, and combating microbes. To understand the metabolic role that saliva plays in the diseased state, we performed untargeted metabolomic profiling of saliva from healthy and periodontitic individuals. Several classes of biochemicals, including dipeptide, amino acid, carbohydrate, lipids, and nucleotide metabolites, were altered, consistent with increased macromolecular degradation of proteins, triacylglycerol, glycerolphospholipids, polysaccharides, and polynucleotides in the individuals with periodontal disease. These changes partially reflected the enhanced host-bacterial interactions in the diseased state as supported by increased levels of bacterially modified amino acids and creatine metabolite. More importantly, the increased lipase, protease, and glycosidase activities associated with periodontitis generated a more favorable energy environment for oral bacteria, potentially exacerbating the disease state.

  19. Degradability, biocompatibility, and osteogenesis of biocomposite scaffolds containing nano magnesium phosphate and wheat protein both in vitro and in vivo for bone regeneration.

    PubMed

    Xia, Yan; Zhou, Panyu; Wang, Fei; Qiu, Chao; Wang, Panfeng; Zhang, Yuntong; Zhao, Liming; Xu, Shuogui

    2016-01-01

    In this study, bioactive scaffold of nano magnesium phosphate (nMP)/wheat protein (WP) composite (MWC) was fabricated. The results revealed that the MWC scaffolds had interconnected not only macropores (sized 400-600 μm) but also micropores (sized 10-20 μm) on the walls of macropores. The MWC scaffolds containing 40 w% nMP had an appropriate degradability in phosphate-buffered saline and produced a weak alkaline microenvironment. In cell culture experiments, the results revealed that the MWC scaffolds significantly promoted the MC3T3-E1 cell proliferation, differentiation, and growth into the scaffolds. The results of synchrotron radiation microcomputed tomography and analysis of the histological sections of the in vivo implantation revealed that the MWC scaffolds evidently improved the new bone formation and bone defects repair as compared with WP scaffolds. Moreover, it was found that newly formed bone tissue continued to increase with the gradual reduction of materials residual in the MWC scaffolds. Furthermore, the immunohistochemical analysis further offered the evidence of the stimulatory effects of MWC scaffolds on osteogenic-related cell differentiation and new bone regeneration. The results indicated that MWC scaffolds with good biocompability and degradability could promote osteogenesis in vivo, which would have potential for bone tissue repair. PMID:27555766

  20. Degradability, biocompatibility, and osteogenesis of biocomposite scaffolds containing nano magnesium phosphate and wheat protein both in vitro and in vivo for bone regeneration

    PubMed Central

    Xia, Yan; Zhou, Panyu; Wang, Fei; Qiu, Chao; Wang, Panfeng; Zhang, Yuntong; Zhao, Liming; Xu, Shuogui

    2016-01-01

    In this study, bioactive scaffold of nano magnesium phosphate (nMP)/wheat protein (WP) composite (MWC) was fabricated. The results revealed that the MWC scaffolds had interconnected not only macropores (sized 400–600 μm) but also micropores (sized 10–20 μm) on the walls of macropores. The MWC scaffolds containing 40 w% nMP had an appropriate degradability in phosphate-buffered saline and produced a weak alkaline microenvironment. In cell culture experiments, the results revealed that the MWC scaffolds significantly promoted the MC3T3-E1 cell proliferation, differentiation, and growth into the scaffolds. The results of synchrotron radiation microcomputed tomography and analysis of the histological sections of the in vivo implantation revealed that the MWC scaffolds evidently improved the new bone formation and bone defects repair as compared with WP scaffolds. Moreover, it was found that newly formed bone tissue continued to increase with the gradual reduction of materials residual in the MWC scaffolds. Furthermore, the immunohistochemical analysis further offered the evidence of the stimulatory effects of MWC scaffolds on osteogenic-related cell differentiation and new bone regeneration. The results indicated that MWC scaffolds with good biocompability and degradability could promote osteogenesis in vivo, which would have potential for bone tissue repair. PMID:27555766

  1. Effect of elevated CO2 on chlorpyriphos degradation and soil microbial activities in tropical rice soil.

    PubMed

    Adak, Totan; Munda, Sushmita; Kumar, Upendra; Berliner, J; Pokhare, Somnath S; Jambhulkar, N N; Jena, M

    2016-02-01

    Impact of elevated CO2 on chlorpyriphos degradation, microbial biomass carbon, and enzymatic activities in rice soil was investigated. Rice (variety Naveen, Indica type) was grown under four conditions, namely, chambered control, elevated CO2 (550 ppm), elevated CO2 (700 ppm) in open-top chambers and open field. Chlorpyriphos was sprayed at 500 g a.i. ha(-1) at maximum tillering stage. Chlorpyriphos degraded rapidly from rice soils, and 88.4% of initially applied chlorpyriphos was lost from the rice soil maintained under elevated CO2 (700 ppm) by day 5 of spray, whereas the loss was 80.7% from open field rice soil. Half-life values of chlorpyriphos under different conditions ranged from 2.4 to 1.7 days with minimum half-life recorded with two elevated CO2 treatments. Increased CO2 concentration led to increase in temperature (1.2 to 1.8 °C) that played a critical role in chlorpyriphos persistence. Microbial biomass carbon and soil enzymatic activities specifically, dehydrogenase, fluorescien diacetate hydrolase, urease, acid phosphatase, and alkaline phosphatase responded positively to elevated CO2 concentrations. Generally, the enzyme activities were highly correlated with each other. Irrespective of the level of CO2, short-term negative influence of chlorpyriphos was observed on soil enzymes till day 7 of spray. Knowledge obtained from this study highlights that the elevated CO2 may negatively influence persistence of pesticide but will have positive effects on soil enzyme activities. PMID:26790432

  2. Effect of elevated CO2 on chlorpyriphos degradation and soil microbial activities in tropical rice soil.

    PubMed

    Adak, Totan; Munda, Sushmita; Kumar, Upendra; Berliner, J; Pokhare, Somnath S; Jambhulkar, N N; Jena, M

    2016-02-01

    Impact of elevated CO2 on chlorpyriphos degradation, microbial biomass carbon, and enzymatic activities in rice soil was investigated. Rice (variety Naveen, Indica type) was grown under four conditions, namely, chambered control, elevated CO2 (550 ppm), elevated CO2 (700 ppm) in open-top chambers and open field. Chlorpyriphos was sprayed at 500 g a.i. ha(-1) at maximum tillering stage. Chlorpyriphos degraded rapidly from rice soils, and 88.4% of initially applied chlorpyriphos was lost from the rice soil maintained under elevated CO2 (700 ppm) by day 5 of spray, whereas the loss was 80.7% from open field rice soil. Half-life values of chlorpyriphos under different conditions ranged from 2.4 to 1.7 days with minimum half-life recorded with two elevated CO2 treatments. Increased CO2 concentration led to increase in temperature (1.2 to 1.8 °C) that played a critical role in chlorpyriphos persistence. Microbial biomass carbon and soil enzymatic activities specifically, dehydrogenase, fluorescien diacetate hydrolase, urease, acid phosphatase, and alkaline phosphatase responded positively to elevated CO2 concentrations. Generally, the enzyme activities were highly correlated with each other. Irrespective of the level of CO2, short-term negative influence of chlorpyriphos was observed on soil enzymes till day 7 of spray. Knowledge obtained from this study highlights that the elevated CO2 may negatively influence persistence of pesticide but will have positive effects on soil enzyme activities.

  3. Degradation characteristics, cell viability and host tissue responses of PDLLA-based scaffold with PRGD and β-TCP nanoparticles incorporation.

    PubMed

    Yi, Jiling; Xiong, Feng; Li, Binbin; Chen, Heping; Yin, Yixia; Dai, Honglian; Li, Shipu

    2016-09-01

    This study is aimed to evaluate the degradation characteristics, cell viability and host tissue responses of PDLLA/PRGD/β-TCP (PRT) composite nerve scaffold, which was fabricated by poly(d, l-lactic acid) (PDLLA), RGD peptide(Gly-Arg-Gly-Asp-Tyr, GRGDY, abbreviated as RGD) modified poly-{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]}(PRGD) and β-tricalcium phosphate (β-TCP). The scaffolds' in vitro degradation behaviors were investigated in detail by analysing changes in weight loss, pH and morphology. Then, the 3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2 -H-tetrazolium bromide (MTT) assay and cell live/dead assay were carried out to assess their cell viability. Moreover, in vivo degradation patterns and host inflammation responses were monitored by subcutaneous implantation of PRT scaffold in rats. Our data showed that, among the tested scaffolds, the PRT scaffold had the best buffering capacity (pH = 6.1-6.3) and fastest degradation rate (12.4%, 8 weeks) during in vitro study, which was contributed by the incorporation of β-TCP nanoparticles. After in vitro and in vivo degradation, the high porosity structure of PRT could be observed using scanning electron microscopy. Meanwhile, the PRT scaffold could significantly promote cell survival. In the PRT scaffold implantation region, less inflammatory cells (especially for neutrophil and lymphocyte) could be detected. These results indicated that the PRT composite scaffold had a good biodegradable property; it could improve cells survival and reduced the adverse host tissue inflammation responses. PMID:27252885

  4. Degradation characteristics, cell viability and host tissue responses of PDLLA-based scaffold with PRGD and β-TCP nanoparticles incorporation.

    PubMed

    Yi, Jiling; Xiong, Feng; Li, Binbin; Chen, Heping; Yin, Yixia; Dai, Honglian; Li, Shipu

    2016-09-01

    This study is aimed to evaluate the degradation characteristics, cell viability and host tissue responses of PDLLA/PRGD/β-TCP (PRT) composite nerve scaffold, which was fabricated by poly(d, l-lactic acid) (PDLLA), RGD peptide(Gly-Arg-Gly-Asp-Tyr, GRGDY, abbreviated as RGD) modified poly-{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]}(PRGD) and β-tricalcium phosphate (β-TCP). The scaffolds' in vitro degradation behaviors were investigated in detail by analysing changes in weight loss, pH and morphology. Then, the 3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2 -H-tetrazolium bromide (MTT) assay and cell live/dead assay were carried out to assess their cell viability. Moreover, in vivo degradation patterns and host inflammation responses were monitored by subcutaneous implantation of PRT scaffold in rats. Our data showed that, among the tested scaffolds, the PRT scaffold had the best buffering capacity (pH = 6.1-6.3) and fastest degradation rate (12.4%, 8 weeks) during in vitro study, which was contributed by the incorporation of β-TCP nanoparticles. After in vitro and in vivo degradation, the high porosity structure of PRT could be observed using scanning electron microscopy. Meanwhile, the PRT scaffold could significantly promote cell survival. In the PRT scaffold implantation region, less inflammatory cells (especially for neutrophil and lymphocyte) could be detected. These results indicated that the PRT composite scaffold had a good biodegradable property; it could improve cells survival and reduced the adverse host tissue inflammation responses.

  5. Multiple Scaffolding Functions of β-Arrestins in the Degradation of G Protein-coupled Receptor Kinase 2*

    PubMed Central

    Nogués, Laura; Salcedo, Alicia; Mayor, Federico; Penela, Petronila

    2011-01-01

    G protein-coupled receptor kinase 2 (GRK2) plays a fundamental role in the regulation of G protein-coupled receptors (GPCRs), and changes in GRK2 expression levels can have an important impact on cell functions. GRK2 is known to be degraded by the proteasome pathway. We have shown previously that β-arrestins participate in enhanced kinase turnover upon GPCR stimulation by facilitating GRK2 phosphorylation by c-Src or by MAPK or by recruiting the Mdm2 E3 ubiquitin ligase to the receptor complex. In this report, we have investigated how such diverse β-arrestin scaffold functions are integrated to modulate GRK2 degradation. Interestingly, we found that in the absence of GPCR activation, β-arrestins do not perform an adaptor role for GRK2/Mdm2 association, but rather compete with GRK2 for direct Mdm2 binding to regulate basal kinase turnover. Upon agonist stimulation, β-arrestins-mediated phosphorylation of GRK2 at serine 670 by MAPK facilitates Mdm2-mediated GRK2 degradation, whereas c-Src-dependent phosphorylation would support the action of an undetermined β-arrestin-recruited ligase in the absence of GPCR activation. The ability of β-arrestins to play different scaffold functions would allow coordination of both Mdm2-dependent and -independent processes aimed at the specific modulation of GRK2 turnover in different signaling contexts. PMID:21081496

  6. 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.

  7. Effect of elevated CO2 on degradation of azoxystrobin and soil microbial activity in rice soil.

    PubMed

    Manna, Suman; Singh, Neera; Singh, V P

    2013-04-01

    An experiment was conducted in open-top chambers (OTC) to study the effect of elevated CO2 (580 ± 20 μmol mol(-1)) on azoxystrobin degradation and soil microbial activities. Results indicated that elevated CO2 did not have any significant effect on the persistence of azoxystrobin in rice-planted soil. The half-life values for the azoxystrobin in rice soils were 20.3 days in control (rice grown at ambient CO2 outdoors), 19.3 days in rice grown under ambient CO2 atmosphere in OTC, and 17.5 days in rice grown under elevated CO2 atmosphere in OTC. Azoxystrobin acid was recovered as the only metabolite of azoxystrobin, but it did not accumulate in the soil/water and was further metabolized. Elevated CO2 enhanced soil microbial biomass (MBC) and alkaline phosphatase activity of soil. Compared with rice grown at ambient CO2 (both outdoors and in OTC), the soil MBC at elevated CO2 increased by twofold. Elevated CO2 did not affect dehydrogenase, fluorescein diacetate, and acid phosphatase activity. Azoxystrobin application to soils, both ambient and elevated CO2, inhibited alkaline phosphates activity, while no effect was observed on other enzymes. Slight increase (1.8-2 °C) in temperature inside OTC did not affect microbial parameters, as similar activities were recorded in rice grown outdoors and in OTC at ambient CO2. Higher MBC in soil at elevated CO2 could be attributed to increased carbon availability in the rhizosphere via plant metabolism and root secretion; however, it did not significantly increase azoxystrobin degradation, suggesting that pesticide degradation was not the result of soil MBC alone. Study suggested that increased CO2 levels following global warming might not adversely affect azoxystrobin degradation. However, global warming is a continuous and cumulative process, therefore, long-term studies are necessary to get more realistic assessment of global warming on fate of pesticide. PMID:22773147

  8. In vitro degradation and fracture toughness of multilayered porous poly(propylene fumarate)/beta-tricalcium phosphate scaffolds.

    PubMed

    Wolfe, Michael S; Dean, David; Chen, Jeffrey E; Fisher, John P; Han, Seungho; Rimnac, Clare M; Mikos, Antonios G

    2002-07-01

    This study investigated the in vitro degradation of poly(propylene fumarate)/beta-tricalcium phosphate (PPF/beta-TCP) scaffolds in pH 7.4 phosphate-buffered saline at 37 degrees C. Scaffold design consisted of three layers: two solid layers about a central layer of porous PPF foam. Solid PPF with molecular weights of 810 and 1450 Da was crosslinked under UV light. PPF foam was prepared by a photocrosslinking, porogen-leaching method with an initial porogen content of 80 wt % and two sizes, 150-300 and 300-500 microm. Comparison of initial and residual weights demonstrated a 14.3 +/- 2.0% loss of mass at 3 weeks and a 16.6 +/- 1.8% loss of mass at 6 weeks. Observed pH values for all constructs remained stable (7.15-7.40) throughout the 3 to 6 weeks. Scanning electron micrographs of these scaffolds revealed some loss of foam material between 3 and 6 weeks; however, foam microarchitecture was intact. Solid PPF fracture toughness was tested for high and low molecular weight PPF, 0.376 +/- 0.004 and 0.134 +/- 0.015 MPa(m)1/2, respectively. These values are roughly one magnitude less than human cortical bone.

  9. A novel porous Fe/Fe-W alloy scaffold with a double-layer structured skeleton: Preparation, in vitro degradability and biocompatibility.

    PubMed

    He, Jin; He, Feng-Li; Li, Da-Wei; Liu, Ya-Li; Yin, Da-Chuan

    2016-06-01

    A novel porous Fe/Fe-W alloy scaffold with a double-layer structured skeleton was prepared for the first time by electrodeposition. The microstructure of the scaffold was analysed by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) and mercury porosimetry. Mechanical property, in vitro degradability and biocompatibility were tested by tensile test, immersion and a cytotoxicity test. The results showed that the scaffolds exhibited a cellular structure that is similar to that of cancellous bone and had a considerably large specific surface area. The skeleton of the scaffolds showed a double-layer structure that was composed of a hollow Fe skeleton wrapped in a thin layer of Fe-W alloy. The tensile strength and the apparent density are close to that of cancellous bone. It was also found that the different surface microstructures showed different effects on in vitro degradability and biocompatibility. In the immersion test, the corrosion rate decreased gradually as the immersion time increased. In the cytotoxicity test, the extraction medium of the pure Fe scaffold showed the lowest cell viability, followed by that of 1.5FeW as a close second. The extraction media of FeW, Fe1.5W and Fe2W were similar, and their cell viability was far above that of the Fe and 1.5FeW scaffolds. The structural style of the scaffolds presented in this paper is potentially useful and applicable to developing degradable scaffolds with a tailored corrosion rate. PMID:26970820

  10. A novel porous Fe/Fe-W alloy scaffold with a double-layer structured skeleton: Preparation, in vitro degradability and biocompatibility.

    PubMed

    He, Jin; He, Feng-Li; Li, Da-Wei; Liu, Ya-Li; Yin, Da-Chuan

    2016-06-01

    A novel porous Fe/Fe-W alloy scaffold with a double-layer structured skeleton was prepared for the first time by electrodeposition. The microstructure of the scaffold was analysed by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) and mercury porosimetry. Mechanical property, in vitro degradability and biocompatibility were tested by tensile test, immersion and a cytotoxicity test. The results showed that the scaffolds exhibited a cellular structure that is similar to that of cancellous bone and had a considerably large specific surface area. The skeleton of the scaffolds showed a double-layer structure that was composed of a hollow Fe skeleton wrapped in a thin layer of Fe-W alloy. The tensile strength and the apparent density are close to that of cancellous bone. It was also found that the different surface microstructures showed different effects on in vitro degradability and biocompatibility. In the immersion test, the corrosion rate decreased gradually as the immersion time increased. In the cytotoxicity test, the extraction medium of the pure Fe scaffold showed the lowest cell viability, followed by that of 1.5FeW as a close second. The extraction media of FeW, Fe1.5W and Fe2W were similar, and their cell viability was far above that of the Fe and 1.5FeW scaffolds. The structural style of the scaffolds presented in this paper is potentially useful and applicable to developing degradable scaffolds with a tailored corrosion rate.

  11. A poly(glycerol sebacate)-coated mesoporous bioactive glass scaffold with adjustable mechanical strength, degradation rate, controlled-release and cell behavior for bone tissue engineering.

    PubMed

    Lin, Dan; Yang, Kai; Tang, Wei; Liu, Yutong; Yuan, Yuan; Liu, Changsheng

    2015-07-01

    Various requirements in the field of tissue engineering have motivated the development of three-dimensional scaffold with adjustable physicochemical properties and biological functions. A series of multiparameter-adjustable mesoporous bioactive glass (MBG) scaffolds with uncrosslinked poly(glycerol sebacate) (PGS) coating was prepared in this article. MBG scaffold was prepared by a modified F127/PU co-templating process and then PGS was coated by a simple adsorption and lyophilization process. Through controlling macropore parameters and PGS coating amount, the mechanical strength, degradation rate, controlled-release and cell behavior of the composite scaffold could be modulated in a wide range. PGS coating successfully endowed MBG scaffold with improved toughness and adjustable mechanical strength covering the bearing range of trabecular bone (2-12MPa). Multilevel degradation rate of the scaffold and controlled-release rate of protein from mesopore could be achieved, with little impact on the protein activity owing to an "ultralow-solvent" coating and "nano-cavity entrapment" immobilization method. In vitro studies indicated that PGS coating promoted cell attachment and proliferation in a dose-dependent manner, without affecting the osteogenic induction capacity of MBG substrate. These results first provide strong evidence that uncrosslinked PGS might also yield extraordinary achievements in traditional MBG scaffold. With the multiparameter adjustability, the composite MBG/PGS scaffolds would have a hopeful prospect in bone tissue engineering. The design considerations and coating method of this study can also be extended to other ceramic-based artificial scaffolds and are expected to provide new thoughts on development of future tissue engineering materials.

  12. Significant degradability enhancement in multilayer coating of polycaprolactone-bioactive glass/gelatin-bioactive glass on magnesium scaffold for tissue engineering applications

    NASA Astrophysics Data System (ADS)

    Yazdimamaghani, Mostafa; Razavi, Mehdi; Vashaee, Daryoosh; Pothineni, Venkata Raveendra; Rajadas, Jayakumar; Tayebi, Lobat

    2015-05-01

    Magnesium (Mg) is a promising candidate to be used in medical products especially as bone tissue engineering scaffolds. The main challenge for using Mg in biomedical applications is its high degradation rate in the body. For this reason, in this study, a multilayer polymeric layer composed of polycaprolactone (PCL) and gelatin (Gel) reinforced with bioactive glass (BaG) particles has been applied on the surface of Mg scaffolds. The materials characteristics of uncoated Mg scaffold, Mg scaffold coated only with PCL-BaG and Mg scaffold coated with PCL-BaG and Gel-BaG have been analyzed and compared in detail. Scanning electron microscope (SEM) equipped with energy dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR) were utilized for microstructural studies. In vitro bioactivity and biodegradation evaluations were carried out by submerging the scaffolds in simulated body fluid (SBF) at pre-determined time points. The results demonstrated that Mg scaffold coated with PCL-BaG and Gel-BaG exhibited significant improvement in biodegradability.

  13. Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. II. In vitro and in vivo biological evaluation.

    PubMed

    Fu, Qiang; Rahaman, Mohamed N; Bal, B Sonny; Bonewald, Lynda F; Kuroki, Keiichi; Brown, Roger F

    2010-10-01

    In Part I, the in vitro degradation of bioactivAR52115e glass scaffolds with a microstructure similar to that of human trabecular bone, but with three different compositions, was investigated as a function of immersion time in a simulated body fluid. The glasses consisted of a silicate (13-93) composition, a borosilicate composition (designated 13-93B1), and a borate composition (13-93B3), in which one-third or all of the SiO2 content of 13-93 was replaced by B2O3, respectively. This work is an extension of Part I, to investigate the effect of the glass composition on the in vitro response of osteogenic MLO-A5 cells to these scaffolds, and on the ability of the scaffolds to support tissue infiltration in a rat subcutaneous implantation model. The results of assays for cell viability and alkaline phosphatase activity showed that the slower degrading silicate 13-93 and borosilicate 13-93B1 scaffolds were far better than the borate 13-93B3 scaffolds in supporting cell proliferation and function. However, all three groups of scaffolds showed the ability to support tissue infiltration in vivo after implantation for 6 weeks. The results indicate that the required bioactivity and degradation rate may be achieved by substituting an appropriate amount of SiO2 in 13-93 glass with B2O3, and that these trabecular glass scaffolds could serve as substrates for the repair and regeneration of contained bone defects.

  14. The scaffold protein Atg11 recruits fission machinery to drive selective mitochondria degradation by autophagy.

    PubMed

    Mao, Kai; Wang, Ke; Liu, Xu; Klionsky, Daniel J

    2013-07-15

    As the cellular power plant, mitochondria play a significant role in homeostasis. To maintain the proper quality and quantity of mitochondria requires both mitochondrial degradation and division. A selective type of autophagy, mitophagy, drives the degradation of excess or damaged mitochondria, whereas division is controlled by a specific fission complex; however, the relationship between these two processes, especially the role of mitochondrial fission during mitophagy, remains unclear. In this study, we report that mitochondrial fission is important for the progression of mitophagy. When mitophagy is induced, the fission complex is recruited to the degrading mitochondria through an interaction between Atg11 and Dnm1; interfering with this interaction severely blocks mitophagy. These data establish a paradigm for selective organelle degradation.

  15. The scaffold protein Atg11 recruits fission machinery to drive selective mitochondria degradation by autophagy

    PubMed Central

    Mao, Kai; Wang, Ke; Liu, Xu; Klionsky, Daniel J.

    2013-01-01

    SUMMARY As the cellular power plant, mitochondria play a significant role in homeostasis. To maintain the proper quality and quantity of mitochondria requires both mitochondrial degradation and division. A selective type of autophagy, mitophagy, drives the degradation of excess or damaged mitochondria, whereas division is controlled by a specific fission complex; however, the relationship between these two processes, especially the role of mitochondrial fission during mitophagy, remains unclear. In this study, we report that mitochondrial fission is important for the progression of mitophagy When mitophagy is induced, the fission complex is recruited to the degrading mitochondria through an interaction between Atg11 and Dnm1; interfering with this interaction severely blocks mitophagy. These data establish a paradigm for selective organelle degradation. PMID:23810512

  16. Tuning tissue growth with scaffold degradation in enzyme-sensitive hydrogels: a mathematical model.

    PubMed

    Akalp, Umut; Bryant, Stephanie J; Vernerey, Franck J

    2016-09-28

    Despite tremendous advances in the field of tissue engineering, a number of obstacles remain that hinder its successful translation to the clinic. One challenge that relates to the use of cells encapsulated in a hydrogel is identifying a hydrogel design that can provide an appropriate environment for cells to successfully synthesize and deposit new matrix molecules while providing a mechanical support that can resist physiological loads at the early stage of implementation. A solution to this problem has been to balance tissue growth and hydrogel degradation. However, identifying this balance is difficult due to the complexity of coupling diffusion, deposition, and degradation mechanisms. Very little is known about the complex behavior of these mechanisms, emphasizing the need for a rigorous mathematical approach that can assist and guide experimental advances. To address this issue, this paper discusses a model for interstitial growth based on mixture theory, that can capture the coupling between cell-mediated hydrogel degradation (i.e., hydrogels containing enzyme-sensitive crosslinks) and the transport of extracellular matrix (ECM) molecules released by encapsulated cells within a hydrogel. Taking cartilage tissue engineering as an example, the model investigates the role of enzymatic degradation on ECM diffusion and its impact on two important outcomes: the extent of ECM transport (and deposition) and the evolution of the hydrogel's mechanical integrity. Numerical results based on finite element analysis show that if properly tuned, enzymatic degradation yields the appearance of a highly localized degradation front propagating away from the cell, which can be immediately followed by a front of growing neotissue. We show that this situation is key to maintaining mechanical properties (e.g., stiffness) while allowing for deposition of new ECM molecules. Overall, our study suggests a hydrogel design that could enable successful tissue engineering (e.g., of

  17. Tuning tissue growth with scaffold degradation in enzyme-sensitive hydrogels: a mathematical model.

    PubMed

    Akalp, Umut; Bryant, Stephanie J; Vernerey, Franck J

    2016-09-28

    Despite tremendous advances in the field of tissue engineering, a number of obstacles remain that hinder its successful translation to the clinic. One challenge that relates to the use of cells encapsulated in a hydrogel is identifying a hydrogel design that can provide an appropriate environment for cells to successfully synthesize and deposit new matrix molecules while providing a mechanical support that can resist physiological loads at the early stage of implementation. A solution to this problem has been to balance tissue growth and hydrogel degradation. However, identifying this balance is difficult due to the complexity of coupling diffusion, deposition, and degradation mechanisms. Very little is known about the complex behavior of these mechanisms, emphasizing the need for a rigorous mathematical approach that can assist and guide experimental advances. To address this issue, this paper discusses a model for interstitial growth based on mixture theory, that can capture the coupling between cell-mediated hydrogel degradation (i.e., hydrogels containing enzyme-sensitive crosslinks) and the transport of extracellular matrix (ECM) molecules released by encapsulated cells within a hydrogel. Taking cartilage tissue engineering as an example, the model investigates the role of enzymatic degradation on ECM diffusion and its impact on two important outcomes: the extent of ECM transport (and deposition) and the evolution of the hydrogel's mechanical integrity. Numerical results based on finite element analysis show that if properly tuned, enzymatic degradation yields the appearance of a highly localized degradation front propagating away from the cell, which can be immediately followed by a front of growing neotissue. We show that this situation is key to maintaining mechanical properties (e.g., stiffness) while allowing for deposition of new ECM molecules. Overall, our study suggests a hydrogel design that could enable successful tissue engineering (e.g., of

  18. 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

  19. Degradation of flubendiamide as affected by elevated CO2, temperature, and carbon mineralization rate in soil.

    PubMed

    Mukherjee, Irani; Das, Shaon Kumar; Kumar, Aman

    2016-10-01

    An experiment was conducted under three levels of atmospheric CO2 [ambient (398 ± 10 μmol mol(-1)), elevated (570 ± 10 μmol mol(-1)) and open condition], three levels of temperature (4, 25, and 40 °C) to study the degradation pattern of flubendiamide in soil and also carbon mineralization in soil. Results of this study revealed that flubendiamide was found to persist longer under outdoor condition (T1/2, 177.0 and 181.1 days) than ambient (T1/2, 168.4 and 172.3 days) and elevated condition (T1/2, 159.3 and 155.3 days) at 1 and 10 μg g(-1) fortification level, respectively. Results also revealed that flubendiamide dissipated faster at 40 °C (T1/2, 189.4 days) than 25 °C (T1/2, 225.3 days). Slower dissipation was recorded at 4 °C (T1/2, 326.3 days). Thus, increased CO2 levels and temperature following global warming might adversely affect flubendiamide degradation in soil. Laboratory study on microbial biomass carbon (MBC) and carbon mineralization (Cmin) in soil revealed that in des-iodo flubendiamide-treated soils, MBC significantly increased up to 45 days and then decreased. Flubendiamide-treated soil showed a non-significantly decreasing trend of soil MBC with time up to the 15th day of incubation and after 15 days significantly decreased up to 90 days of incubation. In des-iodo flubendiamide-treated soil, the evolution of CO2 decreased up to 45 days, which was increased after 45 days up to 90 days. In flubendiamide-treated soil, CO2 evolution decreased up to 30 days and after 45 days, it increased up to 90 days. PMID:27430656

  20. Translating textiles to tissue engineering: Creation and evaluation of microporous, biocompatible, degradable scaffolds using industry relevant manufacturing approaches and human adipose derived stem cells.

    PubMed

    Haslauer, Carla M; Avery, Matthew R; Pourdeyhimi, Behnam; Loboa, Elizabeth G

    2015-07-01

    Polymeric scaffolds have emerged as a means of generating three-dimensional tissues, such as for the treatment of bone injuries and nonunions. In this study, a fibrous scaffold was designed using the biocompatible, degradable polymer poly-lactic acid in combination with a water dispersible sacrificial polymer, EastONE. Fibers were generated via industry relevant, facile scale-up melt-spinning techniques with an islands-in-the-sea geometry. Following removal of EastONE, a highly porous fiber remained possessing 12 longitudinal channels and pores throughout all internal and external fiber walls. Weight loss and surface area characterization confirmed the generation of highly porous fibers as observed via focused ion beam/scanning electron microscopy. Porous fibers were then knit into a three-dimensional scaffold and seeded with human adipose-derived stem cells (hASC). Confocal microscopy images confirmed hASC attachment to the fiber walls and proliferation throughout the knit structure. Quantification of cell-mediated calcium accretion following culture in osteogenic differentiation medium confirmed hASC differentiation throughout the porous constructs. These results suggest incorporation of a sacrificial polymer within islands-in-the-sea fibers generates a highly porous scaffold capable of supporting stem cell viability and differentiation with the potential to generate large three-dimensional constructs for bone regeneration and/or other tissue engineering applications.

  1. Translating Textiles to Tissue Engineering: Creation and Evaluation of Microporous, Biocompatible, Degradable Scaffolds Using Industry Relevant Manufacturing Approaches and Human Adipose Derived Stem Cells

    PubMed Central

    Haslauer, Carla M.; Avery, Matthew R.; Pourdeyhimi, Behnam; Loboa, Elizabeth G.

    2014-01-01

    Polymeric scaffolds have emerged as a means of generating three-dimensional tissues, such as for the treatment of bone injuries and non-unions. In this study, a fibrous scaffold was designed using the biocompatible, degradable polymer poly-lactic acid in combination with a water dispersible sacrificial polymer, EastONE. Fibers were generated via industry relevant, facile scale-up melt-spinning techniques with an islands-in-the-sea geometry. Following removal of EastONE, a highly porous fiber remained possessing 12 longitudinal channels and pores throughout all internal and external fiber walls. Weight loss and surface area characterization confirmed the generation of highly porous fibers as observed via focused ion beam/scanning electron microscopy. Porous fibers were then knit into a three-dimensional scaffold and seeded with human adipose-derived stem cells (hASC). Confocal microscopy images confirmed hASC attachment to the fiber walls and proliferation throughout the knit structure. Quantification of cell-mediated calcium accretion following culture in osteogenic differentiation medium confirmed hASC differentiation throughout the porous constructs. These results suggest incorporation of a sacrificial polymer within islands-in-the-sea fibers generates a highly porous scaffold capable of supporting stem cell viability and differentiation with the potential to generate large three-dimensional constructs for bone regeneration and/or other tissue engineering applications. PMID:25229198

  2. 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.

  3. Degradation kinetics of the main carbohydrates in birch wood during hot water extraction in a batch reactor at elevated temperatures.

    PubMed

    Borrega, Marc; Nieminen, Kaarlo; Sixta, Herbert

    2011-11-01

    Hot water extraction of wood at elevated temperatures may be a suitable method to produce hemicellulose-lean pulps and to recover xylan-derived products from the water extract. In this study, water extractions of birch wood were conducted at temperatures between 180 and 240 °C in a batch reactor. Xylan was extensively removed, whereas cellulose was partly degraded only at temperatures above 180 °C. Under severe extraction conditions, acetic acid content in the water extract was higher than the corresponding amount of acetyl groups in wood. In addition to oligo- and monosaccharides, considerable amounts of furfural and 5-hydroxymethylfurfural (HMF) were recovered from the extracts. After reaching a maximum, the furfural yield remained constant with increasing extraction time. This maximum slightly decreased with increasing extraction temperature, suggesting the preferential formation of secondary degradation products from xylose. Kinetic models fitting experimental data are proposed to explain degradation and conversion reactions of xylan and glucan.

  4. Responses of Aromatic-Degrading Microbial Communities to Elevated Nitrate in Sediments.

    PubMed

    Xu, Meiying; He, Zhili; Zhang, Qin; Liu, Jin; Guo, Jun; Sun, Guoping; Zhou, Jizhong

    2015-10-20

    A high number of aromatic compounds that have been released into aquatic ecosystems have accumulated in sediment because of their low solubility and high hydrophobicity, causing significant hazards to the environment and human health. Since nitrate is an essential nitrogen component and a more thermodynamically favorable electron acceptor for anaerobic respiration, nitrate-based bioremediation has been applied to aromatic-contaminated sediments. However, few studies have focused on the response of aromatic-degrading microbial communities to nitrate addition in anaerobic sediments. Here we hypothesized that high nitrate inputs would stimulate aromatic-degrading microbial communities and their associated degrading processes, thus increasing the bioremediation efficiency in aromatic compound-contaminated sediments. We analyzed the changes of key aromatic-degrading genes in the sediment samples from a field-scale site for in situ bioremediation of an aromatic-contaminated creek in the Pearl River Delta before and after nitrate injection using a functional gene array. Our results showed that the genes involved in the degradation of several kinds of aromatic compounds were significantly enriched after nitrate injection, especially those encoding enzymes for central catabolic pathways of aromatic compound degradation, and most of the enriched genes were derived from nitrate-reducing microorganisms, possibly accelerating bioremediation of aromatic-contaminated sediments. The sediment nitrate concentration was found to be the predominant factor shaping the aromatic-degrading microbial communities. This study provides new insights into our understanding of the influences of nitrate addition on aromatic-degrading microbial communities in sediments. PMID:26390227

  5. Responses of Aromatic-Degrading Microbial Communities to Elevated Nitrate in Sediments.

    PubMed

    Xu, Meiying; He, Zhili; Zhang, Qin; Liu, Jin; Guo, Jun; Sun, Guoping; Zhou, Jizhong

    2015-10-20

    A high number of aromatic compounds that have been released into aquatic ecosystems have accumulated in sediment because of their low solubility and high hydrophobicity, causing significant hazards to the environment and human health. Since nitrate is an essential nitrogen component and a more thermodynamically favorable electron acceptor for anaerobic respiration, nitrate-based bioremediation has been applied to aromatic-contaminated sediments. However, few studies have focused on the response of aromatic-degrading microbial communities to nitrate addition in anaerobic sediments. Here we hypothesized that high nitrate inputs would stimulate aromatic-degrading microbial communities and their associated degrading processes, thus increasing the bioremediation efficiency in aromatic compound-contaminated sediments. We analyzed the changes of key aromatic-degrading genes in the sediment samples from a field-scale site for in situ bioremediation of an aromatic-contaminated creek in the Pearl River Delta before and after nitrate injection using a functional gene array. Our results showed that the genes involved in the degradation of several kinds of aromatic compounds were significantly enriched after nitrate injection, especially those encoding enzymes for central catabolic pathways of aromatic compound degradation, and most of the enriched genes were derived from nitrate-reducing microorganisms, possibly accelerating bioremediation of aromatic-contaminated sediments. The sediment nitrate concentration was found to be the predominant factor shaping the aromatic-degrading microbial communities. This study provides new insights into our understanding of the influences of nitrate addition on aromatic-degrading microbial communities in sediments.

  6. Protection of scaffold protein Isu from degradation by the Lon protease Pim1 as a component of Fe–S cluster biogenesis regulation

    PubMed Central

    Ciesielski, Szymon J.; Schilke, Brenda; Marszalek, Jaroslaw; Craig, Elizabeth A.

    2016-01-01

    Iron–sulfur (Fe–S) clusters, essential protein cofactors, are assembled on the mitochondrial scaffold protein Isu and then transferred to recipient proteins via a multistep process in which Isu interacts sequentially with multiple protein factors. This pathway is in part regulated posttranslationally by modulation of the degradation of Isu, whose abundance increases >10-fold upon perturbation of the biogenesis process. We tested a model in which direct interaction with protein partners protects Isu from degradation by the mitochondrial Lon-type protease. Using purified components, we demonstrated that Isu is indeed a substrate of the Lon-type protease and that it is protected from degradation by Nfs1, the sulfur donor for Fe–S cluster assembly, as well as by Jac1, the J-protein Hsp70 cochaperone that functions in cluster transfer from Isu. Nfs1 and Jac1 variants known to be defective in interaction with Isu were also defective in protecting Isu from degradation. Furthermore, overproduction of Jac1 protected Isu from degradation in vivo, as did Nfs1. Taken together, our results lead to a model of dynamic interplay between a protease and protein factors throughout the Fe–S cluster assembly and transfer process, leading to up-regulation of Isu levels under conditions when Fe–S cluster biogenesis does not meet cellular demands. PMID:26842892

  7. The effects of different crossing-linking conditions of genipin on type I collagen scaffolds: an in vitro evaluation.

    PubMed

    Zhang, Xiujie; Chen, Xueying; Yang, Ting; Zhang, Naili; Dong, Li; Ma, Shaoying; Liu, Xiaoming; Zhou, Mo; Li, Baoxing

    2014-12-01

    The purpose of this paper is to analyze the properties of fabricating rat tail type I collagen scaffolds cross-linked with genipin under different conditions. The porous genipin cross-linked scaffolds are obtained through a two step freeze-drying process. To find out the optimal cross-link condition, we used different genipin concentrations and various cross-linked temperatures to prepare the scaffolds in this study. The morphologies of the scaffolds were characterized by scanning electron microscope, and the mechanical properties of the scaffolds were evaluated under dynamic compression. Additionally, the cross-linking degree was assessed by ninhydrin assay. To investigate the swelling ratio and the in vitro degradation of the collagen scaffold, the tests were also carried out by immersion of the scaffolds in a PBS solution or digestion in a type I collagenase respectively. The morphologies of the non-cross-linked scaffolds presented a lattice-like structure while the cross-linked ones displayed a sheet-like framework. The morphology of the genipin cross-linked scaffolds could be significantly changed by either increasing genipin concentration or the temperature. The swelling ratio of each cross-linked scaffold was much lower than that of the control (non-cross-linked).The ninhydrin assay demonstrated that the higher temperature and genipin concentration could obviously increase the cross-linking efficiency. The in vitro degradation studies indicated that genipin cross-linking can effectively elevate the biostability of the scaffolds. The biocompatibility and cytotoxicity of the scaffolds was evaluated by culturing rat chondrocytes on the scaffold in vitro and by MTT. The results of MTT and the fact that the chondrocytes adhered well to the scaffolds demonstrated that genipin cross-linked scaffolds possessed an excellent biocompatibility and low cytotoxicity. Based on these results, 0.3 % genipin concentrations and 37 °C cross-linked temperatures are

  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. Metabolic effects of elevated temperature on organic acid degradation in ripening Vitis vinifera fruit

    PubMed Central

    Sweetman, C.; Sadras, V. O.; Hancock, R. D.; Soole, K. L.; Ford, C. M.

    2014-01-01

    Berries of the cultivated grapevine Vitis vinifera are notably responsive to temperature, which can influence fruit quality and hence the future compatibility of varieties with their current growing regions. Organic acids represent a key component of fruit organoleptic quality and their content is significantly influenced by temperature. The objectives of this study were to (i) manipulate thermal regimes to realistically capture warming-driven reduction of malate content in Shiraz berries, and (ii) investigate the mechanisms behind temperature-sensitive malate loss and the potential downstream effects on berry metabolism. In the field we compared untreated controls at ambient temperature with longer and milder warming (2–4 °C differential for three weeks; Experiment 1) or shorter and more severe warming (4–6 °C differential for 11 days; Experiment 2). We complemented field trials with control (25/15 °C) and elevated (35/20 °C) day/night temperature controlled-environment trials using potted vines (Experiment 3). Elevating maximum temperatures (4–10 °C above controls) during pre-véraison stages led to higher malate content, particularly with warmer nights. Heating at véraison and ripening stages reduced malate content, consistent with effects typically seen in warm vintages. However, when minimum temperatures were also raised by 4–6 °C, malate content was not reduced, suggesting that the regulation of malate metabolism differs during the day and night. Increased NAD-dependent malic enzyme activity and decreased phosphoenolpyruvate carboxylase and pyruvate kinase activities, as well as the accumulation of various amino acids and γ-aminobutyric acid, suggest enhanced anaplerotic capacity of the TCA cycle and a need for coping with decreased cytosolic pH in heated fruit. PMID:25180109

  10. Metabolic effects of elevated temperature on organic acid degradation in ripening Vitis vinifera fruit.

    PubMed

    Sweetman, C; Sadras, V O; Hancock, R D; Soole, K L; Ford, C M

    2014-11-01

    Berries of the cultivated grapevine Vitis vinifera are notably responsive to temperature, which can influence fruit quality and hence the future compatibility of varieties with their current growing regions. Organic acids represent a key component of fruit organoleptic quality and their content is significantly influenced by temperature. The objectives of this study were to (i) manipulate thermal regimes to realistically capture warming-driven reduction of malate content in Shiraz berries, and (ii) investigate the mechanisms behind temperature-sensitive malate loss and the potential downstream effects on berry metabolism. In the field we compared untreated controls at ambient temperature with longer and milder warming (2-4 °C differential for three weeks; Experiment 1) or shorter and more severe warming (4-6 °C differential for 11 days; Experiment 2). We complemented field trials with control (25/15 °C) and elevated (35/20 °C) day/night temperature controlled-environment trials using potted vines (Experiment 3). Elevating maximum temperatures (4-10 °C above controls) during pre-véraison stages led to higher malate content, particularly with warmer nights. Heating at véraison and ripening stages reduced malate content, consistent with effects typically seen in warm vintages. However, when minimum temperatures were also raised by 4-6 °C, malate content was not reduced, suggesting that the regulation of malate metabolism differs during the day and night. Increased NAD-dependent malic enzyme activity and decreased phosphoenolpyruvate carboxylase and pyruvate kinase activities, as well as the accumulation of various amino acids and γ-aminobutyric acid, suggest enhanced anaplerotic capacity of the TCA cycle and a need for coping with decreased cytosolic pH in heated fruit.

  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. Bone regeneration in a massive rat femur defect through endochondral ossification achieved with chondrogenically differentiated MSCs in a degradable scaffold.

    PubMed

    Harada, Noriko; Watanabe, Yoshinobu; Sato, Kenji; Abe, Satoshi; Yamanaka, Katsuyuki; Sakai, Yuhiro; Kaneko, Tadashi; Matsushita, Takashi

    2014-09-01

    Mesenchymal stem cells (MSCs) are multipotent cells capable of proliferating and differentiating into several lineages. In regenerative medicine, their potential as a resource for tissue-replacement therapy is receiving much attention. However, transplanting MSCs to repair larger bone defects in animal models has so far proved disappointing. Here we report on the healing of both critical-sized (5 mm) and massive (15 mm) full-thickness femur defects in rats by implanting a uniquely fabricated PLGA scaffold seeded with MSCs pre-differentiated in vitro into cartilage-forming chondrocytes (MSC-DCs). This strategy closely mimics endochondral ossification, the process by which long bones develop in nature. It is thought that because the transplanted MSC-DCs induced natural bone formation, the defect size was not critical to the outcome. Crucially, after 8 weeks the mean biomechanical strength of femora with the massive 15 mm implant reached 75% that of a normal rat femur, while in the case of 5 mm implants there was no significant difference. Successful healing was also highly reproducible, with bone union occurring in all treated animals examined radiologically 8 or 16 weeks after surgery.

  13. Effect of cyclic strain on tensile properties of a naturally derived, decellularized tendon scaffold seeded with allogeneic tenocytes and associated messenger RNA expression.

    PubMed

    Whitlock, Patrick W; Seyler, Thorsten M; Northam, Casey N; Smith, Thomas L; Poehling, Gary G; Koman, L Andrew; Van Dyke, Mark E

    2013-01-01

    Naturally derived tendon scaffolds have the potential to improve the treatment of flexor tendon injuries. Seeded and unseeded tendon scaffolds were maintained in the presence or absence of physiologic strain for 7 days. After 7 days, the tensile properties and associated messenger RNA expression were compared. Seeded scaffolds maintained in the absence of strain had significantly lower tensile properties than unseeded tendons and fresh-frozen tendons. The loss of tensile properties was associated with elevated matrix metalloproteinase-2 and collagen III expression. Tensile properties of seeded scaffolds maintained in the presence of strain for 7 days after seeding did not differ from those of fresh-frozen tendons. This study demonstrates that the tensile properties of seeded, naturally derived tendon scaffolds will degrade rapidly in the absence of cyclic strain. Seeded scaffolds used for tendon reconstruction should be maintained under cyclic strain to maintain essential tensile properties.

  14. Degradation studies of 1, 6-diisocyanatohexane-extended poly (1, 4-butylene succinate) - bioactive glass scaffolds for bone tissue repair applications

    NASA Astrophysics Data System (ADS)

    Kaur, Kulwinder; Singh, K. J.; Anand, Vikas

    2016-05-01

    Bio composite scaffolds prepared from polymer and bio glass provide necessary sites for bone tissue regeneration. In the presented work, bioactive glass scaffolds have been prepared from 1, 6-diisocyanatohexane-extended poly (1, 4-butylene succinate) with different amount of bioactive glass powder by solvent casting method. Prepared scaffolds have been characterized by XRD, FTIR and FESEM techniques. Effect of content of bioactive glass on biodegradability has been investigated in detail.

  15. Biocompatibility and Structural Features of Biodegradable Polymer Scaffolds.

    PubMed

    Nasonova, M V; Glushkova, T V; Borisov, V V; Velikanova, E A; Burago, A Yu; Kudryavtseva, Yu A

    2015-11-01

    We performed a comparative analysis of physicochemical properties and biocompatibility of scaffolds of different composition on the basis of biodegradable polymers fabricated by casting and electrospinning methods. For production of polyhydroxyalkanoate-based scaffolds by electrospinning method, the optimal concentration of the polymer was 8-10%. Fiber diameter and properties of the scaffold produced by electrospinning method depended on polymer composition. Addition of polycaprolactone increased elasticity of the scaffolds. Bio- and hemocompatibility of the scaffolds largely depended on the composition formulation and method of scaffold fabrication. Polylactide introduced into the composition of polyhydroxybutyrate-oxyvalerate scaffolds accelerated degradation and increased adhesive properties of the scaffolds. PMID:26608377

  16. Solvent/Non-Solvent Sintering To Make Microsphere Scaffolds

    NASA Technical Reports Server (NTRS)

    Laurencin, Cato T.; Brown, Justin L.; Nair, Lakshmi

    2011-01-01

    A solvent/non-solvent sintering technique has been devised for joining polymeric microspheres to make porous matrices for use as drug-delivery devices or scaffolds that could be seeded with cells for growing tissues. Unlike traditional sintering at elevated temperature and pressure, this technique is practiced at room temperature and pressure and, therefore, does not cause thermal degradation of any drug, protein, or other biochemical with which the microspheres might be loaded to impart properties desired in a specific application. Also, properties of scaffolds made by this technique are more reproducible than are properties of comparable scaffolds made by traditional sintering. The technique involves the use of two miscible organic liquids: one that is and one that is not a solvent for the affected polymer. The polymeric microspheres are placed in a mold having the size and shape of the desired scaffold, then the solvent/non-solvent mixture is poured into the mold to fill the void volume between the microspheres, then the liquid mixture is allowed to evaporate. Some of the properties of the resulting scaffold can be tailored through choice of the proportions of the liquids and the diameter of the microspheres.

  17. 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…

  18. Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.

    PubMed

    Shen, Yue; Yang, Shizhou; Liu, Jianli; Xu, Huazi; Shi, Zhongli; Lin, Zhongqing; Ying, Xiaozhou; Guo, Peng; Lin, Tiao; Yan, Shigui; Huang, Qing; Peng, Lei

    2014-08-13

    Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration. PMID:25033438

  19. Engineering scaffolds integrated with calcium sulfate and oyster shell for enhanced bone tissue regeneration.

    PubMed

    Shen, Yue; Yang, Shizhou; Liu, Jianli; Xu, Huazi; Shi, Zhongli; Lin, Zhongqing; Ying, Xiaozhou; Guo, Peng; Lin, Tiao; Yan, Shigui; Huang, Qing; Peng, Lei

    2014-08-13

    Engineering scaffolds combinging natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. In this study, novel bioactive calcium sulfate/oyster shell (CS/OS) composites were prepared. Comparing to CS scaffold, the CS/OS composites with a controllable degradation rate displayed enhanced mineral nodule formation, higher alkaline phosphate (ALP) activity and increased proliferation rate while treated osteocytes. In CS/OS composites group, elevated mRNA levels of key osteogenic genes including bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (Runx2), osterix (Osx), and osteocalcin (OCN) were observed. Furthermore, The up-regulation of BMP-2 and type I collagen (COL-I) was observed for CS/OS composites relative to a CS group. Scaffolds were implanted into critical-sized femur cavity defects in rabbits to investigate the osteogenic capacity of the composites in vivo. The CS/OS scaffolds with proper suitable times and mechanical strength strongly promoted osteogenic tissue regeneration relative to the regeneration capacity of CS scaffolds, as indicated by the results of histological staining. These results suggest that the OS-modified CS engineering scaffolds with improved mechanical properties and bioactivity would facilitate the development of a new strategy for clinic bone defect regeneration.

  20. The use of UAV to document sloping landscapes to produce digital elevation models to examine environmental degradation

    NASA Astrophysics Data System (ADS)

    Themistocleous, K.; Agapiou, A.; Papadavid, G.; Christoforou, M.; Hadjimitsis, D. G.

    2015-10-01

    This paper focuses on the use of Unmanned Aerial Vehicles (UAVs) over the study area of Pissouri in Cyprus to document the sloping landscapes of the area. The study area has been affected by overgrazing, which has led to shifts in the vegetation patterns and changing microtopography of the soil. The UAV images were used to generate digital elevation models (DEMs) to examine the changes in microtopography. Next to that orthophotos were used to detect changes in vegetation patterns. The combined data of the digital elevation models and the orthophotos will be used to detect the occurrence of catastrophic shifts and mechanisms for desertification in the study area due to overgrazing. This study is part of the "CASCADE- Catastrophic shifts in dryland" project.

  1. Evaluation of biodegradable elastic scaffolds made of anionic polyurethane for cartilage tissue engineering.

    PubMed

    Tsai, Meng-Chao; Hung, Kun-Che; Hung, Shih-Chieh; Hsu, Shan-hui

    2015-01-01

    Biodegradable polyurethane (PU) was synthesized by a water-based process. The process rendered homogenous PU nanoparticles (NPs). Spongy PU scaffolds in large dimensions were obtained by freeze-drying the PU NP dispersion. The spongy scaffolds were characterized in terms of the porous structure, wettability, mechanical properties, degradation behavior, and degradation products. The capacity as cartilage tissue engineering scaffolds was evaluated by growing chondrocytes and mesenchymal stem cells (MSCs) in the scaffolds. Scaffolds made from the PU dispersion had excellent hydrophilicity, porosity, and water absorption. Examination by micro-computed tomography confirmed that PU scaffolds had good pore interconnectivity. The degradation rate of the scaffolds in phosphate buffered saline was much faster than that in papain solution or in deionized water at 37°C. The biodegradable PU appeared to be degraded via the cleavage of ester linkage The intrinsic elastic property of PU and the gyroid-shape porous structure of the scaffolds may have accounted for the outstanding strain recovery (87%) and elongation behavior (257%) of the PU scaffolds, compared to conventional poly(d,l-lactide) (PLA) scaffolds. Chondrocytes were effectively seeded in PU scaffolds without pre-wetting. They grew better and secreted more glycosaminoglycan in PU scaffolds vs. PLA scaffolds. Human MSCs showed greater chondrogenic gene expression in PU scaffolds than in PLA scaffolds after induction. Based on the favorable hydrophilicity, elasticity, and regeneration capacities, the novel biodegradable PU scaffolds may be superior to the conventional biodegradable scaffolds in cartilage tissue engineering applications.

  2. Evaluation of biodegradable elastic scaffolds made of anionic polyurethane for cartilage tissue engineering.

    PubMed

    Tsai, Meng-Chao; Hung, Kun-Che; Hung, Shih-Chieh; Hsu, Shan-hui

    2015-01-01

    Biodegradable polyurethane (PU) was synthesized by a water-based process. The process rendered homogenous PU nanoparticles (NPs). Spongy PU scaffolds in large dimensions were obtained by freeze-drying the PU NP dispersion. The spongy scaffolds were characterized in terms of the porous structure, wettability, mechanical properties, degradation behavior, and degradation products. The capacity as cartilage tissue engineering scaffolds was evaluated by growing chondrocytes and mesenchymal stem cells (MSCs) in the scaffolds. Scaffolds made from the PU dispersion had excellent hydrophilicity, porosity, and water absorption. Examination by micro-computed tomography confirmed that PU scaffolds had good pore interconnectivity. The degradation rate of the scaffolds in phosphate buffered saline was much faster than that in papain solution or in deionized water at 37°C. The biodegradable PU appeared to be degraded via the cleavage of ester linkage The intrinsic elastic property of PU and the gyroid-shape porous structure of the scaffolds may have accounted for the outstanding strain recovery (87%) and elongation behavior (257%) of the PU scaffolds, compared to conventional poly(d,l-lactide) (PLA) scaffolds. Chondrocytes were effectively seeded in PU scaffolds without pre-wetting. They grew better and secreted more glycosaminoglycan in PU scaffolds vs. PLA scaffolds. Human MSCs showed greater chondrogenic gene expression in PU scaffolds than in PLA scaffolds after induction. Based on the favorable hydrophilicity, elasticity, and regeneration capacities, the novel biodegradable PU scaffolds may be superior to the conventional biodegradable scaffolds in cartilage tissue engineering applications. PMID:25460599

  3. Hybrid Macro-Porous Titanium Ornamented by Degradable 3D Gel/nHA Micro-Scaffolds for Bone Tissue Regeneration

    PubMed Central

    Yin, Bo; Ma, Pei; Chen, Jun; Wang, Hai; Wu, Gui; Li, Bo; Li, Qiang; Huang, Zhifeng; Qiu, Guixing; Wu, Zhihong

    2016-01-01

    Porous titanium is a kind of promising material for bone substitution, while its bio-inert property results in demand of modifications to improve the osteointegration capacity. In this study, gelatin (Gel) and nano-hydroxyapatite (nHA) were used to construct 3D micro-scaffolds in the pores of porous titanium in the ratios of Gel:nHA = 1:0, Gel:nHA = 1:1, and Gel:nHA = 1:3, respectively. Cell attachment and proliferation, and gene and protein expression levels of osteogenic markers were evaluated in MC3T3-E1 cells, followed by bone regeneration assessment in a rabbit radius defect model. All hybrid scaffolds with different composition ratio were found to have significant promotional effects in cell adhesion, proliferation and differentiation, in which the group with Gel:nHA = 1:1 showed the best performance in vitro, as well as the most bone regeneration volume in vivo. This 3D micro-scaffolds modification may be an innovative method for porous titanium ornamentation and shows potential application values in clinic. PMID:27092492

  4. Hybrid Macro-Porous Titanium Ornamented by Degradable 3D Gel/nHA Micro-Scaffolds for Bone Tissue Regeneration.

    PubMed

    Yin, Bo; Ma, Pei; Chen, Jun; Wang, Hai; Wu, Gui; Li, Bo; Li, Qiang; Huang, Zhifeng; Qiu, Guixing; Wu, Zhihong

    2016-04-15

    Porous titanium is a kind of promising material for bone substitution, while its bio-inert property results in demand of modifications to improve the osteointegration capacity. In this study, gelatin (Gel) and nano-hydroxyapatite (nHA) were used to construct 3D micro-scaffolds in the pores of porous titanium in the ratios of Gel:nHA = 1:0, Gel:nHA = 1:1, and Gel:nHA = 1:3, respectively. Cell attachment and proliferation, and gene and protein expression levels of osteogenic markers were evaluated in MC3T3-E1 cells, followed by bone regeneration assessment in a rabbit radius defect model. All hybrid scaffolds with different composition ratio were found to have significant promotional effects in cell adhesion, proliferation and differentiation, in which the group with Gel:nHA = 1:1 showed the best performance in vitro, as well as the most bone regeneration volume in vivo. This 3D micro-scaffolds modification may be an innovative method for porous titanium ornamentation and shows potential application values in clinic.

  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. Evident elevation of atmospheric monoterpenes due to degradation-induced species changes in a semi-arid grassland.

    PubMed

    Wang, Hongjun; Wang, Xinming; Zhang, Yanli; Mu, Yujing; Han, Xingguo

    2016-01-15

    Biogenic volatile organic compounds (BVOCs) emitted from plants have substantial effects on atmospheric chemistry/physics and feedbacks on ecosystem function. The on-going climate change and anthropogenic disturbance have been confirmed to cause the evident degradation of grassland with shift of plant community, and hence BVOCs emissions were suspected to be altered due to the different BOVCs emission potentials of different species. In this study, we investigated BVOCs concentration above ground surface during growing season in a degraded semi-arid grassland (41°2' N-45°6' N, 113°5'-117°8') in Inner Mongolia. The observed monoterpenes' concentrations varied from 0.10 to 215.78 μg m(-3) (34.88 ± 9.73 μg m(-3) in average) across 41 sites. Compared to non-degraded grassland, concentrations of monoterpenes were about 180 times higher at the sites dominated by subshrub--Artemisia frigida, a preponderant species under drought stress and over-grazing. The biomass of A. frigida explained 51.39% of the variation of monoterpenes' concentrations. α-pinene, β-pinene and γ-terpinene dominated in the 10 determined monoterpenes, accounting for 37.72 ± 2.98%, 14.65 ± 2.55% and 10.50 ± 2.37% of the total monoterpenes concentration, respectively. Low isoprene concentrations (≤ 3.25 μg m(-3)) were found and sedge biomass contributed about 51.76% to their spatial variation. α-pinene and isoprene emissions at noon were as high as 515.53 ± 88.34 μg m(-2)h(-1) and 7606.19 ± 1073.94 μg m(-2) h(-1) in A. frigida- and sedge-dominated areas where their biomass were 236.90 g m(-2) and 72.37 g m(-2), respectively. Our results suggested that the expansion of A. frigida and sedge caused by over-grazing and climatic stresses may increase local ambient BVOCs concentration in grassland. PMID:26490529

  8. Evident elevation of atmospheric monoterpenes due to degradation-induced species changes in a semi-arid grassland.

    PubMed

    Wang, Hongjun; Wang, Xinming; Zhang, Yanli; Mu, Yujing; Han, Xingguo

    2016-01-15

    Biogenic volatile organic compounds (BVOCs) emitted from plants have substantial effects on atmospheric chemistry/physics and feedbacks on ecosystem function. The on-going climate change and anthropogenic disturbance have been confirmed to cause the evident degradation of grassland with shift of plant community, and hence BVOCs emissions were suspected to be altered due to the different BOVCs emission potentials of different species. In this study, we investigated BVOCs concentration above ground surface during growing season in a degraded semi-arid grassland (41°2' N-45°6' N, 113°5'-117°8') in Inner Mongolia. The observed monoterpenes' concentrations varied from 0.10 to 215.78 μg m(-3) (34.88 ± 9.73 μg m(-3) in average) across 41 sites. Compared to non-degraded grassland, concentrations of monoterpenes were about 180 times higher at the sites dominated by subshrub--Artemisia frigida, a preponderant species under drought stress and over-grazing. The biomass of A. frigida explained 51.39% of the variation of monoterpenes' concentrations. α-pinene, β-pinene and γ-terpinene dominated in the 10 determined monoterpenes, accounting for 37.72 ± 2.98%, 14.65 ± 2.55% and 10.50 ± 2.37% of the total monoterpenes concentration, respectively. Low isoprene concentrations (≤ 3.25 μg m(-3)) were found and sedge biomass contributed about 51.76% to their spatial variation. α-pinene and isoprene emissions at noon were as high as 515.53 ± 88.34 μg m(-2)h(-1) and 7606.19 ± 1073.94 μg m(-2) h(-1) in A. frigida- and sedge-dominated areas where their biomass were 236.90 g m(-2) and 72.37 g m(-2), respectively. Our results suggested that the expansion of A. frigida and sedge caused by over-grazing and climatic stresses may increase local ambient BVOCs concentration in grassland.

  9. 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

  10. Protease degradable electrospun fibrous hydrogels

    PubMed Central

    Wade, Ryan J.; Bassin, Ethan J.; Rodell, Christopher B.; Burdick, Jason A.

    2015-01-01

    Electrospun nanofibers are promising in biomedical applications to replicate features of the natural extracellular matrix (ECM). However, nearly all electrospun scaffolds are either non-degradable or degrade hydrolytically, whereas natural ECM degrades proteolytically, often through matrix metalloproteinases (MMPs). Here, we synthesize reactive macromers that contain protease-cleavable and fluorescent peptides and are able to form both isotropic hydrogels and electrospun fibrous hydrogels through a photoinitiated polymerization. These biomimetic scaffolds are susceptible to protease-mediated cleavage in vitro in a protease dose dependent manner and in vivo in a subcutaneous mouse model using transdermal fluorescent imaging to monitor degradation. Importantly, materials containing an alternate and non-protease-cleavable peptide sequence are stable in both in vitro and in vivo settings. To illustrate the specificity in degradation, scaffolds with mixed fiber populations support selective fiber degradation based on individual fiber degradability. Overall, this represents a novel biomimetic approach to generate protease-sensitive fibrous scaffolds for biomedical applications. PMID:25799370

  11. 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

  12. Porous Biodegradable Metals for Hard Tissue Scaffolds: A Review

    PubMed Central

    Yusop, A. H.; Bakir, A. A.; Shaharom, N. A.; Abdul Kadir, M. R.; Hermawan, H.

    2012-01-01

    Scaffolds have been utilized in tissue regeneration to facilitate the formation and maturation of new tissues or organs where a balance between temporary mechanical support and mass transport (degradation and cell growth) is ideally achieved. Polymers have been widely chosen as tissue scaffolding material having a good combination of biodegradability, biocompatibility, and porous structure. Metals that can degrade in physiological environment, namely, biodegradable metals, are proposed as potential materials for hard tissue scaffolding where biodegradable polymers are often considered as having poor mechanical properties. Biodegradable metal scaffolds have showed interesting mechanical property that was close to that of human bone with tailored degradation behaviour. The current promising fabrication technique for making scaffolds, such as computation-aided solid free-form method, can be easily applied to metals. With further optimization in topologically ordered porosity design exploiting material property and fabrication technique, porous biodegradable metals could be the potential materials for making hard tissue scaffolds. PMID:22919393

  13. Biodegradation and bioresorption of poly(ɛ-caprolactone) nanocomposite scaffolds.

    PubMed

    Mkhabela, Vuyiswa; Ray, Suprakas Sinha

    2015-08-01

    A new type of hybrid three-dimensional scaffolds was prepared using poly(ɛ-caprolactone) (PCL) and chitosan-modified montmorillonite by solvent casting and particulate leaching method. The scaffolds were characterized by scanning electron microscopy coupled with energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and dynamic mechanical analysis to study the structural and mechanical properties. The resulting scaffolds displayed high porosity with highly interconnected pores. EDS analysis confirmed the elemental composition of the scaffolds. The phase composition of the scaffolds was shown by XRD, which also indicated a decrease in crystallinity with the introduction of nanoclay. Biodegradability studies which were conducted in simulated physiological conditions over a period of four weeks revealed that the PCL-based scaffolds degraded by hydrolysis at a slow rate. The overall bioresorbability was also slow, with the composite-based scaffolds recording a faster rate than the neat polymer-based scaffold. PMID:25952165

  14. Synergistic Effect of Carbon Nanotubes and Graphene on Diopside Scaffolds

    PubMed Central

    Liu, Tingting; Wu, Ping; Gao, Chengde; Feng, Pei; Xiao, Tao; Deng, Youwen; Shuai, Cijun; Peng, Shuping

    2016-01-01

    A synergetic effect between carbon nanotubes (CNTs) and graphene on diopside (Di) scaffolds was demonstrated. 3D network architecture in the matrix was formed through the 1D CNTs inlaid among the 2D graphene platelets (GNPs). The mechanical properties of the CNTs/GNPs/Di scaffolds were significantly improved compared with the CNTs/Di scaffolds and GNPs/Di scaffolds. In addition, the scaffolds exhibited excellent apatite-forming ability, a modest degradation rate, and stable mechanical properties in simulated body fluid (SBF). Moreover, cell culturing tests indicated that the scaffolds supported the cells attachment and proliferation. Taken together, the CNTs/GNPs/Di scaffolds offered great potential for bone tissue engineering. PMID:27144173

  15. Protease-degradable electrospun fibrous hydrogels

    NASA Astrophysics Data System (ADS)

    Wade, Ryan J.; Bassin, Ethan J.; Rodell, Christopher B.; Burdick, Jason A.

    2015-03-01

    Electrospun nanofibres are promising in biomedical applications to replicate features of the natural extracellular matrix (ECM). However, nearly all electrospun scaffolds are either non-degradable or degrade hydrolytically, whereas natural ECM degrades proteolytically, often through matrix metalloproteinases. Here we synthesize reactive macromers that contain protease-cleavable and fluorescent peptides and are able to form both isotropic hydrogels and electrospun fibrous hydrogels through a photoinitiated polymerization. These biomimetic scaffolds are susceptible to protease-mediated cleavage in vitro in a protease dose-dependent manner and in vivo in a subcutaneous mouse model using transdermal fluorescent imaging to monitor degradation. Importantly, materials containing an alternate and non-protease-cleavable peptide sequence are stable in both in vitro and in vivo settings. To illustrate the specificity in degradation, scaffolds with mixed fibre populations support selective fibre degradation based on individual fibre degradability. Overall, this represents a novel biomimetic approach to generate protease-sensitive fibrous scaffolds for biomedical applications.

  16. Soy Protein Scaffold Biomaterials for Tissue Engineering and Regenerative Medicine

    NASA Astrophysics Data System (ADS)

    Chien, Karen B.

    Developing functional biomaterials using highly processable materials with tailorable physical and bioactive properties is an ongoing challenge in tissue engineering. Soy protein is an abundant, natural resource with potential use for regenerative medicine applications. Preliminary studies show that soy protein can be physically modified and fabricated into various biocompatible constructs. However, optimized soy protein structures for tissue regeneration (i.e. 3D porous scaffolds) have not yet been designed. Furthermore, little work has established the in vivo biocompatibility of implanted soy protein and the benefit of using soy over other proteins including FDA-approved bovine collagen. In this work, freeze-drying and 3D printing fabrication processes were developed using commercially available soy protein to create porous scaffolds that improve cell growth and infiltration compared to other soy biomaterials previously reported. Characterization of scaffold structure, porosity, and mechanical/degradation properties was performed. In addition, the behavior of human mesenchymal stem cells seeded on various designed soy scaffolds was analyzed. Biological characterization of the cell-seeded scaffolds was performed to assess feasibility for use in liver tissue regeneration. The acute and humoral response of soy scaffolds implanted in an in vivo mouse subcutaneous model was also investigated. All fabricated soy scaffolds were modified using thermal, chemical, and enzymatic crosslinking to change properties and cell growth behavior. 3D printing allowed for control of scaffold pore size and geometry. Scaffold structure, porosity, and degradation rate significantly altered the in vivo response. Freeze-dried soy scaffolds had similar biocompatibility as freeze-dried collagen scaffolds of the same protein content. However, the soy scaffolds degraded at a much faster rate, minimizing immunogenicity. Interestingly, subcutaneously implanted soy scaffolds affected blood

  17. Multifunctional Thin Film Biomatrice Biosensor in a Degradable Scaffold Containing Bone Morphogenetic Protein-2 (BMP-2) for Controlled Release in Skeletal Tissue Engineering

    NASA Astrophysics Data System (ADS)

    McDaniel, Harvey; Lomax, Linda

    2001-03-01

    Bone morphonogenetic proteins (BMP-2) have been under investigation for three decades. Deminerialized bone and extracts of deminerialized bone are o steoinductive with a temporal sequence of bone induction. Native and recombi nant BMP's have shown the ability, thru growth and differentiative factors t o induce de novo bone formation both invitro and invivo. Their principle fun ction is to induce transformation of undifferentiated mesenchymal cells into osteoblasts. Native and recombinant BMP's, when purified and used without carrier disp erse after implantation and exert no effect on bone induction. The delivery system provides the missing component to successsfully applying osteogenic p roteins for clinical need. Biological and physio-chemical properties are str ictly adhered tofor a successful delivery system. The BMP delivery system ca rrier for osteo inductive payload provided; 1)non tumorgenic genecity, 2) no n immunogenecity, 3) water insoluble, 4) biosorbability with predictable enz ymatic degradation, and 5) an optimized surface for compatibility, cell migr ation and attachment with a negative surface change that encouraged target c ell attachment. Being a controlled Release System, it binded the proteins wi th predictible BMP released kinetics. Porosity with interconnecting voids pr otected the BMP from noon specific proteolysis and promoted rapid vascular a nd mesenchymal invasion. Far wide ranging clinical applications of mechanica l and biofunctional requirements were met with the BMP delivery system. Cohe sion and malleability were reqiured forcontour augmentation, and reconstruct ion of the discontinuity defects, prevented dislocation and retained the sha pe and bone replaced the system. Biological systems have elastic activity associated with them. The activi ty was current associated with a time dependant biological/biochemical react ion (enzymic activity). Bioelectric phoenomena associated with charged molec ules in a biologic structure caused

  18. Elastase-Sensitive Elastomeric Scaffolds with Variable Anisotropy for Soft Tissue Engineering

    PubMed Central

    Guan, Jianjun; Fujimoto, Kazuro L.; Wagner, William R.

    2010-01-01

    Purpose To develop elastase-sensitive polyurethane scaffolds that would be applicable to the engineering of mechanically active soft tissues. Methods A polyurethane containing an elastase-sensitive peptide sequence was processed into scaffolds by thermally induced phase separation. Processing conditions were manipulated to alter scaffold properties and anisotropy. The scaffold’s mechanical properties, degradation, and cytocompatibility using muscle-derived stem cells were characterized. Scaffold in vivo degradation was evaluated by subcutaneous implantation. Results When heat transfer was multidirectional, scaffolds had randomly oriented pores. Imposition of a heat transfer gradient resulted in oriented pores. Both scaffolds were flexible and relatively strong with mechanical properties dependent upon fabrication conditions such as solvent type, polymer concentration and quenching temperature. Oriented scaffolds exhibited anisotropic mechanical properties with greater tensile strength in the orientation direction. These scaffolds also supported muscle-derived stem cell growth more effectively than random scaffolds. The scaffolds expressed over 40% weight loss after 56 days in elastase containing buffer. Elastase-sensitive scaffolds were complete degraded after 8 weeks subcutaneous implantation in rats, markedly faster than similar polyurethanes that did not contain the peptide sequence. Conclusion The elastase-sensitive polyurethane scaffolds showed promise for application in soft tissue engineering where controlling scaffold mechanical properties and pore architecture are desirable. PMID:18509596

  19. Biodegradable Fibrous Scaffolds with Diverse Properties by Electrospinning Candidates from a Combinatorial Macromer Library

    PubMed Central

    Metter, Robert B.; Ifkovits, Jamie L.; Hou, Kevin; Vincent, Ludovic; Hsu, Benjamin; Wang, Louis; Mauck, Robert L.; Burdick, Jason A.

    2009-01-01

    The properties of electrospun fibrous scaffolds, including degradation, mechanics and cellular interactions, are important for their use in tissue engineering applications. Although some diversity has been obtained previously in fibrous scaffolds, optimization of scaffold properties relies on iterative techniques in both polymer synthesis and processing. Here, we electrospun candidates from a combinatorial library of biodegradable and photopolymerizable poly(β-amino ester)s (PBAEs) to show that the diversity in properties found in this library is retained when processed into fibrous scaffolds. Specifically, three PBAE macromers were electrospun into scaffolds and possessed similar initial mechanical properties, but exhibited mass loss ranging from rapid (complete degradation within ∼2 weeks) to moderate (complete degradation within ∼ 3 months) to slow (only partial degradation after 3 months). These trends in mechanics and degradation mimicked what was previously observed in the bulk polymers. Although cellular adhesion was dependent on the polymer composition in films, adhesion to scaffolds that were electrospun with gelatin was similar on all formulations and controls. To further illustrate the diverse properties that are attainable in these systems, the fastest and slowest degrading polymers were electrospun together into one scaffold, but as distinct fiber populations. This dual-polymer scaffold exhibited behavior in mass loss and mechanics with time that fell between the single-polymer scaffolds. In general, this work indicates that combinatorial libraries may be an important source of information and specific polymer compositions for the fabrication of electrospun fibrous scaffolds with tunable properties. PMID:19853066

  20. 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.

  1. A review: fabrication of porous polyurethane scaffolds.

    PubMed

    Janik, H; Marzec, M

    2015-03-01

    The aim of tissue engineering is the fabrication of three-dimensional scaffolds that can be used for the reconstruction and regeneration of damaged or deformed tissues and organs. A wide variety of techniques have been developed to create either fibrous or porous scaffolds from polymers, metals, composite materials and ceramics. However, the most promising materials are biodegradable polymers due to their comprehensive mechanical properties, ability to control the rate of degradation and similarities to natural tissue structures. Polyurethanes (PUs) are attractive candidates for scaffold fabrication, since they are biocompatible, and have excellent mechanical properties and mechanical flexibility. PU can be applied to various methods of porous scaffold fabrication, among which are solvent casting/particulate leaching, thermally induced phase separation, gas foaming, emulsion freeze-drying and melt moulding. Scaffold properties obtained by these techniques, including pore size, interconnectivity and total porosity, all depend on the thermal processing parameters, and the porogen agent and solvents used. In this review, various polyurethane systems for scaffolds are discussed, as well as methods of fabrication, including the latest developments, and their advantages and disadvantages.

  2. ASTM International Workshop on Standards & Measurements for Tissue Engineering Scaffolds

    PubMed Central

    Simon, Carl G.; Yaszemski, Michael J.; Ratcliffe, Anthony; Tomlins, Paul; Luginbuehl, Reto; Tesk, John A.

    2016-01-01

    The “Workshop on Standards & Measurements for Tissue Engineering Scaffolds” was held on May 21, 2013 in Indianapolis, IN and was sponsored by the ASTM International (ASTM). The purpose of the workshop was to identify the highest priority items for future standards work for scaffolds used in the development and manufacture of tissue engineered medical products (TEMPs). Eighteen speakers and 78 attendees met to assess current scaffold standards and to prioritize needs for future standards. A key finding was that the ASTM TEMPs subcommittees (F04.41-46) have many active “guide” documents for educational purposes, but that few standard “test methods” or “practices” have been published. Overwhelmingly, the most clearly identified need was standards for measuring the structure of scaffolds, followed by standards for biological characterization, including in vitro testing, animal models and cell-material interactions. The third most pressing need was to develop standards for assessing the mechanical properties of scaffolds. Additional needs included standards for assessing scaffold degradation, clinical outcomes with scaffolds, effects of sterilization on scaffolds, scaffold composition and drug release from scaffolds. Discussions also highlighted the need for additional scaffold reference materials and the need to use them for measurement traceability. Finally, dialogue emphasized the needs to promote the use of standards in scaffold fabrication, characterization, and commercialization and to assess the use and impact of standards in the TEMPs community. Many scaffold standard needs have been identified and focus should now turn to generating these standards to support the use of scaffolds in TEMPs. PMID:25220952

  3. ASTM international workshop on standards and measurements for tissue engineering scaffolds.

    PubMed

    Simon, Carl G; Yaszemski, Michael J; Ratcliffe, Anthony; Tomlins, Paul; Luginbuehl, Reto; Tesk, John A

    2015-07-01

    The "Workshop on Standards & Measurements for Tissue Engineering Scaffolds" was held on May 21, 2013 in Indianapolis, IN, and was sponsored by the ASTM International (ASTM). The purpose of the workshop was to identify the highest priority items for future standards work for scaffolds used in the development and manufacture of tissue engineered medical products (TEMPs). Eighteen speakers and 78 attendees met to assess current scaffold standards and to prioritize needs for future standards. A key finding was that the ASTM TEMPs subcommittees (F04.41-46) have many active "guide" documents for educational purposes, but few standard "test methods" or "practices." Overwhelmingly, the most clearly identified need was standards for measuring the structure of scaffolds, followed by standards for biological characterization, including in vitro testing, animal models and cell-material interactions. The third most pressing need was to develop standards for assessing the mechanical properties of scaffolds. Additional needs included standards for assessing scaffold degradation, clinical outcomes with scaffolds, effects of sterilization on scaffolds, scaffold composition, and drug release from scaffolds. Discussions highlighted the need for additional scaffold reference materials and the need to use them for measurement traceability. Workshop participants emphasized the need to promote the use of standards in scaffold fabrication, characterization, and commercialization. Finally, participants noted that standards would be more broadly accepted if their impact in the TEMPs community could be quantified. Many scaffold standard needs have been identified and focus is turning to generating these standards to support the use of scaffolds in TEMPs.

  4. Degradable Segmented Polyurethane Elastomers for Bone Tissue Engineering: Effect of Polycaprolactone Content

    PubMed Central

    Kavlock, Katherine D.; Whang, Kyumin; Guelcher, Scott A.; Goldstein, Aaron S.

    2016-01-01

    Segmented polyurethanes (PURs) – consisting of degradable poly(α-hydroxy ester) soft segments and amino acid-derived chain extenders – are biocompatible elastomers with tunable mechanical and degradative properties suitable for a variety of tissue engineering applications. In this study, a family of linear PURs synthesized from poly(ε-caprolactone) (PCL) diol, 1,4-diisocyanobutane and tyramine with theoretical PCL contents of 65 to 80 wt% were processed into porous foam scaffolds and evaluated for their ability to support osteoblastic differentiation in vitro. Differential scanning calorimetry and mechanical testing of the foams indicated increasing polymer crystallinity and compressive modulus with increasing PCL content. Next, bone marrow stromal cells (BMSCs) were seeded into PUR scaffolds – as well as poly(lactic-co-glycolic acid) (PLGA) scaffolds – and maintained under osteogenic conditions for 14 and 21 days. Analysis of cell number indicated a systematic decrease in cell density with increasing PUR stiffness at both 14 and 21 days in culture. However, at these same time points the relative mRNA expression for the bone-specific proteins osteocalcin and the growth factors bone morphogenetic protein-2 and vascular endothelial growth factor gene expression were similar among the PURs. Finally, prostaglandin E2 production, alkaline phosphatase activity, and osteopontin mRNA expression were highly elevated on the most-crystalline PUR scaffold as compared to the PLGA and PUR scaffolds. These results suggest that both the modulus and crystallinity of the PUR scaffolds influence cell proliferation and the expression of osteoblastic proteins. PMID:22304961

  5. 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.

  6. Evolutionary design of bone scaffolds with reference to material selection.

    PubMed

    Heljak, M K; Swięszkowski, W; Lam, C X F; Hutmacher, D W; Kurzydłowski, K J

    2012-01-01

    The favourable scaffold for bone tissue engineering should have desired characteristic features, such as adequate mechanical strength and three-dimensional open porosity, which guarantee a suitable environment for tissue regeneration. In fact, the design of such complex structures like bone scaffolds is a challenge for investigators. One of the aims is to achieve the best possible mechanical strength-degradation rate ratio. In this paper we attempt to use numerical modelling to evaluate material properties for designing bone tissue engineering scaffold fabricated via the fused deposition modelling technique. For our studies the standard genetic algorithm was used, which is an efficient method of discrete optimization. For the fused deposition modelling scaffold, each individual strut is scrutinized for its role in the architecture and structural support it provides for the scaffold, and its contribution to the overall scaffold was studied. The goal of the study was to create a numerical tool that could help to acquire the desired behaviour of tissue engineered scaffolds and our results showed that this could be achieved efficiently by using different materials for individual struts. To represent a great number of ways in which scaffold mechanical function loss could proceed, the exemplary set of different desirable scaffold stiffness loss function was chosen.

  7. Degradation behavior at elevated temperature of LaNisub5-xSnsubxHsubz for x between 0.20 and 0.25

    NASA Technical Reports Server (NTRS)

    Bowman, R. C., Jr.; Lindensmith, C. A.; Luo, S.; Flanagan, T. B.; Vogt, T.

    2000-01-01

    Systematic studies of the hydriding behavior of LaNi(sub 5-x)Sn(sub x)H(sub z) alloys with tin contents in the range between 0.20 and 0.25 have revealed changes in the pressure-composition-temperature (PCT) isotherms measured after heating the hydrides above 450 K. These changes are indications of degradation processes and increased disorder within the alloy structure.

  8. Vascular Guidance: Microstructural Scaffold Patterning for Inductive Neovascularization

    PubMed Central

    Muller, Daniel; Chim, Harvey; Bader, Augustinus; Whiteman, Matthew; Schantz, Jan-Thorsten

    2011-01-01

    Current tissue engineering techniques are limited by inadequate vascularisation and perfusion of cell-scaffold constructs. Microstructural patterning through biomimetic vascular channels within a polymer scaffold might induce neovascularization, allowing fabrication of large engineered constructs. The network of vascular channels within a frontal-parietal defect in a patient, originating from the anterior branch of the middle meningeal artery, was modeled using computer-aided design (CAD) techniques and subsequently incorporated into polycaprolactone (PCL) scaffolds fabricated using fused deposition modeling (FDM). Bone marrow-derived mesenchymal stem cells (MSCs) were seeded onto the scaffolds and implanted into a rat model, with an arteriovenous bundle inserted at the proximal extent of the vascular network. After 3 weeks, scaffolds were elevated as a prefabricated composite tissue-polymer flap and transferred using microsurgical technique. Histological examination of explanted scaffolds revealed vascular ingrowth along patterned channels, with abundant capillary and connective tissue formation throughout experimental scaffolds, while control scaffolds showed only granulation tissue. All prefabricated constructs transferred as free flaps survived and were viable. We term this concept “vascular guidance,” whereby neovascularization is guided through customized channels in a scaffold. Our technique might potentially allow fabrication of much larger tissue-engineered constructs than current technologies allow, as well as allowing tailored construct fabrication with a patient-specific vessel network based on CT scan data and CAD technology. PMID:21188080

  9. Electrospun Silk Biomaterial Scaffolds for Regenerative Medicine

    PubMed Central

    Zhang, Xiaohui; Reagan, Michaela R; Kaplan, David L.

    2009-01-01

    Electrospinning is a versatile technique that enables the development of nanofiber-based biomaterial scaffolds. Scaffolds can be generated that are useful for tissue engineering and regenerative medicine since they mimic the nanoscale properties of certain fibrous components of the native extracellular matrix in tissues. Silk is a natural protein with excellent biocompatibility, remarkable mechanical properties as well as tailorable degradability. Integrating these protein polymer advantages with electrospinning results in scaffolds with combined biochemical, topographical and mechanical cues with versatility for a range of biomaterial, cell and tissue studies and applications. This review covers research related to electrospinning of silk, including process parameters, post treatment of the spun fibers, functionalization of nanofibers, and the potential applications for these material systems in regenerative medicine. Research challenges and future trends are also discussed. PMID:19643154

  10. Immune Response to Biologic Scaffold Materials

    PubMed Central

    Badylak, Stephen F.; Gilbert, Thomas W.

    2008-01-01

    Biologic scaffold materials composed of mammalian extracellular matrix are commonly used in regenerative medicine and in surgical procedures for the reconstruction of numerous tissue and organs. These biologic materials are typically allogeneic or xenogeneic in origin and are derived from tissues such as small intestine, urinary bladder, dermis, and pericardium. The innate and acquired host immune response to these biologic materials and the effect of the immune response upon downstream remodeling events has been largely unexplored. Variables that affect the host response include manufacturing processes, the rate of scaffold degradation, and the presence of cross species antigens. This manuscript provides an overview of studies that have evaluated the immune response to biologic scaffold materials and variables that affect this response. PMID:18083531

  11. 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

  12. Salt-leached silk scaffolds with tunable mechanical properties.

    PubMed

    Yao, Danyu; Dong, Sen; Lu, Qiang; Hu, Xiao; Kaplan, David L; Zhang, Bingbo; Zhu, Hesun

    2012-11-12

    Substrate mechanical properties have remarkable influences on cell behavior and tissue regeneration. Although salt-leached silk scaffolds have been used in tissue engineering, applications in softer tissue regeneration can be encumbered with excessive stiffness. In the present study, silk-bound water interactions were regulated by controlling processing to allow the preparation of salt-leached porous scaffolds with tunable mechanical properties. Increasing silk-bound water interactions resulted in reduced silk II (β-sheet crystal) formation during salt-leaching, which resulted in a modulus decrease in the scaffolds. The microstructures as well as degradation behavior were also changed, implying that this water control and salt-leaching approach can be used to achieve tunable mechanical properties. Considering the utility of silk in various fields of biomedicine, the results point to a new approach to generate silk scaffolds with controllable properties to better mimic soft tissues by combining scaffold preparation methods and silk self-assembly in aqueous solutions.

  13. Novel Polymeric Scaffolds Using Protein Microbubbles as Porogen and Growth Factor Carriers

    PubMed Central

    Nair, Ashwin; Thevenot, Paul; Dey, Jagannath; Shen, Jinhui; Sun, Man-Wu; Yang, Jian

    2010-01-01

    Polymeric tissue engineering scaffolds prepared by conventional techniques like salt leaching and phase separation are greatly limited by their poor biomolecule-delivery abilities. Conventional methods of incorporation of various growth factors, proteins, and/or peptides on or in scaffold materials via different crosslinking and conjugation techniques are often tedious and may affect scaffold's physical, chemical, and mechanical properties. To overcome such deficiencies, a novel two-step porous scaffold fabrication procedure has been created in which bovine serum albumin microbubbles (henceforth MB) were used as porogen and growth factor carriers. Polymer solution mixed with MB was phase separated and then lyophilized to create porous scaffold. MB scaffold triggered substantially lesser inflammatory responses than salt-leached and conventional phase-separated scaffolds in vivo. Most importantly, the same technique was used to produce insulin-like growth factor-1 (IGF-1)–eluting porous scaffolds, simply by incorporating IGF-1–loaded MB (MB-IGF-1) with polymer solution before phase separation. In vitro such MB-IGF-1 scaffolds were able to promote cell growth to a much greater extent than scaffold soaked in IGF-1, confirming the bioactivity of the released IGF-1. Further, such MB-IGF-1 scaffolds elicited IGF-1–specific collagen production in the surrounding tissue in vivo. This novel growth factor–eluting scaffold fabrication procedure can be used to deliver a range of single or combination of bioactive biomolecules to substantially promote cell growth and function in degradable scaffold. PMID:19327002

  14. Maltodextrin enhances biofilm elimination by electrochemical scaffold

    PubMed Central

    Sultana, Sujala T.; Call, Douglas R.; Beyenal, Haluk

    2016-01-01

    Electrochemical scaffolds (e-scaffolds) continuously generate low concentrations of H2O2 suitable for damaging wound biofilms without damaging host tissue. Nevertheless, retarded diffusion combined with H2O2 degradation can limit the efficacy of this potentially important clinical tool. H2O2 diffusion into biofilms and bacterial cells can be increased by damaging the biofilm structure or by activating membrane transportation channels by exposure to hyperosmotic agents. We hypothesized that e-scaffolds would be more effective against Acinetobacter baumannii and Staphylococcus aureus biofilms in the presence of a hyperosmotic agent. E-scaffolds polarized at −600 mVAg/AgCl were overlaid onto preformed biofilms in media containing various maltodextrin concentrations. E-scaffold alone decreased A. baumannii and S. aureus biofilm cell densities by (3.92 ± 0.15) log and (2.31 ± 0.12) log, respectively. Compared to untreated biofilms, the efficacy of the e-scaffold increased to a maximum (8.27 ± 0.05) log reduction in A. baumannii and (4.71 ± 0.12) log reduction in S. aureus biofilm cell densities upon 10 mM and 30 mM maltodextrin addition, respectively. Overall ~55% decrease in relative biofilm surface coverage was achieved for both species. We conclude that combined treatment with electrochemically generated H2O2 from an e-scaffold and maltodextrin is more effective in decreasing viable biofilm cell density. PMID:27782161

  15. Engineering functionally graded tissue engineering scaffolds.

    PubMed

    Leong, K F; Chua, C K; Sudarmadji, N; Yeong, W Y

    2008-04-01

    Tissue Engineering (TE) aims to create biological substitutes to repair or replace failing organs or tissues due to trauma or ageing. One of the more promising approaches in TE is to grow cells on biodegradable scaffolds, which act as temporary supports for the cells to attach, proliferate and differentiate; after which the scaffold will degrade, leaving behind a healthy regenerated tissue. Tissues in nature, including human tissues, exhibit gradients across a spatial volume, in which each identifiable layer has specific functions to perform so that the whole tissue/organ can behave normally. Such a gradient is termed a functional gradient. A good TE scaffold should mimic such a gradient, which fulfils the biological and mechanical requirements of the target tissue. Thus, the design and fabrication process of such scaffolds become more complex and the introduction of computer-aided tools will lend themselves well to ease these challenges. This paper reviews the needs and characterization of these functional gradients and the computer-aided systems used to ease the complexity of the scaffold design stage. These include the fabrication techniques capable of building functionally graded scaffolds (FGS) using both conventional and rapid prototyping (RP) techniques. They are able to fabricate both continuous and discrete types of FGS. The challenge in fabricating continuous FGS using RP techniques lies in the development of suitable computer aided systems to facilitate continuous FGS design. What have been missing are the appropriate models that relate the scaffold gradient, e.g. pore size, porosity or material gradient, to the biological and mechanical requirements for the regeneration of the target tissue. The establishment of these relationships will provide the foundation to develop better computer-aided systems to help design a suitable customized FGS.

  16. Preparation and chemical and biological characterization of a pectin/chitosan polyelectrolyte complex scaffold for possible bone tissue engineering applications.

    PubMed

    Coimbra, P; Ferreira, P; de Sousa, H C; Batista, P; Rodrigues, M A; Correia, I J; Gil, M H

    2011-01-01

    In this work, porous scaffolds obtained from the freeze-drying of pectin/chitosan polyelectrolyte complexes were prepared and characterized by FTIR, SEM and weight loss studies. Additionally, the cytotoxicity of the prepared scaffolds was evaluated in vitro, using human osteoblast cells. The results obtained showed that cells adhered to scaffolds and proliferated. The study also confirmed that the degradation by-products of pectin/chitosan scaffold are noncytotoxic.

  17. Development of Composite Porous Scaffolds Based on Collagen and Biodegradable Poly(ester urethane)urea

    PubMed Central

    Guan, Jianjun; Stankus, John J.; Wagner, William R.

    2010-01-01

    Our objective in this work was to develop a flexible, biodegradable scaffold for cell transplantation that would incorporate a synthetic component for strength and flexibility and type I collagen for enzymatic lability and cytocompatibility. A biodegradable poly(ester urethane)urea was synthesized from poly(caprolactone), 1,4-diisocyanatobutane, and putrescine. Using a thermally induced phase separation process, porous scaffolds were created from a mixture containing this polyurethane and 0%, 10%, 20%, or 30% type I collagen. The resulting scaffolds were found to have open, interconnected pores (from 7 to >100 um) and porosities from 58% to 86% depending on the polyurethane/collagen ratio. The scaffolds were also flexible with breaking strains of 82–443% and tensile strengths of 0.97–4.11 MPa depending on preparation conditions. Scaffold degradation was significantly increased when collagenase was introduced into an incubating buffer in a manner that was dependent on the mass fraction of collagen present in the scaffold. Mass losses could be varied from 15% to 59% over 8 weeks. When culturing umbilical artery smooth muscle cells on these scaffolds higher cell numbers were observed over a 4-week culture period in scaffolds containing collagen. In summary, a strong and flexible scaffold system has been developed that can degrade by both hydrolysis and collagenase degradation pathways, as well as support cell growth. This scaffold possesses properties that would make it attractive for future use in soft tissue applications where such mechanical and biological features would be advantageous. PMID:16826792

  18. Novel soy protein scaffolds for tissue regeneration: Material characterization and interaction with human mesenchymal stem cells.

    PubMed

    Chien, Karen B; Shah, Ramille N

    2012-02-01

    Soy protein modified with heat treatment and enzyme crosslinking using transglutaminase in maltodextrin was used to fabricate novel, porous three-dimensional scaffolds through lyophilization. Physical properties of scaffolds were characterized using scanning electron microscopy, mercury intrusion porosimetry, moisture content analysis and mechanical testing. Human mesenchymal stem cells (hMSC) were seeded and cultured in vitro on the scaffolds for up to 2 weeks, and changes in stem cell growth and morphology were examined. The resulting scaffolds had rough surfaces, irregular pores with size distributions between 10 and 125 μm, <5% moisture content and compressive moduli ranging between 50 and 100 Pa. Enzyme treatment significantly lowered the moisture content. Increasing amounts of applied enzyme units lowered the median pore size. Although enzyme treatment did not affect the mechanical properties of the scaffolds, it did increase the degradation time by at least 1 week. These changes in scaffold degradation altered the growth and morphology of seeded hMSC. Cell proliferation was observed in scaffolds containing 3% soy protein isolate treated with 1 U of transglutaminase. These results demonstrate that controlling scaffold degradation rates is crucial for optimizing hMSC growth on soy protein scaffolds and that soy protein scaffolds have the potential to be used in tissue engineering applications.

  19. Novel soy protein scaffolds for tissue regeneration: Material characterization and interaction with human mesenchymal stem cells.

    PubMed

    Chien, Karen B; Shah, Ramille N

    2012-02-01

    Soy protein modified with heat treatment and enzyme crosslinking using transglutaminase in maltodextrin was used to fabricate novel, porous three-dimensional scaffolds through lyophilization. Physical properties of scaffolds were characterized using scanning electron microscopy, mercury intrusion porosimetry, moisture content analysis and mechanical testing. Human mesenchymal stem cells (hMSC) were seeded and cultured in vitro on the scaffolds for up to 2 weeks, and changes in stem cell growth and morphology were examined. The resulting scaffolds had rough surfaces, irregular pores with size distributions between 10 and 125 μm, <5% moisture content and compressive moduli ranging between 50 and 100 Pa. Enzyme treatment significantly lowered the moisture content. Increasing amounts of applied enzyme units lowered the median pore size. Although enzyme treatment did not affect the mechanical properties of the scaffolds, it did increase the degradation time by at least 1 week. These changes in scaffold degradation altered the growth and morphology of seeded hMSC. Cell proliferation was observed in scaffolds containing 3% soy protein isolate treated with 1 U of transglutaminase. These results demonstrate that controlling scaffold degradation rates is crucial for optimizing hMSC growth on soy protein scaffolds and that soy protein scaffolds have the potential to be used in tissue engineering applications. PMID:22019761

  20. The angiogenesis in decellularized scaffold-mediated the renal regeneration

    PubMed Central

    Li, Miaozhong; Xi, Shanshan; Zhang, Sixiao; Liu, Xiaolin; Jiang, Junqun; Wang, Zhibin; Zhang, Jianse; Ding, Yuqiang; Lou, Xinfa; Tang, Maolin

    2016-01-01

    There are increasing numbers of patients underwent partial nephrectomy, and recovery of disturbed renal function is imperative post partial nephrectomy. We previously have demonstrated the decellularized (DC) scaffolds could mediate the residual kidney regeneration and thus improve disturbed renal function after partial nephrectomy. However, the cellular changes including the angiogenesis in the implanted DC scaffold has not yet been elaborated. In this study, we observed that the scaffold promoted the proliferation of human umbilical vein endothelial cells (HUVEC) that adhered to the DC scaffold in vitro. We next examined the pathological changes of the implanted DC graft in vivo, and found a decreased volume of the scaffold and a dramatic angiogenesis within the scaffold. The average microvessel density (aMVD) increased at the early stage, while decreased at the later stage post transplantation. Expression level of vascular endothelial growth factor (VEGF) showed similar dynamic changes. In addition, many endothelial cells (ECs) and endothelial progenitor cells (EPCs) were distributed in the region which contained active angiogenesis in the scaffold. However, the implanted graft became fibrosis and the angiogenesis degraded at final stage roughly 8 weeks post transplantation. Our data indicate that DC scaffold can be vascularized in vivo and possible mechanisms are discussed. PMID:27058889

  1. Oxygen diffusion in marine-derived tissue engineering scaffolds.

    PubMed

    Boccardi, E; Belova, I V; Murch, G E; Boccaccini, A R; Fiedler, T

    2015-06-01

    This paper addresses the computation of the effective diffusivity in new bioactive glass (BG) based tissue engineering scaffolds. High diffusivities facilitate the supply of oxygen and nutrients to grown tissue as well as the rapid disposal of toxic waste products. The present study addresses required novel types of bone tissue engineering BG scaffolds that are derived from natural marine sponges. Using the foam replication method, the scaffold geometry is defined by the porous structure of Spongia Agaricina and Spongia Lamella. These sponges present the advantage of attaining scaffolds with higher mechanical properties (2-4 MPa) due to a decrease in porosity (68-76%). The effective diffusivities of these structures are compared with that of conventional scaffolds based on polyurethane (PU) foam templates, characterised by high porosity (>90%) and lower mechanical properties (>0.05 MPa). Both the spatial and directional variations of diffusivity are investigated. Furthermore, the effect of scaffold decomposition due to immersion in simulated body fluid (SBF) on the diffusivity is addressed. Scaffolds based on natural marine sponges are characterised by lower oxygen diffusivity due to their lower porosity compared with the PU replica foams, which should enable the best oxygen supply to newly formed bone according the numerical results. The oxygen diffusivity of these new BG scaffolds increases over time as a consequence of the degradation in SBF.

  2. 3. General view of elevators no. 2 and no. 3 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. General view of elevators no. 2 and no. 3 in background right, showing relation to associated Washburn Crosby Milling complex in foreground (left to right: utility building, A mill (with scaffolding), wheat house, Humboldt mill; elevator no. 1 in rear with gold medal flour sign), facing southeast - Washburn Crosby Company Elevators No. 2 & 3, 900 & 1000 Second Avenue, South, Minneapolis, Hennepin County, MN

  3. Human responses to augmented virtual scaffolding models.

    PubMed

    Hsiao, Hongwei; Simeonov, Peter; Dotson, Brian; Ammons, Douglas; Kau, Tsui-Ying; Chiou, Sharon

    2005-08-15

    This study investigated the effect of adding real planks, in virtual scaffolding models of elevation, on human performance in a surround-screen virtual reality (SSVR) system. Twenty-four construction workers and 24 inexperienced controls performed walking tasks on real and virtual planks at three virtual heights (0, 6 m, 12 m) and two scaffolding-platform-width conditions (30, 60 cm). Gait patterns, walking instability measurements and cardiovascular reactivity were assessed. The results showed differences in human responses to real vs. virtual planks in walking patterns, instability score and heart-rate inter-beat intervals; it appeared that adding real planks in the SSVR virtual scaffolding model enhanced the quality of SSVR as a human - environment interface research tool. In addition, there were significant differences in performance between construction workers and the control group. The inexperienced participants were more unstable as compared to construction workers. Both groups increased their stride length with repetitions of the task, indicating a possibly confidence- or habit-related learning effect. The practical implications of this study are in the adoption of augmented virtual models of elevated construction environments for injury prevention research, and the development of programme for balance-control training to reduce the risk of falls at elevation before workers enter a construction job. PMID:16253942

  4. Human responses to augmented virtual scaffolding models.

    PubMed

    Hsiao, Hongwei; Simeonov, Peter; Dotson, Brian; Ammons, Douglas; Kau, Tsui-Ying; Chiou, Sharon

    2005-08-15

    This study investigated the effect of adding real planks, in virtual scaffolding models of elevation, on human performance in a surround-screen virtual reality (SSVR) system. Twenty-four construction workers and 24 inexperienced controls performed walking tasks on real and virtual planks at three virtual heights (0, 6 m, 12 m) and two scaffolding-platform-width conditions (30, 60 cm). Gait patterns, walking instability measurements and cardiovascular reactivity were assessed. The results showed differences in human responses to real vs. virtual planks in walking patterns, instability score and heart-rate inter-beat intervals; it appeared that adding real planks in the SSVR virtual scaffolding model enhanced the quality of SSVR as a human - environment interface research tool. In addition, there were significant differences in performance between construction workers and the control group. The inexperienced participants were more unstable as compared to construction workers. Both groups increased their stride length with repetitions of the task, indicating a possibly confidence- or habit-related learning effect. The practical implications of this study are in the adoption of augmented virtual models of elevated construction environments for injury prevention research, and the development of programme for balance-control training to reduce the risk of falls at elevation before workers enter a construction job.

  5. Growth of continuous bonelike mineral within porous poly(lactide-co-glycolide) scaffolds in vitro.

    PubMed

    Murphy, W L; Kohn, D H; Mooney, D J

    2000-04-01

    Strategies to engineer bone have focused on the use of natural or synthetic degradable materials as scaffolds for cell transplantation or as substrates to guide bone regeneration. The basic requirements of the scaffold material are biocompatibility, degradability, mechanical integrity, and osteoconductivity. A major design problem is satisfying each of these requirements with a single scaffold material. This study addresses this problem by describing an approach to combine the biocompatibility and degradability of a polymer scaffold with the osteoconductivity and mechanical reinforcement of a bonelike mineral film. We report the nucleation and growth of a continuous carbonated apatite mineral on the interior pore surfaces of a porous, degradable polymer scaffold via a one step, room temperature incubation process. A 3-dimensional, porous scaffold of the copolymer 85:15 poly(lactide-co-glycolide) was fabricated by a solvent casting, particulate leaching process. Fourier transform IR spectroscopy and scanning electron microscopy (SEM) analysis after different incubation times in a simulated body fluid (SBF) demonstrate the growth of a continuous bonelike apatite layer within the pores of the polymer scaffold. Quantification of phosphate on the scaffold displays the growth and development of the mineral film over time with an incorporation of 0.43 mg of phosphate (equivalent to 0.76 mg of hydroxyapatite) per scaffold after 14 days in SBF. The compressive moduli of polymer scaffolds increased fivefold with formation of a mineral film after a 16-day incubation time as compared to control scaffolds. In summary, this biomimetic treatment provides a simple, one step, room temperature method for surface functionalization and subsequent mineral nucleation and growth on biodegradable polymer scaffolds for tissue engineering.

  6. Development of porous scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Ramay, Hassna Rehman

    In bone tissue engineering, biodegradable scaffolds are used as a temporary biological and mechanical support for new tissue growth. A scaffold must have good biocompatibility, controllable degradation rate, and enough mechanical strength to support bone cell attachment, differentiation, and proliferation as it gradually degrades and finally is completely replaced by new bone tissues. Biological studies and clinical practices have established that a three-dimensional interconnected porous structure is necessary to allow cell attachment, proliferation, and differentiation, and to provide pathways for biofluids. However, the mechanical strength of a material generally decreases as increasing porosity. The conflicting interests between biological and mechanical requirements thus pose a challenge in developing porous scaffolds for load-bearing bone tissue engineering. Two types of ceramic scaffolds, (1) Hydroxaypatite and (2) Hydroxaypatite/tricalcium phosphate, are prepared in this study utilizing a novel technique that combines the gel casting and polymer sponge methods. This technique provides better control over material microstructure and can produce scaffolds with enhanced mechanical toughness and strength. The hydroxyapatite scaffolds prepared by this technique have an open, uniform and interconnected porous structure (˜porosity = 76%) with compressive modulus of 7 GPa, comparable to that of cortical bone, and compressive strength of 5 MPa, comparable to that of cancellous bone. The second type of ceramic scaffold is a biphasic nano composite with tricalcium phosphate as the main matrix reinforced with hydroxyapatite (HA) nano-fibers. The porous scaffold attained a compressive strength of 9.6 MPa (˜porosity = 73%), comparable to the high-end value of cancellous bone. The toughness of the scaffold increased from 1.00 to 1.72 kN/m (˜porosity = 73%), as the addition of HA nano-fibers increased up to 5 wt.%. Polymer scaffolds are prepared using a solid

  7. Three Dimensional Collagen Scaffold Promotes Intrinsic Vascularisation for Tissue Engineering Applications

    PubMed Central

    Chan, Elsa C.; Kuo, Shyh-Ming; Kong, Anne M.; Morrison, Wayne A.; Dusting, Gregory J.; Mitchell, Geraldine M.

    2016-01-01

    Here, we describe a porous 3-dimensional collagen scaffold material that supports capillary formation in vitro, and promotes vascularization when implanted in vivo. Collagen scaffolds were synthesized from type I bovine collagen and have a uniform pore size of 80 μm. In vitro, scaffolds seeded with primary human microvascular endothelial cells suspended in human fibrin gel formed CD31 positive capillary-like structures with clear lumens. In vivo, after subcutaneous implantation in mice, cell-free collagen scaffolds were vascularized by host neovessels, whilst a gradual degradation of the scaffold material occurred over 8 weeks. Collagen scaffolds, impregnated with human fibrinogen gel, were implanted subcutaneously inside a chamber enclosing the femoral vessels in rats. Angiogenic sprouts from the femoral vessels invaded throughout the scaffolds and these degraded completely after 4 weeks. Vascular volume of the resulting constructs was greater than the vascular volume of constructs from chambers implanted with fibrinogen gel alone (42.7±5.0 μL in collagen scaffold vs 22.5±2.3 μL in fibrinogen gel alone; p<0.05, n = 7). In the same model, collagen scaffolds seeded with human adipose-derived stem cells (ASCs) produced greater increases in vascular volume than did cell-free collagen scaffolds (42.9±4.0 μL in collagen scaffold with human ASCs vs 25.7±1.9 μL in collagen scaffold alone; p<0.05, n = 4). In summary, these collagen scaffolds are biocompatible and could be used to grow more robust vascularized tissue engineering grafts with improved the survival of implanted cells. Such scaffolds could also be used as an assay model for studies on angiogenesis, 3-dimensional cell culture, and delivery of growth factors and cells in vivo. PMID:26900837

  8. Three Dimensional Collagen Scaffold Promotes Intrinsic Vascularisation for Tissue Engineering Applications.

    PubMed

    Chan, Elsa C; Kuo, Shyh-Ming; Kong, Anne M; Morrison, Wayne A; Dusting, Gregory J; Mitchell, Geraldine M; Lim, Shiang Y; Liu, Guei-Sheung

    2016-01-01

    Here, we describe a porous 3-dimensional collagen scaffold material that supports capillary formation in vitro, and promotes vascularization when implanted in vivo. Collagen scaffolds were synthesized from type I bovine collagen and have a uniform pore size of 80 μm. In vitro, scaffolds seeded with primary human microvascular endothelial cells suspended in human fibrin gel formed CD31 positive capillary-like structures with clear lumens. In vivo, after subcutaneous implantation in mice, cell-free collagen scaffolds were vascularized by host neovessels, whilst a gradual degradation of the scaffold material occurred over 8 weeks. Collagen scaffolds, impregnated with human fibrinogen gel, were implanted subcutaneously inside a chamber enclosing the femoral vessels in rats. Angiogenic sprouts from the femoral vessels invaded throughout the scaffolds and these degraded completely after 4 weeks. Vascular volume of the resulting constructs was greater than the vascular volume of constructs from chambers implanted with fibrinogen gel alone (42.7±5.0 μL in collagen scaffold vs 22.5±2.3 μL in fibrinogen gel alone; p<0.05, n = 7). In the same model, collagen scaffolds seeded with human adipose-derived stem cells (ASCs) produced greater increases in vascular volume than did cell-free collagen scaffolds (42.9±4.0 μL in collagen scaffold with human ASCs vs 25.7±1.9 μL in collagen scaffold alone; p<0.05, n = 4). In summary, these collagen scaffolds are biocompatible and could be used to grow more robust vascularized tissue engineering grafts with improved the survival of implanted cells. Such scaffolds could also be used as an assay model for studies on angiogenesis, 3-dimensional cell culture, and delivery of growth factors and cells in vivo.

  9. 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

  10. 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.

  11. The anisotropic mechanical behaviour of electro-spun biodegradable polymer scaffolds: Experimental characterisation and constitutive formulation.

    PubMed

    Limbert, Georges; Omar, Rodaina; Krynauw, Hugo; Bezuidenhout, Deon; Franz, Thomas

    2016-01-01

    Electro-spun biodegradable polymer fibrous structures exhibit anisotropic mechanical properties dependent on the degree of fibre alignment. Degradation and mechanical anisotropy need to be captured in a constitutive formulation when computational modelling is used in the development and design optimisation of such scaffolds. Biodegradable polyester-urethane scaffolds were electro-spun and underwent uniaxial tensile testing in and transverse to the direction of predominant fibre alignment before and after in vitro degradation of up to 28 days. A microstructurally-based transversely isotropic hyperelastic continuum constitutive formulation was developed and its parameters were identified from the experimental stress-strain data of the scaffolds at various stages of degradation. During scaffold degradation, maximum stress and strain in circumferential direction decreased from 1.02 ± 0.23 MPa to 0.38 ± 0.004 MPa and from 46 ± 11 % to 12 ± 2 %, respectively. In longitudinal direction, maximum stress and strain decreased from 0.071 ± 0.016 MPa to 0.010 ± 0.007 MPa and from 69 ± 24 % to 8 ± 2 %, respectively. The constitutive parameters were identified for both directions of the non-degraded and degraded scaffold for strain range varying between 0% and 16% with coefficients of determination r(2)>0.871. The six-parameter constitutive formulation proved versatile enough to capture the varying non-linear transversely isotropic behaviour of the fibrous scaffold throughout various stages of degradation.

  12. Engineered Biopolymeric Scaffolds for Chronic Wound Healing.

    PubMed

    Dickinson, Laura E; Gerecht, Sharon

    2016-01-01

    Skin regeneration requires the coordinated integration of concomitant biological and molecular events in the extracellular wound environment during overlapping phases of inflammation, proliferation, and matrix remodeling. This process is highly efficient during normal wound healing. However, chronic wounds fail to progress through the ordered and reparative wound healing process and are unable to heal, requiring long-term treatment at high costs. There are many advanced skin substitutes, which mostly comprise bioactive dressings containing mammalian derived matrix components, and/or human cells, in clinical use. However, it is presently hypothesized that no treatment significantly outperforms the others. To address this unmet challenge, recent research has focused on developing innovative acellular biopolymeric scaffolds as more efficacious wound healing therapies. These biomaterial-based skin substitutes are precisely engineered and fine-tuned to recapitulate aspects of the wound healing milieu and target specific events in the wound healing cascade to facilitate complete skin repair with restored function and tissue integrity. This mini-review will provide a brief overview of chronic wound healing and current skin substitute treatment strategies while focusing on recent engineering approaches that regenerate skin using synthetic, biopolymeric scaffolds. We discuss key polymeric scaffold design criteria, including degradation, biocompatibility, and microstructure, and how they translate to inductive microenvironments that stimulate cell infiltration and vascularization to enhance chronic wound healing. As healthcare moves toward precision medicine-based strategies, the potential and therapeutic implications of synthetic, biopolymeric scaffolds as tunable treatment modalities for chronic wounds will be considered. PMID:27547189

  13. Engineered Biopolymeric Scaffolds for Chronic Wound Healing

    PubMed Central

    Dickinson, Laura E.; Gerecht, Sharon

    2016-01-01

    Skin regeneration requires the coordinated integration of concomitant biological and molecular events in the extracellular wound environment during overlapping phases of inflammation, proliferation, and matrix remodeling. This process is highly efficient during normal wound healing. However, chronic wounds fail to progress through the ordered and reparative wound healing process and are unable to heal, requiring long-term treatment at high costs. There are many advanced skin substitutes, which mostly comprise bioactive dressings containing mammalian derived matrix components, and/or human cells, in clinical use. However, it is presently hypothesized that no treatment significantly outperforms the others. To address this unmet challenge, recent research has focused on developing innovative acellular biopolymeric scaffolds as more efficacious wound healing therapies. These biomaterial-based skin substitutes are precisely engineered and fine-tuned to recapitulate aspects of the wound healing milieu and target specific events in the wound healing cascade to facilitate complete skin repair with restored function and tissue integrity. This mini-review will provide a brief overview of chronic wound healing and current skin substitute treatment strategies while focusing on recent engineering approaches that regenerate skin using synthetic, biopolymeric scaffolds. We discuss key polymeric scaffold design criteria, including degradation, biocompatibility, and microstructure, and how they translate to inductive microenvironments that stimulate cell infiltration and vascularization to enhance chronic wound healing. As healthcare moves toward precision medicine-based strategies, the potential and therapeutic implications of synthetic, biopolymeric scaffolds as tunable treatment modalities for chronic wounds will be considered. PMID:27547189

  14. 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

  15. Towards embryonic-like scaffolds for skin tissue engineering: identification of effector molecules and construction of scaffolds.

    PubMed

    Uijtdewilligen, P J E; Versteeg, E M M; Gilissen, C; van Reijmersdal, S V; Schoppmeyer, R; Wismans, R G; Daamen, W F; van Kuppevelt, T H

    2016-01-01

    Autologous skin grafts are the gold standard for the treatment of burn wounds. In a number of cases, treatment with autologous tissue is not possible and skin substitutes are used. The outcome, however, is not optimal and improvements are needed. Inspired by scarless healing in early embryonic development, we here set out a strategy for the design and construction of embryonic-like scaffolds for skin tissue engineering. This strategy may serve as a general approach in the construction of embryonic-like scaffolds for other tissues/organ. As a first step, key effector molecules upregulated during embryonic and neonatal skin formation were identified using a comparative gene expressing analysis. A set of 20 effector molecules was identified, from which insulin-like growth factor 2 (IGF2) and sonic hedgehog (SHH) were selected for incorporation into a type I collagen-heparin scaffold. Porous scaffolds were constructed using purified collagen fibrils and 6% covalently bound heparin (to bind and protect the growth factors), and IGF2 and SHH were incorporated either individually (~0.7 and 0.4 µg/mg scaffolds) or in combination (combined ~1.5 µg/mg scaffolds). In addition, scaffolds containing hyaluronan (up to 20 µg/mg scaffold) were prepared, based on the up- or downregulation of genes involved in hyaluronan synthesis/degradation and its suggested role in scarless healing. In conclusion, based on a comprehensive gene expression analysis, a set of effector molecules and matrix molecules was identified and incorporated into porous scaffolds. The scaffolds thus prepared may create an 'embryonic-like' environment for cells to recapitulate embryonic events and for new tissues/organs.

  16. 3D conductive nanocomposite scaffold for bone tissue engineering

    PubMed Central

    Shahini, Aref; Yazdimamaghani, Mostafa; Walker, Kenneth J; Eastman, Margaret A; Hatami-Marbini, Hamed; Smith, Brenda J; Ricci, John L; Madihally, Sundar V; Vashaee, Daryoosh; Tayebi, Lobat

    2014-01-01

    Bone healing can be significantly expedited by applying electrical stimuli in the injured region. Therefore, a three-dimensional (3D) ceramic conductive tissue engineering scaffold for large bone defects that can locally deliver the electrical stimuli is highly desired. In the present study, 3D conductive scaffolds were prepared by employing a biocompatible conductive polymer, ie, poly(3,4-ethylenedioxythiophene) poly(4-styrene sulfonate) (PEDOT:PSS), in the optimized nanocomposite of gelatin and bioactive glass. For in vitro analysis, adult human mesenchymal stem cells were seeded in the scaffolds. Material characterizations using hydrogen-1 nuclear magnetic resonance, in vitro degradation, as well as thermal and mechanical analysis showed that incorporation of PEDOT:PSS increased the physiochemical stability of the composite, resulting in improved mechanical properties and biodegradation resistance. The outcomes indicate that PEDOT:PSS and polypeptide chains have close interaction, most likely by forming salt bridges between arginine side chains and sulfonate groups. The morphology of the scaffolds and cultured human mesenchymal stem cells were observed and analyzed via scanning electron microscope, micro-computed tomography, and confocal fluorescent microscope. Increasing the concentration of the conductive polymer in the scaffold enhanced the cell viability, indicating the improved microstructure of the scaffolds or boosted electrical signaling among cells. These results show that these conductive scaffolds are not only structurally more favorable for bone tissue engineering, but also can be a step forward in combining the tissue engineering techniques with the method of enhancing the bone healing by electrical stimuli. PMID:24399874

  17. Stabilized Collagen Scaffolds for Heart Valve Tissue Engineering

    PubMed Central

    Tedder, Mary E.; Liao, Jun; Weed, Benjamin; Stabler, Christopher; Zhang, Henry; Simionescu, Agneta

    2009-01-01

    Scaffolds for heart valve tissue engineering must function immediately after implantation but also need to tolerate cell infiltration and gradual remodeling. We hypothesized that moderately cross-linked collagen scaffolds would fulfill these requirements. To test our hypothesis, scaffolds prepared from decellularized porcine pericardium were treated with penta-galloyl glucose (PGG), a collagen-binding polyphenol, and tested for biodegradation, biaxial mechanical properties, and in vivo biocompatibility. For controls, we used un-cross-linked scaffolds and glutaraldehyde-treated scaffolds. Results confirmed complete pericardium decellularization and the ability of scaffolds to encourage fibroblast chemotaxis and to aid in creation of anatomically correct valve-shaped constructs. Glutaraldehyde cross-linking fully stabilized collagen but did not allow for tissue remodeling and calcified when implanted subdermally in rats. PGG-treated collagen was initially resistant to collagenase and then degraded gradually, indicating partial stabilization. Moreover, PGG-treated pericardium exhibited excellent biaxial mechanical properties, did not calcify in vivo, and supported infiltration by host fibroblasts and subsequent matrix remodeling. In conclusion, PGG-treated acellular pericardium is a promising scaffold for heart valve tissue engineering. PMID:18928400

  18. Stabilized collagen scaffolds for heart valve tissue engineering.

    PubMed

    Tedder, Mary E; Liao, Jun; Weed, Benjamin; Stabler, Christopher; Zhang, Henry; Simionescu, Agneta; Simionescu, Dan T

    2009-06-01

    Scaffolds for heart valve tissue engineering must function immediately after implantation but also need to tolerate cell infiltration and gradual remodeling. We hypothesized that moderately cross-linked collagen scaffolds would fulfill these requirements. To test our hypothesis, scaffolds prepared from decellularized porcine pericardium were treated with penta-galloyl glucose (PGG), a collagen-binding polyphenol, and tested for biodegradation, biaxial mechanical properties, and in vivo biocompatibility. For controls, we used un-cross-linked scaffolds and glutaraldehyde-treated scaffolds. Results confirmed complete pericardium decellularization and the ability of scaffolds to encourage fibroblast chemotaxis and to aid in creation of anatomically correct valve-shaped constructs. Glutaraldehyde cross-linking fully stabilized collagen but did not allow for tissue remodeling and calcified when implanted subdermally in rats. PGG-treated collagen was initially resistant to collagenase and then degraded gradually, indicating partial stabilization. Moreover, PGG-treated pericardium exhibited excellent biaxial mechanical properties, did not calcify in vivo, and supported infiltration by host fibroblasts and subsequent matrix remodeling. In conclusion, PGG-treated acellular pericardium is a promising scaffold for heart valve tissue engineering. PMID:18928400

  19. Triggerable Degradation of Polyurethanes for Tissue Engineering Applications.

    PubMed

    Xu, Cancan; Huang, Yihui; Wu, Jinglei; Tang, Liping; Hong, Yi

    2015-09-16

    Tissue engineered and bioactive scaffolds with different degradation rates are required for the regeneration of diverse tissues/organs. To optimize tissue regeneration in different tissues, it is desirable that the degradation rate of scaffolds can be manipulated to comply with various stages of tissue regeneration. Unfortunately, the degradation of most degradable polymers relies solely on passive controlled degradation mechanisms. To overcome this challenge, we report a new family of reduction-sensitive biodegradable elastomeric polyurethanes containing various amounts of disulfide bonds (PU-SS), in which degradation can be initiated and accelerated with the supplement of a biological product: antioxidant-glutathione (GSH). The polyurethanes can be processed into films and electrospun fibrous scaffolds. Synthesized materials exhibited robust mechanical properties and high elasticity. Accelerated degradation of the materials was observed in the presence of GSH, and the rate of such degradation depends on the amount of disulfide present in the polymer backbone. The polymers and their degradation products exhibited no apparent cell toxicity while the electrospun scaffolds supported fibroblast growth in vitro. The in vivo subcutaneous implantation model showed that the polymers prompt minimal inflammatory responses, and as anticipated, the polymer with the higher disulfide bond amount had faster degradation in vivo. This new family of polyurethanes offers tremendous potential for directed scaffold degradation to promote maximal tissue regeneration. PMID:26312436

  20. Triggerable Degradation of Polyurethanes for Tissue Engineering Applications.

    PubMed

    Xu, Cancan; Huang, Yihui; Wu, Jinglei; Tang, Liping; Hong, Yi

    2015-09-16

    Tissue engineered and bioactive scaffolds with different degradation rates are required for the regeneration of diverse tissues/organs. To optimize tissue regeneration in different tissues, it is desirable that the degradation rate of scaffolds can be manipulated to comply with various stages of tissue regeneration. Unfortunately, the degradation of most degradable polymers relies solely on passive controlled degradation mechanisms. To overcome this challenge, we report a new family of reduction-sensitive biodegradable elastomeric polyurethanes containing various amounts of disulfide bonds (PU-SS), in which degradation can be initiated and accelerated with the supplement of a biological product: antioxidant-glutathione (GSH). The polyurethanes can be processed into films and electrospun fibrous scaffolds. Synthesized materials exhibited robust mechanical properties and high elasticity. Accelerated degradation of the materials was observed in the presence of GSH, and the rate of such degradation depends on the amount of disulfide present in the polymer backbone. The polymers and their degradation products exhibited no apparent cell toxicity while the electrospun scaffolds supported fibroblast growth in vitro. The in vivo subcutaneous implantation model showed that the polymers prompt minimal inflammatory responses, and as anticipated, the polymer with the higher disulfide bond amount had faster degradation in vivo. This new family of polyurethanes offers tremendous potential for directed scaffold degradation to promote maximal tissue regeneration.

  1. In vitro evaluation of alginate/halloysite nanotube composite scaffolds for tissue engineering.

    PubMed

    Liu, Mingxian; Dai, Libing; Shi, Huizhe; Xiong, Sheng; Zhou, Changren

    2015-04-01

    In this study, a series of alginate/halloysite nanotube (HNTs) composite scaffolds were prepared by solution-mixing and freeze-drying method. HNTs are incorporated into alginate to improve both the mechanical and cell-attachment properties of the scaffolds. The interfacial interactions between alginate and HNTs were confirmed by the atomic force microscope (AFM), transmission electron microscope (TEM) and FTIR spectroscopy. The mechanical, morphological, and physico-chemical properties of the composite scaffolds were investigated. The composite scaffolds exhibit significant enhancement in compressive strength and compressive modulus compared with pure alginate scaffold both in dry and wet states. A well-interconnected porous structure with size in the range of 100-200μm and over 96% porosity is found in the composite scaffolds. X-ray diffraction (XRD) result shows that HNTs are uniformly dispersed and partly oriented in the composite scaffolds. The incorporation of HNTs leads to increase in the scaffold density and decrease in the water swelling ratio of alginate. HNTs improve the stability of alginate scaffolds against enzymatic degradation in PBS solution. Thermogravimetrica analysis (TGA) shows that HNTs can improve the thermal stability of the alginate. The mouse fibroblast cells display better attachment to the alginate/HNT composite than those to the pure alginate, suggesting the good cytocompatibility of the composite scaffolds. Alginate/HNT composite scaffolds exhibit great potential for applications in tissue engineering. PMID:25686999

  2. Chitosan-collagen/organomontmorillonite scaffold for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Cao, Xianshuo; Wang, Jun; Liu, Min; Chen, Yong; Cao, Yang; Yu, Xiaolong

    2015-12-01

    A novel composite scaffold based on chitosan-collagen/organomontmorillonite (CS-COL/OMMT) was prepared to improve swelling ratio, biodegradation ratio, biomineralization and mechanical properties for use in tissue engineering applications. In order to expend the basal spacing, montmorillonite (MMT) was modified with sodium dodecyl sulfate (SDS) and was characterized by XRD, TGA and FTIR. The results indicated that the anionic surfactants entered into interlayer of MMT and the basal spacing of MMT was expanded to 3.85 nm. The prepared composite scaffolds were characterized by FTIR, XRD and SEM. The swelling ratio, biodegradation ratio and mechanical properties of composite scaffolds were also studied. The results demonstrated that the scaffold decreased swelling ratio, degradation ratio and improved mechanical and biomineralization properties because of OMMT.

  3. ELEVATING MECHANISM

    DOEpatents

    Frederick, H.S.; Kinsella, M.A.

    1959-02-24

    An elevator is described, which is arranged for movement both in a horizontal and in a vertical direction so that the elevating mechanism may be employed for servicing equipment at separated points in a plant. In accordance with the present invention, the main elevator chassis is suspended from a monorail. The chassis, in turn supports a vertically moveable carriage, a sub- carriage vertically moveable on the carriage, and a turntable carried by the sub- carriage and moveable through an arc of 90 with the equipment attached thereto. In addition, the chassis supports all the means required to elevate or rotate the equipment.

  4. Fabrication and characterization of novel nano-biocomposite scaffold of chitosan-gelatin-alginate-hydroxyapatite for bone tissue engineering.

    PubMed

    Sharma, Chhavi; Dinda, Amit Kumar; Potdar, Pravin D; Chou, Chia-Fu; Mishra, Narayan Chandra

    2016-07-01

    A novel nano-biocomposite scaffold was fabricated in bead form by applying simple foaming method, using a combination of natural polymers-chitosan, gelatin, alginate and a bioceramic-nano-hydroxyapatite (nHAp). This approach of combining nHAp with natural polymers to fabricate the composite scaffold, can provide good mechanical strength and biological property mimicking natural bone. Environmental scanning electron microscopy (ESEM) images of the nano-biocomposite scaffold revealed the presence of interconnected pores, mostly spread over the whole surface of the scaffold. The nHAp particulates have covered the surface of the composite matrix and made the surface of the scaffold rougher. The scaffold has a porosity of 82% with a mean pore size of 112±19.0μm. Swelling and degradation studies of the scaffold showed that the scaffold possesses excellent properties of hydrophilicity and biodegradability. Short term mechanical testing of the scaffold does not reveal any rupturing after agitation under physiological conditions, which is an indicative of good mechanical stability of the scaffold. In vitro cell culture studies by seeding osteoblast cells over the composite scaffold showed good cell viability, proliferation rate, adhesion and maintenance of osteoblastic phenotype as indicated by MTT assay, ESEM of cell-scaffold construct, histological staining and gene expression studies, respectively. Thus, it could be stated that the nano-biocomposite scaffold of chitosan-gelatin-alginate-nHAp has the paramount importance for applications in bone tissue-engineering in future regenerative therapies.

  5. 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

  6. Electrospun scaffolds of silk fibroin and poly(lactide-co-glycolide) for endothelial cell growth.

    PubMed

    Zhou, Wei; Feng, Yakai; Yang, Jing; Fan, Jiaxu; Lv, Juan; Zhang, Li; Guo, Jintang; Ren, Xiangkui; Zhang, Wencheng

    2015-01-01

    Electrospun scaffolds of silk fibroin (SF) and poly(lactide-co-glycolide) (PLGA) were prepared to mimic the morphology and chemistry of the extracellular matrix. The SF/PLGA scaffolds were treated with ethanol to improve their usability. After ethanol treatment the scaffolds exhibited a smooth surface and uniform fibers. SF transformed from random coil conformation to β-sheet structure after ethanol treatment, so that the SF/PLGA scaffolds showed low hydrophilicity and dissolving rate in water. The mechanical properties and the hydrophilicity of the blended fibrous scaffolds were affected by the weight ratio of SF and PLGA. During degradation of ethanol-treated SF/PLGA scaffolds in vitro, the fibers became thin along with the degradation time. Human umbilical vein endothelial cells (HUVECs) were seeded onto the ethanol-treated nanofibrous scaffolds for cell viability, attachment and morphogenesis studies. These SF/PLGA scaffolds could enhance the viability, spreading and attachment of HUVECs. Based on these results, these ethanol-treated scaffolds are proposed to be a good candidate for endothelial cell growth. PMID:25601671

  7. Iron Oxide-labeled Collagen Scaffolds for Non-invasive MR Imaging in Tissue Engineering

    PubMed Central

    Mertens, Marianne E.; Hermann, Alina; Bühren, Anne; Olde-Damink, Leon; Möckel, Diana; Gremse, Felix; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

    2013-01-01

    Non-invasive imaging holds significant potential for implementation in tissue engineering. It can e.g. be used to monitor the localization and function of tissue-engineered implants, as well as their resorption and remodelling. Thus far, however, the vast majority of efforts in this area of research have focused on the use of ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticle-labeled cells, colonizing the scaffolds, to indirectly image the implant material. Reasoning that directly labeling scaffold materials might be more beneficial (enabling imaging also in case of non-cellularized implants), more informative (enabling the non-invasive visualization and quantification of scaffold degradation) and more easy to translate into the clinic (since cell-free materials are less complex from a regulatory point-of-view), we here prepared three different types of USPIO nanoparticles, and incorporated them both passively and actively (via chemical conjugation; during collagen crosslinking) into collagen-based scaffold materials. We furthermore optimized the amount of USPIO incorporated into the scaffolds, correlated the amount of entrapped USPIO with MR signal intensity, showed that the labeled scaffolds are highly biocompatible, demonstrated that scaffold degradation can be visualized using MRI and provided initial proof-of-principle for the in vivo visualization of the scaffolds. Consequently, USPIO-labeled scaffold materials seem to be highly suitable for image-guided tissue engineering applications. PMID:24569840

  8. A Silk-Based Scaffold Platform with Tunable Architecture for Engineering Critically-Sized Tissue Constructs

    PubMed Central

    Wray, Lindsay S.; Rnjak-Kovacina, Jelena; Mandal, Biman B.; Schmidt, Daniel F.; Seok, Eun; Kaplan, David L.

    2012-01-01

    In the field of tissue engineering and regenerative medicine there is significant unmet need for critically-sized, fully degradable biomaterial scaffold systems with tunable properties for optimizing tissue formation in vitro and tissue regeneration in vivo. To address this need, we have developed a silk-based scaffold platform that has tunable material properties, including localized and bioactive functionalization, degradation rate, and mechanical properties and that provides arrays of linear hollow channels for delivery of oxygen and nutrients throughout the scaffold bulk. The scaffolds can be assembled with dimensions that range from millimeters to centimeters, addressing the need for a critically-sized platform for tissue formation. We demonstrate that the hollow channel arrays support localized and confluent endothelialization. This new platform offers a unique and versatile tool for engineering `tailored' scaffolds for a range of tissue engineering and regenerative medicine needs. PMID:23036961

  9. Fabrication and in vitro characterization of bioactive glass composite scaffolds for bone regeneration.

    PubMed

    Poh, Patrina S P; Hutmacher, Dietmar W; Stevens, Molly M; Woodruff, Maria A

    2013-12-01

    Here we fabricate and characterize bioactive composite scaffolds for bone tissue engineering applications. 45S5 Bioglass® (45S5) or strontium-substituted bioactive glass (SrBG) were incorporated into polycaprolactone (PCL) and fabricated into 3D bioactive composite scaffolds utilizing additive manufacturing technology. We show that composite scaffolds (PCL/45S5 and PCL/SrBG) can be reproducibly manufactured with a scaffold morphology highly resembling that of PCL scaffolds. Additionally, micro-CT analysis reveals BG particles were homogeneously distributed throughout the scaffolds. Mechanical data suggested that PCL/45S5 and PCL/SrBG composite scaffolds have higher compressive Young's modulus compared to PCL scaffolds at similar porosity (∼75%). After 1 day in accelerated degradation conditions using 5M NaOH, PCL/SrBG, PCL/45S5 and PCL lost 48.6 ± 3.8%, 12.1 ± 1% and 1.6 ± 1% of the original mass, respectively. In vitro studies were conducted using MC3T3 cells under normal and osteogenic conditions. All scaffolds were shown to be non-cytotoxic, and supported cell attachment and proliferation. Our results also indicate that the inclusion of bioactive glass (BG) promotes precipitation of calcium phosphate on the scaffold surfaces which leads to earlier cell differentiation and matrix mineralization when compared to PCL scaffolds. However, as indicated by alkaline phosphatase activity, no significant difference in osteoblast differentiation was found between PCL/45S5 and PCL/SrBG scaffolds. These results suggest that PCL/45S5 and PCL/SrBG composite scaffolds show potential as next generation bone scaffolds.

  10. Optimization of keratin/alginate scaffold using RSM and its characterization for tissue engineering.

    PubMed

    Gupta, Pratima; Nayak, Kush Kumar

    2016-04-01

    The scaffold for tissue engineering was fabricated from a binary blend of keratin/alginate. The concentration and ratio of keratin and alginate was optimized by response surface methodology in a scaffold. The structural compatibility between keratin and alginate was examined by X-ray diffractometer and Fourier transforms infrared spectroscopy. Apparent porosity of the scaffold was calculated by Archimedes principles and its observed value of was found 96.25 ± 0.04%. The pore size of the scaffold was observed in the range between 10 and 200 μm. Tensile strength (0.33 ± 0.26 MPa) and percent of elongation at break (23.33 ± 2.52%) are the reported mechanical strength of the scaffold. Positive antimicrobial activity and in vitro degradation further confirms the fabrication of a scaffold required for tissue engineering application. PMID:26691383

  11. Optimization of keratin/alginate scaffold using RSM and its characterization for tissue engineering.

    PubMed

    Gupta, Pratima; Nayak, Kush Kumar

    2016-04-01

    The scaffold for tissue engineering was fabricated from a binary blend of keratin/alginate. The concentration and ratio of keratin and alginate was optimized by response surface methodology in a scaffold. The structural compatibility between keratin and alginate was examined by X-ray diffractometer and Fourier transforms infrared spectroscopy. Apparent porosity of the scaffold was calculated by Archimedes principles and its observed value of was found 96.25 ± 0.04%. The pore size of the scaffold was observed in the range between 10 and 200 μm. Tensile strength (0.33 ± 0.26 MPa) and percent of elongation at break (23.33 ± 2.52%) are the reported mechanical strength of the scaffold. Positive antimicrobial activity and in vitro degradation further confirms the fabrication of a scaffold required for tissue engineering application.

  12. Surface modification of biodegradable porous Mg bone scaffold using polycaprolactone/bioactive glass composite.

    PubMed

    Yazdimamaghani, Mostafa; Razavi, Mehdi; Vashaee, Daryoosh; Tayebi, Lobat

    2015-04-01

    A reduction in the degradation rate of magnesium (Mg) and its alloys is in high demand to enable these materials to be used in orthopedic applications. For this purpose, in this paper, a biocompatible polymeric layer reinforced with a bioactive ceramic made of polycaprolactone (PCL) and bioactive glass (BG) was applied on the surface of Mg scaffolds using dip-coating technique under low vacuum. The results indicated that the PCL-BG coated Mg scaffolds exhibited noticeably enhanced bioactivity compared to the uncoated scaffold. Moreover, the mechanical integrity of the Mg scaffolds was improved using the PCL-BG coating on the surface. The stable barrier property of the coatings effectively delayed the degradation activity of Mg scaffold substrates. Moreover, the coatings induced the formation of apatite layer on their surface after immersion in the SBF, which can enhance the biological bone in-growth and block the microcracks and pore channels in the coatings, thus prolonging their protective effect. Furthermore, it was shown that a three times increase in the concentration of PCL-BG noticeably improved the characteristics of scaffolds including their degradation resistance and mechanical stability. Since bioactivity, degradation resistance and mechanical integrity of a bone substitute are the key factors for repairing and healing fractured bones, we suggest that PCL-BG is a suitable coating material for surface modification of Mg scaffolds.

  13. A tunable protein-based scaffold for the study of central nervous system regeneration

    NASA Astrophysics Data System (ADS)

    Straley, Karin

    Central nervous system (CNS) injuries pose a significant and potentially debilitating health problem in society today and, to date, no successful clinical repair strategies have been advanced. The development of effective treatments is severely hindered by the quick formation of a complex, inhibitory scar at the site of CNS injury. This scar both physically blocks and chemically suppresses nerve regeneration. It has been hypothesized that combinatorial approaches involving biomaterial scaffolds, cell transplantation, and pro-survival factors, which provide a more permissive growth environment, have the highest chance of stimulating regeneration. The work completed in this thesis focuses on the design and characterization of a biomimetic hydrogel scaffold constructed from chemically crosslinked recombinant proteins. This protein-based scaffold has been designed to offer a flexible platform for the systematic optimization of key scaffold design parameters, such as mechanical strength, degradation, cellular interaction, molecule delivery, and topography. Specifically, a collection of proteins containing sequences previously shown to enhance cell adhesion, to promote neurite extension, and to exhibit varying susceptibility to cleavage by neurite-secreted proteases were synthesized to serve as the polymer backbone for the scaffold. Experiments were conducted to analyze the capacity of scaffolds, constructed from single proteins or mixtures of proteins, to independently control cell behavior, scaffold degradation properties, and scaffold mechanical properties based upon differences in the primary protein sequence and crosslinking conditions. In addition, composite scaffolds constructed by layered spatial deposition of chemically crosslinked, protease-degradable proteins were applied to the formation of dynamic internal, three-dimensional scaffold patterns that can be directly coupled to molecule delivery. Overall, this work demonstrates the tunable and bio

  14. 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

  15. The effect of scaffold-cell entrapment capacity and physico-chemical properties on cartilage regeneration.

    PubMed

    Hendriks, J A A; Moroni, L; Riesle, J; de Wijn, J R; van Blitterswijk, C A

    2013-06-01

    An important tenet in designing scaffolds for regenerative medicine consists in mimicking the dynamic mechanical properties of the tissues to be replaced to facilitate patient rehabilitation and restore daily activities. In addition, it is important to determine the contribution of the forming tissue to the mechanical properties of the scaffold during culture to optimize the pore network architecture. Depending on the biomaterial and scaffold fabrication technology, matching the scaffolds mechanical properties to articular cartilage can compromise the porosity, which hampers tissue formation. Here, we show that scaffolds with controlled and interconnected pore volume and matching articular cartilage dynamic mechanical properties, are indeed effective to support tissue regeneration by co-cultured primary and expanded chondrocyte (1:4). Cells were cultured on scaffolds in vitro for 4 weeks. A higher amount of cartilage specific matrix (ECM) was formed on mechanically matching (M) scaffolds after 28 days. A less protein adhesive composition supported chondrocytes rounded morphology, which contributed to cartilaginous differentiation. Interestingly, the dynamic stiffness of matching constructs remained approximately at the same value after culture, suggesting a comparable kinetics of tissue formation and scaffold degradation. Cartilage regeneration in matching scaffolds was confirmed subcutaneously in vivo. These results imply that mechanically matching scaffolds with appropriate physico-chemical properties support chondrocyte differentiation.

  16. Preparation and Evaluation of Gelatin-Chitosan-Nanobioglass 3D Porous Scaffold for Bone Tissue Engineering

    PubMed Central

    Maji, Kanchan; Dasgupta, Sudip; Pramanik, Krishna; Bissoyi, Akalabya

    2016-01-01

    The aim of the present study was to prepare and characterize bioglass-natural biopolymer based composite scaffold and evaluate its bone regeneration ability. Bioactive glass nanoparticles (58S) in the size range of 20–30 nm were synthesized using sol-gel method. Porous scaffolds with varying bioglass composition from 10 to 30 wt% in chitosan, gelatin matrix were fabricated using the method of freeze drying of its slurry at 40 wt% solids loading. Samples were cross-linked with glutaraldehyde to obtain interconnected porous 3D microstructure with improved mechanical strength. The prepared scaffolds exhibited >80% porosity with a mean pore size range between 100 and 300 microns. Scaffold containing 30 wt% bioglass (GCB 30) showed a maximum compressive strength of 2.2 ± 0.1 MPa. Swelling and degradation studies showed that the scaffold had excellent properties of hydrophilicity and biodegradability. GCB 30 scaffold was shown to be noncytotoxic and supported mesenchymal stem cell attachment, proliferation, and differentiation as indicated by MTT assay and RUNX-2 expression. Higher cellular activity was observed in GCB 30 scaffold as compared to GCB 0 scaffold suggesting the fact that 58S bioglass nanoparticles addition into the scaffold promoted better cell adhesion, proliferation, and differentiation. Thus, the study showed that the developed composite scaffolds are potential candidates for regenerating damaged bone tissue. PMID:26884764

  17. Processing and characterization of chitosan/PVA and methylcellulose porous scaffolds for tissue engineering.

    PubMed

    Kanimozhi, K; Khaleel Basha, S; Sugantha Kumari, V

    2016-04-01

    Biomimetic porous scaffold chitosan/poly(vinyl alcohol) CS/PVA containing various amounts of methylcellulose (MC) (25%, 50% and 75%) incorporated in CS/PVA blend was successfully produced by a freeze drying method in the present study. The composite porous scaffold membranes were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), swelling degree, porosity, degradation of films in Hank's solution and the mechanical properties. Besides these characterizations, the antibacterial activity of the prepared scaffolds was tested, toward the bacterial species Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli). FTIR, XRD and DSC demonstrated that there was strong intermolecular hydrogen bonding between the molecules of CS/PVA and MC. The crystalline microstructure of the scaffold membranes was not well developed. SEM images showed that the morphology and diameter of the scaffolds were mainly affected by the weight ratio of MC. By increasing the MC content in the hybrid scaffolds, their swelling capacity and porosity increased. The mechanical properties of these scaffolds in dry and swollen state were greatly improved with high swelling ratio. The elasticity of films was also significantly improved by the incorporation of MC, and the scaffolds could also bear a relative high tensile strength. These findings suggested that the developed scaffold possess the prerequisites and can be used as a scaffold for tissue engineering. PMID:26838875

  18. Electrospun biodegradable calcium containing poly(ester-urethane)urea: synthesis, fabrication, in vitro degradation, and biocompatibility evaluation.

    PubMed

    Nair, Priya A; Ramesh, P

    2013-07-01

    In this work an in vitro degradable poly(ester-urethane)urea (PEUU) was synthesized using polycaprolactone diol, hexamethylene diisocyanate, and calcium salt of p-aminobenzoic acid. The synthesized polymer was characterized by (1) H-NMR and FTIR spectroscopy and viscosity studies. Scaffolds having random micro fibrous structures were fabricated from PEUU by electrospinning process. The thermal properties of the scaffold were evaluated by thermogravimetric analysis and dynamic mechanical analysis. The mechanical property evaluation showed that the scaffold possess sufficiently high tensile strength of 16 MPa. The in vitro degradation studies of the electrospun scaffold were carried out in phosphate buffer saline for 6 months. The average mass loss of the scaffold after 6 months of hydrolytic degradation was 25%. FTIR spectroscopy study confirmed the degradation of the PEUU from decrease in intensity of 1400 cm(-1) peak corresponding to ionic carboxylate group. Presence of amine group and calcium ions in the degradation medium further confirmed the degradation of the hard segment in the hydrolytic medium. The mechanical property evaluation of the scaffold indicated a gradual decrease in tensile strength and modulus whereas percentage elongation of the scaffold increases with time of in vitro degradation. The morphological evaluation of the scaffold after degradation by SEM shows evidence of broken fibers and pores in the scaffold. Preliminary in vitro cytotoxicity test demonstrated that both the material and the degradation products were noncytotoxic in nature and the material showed good proliferation to L-929 cells.

  19. 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…

  20. The Potential to Improve Cell Infiltration in Composite Fiber-Aligned Electrospun Scaffolds by the Selective Removal of Sacrificial Fibers

    PubMed Central

    Baker, Brendon M.; Gee, Albert O.; Metter, Robert B.; Nathan, Ashwin S.; Marklein, Ross L.; Burdick, Jason A.; Mauck, Robert L.

    2008-01-01

    Aligned electrospun scaffolds are a promising tool for engineering fibrous musculoskeletal tissues as they reproduce the mechanical anisotropy of these tissues and can direct ordered neo-tissue formation. However, these scaffolds suffer from a slow cellular infiltration rate, likely due in part to their dense fiber packing. We hypothesized that cell ingress could be expedited in scaffolds by increasing porosity, while at the same time preserving overall scaffold anisotropy. To test this hypothesis, poly(ε-caprolactone) (a slow-degrading polyester) and poly(ethylene oxide) (a water-soluble polymer) were co-electrospun from two separate spinnerets to form dual-polymer composite fiber-aligned scaffolds. Adjusting fabrication parameters produced aligned scaffolds with a full range of sacrificial (PEO) fiber contents. Tensile properties of scaffolds were a function of the ratio of PCL to PEO in the composite scaffolds, and were altered in a predictable fashion with removal of the PEO component. When seeded with mesenchymal stem cells (MSCs), increases in the starting sacrificial fraction (and porosity) improved cell infiltration and distribution after three weeks in culture. In pure PCL scaffolds, cells lined the scaffold periphery, while scaffolds containing >50% sacrificial PEO content had cells present throughout the scaffold. These findings indicate that cell infiltration can be expedited in dense fibrous assemblies with the removal of sacrificial fibers. This strategy may enhance in vitro and in vivo formation and maturation of a functional constructs for fibrous tissue engineering. PMID:18313138

  1. Scaffolds and cells for tissue regeneration: different scaffold pore sizes-different cell effects.

    PubMed

    Bružauskaitė, Ieva; Bironaitė, Daiva; Bagdonas, Edvardas; Bernotienė, Eiva

    2016-05-01

    During the last decade biomaterial sciences and tissue engineering have become new scientific fields supplying rising demand of regenerative therapy. Tissue engineering requires consolidation of a broad knowledge of cell biology and modern biotechnology investigating biocompatibility of materials and their application for the reconstruction of damaged organs and tissues. Stem cell-based tissue regeneration started from the direct cell transplantation into damaged tissues or blood vessels. However, it is difficult to track transplanted cells and keep them in one particular place of diseased organ. Recently, new technologies such as cultivation of stem cell on the scaffolds and subsequently their implantation into injured tissue have been extensively developed. Successful tissue regeneration requires scaffolds with particular mechanical stability or biodegradability, appropriate size, surface roughness and porosity to provide a suitable microenvironment for the sufficient cell-cell interaction, cell migration, proliferation and differentiation. Further functioning of implanted cells highly depends on the scaffold pore sizes that play an essential role in nutrient and oxygen diffusion and waste removal. In addition, pore sizes strongly influence cell adhesion, cell-cell interaction and cell transmigration across the membrane depending on the various purposes of tissue regeneration. Therefore, this review will highlight contemporary tendencies in application of non-degradable scaffolds and stem cells in regenerative medicine with a particular focus on the pore sizes significantly affecting final recover of diseased organs.

  2. Indirect additive manufacturing as an elegant tool for the production of self-supporting low density gelatin scaffolds.

    PubMed

    Van Hoorick, Jasper; Declercq, Heidi; De Muynck, Amelie; Houben, Annemie; Van Hoorebeke, Luc; Cornelissen, Ria; Van Erps, Jürgen; Thienpont, Hugo; Dubruel, Peter; Van Vlierberghe, Sandra

    2015-10-01

    The present work describes for the first time the production of self-supporting low gelatin density (<10 w/v%) porous scaffolds using methacrylamide-modified gelatin as an extracellular matrix mimicking component. As porous scaffolds starting from low gelatin concentrations cannot be realized with the conventional additive manufacturing techniques in the abscence of additives, we applied an indirect fused deposition modelling approach. To realize this, we have printed a sacrificial polyester scaffold which supported the hydrogel material during UV crosslinking, thereby preventing hydrogel structure collapse. After complete curing, the polyester scaffold was selectively dissolved leaving behind a porous, interconnective low density gelatin scaffold. Scaffold structural analysis indicated the success of the selected indirect additive manufacturing approach. Physico-chemical testing revealed scaffold properties (mechanical, degradation, swelling) to depend on the applied gelatin concentration and methacrylamide content. Preliminary biocompatibility studies revealed the cell-interactive and biocompatible properties of the materials developed.

  3. Indirect additive manufacturing as an elegant tool for the production of self-supporting low density gelatin scaffolds.

    PubMed

    Van Hoorick, Jasper; Declercq, Heidi; De Muynck, Amelie; Houben, Annemie; Van Hoorebeke, Luc; Cornelissen, Ria; Van Erps, Jürgen; Thienpont, Hugo; Dubruel, Peter; Van Vlierberghe, Sandra

    2015-10-01

    The present work describes for the first time the production of self-supporting low gelatin density (<10 w/v%) porous scaffolds using methacrylamide-modified gelatin as an extracellular matrix mimicking component. As porous scaffolds starting from low gelatin concentrations cannot be realized with the conventional additive manufacturing techniques in the abscence of additives, we applied an indirect fused deposition modelling approach. To realize this, we have printed a sacrificial polyester scaffold which supported the hydrogel material during UV crosslinking, thereby preventing hydrogel structure collapse. After complete curing, the polyester scaffold was selectively dissolved leaving behind a porous, interconnective low density gelatin scaffold. Scaffold structural analysis indicated the success of the selected indirect additive manufacturing approach. Physico-chemical testing revealed scaffold properties (mechanical, degradation, swelling) to depend on the applied gelatin concentration and methacrylamide content. Preliminary biocompatibility studies revealed the cell-interactive and biocompatible properties of the materials developed. PMID:26411443

  4. Vaporizable Scaffolds for Fabricating Thermoelectric Modules

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeffrey; Yen, Shiao-pin; Fleurial, Jean-Pierre; Paik, Jong-Ah

    2006-01-01

    A process for fabricating thermoelectric modules with vacuum gaps separating the thermoelectric legs has been conceived, and the feasibility of some essential parts of the process has been demonstrated. The vacuum gaps are needed to electrically insulate the legs from each other. The process involves the use of scaffolding in the form of sheets of a polymer to temporarily separate the legs by the desired distance, which is typically about 0.5 mm. During a bonding subprocess that would take place in a partial vacuum at an elevated temperature, the polymer would be vaporized, thereby creating the vacuum gaps.

  5. Regenerated cellulose scaffolds: Preparation, characterization and toxicological evaluation.

    PubMed

    de Araújo Júnior, Adalberto M; Braido, Guilherme; Saska, Sybele; Barud, Hernane S; Franchi, Leonardo P; Assunção, Rosana M N; Scarel-Caminaga, Raquel M; Capote, Ticiana S O; Messaddeq, Younès; Ribeiro, Sidney J L

    2016-01-20

    Regenerated cellulose scaffolds (RCS) may be used as alloplastic materials for tissue repair. In this work, the RCS were obtained by viscose process and characterized by scanning electron microscopy (SEM), wide angle X-ray diffraction (WAXD), Fourier transform infrared spectroscopy (FTIR) and thermogravimetry analysis (TG). In vitro enzymatic degradation assay and toxicological assays were also evaluated. The physicochemical characterizations revealed the formation of a porous material with distinct thermal profile and crystallinity compared to pristine cellulose pulp. Enzymatic degradation assay revealed that lysozyme showed a mildest catalytic action when compared to cellulase, Tricoderma reesei (Tr). Nevertheless, both enzymes were efficient for degrading the RCS. RCS did not show cytotoxicity, mutagenic or genotoxic effects. The systematically characterization of this work suggests that RCS presented distinct features that make it a viable material for future studies related to the development of scaffolds for biological applications.

  6. 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

  7. Bioactive composite materials for tissue engineering scaffolds.

    PubMed

    Boccaccini, Aldo R; Blaker, Jonny J

    2005-05-01

    Synthetic bioactive and bioresorbable composite materials are becoming increasingly important as scaffolds for tissue engineering. Next-generation biomaterials should combine bioactive and bioresorbable properties to activate in vivo mechanisms of tissue regeneration, stimulating the body to heal itself and leading to replacement of the scaffold by the regenerating tissue. Certain bioactive ceramics such as tricalcium phosphate and hydroxyapatite as well as bioactive glasses, such as 45S5 Bioglass, react with physiologic fluids to form tenacious bonds with hard (and in some cases soft) tissue. However, these bioactive materials are relatively stiff, brittle and difficult to form into complex shapes. Conversely, synthetic bioresorbable polymers are easily fabricated into complex structures, yet they are too weak to meet the demands of surgery and the in vivo physiologic environment. Composites of tailored physical, biologic and mechanical properties as well as predictable degradation behavior can be produced combining bioresorbable polymers and bioactive inorganic phases. This review covers recent international research presenting the state-of-the-art development of these composite systems in terms of material constituents, fabrication technologies, structural and bioactive properties, as well as in vitro and in vivo characteristics for applications in tissue engineering and tissue regeneration. These materials may represent the effective optimal solution for tailored tissue engineering scaffolds, making tissue engineering a realistic clinical alternative in the near future.

  8. Preparation and characterization of (PCL-crosslinked-PEG)/hydroxyapatite as bone tissue engineering scaffolds.

    PubMed

    Koupaei, Narjes; Karkhaneh, Akbar; Daliri Joupari, Morteza

    2015-12-01

    In this study, interconnected porous bioactive scaffolds were synthesized for bone tissue engineering. At the first step, poly( ɛ-caprolactone) (PCL) diols were diacrylated with acryloyl chloride. Then, the scaffolds were synthesized by radical crosslinking reaction of PCL and poly(ethyleneglycol) (PEG) diacrylates in the presence of hydroxyapatite (HA) particles. Morphological, swelling, thermal, and mechanical characteristics as well as degradability of the scaffolds were investigated. Results showed that increasing the ratio of PEG to PCL led to significant increase of swelling ratio and degradation rate, and decrease of crystallinity and compressive modulus of the networks, respectively. It was found that the incorporation of HA particles with the polymer matrices resulted in an augmented crystallinity, a decreased swelling ratio, and also a significantly increased compressive modulus of the networks. Cytocompatability and osteoconductivity of the scaffolds were assessed by MTT and alkaline phosphatase (ALP) assays, respectively. The results confirmed the cytocompatible nature of PCL/PEG/HA scaffolds with no toxicity. MG-63 cells attached and spread on the pore walls offered by the scaffolds. PCL/PEG/HA scaffolds compared with PCL/PEG ones showed higher ALP activity. Thus, the results indicated that the PCL/PEG/HA scaffolds have the potential of being used as promising substrates in bone tissue engineering.

  9. Cellulose acetate based 3-dimensional electrospun scaffolds for skin tissue engineering applications.

    PubMed

    Atila, Deniz; Keskin, Dilek; Tezcaner, Ayşen

    2015-11-20

    Skin defects that are not able to regenerate by themselves are among the major problems faced. Tissue engineering approach holds promise for treating such defects. Development of tissue-mimicking-scaffolds that can promote healing process receives an increasing interest in recent years. In this study, 3-dimensional electrospun cellulose acetate (CA) pullulan (PULL) scaffolds were developed for the first time. PULL was intentionally used to obtain 3D structures with adjustable height. It was removed from the electrospun mesh to increase the porosity and biostability. Different ratios of the polymers were electrospun and analyzed with respect to degradation, porosity, and mechanical properties. It has been observed that fiber diameter, thickness and porosity of scaffolds increased with increased PULL content, on the other hand this resulted with higher degradation of scaffolds. Mechanical strength of scaffolds was improved after PULL removal suggesting their suitability as cell carriers. Cell culture studies were performed with the selected scaffold group (CA/PULL: 50/50) using mouse fibroblastic cell line (L929). In vitro cell culture tests showed that cells adhered, proliferated and populated CA/PULL (50/50) scaffolds showing that they are cytocompatible. Results suggest that uncrosslinked CA/PULL (50/50) electrospun scaffolds hold potential for skin tissue engineering applications. PMID:26344279

  10. Cellulose acetate based 3-dimensional electrospun scaffolds for skin tissue engineering applications.

    PubMed

    Atila, Deniz; Keskin, Dilek; Tezcaner, Ayşen

    2015-11-20

    Skin defects that are not able to regenerate by themselves are among the major problems faced. Tissue engineering approach holds promise for treating such defects. Development of tissue-mimicking-scaffolds that can promote healing process receives an increasing interest in recent years. In this study, 3-dimensional electrospun cellulose acetate (CA) pullulan (PULL) scaffolds were developed for the first time. PULL was intentionally used to obtain 3D structures with adjustable height. It was removed from the electrospun mesh to increase the porosity and biostability. Different ratios of the polymers were electrospun and analyzed with respect to degradation, porosity, and mechanical properties. It has been observed that fiber diameter, thickness and porosity of scaffolds increased with increased PULL content, on the other hand this resulted with higher degradation of scaffolds. Mechanical strength of scaffolds was improved after PULL removal suggesting their suitability as cell carriers. Cell culture studies were performed with the selected scaffold group (CA/PULL: 50/50) using mouse fibroblastic cell line (L929). In vitro cell culture tests showed that cells adhered, proliferated and populated CA/PULL (50/50) scaffolds showing that they are cytocompatible. Results suggest that uncrosslinked CA/PULL (50/50) electrospun scaffolds hold potential for skin tissue engineering applications.

  11. Poly(ɛ-caprolactone)/gelatin composite electrospun scaffolds with porous crater-like structures for tissue engineering.

    PubMed

    Hwang, Patrick T J; Murdock, Kyle; Alexander, Grant C; Salaam, Amanee D; Ng, Joshua I; Lim, Dong-Jin; Dean, Derrick; Jun, Ho-Wook

    2016-04-01

    Electrospinning has been widely used to fabricate scaffolds imitating the structure of natural extracellular matrix (ECM). However, conventional electrospinning produces tightly compacted nanofiber layers with only small superficial pores and a lack of bioactivity, which limit the usefulness of electrospinning in biomedical applications. Thus, a porous poly(ε-caprolactone) (PCL)/gelatin composite electrospun scaffold with crater-like structures was developed. Porous crater-like structures were created on the scaffold by a gas foaming/salt leaching process; this unique fiber structure had more large pore areas and higher porosity than the conventional electrospun fiber network. Various ratios of PCL/gelatin (concentration ratios: 100/0, 75/25, and 50/50) composite electrospun scaffolds with and without crater-like structures were characterized by their microstructures, surface chemistry, degradation, mechanical properties, and ability to facilitate cell growth and infiltration. The combination of PCL and gelatin endowed the scaffold with both structural stability of PCL and bioactivity of gelatin. All ratios of scaffolds with crater-like structures showed fairly similar surface chemistry, degradation rates, and mechanical properties to equivalent scaffolds without crater-like structures; however, craterized scaffolds displayed higher human mesenchymal stem cell (hMSC) proliferation and infiltration throughout the scaffolds after 7-day culture. Therefore, these results demonstrated that PCL/gelatin composite electrospun scaffolds with crater-like structures can provide a structurally and biochemically improved three-dimensional ECM-mimicking microenvironment. PMID:26567028

  12. Poly(ɛ-caprolactone)/gelatin composite electrospun scaffolds with porous crater-like structures for tissue engineering.

    PubMed

    Hwang, Patrick T J; Murdock, Kyle; Alexander, Grant C; Salaam, Amanee D; Ng, Joshua I; Lim, Dong-Jin; Dean, Derrick; Jun, Ho-Wook

    2016-04-01

    Electrospinning has been widely used to fabricate scaffolds imitating the structure of natural extracellular matrix (ECM). However, conventional electrospinning produces tightly compacted nanofiber layers with only small superficial pores and a lack of bioactivity, which limit the usefulness of electrospinning in biomedical applications. Thus, a porous poly(ε-caprolactone) (PCL)/gelatin composite electrospun scaffold with crater-like structures was developed. Porous crater-like structures were created on the scaffold by a gas foaming/salt leaching process; this unique fiber structure had more large pore areas and higher porosity than the conventional electrospun fiber network. Various ratios of PCL/gelatin (concentration ratios: 100/0, 75/25, and 50/50) composite electrospun scaffolds with and without crater-like structures were characterized by their microstructures, surface chemistry, degradation, mechanical properties, and ability to facilitate cell growth and infiltration. The combination of PCL and gelatin endowed the scaffold with both structural stability of PCL and bioactivity of gelatin. All ratios of scaffolds with crater-like structures showed fairly similar surface chemistry, degradation rates, and mechanical properties to equivalent scaffolds without crater-like structures; however, craterized scaffolds displayed higher human mesenchymal stem cell (hMSC) proliferation and infiltration throughout the scaffolds after 7-day culture. Therefore, these results demonstrated that PCL/gelatin composite electrospun scaffolds with crater-like structures can provide a structurally and biochemically improved three-dimensional ECM-mimicking microenvironment.

  13. Preparation and characterization of aligned porous PCL/zein scaffolds as drug delivery systems via improved unidirectional freeze-drying method.

    PubMed

    Fereshteh, Zeinab; Fathi, Mohammadhossein; Bagri, Akbar; Boccaccini, Aldo R

    2016-11-01

    A novel type of drug-delivery scaffold based on poly(ε-caprolactone) (PCL) and zein blends was prepared by improved unidirectional freeze-drying. Scaffolds with tube-like pore structure and high porosity, up to 89%, were obtained by adjusting the concentration of the PCL and zein solutions. Characters of the prepared scaffolds, such as microstructural, porosity, and compressive strength, were evaluated. The hydrophilicity and the degradability of the composite films were investigated in contact with phosphate buffer saline (PBS). It was found that the presence of zein accelerates the degradation rate of the scaffolds in the period time of investigation (28days). The results showed an acceptable way for controlling the in vitro degradation behavior of PCL composite scaffolds by adapting the concentration of zein. In vitro protein release and degradation results revealed that the absolute weight loss of the PCL/zein scaffolds exhibited an increasing trend by increasing the amount of zein concentration in the scaffolds. The drug delivery capability of the scaffolds was tested using tetracycline hydrochloride (TCH). Sustained release of the drug was obtained, and it was found that the proportion of zein in the scaffold had a great impact on the drug release kinetics. The results demonstrated the potential of the PCL/zein biocomposite scaffolds as a suitable candidate in tissue engineering strategies for bone defect treatment. PMID:27524061

  14. 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…

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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

  1. 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.

  2. 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

  3. In vivo study of porous strontium-doped calcium polyphosphate scaffolds for bone substitute applications.

    PubMed

    Tian, Meng; Chen, Feng; Song, Wei; Song, Yancheng; Chen, Yuanwei; Wan, Changxiu; Yu, Xixun; Zhang, Xiaohua

    2009-07-01

    The purpose of this study was to investigate in vivo biocompatibility and osteogenesis as well as degradability of the porous strontium-doped calcium polyphosphate (SCPP) scaffolds as a biomaterial for bone substitute applications. The evaluation was performed on a rabbit model over a period of 16 weeks by histology combined with image analysis, X-ray microradiography and immunohistochemistry methods. The histological and X-ray microradiographic results showed that the SCPP scaffold exhibited good biocompatibility and extensive osteoconductivity with host bone. Moreover, a significant more bone formation was observed in the SCPP group compared with that in the CPP group, especially at the initial stage after implantation. New bone volumes (NBVs) of the SCPP group determined at week 4, 8 and 16 were 14, 27 and 45%, respectively. Accordingly, NBVs of the CPP group were 10, 19 and 40%. Immunohistochemical results revealed that both the expression of collagen type I and bone morphogenetic proteins in the SCPP group were higher than that in the CPP group, which might be associated with the release of strontium ions during the implantation. In addition, during 16 weeks implantation the SCPP scaffold exhibited similar degradability with the CPP scaffold in vivo. Both scaffolds showed the greatest degradation rate for the first 4 weeks, and then the degradation rate gradually decreased. The results presented in this study demonstrated that SCPP scaffold can be considered as a biocompatible material, making it attractive for bone substitute application purposes. PMID:19267259

  4. Hybrid scaffold bearing polymer-siloxane Schiff base linkage for bone tissue engineering.

    PubMed

    Nair, Bindu P; Gangadharan, Dhanya; Mohan, Neethu; Sumathi, Babitha; Nair, Prabha D

    2015-01-01

    Scaffolds that can provide the requisite biological cues for the fast regeneration of bone are highly relevant to the advances in tissue engineering and regenerative medicine. In the present article, we report the fabrication of a chitosan-gelatin-siloxane scaffold bearing interpolymer-siloxane Schiff base linkage, through a single-step dialdehyde cross-linking and freeze-drying method using 3-aminopropyltriethoxysilane as the siloxane precursor. Swelling of the scaffolds in phosphate buffered saline indicates enhancement with increase in siloxane concentration, whereas compressive moduli of the wet scaffolds reveal inverse dependence, owing to the presence of siloxane, rich in silanol groups. It is suggested that through the strategy of dialdehyde cross-linking, a limiting siloxane loading of 20 wt.% into a chitosan -gelatin matrix should be considered ideal for bone tissue engineering, because the scaffold made with 30 wt.% siloxane loading degrades by 48 wt.%, in 21 days. The hybrid scaffolds bearing Schiff base linkage between the polymer and siloxane, unlike the stable linkages in earlier reports, are expected to give a faster release of siloxanes and enhancement in osteogenesis. This is verified by the in vitro evaluation of the hybrid scaffolds using rabbit adipose mesenchymal stem cells, which revealed osteogenic cell-clusters on a polymer-siloxane scaffold, enhanced alkaline phosphatase activity and the expression of bone-specific genes, whereas the control scaffold without siloxane supported more of cell-proliferation than differentiation. A siloxane concentration dependent enhancement in osteogenic differentiation is also observed.

  5. Design and fabrication of biomimetic multiphased scaffolds for ligament-to-bone fixation.

    PubMed

    He, Jiankang; Zhang, Wenyou; Liu, Yaxiong; Li, Xiang; Li, Dichen; Jin, Zhongmin

    2015-05-01

    Conventional ligament grafts with single material composition cannot effectively integrate with the host bones due to mismatched properties and eventually affect their long-term function in vivo. Here we presented a multi-material strategy to design and fabricate composite scaffolds including ligament, interface and bone multiphased regions. The interface region consists of triphasic layers with varying material composition and porous structure to mimic native ligament-to-bone interface while the bone region contains polycaprolactone (PCL) anchor and microchanneled ceramic scaffolds to potentially provide combined mechanical and biological implant-bone fixation. Finite element analysis (FEA) demonstrated that the multiphased scaffolds with interference value smaller than 0.5 mm could avoid the fracture of ceramic scaffold during the implantation process, which was validated by in-vitro implanting the multiphased scaffolds into porcine joint bones. Pull-out experiment showed that the initial fixation between the multiphased scaffolds with 0.47 mm interference and the host bones could withstand the maximum force of 360.31±97.51 N, which can be improved by reinforcing the ceramic scaffolds with biopolymers. It is envisioned that the multiphased scaffold could potentially induce the regeneration of a new bone as well as interfacial tissue with the gradual degradation of the scaffold and subsequently realize long-term biological fixation of the implant with the host bone. PMID:25746239

  6. Rheological, biocompatibility and osteogenesis assessment of fish collagen scaffold for bone tissue engineering.

    PubMed

    Elango, Jeevithan; Zhang, Jingyi; Bao, Bin; Palaniyandi, Krishnamoorthy; Wang, Shujun; Wenhui, Wu; Robinson, Jeya Shakila

    2016-10-01

    In the present investigation, an attempt was made to find an alternative to mammalian collagen with better osteogenesis ability. Three types of collagen scaffolds - collagen, collagen-chitosan (CCH), and collagen-hydroxyapatite (CHA) - were prepared from the cartilage of Blue shark and investigated for their physico-functional and mechanical properties in relation to biocompatibility and osteogenesis. CCH scaffold was superior with pH 4.5-4.9 and viscosity 9.7-10.9cP. Notably, addition of chitosan and HA (hydroxyapatite) improved the stiffness (11-23MPa) and degradation rate but lowered the water binding capacity and porosity of the scaffold. Interestingly, CCH scaffolds remained for 3days before complete in-vitro biodegradation. The decreased amount of viable T-cells and higher level of FAS/APO-1 were substantiated the biocompatibility properties of prepared collagen scaffolds. Osteogenesis study revealed that the addition of CH and HA in both fish and mammalian collagen scaffolds could efficiently promote osteoblast cell formation. The ALP activity was significantly high in CHA scaffold-treated osteoblast cells, which suggests an enhanced bone-healing process. Therefore, the present study concludes that the composite scaffolds prepared from fish collagen with higher stiffness, lower biodegradation rate, better biocompatible, and osteogenesis properties were suitable biomaterial for a bone tissue engineering application as an alternative to mammalian collagen scaffolds. PMID:27211297

  7. Design and fabrication of biomimetic multiphased scaffolds for ligament-to-bone fixation.

    PubMed

    He, Jiankang; Zhang, Wenyou; Liu, Yaxiong; Li, Xiang; Li, Dichen; Jin, Zhongmin

    2015-05-01

    Conventional ligament grafts with single material composition cannot effectively integrate with the host bones due to mismatched properties and eventually affect their long-term function in vivo. Here we presented a multi-material strategy to design and fabricate composite scaffolds including ligament, interface and bone multiphased regions. The interface region consists of triphasic layers with varying material composition and porous structure to mimic native ligament-to-bone interface while the bone region contains polycaprolactone (PCL) anchor and microchanneled ceramic scaffolds to potentially provide combined mechanical and biological implant-bone fixation. Finite element analysis (FEA) demonstrated that the multiphased scaffolds with interference value smaller than 0.5 mm could avoid the fracture of ceramic scaffold during the implantation process, which was validated by in-vitro implanting the multiphased scaffolds into porcine joint bones. Pull-out experiment showed that the initial fixation between the multiphased scaffolds with 0.47 mm interference and the host bones could withstand the maximum force of 360.31±97.51 N, which can be improved by reinforcing the ceramic scaffolds with biopolymers. It is envisioned that the multiphased scaffold could potentially induce the regeneration of a new bone as well as interfacial tissue with the gradual degradation of the scaffold and subsequently realize long-term biological fixation of the implant with the host bone.

  8. Scaffolds containing chitosan/carboxymethyl cellulose/mesoporous wollastonite for bone tissue engineering.

    PubMed

    Sainitya, R; Sriram, M; Kalyanaraman, V; Dhivya, S; Saravanan, S; Vairamani, M; Sastry, T P; Selvamurugan, N

    2015-09-01

    Scaffold based bone tissue engineering utilizes a variety of biopolymers in different combinations aiming to deliver optimal properties required for bone regeneration. In the current study, we fabricated bio-composite scaffolds containing chitosan (CS), carboxymethylcellulose (CMC) with varied concentrations of mesoporous wollastonite (m-WS) particles by the freeze drying method. The CS/CMC/m-WS scaffolds were characterized by the SEM, EDS and FT-IR studies. Addition of m-WS particles had no effect on altering the porosity of the scaffolds. m-WS particles at 0.5% concentration in the CS/CMC scaffolds showed significant improvement in the bio-mineralization and protein adsorption properties. Addition of m-WS particles in the CS/CMC scaffolds significantly reduced their swelling and degradation properties. The CS/CMC/m-WS scaffolds also showed cyto-friendly nature to human osteoblastic cells. The osteogenic potential of CS/CMC/m-WS scaffolds was confirmed by calcium deposition and expression of an osteoblast specific microRNA, pre-mir-15b. Thus, the current investigations support the use of CS/CMC/m-WS scaffolds for bone tissue engineering applications.

  9. Porous nanoapatite scaffolds synthesized using an approach of interfacial mineralization reaction and their bioactivity.

    PubMed

    Wang, Jianxin; Yan, Haoran; Chen, Taijun; Wang, Yingying; Li, Huiyong; Zhi, Wei; Feng, Bo; Weng, Jie; Zhu, Minghua

    2014-11-01

    There is a growing interest in the use of calcium phosphate, used to fabricate porous scaffolds for bone tissue regeneration and repair. However, it is difficult to obtain interconnected pores with very high porosity and to engineer the topography of the pore walls for calcium phosphate ceramic scaffolds. In this study, a novelty method interfacial mineralization reaction was used to fabricate porous nano-calcium phosphate ceramic scaffolds with three-dimensional surface topography of walls, which was tuned using different surfactants; using this method, porous scaffolds with different shapes were obtained, which demonstrates that interfacial mineralization reaction is not only a good method to prepare porous ceramic scaffolds of calcium phosphate but also an efficient approach to engineer the topography of the pore walls. The as-prepared porous ceramic scaffolds have also been proved to have good biocompatibility, bioactivity, and biodegradability, which are necessary for the clinical application. In vivo experimental results revealed that not only osteoconduction but also osteoinduction was responsible for the bone formation in our scaffolds, which accelerated the formation of new bone, and that the degradation process of our porous scaffolds could match osteoinduction, mineralization of matrix and bone, and reconstruction of new bone very well, and porous scaffolds could be completely substituted by the new bone.

  10. Scaffolds containing chitosan/carboxymethyl cellulose/mesoporous wollastonite for bone tissue engineering.

    PubMed

    Sainitya, R; Sriram, M; Kalyanaraman, V; Dhivya, S; Saravanan, S; Vairamani, M; Sastry, T P; Selvamurugan, N

    2015-09-01

    Scaffold based bone tissue engineering utilizes a variety of biopolymers in different combinations aiming to deliver optimal properties required for bone regeneration. In the current study, we fabricated bio-composite scaffolds containing chitosan (CS), carboxymethylcellulose (CMC) with varied concentrations of mesoporous wollastonite (m-WS) particles by the freeze drying method. The CS/CMC/m-WS scaffolds were characterized by the SEM, EDS and FT-IR studies. Addition of m-WS particles had no effect on altering the porosity of the scaffolds. m-WS particles at 0.5% concentration in the CS/CMC scaffolds showed significant improvement in the bio-mineralization and protein adsorption properties. Addition of m-WS particles in the CS/CMC scaffolds significantly reduced their swelling and degradation properties. The CS/CMC/m-WS scaffolds also showed cyto-friendly nature to human osteoblastic cells. The osteogenic potential of CS/CMC/m-WS scaffolds was confirmed by calcium deposition and expression of an osteoblast specific microRNA, pre-mir-15b. Thus, the current investigations support the use of CS/CMC/m-WS scaffolds for bone tissue engineering applications. PMID:26188305

  11. Nanoclay-Enriched Poly(ɛ-caprolactone) Electrospun Scaffolds for Osteogenic Differentiation of Human Mesenchymal Stem Cells

    PubMed Central

    Gaharwar, Akhilesh K.; Mukundan, Shilpaa; Karaca, Elif; Dolatshahi-Pirouz, Alireza; Patel, Alpesh; Rangarajan, Kaushik; Mihaila, Silvia M.; Iviglia, Giorgio; Zhang, Hongbin

    2014-01-01

    Musculoskeletal tissue engineering aims at repairing and regenerating damaged tissues using biological tissue substitutes. One approach to achieve this aim is to develop osteoconductive scaffolds that facilitate the formation of functional bone tissue. We have fabricated nanoclay-enriched electrospun poly(ɛ-caprolactone) (PCL) scaffolds for osteogenic differentiation of human mesenchymal stem cells (hMSCs). A range of electrospun scaffolds is fabricated by varying the nanoclay concentrations within the PCL scaffolds. The addition of nanoclay decreases fiber diameter and increases surface roughness of electrospun fibers. The enrichment of PCL scaffold with nanoclay promotes in vitro biomineralization when subjected to simulated body fluid (SBF), indicating bioactive characteristics of the hybrid scaffolds. The degradation rate of PCL increases due to the addition of nanoclay. In addition, a significant increase in crystallization temperature of PCL is also observed due to enhanced surface interactions between PCL and nanoclay. The effect of nanoclay on the mechanical properties of electrospun fibers is also evaluated. The feasibility of using nanoclay-enriched PCL scaffolds for tissue engineering applications is investigated in vitro using hMSCs. The nanoclay-enriched electrospun PCL scaffolds support hMSCs adhesion and proliferation. The addition of nanoclay significantly enhances osteogenic differentiation of hMSCs on the electrospun scaffolds as evident by an increase in alkaline phosphates activity of hMSCs and higher deposition of mineralized extracellular matrix compared to PCL scaffolds. Given its unique bioactive characteristics, nanoclay-enriched PCL fibrous scaffold may be used for musculoskeletal tissue engineering. PMID:24842693

  12. Nanoclay-enriched poly(ɛ-caprolactone) electrospun scaffolds for osteogenic differentiation of human mesenchymal stem cells.

    PubMed

    Gaharwar, Akhilesh K; Mukundan, Shilpaa; Karaca, Elif; Dolatshahi-Pirouz, Alireza; Patel, Alpesh; Rangarajan, Kaushik; Mihaila, Silvia M; Iviglia, Giorgio; Zhang, Hongbin; Khademhosseini, Ali

    2014-08-01

    Musculoskeletal tissue engineering aims at repairing and regenerating damaged tissues using biological tissue substitutes. One approach to achieve this aim is to develop osteoconductive scaffolds that facilitate the formation of functional bone tissue. We have fabricated nanoclay-enriched electrospun poly(ɛ-caprolactone) (PCL) scaffolds for osteogenic differentiation of human mesenchymal stem cells (hMSCs). A range of electrospun scaffolds is fabricated by varying the nanoclay concentrations within the PCL scaffolds. The addition of nanoclay decreases fiber diameter and increases surface roughness of electrospun fibers. The enrichment of PCL scaffold with nanoclay promotes in vitro biomineralization when subjected to simulated body fluid (SBF), indicating bioactive characteristics of the hybrid scaffolds. The degradation rate of PCL increases due to the addition of nanoclay. In addition, a significant increase in crystallization temperature of PCL is also observed due to enhanced surface interactions between PCL and nanoclay. The effect of nanoclay on the mechanical properties of electrospun fibers is also evaluated. The feasibility of using nanoclay-enriched PCL scaffolds for tissue engineering applications is investigated in vitro using hMSCs. The nanoclay-enriched electrospun PCL scaffolds support hMSCs adhesion and proliferation. The addition of nanoclay significantly enhances osteogenic differentiation of hMSCs on the electrospun scaffolds as evident by an increase in alkaline phosphates activity of hMSCs and higher deposition of mineralized extracellular matrix compared to PCL scaffolds. Given its unique bioactive characteristics, nanoclay-enriched PCL fibrous scaffold may be used for musculoskeletal tissue engineering. PMID:24842693

  13. Biodegradable lysine-derived polyurethane scaffolds promote healing in a porcine full-thickness excisional wound model

    PubMed Central

    Adolph, Elizabeth J.; Pollins, Alonda C.; Cardwell, Nancy L.; Davidson, Jeffrey M.; Guelcher, Scott A.; Nanney, Lillian B.

    2014-01-01

    Lysine-derived polyurethane scaffolds (LTI-PUR) support cutaneous wound healing in loose-skinned small animal models. Due to the physiological and anatomical similarities of human and pig skin we investigated the capacity of LTI-PUR scaffolds to support wound healing in a porcine excisional wound model. Modifications to scaffold design included the addition of carboxymethylcellulose (CMC) as a porogen to increase interconnectivity and an additional plasma treatment (Plasma) to decrease surface hydrophobicity. All LTI-PUR scaffold and formulations supported cellular infiltration and were biodegradable. At 15 days, CMC and Plasma scaffolds simulated increased macrophages more so than LTI PUR or no treatment. This response was consistent with macrophage-mediated oxidative degradation of the lysine component of the scaffolds. Cell proliferation was similar in control and scaffold treated wounds at 8 and 15 days. Neither apoptosis nor blood vessel area density showed significant differences in the presence of any of the scaffold variations compared to untreated wounds, providing further evidence that these synthetic biomaterials had no adverse effects on those pivotal wound healing processes. During the critical phase of granulation tissue formation in full thickness porcine excisional wounds, LTI-PUR scaffolds supported tissue infiltration, while undergoing biodegradation. Modifications to scaffold fabrication modify the reparative process. This study emphasizes the biocompatibility and favorable cellular responses of PUR scaffolding formulations in a clinically relevant animal model. PMID:25290884

  14. Electrospinning polymer blends for biomimetic scaffolds for ACL tissue engineering

    NASA Astrophysics Data System (ADS)

    Garcia, Vanessa Lizeth

    The anterior cruciate ligament (ACL) rupture is one of the most common knee injuries. Current ACL reconstructive strategies consist of using an autograft or an allograft to replace the ligament. However, limitations have led researchers to create tissue engineered grafts, known as scaffolds, through electrospinning. Scaffolds made of natural and synthetic polymer blends have the potential to promote cell adhesion while having strong mechanical properties. However, enzymes found in the knee are known to degrade tissues and affect the healing of intra-articular injuries. Results suggest that the natural polymers used in this study modify the thermal properties and tensile strength of the synthetic polymers when blended. Scanning electron microscopy display bead-free and enzyme biodegradability of the fibers. Raman spectroscopy confirms the presence of the natural and synthetic polymers in the scaffolds while, amino acid analysis present the types of amino acids and their concentrations found in the natural polymers.

  15. Biomaterials and scaffold design: key to tissue-engineering cartilage.

    PubMed

    Raghunath, Joanne; Rollo, John; Sales, Kevin M; Butler, Peter E; Seifalian, Alexander M

    2007-02-01

    Cartilage remains one of the most challenging tissues to reconstruct or replace, owing to its complex geometry in facial structures and mechanical strength at articular surfaces in joints. This non-vascular tissue has poor replicative capacity and damage results in its functionally inferior repair tissue, fibrocartilage. This has led to a drive for advancements in tissue engineering. The variety of polymers and fabrication techniques available continues to expand. Pore size, porosity, biocompatibility, shape specificity, integration with native tissue, degradation tailored to rate of neocartilage formation and cost efficiency are important factors which need consideration in the development of a scaffold. The present review considers the current polymers and fabrication methodologies used in scaffold engineering for cartilage and postulates whether we are closer to developing the ideal scaffold for clinical application.

  16. Enzymatic mineralization of silk scaffolds.

    PubMed

    Samal, Sangram K; Dash, Mamoni; Declercq, Heidi A; Gheysens, Tom; Dendooven, Jolien; Van Der Voort, Pascal; Cornelissen, Ria; Dubruel, Peter; Kaplan, David L

    2014-07-01

    The present study focuses on the alkaline phosphatase (ALP) mediated formation of apatitic minerals on porous silk fibroin protein (SFP) scaffolds. Porous SFP scaffolds impregnated with different concentrations of ALP are homogeneously mineralized under physiological conditions. The mineral structure is apatite while the structures differ as a function of the ALP concentration. Cellular adhesion, proliferation, and colonization of osteogenic MC3T3 cells improve on the mineralized SFP scaffolds. These findings suggest a simple process to generate mineralized scaffolds that can be used to enhanced bone tissue engineering-related utility. PMID:24610728

  17. Fabrication of fibrinogen/P(LLA-CL) hybrid nanofibrous scaffold for potential soft tissue engineering applications.

    PubMed

    He, Chuanglong; Xu, Xiaohong; Zhang, Fan; Cao, Lijun; Feng, Wei; Wang, Hongsheng; Mo, Xiumei

    2011-06-01

    Coelectrospinning of native proteins and elastic synthetic polymers is an attractive technique to fabricate hybrid fibrous scaffolds that combine the bioactivity and mechanical features of each material component. In this study, hybrid fibrous scaffolds composed of synthetic P(LLA-CL) elastomeric and naturally derived fibrinogen protein were fabricated and characterized for their bioactive and physiochemical properties. Fiber diameters of hybrid scaffolds increased with increasing P(LLA-CL) content, and the shape of fibers changed from cylindrical shape on pure polymer scaffolds to flat structure on hybrid scaffolds. Characterizations of ATR-FTIR, XRD, and thermal properties indicated that the hybrid scaffolds contain two different phases, one composed of pure fibrinogen and the other corresponding to a mixture of fibrinogen and P(LLA-CL), and no obvious chemical reaction takes place between two components. The hybrid fibrous scaffolds showed tailorable degradation rates than pure P(LLA-CL) and higher mechanical properties than pure fibrinogen, and both tensile strength and breaking strain increased with increasing P(LLA-CL) content. In Vitro studies revealed that L929 cells on hybrid scaffolds achieved relatively higher level of cell attachment after 12 h of culture and significant increased cell proliferation rate after 7 days of culture, when compared with pure fibrinogen and P(LLA-CL) scaffolds, and the cells exhibited a spreading polygonal shape on the hybrid fibrous surfaces compared to a round shape on surfaces of pure polymer scaffolds. Therefore, the fibrinogen/P(LLA-CL) hybrid fibrous scaffolds possess the combined benefits of each individual component, which make it capable as scaffolds for soft tissue reconstruction.

  18. Monocular Elevation Deficiency - Double Elevator Palsy

    MedlinePlus

    ... Eye Terms Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? ...

  19. Instruction, Cognitive Scaffolding, and Motivational Scaffolding in Writing Center Tutoring

    ERIC Educational Resources Information Center

    Mackiewicz, Jo; Thompson, Isabelle

    2014-01-01

    In this study, we quantitatively analyze the discourse of experienced writing center tutors in 10 highly satisfactory conferences. Specifically, we analyze tutors' instruction, cognitive scaffolding, and motivational scaffolding, all tutoring strategies identified in prior research from other disciplines as educationally effective. We find…

  20. PEP_scaffolder: using (homologous) proteins to scaffold genomes

    PubMed Central

    Zhu, Bai-Han; Song, Ying-Nan; Xue, Wei; Xu, Gui-Cai; Xiao, Jun; Sun, Ming-Yuan; Sun, Xiao-Wen; Li, Jiong-Tang

    2016-01-01

    Motivation: Recovering the gene structures is one of the important goals of genome assembly. In low-quality assemblies, and even some high-quality assemblies, certain gene regions are still incomplete; thus, novel scaffolding approaches are required to complete gene regions. Results: We developed an efficient and fast genome scaffolding method called PEP_scaffolder, using proteins to scaffold genomes. The pipeline aims to recover protein-coding gene structures. We tested the method on human contigs; using human UniProt proteins as guides, the improvement on N50 size was 17% increase with an accuracy of ∼97%. PEP_scaffolder improved the proportion of fully covered proteins among all proteins, which was close to the proportion in the finished genome. The method provided a high accuracy of 91% using orthologs of distant species. Tested on simulated fly contigs, PEP_scaffolder outperformed other scaffolders, with the shortest running time and the highest accuracy. Availability and Implementation: The software is freely available at http://www.fishbrowser.org/software/PEP_scaffolder/ Contact: lijt@cafs.ac.cn Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27334475

  1. Biotemplated syntheses of macroporous materials for bone tissue engineering scaffolds and experiments in vitro and vivo.

    PubMed

    Li, Xing; Zhao, Yayun; Bing, Yue; Li, Yaping; Gan, Ning; Guo, Zhiyong; Peng, Zhaoxiang; Zhu, Yabin

    2013-06-26

    The macroporous materials were prepared from the transformation of cuttlebone as biotemplates under hydrothermal reactions and characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric/differential thermal analyses (TG-DTA), and scanning electron microscopy (SEM). Cell experimental results showed that the prepared materials as bone tissue engineering scaffolds or fillers had fine biocompatibility suitable for adhesion and proliferation of the hMSCs (human marrow mesenchymal stem cells). Histological analyses were carried out by implanting the scaffolds into a rabbit femur, where the bioresorption, degradation, and biological activity of the scaffolds were observed in the animal body. The prepared scaffolds kept the original three-dimensional frameworks with the ordered porous structures, which made for blood circulation, nutrition supply, and the cells implantation. The biotemplated syntheses could provide a new effective approach to prepare the bone tissue engineering scaffold materials. PMID:23742223

  2. Modified gum arabic cross-linked gelatin scaffold for biomedical applications.

    PubMed

    Sarika, P R; Cinthya, Kuriakose; Jayakrishnan, A; Anilkumar, P R; James, Nirmala Rachel

    2014-10-01

    The present work deals with development of modified gum arabic cross-linked gelatin scaffold for cell culture. A new biocompatible scaffold was developed by cross-linking gelatin (Gel) with gum arabic, a polysaccharide. Gum arabic was subjected to periodate oxidation to obtain gum arabic aldehyde (GAA). GAA was reacted with gelatin under appropriate pH to prepare the cross-linked hydrogel. Cross-linking occurred due to Schiff's base reaction between aldehyde groups of oxidized gum arabic and amino groups of gelatin. The scaffold prepared from the hydrogel was characterized by swelling properties, degree of cross-linking, in vitro degradation and scanning electron microscopy (SEM). Cytocompatibility evaluation using L-929 and HepG2 cells confirmed non-cytotoxic and non-adherent nature of the scaffold. These properties are essential for generating multicellular spheroids and hence the scaffold is proposed to be a suitable candidate for spheroid cell culture. PMID:25175214

  3. Collagen/chitosan porous bone tissue engineering composite scaffold incorporated with Ginseng compound K.

    PubMed

    Muthukumar, Thangavelu; Aravinthan, Adithan; Sharmila, Judith; Kim, Nam Soo; Kim, Jong-Hoon

    2016-11-01

    In this study, suitable scaffold materials for bone tissue engineering were successfully prepared using fish scale collagen, hydroxyapatite, chitosan, and beta-tricalcium phosphate. Porous composite scaffolds were prepared by freeze drying method. The Korean traditional medicinal ginseng compound K, a therapeutic agent for the treatment of osteoporosis that reduces inflammation and enhances production of bone morphogenetic protein-2, was incorporated into the composite scaffold. The scaffold was characterized for pore size, swelling, density, degradation, mineralization, cell viability and attachment, and its morphological features were examined using scanning electron microscopy. This characterization and in vitro analysis showed that the prepared scaffold was biocompatible and supported the growth of MG-63 cells, and therefore has potential as an alternative approach for bone regeneration. PMID:27516305

  4. Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks

    NASA Astrophysics Data System (ADS)

    Griffin, Donald R.; Weaver, Westbrook M.; Scumpia, Philip O.; di Carlo, Dino; Segura, Tatiana

    2015-07-01

    Injectable hydrogels can provide a scaffold for in situ tissue regrowth and regeneration, yet gel degradation before tissue reformation limits the gels' ability to provide physical support. Here, we show that this shortcoming can be circumvented through an injectable, interconnected microporous gel scaffold assembled from annealed microgel building blocks whose chemical and physical properties can be tailored by microfluidic fabrication. In vitro, cells incorporated during scaffold formation proliferated and formed extensive three-dimensional networks within 48 h. In vivo, the scaffolds facilitated cell migration that resulted in rapid cutaneous-tissue regeneration and tissue-structure formation within five days. The combination of microporosity and injectability of these annealed gel scaffolds should enable novel routes to tissue regeneration and formation in vivo.

  5. Boron nitride nanotubes included thermally cross-linked gelatin-glucose scaffolds show improved properties.

    PubMed

    Şen, Özlem; Culha, Mustafa

    2016-02-01

    Boron nitride nanotubes (BNNTs) are increasingly investigated for their medical and biomedical applications due to their unique properties such as resistance to oxidation, thermal and electrical insulation, and biocompatibility. BNNTs can be used to enhance mechanical strength of biomedical structures such as scaffolds in tissue engineering applications. In this study, we report the use of BNNTs and hydroxylated BNNTs (BNNT-OH) to improve the properties of gelatin-glucose scaffolds prepared with electrospinning technique. Human dermal fibroblast (HDF) cells are used for the toxicity assessment and cell seeding studies. It is found that the addition of BNNTs into the scaffold does not influence cell viability, decreases the scaffold degradation rate, and improves cell attachment and proliferation compared to only-gelatin scaffold.

  6. 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

  7. Potential of a PLA-PEO-PLA-based scaffold for skin tissue engineering: in vitro evaluation.

    PubMed

    Garric, Xavier; Guillaume, Olivier; Dabboue, Hinda; Vert, Michel; Molès, Jean-Pierre

    2012-01-01

    This study aimed to investigate the in vitro behaviour of porous degradable scaffolds of the PLA-PEO-PLA-type designed prior to in vivo evaluation for skin tissue engineering. Two tri-block co-polymers were synthesized from PEO and DL-lactide and their degradation was studied under conditions that mimic a cutaneous wound environment. 3-D porous scaffolds with interconnected pores were fabricated using the salt leaching method and characterized by ESEM and Hg porosimetry. The degrading action of gamma sterilization was studied on the co-polymers. The less degraded one was selected to make porous scaffolds on which human dermal fibroblasts and human epidermal keratinocytes were cultured. The capacity of such scaffolds to act as a dermal equivalent was also considered. Colonization by human dermal fibroblasts was shown after hematoxylin staining and the production of major proteins normally found in the extracellular matrix was assessed by Western blotting of protein extracts. Finally, a skin substitute was generated by seeding human keratinocytes on the dermal equivalent and a new epidermis was characterized by using immuno-histological staining. Results show that gamma sterilization and that degradation under conditions that mimic skin wound healing were acceptable. The fact that fibroblasts produce extracellular matrix and that keratinocytes generated an epidermal barrier argues in favour of the interest of this type of porous scaffold for skin reconstruction.

  8. Potential of a PLA-PEO-PLA-based scaffold for skin tissue engineering: in vitro evaluation.

    PubMed

    Garric, Xavier; Guillaume, Olivier; Dabboue, Hinda; Vert, Michel; Molès, Jean-Pierre

    2012-01-01

    This study aimed to investigate the in vitro behaviour of porous degradable scaffolds of the PLA-PEO-PLA-type designed prior to in vivo evaluation for skin tissue engineering. Two tri-block co-polymers were synthesized from PEO and DL-lactide and their degradation was studied under conditions that mimic a cutaneous wound environment. 3-D porous scaffolds with interconnected pores were fabricated using the salt leaching method and characterized by ESEM and Hg porosimetry. The degrading action of gamma sterilization was studied on the co-polymers. The less degraded one was selected to make porous scaffolds on which human dermal fibroblasts and human epidermal keratinocytes were cultured. The capacity of such scaffolds to act as a dermal equivalent was also considered. Colonization by human dermal fibroblasts was shown after hematoxylin staining and the production of major proteins normally found in the extracellular matrix was assessed by Western blotting of protein extracts. Finally, a skin substitute was generated by seeding human keratinocytes on the dermal equivalent and a new epidermis was characterized by using immuno-histological staining. Results show that gamma sterilization and that degradation under conditions that mimic skin wound healing were acceptable. The fact that fibroblasts produce extracellular matrix and that keratinocytes generated an epidermal barrier argues in favour of the interest of this type of porous scaffold for skin reconstruction. PMID:21888762

  9. The History of GalaFLEX P4HB Scaffold

    PubMed Central

    Williams, Simon F.; Martin, David P.; Moses, Arikha C.

    2016-01-01

    The GalaFLEX Scaffold (Galatea Surgical, Inc., Lexington, MA) for plastic and reconstructive surgery belongs to a new generation of products for soft tissue reinforcement made from poly-4-hydroxybutyrate (P4HB). Other members of this new family of products include MonoMax Suture (Aesculap AG, Tuttlingen, Germany) for soft tissue approximation, BioFiber Scaffold (Tornier, Inc., Edina, MN) for tendon repair, and Phasix Mesh (C.R. Bard, Inc., Murray Hill, NJ) for hernia repair. Each of these fully resorbable products provides prolonged strength retention, typically 50% to 70% strength retention at 12 weeks, and facilitates remodeling in vivo to provide a strong, lasting repair. P4HB belongs to a naturally occurring class of biopolymers and fibers made from it are uniquely strong, flexible, and biocompatible. GalaFLEX Scaffold is comprised of high-strength, resorbable P4HB monofilament fibers. It is a knitted macroporous scaffold intended to elevate, reinforce, and repair soft tissue. The scaffold acts as a lattice for new tissue growth, which is rapidly vascularized and becomes fully integrated with adjacent tissue as the fibers resorb. In this review, we describe the development of P4HB, its production, properties, safety, and biocompatibility of devices made from P4HB. Early clinical results and current clinical applications of products made from P4HB are also discussed. The results of post-market clinical studies evaluating the GalaFLEX Scaffold in rhytidectomy and cosmetic breast surgery demonstrate that the scaffold can reinforce lifted soft tissue, resulting in persistent surgical results in the face and neck at one year, and provide lower pole stability after breast lift at one year. PMID:27697885

  10. Porous magnesium/PLGA composite scaffolds for enhanced bone regeneration following tooth extraction.

    PubMed

    Brown, Andrew; Zaky, Samer; Ray, Herbert; Sfeir, Charles

    2015-01-01

    Sixty percent of implant-supported dental prostheses require bone grafting to enhance bone quantity and quality prior to implant placement. We have developed a metallic magnesium particle/PLGA composite scaffold to overcome the limitations of currently used dental bone grafting materials. This is the first report of porous metallic magnesium/PLGA scaffolds synthesized using a solvent casting, salt leaching method. We found that incorporation of varying amounts of magnesium into the PLGA scaffolds increased the compressive strength and modulus, as well as provided a porous structure suitable for cell infiltration, as measured by mercury intrusion porosimetry. Additionally, combining basic-degrading magnesium with acidic-degrading PLGA led to an overall pH buffering effect and long-term release of magnesium over the course of a 10-week degradation assay, as measured with inductively coupled plasma-atomic emission spectroscopy. Using an indirect proliferation assay adapted from ISO 10993:5, it was found that extracts of medium from degrading magnesium/PLGA scaffolds increased bone marrow stromal cell proliferation in vitro, a phenomenon observed by other groups investigating magnesium's impact on cells. Finally, magnesium/PLGA scaffold biocompatibility was assessed in a canine socket preservation model. Micro-computed tomography and histological analysis showed the magnesium/PLGA scaffolds to be safer and more effective at preserving bone height than empty controls. Three-dimensional magnesium/PLGA composite scaffolds show promise for dental socket preservation and also, potentially, orthopedic bone regeneration. These scaffolds could decrease inflammation observed with clinically used PLGA devices, as well as enhance osteogenesis, as observed with previously studied magnesium devices.

  11. In vitro characterization of chitosan-gelatin scaffolds for tissue engineering.

    PubMed

    Huang, Yan; Onyeri, Stella; Siewe, Mbonda; Moshfeghian, Aliakbar; Madihally, Sundararajan V

    2005-12-01

    Recently, chitosan-gelatin scaffolds have gained much attention in various tissue engineering applications. However, the underlying cell-matrix interactions remain unclear in addition to the scaffold degradation and mechanical characteristics. In this study, we evaluated (i) the degradation kinetics of chitosan and chitosan-gelatin scaffolds in the presence of 10mg/L of lysozyme for dimensional stability, weight loss, and pH changes for a period of 2 months, (ii) tensile and compressive properties of films and scaffolds in wet state at 37 degrees C, (iii) viability of fibroblasts and human umbilical vein endothelial cells (HUVECs) on scaffolds, and (iv) the alteration in cell spreading characteristics, cytoskeletal actin distribution, focal adhesion kinase (FAK) distribution and PECAM-1 expression of HUVECs under static and 4.5, 8.5, 13 and 18 dyn/cm2 shear stress conditions. Degradation results showed that gelatin-containing chitosan scaffolds had faster degradation rate and significant loss of material than chitosan. Mechanical properties of chitosan are affected by the addition of gelatin although there was no clear trend. Three-dimensional chitosan and chitosan-gelatin scaffolds supported fibroblast viability equally. However, chitosan membranes decreased cell-spreading area, disrupted F-actin and localized FAK in the nucleus of HUVECs. Importantly, the lowest shear stress tested (4.5 dyn/cm2) for 3 h washed away cells on chitosan suggesting weak cell adhesion. In the blends, effect of gelatin was dominant; actin and FAK distribution were comparable to gelatin in static culture. However, at higher shear stresses, presence of chitosan inhibited shear-induced increase in cell spreading and weakened cell adhesive strength. No significant differences were observed in PECAM-1 expression. In summary, these results showed significant influence of blending gelatin with chitosan on scaffold properties and cellular behavior. PMID:16005510

  12. Mechanical properties evolution of a PLGA-PLCL composite scaffold for ligament tissue engineering under static and cyclic traction-torsion in vitro culture conditions.

    PubMed

    Kahn, Cyril J F; Ziani, Kahina; Zhang, Ye Min; Liu, Jian; Tran, Nguyen; Babin, Jérôme; de Isla, Natalia; Six, Jean-Luc; Wang, Xiong

    2013-01-01

    This study aims to investigate the in vitro degradation of a poly(L-lactic-co-glycolic acid)-poly(L-lactic-co-ϵ-caprolactone) (PLGA-PLCL) composite scaffold's mechanical properties under static culture condition and 2 h period per day of traction-torsion cyclic culture conditions of simultaneous 10% uniaxial strain and 90° of torsion cycles at 0.33 Hz. Scaffolds were cultured in static conditions, during 28 days, with or without cell seeded or under dynamic conditions during 14 days in a bioreactor. Scaffolds' biocompatibility and proliferation were investigated with Alamar Blue tests and cell nuclei staining. Scaffolds' mechanical properties were tested during degradation by uniaxial traction test. The PLGA-PLCL composite scaffold showed a good cytocompatibility and a high degree of colonization in static conditions. Mechanical tests showed a competition between two process of degradation which have been associated to hydrolytic and enzymatic degradation for the reinforce yarn in poly(L-lactic-co-glycolic acid) (PLGA). The enzymatic degradation led to a decrease effect on mechanical properties of cell-seeded scaffolds during the 21st days, but the hydrolytic degradation was preponderant at day 28. In conclusion, the structure of this scaffold is adapted to culture in terms of biocompatibility and cell orientation (microfiber) but must be improved by delaying the degradation of it reinforce structure in PLGA.

  13. Fabrication and characterization of porous EH scaffolds and EH-PEG bilayers.

    PubMed

    Falco, Erin E; Coates, Emily E; Li, Erik; Roth, J Scott; Fisher, John P

    2011-06-01

    Biomaterials made from synthetic polymers are becoming more pervasive in the medical field. Synthetic polymers are particularly advantageous as their chemical and mechanical properties can be easily tailored to a specific application. This work characterizes polymer scaffolds derived from the cyclic acetal monomer 5-ethyl-5-(hydroxymethyl)-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD). Both porous scaffolds and bilayer scaffolds based upon the EHD monomer were fabricated, and the resulting scaffolds' degradation and mechanical properties were studied. The results showed that by modifying the architecture of an EH scaffold, either by adding a porous network or a poly(ethylene glycol) (PEG) coating, the degradation and Young's modulus of the biomaterial can be significant altered. However, results also indicated that these architectural modifications can be accomplished without a significant loss in the flexural strength of the scaffold. Therefore, we suggest that porous EH scaffolds, and particularly porous EH-PEG bilayers, may be especially useful in dynamic tissue environments due to their advantageous architectural and mechanical properties. PMID:21442727

  14. Microwave-assisted synthesis of porous chitosan-modified montmorillonite-hydroxyapatite composite scaffolds.

    PubMed

    Kar, Sumanta; Kaur, Tejinder; Thirugnanam, A

    2016-01-01

    In this study, a porous chitosan-organically modified montmorillonite-hydroxyapatite (CS-OM-HA) composite scaffold was developed by combining microwave irradiation and gas foaming method. Hydroxyapatite (HA) particles of size ∼ 65 nm were synthesized and characterized by X-ray diffraction (XRD) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The prepared composite scaffolds were characterized using ATR-FTIR, XRD, mercury intrusion porosimeter (MIP) and scanning electron microscopy (SEM) studies. The synergistic effect of HA and OM on the mechanical and in vitro biological properties (swelling, degradation, protein adsorption and bioactivity) of the composite scaffolds were evaluated. Swelling, degradation, mechanical property, bioactivity and protein adsorption studies of CS-OM-HA composite scaffolds have shown desirable results in comparison with the pure CS and CS-OM composite scaffolds. CS-OM-HA composite scaffolds were also found to be non-cytotoxic to MG 63 osteoblast cell lines. From the study, it can be concluded that the novel CS-OM-HA composite scaffold with improved mechanical and in vitro biological properties has wide potential in non-load bearing bone tissue engineering applications.

  15. Laser fabrication of three-dimensional CAD scaffolds from photosensitive gelatin for applications in tissue engineering.

    PubMed

    Ovsianikov, Aleksandr; Deiwick, Andrea; Van Vlierberghe, Sandra; Dubruel, Peter; Möller, Lena; Dräger, Gerald; Chichkov, Boris

    2011-04-11

    In the present work, 3D CAD scaffolds for tissue engineering applications were developed starting from methacrylamide-modified gelatin (GelMOD) using two-photon polymerization (2PP). The scaffolds were cross-linked employing the biocompatible photoinitiator Irgacure 2959. Because gelatin is derived from collagen (i.e., the main constituent of the ECM), the developed materials mimic the cellular microenvironment from a chemical point of view. In addition, by applying the 2PP technique, structural properties of the cellular microenvironment can also be mimicked. Furthermore, in vitro degradation assays indicated that the enzymatic degradation capability of gelatin is preserved for the methacrylamide-modified derivative. An in depth morphological analysis of the 2PP-fabricated scaffolds demonstrated that the parameters of the CAD model are reproduced with great precision, including the ridge-like surface topography on the order of 1.5 μm. The developed scaffolds showed an excellent stability in culture medium. In a final part of the present work, the suitability of the developed scaffolds for tissue engineering applications was verified. The results indicated that the applied materials are suitable to support porcine mesenchymal stem cell adhesion and subsequent proliferation. Upon applying osteogenic stimulation, the seeded cells differentiated into the anticipated lineage. Energy dispersive X-ray (EDX) analysis showed the induced calcification of the scaffolds. The results clearly indicate that 2PP is capable of manufacturing precisely constructed 3D tissue engineering scaffolds using photosensitive polymers as starting material. PMID:21366287

  16. Bone tissue engineering with a collagen–hydroxyapatite scaffold and culture expanded bone marrow stromal cells

    PubMed Central

    Villa, Max M.; Wang, Liping; Huang, Jianping; Rowe, David W.; Wei, Mei

    2015-01-01

    Osteoprogenitor cells combined with supportive biomaterials represent a promising approach to advance the standard of care for bone grafting procedures. However, this approach faces challenges, including inconsistent bone formation, cell survival in the implant, and appropriate biomaterial degradation. We have developed a collagen–hydroxyapatite (HA) scaffold that supports consistent osteogenesis by donor derived osteoprogenitors, and is more easily degraded than a pure ceramic scaffold. Herein, the material properties are characterized as well as cell attachment, viability, and progenitor distribution in vitro. Furthermore, we examined the biological performance in vivo in a critical-size mouse calvarial defect. To aid in the evaluation of the in-house collagen–HA scaffold, the in vivo performance was compared with a commercial collagen–HA scaffold (Healos®, Depuy). The in-house collagen–HA scaffold supported consistent bone formation by predominantly donor-derived osteoblasts, nearly completely filling a 3.5 mm calvarial defect with bone in all samples (n=5) after 3 weeks of implantation. In terms of bone formation and donor cell retention at 3 weeks postimplantation, no statistical difference was found between the in-house and commercial scaffold following quantitative histomorphometry. The collagen–HA scaffold presented here is an open and well-defined platform that supports robust bone formation and should facilitate the further development of collagen–hydroxyapatite biomaterials for bone tissue engineering. PMID:24909953

  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. Directional and temporal variation of the mechanical properties of robocast scaffold during resorption.

    PubMed

    Waygood, J; Murch, G E; Fiedler, T

    2015-09-01

    This paper addresses the mechanical behavior of robocast PCL-Bioglass(®) scaffolds. These structures can be used as 3rd generation implants in tissue engineering to support the regrowth of damaged tissue, in particular bone. After successful tissue regeneration the scaffolds slowly dissolve leaving no foreign material permanently inside the body. However, to avoid mechanical separation from surrounding tissue they must exhibit similar mechanical properties. The present study introduces a detailed numerical study focusing on the determination of effective mechanical material properties, their anisotropy, and mechanical degradation due to scaffold resorption. In order to accurately capture the complex scaffold geometry, micro-computed tomography scans of actual samples are conducted. The resulting three-dimensional data are directly converted into finite element calculation models. Numerical compressive tests of these unmodified models are repeated for three perpendicular directions to investigate mechanical anisotropy, after which the effect of scaffold degradation due to exposure to body fluid is simulated. To this end, two different resorption models, namely surface erosion and bulk degradation, are applied to the micro-computed tomography data. The modified geometry data are then converted into calculation models and numerical compression tests then allow the prediction of the mechanical properties of partially resorbed scaffolds.

  19. Chitosan-based hydrogel tissue scaffolds made by 3D plotting promotes osteoblast proliferation and mineralization.

    PubMed

    Liu, I-Hsin; Chang, Shih-Hsin; Lin, Hsin-Yi

    2015-05-13

    A 3D plotting system was used to make chitosan-based tissue scaffolds with interconnected pores using pure chitosan (C) and chitosan cross-linked with pectin (CP) and genipin (CG). A freeze-dried chitosan scaffold (CF/D) was made to compare with C, to observe the effects of structural differences. The fiber size, pore size, porosity, compression strength, swelling ratio, drug release efficacy, and cumulative weight loss of the scaffolds were measured. Osteoblasts were cultured on the scaffolds and their proliferation, type I collagen production, alkaline phosphatase activity, calcium deposition, and morphology were observed. C had a lower swelling ratio, degradation, porosity and drug release efficacy and a higher compressional stiffness and cell proliferation compared to CF/D (p < 0.05). Of the 3D-plotted samples, cells on CP exhibited the highest degree of mineralization after 21 d (p < 0.05). CP also had the highest swelling ratio and fastest drug release, followed by C and CG (p < 0.05). Both CP and CG were stiffer and degraded more slowly in saline solution than C (p < 0.05). In summary, 3D-plotted scaffolds were stronger, less likely to degrade and better promoted osteoblast cell proliferation in vitro compared to the freeze-dried scaffolds. C, CP and CG were structurally similar, and the different crosslinking caused significant changes in their physical and biological performances.

  20. Chitosan-based hydrogel tissue scaffolds made by 3D plotting promotes osteoblast proliferation and mineralization.

    PubMed

    Liu, I-Hsin; Chang, Shih-Hsin; Lin, Hsin-Yi

    2015-06-01

    A 3D plotting system was used to make chitosan-based tissue scaffolds with interconnected pores using pure chitosan (C) and chitosan cross-linked with pectin (CP) and genipin (CG). A freeze-dried chitosan scaffold (CF/D) was made to compare with C, to observe the effects of structural differences. The fiber size, pore size, porosity, compression strength, swelling ratio, drug release efficacy, and cumulative weight loss of the scaffolds were measured. Osteoblasts were cultured on the scaffolds and their proliferation, type I collagen production, alkaline phosphatase activity, calcium deposition, and morphology were observed. C had a lower swelling ratio, degradation, porosity and drug release efficacy and a higher compressional stiffness and cell proliferation compared to CF/D (p < 0.05). Of the 3D-plotted samples, cells on CP exhibited the highest degree of mineralization after 21 d (p < 0.05). CP also had the highest swelling ratio and fastest drug release, followed by C and CG (p < 0.05). Both CP and CG were stiffer and degraded more slowly in saline solution than C (p < 0.05). In summary, 3D-plotted scaffolds were stronger, less likely to degrade and better promoted osteoblast cell proliferation in vitro compared to the freeze-dried scaffolds. C, CP and CG were structurally similar, and the different crosslinking caused significant changes in their physical and biological performances. PMID:25970802

  1. The scaffold tree: an efficient navigation in the scaffold universe.

    PubMed

    Ertl, Peter; Schuffenhauer, Ansgar; Renner, Steffen

    2011-01-01

    The Scaffold Tree algorithm (J Chem Inf Model 47:47-58, 2007) allows to organize large molecular data sets by arranging sets of molecules into a unique tree hierarchy based on their scaffolds, with scaffolds forming leaf nodes of such tree. The hierarchy is created by iterative removal of rings from more complex scaffolds using chemically meaningful set of rules, until a single, root ring is obtained. The classification is deterministic, data set independent, and scales linearly with the number of compounds included in the data set. In this review we summarize the basic principles of the Scaffold Tree methodology and review its applications, which appeared in recent medicinal chemistry literature, including the use of Scaffold Trees for visualization of large chemical data sets, compound clustering, and the identification of novel bioactive molecules. References to several computer programs, including also free tools available on the Internet, allowing to perform classification and visualization of molecules based on their scaffolds are also provided. PMID:20838972

  2. Control of crosslinking for tailoring collagen-based scaffolds stability and mechanics

    PubMed Central

    Davidenko, N.; Schuster, C.F.; Bax, D.V.; Raynal, N.; Farndale, R.W.; Best, S.M.; Cameron, R.E.

    2015-01-01

    We provide evidence to show that the standard reactant concentrations used in tissue engineering to cross-link collagen-based scaffolds are up to 100 times higher than required for mechanical integrity in service, and stability against degradation in an aqueous environment. We demonstrate this with a detailed and systematic study by comparing scaffolds made from (a) collagen from two different suppliers, (b) gelatin (a partially denatured collagen) and (c) 50% collagen–50% gelatin mixtures. The materials were processed, using lyophilisation, to produce homogeneous, highly porous scaffolds with isotropic architectures and pore diameters ranging from 130 to 260 μm. Scaffolds were cross-linked using a carbodiimide treatment, to establish the effect of the variations in crosslinking conditions (down to very low concentrations) on the morphology, swelling, degradation and mechanical properties of the scaffolds. Carbodiimide concentration of 11.5 mg/ml was defined as the standard (100%) and was progressively diluted down to 0.1%. It was found that 10-fold reduction in the carbodiimide content led to the significant increase (almost 4-fold) in the amount of free amine groups (primarily on collagen lysine residues) without compromising mechanics and stability in water of all resultant scaffolds. The importance of this finding is that, by reducing cross-linking, the corresponding cell-reactive carboxylate anions (collagen glutamate or aspartate residues) that are essential for integrin-mediated binding remain intact. Indeed, a 10-fold reduction in carbodiimide crosslinking resulted in near native-like cell attachment to collagen scaffolds. We have demonstrated that controlling the degree of cross-linking, and hence retaining native scaffold chemistry, offers a major step forward in the biological performance of collagen- and gelatin-based tissue engineering scaffolds. Statement of Significance This work developed collagen and gelatine-based scaffolds with structural

  3. 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

  4. 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.

  5. A biomimetic scaffold for culturing limbal stem cells: a promising alternative for clinical transplantation.

    PubMed

    Dravida, Subhadra; Gaddipati, Subhash; Griffith, May; Merrett, Kim; Lakshmi Madhira, Soundarya; Sangwan, Virender S; Vemuganti, Geeta K

    2008-07-01

    Limbal tissues can be cultured on various types of scaffolds to create a sheet of limbal-corneal epithelium for research as well as clinical transplantation. An optically clear, biocompatible, biomimetic scaffold would be an ideal replacement graft for transplanting limbal stem cells. In this study, we evaluated the physical and culture characteristics of the recombinant human cross-linked collagen scaffold (RHC-III scaffold) and compared it with denuded human amniotic membrane (HAM). Optical/mechanical properties and microbial susceptibility were measured for the scaffolds. With the approval of the institutional review board, 2 mm fresh human limbal tissues were cultured on 2.5 x 2.5 cm(2) scaffolds in a medium containing autologous serum in a feeder cell-free submerged system. The cultured cell systems were characterized by morphology and immunohistochemistry for putative stem cells and differentiated cell markers. The refractive index (RI) and tensile strength of the RHC-III scaffold were comparable to human cornea, with delayed in vitro degradation compared to HAM. RHC-III scaffolds were 10-fold less susceptible to microbial growth. Cultures were initiated on day 1, expanded to form a monolayer by day 3 and covered the entire growth surface in 10 days. Stratified epithelium on the scaffolds was visualized by transmission electron microscopy. The cultured cells showed p63 and ABCG2 positivity in the basal layer and were immunoreactive for cytokeratin K3 and K12 in the suprabasal layers. RHC-III scaffold supports and retains the growth and stemness of limbal stem cells, in addition to resembling human cornea; thus, it could be a good replacement scaffold for growing cells for clinical transplantation. PMID:18512269

  6. Porous ovalbumin scaffolds with tunable properties: a resource-efficient biodegradable material for tissue engineering applications.

    PubMed

    Luo, Baiwen; Choong, Cleo

    2015-01-01

    Natural materials are promising alternatives to synthetic materials used in tissue engineering applications as they have superior biocompatibility and promote better cell attachment and proliferation. Ovalbumin, a natural polymer found in avian egg white, is an example of a nature-derived material. Despite the availability and reported biocompatibility of ovalbumin, limited research has been carried out to investigate the efficacy of ovalbumin-based scaffolds for adipose tissue engineering applications. Hence, the current study was carried out to investigate the effect of different crosslinkers on ovalbumin scaffold properties as first step towards the development of ovalbumin-based scaffolds for adipose tissue engineering applications. In this study, highly porous three-dimensional scaffolds were fabricated by using three different crosslinkers: glutaraldehyde, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and 1,4-butanediol diglycidyl ether. Results showed that the overall scaffold properties such as morphology, pore size and mechanical properties could be modulated based on the type and concentration of crosslinkers used during the fabrication process. Subsequently, the efficacy of the different scaffolds for supporting cell proliferation was investigated. In vitro degradation was also carried on for the best scaffold based on the mechanical and cellular results. Overall, this study is a demonstration of the viability of ovalbumin-based scaffolds as cell carriers for soft tissue engineering applications. PMID:25158688

  7. Biodegradable mesoporous calcium-magnesium silicate-polybutylene succinate scaffolds for osseous tissue engineering.

    PubMed

    Zhang, Xinxin; Zhang, Chi; Xu, Wei; Zhong, Biao; Lin, Feng; Zhang, Jian; Wang, Quanxiang; Ji, Jiajin; Wei, Jie; Zhang, Yang

    2015-01-01

    The structural features of bone engineering scaffolds are expected to exhibit osteoinductive behavior and promote cell adhesion, proliferation, and differentiation. In the present study, we employed synthesized ordered mesoporous calcium-magnesium silicate (om-CMS) and polybutylene succinate (PBSu) to develop a novel scaffold with potential applications in osseous tissue engineering. The characteristics, in vitro bioactivity of om-CMS/PBSu scaffold, as well as the cellular responses of MC3T3-E1 cells to the composite were investigated. Our results showed that the om-CMS/PBSu scaffold possesses a large surface area and highly ordered channel pores, resulting in improved degradation and biocompatibility compared to the PBSu scaffold. Moreover, the om-CMS/PBSu scaffold exhibited significantly higher bioactivity and induced apatite formation on its surface after immersion in the simulated body fluid. In addition, the om-CMS/PBSu scaffold provided a high surface area for cell attachment and released Ca, Mg, and Si ions to stimulate osteoblast proliferation. The unique surface characteristics and higher biological efficacy of the om-CMS/PBSu scaffold suggest that it has great potential for being developed into a system that can be employed in osseous tissue engineering. PMID:26604746

  8. Biodegradable mesoporous calcium–magnesium silicate-polybutylene succinate scaffolds for osseous tissue engineering

    PubMed Central

    Zhang, Xinxin; Zhang, Chi; Xu, Wei; Zhong, Biao; Lin, Feng; Zhang, Jian; Wang, Quanxiang; Ji, Jiajin; Wei, Jie; Zhang, Yang

    2015-01-01

    The structural features of bone engineering scaffolds are expected to exhibit osteoinductive behavior and promote cell adhesion, proliferation, and differentiation. In the present study, we employed synthesized ordered mesoporous calcium–magnesium silicate (om-CMS) and polybutylene succinate (PBSu) to develop a novel scaffold with potential applications in osseous tissue engineering. The characteristics, in vitro bioactivity of om-CMS/PBSu scaffold, as well as the cellular responses of MC3T3-E1 cells to the composite were investigated. Our results showed that the om-CMS/PBSu scaffold possesses a large surface area and highly ordered channel pores, resulting in improved degradation and biocompatibility compared to the PBSu scaffold. Moreover, the om-CMS/PBSu scaffold exhibited significantly higher bioactivity and induced apatite formation on its surface after immersion in the simulated body fluid. In addition, the om-CMS/PBSu scaffold provided a high surface area for cell attachment and released Ca, Mg, and Si ions to stimulate osteoblast proliferation. The unique surface characteristics and higher biological efficacy of the om-CMS/PBSu scaffold suggest that it has great potential for being developed into a system that can be employed in osseous tissue engineering. PMID:26604746

  9. Woven silk fabric-reinforced silk nanofibrous scaffolds for regenerating load-bearing soft tissues.

    PubMed

    Han, F; Liu, S; Liu, X; Pei, Y; Bai, S; Zhao, H; Lu, Q; Ma, F; Kaplan, D L; Zhu, H

    2014-02-01

    Although three-dimensional (3-D) porous regenerated silk scaffolds with outstanding biocompatibility, biodegradability and low inflammatory reactions have promising application in different tissue regeneration, the mechanical properties of regenerated scaffolds, especially suture retention strength, must be further improved to satisfy the requirements of clinical applications. This study presents woven silk fabric-reinforced silk nanofibrous scaffolds aimed at dermal tissue engineering. To improve the mechanical properties, silk scaffolds prepared by lyophilization were reinforced with degummed woven silk fabrics. The ultimate tensile strength, elongation at break and suture retention strength of the scaffolds were significantly improved, providing suitable mechanical properties strong enough for clinical applications. The stiffness and degradation behaviors were then further regulated by different after-treatment processes, making the scaffolds more suitable for dermal tissue regeneration. The in vitro cell culture results indicated that these scaffolds maintained their excellent biocompatibility after being reinforced with woven silk fabrics. Without sacrifice of porous structure and biocompatibility, the fabric-reinforced scaffolds with better mechanical properties could facilitate future clinical applications of silk as matrices in skin repair. PMID:24090985

  10. Porous ovalbumin scaffolds with tunable properties: a resource-efficient biodegradable material for tissue engineering applications.

    PubMed

    Luo, Baiwen; Choong, Cleo

    2015-01-01

    Natural materials are promising alternatives to synthetic materials used in tissue engineering applications as they have superior biocompatibility and promote better cell attachment and proliferation. Ovalbumin, a natural polymer found in avian egg white, is an example of a nature-derived material. Despite the availability and reported biocompatibility of ovalbumin, limited research has been carried out to investigate the efficacy of ovalbumin-based scaffolds for adipose tissue engineering applications. Hence, the current study was carried out to investigate the effect of different crosslinkers on ovalbumin scaffold properties as first step towards the development of ovalbumin-based scaffolds for adipose tissue engineering applications. In this study, highly porous three-dimensional scaffolds were fabricated by using three different crosslinkers: glutaraldehyde, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and 1,4-butanediol diglycidyl ether. Results showed that the overall scaffold properties such as morphology, pore size and mechanical properties could be modulated based on the type and concentration of crosslinkers used during the fabrication process. Subsequently, the efficacy of the different scaffolds for supporting cell proliferation was investigated. In vitro degradation was also carried on for the best scaffold based on the mechanical and cellular results. Overall, this study is a demonstration of the viability of ovalbumin-based scaffolds as cell carriers for soft tissue engineering applications.

  11. 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

  12. 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

  13. Mechanical evaluation of gradient electrospun scaffolds with 3D printed ring reinforcements for tracheal defect repair.

    PubMed

    Ott, Lindsey M; Zabel, Taylor A; Walker, Natalie K; Farris, Ashley L; Chakroff, Jason T; Ohst, Devan G; Johnson, Jed K; Gehrke, Steven H; Weatherly, Robert A; Detamore, Michael S

    2016-04-01

    Tracheal stenosis can become a fatal condition, and current treatments include augmentation of the airway with autologous tissue. A tissue-engineered approach would not require a donor source, while providing an implant that meets both surgeons' and patients' needs. A fibrous, polymeric scaffold organized in gradient bilayers of polycaprolactone (PCL) and poly-lactic-co-glycolic acid (PLGA) with 3D printed structural ring supports, inspired by the native trachea rings, could meet this need. The purpose of the current study was to characterize the tracheal scaffolds with mechanical testing models to determine the design most suitable for maintaining a patent airway. Degradation over 12 weeks revealed that scaffolds with the 3D printed rings had superior properties in tensile and radial compression, with at least a three fold improvement and 8.5-fold improvement, respectively, relative to the other scaffold groups. The ringed scaffolds produced tensile moduli, radial compressive forces, and burst pressures similar to or exceeding physiological forces and native tissue data. Scaffolds with a thicker PCL component had better suture retention and tube flattening recovery properties, with the monolayer of PCL (PCL-only group) exhibiting a 2.3-fold increase in suture retention strength (SRS). Tracheal scaffolds with ring reinforcements have improved mechanical properties, while the fibrous component increased porosity and cell infiltration potential. These scaffolds may be used to treat various trachea defects (patch or circumferential) and have the potential to be employed in other tissue engineering applications. PMID:27097554

  14. Long-term effects of knitted silk-collagen sponge scaffold on anterior cruciate ligament reconstruction and osteoarthritis prevention.

    PubMed

    Shen, Weiliang; Chen, Xiao; Hu, Yejun; Yin, Zi; Zhu, Ting; Hu, Jiajie; Chen, Jialin; Zheng, Zefeng; Zhang, Wei; Ran, Jisheng; Heng, Boon Chin; Ji, Junfeng; Chen, Weishan; Ouyang, Hong-Wei

    2014-09-01

    Anterior cruciate ligament (ACL) is difficult to heal after injury due to the dynamic fluid environment of joint. Previously, we have achieved satisfactory regeneration of subcutaneous tendon/ligament with knitted silk-collagen sponge scaffold due to its specific "internal-space-preservation" property. This study aims to investigate the long-term effects of knitted silk-collagen sponge scaffold on ACL regeneration and osteoarthritis prevention. The knitted silk-collagen sponge scaffold was fabricated and implanted into a rabbit ACL injury model. The knitted silk-collagen sponge scaffold was found to enhance migration and adhesion of spindle-shaped cells into the scaffold at 2 months post-surgery. After 6 months, ACL treated with the knitted silk-collagen sponge scaffold exhibited increased expression of ligament genes and better microstructural morphology. After 18 months, the knitted silk-collagen sponge scaffold-treated group had more mature ligament structure and direct ligament-to-bone healing. Implanted knitted silk-collagen sponge scaffolds degraded much more slowly compared to subcutaneous implantation. Furthermore, the knitted silk-collagen sponge scaffold effectively protected joint surface cartilage and preserved joint space for up to 18 months post-surgery. These findings thus demonstrated that the knitted silk-collagen sponge scaffold can regenerate functional ACL and prevent osteoarthritis in the long-term, suggesting its clinical use as a functional bioscaffold for ACL reconstruction.

  15. Elevation changes

    USGS Publications Warehouse

    Jayko, A. S.; Marshall, G.A.; Carver, G.A.

    1992-01-01

    Elevation changes, as well as horizontal displacements of the Earth's surface, are an expected consequence of dip-slip displacement on earthquake faults. the rock surrounding and overlying the fault is forced to stretch and bend to accommodate fault slip. Slip in the case of the April 25 mainshock is thought to have occurred on a gently inclined plane dipping to the northeast at a small angle (see article on preliminary seismological results in this issue).The associated fault-plane solution implies that rock overlying the fault plane (the hanging-wall block west and south of the epicenter) rose and shifted to the northeast. The map on the next page shows the location of the epicenter and approximate extent of uplift and subsidence derived from estimates of the geometry, location. and slip on the buried fault plane. 

  16. Hydroxyapatite-reinforced collagen tissue engineering scaffolds

    NASA Astrophysics Data System (ADS)

    Kane, Robert J.

    Scaffolds have been fabricated from a wide variety of materials and most have showed some success, either as bone graft substitutes or as tissue engineering scaffolds. However, all current scaffold compositions and architectures suffer from one or more flaws including poor mechanical properties, lack of biological response, nondegradability, or a scaffold architecture not conducive to osteointegration. Biomimetic approaches to scaffold design using the two main components of bone tissue, collagen and hydroxyapatite, resulted in scaffolds with superior biological properties but relatively poor mechanical properties and scaffold architecture. It was hypothesized that by optimizing scaffold composition and architecture, HA-collagen bone tissue engineering scaffolds could provide both an excellent biological response along with improved structural properties. The mechanical properties of freeze-dried HA-collagen scaffolds, the most common type of porous HA-collagen material, were first shown to be increased by the addition of HA reinforcements, but scaffold stiffness still fell far short of the desired range. Based on limitations inherent in the freeze-dried process, a new type of leached-porogen scaffold fabrication process was developed. Proof-of-concept scaffolds demonstrated the feasibility of producing leached-porogen HA-collagen materials, and the scaffold architecture was optimized though careful selection of porogen particle size and shape along with an improved crosslinking technique. The final scaffolds exhibited substantially increased compressive modulus compared to previous types HA-collagen scaffolds, while the porosity, pore size, and scaffold permeability were tailored to be suitable for bone tissue ingrowth. An in vitro study demonstrated the capacity of the leached-porogen scaffolds to serve as a substrate for the differentiation of osteoblasts and subsequent production of new bone tissue. The new leached-porogen scaffold HA-collagen scaffolds were

  17. Using Scaffolds in Problem-Based Hypermedia

    ERIC Educational Resources Information Center

    Su, Yuyan; Klein, James D.

    2010-01-01

    This study investigated the use of scaffolds in problem-based hypermedia. Three hundred and twelve undergraduate students enrolled in a computer literacy course worked in project teams to use a hypermedia PBL program focused on designing a personal computer. The PBL program included content scaffolds, metacognitive scaffolds, or no scaffolds.…

  18. Electrospun multifunctional tissue engineering scaffolds

    NASA Astrophysics Data System (ADS)

    Wang, Chong; Wang, Min

    2014-03-01

    Tissue engineering holds great promises in providing successful treatments of human body tissue loss that current methods are unable to treat or unable to achieve satisfactory clinical outcomes. In scaffold-based tissue engineering, a highperformance scaffold underpins the success of a tissue engineering strategy and a major direction in the field is to create multifunctional tissue engineering scaffolds for enhanced biological performance and for regenerating complex body tissues. Electrospinning can produce nanofibrous scaffolds that are highly desirable for tissue engineering. The enormous interest in electrospinning and electrospun fibrous structures by the science, engineering and medical communities has led to various developments of the electrospinning technology and wide investigations of electrospun products in many industries, including biomedical engineering, over the past two decades. It is now possible to create novel, multicomponent tissue engineering scaffolds with multiple functions. This article provides a concise review of recent advances in the R & D of electrospun multifunctional tissue engineering scaffolds. It also presents our philosophy and research in the designing and fabrication of electrospun multicomponent scaffolds with multiple functions.

  19. Exploring the scaffold universe of kinase inhibitors.

    PubMed

    Hu, Ye; Bajorath, Jürgen

    2015-01-01

    The scaffold concept was applied to systematically determine, analyze, and compare core structures of kinase inhibitors. From publicly available inhibitors of the human kinome, scaffolds and cyclic skeletons were systematically extracted and organized taking activity data, structural relationships, and retrosynthetic criteria into account. Scaffold coverage varied greatly across the kinome, and many scaffolds representing compounds with different activity profiles were identified. The majority of kinase inhibitor scaffolds were involved in well-defined yet distinct structural relationships, which had different consequences on compound activity. Scaffolds exclusively representing highly potent compounds were identified as well as structurally analogous scaffolds with very different degrees of promiscuity. Scaffold relationships presented herein suggest a variety of hypotheses for inhibitor design. Our detailed organization of the kinase inhibitor scaffold universe with respect to different activity and structural criteria, all scaffolds, and the original compound data assembled for our analysis are made freely available.

  20. Ectopic osteogenesis and scaffold biodegradation of nano-hydroxyapatite-chitosan in a rat model.

    PubMed

    He, Yiqun; Dong, Youhai; Cui, Fuzhai; Chen, Xujun; Lin, Rongqiang

    2015-01-01

    The bone-formation and scaffold-biodegradation processes have not been fully characterized. This study aimed to determine the osteogenic ability of nHA-CS osteo-induced bone marrow mesenchymal stem cell (BMSC) composites and to explore the relationship between bone formation and scaffold biodegradation. The nHA-CS osteo-induced BMSC composites (nHA-CS+cells group) and the nHA-CS scaffolds (nHA-CS group) were implanted into the femoral spatium intermusculare of SD rats. At 2, 4, 6, 8, and 12 weeks post-implantation, the rat femurs were scanned using computerized tomography (CT), and the CT values of the implants were measured and comparatively analyzed. The implants were then harvested and subjected to hematoxylin and eosin (HE) and Masson's trichrome staining, and the percentages of bone area, scaffold area and collagen area were compared between the two groups. The CT values of the implants were higher in the nHA-CS+cells group than the nHA-CS group at the same time points (P < 0.05). Histological analysis revealed that de novo bone and collagen formation in the pores of the scaffolds gradually increased from 2 weeks post-implantation in both groups and that the scaffold gradually degraded as bone formation proceeded. However, more de novo bone and collagen formation and scaffold degradation occurred in the nHA-CS+cells group than in the nHA-CS group at the same time points (P < 0.05). In conclusion, nHA-CS osteo-induced BMSC composites are promising bone tissue engineering substitutes, and osteo-induced BMSCs can significantly enhance the osteogenic ability and play an active role in the degradation of nHA-CS scaffolds on par with bone formation. PMID:26258851

  1. Biodegradable Fibrous Scaffolds with Tunable Properties Formed from Photocrosslinkable Poly(glycerol sebacate)

    PubMed Central

    Ifkovits, Jamie L.; Devlin, Jeffrey J.; Eng, George; Martens, Timothy P.; Vunjak-Novakovic, Gordana; Burdick, Jason A.

    2009-01-01

    It is becoming increasingly apparent that the architecture and mechanical properties of scaffolds, particularly with respect to mimicking features of natural tissues, are important for tissue engineering applications. Acrylated poly(glycerol sebacate) (Acr-PGS) is a material that can be crosslinked upon exposure to ultraviolet light, leading to networks with tunable mechanical and degradation properties through simple changes during Acr-PGS synthesis. For example, the number of acrylate functional groups on the macromer dictates the concentration of crosslinks formed in the resulting network. Three macromers were synthesized that form networks that vary dramatically with respect to their tensile modulus (~30 kPa to 6.6 MPa) and degradation behavior (~20 to 100% mass loss at 12 weeks) based on the extent of acrylation (~1 to 24%). These macromers were processed into biodegradable fibrous scaffolds using electrospinning, with gelatin as a carrier polymer to facilitate fiber formation and cell adhesion. The resulting scaffolds were also diverse with respect to their mechanics (tensile modulus ranging from ~60 kPa to 1 MPa) and degradation (~45 to 70% mass loss by 12 weeks). Mesenchymal stem cell adhesion and proliferation on all fibrous scaffolds was indistinguishable from controls. The scaffolds showed similar diversity when implanted on the surface of hearts in a rat model of acute myocardial infarction and demonstrated a dependence on scaffold thickness and chemistry in the host response. In summary, these diverse scaffolds with tailorable chemical, structural, mechanical and degradation properties are potentially useful for the engineering of a wide range of soft tissues. PMID:20160937

  2. Oxidation-Induced Degradable Nanogels for Iron Chelation

    PubMed Central

    Liu, Zhi; Wang, Yan; Purro, Max; Xiong, May P.

    2016-01-01

    Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation-sensitive host-guest crosslinkers between β-cyclodextrin (β-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID:26868174

  3. Nanotechnology Biomimetic Cartilage Regenerative Scaffolds

    PubMed Central

    Sardinha, Jose Paulo; Myers, Simon

    2014-01-01

    Cartilage has a limited regenerative capacity. Faced with the clinical challenge of reconstruction of cartilage defects, the field of cartilage engineering has evolved. This article reviews current concepts and strategies in cartilage engineering with an emphasis on the application of nanotechnology in the production of biomimetic cartilage regenerative scaffolds. The structural architecture and composition of the cartilage extracellular matrix and the evolution of tissue engineering concepts and scaffold technology over the last two decades are outlined. Current advances in biomimetic techniques to produce nanoscaled fibrous scaffolds, together with innovative methods to improve scaffold biofunctionality with bioactive cues are highlighted. To date, the majority of research into cartilage regeneration has been focused on articular cartilage due to the high prevalence of large joint osteoarthritis in an increasingly aging population. Nevertheless, the principles and advances are applicable to cartilage engineering for plastic and reconstructive surgery. PMID:24883273

  4. Multilayered Magnetic Gelatin Membrane Scaffolds

    PubMed Central

    Samal, Sangram K.; Goranov, Vitaly; Dash, Mamoni; Russo, Alessandro; Shelyakova, Tatiana; Graziosi, Patrizio; Lungaro, Lisa; Riminucci, Alberto; Uhlarz, Marc; Bañobre-López, Manuel; Rivas, Jose; Herrmannsdörfer, Thomas; Rajadas, Jayakumar; De Smedt, Stefaan; Braeckmans, Kevin; Kaplan, David L.; Dediu, V. Alek

    2016-01-01

    A versatile approach for the design and fabrication of multilayer magnetic scaffolds with tunable magnetic gradients is described. Multilayer magnetic gelatin membrane scaffolds with intrinsic magnetic gradients were designed to encapsulate magnetized bioagents under an externally applied magnetic field for use in magnetic-field-assisted tissue engineering. The temperature of the individual membranes increased up to 43.7 °C under an applied oscillating magnetic field for 70 s by magnetic hyperthermia, enabling the possibility of inducing a thermal gradient inside the final 3D multilayer magnetic scaffolds. On the basis of finite element method simulations, magnetic gelatin membranes with different concentrations of magnetic nanoparticles were assembled into 3D multilayered scaffolds. A magnetic-gradient-controlled distribution of magnetically labeled stem cells was demonstrated in vitro. This magnetic biomaterial–magnetic cell strategy can be expanded to a number of different magnetic biomaterials for various tissue engineering applications. PMID:26451743

  5. Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties.

    PubMed

    Mehrasa, Mohammad; Asadollahi, Mohammad Ali; Nasri-Nasrabadi, Bijan; Ghaedi, Kamran; Salehi, Hossein; Dolatshahi-Pirouz, Alireza; Arpanaei, Ayyoob

    2016-09-01

    Poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical properties as well as in vitro degradation behavior of scaffolds were investigated. The mean diameters of nanofibers were 974±68nm for the pure PLGA scaffolds vs 832±70, 764±80, and 486±64 for the PLGA/gelatin, PLGA/10wt% MSNPs, and the PLGA/gelatin/10wt% MSNPs scaffolds, respectively. The results suggested that the incorporation of gelatin and MSNPs into PLGA-based scaffolds enhances the hydrophilicity of scaffolds due to an increase of hydrophilic functional groups on the surface of nanofibers. With porosity examination, it was concluded that the incorporation of MSNPs and gelatin decrease the porosity of scaffolds. Nanoparticles also improved the tensile mechanical properties of scaffolds. Using in vitro degradation analysis, it was shown that the addition of nanoparticles to the nanofibers matrix increases the weight loss percentage of PLGA-based samples, whereas it decreases the weight loss percentage in the PLGA/gelatin composites. Cultivation of rat pheochromocytoma cell line (PC12), as precursor cells of dopaminergic neural cells, on the scaffolds demonstrated that the introduction of MSNPs into PLGA and PLGA/gelatin matrix leads to improved cell attachment and proliferation and enhances cellular processes. PMID:27207035

  6. Three-Dimensional Elastomeric Scaffolds Designed with Cardiac-Mimetic Structural and Mechanical Features

    PubMed Central

    Neal, Rebekah A.; Jean, Aurélie; Park, Hyoungshin; Wu, Patrick B.; Hsiao, James; Engelmayr, George C.; Langer, Robert

    2013-01-01

    Tissue-engineered constructs, at the interface of material science, biology, engineering, and medicine, have the capacity to improve outcomes for cardiac patients by providing living cells and degradable biomaterials that can regenerate the native myocardium. With an ultimate goal of both delivering cells and providing mechanical support to the healing heart, we designed three-dimensional (3D) elastomeric scaffolds with (1) stiffnesses and anisotropy mimicking explanted myocardial specimens as predicted by finite-element (FE) modeling, (2) systematically varied combinations of rectangular pore pattern, pore aspect ratio, and strut width, and (3) structural features approaching tissue scale. Based on predicted mechanical properties, three scaffold designs were selected from eight candidates for fabrication from poly(glycerol sebacate) by micromolding from silicon wafers. Large 20×20 mm scaffolds with high aspect ratio features (5:1 strut height:strut width) were reproducibly cast, cured, and demolded at a relatively high throughput. Empirically measured mechanical properties demonstrated that scaffolds were cardiac mimetic and validated FE model predictions. Two-layered scaffolds providing fully interconnected pore networks were fabricated by layer-by-layer assembly. C2C12 myoblasts cultured on one-layered scaffolds exhibited specific patterns of cell elongation and interconnectivity that appeared to be guided by the scaffold pore pattern. Neonatal rat heart cells cultured on two-layered scaffolds for 1 week were contractile, both spontaneously and in response to electrical stimulation, and expressed sarcomeric α-actinin, a cardiac biomarker. This work not only demonstrated several scaffold designs that promoted functional assembly of rat heart cells, but also provided the foundation for further computational and empirical investigations of 3D elastomeric scaffolds for cardiac tissue engineering. PMID:23190320

  7. Collagen scaffolds derived from fresh water fish origin and their biocompatibility.

    PubMed

    Pati, Falguni; Datta, Pallab; Adhikari, Basudam; Dhara, Santanu; Ghosh, Kuntal; Das Mohapatra, Pradeep Kumar

    2012-04-01

    Collagen, a major component of native extracellular matrix, has diverse biomedical applications. However, its application is limited due to lack of cost-effective production and risk of disease transmission from bovine sources currently utilized. This study describes fabrication and characterization of nano/micro fibrous scaffolds utilizing collagen extracted from fresh water fish origin. This is the first time collagen extracted from fresh water fish origin was studied for their biocompatibility and immunogenicity. The nano/micro fibrous collagen scaffolds were fabricated through self-assembly owing to its amphiphilic nature and were subsequently cross-linked. In vitro degradation study revealed higher stability of the cross-linked scaffolds with only ~50% reduction of mass in 30 days, while the uncross-linked one degraded completely in 4 days. Further, minimal inflammatory response was observed when collagen solution was injected in mice with or without adjuvant, without significant dilution of sera. The fish collagen scaffolds exhibited considerable cell viability and were comparable with that of bovine collagen. SEM and fluorescence microscopic analysis revealed significant proliferation rate of cells on the scaffolds and within 5 days the cells were fully confluent. These findings indicated that fish collagen scaffolds derived from fresh water origin were highly biocompatible in nature.

  8. Polyphenol-Stabilized Tubular Elastin Scaffolds for Tissue Engineered Vascular Grafts

    PubMed Central

    Chuang, Ting-Hsien; Stabler, Christopher; Simionescu, Agneta

    2009-01-01

    Tissue-engineered vascular grafts require elastic, acellular porous scaffolds with controlled biodegradability and properties matching those of natural arteries. Elastin would be a desirable component for such applications, but elastin does not easily regenerate experimentally. Our approach is to develop tubular elastin scaffolds using decellularization and removal of collagen from porcine carotid arteries (∼5 mm diameter) using alkaline extraction. Because elastin is susceptible to rapid degeneration after implantation, scaffolds were further treated with penta-galloyl glucose (PGG), an established polyphenolic elastin-stabilizing agent. Scaffolds were compared in vitro with detergent-decellularized arteries for structure, composition, resistance to degradation, mechanical properties, and cytotoxicity and in vivo for cell infiltration and remodeling potential. Results showed effective decellularization and almost complete collagen removal by alkaline extraction. PGG-treated elastin scaffolds proved to be resistant to elastase digestion in vitro, maintained their cylindrical shapes, showed high resistance to burst pressures, and supported growth of endothelial cells and fibroblasts. In vivo results showed that PGG treatment reduced the rate of elastin biodegradation and controlled cell infiltration but did not hamper new collagen and proteoglycan deposition and secretion of matrix-degrading proteases. Alkali-purified, PGG-treated tubular arterial elastin scaffolds exhibit many desirable properties to be recommended for clinical applications as vascular grafts. PMID:19254115

  9. Accelerated wound healing by injectable microporous gel scaffolds assembled from annealed building blocks

    PubMed Central

    Griffin, Donald R.; Weaver, Westbrook M.; Scumpia, Philip; Di Carlo, Dino; Segura, Tatiana

    2015-01-01

    Summary Injectable hydrogels can provide a scaffold for in situ tissue regrowth and regeneration, however these injected materials require gel degradation prior to tissue reformation limiting their ability to provide physical support. We have created a new class of injectable biomaterial that circumvents this challenge by providing an interconnected microporous network for simultaneous tissue reformation and material degradation. We assemble monodisperse micro-gel building blocks into an interconnected microporous annealed particle (MAP) scaffold. Through microfluidic formation, we tailor the chemical and physical properties of the building blocks, providing downstream control of the physical and chemical properties of the assembled MAP scaffold. In vitro, cells incorporated during MAP scaffold formation proliferated and formed extensive 3D networks within 48 hours. In vivo, the injectable MAP scaffold facilitated cell migration resulting in rapid cutaneous tissue regeneration and tissue structure formation within 5 days. The combination of microporosity and injectability achieved with MAP scaffolds will enable novel routes to tissue regeneration in vivo and tissue creation de novo. PMID:26030305

  10. In vivo biocompatibility and mechanical properties of porous zein scaffolds.

    PubMed

    Wang, Hua-Jie; Gong, Sheng-Ju; Lin, Zhi-Xin; Fu, Jian-Xi; Xue, Song-Tao; Huang, Jing-Chun; Wang, Jin-Ye

    2007-09-01

    In our previous study, a three-dimensional zein porous scaffold with a compressive Young's modulus of up to 86.6+/-19.9 MPa and a compressive strength of up to 11.8+/-1.7 MPa was prepared, and was suitable for culture of mesenchymal stem cells (MSCs) in vitro. In this study, we examined its tissue compatibility in a rabbit subcutaneous implantation model; histological analysis revealed a good tissue response and degradability. To improve its mechanical property (especially the brittleness), the scaffolds were prepared using the club-shaped mannitol as the porogen, and stearic acid or oleic acid was added. The scaffolds obtained had an interconnected tubular pore structure, 100-380 microm in pore size, and about 80% porosity. The maximum values of the compressive strength and modulus, the tensile strength and modulus, and the flexural strength and modulus were obtained at the lowest porosity, reaching 51.81+/-8.70 and 563.8+/-23.4 MPa; 3.91+/-0.86 and 751.63+/-58.85 MPa; and 17.71+/-3.02 and 514.39+/-19.02 MPa, respectively. Addition of 15% stearic acid or 20% oleic acid did not affect the proliferation and osteogenic differentiation of MSCs, and a successful improvement of mechanical properties, especially the brittleness of the zein scaffold could be achieved.

  11. Polyurethane-based scaffolds for myocardial tissue engineering.

    PubMed

    Chiono, Valeria; Mozetic, Pamela; Boffito, Monica; Sartori, Susanna; Gioffredi, Emilia; Silvestri, Antonella; Rainer, Alberto; Giannitelli, Sara Maria; Trombetta, Marcella; Nurzynska, Daria; Di Meglio, Franca; Castaldo, Clotilde; Miraglia, Rita; Montagnani, Stefania; Ciardelli, Gianluca

    2014-02-01

    Bi-layered scaffolds with a 0°/90° lay-down pattern were prepared by melt-extrusion additive manufacturing (AM) using a poly(ester urethane) (PU) synthesized from poly(ε-caprolactone) diol, 1,4-butandiisocyanate and l-lysine ethyl ester dihydrochloride chain extender. Rheological analysis and differential scanning calorimetry of the starting material showed that compression moulded PU films were in the molten state at a higher temperature than 155°C. The AM processing temperature was set at 155°C after verifying the absence of PU thermal degradation phenomena by isothermal thermogravimetry analysis and rheological characterization performed at 165°C. Scaffolds highly reproduced computer-aided design geometry and showed an elastomeric-like behaviour which is promising for applications in myocardial regeneration. PU scaffolds supported the adhesion and spreading of human cardiac progenitor cells (CPCs), whereas they did not stimulate CPC proliferation after 1-14 days culture time. In the future, scaffold surface functionalization with bioactive peptides/proteins will be performed to specifically guide CPC behaviour.

  12. Electrospinning of PCL/PVP blends for tissue engineering scaffolds.

    PubMed

    Kim, Gyeong-Man; Le, Kim Huyen Trang; Giannitelli, Sara Maria; Lee, Yu Jin; Rainer, Alberto; Trombetta, Marcella

    2013-06-01

    Currently, one of the main drawbacks of using poly(ε-caprolactone) in the biomedical and pharmaceutical fields is represented by its low biodegradation rate. To overcome this limitation, electrospinning of PCL blended with a water-soluble poly(N-vinyl-2-pyrrolidone) was used to fabricate scaffolds with tunable fiber surface morphology and controllable degradation rates. Electrospun scaffolds revealed a highly immiscible blend state. The incorporated PVP phase was dispersed as inclusions within the electrospun fibers, and then easily extracted by immersing them in cell culture medium, exhibiting nanoporosity on the fiber surface. As a striking result, nanoporosity facilitated not only fiber biodegradation rates, but also improved cell attachment and spreading on the blend electrospun scaffolds. The present findings demonstrate that simultaneous electrospinning technique for PCL with water-soluble PVP provides important insights for successful tuning biodegradation rate for the PCL electrospun scaffolds but not limited to expand other high valuable biocompatible polymers for the future biomedical applications, ranging from tissue regeneration to controlled drug delivery. PMID:23468162

  13. Material properties and bone marrow stromal cells response to in situ crosslinkable RGD-functionlized lactide-co-glycolide scaffolds.

    PubMed

    Jabbari, Esmaiel; He, Xuezhong; Valarmathi, Mani T; Sarvestani, Alireza S; Xu, Weijie

    2009-04-01

    In situ crosslinkable biomaterials with degradation profiles that can be tailored to a particular application are indispensable for treating irregularly shaped defects and for fabrication of shape-selective scaffolds. The objective of this work was to synthesize ultra low molecular weight functionalized PLA and PLGA macromers that can be grafted with bioactive peptides and crosslinked in situ to fabricate biodegradable functional scaffolds. In situ crosslinkable lactide-co-glycolide macromer (cMLGA; "c" for crosslinkable, "M" for macromer, and "LGA" for lactide-co-glycolide) was synthesized by anionic polymerization of lactide and glycolide monomers followed by condensation polymerization with fumaryl chloride. The cMLA (100% L-lactide) and cMLGA macromers formed porous crosslinked scaffolds with NVP as the crosslinker. The mass loss of the crosslinked cMLA and cMLGA was linear with incubation time in vitro (zero-order degradation) and the degradation rate depended on the ratio of lactide to glycolide. cMLGA scaffold with 1:1 lactide to glycolide ratio completely degraded after 4 weeks while the cMLA lost less than 40% of its initial mass after 35 weeks. When cMLA scaffold was functionalized with acrylated integrin-binding Ac-GRGD amino acid sequence, bone marrow stromal (BMS) cells attached and spread on the cMLA scaffold and exhibited focal-point cell adhesion. The mRNA expression levels of collagen-1alpha, osteonectin, and osteopontin for BMS cells seeded in the scaffolds with 1 and 5% Ac-GRGD were upregulated compared with those without Ac-GRGD. cMLGA is attractive as in situ crosslinkable macromer for fabrication of functional scaffolds with degradation characteristics that can be tailored to a particular application. PMID:18431754

  14. Low-Temperature Additive Manufacturing of Biomimic Three-Dimensional Hydroxyapatite/Collagen Scaffolds for Bone Regeneration.

    PubMed

    Lin, Kai-Feng; He, Shu; Song, Yue; Wang, Chun-Mei; Gao, Yi; Li, Jun-Qin; Tang, Peng; Wang, Zheng; Bi, Long; Pei, Guo-Xian

    2016-03-23

    Low-temperature additive manufacturing (AM) holds promise for fabrication of three-dimensional (3D) scaffolds containing bioactive molecules and/or drugs. Due to the strict technical limitations of current approaches, few materials are suitable for printing at low temperature. Here, a low-temperature robocasting method was employed to print biomimic 3D scaffolds for bone regeneration using a routine collagen-hydroxyapatite (CHA) composite material, which is too viscous to be printed via normal 3D printing methods at low temperature. The CHA scaffolds had excellent 3D structure and maintained most raw material properties after printing. Compared to nonprinted scaffolds, printed scaffolds promoted bone marrow stromal cell proliferation and improved osteogenic outcome in vitro. In a rabbit femoral condyle defect model, the interconnecting pores within the printed scaffolds facilitated cell penetration and mineralization before the scaffolds degraded and enhanced repair, compared to nonprinted CHA scaffolds. Additionally, the optimal printing parameters for 3D CHA scaffolds were investigated; 600-μm-diameter rods were optimal in terms of moderate mechanical strength and better repair outcome in vivo. This low-temperature robocasting method could enable a variety of bioactive molecules to be incorporated into printed CHA materials and provides a method of bioprinting biomaterials without compromising their natural properties.

  15. 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

  16. Evaluation of bone matrix gelatin/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering.

    PubMed

    Wang, Z H; Zhang, J; Zhang, Q; Gao, Y; Yan, J; Zhao, X Y; Yang, Y Y; Kong, D M; Zhao, J; Shi, Y X; Li, X L

    2016-01-01

    This study was designed to evaluate bone matrix gelatin (BMG)/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering. Chondrocytes were isolated from costal cartilage of Sprague-Dawley rats and seeded on BMG/fibrin glue or chitosan/gelatin composite scaffolds. After different in vitro culture durations, the scaffolds were subjected to hematoxylin and eosin, Masson's trichrome, and toluidine blue staining, anti-collagen II and anti-aggrecan immunohistochemistry, and scanning electronic microscopy (SEM) analysis. After 2 weeks of culture, chondrocytes were distributed evenly on the surfaces of both scaffolds. Cell numbers and the presence of extracellular matrix components were markedly increased after 8 weeks of culture, and to a greater extent on the chitosan/gelatin scaffold. The BMG/fibrin glue scaffold showed signs of degradation after 8 weeks. Immunofluorescence analysis confirmed higher levels of collagen II and aggrecan using the chitosan/gelatin scaffold. SEM revealed that the majority of cells on the surface of the BMG/fibrin glue scaffold demonstrated a round morphology, while those in the chitosan/gelatin group had a spindle-like shape, with pseudopodia. Chitosan/gelatin scaffolds appear to be superior to BMG/ fibrin glue constructs in supporting chondrocyte attachment, proliferation, and biosynthesis of cartilaginous matrix components. PMID:27525846

  17. Fish collagen-based scaffold containing PLGA microspheres for controlled growth factor delivery in skin tissue engineering.

    PubMed

    Cao, Huan; Chen, Ming-Mao; Liu, Yan; Liu, Yuan-Yuan; Huang, Yu-Qing; Wang, Jian-Hua; Chen, Jing-Di; Zhang, Qi-Qing

    2015-12-01

    To design a scaffold controlled release system for skin tissue engineering, fish collagen/chitosan/chondroitin sulfate scaffolds were fabricated by freeze-drying and incorporated with bFGF-loaded PLGA microspheres (MPs). SEM showed that the scaffolds exhibited an interconnected porous structure, and the spherical MPs were uniformly distributed into the scaffolds. The higher swelling and degradation rate of scaffolds/MPs could lead to a higher diffusion rate of MPs from the scaffolds, causing an increase in the protein release. The release rate of proteins could be adjusted by the size of MPs and the ratio of collagen to chitosan of scaffolds. Circular dichroism spectroscopy and MTT of bFGF after release indicated that the released bFGF retained its structural integrity and bioactivity during preparation. Cell proliferation and in vivo evaluation results suggested that the scaffolds/MPs had a good biocompatibility and an ability to promote fibroblast cell proliferation and skin tissue regeneration. These results demonstrated that this scaffold/MP controlled release system has the potential for skin tissue engineering.

  18. 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.

  19. 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

  20. Biodegradable CSMA/PECA/Graphene Porous Hybrid Scaffold for Cartilage Tissue Engineering.

    PubMed

    Liao, JinFeng; Qu, Ying; Chu, BingYang; Zhang, XiaoNing; Qian, ZhiYong

    2015-01-01

    Owing to the limited repair capacity of articular cartilage, it is essential to develop tissue-engineered cartilage for patients suffering from joint disease and trauma. Herein, we prepared a novel hybrid scaffold composed of methacrylated chondroitin sulfate (CSMA), poly(ethylene glycol) methyl ether-ε-caprolactone-acryloyl chloride (MPEG-PCL-AC, PECA was used as abbreviation for MPEG-PCL-AC) and graphene oxide (GO) and evaluated its potential application in cartilage tissue engineering. To mimic the natural extracellular matrix (ECM) of cartilage, the scaffold had an adequate pore size, porosity, swelling ability, compression modulus and conductivity. Cartilage cells contacted with the scaffold remained viable and showed growth potential. Furthermore, CSMA/PECA/GO scaffold was biocompatible and had a favorable degradation rate. In the cartilage tissue repair of rabbit, Micro-CT and histology observation showed the group of CSMA/PECA/GO scaffold with cellular supplementation had better chondrocyte morphology, integration, continuous subchondral bone, and much thicker newly formed cartilage compared with scaffold group and control group. Our results show that the CSMA/PECA/GO hybrid porous scaffold can be applied in articular cartilage tissue engineering and may have great potential to in other types of tissue engineering applications. PMID:25961959

  1. Silk fibroin/poly (vinyl alcohol) blend scaffolds for controlled delivery of curcumin.

    PubMed

    Li, Xiaomeng; Qin, Jinli; Ma, Jun

    2015-06-01

    A silk fibroin/poly (vinyl alcohol) porous scaffold with a water vapor transmission rate of 2125 ± 464 g/m(2)/day has been developed via thermally induced phase separation (gelation) and freeze-drying process. A hierarchical architecture of micropores and nanofibers was observed inside the scaffolds, and the related structures were analyzed. The viability and proliferation of 3T3 fibroblasts were examined, which indicated that the scaffolds exerted low cytotoxicity. After loading curcumin, the scaffolds can suppress the growth of 3T3 fibroblasts. The release behavior of curcumin from the scaffolds was investigated. At pH = 7.2, the release profiles showed no significant difference for the loading amounts of 0.5 mg and 0.25 mg per sample. Meanwhile, the cumulative amount of released drug at pH = 5.7 was significantly more than that in neutral solution due to more degradation of the scaffolds. It was suggested that the silk fibroin/poly (vinyl alcohol) blend scaffolds could be potentially used as wound dressing materials. PMID:26816634

  2. Fabrication of gelatin-strontium substituted calcium phosphate scaffolds with unidirectional pores for bone tissue engineering.

    PubMed

    Wu, Yu-Chun; Lin, Wei-Yu; Yang, Chyun-Yu; Lee, Tzer-Min

    2015-03-01

    This study fabricated homogeneous gelatin-strontium substituted calcium phosphate composites via coprecipitation in a gelatin solution. Unidirectional porous scaffolds with an oriented microtubular structure were then manufactured using freeze-drying technology. The resulting structure and pore alignment were determined using scanning electron microscopy. The pore size were in the range of 200-400 μm, which is considered ideal for the engineering of bone tissue. The scaffolds were further characterized using energy dispersive spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Hydroxyapatite was the main calcium phosphate compound in the scaffolds, with strontium incorporated into the crystal structure. The porosity of the scaffolds decreased with increasing concentration of calcium-phosphate. The compressive strength in the longitudinal direction was two to threefold higher than that observed in the transverse direction. Our results demonstrate that the composite scaffolds degraded by approximately 20 % after 5 weeks. Additionally, in vitro results reveal that the addition of strontium significantly increased human osteoblastic cells proliferation. Scaffolds containing strontium with a Sr-CaP/(gelatin + Sr-CaP) ratio of 50 % provided the most suitable environment for cell proliferation, particularly under dynamic culture conditions. This study demonstrates the considerable potential of composite scaffolds composed of gelatin-strontium-substituted calcium phosphate for applications in bone tissue engineering.

  3. Silk fibroin/poly (vinyl alcohol) blend scaffolds for controlled delivery of curcumin

    PubMed Central

    Li, Xiaomeng; Qin, Jinli; Ma, Jun

    2015-01-01

    A silk fibroin/poly (vinyl alcohol) porous scaffold with a water vapor transmission rate of 2125 ± 464 g/m2/day has been developed via thermally induced phase separation (gelation) and freeze-drying process. A hierarchical architecture of micropores and nanofibers was observed inside the scaffolds, and the related structures were analyzed. The viability and proliferation of 3T3 fibroblasts were examined, which indicated that the scaffolds exerted low cytotoxicity. After loading curcumin, the scaffolds can suppress the growth of 3T3 fibroblasts. The release behavior of curcumin from the scaffolds was investigated. At pH = 7.2, the release profiles showed no significant difference for the loading amounts of 0.5 mg and 0.25 mg per sample. Meanwhile, the cumulative amount of released drug at pH = 5.7 was significantly more than that in neutral solution due to more degradation of the scaffolds. It was suggested that the silk fibroin/poly (vinyl alcohol) blend scaffolds could be potentially used as wound dressing materials. PMID:26816634

  4. Fabrication of gelatin-strontium substituted calcium phosphate scaffolds with unidirectional pores for bone tissue engineering.

    PubMed

    Wu, Yu-Chun; Lin, Wei-Yu; Yang, Chyun-Yu; Lee, Tzer-Min

    2015-03-01

    This study fabricated homogeneous gelatin-strontium substituted calcium phosphate composites via coprecipitation in a gelatin solution. Unidirectional porous scaffolds with an oriented microtubular structure were then manufactured using freeze-drying technology. The resulting structure and pore alignment were determined using scanning electron microscopy. The pore size were in the range of 200-400 μm, which is considered ideal for the engineering of bone tissue. The scaffolds were further characterized using energy dispersive spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Hydroxyapatite was the main calcium phosphate compound in the scaffolds, with strontium incorporated into the crystal structure. The porosity of the scaffolds decreased with increasing concentration of calcium-phosphate. The compressive strength in the longitudinal direction was two to threefold higher than that observed in the transverse direction. Our results demonstrate that the composite scaffolds degraded by approximately 20 % after 5 weeks. Additionally, in vitro results reveal that the addition of strontium significantly increased human osteoblastic cells proliferation. Scaffolds containing strontium with a Sr-CaP/(gelatin + Sr-CaP) ratio of 50 % provided the most suitable environment for cell proliferation, particularly under dynamic culture conditions. This study demonstrates the considerable potential of composite scaffolds composed of gelatin-strontium-substituted calcium phosphate for applications in bone tissue engineering. PMID:25773230

  5. Improving effects of chitosan nanofiber scaffolds on osteoblast proliferation and maturation

    PubMed Central

    Ho, Ming-Hua; Liao, Mei-Hsiu; Lin, Yi-Ling; Lai, Chien-Hao; Lin, Pei-I; Chen, Ruei-Ming

    2014-01-01

    Osteoblast maturation plays a key role in regulating osteogenesis. Electrospun nanofibrous products were reported to possess a high surface area and porosity. In this study, we developed chitosan nanofibers and examined the effects of nanofibrous scaffolds on osteoblast maturation and the possible mechanisms. Macro- and micro observations of the chitosan nanofibers revealed that these nanoproducts had a flat surface and well-distributed fibers with nanoscale diameters. Mouse osteoblasts were able to attach onto the chitosan nanofiber scaffolds, and the scaffolds degraded in a time-dependent manner. Analysis by scanning electron microscopy further showed mouse osteoblasts adhered onto the scaffolds along the nanofibers, and cell–cell communication was also detected. Mouse osteoblasts grew much better on chitosan nanofiber scaffolds than on chitosan films. In addition, human osteoblasts were able to adhere and grow on the chitosan nanofiber scaffolds. Interestingly, culturing human osteoblasts on chitosan nanofiber scaffolds time-dependently increased DNA replication and cell proliferation. In parallel, administration of human osteoblasts onto chitosan nanofibers significantly induced osteopontin, osteocalcin, and alkaline phosphatase (ALP) messenger (m)RNA expression. As to the mechanism, chitosan nanofibers triggered runt-related transcription factor 2 mRNA and protein syntheses. Consequently, results of ALP-, alizarin red-, and von Kossa-staining analyses showed that chitosan nanofibers improved osteoblast mineralization. Taken together, results of this study demonstrate that chitosan nanofibers can stimulate osteoblast proliferation and maturation via runt-related transcription factor 2-mediated regulation of osteoblast-associated osteopontin, osteocalcin, and ALP gene expression. PMID:25246786

  6. Biodegradable CSMA/PECA/Graphene Porous Hybrid Scaffold for Cartilage Tissue Engineering

    PubMed Central

    Liao, JinFeng; Qu, Ying; Chu, BingYang; Zhang, XiaoNing; Qian, ZhiYong

    2015-01-01

    Owing to the limited repair capacity of articular cartilage, it is essential to develop tissue-engineered cartilage for patients suffering from joint disease and trauma. Herein, we prepared a novel hybrid scaffold composed of methacrylated chondroitin sulfate (CSMA), poly(ethylene glycol) methyl ether-ε-caprolactone-acryloyl chloride (MPEG-PCL-AC, PECA was used as abbreviation for MPEG-PCL-AC) and graphene oxide (GO) and evaluated its potential application in cartilage tissue engineering. To mimic the natural extracellular matrix (ECM) of cartilage, the scaffold had an adequate pore size, porosity, swelling ability, compression modulus and conductivity. Cartilage cells contacted with the scaffold remained viable and showed growth potential. Furthermore, CSMA/PECA/GO scaffold was biocompatible and had a favorable degradation rate. In the cartilage tissue repair of rabbit, Micro-CT and histology observation showed the group of CSMA/PECA/GO scaffold with cellular supplementation had better chondrocyte morphology, integration, continuous subchondral bone, and much thicker newly formed cartilage compared with scaffold group and control group. Our results show that the CSMA/PECA/GO hybrid porous scaffold can be applied in articular cartilage tissue engineering and may have great potential to in other types of tissue engineering applications. PMID:25961959

  7. Surface Entrapment of Fibronectin on Electrospun PLGA Scaffolds for Periodontal Tissue Engineering

    PubMed Central

    Gritsch, Kerstin; Salles, Vincent; Attik, Ghania N.; Grosgogeat, Brigitte

    2014-01-01

    Abstract Nowadays, the challenge in the tissue engineering field consists in the development of biomaterials designed to regenerate ad integrum damaged tissues. Despite the current use of bioresorbable polyesters such as poly(l-lactide) (PLA), poly(d,l-lactide-co-glycolide) (PLGA), and poly-ɛ-caprolactone in soft tissue regeneration researches, their hydrophobic properties negatively influence the cell adhesion. Here, to overcome it, we have developed a fibronectin (FN)-functionalized electrospun PLGA scaffold for periodontal ligament regeneration. Functionalization of electrospun PLGA scaffolds was performed by alkaline hydrolysis (0.1 or 0.01 M NaOH). Then, hydrolyzed scaffolds were coated by simple deposition of an FN layer (10 μg/mL). FN coating was evidenced by X-ray photoelectron analysis. A decrease of contact angle and greater cell adhesion to hydrolyzed, FN-coated PLGA scaffolds were noticed. Suitable degradation behavior without pH variations was observed for all samples up to 28 days. All treated materials presented strong shrinkage, fiber orientation loss, and collapsed fibers. However, functionalization process using 0.01 M NaOH concentration resulted in unchanged scaffold porosity, preserved chemical composition, and similar mechanical properties compared with untreated scaffolds. The proposed simplified method to functionalize electrospun PLGA fibers is an efficient route to make polyester scaffolds more biocompatible and shows potential for tissue engineering. PMID:24940563

  8. [Research progress on application of carbon nanotubes in bone tissue engineering scaffold].

    PubMed

    Yao, Mengzhu; Sheng, Xiaoxia; Lin, Jun; Gao, Jianqing

    2016-03-01

    Carbon nanotubes possess excellent mechanical and electrical properties and demonstrate broad application prospects in medical fields. Carbon nanotubes are composed of inorganic materials, natural biodegradable polymer or synthetic biodegradable polymer. The composite bone tissue engineering scaffolds are constructed by particle-hole method, lyophilization, microsphere aggregation method, electrostatic spinning or three-dimensional printing. Composite scaffolds overcome the shortcomings of single material and have good biocompatibility, osteoconduction and osteoinduction. With the study of surface chemistry, toxicology, and biocompatibility, a degradable "human-friendly" carbon nanotubes composite bone tissue scaffold will be available; and under the drive of new fabrication techniques, the clinical application of carbon nanotubes composite bone tissue engineering scaffolds will be better developed.

  9. Development and characterization of novel porous 3D alginate-cockle shell powder nanobiocomposite bone scaffold.

    PubMed

    Bharatham, B Hemabarathy; Abu Bakar, Md Zuki; Perimal, Enoch Kumar; Yusof, Loqman Mohamed; Hamid, Muhajir

    2014-01-01

    A novel porous three-dimensional bone scaffold was developed using a natural polymer (alginate/Alg) in combination with a naturally obtained biomineral (nano cockle shell powder/nCP) through lyophilization techniques. The scaffold was developed in varying composition mixture of Alg-nCP and characterized using various evaluation techniques as well as preliminary in vitro studies on MG63 human osteoblast cells. Morphological observations using SEM revealed variations in structures with the use of different Alg-nCP composition ratios. All the developed scaffolds showed a porous structure with pore sizes ideal for facilitating new bone growth; however, not all combination mixtures showed subsequent favorable characteristics to be used for biological applications. Scaffolds produced using the combination mixture of 40% Alg and 60% nCP produced significantly promising results in terms of mechanical strength, degradation rate, and increased cell proliferation rates making it potentially the optimum composition mixture of Alg-nCP with future application prospects.

  10. Effect of glucose content on thermally cross-linked fibrous gelatin scaffolds for tissue engineering.

    PubMed

    Siimon, Kaido; Reemann, Paula; Põder, Annika; Pook, Martin; Kangur, Triin; Kingo, Külli; Jaks, Viljar; Mäeorg, Uno; Järvekülg, Martin

    2014-09-01

    Thermally cross-linked glucose-containing electrospun gelatin meshes were studied as possible cell substrate materials. FTIR analysis was used to study the effect of glucose on cross-linking reactions. It was found that the presence of glucose increases the extent of cross-linking of fibrous gelatin scaffolds, which in return determines scaffold properties and their usability in tissue engineering applications. Easy to handle fabric-like scaffolds were obtained from blends containing up to 15% glucose. Maximum extent of cross-linking was reached at nearly 20% glucose content. Cross-linking effectively resulted in decreased solubility and increased resistance to enzymatic degradation. Preliminary short-term cell culture experiments indicate that such thermally cross-linked gelatin-glucose scaffolds are suitable for tissue engineering applications. PMID:25063151

  11. [Research progress on application of carbon nanotubes in bone tissue engineering scaffold].

    PubMed

    Yao, Mengzhu; Sheng, Xiaoxia; Lin, Jun; Gao, Jianqing

    2016-03-01

    Carbon nanotubes possess excellent mechanical and electrical properties and demonstrate broad application prospects in medical fields. Carbon nanotubes are composed of inorganic materials, natural biodegradable polymer or synthetic biodegradable polymer. The composite bone tissue engineering scaffolds are constructed by particle-hole method, lyophilization, microsphere aggregation method, electrostatic spinning or three-dimensional printing. Composite scaffolds overcome the shortcomings of single material and have good biocompatibility, osteoconduction and osteoinduction. With the study of surface chemistry, toxicology, and biocompatibility, a degradable "human-friendly" carbon nanotubes composite bone tissue scaffold will be available; and under the drive of new fabrication techniques, the clinical application of carbon nanotubes composite bone tissue engineering scaffolds will be better developed. PMID:27273990

  12. Tunable tissue scaffolds fabricated by in situ crosslink in phase separation system

    PubMed Central

    Liu, Xifeng; Chen, Wenjian; Gustafson, Carl T.; Miller, A. Lee; Waletzki, Brian E.; Yaszemski, Michael J.; Lu, Lichun

    2015-01-01

    Three-dimensional (3-D) scaffolds with intrinsic porous structures are desirable in various tissue regeneration applications. In this study, a unique method that combines thermally induced phase separation with a photocrosslinking process was developed for the fabrication of 3-D crosslinked polymer scaffolds with densely interconnected porous structures. Biodegradable poly(propylene fumarate)-co-poly(L-lactic acid) with crosslinkable fumarate bonds were used as the structural polymer material and a dioxane/water binary system was applied for the phase separation. By altering the polymer composition (9, 5 and 3 wt%), different types of scaffolds with distinct morphology, mechanical strength, degradation rate, cell growth and morphology, and extracellular matrix production were fabricated. These crosslinked 3-D porous scaffolds with tunable strength and biological responses show promise for potential applications in regenerative therapies, including bone and neural tissue engineering. PMID:26989479

  13. Exploiting novel sterilization techniques for porous polyurethane scaffolds.

    PubMed

    Bertoldi, Serena; Farè, Silvia; Haugen, Håvard Jostein; Tanzi, Maria Cristina

    2015-05-01

    Porous polyurethane (PU) structures raise increasing interest as scaffolds in tissue engineering applications. Understanding the effects of sterilization on their properties is mandatory to assess their potential use in the clinical practice. The aim of this work is the evaluation of the effects of two innovative sterilization techniques (i.e. plasma, Sterrad(®) system, and ozone) on the morphological, chemico-physical and mechanical properties of a PU foam synthesized by gas foaming, using water as expanding agent. In addition, possible toxic effects of the sterilization were evaluated by in vitro cytotoxicity tests. Plasma sterilization did not affect the morphological and mechanical properties of the PU foam, but caused at some extent degradative phenomena, as detected by infrared spectroscopy. Ozone sterilization had a major effect on foam morphology, causing the formation of new small pores, and stronger degradation and oxidation on the structure of the material. These modifications affected the mechanical properties of the sterilized PU foam too. Even though, no cytotoxic effects were observed after both plasma and ozone sterilization, as confirmed by the good values of cell viability assessed by Alamar Blue assay. The results here obtained can help in understanding the effects of sterilization procedures on porous polymeric scaffolds, and how the scaffold morphology, in particular porosity, can influence the effects of sterilization, and viceversa. PMID:25893387

  14. Utility Towers, Insulator Detail, Front Elevation, Side Elevation, Elevation, Double ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Utility Towers, Insulator Detail, Front Elevation, Side Elevation, Elevation, Double Pole Tower, Single Pole Tower - La Bajada Historic Trails and Roads, Approximately 1 mile East/Northeast of intersection of State Highway 16 and Indian Service Road 841, La Bajada, Santa Fe County, NM

  15. Neuronal Networks on Nanocellulose Scaffolds.

    PubMed

    Jonsson, Malin; Brackmann, Christian; Puchades, Maja; Brattås, Karoline; Ewing, Andrew; Gatenholm, Paul; Enejder, Annika

    2015-11-01

    Proliferation, integration, and neurite extension of PC12 cells, a widely used culture model for cholinergic neurons, were studied in nanocellulose scaffolds biosynthesized by Gluconacetobacter xylinus to allow a three-dimensional (3D) extension of neurites better mimicking neuronal networks in tissue. The interaction with control scaffolds was compared with cationized nanocellulose (trimethyl ammonium betahydroxy propyl [TMAHP] cellulose) to investigate the impact of surface charges on the cell interaction mechanisms. Furthermore, coatings with extracellular matrix proteins (collagen, fibronectin, and laminin) were investigated to determine the importance of integrin-mediated cell attachment. Cell proliferation was evaluated by a cellular proliferation assay, while cell integration and neurite propagation were studied by simultaneous label-free Coherent anti-Stokes Raman Scattering and second harmonic generation microscopy, providing 3D images of PC12 cells and arrangement of nanocellulose fibrils, respectively. Cell attachment and proliferation were enhanced by TMAHP modification, but not by protein coating. Protein coating instead promoted active interaction between the cells and the scaffold, hence lateral cell migration and integration. Irrespective of surface modification, deepest cell integration measured was one to two cell layers, whereas neurites have a capacity to integrate deeper than the cell bodies in the scaffold due to their fine dimensions and amoeba-like migration pattern. Neurites with lengths of >50 μm were observed, successfully connecting individual cells and cell clusters. In conclusion, TMAHP-modified nanocellulose scaffolds promote initial cellular scaffold adhesion, which combined with additional cell-scaffold treatments enables further formation of 3D neuronal networks.

  16. Neuronal Networks on Nanocellulose Scaffolds.

    PubMed

    Jonsson, Malin; Brackmann, Christian; Puchades, Maja; Brattås, Karoline; Ewing, Andrew; Gatenholm, Paul; Enejder, Annika

    2015-11-01

    Proliferation, integration, and neurite extension of PC12 cells, a widely used culture model for cholinergic neurons, were studied in nanocellulose scaffolds biosynthesized by Gluconacetobacter xylinus to allow a three-dimensional (3D) extension of neurites better mimicking neuronal networks in tissue. The interaction with control scaffolds was compared with cationized nanocellulose (trimethyl ammonium betahydroxy propyl [TMAHP] cellulose) to investigate the impact of surface charges on the cell interaction mechanisms. Furthermore, coatings with extracellular matrix proteins (collagen, fibronectin, and laminin) were investigated to determine the importance of integrin-mediated cell attachment. Cell proliferation was evaluated by a cellular proliferation assay, while cell integration and neurite propagation were studied by simultaneous label-free Coherent anti-Stokes Raman Scattering and second harmonic generation microscopy, providing 3D images of PC12 cells and arrangement of nanocellulose fibrils, respectively. Cell attachment and proliferation were enhanced by TMAHP modification, but not by protein coating. Protein coating instead promoted active interaction between the cells and the scaffold, hence lateral cell migration and integration. Irrespective of surface modification, deepest cell integration measured was one to two cell layers, whereas neurites have a capacity to integrate deeper than the cell bodies in the scaffold due to their fine dimensions and amoeba-like migration pattern. Neurites with lengths of >50 μm were observed, successfully connecting individual cells and cell clusters. In conclusion, TMAHP-modified nanocellulose scaffolds promote initial cellular scaffold adhesion, which combined with additional cell-scaffold treatments enables further formation of 3D neuronal networks. PMID:26398224

  17. Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells

    PubMed Central

    Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C.

    2016-01-01

    Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications. PMID:27403430

  18. Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells.

    PubMed

    Finoli, Anthony; Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C

    2016-01-01

    Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications.

  19. Poly(hydroxybutyrate)/cellulose acetate blend nanofiber scaffolds: Preparation, characterization and cytocompatibility.

    PubMed

    Zhijiang, Cai; Yi, Xu; Haizheng, Yang; Jia, Jianru; Liu, Yuanpei

    2016-01-01

    Poly(hydroxybutyrate) (PHB)/cellulose acetate (CA) blend nanofiber scaffolds were fabricated by electrospinning using the blends of chloroform and DMF as solvent. The blend nanofiber scaffolds were characterized by SEM, FTIR, XRD, DSC, contact angle and tensile test. The blend nanofibers exhibited cylindrical, uniform, bead-free and random orientation with the diameter ranged from 80-680 nm. The scaffolds had very well interconnected porous fibrous network structure and large aspect surface areas. It was found that the presence of CA affected the crystallization of PHB due to formation of intermolecular hydrogen bonds, which restricted the preferential orientation of PHB molecules. The DSC result showed that the PHB and CA were miscible in the blend nanofiber. An increase in the glass transition temperature was observed with increasing CA content. Additionally, the mechanical properties of blend nanofiber scaffolds were largely influenced by the weight ratio of PHB/CA. The tensile strength, yield strength and elongation at break of the blend nanofiber scaffolds increased from 3.3 ± 0.35 MPa, 2.8 ± 0.26 MPa, and 8 ± 0.77% to 5.05 ± 0.52 MPa, 4.6 ± 0.82 MPa, and 17.6 ± 1.24% by increasing PHB content from 60% to 90%, respectively. The water contact angle of blend nanofiber scaffolds decreased about 50% from 112 ± 2.1° to 60 ± 0.75°. The biodegradability was evaluated by in vitro degradation test and the results revealed that the blend nanofiber scaffolds showed much higher degradation rates than the neat PHB. The cytocompatibility of the blend nanofiber scaffolds was preliminarily evaluated by cell adhesion studies. The cells incubated with PHB/CA blend nanofiber scaffold for 48 h were capable of forming cell adhesion and proliferation. It showed much better biocompatibility than pure PHB film. Thus, the prepared PHB/CA blend nanofiber scaffolds are bioactive and may be more suitable for cell proliferation suggesting that these scaffolds can be used for

  20. Poly(hydroxybutyrate)/cellulose acetate blend nanofiber scaffolds: Preparation, characterization and cytocompatibility.

    PubMed

    Zhijiang, Cai; Yi, Xu; Haizheng, Yang; Jia, Jianru; Liu, Yuanpei

    2016-01-01

    Poly(hydroxybutyrate) (PHB)/cellulose acetate (CA) blend nanofiber scaffolds were fabricated by electrospinning using the blends of chloroform and DMF as solvent. The blend nanofiber scaffolds were characterized by SEM, FTIR, XRD, DSC, contact angle and tensile test. The blend nanofibers exhibited cylindrical, uniform, bead-free and random orientation with the diameter ranged from 80-680 nm. The scaffolds had very well interconnected porous fibrous network structure and large aspect surface areas. It was found that the presence of CA affected the crystallization of PHB due to formation of intermolecular hydrogen bonds, which restricted the preferential orientation of PHB molecules. The DSC result showed that the PHB and CA were miscible in the blend nanofiber. An increase in the glass transition temperature was observed with increasing CA content. Additionally, the mechanical properties of blend nanofiber scaffolds were largely influenced by the weight ratio of PHB/CA. The tensile strength, yield strength and elongation at break of the blend nanofiber scaffolds increased from 3.3 ± 0.35 MPa, 2.8 ± 0.26 MPa, and 8 ± 0.77% to 5.05 ± 0.52 MPa, 4.6 ± 0.82 MPa, and 17.6 ± 1.24% by increasing PHB content from 60% to 90%, respectively. The water contact angle of blend nanofiber scaffolds decreased about 50% from 112 ± 2.1° to 60 ± 0.75°. The biodegradability was evaluated by in vitro degradation test and the results revealed that the blend nanofiber scaffolds showed much higher degradation rates than the neat PHB. The cytocompatibility of the blend nanofiber scaffolds was preliminarily evaluated by cell adhesion studies. The cells incubated with PHB/CA blend nanofiber scaffold for 48 h were capable of forming cell adhesion and proliferation. It showed much better biocompatibility than pure PHB film. Thus, the prepared PHB/CA blend nanofiber scaffolds are bioactive and may be more suitable for cell proliferation suggesting that these scaffolds can be used for

  1. Characterization of novel akermanite:poly-ϵ-caprolactone scaffolds for human adipose-derived stem cells bone tissue engineering.

    PubMed

    Zanetti, A S; McCandless, G T; Chan, J Y; Gimble, J M; Hayes, D J

    2015-04-01

    In this study, three different akermanite:poly-ϵ-caprolactone (PCL) composite scaffolds (wt%: 75:25, 50:50, 25:75) were characterized in terms of structure, compression strength, degradation rate and in vitro biocompatibility to human adipose-derived stem cells (hASC). Pure ceramic scaffolds [CellCeram™, custom-made, 40:60 wt%; β-tricalcium phosphate (β-TCP):hydroxyapatite (HA); and akermanite] and PCL scaffolds served as experimental controls. Compared to ceramic scaffolds, the authors hypothesized that optimal akermanite:PCL composites would have improved compression strength and comparable biocompatibility to hASC. Electron microscopy analysis revealed that PCL-containing scaffolds had the highest porosity but CellCeram™ had the greatest pore size. In general, compression strength in PCL-containing scaffolds was greater than in ceramic scaffolds. PCL-containing scaffolds were also more stable in culture than ceramic scaffolds. Nonetheless, mass losses after 21 days were observed in all scaffold types. Reduced hASC metabolic activity and increased cell detachment were observed after acute exposure to akermanite:PCL extracts (wt%: 75:25, 50:50). Among the PCL-containing scaffolds, hASC cultured for 21 days on akermanite:PCL (wt%: 75:25) discs displayed the highest viability, increased expression of osteogenic markers (alkaline phosphatase and osteocalcin) and lowest IL-6 expression. Together, the results indicate that akermanite:PCL composites may have appropriate mechanical and biocompatibility properties for use as bone tissue scaffolds.

  2. Bioresorbable scaffolds on the bench.

    PubMed

    Ormiston, John; Motreff, Pascal; Darremont, Olivier; Webber, Bruce; Guerin, Patrice; Webster, Mark

    2015-01-01

    Bioresorbable scaffolds (BRS) in bifurcations have all of the potential advantages of BRS in non-bifurcating lesions and, in addition, the absorption of side branch (SB) ostial struts may at least partially release the branch from "jail". Polymeric BRS struts may break when post-dilated beyond their safe limits and multiple fractures may lead to adverse clinical events. Bench testing provides insights into the behaviour of different BRS in bifurcations and helps the interventional cardiologist to choose, deliver and post-dilate appropriately. Bench testing of polymeric BRS must be in a water bath at 37ºC as polymer performance is temperature sensitive. Balloon dilatation through the side of a BRS or a durable metallic stent causes distortion corrected by mini-kissing balloon post-dilatation (mini-KBPD) where the SB balloon extends only a short distance into the main branch (MB), limiting the length of MB scaffold exposed to the inflation of two balloons. The safe pressure threshold for SB dilatation of a 3.0 mm Absorb scaffold with a 3.0 mm non-compliant balloon is 10 atm and for mini-KBPD with two 3.0 mm balloons it is 5 atm. Strategies such as culotte, crush and simultaneous kissing scaffolds (SKS) may not be appropriate for the current Absorb scaffold. PMID:25983158

  3. Osteogenic Scaffolds for Bone Reconstruction

    PubMed Central

    Li, Ling-jiang; Liu, Ning; Liu, Qing; Jia, Lian-shun; Yuan, Wen

    2012-01-01

    Abstract A highly osteogenic hybrid bioabsorbable scaffold was developed for bone reconstruction/augmentation. Through the use of a solid free-form fabrication technology, a bioabsorbable polycaprolactone (PCL) cage scaffold with a desired size and shape was produced and then filled with osteogenic bone graft particles, that is, morselized autologous bone chips. A rabbit total lamina defect model was chosen to demonstrate its efficacy in regenerating bone with a complicated anatomic shape. Both iliac bone and morselized iliac bone grafts were used in this study for comparison purposes. Serum osteocalcin and collagen type I cross-linked C-terminal telopeptide (CTx) determination showed that active bone remodeling occurred after bone grafts were implanted. X-ray images showed that the bony defects were completely filled with bone mass in all the groups with bone grafts. However, biomechanical tests showed that only the iliac bone and hybrid scaffold groups could restore the mechanical properties to the normal level after 10 weeks of implantation. A histology study showed that both iliac and hybrid scaffold groups had extensive new bone formation, and no adhesion and fibrosis were found. These results indicated that this osteogenic hybrid scaffold can be a good alternative to autologous iliac bone, because it does not need a second iliac bone-harvesting surgery, and thus the morbidity and the possible infections that are often associated with the bone harvesting surgery can be avoided. PMID:23515416

  4. Rapid Engineering of Three-Dimensional, Multicellular Tissues With Polymeric Scaffolds

    NASA Technical Reports Server (NTRS)

    Gonda, Steve R.; Jordan, Jacqueline; Fraga, Denise N.

    2007-01-01

    A process has been developed for the rapid tissue engineering of multicellular-tissue-equivalent assemblies by the controlled enzymatic degradation of polymeric beads in a low-fluid-shear bioreactor. In this process, the porous polymeric beads serve as temporary scaffolds to support the assemblies of cells in a tissuelike 3D configuration during the critical initial growth phases of attachment of anchorage-dependent cells, aggregation of the cells, and formation of a 3D extracellular matrix. Once the cells are assembled into a 3D array and enmeshed in a structural supportive 3D extracellular matrix (ECM), the polymeric scaffolds can be degraded in the low-fluid-shear environment of the NASA-designed bioreactor. The natural 3D tissuelike assembly, devoid of any artificial support structure, is maintained in the low-shear bioreactor environment by the newly formed natural cellular/ECM. The elimination of the artificial scaffold allows normal tissue structure and function.

  5. Approaches to Neural Tissue Engineering Using Scaffolds for Drug Delivery

    PubMed Central

    Willerth, Stephanie M.; Sakiyama-Elbert, Shelly E.

    2007-01-01

    This review seeks to give an overview of the current approaches to drug delivery from scaffolds for neural tissue engineering applications. The challenges presented by attempting to replicate the three types of nervous tissue (brain, spinal cord, and peripheral nerve) are summarized. Potential scaffold materials (both synthetic and natural) and target drugs are discussed with the benefits and drawbacks given. Finally, common methods of drug delivery, including degradable/diffusion-based delivery systems, affinity-based delivery systems, immobilized drug delivery systems, and electrically controlled drug delivery systems, are examined and critiqued. Based on the current body of work, suggestions for future directions of research in the field of neural tissue engineering are presented. PMID:17482308

  6. 29 CFR 1910.28 - Safety requirements for scaffolding.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirements for scaffolding. (a) General requirements for all scaffolds. (1) Scaffolds shall be furnished and... § 1910.26. (2) The footing or anchorage for scaffolds shall be sound, rigid, and capable of carrying the... brick, or concrete blocks shall not be used to support scaffolds or planks. (3) (4) Scaffolds and...

  7. 29 CFR 1910.28 - Safety requirements for scaffolding.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirements for scaffolding. (a) General requirements for all scaffolds. (1) Scaffolds shall be furnished and... § 1910.26. (2) The footing or anchorage for scaffolds shall be sound, rigid, and capable of carrying the... brick, or concrete blocks shall not be used to support scaffolds or planks. (3) (4) Scaffolds and...

  8. 29 CFR 1910.28 - Safety requirements for scaffolding.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requirements for scaffolding. (a) General requirements for all scaffolds. (1) Scaffolds shall be furnished and... 1910.26. (2) The footing or anchorage for scaffolds shall be sound, rigid, and capable of carrying the... brick, or concrete blocks shall not be used to support scaffolds or planks. (3) (4) Scaffolds and...

  9. 29 CFR 1910.28 - Safety requirements for scaffolding.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirements for scaffolding. (a) General requirements for all scaffolds. (1) Scaffolds shall be furnished and... § 1910.26. (2) The footing or anchorage for scaffolds shall be sound, rigid, and capable of carrying the... brick, or concrete blocks shall not be used to support scaffolds or planks. (3) (4) Scaffolds and...

  10. Scaffold pore space modulation through intelligent design of dissolvable microparticles.

    PubMed

    Liebschner, Michael A K; Wettergreen, Matthew

    2012-01-01

    The goal of this area of research is to manipulate the pore space of scaffolds through the application of an intelligent design concept on dissolvable microparticles. To accomplish this goal, we developed an efficient and repeatable process for fabrication of microparticles from multiple materials using a combination of rapid prototyping (RP) and soft lithography. Phase changed 3D printing was used to create masters for PDMS molds. A photocrosslinkable polymer was then delivered into these molds to make geometrically complex 3D microparticles. This repeatable process has demonstrated to generate the objects with greater than 95% repeatability with complete pattern transfer. This process was illustrated for three different shapes of various complexities. The shapes were based on the extrusion of 2D shapes. This may allow simplification of the fabrication process in the future combined with a direct transfer of the findings. Altering the shapes of particles used for porous scaffold fabrication will allow for tailoring of the pore shapes, and therefore their biological function within a porous tissue engineering scaffold. Through permeation experiments, we have shown that the pore geometry may alter the permeability coefficient of scaffolds while influencing mechanical properties to a lesser extent. By selecting different porogen shapes, the nutrition transport and scaffold degradation can be significantly influenced with minimal effect on the mechanical integrity of the construct. In addition, the different shapes may allow a control of drug release by modifying their surface-to-volume ratio, which could modulate drug delivery over time. While soft lithography is currently used with photolithography, its high precision is offset by high cost of production. The employment of RP to a specific resolution offers a much less expensive alternative with increased throughput due to the speed of current RP systems.

  11. Surface biology of collagen scaffold explains blocking of wound contraction and regeneration of skin and peripheral nerves.

    PubMed

    Yannas, I V; Tzeranis, D; So, P T

    2015-12-23

    We review the details of preparation and of the recently elucidated mechanism of biological (regenerative) activity of a collagen scaffold (dermis regeneration template, DRT) that has induced regeneration of skin and peripheral nerves (PN) in a variety of animal models and in the clinic. DRT is a 3D protein network with optimized pore size in the range 20-125 µm, degradation half-life 14 ± 7 d and ligand densities that exceed 200 µM α1β1 or α2β1 ligands. The pore has been optimized to allow migration of contractile cells (myofibroblasts, MFB) into the scaffold and to provide sufficient specific surface for cell-scaffold interaction; the degradation half-life provides the required time window for satisfactory binding interaction of MFB with the scaffold surface; and the ligand density supplies the appropriate ligands for specific binding of MFB on the scaffold surface. A dramatic change in MFB phenotype takes place following MFB-scaffold binding which has been shown to result in blocking of wound contraction. In both skin wounds and PN wounds the evidence has shown clearly that contraction blocking by DRT is followed by induction of regeneration of nearly perfect organs. The biologically active structure of DRT is required for contraction blocking; well-matched collagen scaffold controls of DRT, with structures that varied from that of DRT, have failed to induce regeneration. Careful processing of collagen scaffolds is required for adequate biological activity of the scaffold surface. The newly understood mechanism provides a relatively complete paradigm of regenerative medicine that can be used to prepare scaffolds that may induce regeneration of other organs in future studies.

  12. Electrospun silk fibroin/poly(lactide-co-ε-caprolactone) nanofibrous scaffolds for bone regeneration

    PubMed Central

    Wang, Zi; Lin, Ming; Xie, Qing; Sun, Hao; Huang, Yazhuo; Zhang, DanDan; Yu, Zhang; Bi, Xiaoping; Chen, Junzhao; Wang, Jing; Shi, Wodong; Gu, Ping; Fan, Xianqun

    2016-01-01

    Background Tissue engineering has become a promising therapeutic approach for bone regeneration. Nanofibrous scaffolds have attracted great interest mainly due to their structural similarity to natural extracellular matrix (ECM). Poly(lactide-co-ε-caprolactone) (PLCL) has been successfully used in bone regeneration, but PLCL polymers are inert and lack natural cell recognition sites, and the surface of PLCL scaffold is hydrophobic. Silk fibroin (SF) is a kind of natural polymer with inherent bioactivity, and supports mesenchymal stem cell attachment, osteogenesis, and ECM deposition. Therefore, we fabricated hybrid nanofibrous scaffolds by adding different weight ratios of SF to PLCL in order to find a scaffold with improved properties for bone regeneration. Methods Hybrid nanofibrous scaffolds were fabricated by blending different weight ratios of SF with PLCL. Human adipose-derived stem cells (hADSCs) were seeded on SF/PLCL nanofibrous scaffolds of various ratios for a systematic evaluation of cell adhesion, proliferation, cytotoxicity, and osteogenic differentiation; the efficacy of the composite of hADSCs and scaffolds in repairing critical-sized calvarial defects in rats was investigated. Results The SF/PLCL (50/50) scaffold exhibited favorable tensile strength, surface roughness, and hydrophilicity, which facilitated cell adhesion and proliferation. Moreover, the SF/PLCL (50/50) scaffold promoted the osteogenic differentiation of hADSCs by elevating the expression levels of osteogenic marker genes such as BSP, Ocn, Col1A1, and OPN and enhanced ECM mineralization. In vivo assays showed that SF/PLCL (50/50) scaffold improved the repair of the critical-sized calvarial defect in rats, resulting in increased bone volume, higher trabecular number, enhanced bone mineral density, and increased new bone areas, compared with the pure PLCL scaffold. Conclusion The SF/PLCL (50/50) nanofibrous scaffold facilitated hADSC proliferation and osteogenic differentiation in

  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. PMID:25769230

  14. 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.

  15. Large defect-tailored composite scaffolds for in vivo bone regeneration.

    PubMed

    Ronca, Alfredo; Guarino, Vincenzo; Raucci, Maria Grazia; Salamanna, Francesca; Martini, Lucia; Zeppetelli, Stefania; Fini, Milena; Kon, Elisaveta; Filardo, G; Marcacci, Maurilio; Ambrosio, Luigi

    2014-11-01

    The discovery of new strategies to repair large segmental bone defects is currently an open challenge for worldwide clinicians. In the treatment of critical-sized bone defects, an alternative strategy to traditional bone grafting is always more frequently the use of tailor-made scaffolds modelled on the final size and shape of the implant site. Here, poly-ε-caprolactone-based composite scaffolds including poly-L-lactic acid continuous fibres and hyaluronan derivates (i.e. HYAFF11®) have been investigated for the peculiar 3D architecture characterized by interconnected macroporous networks and tunable mechanical properties. Composite scaffolds were immersed in simulated body fluid solution in order to support in vivo tissue in-growth. Scaffolds loaded with autologous cells (bone marrow stromal cells) plus platelet-rich plasma and osteoconductive protein such bone morphogenetic protein-7 were also tested to evaluate eventual enhancement in bone regeneration. The morphological and mechanical properties of poly-L-lactic acid-reinforced composite scaffolds have been studied to identify the optimal scaffold design to match the implant-site requirements of sheep metatarsal defects. Dynamic mechanical tests allowed to underline the viscoelastic response of the scaffold - resulting in elastic moduli from 2.5 to 1.3 MPa, suitable to temporarily support the structural function of damaged bone tissue. In vivo preliminary investigations in a sheep model of metatarsus shaft defect also showed the attitude of the scaffold to promote osteogenesis, preferentially in association with bone marrow stromal cell and platelet-rich plasma, even if the highest amount of mature bone was reached in the case of scaffold loaded with human bone morphogenetic protein-7 released via hydrolytic degradation of HYAFF11® phases in the implant site.

  16. In vitro biodegradation of designed tubular scaffolds of electrospun protein/polyglyconate blend fibers.

    PubMed

    Zhang, Xing; Thomas, Vinoy; Vohra, Yogesh K

    2009-04-01

    Electrospun polyglyconate (Maxon) and its blends with proteins such as gelatin and elastin, with a spatially designed layer structure, were prepared as potential scaffolds for vascular tissue engineering. In vitro biodegradation of the electrospun tubular protein/Maxon scaffolds in phosphate buffered saline (pH = 7.3) was studied for the first time. The biodegradation is manifested by uptake of the PBS medium by the hydrophilic proteins and also by the mass loss due to the removal of degraded fragments and uncrosslinked proteins from the matrices. The effect of degradation on the structure-property relations was evaluated by IR, XRD, and DSC analyses of the aged scaffolds. The degradation of amorphous phase of Maxon in the early stages of aging has resulted in an increase in the crystallinity of the polymer. SEM analysis indicated a significant change in nanofiber morphology and fiber-breaking. The mass loss and fiber breaking have negatively impacted the mechanical properties and the effect was maximum at 15-20 days of aging. The scaffold containing low molecular weight buffer soluble elastin revealed relatively better degradation properties compared to that containing high molecular weight buffer insoluble elastin.

  17. In vitro chondrogenesis with lysozyme susceptible bacterial cellulose as a scaffold.

    PubMed

    Yadav, Vikas; Sun, Lin; Panilaitis, Bruce; Kaplan, David L

    2015-12-01

    A current focus of tissue engineering is the use of adult human mesenchymal stem cells (hMSCs) as an alternative to autologous chondrocytes for cartilage repair. Several natural and synthetic polymers (including cellulose) have been explored as a biomaterial scaffold for cartilage tissue engineering. While bacterial cellulose (BC) has been used in tissue engineering, its lack of degradability in vivo and high crystallinity restricts widespread applications in the field. Recently we reported the formation of a novel bacterial cellulose that is lysozyme-susceptible and -degradable in vivo from metabolically engineered Gluconacetobacter xylinus. Here we report the use of this modified bacterial cellulose (MBC) for cartilage tissue engineering using hMSCs. MBC's glucosaminoglycan-like chemistry, combined with in vivo degradability, suggested opportunities to exploit this novel polymer in cartilage tissue engineering. We have observed that, like BC, MBC scaffolds support cell attachment and proliferation. Chondrogenesis of hMSCs in the MBC scaffolds was demonstrated by real-time RT-PCR analysis for cartilage-specific extracellular matrix (ECM) markers (collagen type II, aggrecan and SOX9) as well as histological and immunohistochemical evaluations of cartilage-specific ECM markers. Further, the attachment, proliferation, and differentiation of hMSCs in MBC showed unique characteristics. For example, after 4 weeks of cultivation, the spatial cell arrangement and collagen type-II and ACAN distribution resembled those in native articular cartilage tissue, suggesting promise for these novel in vivo degradable scaffolds for chondrogenesis.

  18. Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction

    PubMed Central

    Hu, Jianfei; Neiswinger, Johnathan; Zhang, Jin; Zhu, Heng; Qian, Jiang

    2015-01-01

    Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process. PMID:26393507

  19. Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction.

    PubMed

    Hu, Jianfei; Neiswinger, Johnathan; Zhang, Jin; Zhu, Heng; Qian, Jiang

    2015-01-01

    Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process.

  20. 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

  1. Hyperbranched poly(glycidol)/poly(ethylene oxide) crosslinked hydrogel for tissue engineering scaffold using e-beams.

    PubMed

    Haryanto; Singh, Deepti; Huh, Pil Ho; Kim, Seong Cheol

    2016-01-01

    A microporous hydrogel scaffold was developed from hyperbranched poly(glycidol) (HPG) and poly(ethylene oxide) (PEO) using electron beam (e-beam) induced cross-linking for tissue engineering applications. In this study, HPG was synthesized from glycidol using trimethylol propane as a core initiator and cross-linked hydrogels were made using 0, 10, 20, and 30% HPG with respect to PEO. The effects of %-HPG on the swelling ratio, cross-linking density, mechanical properties, morphology, degradation, and cytotoxicity of the hydrogel scaffolds were then investigated. Increasing the HPG content increased the pore size of the hydrogel scaffold, as well as the porosity, elongation at break, degree of degradation and swelling ratio. In contrast, the presence of HPG decreased the cross-linking density of the hydrogel. There was no significant difference in compressive modulus and tensile strength of all compositions. The pore size of hydrogel scaffolds could be easily tailored by controlling the content of HPG in the polymer blend. Evaluation of the cytotoxicity demonstrated that HPG/PEO hydrogel scaffold has potential for use as a matrix for cellular attachment and proliferation. These results indicate that cross-linked HPG/PEO hydrogel can function as a potential material for tissue engineering scaffolds. Moreover, a facile method to prepare hydrogel microporous scaffolds for tissue engineering by e-beam irradiation was developed.

  2. Design and Fabrication of a Biodegradable, Covalently Crosslinked Shape-Memory Alginate Scaffold for Cell and Growth Factor Delivery

    PubMed Central

    Wang, Lin; Shansky, Janet; Borselli, Cristina; Mooney, David

    2012-01-01

    The successful use of transplanted cells and/or growth factors for tissue repair is limited by a significant cell loss and/or rapid growth factor diffusion soon after implantation. Highly porous alginate scaffolds formed with covalent crosslinking have been used to improve cell survival and growth factor release kinetics, but require open-wound surgical procedures for insertion and have not previously been designed to readily degrade in vivo. In this study, a biodegradable, partially crosslinked alginate scaffold with shape-memory properties was fabricated for minimally invasive surgical applications. A mixture of high and low molecular weight partially oxidized alginate modified with RGD peptides was covalently crosslinked using carbodiimide chemistry. The scaffold was compressible 11-fold and returned to its original shape when rehydrated. Scaffold degradation properties in vitro indicated ∼85% mass loss by 28 days. The greater than 90% porous scaffolds released the recombinant growth factor insulin-like growth factor-1 over several days in vitro and allowed skeletal muscle cell survival, proliferation, and migration from the scaffold over a 28-day period. The compressible scaffold thus has the potential to be delivered by a minimally invasive technique, and when rehydrated in vivo with cells and/or growth factors, could serve as a temporary delivery vehicle for tissue repair. PMID:22646518

  3. Rethinking Scaffolding in the Information Age

    ERIC Educational Resources Information Center

    Yelland, Nicola; Masters, Jennifer

    2007-01-01

    This paper addresses the use of scaffolding in learning contexts that incorporate technologically based novel problems. We suggest that in computer contexts extended conceptualisations of scaffolding are needed in order to gain greater insights into teaching and learning processes. Our work has revealed that traditional forms of scaffolding, based…

  4. Designing Online Scaffolds for Interactive Computer Simulation

    ERIC Educational Resources Information Center

    Chen, Ching-Huei; Wu, I-Chia; Jen, Fen-Lan

    2013-01-01

    The purpose of this study was to examine the effectiveness of online scaffolds in computer simulation to facilitate students' science learning. We first introduced online scaffolds to assist and model students' science learning and to demonstrate how a system embedded with online scaffolds can be designed and implemented to help high…

  5. Effect of Low Temperature Ethylene Oxide and Electron Beam Sterilization on the In Vitro and In Vivo Function of Reconstituted Extracellular Matrix-Derived Scaffolds

    PubMed Central

    Proffen, Benedikt L.; Perrone, Gabriel S.; Fleming, Braden C.; Sieker, Jakob T.; Kramer, Joshua; Hawes, Michael L.; Murray, Martha M.

    2015-01-01

    Reconstituted extracellular matrix (ECM) -derived scaffolds are commonly utilized in preclinical tissue engineering studies as delivery vehicles for cells and growth factors. Translation into clinical use requires identifying a sterilization method that effectively removes bacteria but doesn’t harm scaffold function. To determine effectiveness of sterilization and impact on ECM scaffold integrity and function low temperature ethylene oxide and 15kGy electron beam irradiation techniques were evaluated. Scaffold sterility was assessed in accordance to United States Pharmacopeia Chapter 71. Scaffold matrix degradation was determined in vitro using enzymatic resistance tests and gel electrophoresis. Scaffold mechanics including elastic modulus, yield stress and collapse modulus were tested. Lastly, 14 Yorkshire pigs underwent ACL transection and bio-enhanced ACL repair using sterilized scaffolds. Histologic response of ligament, synovium and lymph nodes was compared at 4, 6, and 8 weeks. Ethylene oxide as well as electron beam irradiation yielded sterile scaffolds. Scaffold resistance to enzymatic digestion and protein integrity slightly decreased after electron beam irradiation while ethylene oxide altered scaffold matrix. Scaffold elastic modulus and yield stress were increased after electron beam treatment, while collapse modulus was increased after ethylene oxide treatment. No significant changes in ACL dimensions, in vivo scaffold resorption rate, or histologic response of synovium, ligament and lymph nodes with either terminal sterilization technique were detectable. In conclusion, this study identifies two methods to terminally sterilize an ECM scaffold. In vitro scaffold properties were slightly changed without significantly influencing the biologic responses of the surrounding tissues in vivo. This is a critical step toward translating new tissue engineering strategies to clinical trials. PMID:26088294

  6. RHOBTB3 promotes proteasomal degradation of HIFα through facilitating hydroxylation and suppresses the Warburg effect

    PubMed Central

    Zhang, Chen-Song; Liu, Qi; Li, Mengqi; Lin, Shu-Yong; Peng, Yongying; Wu, Di; Li, Terytty Yang; Fu, Qiang; Jia, Weiping; Wang, Xinjun; Ma, Teng; Zong, Yue; Cui, Jiwen; Pu, Chengfei; Lian, Guili; Guo, Huiling; Ye, Zhiyun; Lin, Sheng-Cai

    2015-01-01

    Hypoxia-inducible factors (HIFs) are master regulators of adaptive responses to low oxygen, and their α-subunits are rapidly degraded through the ubiquitination-dependent proteasomal pathway after hydroxylation. Aberrant accumulation or activation of HIFs is closely linked to many types of cancer. However, how hydroxylation of HIFα and its delivery to the ubiquitination machinery are regulated remains unclear. Here we show that Rho-related BTB domain-containing protein 3 (RHOBTB3) directly interacts with the hydroxylase PHD2 to promote HIFα hydroxylation. RHOBTB3 also directly interacts with the von Hippel-Lindau (VHL) protein, a component of the E3 ubiquitin ligase complex, facilitating ubiquitination of HIFα. Remarkably, RHOBTB3 dimerizes with LIMD1, and constructs a RHOBTB3/LIMD1-PHD2-VHL-HIFα complex to effect the maximal degradation of HIFα. Hypoxia reduces the RHOBTB3-centered complex formation, resulting in an accumulation of HIFα. Importantly, the expression level of RHOBTB3 is greatly reduced in human renal carcinomas, and RHOBTB3 deficiency significantly elevates the Warburg effect and accelerates xenograft growth. Our work thus reveals that RHOBTB3 serves as a scaffold to organize a multi-subunit complex that promotes the hydroxylation, ubiquitination and degradation of HIFα. PMID:26215701

  7. A tubular gelatin scaffold capable of the time-dependent controlled release of epidermal growth factor and mitomycin C.

    PubMed

    Zhu, Jixiang; Yang, Fanwen; He, Fupo; Tian, Xiumei; Tang, Shuo; Chen, Xiaoming

    2015-11-01

    A tubular gelatin scaffold for the time-dependent controlled release of epidermal growth factor (EGF) and mitomycin C (MMC) was fabricated. EGF was incorporated using silk fibroin carriers, and MMC was planted using polylactide (PLA) microspheres. The relationship between scaffold properties and crosslinking degrees was evaluated. As the crosslinking degree was increased from 23.7% to 65.3%, the mechanical properties of the scaffold obviously improved, and the compressive modulus increased to approximately 65kPa. The mass degradation of the scaffold was also controlled from 9 days to approximately 1 month. In vitro release tests indicated that the scaffold mainly released EGF in the early period and MMC in the later period. Urethral epithelial cells (UECs) and urethral scar derived fibroblast cells (UFCs) were coseeded in the scaffold at a ratio of 1:1. After 9 days of coculture, immunostaining results displayed that the proportion of UECs continuously increased to approximately 71%. These changes in cell proportion were confirmed by the results of Western blot analysis. Therefore, the scaffold promoted the growth but inhibited the regeneration of UFCs. This scaffold for time-dependent controlled release of multiple biofactors may be potentially useful in urethral reconstruction and other tissue engineering studies.

  8. Chitosan scaffolds for in vitro buffalo embryonic stem-like cell culture: an approach to tissue engineering.

    PubMed

    Thein-Han, Wah W; Kitiyanant, Yindee

    2007-01-01

    Three-dimensional (3D) porous chitosan scaffolds are attractive candidates for tissue engineering applications. Chitosan scaffolds of 70, 88, and 95% degree of deacetylation (% DD) with the same molecular weight were developed and their properties with buffalo embryonic stem-like (ES-like) cells were investigated in vitro. Scaffolds were fabricated by freezing and lyophilization. They showed open pore structure with interconnecting pores under scanning electron microscopy (SEM). Higher % DD chitosan scaffolds had greater mechanical strength, slower degradation rate, lower water uptake ability, but similar water retention ability, when compared to lower % DD chitosan. As a strategy to tissue engineering, buffalo ES-like cells were cultured on scaffolds for 28 days. It appeared that chitosan was cytocompatible and cells proliferated well on 88 and 95% DD scaffolds. In addition, the buffalo ES-like cells maintained their pluripotency during the culture period. Furthermore, the SEM and histological study showed that the polygonal buffalo ES-like cells proliferated well and attached to the pores. This study proved that 3D biodegradable highly deacetylated chitosan scaffolds are promising candidates for ES-like cell based tissue engineering and this chitosan scaffold and ES cell based system can be used as in vitro model for subsequent clinical applications.

  9. Fabrication and characterization of Mg/P(LLA-CL)-blended nanofiber scaffold.

    PubMed

    Li, Heyu; Wu, Tong; Zheng, Yufeng; El-Hamshary, Hany; Al-Deyab, Salem S; Mo, Xiumei

    2014-07-01

    Poly(l-lactic acid-co-ε-caprolactone) (P(LLA-CL)) is a kind of copolymer polymerized from lactic acid and ε-caprolactone. Electrospun P(LLA-CL) nanofibers have good biocompatibility, biodegradability, and mechanical property. However, this type of nanofibers will produce acid groups during the degradation, so that, the pH value of the environment will decrease and result in tissue inflammation. On the other hand, Magnesium (Mg) alloy tissue engineering scaffolds will show alkaline during the degradation because of the electrochemical corrosion. Based on the principle of acid-based neutralization, combination of these two kinds of materials through electrospinning could keep the pH of the degradation environment neutral. In this paper, fabrication and characterization of Mg/P(LLA-CL)-blended nanofiber scaffolds with different ratios will be studied by scanning electron microscopy and universal materials testing machines to observe the morphology and mechanical properties of nanofibers, respectively. Furthermore, PIECs were cultured and seeded on the scaffolds for different time to evaluate the proliferation behavior on the scaffolds by MTT assay. The degradation tests of the samples lasted for three months in phosphate-buffered saline to evaluate the pH values of degradation solutions and the weight loss of nanofibers during degradation. The results showed that the mechanical property and biocompatibility of Mg/P(LLA-CL)-blended nanofibers were worse than that of pure P(LLA-CL). Moreover, the addition of Mg in the nanofibers accelerated the weight loss of the Mg/P(LLA-CL) blending fibers and increased the pH values of the environment during degradation of Mg/P(LLA-CL)-blended nanofibers.

  10. Preparation and characterization of polyhydroxyalkanoates macroporous scaffold through enzyme-mediated modifications.

    PubMed

    Ansari, Nor Faezah; Amirul, A A

    2013-06-01

    Polyhydroxyalkanoates (PHAs) are hydrophobic biodegradable thermoplastics that have received considerable attention in biomedical applications due to their biocompatibility, mechanical properties, and biodegradability. In this study, the degradation rate was regulated by optimizing the interaction of parameters that influence the enzymatic degradation of P(3HB) film using response surface methodology (RSM). The RSM model was experimentally validated yielding a maximum 21 % weight loss, which represents onefold increment in percentage weight loss in comparison with the conventional method. By using the optimized condition, the enzymatic degradation by an extracellular PHA depolymerase from Acidovorax sp. DP5 was studied at 37 °C and pH 9.0 on different types of PHA films with various monomer compositions. Surface modification of scaffold was employed using enzymatic technique to create highly porous scaffold with a large surface to volume ratio, which makes them attractive as potential tissue scaffold in biomedical field. Scanning electron microscopy revealed that the surface of salt-leached films was more porous compared with the solvent-cast films, and hence, increased the degradation rate of salt-leached films. Apparently, enzymatic degradation behaviors of PHA films were determined by several factors such as monomer composition, crystallinity, molecular weight, porosity, and roughness of the surface. The hydrophilicity and water uptake of degraded salt-leached film of P(3HB-co-70%4HB) were enhanced by incorporating chitosan or alginate. Salt-leached technique followed by partial enzymatic degradation would enhance the cell attachment and suitable for biomedical as a scaffold.

  11. Problem Solving, Scaffolding and Learning

    ERIC Educational Resources Information Center

    Lin, Shih-Yin

    2012-01-01

    Helping students to construct robust understanding of physics concepts and develop good solving skills is a central goal in many physics classrooms. This thesis examine students' problem solving abilities from different perspectives and explores strategies to scaffold students' learning. In studies involving analogical problem solving…

  12. Strategic Scaffolding for Scientific Inquiry

    ERIC Educational Resources Information Center

    Shelton, Angela; Natarajan, Uma; Willard, Catherine; Kane, Tera; Ketelhut, Diane Jass; Schifter, Catherine

    2013-01-01

    Though many national and international science organizations stress the importance of integrating scientific inquiry into classroom instruction, this is often difficult for teachers. Moreover, assessing and scaffolding inquiry skills for students can be even more of a challenge. This paper investigated the student performances in an inquiry-based,…

  13. Enhanced depth-independent chondrocyte proliferation and gene expression in an ultrasound bioreactor and an assessment of ultrasound dampening in the scaffold

    PubMed Central

    Thakurta, Sanjukta Guha; Kraft, Mikail; Viljoen, Hendrik J.; Subramanian, Anuradha

    2014-01-01

    Chondrocyte seeded scaffolds were cultured in an ultrasound (US) assisted bioreactor, which supplied the cells with acoustic energy around resonance frequencies (~5.0 MHz). Polyurethane-polycarbonate (BM), chitosan (CS) and chitosan-nButanol (CSB) based scaffolds with varying porosities were chosen and the following US regimen was employed: 15 kPa and 60kPa, 5 mins/application and 6 application/day for 21 days. Non-stimulated scaffolds served as control. For BM scaffolds, US stimulation significantly impacted cell proliferation, and the depth dependent cell population density compared to controls. Highest COL2A1/COL1A1 ratios and ACAN mRNA were noted on US treated BM scaffolds compared to controls. Similar trend was noted on US treated cell-seeded CS and CSB scaffolds, but COL2A1/COL1A1 ratios were significantly lower compared to BM scaffolds. Expression of SOX9 was also elevated under US and paralleled the ratio of COL2A1/COL1A1. As an original contribution, a simplified mathematical model based on Biot theory was developed to understand the propagation of the incident US wave through the scaffolds and the model analysis was connected to cellular responses. Scaffold architecture influenced the distribution of US field; with the US field being the least attenuated in BM scaffolds, thus coupling more mechanical energy into cells, leading to increased cellular activity. PMID:25065549

  14. Enhanced depth-independent chondrocyte proliferation and phenotype maintenance in an ultrasound bioreactor and an assessment of ultrasound dampening in the scaffold.

    PubMed

    Guha Thakurta, Sanjukta; Kraft, Mikail; Viljoen, Hendrik J; Subramanian, Anuradha

    2014-11-01

    Chondrocyte-seeded scaffolds were cultured in an ultrasound (US)-assisted bioreactor, which supplied the cells with acoustic energy around resonance frequencies (~5.0 MHz). Polyurethane-polycarbonate (BM), chitosan (CS) and chitosan-n-butanol (CSB) based scaffolds with varying porosities were chosen and the following US regimen was employed: 15 kPa and 60 kPa, 5 min per application and 6 applications per day for 21 days. Non-stimulated scaffolds served as control. For BM scaffolds, US stimulation significantly impacted cell proliferation and depth-independent cell population density compared to controls. The highest COL2A1/COL1A1 ratios and ACAN mRNA were noted on US-treated BM scaffolds compared to controls. A similar trend was noted on US-treated cell-seeded CS and CSB scaffolds, though COL2A1/COL1A1 ratios were significantly lower compared to BM scaffolds. Expression of Sox-9 was also elevated under US and paralleled the COL2A1/COL1A1 ratio. As an original contribution, a simplified mathematical model based on Biot theory was developed to understand the propagation of the incident US wave through the scaffolds and the model analysis was connected to cellular responses. Scaffold architecture influenced the distribution of US field, with the US field being the least attenuated in BM scaffolds, thus coupling more mechanical energy into cells, and leading to increased cellular activity. PMID:25065549

  15. Monosaccharide-Responsive Phenylboronate-Polyol Cell Scaffolds for Cell Sheet and Tissue Engineering Applications

    PubMed Central

    Reddy, Rachamalla Maheedhar; Srivastava, Akshay; Kumar, Ashok

    2013-01-01

    Analyte-responsive smart polymeric materials are of great interest and have been actively investigated in the field of regenerative medicine. Phenylboronate containing copolymers form gels with polyols under alkaline conditions. Monosaccharides, by virtue of their higher affinity towards boronate, can displace polyols and solubilize such gels. In the present study, we investigate the possibility of utilizing phenylboronate-polyol interactions at physiological pH in order to develop monosaccharide-responsive degradable scaffold materials for systems dealing with cells and tissues. Amine assisted phenylboronate-polyol interactions were employed to develop novel hydrogel and cryogel scaffolds at neutral pH. The scaffolds displayed monosaccharide inducible gel-sol phase transformability. In vitro cell culture studies demonstrated the ability of scaffolds to support cell adhesion, viability and proliferation. Fructose induced gel degradation is used to recover cells cultured on the hydrogels. The cryogels displayed open macroporous structure and superior mechanical properties. These novel phase transformable phenylboronate-polyol based scaffolds displayed a great potential for various cell sheet and tissue engineering applications. Their monosaccharide responsiveness at physiological pH is very useful and can be utilized in the fields of cell immobilization, spheroid culture, saccharide recognition and analyte-responsive drug delivery. PMID:24167587

  16. 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

  17. Fabrication and development of artificial osteochondral constructs based on cancellous bone/hydrogel hybrid scaffold.

    PubMed

    Song, Kedong; Li, Liying; Yan, Xinyu; Zhang, Yu; Li, Ruipeng; Wang, Yiwei; Wang, Ling; Wang, Hong; Liu, Tianqing

    2016-06-01

    Using tissue engineering techniques, an artificial osteochondral construct was successfully fabricated to treat large osteochondral defects. In this study, porcine cancellous bones and chitosan/gelatin hydrogel scaffolds were used as substitutes to mimic bone and cartilage, respectively. The porosity and distribution of pore size in porcine bone was measured and the degradation ratio and swelling ratio for chitosan/gelatin hydrogel scaffolds was also determined in vitro. Surface morphology was analyzed with the scanning electron microscope (SEM). The physicochemical properties and the composition were tested by using an infrared instrument. A double layer composite scaffold was constructed via seeding adipose-derived stem cells (ADSCs) induced to chondrocytes and osteoblasts, followed by inoculation in cancellous bones and hydrogel scaffolds. Cell proliferation was assessed through Dead/Live staining and cellular activity was analyzed with IpWin5 software. Cell growth, adhesion and formation of extracellular matrix in composite scaffolds blank cancellous bones or hydrogel scaffolds were also analyzed. SEM analysis revealed a super porous internal structure of cancellous bone scaffolds and pore size was measured at an average of 410 ± 59 μm while porosity was recorded at 70.6 ± 1.7 %. In the hydrogel scaffold, the average pore size was measured at 117 ± 21 μm and the porosity and swelling rate were recorded at 83.4 ± 0.8 % and 362.0 ± 2.4 %, respectively. Furthermore, the remaining hydrogel weighed 80.76 ± 1.6 % of the original dry weight after hydration in PBS for 6 weeks. In summary, the cancellous bone and hydrogel composite scaffold is a promising biomaterial which shows an essential physical performance and strength with excellent osteochondral tissue interaction in situ. ADSCs are a suitable cell source for osteochondral composite reconstruction. Moreover, the bi-layered scaffold significantly enhanced cell proliferation compared to the cells seeded on

  18. Europium-Containing Mesoporous Bioactive Glass Scaffolds for Stimulating in Vitro and in Vivo Osteogenesis.

    PubMed

    Wu, Chengtie; Xia, Lunguo; Han, Pingping; Mao, Lixia; Wang, Jiacheng; Zhai, Dong; Fang, Bing; Chang, Jiang; Xiao, Yin

    2016-05-11

    Bone tissue engineering offers a possible strategy for regenerating large bone defects, in which how to design beneficial scaffolds for accelerating bone formation remains significantly challenging. Europium, as an important rare earth element, has been used as a solid-state lighting material. However, there are few reports on whether Eu can be used for labeling bone tissue engineering scaffolds, and its biological effect on bone cells and bone tissue regeneration is unknown. In this study, we incorporated Eu into mesoporous bioactive glass (Eu-MBG) scaffolds by an in situ cotemplate method to achieve a bifunctional biomaterial with biolabeling and bone regeneration. The prepared Eu-MBG scaffolds have highly interconnective large pores (300-500 μm), a high specific surface area (140-290 m(2)/g), and well-ordered mesopores (5 nm) as well as uniformly distributed Eu. The incorporation of 2-5 mol % Eu into MBG scaffolds gives them a luminescent property. The in vitro degradation of Eu-MBG scaffolds has a functional effect on the change of the luminescence intensity. In addition, Eu-MBG can be used for labeling bone marrow stromal cells (BMSCs) in vitro and still presents a distinct luminescence signal in deep bone tissues in vivo to label new bone tissue via release of Eu ions. Furthermore, the incorporation of different contents of Eu (1, 2, and 5 mol %) into MBG scaffolds significantly enhances the osteogenic gene expression of BMSCs in the scaffolds. The Eu- and Si-containing ionic products released from Eu-MBG scaffolds distinctly promote the osteogenic differentiation of BMSCs. Critically sized femur defects in ovariectomized (OVX) rats are created to simulate an osteoporotic phenotype. The results show that Eu-MBG scaffolds significantly stimulate new bone formation in osteoporotic bone defects when compared to MBG scaffolds alone and Eu may be involved in the acceleration of bone regeneration in OVX rats. Our study for the first time reports that the

  19. Fabrication and development of artificial osteochondral constructs based on cancellous bone/hydrogel hybrid scaffold.

    PubMed

    Song, Kedong; Li, Liying; Yan, Xinyu; Zhang, Yu; Li, Ruipeng; Wang, Yiwei; Wang, Ling; Wang, Hong; Liu, Tianqing

    2016-06-01

    Using tissue engineering techniques, an artificial osteochondral construct was successfully fabricated to treat large osteochondral defects. In this study, porcine cancellous bones and chitosan/gelatin hydrogel scaffolds were used as substitutes to mimic bone and cartilage, respectively. The porosity and distribution of pore size in porcine bone was measured and the degradation ratio and swelling ratio for chitosan/gelatin hydrogel scaffolds was also determined in vitro. Surface morphology was analyzed with the scanning electron microscope (SEM). The physicochemical properties and the composition were tested by using an infrared instrument. A double layer composite scaffold was constructed via seeding adipose-derived stem cells (ADSCs) induced to chondrocytes and osteoblasts, followed by inoculation in cancellous bones and hydrogel scaffolds. Cell proliferation was assessed through Dead/Live staining and cellular activity was analyzed with IpWin5 software. Cell growth, adhesion and formation of extracellular matrix in composite scaffolds blank cancellous bones or hydrogel scaffolds were also analyzed. SEM analysis revealed a super porous internal structure of cancellous bone scaffolds and pore size was measured at an average of 410 ± 59 μm while porosity was recorded at 70.6 ± 1.7 %. In the hydrogel scaffold, the average pore size was measured at 117 ± 21 μm and the porosity and swelling rate were recorded at 83.4 ± 0.8 % and 362.0 ± 2.4 %, respectively. Furthermore, the remaining hydrogel weighed 80.76 ± 1.6 % of the original dry weight after hydration in PBS for 6 weeks. In summary, the cancellous bone and hydrogel composite scaffold is a promising biomaterial which shows an essential physical performance and strength with excellent osteochondral tissue interaction in situ. ADSCs are a suitable cell source for osteochondral composite reconstruction. Moreover, the bi-layered scaffold significantly enhanced cell proliferation compared to the cells seeded on

  20. Chitin scaffolds in tissue engineering.

    PubMed

    Jayakumar, Rangasamy; Chennazhi, Krishna Prasad; Srinivasan, Sowmya; Nair, Shantikumar V; Furuike, Tetsuya; Tamura, Hiroshi

    2011-01-01

    Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine.

  1. Chitin Scaffolds in Tissue Engineering

    PubMed Central

    Jayakumar, Rangasamy; Chennazhi, Krishna Prasad; Srinivasan, Sowmya; Nair, Shantikumar V.; Furuike, Tetsuya; Tamura, Hiroshi

    2011-01-01

    Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine. PMID:21673928

  2. A novel open-porous magnesium scaffold with controllable microstructures and properties for bone regeneration

    NASA Astrophysics Data System (ADS)

    Cheng, Meng-Qi; Wahafu, Tuerhongjiang; Jiang, Guo-Feng; Liu, Wei; Qiao, Yu-Qin; Peng, Xiao-Chun; Cheng, Tao; Zhang, Xian-Long; He, Guo; Liu, Xuan-Yong

    2016-04-01

    The traditional production methods of porous magnesium scaffolds are difficult to accurately control the pore morphologies and simultaneously obtain appropriate mechanical properties. In this work, two open-porous magnesium scaffolds with different pore size but in the nearly same porosity are successfully fabricated with high-purity Mg ingots through the titanium wire space holder (TWSH) method. The porosity and pore size can be easily, precisely and individually controlled, as well as the mechanical properties also can be regulated to be within the range of human cancellous bone by changing the orientation of pores without sacrifice the requisite porous structures. In vitro cell tests indicate that the scaffolds have good cytocompatibility and osteoblastic differentiation properties. In vivo findings demonstrate that both scaffolds exhibit acceptable inflammatory responses and can be almost fully degraded and replaced by newly formed bone. More importantly, under the same porosity, the scaffolds with larger pore size can promote early vascularization and up-regulate collagen type 1 and OPN expression, leading to higher bone mass and more mature bone formation. In conclusion, a new method is introduced to develop an open-porous magnesium scaffold with controllable microstructures and mechanical properties, which has great potential clinical application for bone reconstruction in the future.

  3. Skeletal muscle regeneration via engineered tissue culture over electrospun nanofibrous chitosan/PVA scaffold.

    PubMed

    Kheradmandi, Mahsa; Vasheghani-Farahani, Ebrahim; Ghiaseddin, Ali; Ganji, Fariba

    2016-07-01

    Skeletal muscle tissue shows a remarkable potential in regeneration of injured tissue. However, in some of chronic and volumetric muscle damages, the native tissue is incapable to repair and remodeling the trauma. In the same condition, stem-cell therapy increased regeneration in situations of deficient muscle repair, but the major problem seems to be the lack of ability to attachment and survive of injected cells on the exact location. In this study, chitosan/poly(vinyl alcohol) nanofibrous scaffold was studied to promote cell attachment and provide mechanical support during regeneration. Scaffold was characterized using scanning electron microscope, X-ray diffraction, and tensile test. Degradation and swelling behavior of scaffold were studied for 20 days. The cell-scaffold interaction was characterized by MTT assay for 10 days and in vivo biocompatibility of scaffold in a rabbit model was evaluated. Results showed that cells had a good viability, adhesion, growth, and spread on the scaffold, which make this mat a desirable engineered muscular graft. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1720-1727, 2016.

  4. A novel open-porous magnesium scaffold with controllable microstructures and properties for bone regeneration

    PubMed Central

    Cheng, Meng-qi; Wahafu, Tuerhongjiang; Jiang, Guo-feng; Liu, Wei; Qiao, Yu-qin; Peng, Xiao-chun; Cheng, Tao; Zhang, Xian-long; He, Guo; Liu, Xuan-yong

    2016-01-01

    The traditional production methods of porous magnesium scaffolds are difficult to accurately control the pore morphologies and simultaneously obtain appropriate mechanical properties. In this work, two open-porous magnesium scaffolds with different pore size but in the nearly same porosity are successfully fabricated with high-purity Mg ingots through the titanium wire space holder (TWSH) method. The porosity and pore size can be easily, precisely and individually controlled, as well as the mechanical properties also can be regulated to be within the range of human cancellous bone by changing the orientation of pores without sacrifice the requisite porous structures. In vitro cell tests indicate that the scaffolds have good cytocompatibility and osteoblastic differentiation properties. In vivo findings demonstrate that both scaffolds exhibit acceptable inflammatory responses and can be almost fully degraded and replaced by newly formed bone. More importantly, under the same porosity, the scaffolds with larger pore size can promote early vascularization and up-regulate collagen type 1 and OPN expression, leading to higher bone mass and more mature bone formation. In conclusion, a new method is introduced to develop an open-porous magnesium scaffold with controllable microstructures and mechanical properties, which has great potential clinical application for bone reconstruction in the future. PMID:27071777

  5. Construction of a 3D rGO-collagen hybrid scaffold for enhancement of the neural differentiation of mesenchymal stem cells

    NASA Astrophysics Data System (ADS)

    Guo, Weibo; Wang, Shu; Yu, Xin; Qiu, Jichuan; Li, Jianhua; Tang, Wei; Li, Zhou; Mou, Xiaoning; Liu, Hong; Wang, Zhonglin

    2016-01-01

    The cell-material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold because the surface of the scaffold can determine the fate of stem cells. A conductive surface is required for a scaffold to direct stem cells toward neural differentiation. However, most conductive polymers are toxic and not amenable to biological degradation, which restricts the design of neural tissue engineering scaffolds. In this study, we used a bioactive three-dimensional (3D) porcine acellular dermal matrix (PADM), which is mainly composed of type I collagen, as a basic material and successfully assembled a layer of reduced graphene oxide (rGO) nanosheets on the surface of the PADM channels to obtain a porous 3D, biodegradable, conductive and biocompatible PADM-rGO hybrid neural tissue engineering scaffold. Compared with the PADM scaffold, assembling the rGO into the scaffold did not induce a significant change in the microstructure but endowed the PADM-rGO hybrid scaffold with good conductivity. A comparison of the neural differentiation of rat bone-marrow-derived mesenchymal stem cells (MSCs) was performed by culturing the MSCs on PADM and PADM-rGO scaffolds in neuronal culture medium, followed by the determination of gene expression and immunofluorescence staining. The results of both the gene expression and protein level assessments suggest that the rGO-assembled PADM scaffold may promote the differentiation of MSCs into neuronal cells with higher protein and gene expression levels after 7 days under neural differentiation conditions. This study demonstrated that the PADM-rGO hybrid scaffold is a promising scaffold for neural tissue engineering; this scaffold can not only support the growth of MSCs at a high proliferation rate but also enhance the differentiation of MSCs into neural cells.The cell-material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold

  6. Gold and Hydroxyapatite Nano-Composite Scaffolds for Anterior Cruciate Ligament Reconstruction: In Vitro Characterization.

    PubMed

    Smith, S E; White, R A; Grant, D A; Grant, S A

    2016-01-01

    Current anterior cruciate ligament (ACL) graft replacement materials often fail due to the lack of biological integration. While many newly developed extracellular matrix based scaffolds show good biocompatibility they often do not entice cellular remodeling and the rebuilding of a functional ligament. We have proposed the conjugation of gold nanoparticles (AuNP) and hydroxyapatite nanoparticles (nano-HAp) to acellular tissue to enhance cell attachment and proliferation while maintaining an improved degradation resistance and open microstructure. We are the first to investigate the double conjugation of AuNP and nano-HAp onto decellularized tissue to improve the tissue remodeling response. Decellularized porcine diaphragm was crosslinked with two types of nano-HAp and amine-functionalized AuNP with 1-ethyl-3-(3-dimethlaminopropyl) carbodiimide (EDC) crosslinker. Scaffolds were characterized using electron microscopy, differential scanning calorimetry, and fibroblast assays. Results demonstrated that scaffolds with nano-HAp have increased thermal stability at low levels of crosslinking. The open microstructure of the scaffold was not compromised allowing for cell migration while still providing increased degradation resistance. The addition of < 200 nm nano-HAp decreased cell viability compared to scaffolds without nanoparticles, but the addition of AuNP to scaffolds showed enhanced cell viability in the presence of < 200 nm nano-HAp. The addition of < 40 nm nano-HAp showed an increase in cell viability compared to scaffolds crosslinked without nanoparticles. It is concluded that attaching AuNP and < 40nm nano-HAp to extracellular matrices may improve overall properties. PMID:27398580

  7. Co-cultured tissue-specific scaffolds for tendon/bone interface engineering

    PubMed Central

    Bumgardner, Joel D; Cole, Judith A; Smith, Richard A; Haggard, Warren O

    2014-01-01

    The tendon/ligament-to-bone interface has a complex organization to enable transfer of forces through the tendon/ligament to the bone. The purpose of this study is to create a co-culture environment enabling a tissue-specific tendon region and tissue-specific bone region on a degradable scaffold, using NIH 3T3 fibroblast–deposited extracellular matrix and MC 3T3 osteoblast–deposited extracellular matrix, respectively. Before full characterization of the deposited extracellular matrix coating can be analyzed, co-culture parameters including culture medium and seeding technique should be addressed. An appropriate medium formulation was developed to reduce fibroblast to osteoblast mineralization by adjusting beta-glycerophosphate concentrations. Standard growth medium with fetal bovine serum + 3 mM beta-glycerophosphate + 25 µg/mL ascorbic acid was found to be the most suitable formulation evaluated in these study conditions. Seeding and cell migration studies of co-cultured fibroblast- and osteoblast-specific scaffolds were performed to identify whether tissue regions could be created on the scaffold. Fibroblast and osteoblast regions were successfully seeded and little to no cell migration was observed up to 42 h after seeding. Finally, a preliminary analysis of basic extracellular matrix components was measured in the fibroblast, osteoblast, and transition regions. Tissue-specific DNA, glycosaminoglycan, and collagen were found in uniform amounts on the scaffolds and were not different significantly between scaffold regions. In conclusion, initial steps to create tissue-specific fibroblast and osteoblast regions on a degradable scaffold were successful in preparation for further characterization investigations as a tendon-to-bone interface scaffold. PMID:25383167

  8. Co-cultured tissue-specific scaffolds for tendon/bone interface engineering.

    PubMed

    Cooper, Jared O; Bumgardner, Joel D; Cole, Judith A; Smith, Richard A; Haggard, Warren O

    2014-01-01

    The tendon/ligament-to-bone interface has a complex organization to enable transfer of forces through the tendon/ligament to the bone. The purpose of this study is to create a co-culture environment enabling a tissue-specific tendon region and tissue-specific bone region on a degradable scaffold, using NIH 3T3 fibroblast-deposited extracellular matrix and MC 3T3 osteoblast-deposited extracellular matrix, respectively. Before full characterization of the deposited extracellular matrix coating can be analyzed, co-culture parameters including culture medium and seeding technique should be addressed. An appropriate medium formulation was developed to reduce fibroblast to osteoblast mineralization by adjusting beta-glycerophosphate concentrations. Standard growth medium with fetal bovine serum + 3 mM beta-glycerophosphate + 25 µg/mL ascorbic acid was found to be the most suitable formulation evaluated in these study conditions. Seeding and cell migration studies of co-cultured fibroblast- and osteoblast-specific scaffolds were performed to identify whether tissue regions could be created on the scaffold. Fibroblast and osteoblast regions were successfully seeded and little to no cell migration was observed up to 42 h after seeding. Finally, a preliminary analysis of basic extracellular matrix components was measured in the fibroblast, osteoblast, and transition regions. Tissue-specific DNA, glycosaminoglycan, and collagen were found in uniform amounts on the scaffolds and were not different significantly between scaffold regions. In conclusion, initial steps to create tissue-specific fibroblast and osteoblast regions on a degradable scaffold were successful in preparation for further characterization investigations as a tendon-to-bone interface scaffold.

  9. Gold and Hydroxyapatite Nano-Composite Scaffolds for Anterior Cruciate Ligament Reconstruction: In Vitro Characterization.

    PubMed

    Smith, S E; White, R A; Grant, D A; Grant, S A

    2016-01-01

    Current anterior cruciate ligament (ACL) graft replacement materials often fail due to the lack of biological integration. While many newly developed extracellular matrix based scaffolds show good biocompatibility they often do not entice cellular remodeling and the rebuilding of a functional ligament. We have proposed the conjugation of gold nanoparticles (AuNP) and hydroxyapatite nanoparticles (nano-HAp) to acellular tissue to enhance cell attachment and proliferation while maintaining an improved degradation resistance and open microstructure. We are the first to investigate the double conjugation of AuNP and nano-HAp onto decellularized tissue to improve the tissue remodeling response. Decellularized porcine diaphragm was crosslinked with two types of nano-HAp and amine-functionalized AuNP with 1-ethyl-3-(3-dimethlaminopropyl) carbodiimide (EDC) crosslinker. Scaffolds were characterized using electron microscopy, differential scanning calorimetry, and fibroblast assays. Results demonstrated that scaffolds with nano-HAp have increased thermal stability at low levels of crosslinking. The open microstructure of the scaffold was not compromised allowing for cell migration while still providing increased degradation resistance. The addition of < 200 nm nano-HAp decreased cell viability compared to scaffolds without nanoparticles, but the addition of AuNP to scaffolds showed enhanced cell viability in the presence of < 200 nm nano-HAp. The addition of < 40 nm nano-HAp showed an increase in cell viability compared to scaffolds crosslinked without nanoparticles. It is concluded that attaching AuNP and < 40nm nano-HAp to extracellular matrices may improve overall properties.

  10. Calcium silicate ceramic scaffolds toughened with hydroxyapatite whiskers for bone tissue engineering

    SciTech Connect

    Feng, Pei; Wei, Pingpin; Li, Pengjian; Gao, Chengde; Shuai, Cijun; Peng, Shuping

    2014-11-15

    Calcium silicate possessed excellent biocompatibility, bioactivity and degradability, while the high brittleness limited its application in load-bearing sites. Hydroxyapatite whiskers ranging from 0 to 30 wt.% were incorporated into the calcium silicate matrix to improve the strength and fracture resistance. Porous scaffolds were fabricated by selective laser sintering. The effects of hydroxyapatite whiskers on the mechanical properties and toughening mechanisms were investigated. The results showed that the scaffolds had a uniform and continuous inner network with the pore size ranging between 0.5 mm and 0.8 mm. The mechanical properties were enhanced with increasing hydroxyapatite whiskers, reached a maximum at 20 wt.% (compressive strength: 27.28 MPa, compressive Young's modulus: 156.2 MPa, flexural strength: 15.64 MPa and fracture toughness: 1.43 MPa·m{sup 1/2}) and then decreased by addition of more hydroxyapatite whiskers. The improvement of mechanical properties was due to whisker pull-out, crack deflection and crack bridging. Moreover, the degradation rate decreased with the increase of hydroxyapatite whisker content. A layer of bone-like apatite was formed on the scaffold surfaces after being soaked in simulated body fluid. Human osteoblast-like MG-63 cells spread well on the scaffolds and proliferated with increasing culture time. These findings suggested that the calcium silicate scaffolds reinforced with hydroxyapatite whiskers showed great potential for bone regeneration and tissue engineering applications. - Highlights: • HA whiskers were incorporated into CS to improve the properties. • The scaffolds were successfully fabricated by SLS. • Toughening mechanisms was whisker pull-out, crack deflection and bridging. • The scaffolds showed excellent apatite forming ability.

  11. Hyaluronic Acid Hydrogels with Controlled Degradation Properties for Oriented Bone Regeneration

    PubMed Central

    Patterson, J; Siew, R; Herring, SW; Lin, ASP; Guldberg, R; Stayton, PS

    2010-01-01

    Non-healing fractures can result from trauma, disease, or age-related bone loss. While many treatments focus on restoring bone volume, few try to recapitulate bone organization. However, the native architecture of bone is optimized to provide its necessary mechanical properties. Hyaluronic acid (HA) hydrogel scaffold systems with tunable degradation properties were developed for the controlled delivery of osteoinductive and angiogenic growth factors, thus affecting the quantity and quality of regenerated tissue. HA hydrogels were designed to degrade at fast, intermediate, and slow rates due to hydrolysis and further provided controlled release of cationic proteins due to electrostatic interactions. Scaffolds delivering bone morphogenetic protein-2 (BMP-2) were evaluated in a rat calvarial bone critical size defect model. BMP-2 delivery from the HA hydrogels had a clear osteoinductive effect in vivo and, for all hydrogel types, BMP-2 delivery resulted in significant mineralization compared to control hydrogels. The temporal progression of this effect could be modulated by altering the degradation rate of the scaffold. All three degradation rates tested resulted in similar amounts of mineral formation at the latest (six week) time point examined. Interestingly, however, the fastest and slowest degrading scaffolds seemed to result in more organized bone than the intermediate degrading scaffold, which was designed to degrade in 6–8 weeks to match the healing time. Additionally, healing could be enhanced by co-delivery of vascular endothelial growth factor along with BMP-2. PMID:20573393

  12. Clinical applications of naturally derived biopolymer-based scaffolds for regenerative medicine.

    PubMed

    Stoppel, Whitney L; Ghezzi, Chiara E; McNamara, Stephanie L; Black, Lauren D; Kaplan, David L

    2015-03-01

    Naturally derived polymeric biomaterials, such as collagens, silks, elastins, alginates, and fibrins are utilized in tissue engineering due to their biocompatibility, bioactivity, and tunable mechanical and degradation kinetics. The use of these natural biopolymers in biomedical applications is advantageous because they do not release cytotoxic degradation products, are often processed using environmentally-friendly aqueous-based methods, and their degradation rates within biological systems can be manipulated by modifying the starting formulation or processing conditions. For these reasons, many recent in vivo investigations and FDA-approval of new biomaterials for clinical use have utilized natural biopolymers as matrices for cell delivery and as scaffolds for cell-free support of native tissues. This review highlights biopolymer-based scaffolds used in clinical applications for the regeneration and repair of native tissues, with a focus on bone, skeletal muscle, peripheral nerve, cardiac muscle, and cornea substitutes.

  13. Construction of a 3D rGO-collagen hybrid scaffold for enhancement of the neural differentiation of mesenchymal stem cells.

    PubMed

    Guo, Weibo; Wang, Shu; Yu, Xin; Qiu, Jichuan; Li, Jianhua; Tang, Wei; Li, Zhou; Mou, Xiaoning; Liu, Hong; Wang, Zhonglin

    2016-01-28

    The cell-material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold because the surface of the scaffold can determine the fate of stem cells. A conductive surface is required for a scaffold to direct stem cells toward neural differentiation. However, most conductive polymers are toxic and not amenable to biological degradation, which restricts the design of neural tissue engineering scaffolds. In this study, we used a bioactive three-dimensional (3D) porcine acellular dermal matrix (PADM), which is mainly composed of type I collagen, as a basic material and successfully assembled a layer of reduced graphene oxide (rGO) nanosheets on the surface of the PADM channels to obtain a porous 3D, biodegradable, conductive and biocompatible PADM-rGO hybrid neural tissue engineering scaffold. Compared with the PADM scaffold, assembling the rGO into the scaffold did not induce a significant change in the microstructure but endowed the PADM-rGO hybrid scaffold with good conductivity. A comparison of the neural differentiation of rat bone-marrow-derived mesenchymal stem cells (MSCs) was performed by culturing the MSCs on PADM and PADM-rGO scaffolds in neuronal culture medium, followed by the determination of gene expression and immunofluorescence staining. The results of both the gene expression and protein level assessments suggest that the rGO-assembled PADM scaffold may promote the differentiation of MSCs into neuronal cells with higher protein and gene expression levels after 7 days under neural differentiation conditions. This study demonstrated that the PADM-rGO hybrid scaffold is a promising scaffold for neural tissue engineering; this scaffold can not only support the growth of MSCs at a high proliferation rate but also enhance the differentiation of MSCs into neural cells. PMID:26750302

  14. Construction of a 3D rGO-collagen hybrid scaffold for enhancement of the neural differentiation of mesenchymal stem cells.

    PubMed

    Guo, Weibo; Wang, Shu; Yu, Xin; Qiu, Jichuan; Li, Jianhua; Tang, Wei; Li, Zhou; Mou, Xiaoning; Liu, Hong; Wang, Zhonglin

    2016-01-28

    The cell-material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold because the surface of the scaffold can determine the fate of stem cells. A conductive surface is required for a scaffold to direct stem cells toward neural differentiation. However, most conductive polymers are toxic and not amenable to biological degradation, which restricts the design of neural tissue engineering scaffolds. In this study, we used a bioactive three-dimensional (3D) porcine acellular dermal matrix (PADM), which is mainly composed of type I collagen, as a basic material and successfully assembled a layer of reduced graphene oxide (rGO) nanosheets on the surface of the PADM channels to obtain a porous 3D, biodegradable, conductive and biocompatible PADM-rGO hybrid neural tissue engineering scaffold. Compared with the PADM scaffold, assembling the rGO into the scaffold did not induce a significant change in the microstructure but endowed the PADM-rGO hybrid scaffold with good conductivity. A comparison of the neural differentiation of rat bone-marrow-derived mesenchymal stem cells (MSCs) was performed by culturing the MSCs on PADM and PADM-rGO scaffolds in neuronal culture medium, followed by the determination of gene expression and immunofluorescence staining. The results of both the gene expression and protein level assessments suggest that the rGO-assembled PADM scaffold may promote the differentiation of MSCs into neuronal cells with higher protein and gene expression levels after 7 days under neural differentiation conditions. This study demonstrated that the PADM-rGO hybrid scaffold is a promising scaffold for neural tissue engineering; this scaffold can not only support the growth of MSCs at a high proliferation rate but also enhance the differentiation of MSCs into neural cells.

  15. TRIS buffer in simulated body fluid distorts the assessment of glass-ceramic scaffold bioactivity.

    PubMed

    Rohanová, Dana; Boccaccini, Aldo Roberto; Yunos, Darmawati Mohamad; Horkavcová, Diana; Březovská, Iva; Helebrant, Aleš

    2011-06-01

    The paper deals with the characterisation of the bioactive phenomena of glass-ceramic scaffold derived from Bioglass® (containing 77 wt.% of crystalline phases Na(2)O·2CaO·3SiO(2) and CaO·SiO(2) and 23 wt.% of residual glass phase) using simulated body fluid (SBF) buffered with tris-(hydroxymethyl) aminomethane (TRIS). A significant effect of the TRIS buffer on glass-ceramic scaffold dissolution in SBF was detected. To better understand the influence of the buffer, the glass-ceramic scaffold was exposed to a series of in vitro tests using different media as follows: (i) a fresh liquid flow of SBF containing tris (hydroxymethyl) aminomethane; (ii) SBF solution without TRIS buffer; (iii) TRIS buffer alone; and (iv) demineralised water. The in vitro tests were provided under static and dynamic arrangements. SBF buffered with TRIS dissolved both the crystalline and residual glass phases of the scaffold and a crystalline form of hydroxyapatite (HAp) developed on the scaffold surface. In contrast, when TRIS buffer was not present in the solutions only the residual glassy phase dissolved and an amorphous calcium phosphate (Ca-P) phase formed on the scaffold surface. It was confirmed that the TRIS buffer primarily dissolved the crystalline phase of the glass-ceramic, doubled the dissolving rate of the scaffold and moreover supported the formation of crystalline HAp. This significant effect of the buffer TRIS on bioactive glass-ceramic scaffold degradation in SBF has not been demonstrated previously and should be considered when analysing the results of SBF immersion bioactivity tests of such systems.

  16. Fabrication of modified and functionalized polycaprolactone nanofibre scaffolds for vascular tissue engineering

    NASA Astrophysics Data System (ADS)

    Venugopal, J.; Zhang, Y. Z.; Ramakrishna, S.

    2005-10-01

    Electrospun polymer nanofibres were originally developed for their durability and resistance to all forms of degradation and biodegradation. Some polymer nanofibres are biocompatible and biodegradable and therefore suitable for replacement of structurally or physiologically deficient tissues and organs in humans. Here, biocompatible polycaprolactone (PCL) nanofibre scaffolds modified with collagen types I and III were used for vascular tissue engineering. Coronary artery smooth muscle cells (SMCs) were grown on PCL nanofibres, modified PCL/collagen biocomposite nanofibres and collagen nanofibres. The results show that the modified PCL/collagen biocomposite nanofibre scaffolds provide required mechanical properties for regulation of normal cell function in vascular tissue engineering.

  17. 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

  18. A photocurable hydrogel/elastomer composite scaffold with bi-continuous morphology for cell encapsulation.

    PubMed

    Hayami, James W S; Waldman, Stephen D; Amsden, Brian G

    2011-12-01

    A photocurable two-phase scaffold with a bi-continuous morphology was designed and characterized for the repair of load bearing soft tissues. An N-methacrylate glycol chitosan (MGC) hydrogel phase was used to distribute the cells and enable cell growth once crosslinked. The second phase, an elastomerprepared from a star-poly(ε-caprolactone-co-D,L-lactide) triacrylate, was used to enhance the mechanical properties. Chondrocytes were photocrosslinked within the bi-continuous scaffolds and proliferated, increased metabolic activity and accumulated extracellular matrix over a 14 d culture period. Also during this time no significant material degradation was observed. PMID:22012746

  19. Mechanical properties, biological behaviour and drug release capability of nano TiO2-HAp-Alginate composite scaffolds for potential application as bone implant material.

    PubMed

    Naik, Kshipra; Chandran, V Girish; Rajashekaran, Raghavan; Waigaonkar, Sachin; Kowshik, Meenal

    2016-09-01

    Nanocomposite scaffolds of TiO2 and hydroxyapatite nanoparticles with alginate as the binding agent were fabricated using the freeze drying technique. TiO2, hydroxyapatite and alginate were used in the ratio of 1:1:4. The scaffolds were characterized using X-ray diffraction, fourier transform infrared spectroscopy, and scanning electron microscopy. The biocompatibility of the scaffolds was evaluated using cell adhesion and MTT assay on osteosarcoma (MG-63) cells. Scanning electron microscopy analysis revealed that cells adhered to the surface of the scaffolds with good spreading. The mechanical properties of the scaffolds were investigated using dynamic mechanical analysis. The swelling ability, porosity, in vitro degradation, and biomineralization of the scaffolds were also evaluated. The results indicated controlled swelling, limited degradation, and enhanced biomineralization. Further, drug delivery studies of the scaffolds using the chemotherapeutic drug methotrexate exhibited an ideal drug release profile. These scaffolds are proposed as potential candidates for bone tissue engineering and drug delivery applications. PMID:27485954

  20. Balancing mechanical strength with bioactivity in chitosan-calcium phosphate 3D microsphere scaffolds for bone tissue engineering: air- vs. freeze-drying processes.

    PubMed

    Nguyen, D T; McCanless, J D; Mecwan, M M; Noblett, A P; Haggard, W O; Smith, R A; Bumgardner, J D

    2013-01-01

    The objective of this study was to evaluate the potential benefit of 3D composite scaffolds composed of chitosan and calcium phosphate for bone tissue engineering. Additionally, incorporation of mechanically weak lyophilized microspheres within those air-dried (AD) was considered for enhanced bioactivity. AD microsphere, alone, and air- and freeze-dried microsphere (FDAD) 3D scaffolds were evaluated in vitro using a 28-day osteogenic culture model with the Saos-2 cell line. Mechanical testing, quantitative microscopy, and lysozyme-driven enzymatic degradation of the scaffolds were also studied. FDAD scaffold showed a higher concentration (p < 0.01) in cells per scaffold mass vs. AD constructs. Collagen was ∼31% greater (p < 0.01) on FDAD compared to AD scaffolds not evident in microscopy of microsphere surfaces. Alternatively, AD scaffolds demonstrated a superior threefold increase in compressive strength over FDAD (12 vs. 4 MPa) with minimal degradation. Inclusion of FD spheres within the FDAD scaffolds allowed increased cellular activity through improved seeding, proliferation, and extracellular matrix production (as collagen), although mechanical strength was sacrificed through introduction of the less stiff, porous FD spheres.

  1. Mechanical properties, biological behaviour and drug release capability of nano TiO2-HAp-Alginate composite scaffolds for potential application as bone implant material.

    PubMed

    Naik, Kshipra; Chandran, V Girish; Rajashekaran, Raghavan; Waigaonkar, Sachin; Kowshik, Meenal

    2016-09-01

    Nanocomposite scaffolds of TiO2 and hydroxyapatite nanoparticles with alginate as the binding agent were fabricated using the freeze drying technique. TiO2, hydroxyapatite and alginate were used in the ratio of 1:1:4. The scaffolds were characterized using X-ray diffraction, fourier transform infrared spectroscopy, and scanning electron microscopy. The biocompatibility of the scaffolds was evaluated using cell adhesion and MTT assay on osteosarcoma (MG-63) cells. Scanning electron microscopy analysis revealed that cells adhered to the surface of the scaffolds with good spreading. The mechanical properties of the scaffolds were investigated using dynamic mechanical analysis. The swelling ability, porosity, in vitro degradation, and biomineralization of the scaffolds were also evaluated. The results indicated controlled swelling, limited degradation, and enhanced biomineralization. Further, drug delivery studies of the scaffolds using the chemotherapeutic drug methotrexate exhibited an ideal drug release profile. These scaffolds are proposed as potential candidates for bone tissue engineering and drug delivery applications.

  2. Sensate Scaffolds Can Reliably Detect Joint Loading

    PubMed Central

    Bliss, C. L.; Szivek, J. A.; Tellis, B. C.; Margolis, D. S.; Schnepp, A. B.; Ruth, J. T.

    2008-01-01

    Treatment of cartilage defects is essential to the prevention of osteoarthritis. Scaffold-based cartilage tissue engineering shows promise as a viable technique to treat focal defects. Added functionality can be achieved by incorporating strain gauges into scaffolds, thereby providing a real-time diagnostic measurement of joint loading. Strain-gauged scaffolds were placed into the medial femoral condyles of 14 adult canine knees and benchtop tested. Loads between 75 and 130 N were applied to the stifle joints at 30°, 50°, and 70° of flexion. Strain-gauged scaffolds were able to reliably assess joint loading at all applied flexion angles and loads. Pressure sensitive films were used to determine joint surface pressures during loading and to assess the effect of scaffold placement on joint pressures. A comparison of peak pressures in control knees and joints with implanted scaffolds, as well as a comparison of pressures before and after scaffold placement, showed that strain-gauged scaffold implantation did not significantly alter joint pressures. Future studies could possibly use strain-gauged scaffolds to clinically establish normal joint loads and to determine loads that are damaging to both healthy and tissue-engineered cartilage. Strain-gauged scaffolds may significantly aid the development of a functional engineered cartilage tissue substitute as well as provide insight into the native environment of cartilage. PMID:16941586

  3. Tailoring chitosan/collagen scaffolds for tissue engineering: Effect of composition and different crosslinking agents on scaffold properties.

    PubMed

    Martínez, A; Blanco, M D; Davidenko, N; Cameron, R E

    2015-11-01

    Chitosan/collagen (Chit/Col) blends have demonstrated great potential for use in tissue engineering (TE) applications. However, there exists a lack of detailed study on the influence of important design parameters (i.e, component ratio or crosslinking methods) on the essential properties of the scaffolds (morphology, mechanical stiffness, swelling, degradation and cytotoxicity). This work entailed a systematic study of these essential properties of three Chit/Col compositions, covering a wide range of component ratios and using different crosslinking methods. Our results showed the possibility of tailoring these properties by changing component ratios, since different interactions occurred between Chit/Col: samples with Chit-enriched compositions showed a hydrogen-bonding type complex (HC), whereas a self-crosslinking phenomenon was induced in Col-enriched scaffolds. Additionally, material and biological properties of the resultant matrices were further adjusted and tuned by changing crosslinking conditions. In such way, we obtained a wide range of scaffolds whose properties were tailored to meet specific needs of TE applications.

  4. Tailoring chitosan/collagen scaffolds for tissue engineering: Effect of composition and different crosslinking agents on scaffold properties.

    PubMed

    Martínez, A; Blanco, M D; Davidenko, N; Cameron, R E

    2015-11-01

    Chitosan/collagen (Chit/Col) blends have demonstrated great potential for use in tissue engineering (TE) applications. However, there exists a lack of detailed study on the influence of important design parameters (i.e, component ratio or crosslinking methods) on the essential properties of the scaffolds (morphology, mechanical stiffness, swelling, degradation and cytotoxicity). This work entailed a systematic study of these essential properties of three Chit/Col compositions, covering a wide range of component ratios and using different crosslinking methods. Our results showed the possibility of tailoring these properties by changing component ratios, since different interactions occurred between Chit/Col: samples with Chit-enriched compositions showed a hydrogen-bonding type complex (HC), whereas a self-crosslinking phenomenon was induced in Col-enriched scaffolds. Additionally, material and biological properties of the resultant matrices were further adjusted and tuned by changing crosslinking conditions. In such way, we obtained a wide range of scaffolds whose properties were tailored to meet specific needs of TE applications. PMID:26256388

  5. In vitro comparative study of two decellularization protocols in search of an optimal myocardial scaffold for recellularization

    PubMed Central

    Perea-Gil, Isaac; Uriarte, Juan J; Prat-Vidal, Cristina; Gálvez-Montón, Carolina; Roura, Santiago; Llucià-Valldeperas, Aida; Soler-Botija, Carolina; Farré, Ramon; Navajas, Daniel; Bayes-Genis, Antoni

    2015-01-01

    Introduction. Selection of a biomaterial-based scaffold that mimics native myocardial extracellular matrix (ECM) architecture can facilitate functional cell attachment and differentiation. Although decellularized myocardial ECM accomplishes these premises, decellularization processes may variably distort or degrade ECM structure. Materials and methods. Two decellularization protocols (DP) were tested on porcine heart samples (epicardium, mid myocardium and endocardium). One protocol, DP1, was detergent-based (SDS and Triton X-100), followed by DNase I treatment. The other protocol, DP2, was focused in trypsin and acid with Triton X-100 treatments. Decellularized myocardial scaffolds were reseeded by embedding them in RAD16-I peptidic hydrogel with adipose tissue-derived progenitor cells (ATDPCs). Results. Both protocols yielded acellular myocardial scaffolds (~82% and ~94% DNA reduction for DP1 and DP2, respectively). Ultramicroscopic assessment of scaffolds was similar for both protocols and showed filamentous ECM with preserved fiber disposition and structure. DP1 resulted in more biodegradable scaffolds (P = 0.04). Atomic force microscopy revealed no substantial ECM stiffness changes post-decellularization compared to native tissue. The Young’s modulus did not differ between heart layers (P = 0.69) or decellularization protocols (P = 0.15). After one week, recellularized DP1 scaffolds contained higher cell density (236 ± 106 and 98 ± 56 cells/mm2 for recellularized DP1 and DP2 scaffolds, respectively; P = 0.04). ATDPCs in both DP1 and DP2 scaffolds expressed the endothelial marker isolectin B4, but only in the DP1 scaffold ATDPCs expressed the cardiac markers GATA4, connexin43 and cardiac troponin T. Conclusions. In our hands, DP1 produced myocardial scaffolds with higher cell repopulation and promotes ATDPCs expression of endothelial and cardiomyogenic markers. PMID:26045895

  6. Bone regeneration in rat calvarial defects implanted with fibrous scaffolds composed of a mixture of silicate and borate bioactive glasses.

    PubMed

    Gu, Yifei; Huang, Wenhai; Rahaman, Mohamed N; Day, Delbert E

    2013-11-01

    Previous studies have evaluated the capacity of porous scaffolds composed of a single bioactive glass to regenerate bone. In the present study, scaffolds composed of a mixture of two different bioactive glasses (silicate 13-93 and borate 13-93B3) were created and evaluated for their response to osteogenic MLO-A5 cells in vitro and their capacity to regenerate bone in rat calvarial defects in vivo. The scaffolds, which have similar microstructures (porosity=58-67%) and contain 0, 25, 50 and 100 wt.% 13-93B3 glass, were fabricated by thermally bonding randomly oriented short fibers. The silicate 13-93 scaffolds showed a better capacity to support cell proliferation and alkaline phosphatase activity than the scaffolds containing borate 13-93B3 fibers. The amount of new bone formed in the defects implanted with the 13-93 scaffolds at 12 weeks was 31%, compared to values of 25, 17 and 20%, respectively, for the scaffolds containing 25, 50 and 100% 13-93B3 glass. The amount of new bone formed in the 13-93 scaffolds was significantly higher than in the scaffolds containing 50 and 100% 13-93B3 glass. While the 13-93 fibers were only partially converted to hydroxyapatite at 12 weeks, the 13-93B3 fibers were fully converted and formed a tubular morphology. Scaffolds composed of an optimized mixture of silicate and borate bioactive glasses could provide the requisite architecture to guide bone regeneration combined with a controllable degradation rate that could be beneficial for bone and tissue healing.

  7. A Scaffolding Design Framework for Software to Support Science Inquiry

    ERIC Educational Resources Information Center

    Quintana, Chris; Reiser, Brian J.; Davis, Elizabeth A.; Krajcik, Joseph; Fretz, Eric; Duncan, Ravit Golan; Kyza, Eleni; Edelson, Daniel; Soloway, Elliot

    2004-01-01

    The notion of scaffolding learners to help them succeed in solving problems otherwise too difficult for them is an important idea that has extended into the design of scaffolded software tools for learners. However, although there is a growing body of work on scaffolded tools, scaffold design, and the impact of scaffolding, the field has not yet…

  8. Repairing rabbit radial defects by combining bone marrow stroma stem cells with bone scaffold material comprising a core-cladding structure.

    PubMed

    Wu, H; Liu, G H; Wu, Q; Yu, B

    2015-10-05

    We prepared a bone scaffold material comprising a PLGA/β-TCP core and a Type I collagen cladding, and recombined it with bone marrow stroma stem cells (BMSCs) to evaluate its potential for use in bone tissue engineering by in vivo and in vitro experiments. PLGA/β-TCP without a cladding was used for comparison. The adherence rate of the BMSCs to the scaffold was determined by cell counting. Cell proliferation rate was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The osteogenic capability was evaluated by alkaline phosphatase activity. The scaffold materials were recombined with the BMSCs and implanted into a large segmental rabbit radial defect model to evaluate defect repair. Osteogenesis was assessed in the scaffold materials by histological and double immunofluorescence labeling, etc. The adherence number, proliferation number, and alkaline phosphatase expression of the cells on the bone scaffold material with core-cladding structure were significantly higher than the corresponding values in the PLGA/β-TCP composite scaffold material (P < 0.05). An in vivo test indicated that the bone scaffold material with core-cladding structure completely degraded at the bone defect site and bone formation was completed. The rabbit large sentimental radial defect was successfully repaired. The degradation and osteogenesis rates matched well. The bone scaffold with core-cladding structure exhibited better osteogenic activity and capacity to repair a large segmental bone defect compared to the PLGA/β-TCP composite scaffold. The bone scaffold with core-cladding structure has excellent physical properties and biocompatibility. It is an ideal scaffold material for bone tissue engineering.

  9. Engineered porous scaffolds for periprosthetic infection prevention.

    PubMed

    Iviglia, Giorgio; Cassinelli, Clara; Bollati, Daniele; Baino, Francesco; Torre, Elisa; Morra, Marco; Vitale-Brovarone, Chiara

    2016-11-01

    Periprosthetic infection is a consequence of implant insertion procedures and strategies for its prevention involve either an increase in the rate of new bone formation or the release of antibiotics such as vancomycin. In this work we combined both strategies and developed a novel, multifunctional three-dimensional porous scaffold that was produced using hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), coupled with a pectin (PEC)-chitosan (CHIT) polyelectrolyte (PEI), and loaded with vancomycin (VCA). By this approach, a controlled vancomycin release was achieved and serial bacterial dilution test demonstrated that, after 1week, the engineered construct still inhibits the bacterial growth. Degradation tests show an excellent behavior in a physiological and acidic environment (<10% of mass loss). Furthermore, the PEI coating shows an anti-inflammatory response, and good cell proliferation and migration were demonstrated in vitro using osteoblast SAOS-2 cell line. This new engineered construct exhibits excellent properties both as an antibacterial material and as a stimulator of bone formation, which makes it a good candidate to contrast periprosthetic infection. PMID:27524071

  10. Development of a 3D polymer reinforced calcium phosphate cement scaffold for cranial bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Alge, Daniel L.

    The repair of critical-sized cranial bone defects represents an important clinical challenge. The limitations of autografts and alloplastic materials make a bone tissue engineering strategy desirable, but success depends on the development of an appropriate scaffold. Key scaffold properties include biocompatibility, osteoconductivity, sufficient strength to maintain its structure, and resorbability. Furthermore, amenability to rapid prototyping fabrication methods is desirable, as these approaches offer precise control over scaffold architecture and have the potential for customization. While calcium phosphate cements meet many of these criteria due to their composition and their injectability, which can be leveraged for scaffold fabrication via indirect casting, their mechanical properties are a major limitation. Thus, the overall goal of this work was to develop a 3D polymer reinforced calcium phosphate cement scaffold for use in cranial bone tissue engineering. Dicalcium phosphate dihydrate (DCPD) setting cements are of particular interest because of their excellent resorbability. We demonstrated for the first time that DCPD cement can be prepared from monocalcium phosphate monohydrate (MCPM)/hydroxyapatite (HA) mixtures. However, subsequent characterization revealed that MCPM/HA cements rapidly convert to HA during degradation, which is undesirable and led us to choose a more conventional formulation for scaffold fabrication. In addition, we developed a novel method for calcium phosphate cement reinforcement that is based on infiltrating a pre-set cement structure with a polymer, and then crosslinking the polymer in situ. Unlike prior methods of cement reinforcement, this method can be applied to the reinforcement of 3D scaffolds fabricated by indirect casting. Using our novel method, composites of poly(propylene fumarate) (PPF) reinforced DCPD were prepared and demonstrated as excellent candidate scaffold materials, as they had increased strength and ductility

  11. Scaffold Design for Bone Regeneration

    PubMed Central

    Polo-Corrales, Liliana; Latorre-Esteves, Magda; Ramirez-Vick, Jaime E.

    2014-01-01

    The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues. PMID:24730250

  12. Hydrogels and scaffolds for immunomodulation.

    PubMed

    Singh, Ankur; Peppas, Nicholas A

    2014-10-01

    For over two decades, immunologists and biomaterials scientists have co-existed in parallel world with the rationale of understanding the molecular profile of immune responses to vaccination, implantation, and treating incurable diseases. Much of the field of biomaterial-based immunotherapy has relied on evaluating model antigens such as chicken egg ovalbumin in mouse models but their relevance to humans has been point of much discussion. Nevertheless, such model antigens have provided important insights into the mechanisms of immune regulation and served as a proof-of-concept for plethora of biomaterial-based vaccines. After years of extensive development of numerous biomaterials for immunomodulation, it is only recently that an experimental scaffold vaccine implanted beneath the skin has begun to use the human model to study the immune responses to cancer vaccination by co-delivering patient-derived tumor lysates and immunomodulatory proteins. If successful, this scaffold vaccine will change the way we approached untreatable cancers, but more importantly, will allow a faster and more rational translation of therapeutic regimes to other cancers, chronic infections, and autoimmune diseases. Most materials reviews have focused on immunomodulatory adjuvants and micro-nano-particles. Here we provide an insight into emerging hydrogel and scaffold based immunomodulatory approaches that continue to demonstrate efficacy against immune associated diseases.

  13. Hydrogels and scaffolds for immunomodulation

    PubMed Central

    2014-01-01

    For over two decades, immunologists and biomaterials scientists have co-existed in parallel world with the rationale of understanding the molecular profile of immune responses to vaccination, implantation, and treating incurable diseases. Much of the field of biomaterials-based immunotherapy has relied on evaluating model antigens such as chicken egg ovalbumin in mouse models but their relevance to humans has been point of much discussion. Nevertheless, such model antigens have provided important insights about the mechanisms of immune regulation and served as a proof-of-concept for plethora of biomaterials-based vaccines. After years of extensive development of numerous biomaterials for immunomodulation, it is only recently that an experimental scaffold vaccine implanted beneath the skin has begun to use the human model to study the immune responses to cancer vaccination by co-delivering patient-derived tumor lysates and immunomodulatory proteins. If successful, this scaffold vaccine will change the way we approached untreatable cancers, but more importantly, will allow a faster and more rational translation of therapeutic regimes to other cancers, chronic infections, and autoimmune diseases. Most materials reviews have focused on immunomodulatory adjuvants and micro-nano-particles. Here we provide an insight into emerging hydrogel and scaffold based immunomodulatory approaches that continue to demonstrate efficacy against immune associated diseases. PMID:25155610

  14. The effect of porosity on cell ingrowth into accurately defined, laser-made, polylactide-based 3D scaffolds

    NASA Astrophysics Data System (ADS)

    Danilevicius, Paulius; Georgiadi, Leoni; Pateman, Christopher J.; Claeyssens, Frederik; Chatzinikolaidou, Maria; Farsari, Maria

    2015-05-01

    The aim of this study is to demonstrate the accuracy required for the investigation of the role of solid scaffolds' porosity in cell proliferation. We therefore present a qualitative investigation into the effect of porosity on MC3T3-E1 pre-osteoblastic cell ingrowth of three-dimensional (3D) scaffolds fabricated by direct femtosecond laser writing. The material we used is a purpose made photosensitive pre-polymer based on polylactide. We designed and fabricated complex, geometry-controlled 3D scaffolds with pore sizes ranging from 25 to 110 μm, representing porosities 70%, 82%, 86%, and 90%. The 70% porosity scaffolds did not support cell growth initially and in the long term. For the other porosities, we found a strong adhesion of the pre-osteoblastic cells from the first hours after seeding and a remarkable proliferation increase after 3 weeks and up to 8 weeks. The 86% porosity scaffolds exhibited a higher efficiency compared to 82% and 90%. In addition, bulk material degradation studies showed that the employed, highly-acrylated polylactide is degradable. These findings support the potential use of the proposed material and the scaffold fabrication technique in bone tissue engineering.

  15. Investigation of thermal degradation with extrusion-based dispensing modules for 3D bioprinting technology.

    PubMed

    Lee, Hyungseok; Yoo, James J; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-02-04

    Recently, numerous three-dimensional (3D) bioprinting systems have been introduced for the artificial regeneration of tissues. Among them, the extrusion-based dispensing module is the most widely used because of the processability it gives various biomaterials. The module uses high forces and temperature to dispense materials through a micro-nozzle. Generally, the harsh conditions induce thermal degradation of the material in the dispensing procedure. The thermal degradation affects the properties of the materials, and the change of the properties should be carefully controlled, because it severely affects the regeneration of tissues. Therefore, in this research, the relationship between the dispensing module and the thermal degradation of material was investigated. Extrusion-based dispensing modules can be divided into the syringe type (ST) and filament type (FT) based on working principles. We prepared a poly lactic-co-glycolic acid (PLGA) scaffold with the two methods at various time points. Then, the characteristics of the printed scaffolds were assessed by measuring molecular weight (M w), glass transition temperature (T g), in vitro degradation, compressive modulus, and cytocompatibility. The results showed that the PLGA scaffold with the FT dispensing module maintained its properties regardless of printing time points. In contrast, severe thermal degradation was observed in the scaffold group prepared by the ST dispensing module. Consequentially, it was obvious that the FT dispensing module was more suitable for producing scaffolds without severe thermal degradation.

  16. Investigation of thermal degradation with extrusion-based dispensing modules for 3D bioprinting technology.

    PubMed

    Lee, Hyungseok; Yoo, James J; Kang, Hyun-Wook; Cho, Dong-Woo

    2016-03-01

    Recently, numerous three-dimensional (3D) bioprinting systems have been introduced for the artificial regeneration of tissues. Among them, the extrusion-based dispensing module is the most widely used because of the processability it gives various biomaterials. The module uses high forces and temperature to dispense materials through a micro-nozzle. Generally, the harsh conditions induce thermal degradation of the material in the dispensing procedure. The thermal degradation affects the properties of the materials, and the change of the properties should be carefully controlled, because it severely affects the regeneration of tissues. Therefore, in this research, the relationship between the dispensing module and the thermal degradation of material was investigated. Extrusion-based dispensing modules can be divided into the syringe type (ST) and filament type (FT) based on working principles. We prepared a poly lactic-co-glycolic acid (PLGA) scaffold with the two methods at various time points. Then, the characteristics of the printed scaffolds were assessed by measuring molecular weight (M w), glass transition temperature (T g), in vitro degradation, compressive modulus, and cytocompatibility. The results showed that the PLGA scaffold with the FT dispensing module maintained its properties regardless of printing time points. In contrast, severe thermal degradation was observed in the scaffold group prepared by the ST dispensing module. Consequentially, it was obvious that the FT dispensing module was more suitable for producing scaffolds without severe thermal degradation. PMID:26844711

  17. Functionalized scaffolds to enhance tissue regeneration

    PubMed Central

    Guo, Baolin; Lei, Bo; Li, Peng; Ma, Peter X.

    2015-01-01

    Tissue engineering scaffolds play a vital role in regenerative medicine. It not only provides a temporary 3-dimensional support during tissue repair, but also regulates the cell behavior, such as cell adhesion, proliferation and differentiation. In this review, we summarize the development and trends of functional scaffolding biomaterials including electrically conducting hydrogels and nanocomposites of hydroxyapatite (HA) and bioactive glasses (BGs) with various biodegradable polymers. Furthermore, the progress on the fabrication of biomimetic nanofibrous scaffolds from conducting polymers and composites of HA and BG via electrospinning, deposition and thermally induced phase separation is discussed. Moreover, bioactive molecules and surface properties of scaffolds are very important during tissue repair. Bioactive molecule-releasing scaffolds and antimicrobial surface coatings for biomedical implants and scaffolds are also reviewed. PMID:25844177

  18. Improving bone repair of femoral and radial defects in rabbit by incorporating PRP into PLGA/CPC composite scaffold with unidirectional pore structure.

    PubMed

    He, Fupo; Chen, Yan; Li, Jiyan; Lin, Bomiao; Ouyang, Yi; Yu, Bo; Xia, Yuanyou; Yu, Bo; Ye, Jiandong

    2015-04-01

    In this study, a platelet-rich plasma poly(lactic-co-glycolic acid) (PRP-PLGA)/calcium phosphate cement (CPC) composite scaffold was prepared by incorporating PRP into PLGA/CPC scaffold with unidirectional pore structure, which was fabricated by the unidirectional freeze casting of CPC slurry and the following infiltration of PLGA. The results from in vitro cell experiments and in vivo implantation in femoral defects manifested that incorporation of PRP into PLGA/CPC scaffold improved in vitro cell response (cell attachment, proliferation, and differentiation), and markedly boosted bone formation, angiogenesis and material degradation. The incorporation of PRP into scaffold showed more outstanding improvement in osteogenesis as the scaffolds were used to repair the segmental radial defects, especially at the early stage. The new bone tissues grew along the unidirectional lamellar pores of scaffold. At 12 weeks postimplantation, the segmental radial defects treated with PRP-PLGA/CPC scaffold had almost recuperated, whereas treated with the scaffold without PRP was far from healed. Taken together, the PRP-PLGA/CPC scaffold with unidirectional pore structure is a promising candidate to repair bone defects at various sites.

  19. In vitro evaluation of the biological performance of macro/micro-porous silk fibroin and silk-nano calcium phosphate scaffolds.

    PubMed

    Yan, L-P; Oliveira, J M; Oliveira, A L; Reis, R L

    2015-05-01

    This study evaluates the biological performance of salt-leached macro/microporous silk scaffolds (S16) and silk-nano calcium phosphate scaffolds (SC16), both deriving from a 16 wt % aqueous SF solution. Enzymatic degradation results showed that the silk-based scaffolds presented desirable biostability, and the incorporation of calcium phosphate further improved the scaffolds' biostability. Human adipose tissue derived stromal cells (hASCs) were cultured onto the scaffolds in vitro. The Alamar blue assay and DNA content revealed that both scaffolds were non-cytotoxic and can support the viability and proliferation of the hASCs. Scanning electron microscopy observation demonstrated that the microporous structure was beneficial for the cell adhesion while the macroporous structure favored the cell migration and proliferation. The histological analysis displayed abundant extracellular matrix formed inside the scaffolds, leading to the significant increase of scaffolds' modulus. These results revealed that S16 and SC16 could be promising alternatives for cartilage and bone tissue engineering scaffolding applications, respectively.

  20. 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.

  1. 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

  2. Improved biocomposite development of poly(vinyl alcohol) and hydroxyapatite for tissue engineering scaffold fabrication using selective laser sintering.

    PubMed

    Wiria, Florencia Edith; Chua, Chee Kai; Leong, Kah Fai; Quah, Zai Yan; Chandrasekaran, Margam; Lee, Mun Wai

    2008-03-01

    In scaffold guided tissue engineering (TE), temporary three-dimensional scaffolds are essential to guide and support cell proliferation. Selective Laser Sintering (SLS) is studied for the development of such scaffolds by eliminating pore spatial control problems faced in conventional scaffolds fabrication methods. SLS offers good user control over the scaffold's microstructures by adjusting its main processing parameters, namely the laser power, scan speed and part bed temperature. This research focuses on the improvements in the fabrication of TE scaffolds using SLS with powder biomaterials, namely hydroxyapatite (HA) and poly(vinyl alcohol) (PVA). Grinding of as-received PVA powder to varying particle sizes and two methods of mixing are investigated as the preparation process to determine a better mixing method that would enhance the mixture homogeneity. Suitable sintering conditions for the improved biocomposite are then achieved by varying the important process parameters such as laser power, scan speed and part bed temperature.SLS fabricated samples are characterized using Fourier Transform Infrared Spectrometer (FTIR) and Scanning Electron Microscope (SEM). FTIR results show that the grinding and sintering processes neither compromise the chemical composition of the PVA nor cause undue degradation. Visual analysis of the grinding, powder mixing and sintering effect are carried out with SEM. The SEM observations show improvements in the sintering effects. The favorable outcome ascertains PVA/HA biocomposite as a suitable material to be processed by SLS for TE scaffolds. PMID:17665112

  3. 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

  4. Heparin functionalized polyaspartamide/polyester scaffold for potential blood vessel regeneration.

    PubMed

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

    2014-05-01

    An interesting issue in tissue engineering is the development of a biodegradable vascular graft able to substitute a blood vessel and to allow its complete regeneration. Here, we report a new scaffold potentially useful as a synthetic vascular graft, produced through the electrospinning of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-D,L-aspartamide-graft-polylactic acid (PHEA-EDA-g-PLA) in the presence of polycaprolactone (PCL). The scaffold degradation profile has been evaluated as well as the possibility to bind heparin to electrospun fibers, being it a known anticoagulant molecule able to bind growth factors. In vitro cell compatibility has been investigated using human vascular endothelial cells (ECV 304) and the ability of heparinized PHEA-EDA-g-PLA/PCL scaffold to retain basic fibroblast growth factor has been evaluated in comparison with not heparinized sample.

  5. Recent advances in bone tissue engineering scaffolds

    PubMed Central

    Bose, Susmita; Roy, Mangal; Bandyopadhyay, Amit

    2012-01-01

    Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, biodegradable materials that harbor different growth factors, drugs, genes or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved. PMID:22939815

  6. Multilayered electrospun scaffolds for tendon tissue engineering.

    PubMed

    Chainani, Abby; Hippensteel, Kirk J; Kishan, Alysha; Garrigues, N William; Ruch, David S; Guilak, Farshid; Little, Dianne

    2013-12-01

    Full-thickness rotator cuff tears are one of the most common causes of shoulder pain in people over the age of 65. High retear rates and poor functional outcomes are common after surgical repair, and currently available extracellular matrix scaffold patches have limited abilities to enhance new tendon formation. In this regard, tissue-engineered scaffolds may provide a means to improve repair of rotator cuff tears. Electrospinning provides a versatile method for creating nanofibrous scaffolds with controlled architectures, but several challenges remain in its application to tissue engineering, such as cell infiltration through the full thickness of the scaffold as well as control of cell growth and differentiation. Previous studies have shown that ligament-derived extracellular matrix may enhance differentiation toward a tendon or ligament phenotype by human adipose stem cells (hASCs). In this study, we investigated the use of tendon-derived extracellular matrix (TDM)-coated electrospun multilayered scaffolds compared to fibronectin (FN) or phosphate-buffered saline (PBS) coating for use in rotator cuff tendon tissue engineering. Multilayered poly(ɛ-caprolactone) scaffolds were prepared by sequentially collecting electrospun layers onto the surface of a grounded saline solution into a single scaffold. Scaffolds were then coated with TDM, FN, or PBS and seeded with hASCs. Scaffolds were maintained without exogenous growth factors for 28 days in culture and evaluated for protein content (by immunofluorescence and biochemical assay), markers of tendon differentiation, and tensile mechanical properties. The collagen content was greatest by day 28 in TDM-scaffolds. Gene expression of type I collagen, decorin, and tenascin C increased over time, with no effect of scaffold coating. Sulfated glycosaminoglycan and dsDNA contents increased over time in culture, but there was no effect of scaffold coating. The Young's modulus did not change over time, but yield strain

  7. Cell–scaffold interaction within engineered tissue

    SciTech Connect

    Chen, Haiping; Liu, Yuanyuan Jiang, Zhenglong; Chen, Weihua; Yu, Yongzhe; Hu, Qingxi

    2014-05-01

    The structure of a tissue engineering scaffold plays an important role in modulating tissue growth. A novel gelatin–chitosan (Gel–Cs) scaffold with a unique structure produced by three-dimensional printing (3DP) technology combining with vacuum freeze-drying has been developed for tissue-engineering applications. The scaffold composed of overall construction, micro-pore, surface morphology, and effective mechanical property. Such a structure meets the essential design criteria of an ideal engineered scaffold. The favorable cell–matrix interaction supports the active biocompatibility of the structure. The structure is capable of supporting cell attachment and proliferation. Cells seeded into this structure tend to maintain phenotypic shape and secreted large amounts of extracellular matrix (ECM) and the cell growth decreased the mechanical properties of scaffold. This novel biodegradable scaffold has potential applications for tissue engineering based upon its unique structure, which acts to support cell growth. - Highlights: • The scaffold is not only for providing a surface for cell residence but also for determining cell phenotype and retaining structural integrity. • The mechanical property of scaffold can be affected by activities of cell. • The scaffold provides a microenvironment for cell attachment, growth, and migration.

  8. 1. GREAT NORTHERN ELEVATORS. 1900 STEEL ELEVATOR WITH SQUARE BINS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. GREAT NORTHERN ELEVATORS. 1900 STEEL ELEVATOR WITH SQUARE BINS (AS OPPOSED) TO THE SIMILAR STEEL ELEVATOR IN BUFFALO NEW YORK WITH ROUND ELEVATOR BINS. - Great Northern Elevator "S", Saint Louis Bay, Superior, Douglas County, WI

  9. Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications

    PubMed Central

    Yildirimer, Lara; Buanz, Asma; Gaisford, Simon; Malins, Edward L.; Remzi Becer, C.; Moiemen, Naiem; Reynolds, Gary M.; Seifalian, Alexander M.

    2015-01-01

    Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials’ viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications. PMID:26463421

  10. Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications.

    PubMed

    Yildirimer, Lara; Buanz, Asma; Gaisford, Simon; Malins, Edward L; Remzi Becer, C; Moiemen, Naiem; Reynolds, Gary M; Seifalian, Alexander M

    2015-10-14

    Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials' viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications.

  11. Finalizing the properties of porous scaffolds of aliphatic polyesters through radiation sterilization.

    PubMed

    Plikk, Peter; Odelius, Karin; Hakkarainen, Minna; Albertsson, A C

    2006-11-01

    Porous scaffolds made of various L,L-lactide (LLA), 1,5-dioxepane-2-one (DXO) and epsilon-caprolactone (CL) copolymers were sterilized by EB- and gamma-irradiation. Differences in the comonomers, composition and the microstructure of the starting materials were used to influence the degradation mechanism and susceptibility towards irradiation and by this means to achieve sterilized scaffolds with predicted end-properties. The chemical changes and the formation of low-molecular-weight products were determined by SEC, 1H nuclear magnetic resonance (NMR), 13C NMR and gas chromatography-mass spectrometry (GC-MS). The degradation mechanism changed from random chain scission to cross-linking depending on the choice of monomers, the copolymer composition and the monomer sequences. Copolymerization of LLA with small amounts of CL or DXO increased the stability compared to that of the LLA homopolymer. Changing DXO to CL in a LLA copolymer also increased the stability. The type of radiation and the microstructure of the copolymer chains determined which of the monomer sequences were more prone to degrade. The most abundant low-molecular-weight product identified after sterilization was DXO monomer. Traces of LLA and CL monomers were also identified. Modification of the copolyester microstructure changed the degradation mechanism and the susceptibility towards irradiation. This allows the use of radiation sterilization to finalize the scaffold properties. PMID:16846641

  12. Hydrolytic and oxidative degradation of electrospun supramolecular biomaterials: In vitro degradation pathways.

    PubMed

    Brugmans, M C P; Sӧntjens, S H M; Cox, M A J; Nandakumar, A; Bosman, A W; Mes, T; Janssen, H M; Bouten, C V C; Baaijens, F P T; Driessen-Mol, A

    2015-11-01

    The emerging field of in situ tissue engineering (TE) of load bearing tissues places high demands on the implanted scaffolds, as these scaffolds should provide mechanical stability immediately upon implantation. The new class of synthetic supramolecular biomaterial polymers, which contain non-covalent interactions between the polymer chains, thereby forming complex 3D structures by self assembly. Here, we have aimed to map the degradation characteristics of promising (supramolecular) materials, by using a combination of in vitro tests. The selected biomaterials were all polycaprolactones (PCLs), either conventional and unmodified PCL, or PCL with supramolecular hydrogen bonding moieties (either 2-ureido-[1H]-pyrimidin-4-one or bis-urea units) incorporated into the backbone. As these materials are elastomeric, they are suitable candidates for cardiovascular TE applications. Electrospun scaffold strips of these materials were incubated with solutions containing enzymes that catalyze hydrolysis, or solutions containing oxidative species. At several time points, chemical, morphological, and mechanical properties were investigated. It was demonstrated that conventional and supramolecular PCL-based polymers respond differently to enzyme-accelerated hydrolytic or oxidative degradation, depending on the morphological and chemical composition of the material. Conventional PCL is more prone to hydrolytic enzymatic degradation as compared to the investigated supramolecular materials, while, in contrast, the latter materials are more susceptible to oxidative degradation. Given the observed degradation pathways of the examined materials, we are able to tailor degradation characteristics by combining selected PCL backbones with additional supramolecular moieties. The presented combination of in vitro test methods can be employed to screen, limit, and select biomaterials for pre-clinical in vivo studies targeted to different clinical applications. PMID:26316031

  13. Hydrolytic and oxidative degradation of electrospun supramolecular biomaterials: In vitro degradation pathways.

    PubMed

    Brugmans, M C P; Sӧntjens, S H M; Cox, M A J; Nandakumar, A; Bosman, A W; Mes, T; Janssen, H M; Bouten, C V C; Baaijens, F P T; Driessen-Mol, A

    2015-11-01

    The emerging field of in situ tissue engineering (TE) of load bearing tissues places high demands on the implanted scaffolds, as these scaffolds should provide mechanical stability immediately upon implantation. The new class of synthetic supramolecular biomaterial polymers, which contain non-covalent interactions between the polymer chains, thereby forming complex 3D structures by self assembly. Here, we have aimed to map the degradation characteristics of promising (supramolecular) materials, by using a combination of in vitro tests. The selected biomaterials were all polycaprolactones (PCLs), either conventional and unmodified PCL, or PCL with supramolecular hydrogen bonding moieties (either 2-ureido-[1H]-pyrimidin-4-one or bis-urea units) incorporated into the backbone. As these materials are elastomeric, they are suitable candidates for cardiovascular TE applications. Electrospun scaffold strips of these materials were incubated with solutions containing enzymes that catalyze hydrolysis, or solutions containing oxidative species. At several time points, chemical, morphological, and mechanical properties were investigated. It was demonstrated that conventional and supramolecular PCL-based polymers respond differently to enzyme-accelerated hydrolytic or oxidative degradation, depending on the morphological and chemical composition of the material. Conventional PCL is more prone to hydrolytic enzymatic degradation as compared to the investigated supramolecular materials, while, in contrast, the latter materials are more susceptible to oxidative degradation. Given the observed degradation pathways of the examined materials, we are able to tailor degradation characteristics by combining selected PCL backbones with additional supramolecular moieties. The presented combination of in vitro test methods can be employed to screen, limit, and select biomaterials for pre-clinical in vivo studies targeted to different clinical applications.

  14. In vitro cartilage tissue engineering with 3D porous aqueous-derived silk scaffolds and mesenchymal stem cells.

    PubMed

    Wang, Yongzhong; Kim, Ung-Jin; Blasioli, Dominick J; Kim, Hyeon-Joo; Kaplan, David L

    2005-12-01

    Adult cartilage tissue has limited self-repair capacity, especially in the case of severe damages caused by developmental abnormalities, trauma, or aging-related degeneration like osteoarthritis. Adult mesenchymal stem cells (MSCs) have the potential to differentiate into cells of different lineages including bone, cartilage, and fat. In vitro cartilage tissue engineering using autologous MSCs and three-dimensional (3-D) porous scaffolds has the potential for the successful repair of severe cartilage damage. Ideally, scaffolds designed for cartilage tissue engineering should have optimal structural and mechanical properties, excellent biocompatibility, controlled degradation rate, and good handling characteristics. In the present work, a novel, highly porous silk scaffold was developed by an aqueous process according to these criteria and subsequently combined with MSCs for in vitro cartilage tissue engineering. Chondrogenesis of MSCs in the silk scaffold was evident by real-time RT-PCR analysis for cartilage-specific ECM gene markers, histological and immunohistochemical evaluations of cartilage-specific ECM components. Dexamethasone and TGF-beta3 were essential for the survival, proliferation and chondrogenesis of MSCs in the silk scaffolds. The attachment, proliferation, and differentiation of MSCs in the silk scaffold showed unique characteristics. After 3 weeks of cultivation, the spatial cell arrangement and the collagen type-II distribution in the MSCs-silk scaffold constructs resembles those in native articular cartilage tissue, suggesting promise for these novel 3-D degradable silk-based scaffolds in MSC-based cartilage repair. Further in vivo evaluation is necessary to fully recognize the clinical relevance of these observations.

  15. The Space Elevator

    NASA Astrophysics Data System (ADS)

    Laubscher, Bryan E.

    2005-09-01

    The Space Elevator is conceived to be a carbon nanotube ribbon stretching from an Earth station in the ocean on the equator to far beyond geosynchronous altitude. This elevator co-rotates with the Earth. Climbers ascend the ribbon using power beamed from Earth to launch spacecraft in orbit or to other worlds. The requirements of the ribbon material, challenges to the building of the space elevator, deployment and the promise of the space elevator are briefly discussed in this paper.

  16. The Potential of Encapsulating “Raw Materials” in 3D Osteochondral Gradient Scaffolds

    PubMed Central

    Mohan, Neethu; Gupta, Vineet; Sridharan, BanuPriya; Sutherland, Amanda; Detamore, Michael S.

    2015-01-01

    Scaffolds with continuous gradients in material composition and bioactive signals enable a smooth transition of properties at the interface. Components like chondroitin sulfate (CS) and bioactive glass (BG) in 3D scaffolds may serve as “raw materials” for synthesis of new extracellular matrix (ECM), and may have the potential to completely or partially replace expensive growth factors. We hypothesized that scaffolds with gradients of ECM components would enable superior performance of engineered constructs. Raw material encapsulation altered the appearance, structure, porosity, and degradation of the scaffolds. They allowed the scaffolds to better retain their 3D structure during culture and provided a buffering effect to the cells in culture. Following seeding of rat mesenchymal stem cells, there were several instances where glycosaminoglycan (GAG), collagen, or calcium contents were higher with the scaffolds containing raw materials (CS or BG) than with those containing transforming growth factor (TGF)-β3 or bone morphogenetic protein (BMP)-2. It was also noteworthy that a combination of both CS and TGF-β3 increased the secretion of collagen type II. Moreover, cells seeded in scaffolds containing opposing gradients of CS/TGF-β3 and BG/BMP-2 produced clear regional variations in the secretion of tissue-specific ECM. The study demonstrated raw materials have the potential to create a favorable microenvironment for cells; they can significantly enhance the synthesis of certain extracellular matrix (ECM) components when compared to expensive growth factors; either alone or in combination with growth factors they can enhance the secretion of tissue specific matrix proteins. Raw materials are promising candidates that can be used to either replace or be used in combination with growth factors. Success with raw materials in lieu of growth factors could have profound implications in terms of lower cost and faster regulatory approval for more rapid translation of

  17. Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold

    PubMed Central

    Lv, Y. M.; Yu, Q. S.

    2015-01-01

    Objectives The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. Methods The bone–cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid–hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. Results After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. Conclusion This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56–64 PMID:25837672

  18. Towards an ideal polymer scaffold for tendon/ligament tissue engineering

    NASA Astrophysics Data System (ADS)

    Sahoo, Sambit; Ouyang, Hong Wei; Goh, James Cho-Hong; Tay, Tong-Earn; Toh, Siew Lok

    2005-04-01

    Tissue engineering holds promise in treating injured tendons and ligaments by replacing the injured tissues with "engineered tissues" with identical mechanical and functional characteristics. A biocompatible, biodegradable, porous scaffold with optimized architecture, sufficient surface area for cell attachment, growth and proliferation, faborable mechanical properties, and suitable degradation rate is a pre-requisite to achieve success with this aproach. Knitted poly(lactide-co-glycolide) (PLGA) scaffolds comprising of microfibers of 25 micron diameter were coated with PLGA nanofibers on their surfaces by electrospinning technique. A cell suspension of pig bone marrow stromal cells (BMSC) was seeded on the scaffolds by pipetting, and the cell-scaffold constructs were cultured in a CO2 incubator, at 37°C for 1-2 weeks. The "engineered tissues" were then assessed for cell attachment and proliferation, tissue formation, and mechanical properties. Nanofibers, of diameter 300-900 nm, were spread randomly over the knitted scaffold. The reduction in pore-size from about 1 mm (in the knitted scaffold) to a few micrometers (in the nano-microscaffold) allowed cell seeding by direct pipetting, and eliminated the need of a cell-delivery system like fibrin gel. BMSCs were seen to attach and proliferate well on the nano-microscaffold, producing abundant extracellular matrix. Mechanical testing revealed that the cell-seeded nano-microscaffolds possessed slightly higher values of failure load, elastic-region stiffness and toe-region stiffness, than the unseeded scaffolds. The combination of superior mechanical strength and integrity of knitted microfibers, with the large surface area and improved hydrophilicity of the electrospun nanofibers facilitated cell attachment and new tissue formation. This holds promise in tissue engineering of tendon/ligament.

  19. A Transient Cell-Shielding Method for Viable MSC Delivery within Hydrophobic Scaffolds Polymerized In Situ

    PubMed Central

    Guo, Ruijing; Ward, Catherine L.; Davidson, Jeffrey M.; Duvall, Craig L.; Wenke, Joseph C.

    2015-01-01

    Cell-based therapies have emerged as promising approaches for regenerative medicine. Hydrophobic poly(ester urethane)s offer the advantages of robust mechanical properties, cell attachment without the use of peptides, and controlled degradation by oxidative and hydrolytic mechanisms. However, the application of injectable hydrophobic polymers to cell delivery is limited by the challenges of protecting cells from reaction products and creating a macroporous architecture post-cure. We designed injectable carriers for cell delivery derived from reactive, hydrophobic polyisocyanate and polyester triol precursors. To overcome cell death caused by reaction products from in situ polymerization, we encapsulated bone marrow-derived stem cells (BMSCs) in fast-degrading, oxidized alginate beads prior to mixing with the hydrophobic precursors. Cells survived the polymerization at >70% viability, and rapid dissolution of oxidized alginate beads after the scaffold cured created interconnected macropores that facilitated cellular adhesion to the scaffold in vitro. Applying this injectable system to deliver BMSCs to rat excisional skin wounds showed that the scaffolds supported survival of transplanted cells and infiltration of host cells, which improved new tissue formation compared to both implanted, pre-formed scaffolds seeded with cells and acellular controls. Our design is the first to enable injectable delivery of settable, hydrophobic scaffolds where cell encapsulation provides a mechanism for both temporary cytoprotection during polymerization and rapid formation of macropores post-polymerization. This simple approach provides potential advantages for cell delivery relative to hydrogel technologies, which have weaker mechanical properties and require incorporation of peptides to achieve cell adhesion and degradability. PMID:25907036

  20. Indirect three-dimensional printing: A method for fabricating polyurethane-urea based cardiac scaffolds.

    PubMed

    Hernández-Córdova, R; Mathew, D A; Balint, R; Carrillo-Escalante, H J; Cervantes-Uc, J M; Hidalgo-Bastida, L A; Hernández-Sánchez, F

    2016-08-01

    Biomaterial scaffolds are a key part of cardiac tissue engineering therapies. The group has recently synthesized a novel polycaprolactone based polyurethane-urea copolymer that showed improved mechanical properties compared with its previously published counterparts. The aim of this study was to explore whether indirect three-dimensional (3D) printing could provide a means to fabricate this novel, biodegradable polymer into a scaffold suitable for cardiac tissue engineering. Indirect 3D printing was carried out through printing water dissolvable poly(vinyl alcohol) porogens in three different sizes based on a wood-stack model, into which a polyurethane-urea solution was pressure injected. The porogens were removed, leading to soft polyurethane-urea scaffolds with regular tubular pores. The scaffolds were characterized for their compressive and tensile mechanical behavior; and their degradation was monitored for 12 months under simulated physiological conditions. Their compatibility with cardiac myocytes and performance in novel cardiac engineering-related techniques, such as aggregate seeding and bi-directional perfusion, was also assessed. The scaffolds were found to have mechanical properties similar to cardiac tissue, and good biocompatibility with cardiac myocytes. Furthermore, the incorporated cells preserved their phenotype with no signs of de-differentiation. The constructs worked well in perfusion experiments, showing enhanced seeding efficiency. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1912-1921, 2016. PMID:26991636

  1. Graphene-based electroresponsive scaffolds as polymeric implants for on-demand drug delivery.

    PubMed

    Servant, Ania; Leon, Veronica; Jasim, Dhifaf; Methven, Laura; Limousin, Patricia; Fernandez-Pacheco, Ester Vazquez; Prato, Maurizio; Kostarelos, Kostas

    2014-08-01

    Stimuli-responsive biomaterials have attracted significant attention in the field of polymeric implants designed as active scaffolds for on-demand drug delivery. Conventional porous scaffolds suffer from drawbacks such as molecular diffusion and material degradation, allowing in most cases only a zero-order drug release profile. The possibility of using external stimulation to trigger drug release is particularly enticing. In this paper, the fabrication of previously unreported graphene hydrogel hybrid electro-active scaffolds capable of controlled small molecule release is presented. Pristine ball-milled graphene sheets are incorporated into a three dimensional macroporous hydrogel matrix to obtain hybrid gels with enhanced mechanical, electrical, and thermal properties. These electroactive scaffolds demonstrate controlled drug release in a pulsatile fashion upon the ON/OFF application of low electrical voltages, at low graphene concentrations (0.2 mg mL(-1) ) and by maintaining their structural integrity. Moreover, the in vivo performance of these electroactive scaffolds to release drug molecules without any "resistive heating" is demonstrated. In this study, an illustration of how the heat dissipating properties of graphene can provide significant and previously unreported advantages in the design of electroresponsive hydrogels, able to maintain optimal functionality by overcoming adverse effects due to unwanted heating, is offered.

  2. Graphene-based electroresponsive scaffolds as polymeric implants for on-demand drug delivery.

    PubMed

    Servant, Ania; Leon, Veronica; Jasim, Dhifaf; Methven, Laura; Limousin, Patricia; Fernandez-Pacheco, Ester Vazquez; Prato, Maurizio; Kostarelos, Kostas

    2014-08-01

    Stimuli-responsive biomaterials have attracted significant attention in the field of polymeric implants designed as active scaffolds for on-demand drug delivery. Conventional porous scaffolds suffer from drawbacks such as molecular diffusion and material degradation, allowing in most cases only a zero-order drug release profile. The possibility of using external stimulation to trigger drug release is particularly enticing. In this paper, the fabrication of previously unreported graphene hydrogel hybrid electro-active scaffolds capable of controlled small molecule release is presented. Pristine ball-milled graphene sheets are incorporated into a three dimensional macroporous hydrogel matrix to obtain hybrid gels with enhanced mechanical, electrical, and thermal properties. These electroactive scaffolds demonstrate controlled drug release in a pulsatile fashion upon the ON/OFF application of low electrical voltages, at low graphene concentrations (0.2 mg mL(-1) ) and by maintaining their structural integrity. Moreover, the in vivo performance of these electroactive scaffolds to release drug molecules without any "resistive heating" is demonstrated. In this study, an illustration of how the heat dissipating properties of graphene can provide significant and previously unreported advantages in the design of electroresponsive hydrogels, able to maintain optimal functionality by overcoming adverse effects due to unwanted heating, is offered. PMID:24799416

  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. Biomimetic poly(lactide) based fibrous scaffolds for ligament tissue engineering.

    PubMed

    Surrao, Denver C; Waldman, Stephen D; Amsden, Brian G

    2012-11-01

    The aim of this study was to fabricate a fibrous scaffold that closely resembled the micro-structural architecture and mechanical properties of collagen fibres found in the anterior cruciate ligament (ACL). To achieve this aim, fibrous scaffolds were made by electrospinning L-lactide based polymers. L-Lactide was chosen primarily due to its demonstrated biocompatibility, biodegradability and high modulus. The electrospun fibres were collected in tension on a rotating wire mandrel. Upon treating these fibres in a heated aqueous environment, they possessed a crimp-like pattern having a wavelength and amplitude similar to that of native ACL collagen. Of the polymer fibre scaffolds studied, those made from poly(L-lactide-co-D,L-lactide) PLDLA exhibited the highest modulus and were also the most resilient to in vitro hydrolytic degradation, undergoing a slight decrease in modulus compared to the other polymeric fibres over a 6 month period. Bovine fibroblasts seeded on the wavy, crimp-like PLDLA fibres attached, proliferated and deposited extracellular matrix (ECM) molecules on the surface of the fibrous scaffold. In addition, the deposited ECM exhibited bundle formation that resembled the fascicles found in native ACL. These findings demonstrate the importance of replicating the geometric microenvironment in developing effective tissue engineering scaffolds. PMID:22828380

  5. Engineering of a polymer layered bio-hybrid heart valve scaffold.

    PubMed

    Jahnavi, S; Kumary, T V; Bhuvaneshwar, G S; Natarajan, T S; Verma, R S

    2015-06-01

    Current treatment strategy for end stage valve disease involves either valvular repair or replacement with homograft/mechanical/bioprosthetic valves. In cases of recurrent stenosis/ regurgitation, valve replacement is preferred choice of treatment over valvular repair. Currently available mechanical valves primarily provide durability whereas bioprosthetic valves have superior tissue compatibility but both lack remodelling and regenerative properties making their utility limited in paediatric patients. With advances in tissue engineering, attempts have been made to fabricate valves with regenerative potential using various polymers, decellularized tissues and hybrid scaffolds. To engineer an ideal heart valve, decellularized bovine pericardium extracellular matrix (DBPECM) is an attractive biocompatible scaffold but has weak mechanical properties and rapid degradation. However, DBPECM can be modified with synthetic polymers to enhance its mechanical properties. In this study, we developed a Bio-Hybrid scaffold with non-cross linked DBPECM in its native structure coated with a layer of Polycaprolactone-Chitosan (PCL-CH) nanofibers that displayed superior mechanical properties. Surface and functional studies demonstrated integration of PCL-CH to the DBPECM with enhanced bio and hemocompatibility. This engineered Bio-Hybrid scaffold exhibited most of the physical, biochemical and functional properties of the native valve that makes it an ideal scaffold for fabrication of cardiac valve with regenerative potential. PMID:25842134

  6. Engineering of a polymer layered bio-hybrid heart valve scaffold.

    PubMed

    Jahnavi, S; Kumary, T V; Bhuvaneshwar, G S; Natarajan, T S; Verma, R S

    2015-06-01

    Current treatment strategy for end stage valve disease involves either valvular repair or replacement with homograft/mechanical/bioprosthetic valves. In cases of recurrent stenosis/ regurgitation, valve replacement is preferred choice of treatment over valvular repair. Currently available mechanical valves primarily provide durability whereas bioprosthetic valves have superior tissue compatibility but both lack remodelling and regenerative properties making their utility limited in paediatric patients. With advances in tissue engineering, attempts have been made to fabricate valves with regenerative potential using various polymers, decellularized tissues and hybrid scaffolds. To engineer an ideal heart valve, decellularized bovine pericardium extracellular matrix (DBPECM) is an attractive biocompatible scaffold but has weak mechanical properties and rapid degradation. However, DBPECM can be modified with synthetic polymers to enhance its mechanical properties. In this study, we developed a Bio-Hybrid scaffold with non-cross linked DBPECM in its native structure coated with a layer of Polycaprolactone-Chitosan (PCL-CH) nanofibers that displayed superior mechanical properties. Surface and functional studies demonstrated integration of PCL-CH to the DBPECM with enhanced bio and hemocompatibility. This engineered Bio-Hybrid scaffold exhibited most of the physical, biochemical and functional properties of the native valve that makes it an ideal scaffold for fabrication of cardiac valve with regenerative potential.

  7. Characterization of Silk Fibroin/Chitosan 3D Porous Scaffold and In Vitro Cytology

    PubMed Central

    Zeng, Shuguang; Liu, Lei; Shi, Yong; Qiu, Junqi; Fang, Wei; Rong, Mingdeng; Guo, Zehong; Gao, Wenfeng

    2015-01-01

    Bone tissue engineering is a powerful tool to treat bone defects caused by trauma, infection, tumors and other factors. Both silk fibroin (SF) and chitosan (CS) are non-toxic and have good biocompatibility, but are poor biological scaffolds when used alone. In this study, the microscopic structure and related properties of SF/CS composite scaffolds with different component ratios were examined. The scaffold material most suitable for osteoblast growth was determined, and these results offer an experimental basis for the future reconstruction of bone defects. First, via freeze-drying and chemical crosslinking methods, SF/CS composites with different component ratios were prepared and their structure was characterized. Changes in the internal structure of the SF and CS mixture were observed, confirming that the mutual modification between the two components was complete and stable. The internal structure of the composite material was porous and three-dimensional with a porosity above 90%. We next studied the pore size, swelling ratio, water absorption ratio, degradation and in vitro cell proliferation. For the 40% SF-60% CS group, the pore size of the scaffold was suitable for the growth of osteoblasts, and the rate of degradation was steady. This favors the early adhesion, growth and proliferation of MG-63 cells. In addition to good biocompatibility and satisfactory cell affinity, this material promotes the secretion of extracellular matrix materials by osteoblasts. Thus, 40% SF-60% CS is a good material for bone tissue engineering. PMID:26083846

  8. Carbon nanotubes as vaccine scaffolds

    PubMed Central

    Scheinberg, David A.; McDevitt, Michael R.; Dao, Tao; Mulvey, Justin J.; Feinberg, Evan; Alidori, Simone

    2013-01-01

    Carbon nanotubes display characteristics that are potentially useful in their development as scaffolds for vaccine compositions. These features include stability in vivo, lack of intrinsic immunogenicity, low toxicity, and the ability to be appended with multiple copies of antigens. In addition, the particulate nature of carbon nanotubes and their unusual properties of rapid entry into antigen-presenting cells, such as dendritic cells, make them especially useful as carriers of antigens. Early attempts demonstrating carbon nanotube-based vaccines can be used in both infectious disease settings and cancer are promising. PMID:23899863

  9. Chromosome Scaffold is a Double-Stranded Assembly of Scaffold Proteins

    PubMed Central

    Poonperm, Rawin; Takata, Hideaki; Hamano, Tohru; Matsuda, Atsushi; Uchiyama, Susumu; Hiraoka, Yasushi; Fukui, Kiichi

    2015-01-01

    Chromosome higher order structure has been an enigma for over a century. The most important structural finding has been the presence of a chromosome scaffold composed of non-histone proteins; so-called scaffold proteins. However, the organization and function of the scaffold are still controversial. Here, we use three dimensional-structured illumination microscopy (3D-SIM) and focused ion beam/scanning electron microscopy (FIB/SEM) to reveal the axial distributions of scaffold proteins in metaphase chromosomes comprising two strands. We also find that scaffold protein can adaptably recover its original localization after chromosome reversion in the presence of cations. This reversion to the original morphology underscores the role of the scaffold for intrinsic structural integrity of chromosomes. We therefore propose a new structural model of the chromosome scaffold that includes twisted double strands, consistent with the physical properties of chromosomal bending flexibility and rigidity. Our model provides new insights into chromosome higher order structure. PMID:26132639

  10. Direct Ink Writing of Highly Porous and Strong Glass Scaffolds for Load-bearing Bone Defects Repair and Regeneration

    PubMed Central

    Fu, Qiang; Saiz, Eduardo; Tomsia, Antoni P.

    2011-01-01

    The quest for synthetic materials to repair load-bearing bone lost because of trauma, cancer, or congenital bone defects requires development of porous and high-performance scaffolds with exceptional mechanical strength. However, the low mechanical strength of porous bioactive ceramic and glass scaffolds, compared with that of human cortical bone, has limited their use for these applications. In the present work, bioactive 6P53B glass scaffolds with superior mechanical strength were fabricated using a direct ink writing technique. The rheological properties of Pluronic® F-127 (referred to hereafter simply as F-127) hydrogel-based inkswere optimized for the printing of features as fine as 30 μm and of the three-dimensional scaffolds. The mechanical strength and in vitro degradation of the scaffolds were assessed in a simulated body fluid (SBF). The sintered glass scaffolds show a compressive strength (136 ± 22 MPa) comparable to that of human cortical bone (100-150 MPa), while the porosity (60%) is in the range of that of trabecular bone (50-90%).The strength is ~100 times that of polymer scaffolds and 4–5 times that of ceramic and glass scaffolds with comparable porosities. Despite the strength decrease resulting from weight loss during immersion in an SBF, the value (77 MPa) is still far above that of trabecular bone after three weeks. The ability to create both porous and strong structures opens a new avenue for fabricating scaffolds for load-bearing bone defect repair and regeneration. PMID:21745606

  11. The application of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds for tendon repair in the rat model.

    PubMed

    Webb, William R; Dale, Tina P; Lomas, Alex J; Zeng, Guodong; Wimpenny, Ian; El Haj, Alicia J; Forsyth, Nicholas R; Chen, Guo-Qiang

    2013-09-01

    Tendon injuries and defects present a substantial burden to global healthcare economies. There are no synthetic/biosynthesised implants available which can restore full function or match the mechanical properties of native tendon. Therefore, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) was investigated for its utility as a scaffold in a rat Achilles tendon repair model. Porous PHBHHx tubes and fibres were prepared with particle leaching and extrusion methods, respectively. Collagen gels reinforced by polymer fibres were inserted into the lumen of scaffold tubes to create the operational scaffold unit. Mechanical testing demonstrated that PHBHHx scaffolds had comparable mechanical properties to rat tendon, with maximal loads of 23.73 ± 1.08 N, compared to 17.35 ± 1.76 N in undamaged rat Achilles tendon. Sprague-Dawley (SD) rats were split into four experimental groups: control, PHBHHx scaffold only, PHBHHx scaffold and collagen, PHBHHx scaffold, collagen and tenocyte compositions for implantation to repair an induced Achilles tendon defect. No secondary immune response to PHBHHx was observed over a 40 days period of implantation. Movement was restored in PHBHHx scaffold-collagen-tenocyte recipient rats at an earlier time point than in other experimental groups, with complete load-bearing and function returning 20 days post-surgery as determined by the Achilles Functional Index. In vitro testing of tendon constructs after 40 days demonstrated reductions in PHBHHx molecular weight and polydispersity index accompanied by an increase in mean chain length indicating degradation of smaller polymer chain subunits. Similarly a reduction in PHBHHx tube ultimate tensile strength and elastic modulus was observed. Histological analysis provided evidence of tissue remodelling and cell alignment. In summary, PHBHHx scaffolds have been successfully applied in an in vivo tendon repair model raising promise for future utility in tissue engineering applications.

  12. New poly(ester urea) derived from L-leucine: electrospun scaffolds loaded with antibacterial drugs and enzymes.

    PubMed

    Díaz, Angélica; del Valle, Luis J; Tugushi, David; Katsarava, Ramaz; Puiggalí, Jordi

    2015-01-01

    Electrospun scaffolds from an amino acid containing poly(ester urea) (PEU) were developed as promising materials in the biomedical field and specifically in tissue engineering applications. The selected poly(ester urea) was obtained with a high yield and molecular weight by reaction of phosgene with a bis(α-aminoacyl)-α,ω-diol-diester monomer. The polymer having L-leucine, 1,6-hexanediol and carbonic acid units had a semicrystalline character and relatively high glass transition and melting temperatures. Furthermore it was highly soluble in most organic solvents, an interesting feature that facilitated the electrospinning process and the effective incorporation of drugs with bactericidal activity (e.g. biguanide derivatives such as clorhexidine and polyhexamethylenebiguanide) and enzymes (e.g. α-chymotrypsin) that accelerated the degradation process. Continuous micro/nanofibers were obtained under a wide range of processing conditions, being diameters of electrospun fibers dependent on the drug and solvent used. Poly(ester urea) samples were degradable in media containing lipases and proteinases but the degradation rate was highly dependent on the surface area, being specifically greater for scaffolds with respect to films. The high hydrophobicity of new scaffolds had repercussions on enzymatic degradability since different weight loss rates were found depending on how samples were exposed to the medium (e.g. forced or non-forced immersion). New scaffolds were biocompatible, as demonstrated by adhesion and proliferation assays performed with fibroblast and epithelial cells.

  13. Composite scaffolds for cartilage tissue engineering.

    PubMed

    Moutos, Franklin T; Guilak, Farshid

    2008-01-01

    Tissue engineering remains a promising therapeutic strategy for the repair or regeneration of diseased or damaged tissues. Previous approaches have typically focused on combining cells and bioactive molecules (e.g., growth factors, cytokines and DNA fragments) with a biomaterial scaffold that functions as a template to control the geometry of the newly formed tissue, while facilitating the attachment, proliferation, and differentiation of embedded cells. Biomaterial scaffolds also play a crucial role in determining the functional properties of engineered tissues, including biomechanical characteristics such as inhomogeneity, anisotropy, nonlinearity or viscoelasticity. While single-phase, homogeneous materials have been used extensively to create numerous types of tissue constructs, there continue to be significant challenges in the development of scaffolds that can provide the functional properties of load-bearing tissues such as articular cartilage. In an attempt to create more complex scaffolds that promote the regeneration of functional engineered tissues, composite scaffolds comprising two or more distinct materials have been developed. This paper reviews various studies on the development and testing of composite scaffolds for the tissue engineering of articular cartilage, using techniques such as embedded fibers and textiles for reinforcement, embedded solid structures, multi-layered designs, or three-dimensionally woven composite materials. In many cases, the use of composite scaffolds can provide unique biomechanical and biological properties for the development of functional tissue engineering scaffolds.

  14. Information Scaffolding: Application to Technical Animation

    ERIC Educational Resources Information Center

    Newman, Catherine Claire

    2010-01-01

    Information Scaffolding is a user-centered approach to information design; a method devised to aid "everyday" authors in information composition. Information Scaffolding places a premium on audience-centered documents by emphasizing the information needs and motivations of a multimedia document's intended audience. The aim of this…

  15. Recombinant protein scaffolds for tissue engineering.

    PubMed

    Werkmeister, Jerome A; Ramshaw, John A M

    2012-02-01

    New biological materials for tissue engineering are now being developed using common genetic engineering capabilities to clone and express a variety of genetic elements that allow cost-effective purification and scaffold fabrication from these recombinant proteins, peptides or from chimeric combinations of these. The field is limitless as long as the gene sequences are known. The utility is dependent on the ease, product yield and adaptability of these protein products to the biomedical field. The development of recombinant proteins as scaffolds, while still an emerging technology with respect to commercial products, is scientifically superior to current use of natural materials or synthetic polymer scaffolds, in terms of designing specific structures with desired degrees of biological complexities and motifs. In the field of tissue engineering, next generation scaffolds will be the key to directing appropriate tissue regeneration. The initial period of biodegradable synthetic scaffolds that provided shape and mechanical integrity, but no biological information, is phasing out. The era of protein scaffolds offers distinct advantages, particularly with the combination of powerful tools of molecular biology. These include, for example, the production of human proteins of uniform quality that are free of infectious agents and the ability to make suitable quantities of proteins that are found in low quantity or are hard to isolate from tissue. For the particular needs of tissue engineering scaffolds, fibrous proteins like collagens, elastin, silks and combinations of these offer further advantages of natural well-defined structural scaffolds as well as endless possibilities of controlling functionality by genetic manipulation.

  16. Teaching Writing: A Multilayered Participatory Scaffolding Practice

    ERIC Educational Resources Information Center

    Dix, Stephanie

    2016-01-01

    This article adds to the research on teachers' writing pedagogy. It reviews and challenges the research literature on scaffolding as an instructional practice and presents a more inclusive framework for analysis. As student participation and voice were absent from much of the literature, a participatory scaffolding framework was developed to…

  17. Lithographically defined 3-dimensional graphene scaffolds

    NASA Astrophysics Data System (ADS)

    Burckel, D. Bruce; Xiao, Xiaoyin; Polsky, Ronen

    2015-09-01

    Interferometrically defined 3D photoresist scaffolds are formed through a series of three successive two-beam interference exposures, a post exposure bake and development. Heating the resist scaffold in a reducing atmosphere to > 1000 °C, results in the conversion of the resist structure into a carbon scaffold through pyrolysis, resulting in a 3D sp3- bonded glassy carbon scaffold which maintains the same in-plane morphology as the resist despite significant shrinkage. The carbon scaffolds are readily modified using a variety of deposition methods such as electrochemical, sputtering and CVD/ALD. Remarkably, sputtering metal into scaffolds with ~ 5 unit cells tall results in conformal coating of the scaffold with the metal. When the metal is a transition metal such as nickel, the scaffold can be re-annealed, during which time the carbon diffuses through the nickel, emerging on the exterior of the nickel as sp2-bonded carbon, termed 3D graphene. This paper details the fabrication, characterization and some potential applications for these structures.

  18. A Conceptualisation of Whole-Class Scaffolding

    ERIC Educational Resources Information Center

    Smit, Jantien; van Eerde, Henriëtte A. A.; Bakker, Arthur

    2013-01-01

    The concept of scaffolding refers to temporary and adaptive support, originally in dyadic adult-child interaction. It has become widely used, also in whole-class settings, but often in loose ways. The aim of this paper is to theoretically and empirically ground a conceptualisation of whole-class scaffolding so that it remains close to the origin…

  19. Metacognitive Scaffolding in an Innovative Learning Arrangement

    ERIC Educational Resources Information Center

    Molenaar, Inge; van Boxtel, Carla A. M.; Sleegers, Peter J. C.

    2011-01-01

    This study examined the effects of metacognitive scaffolds on learning outcomes of collaborating students in an innovative learning arrangement. The triads were supported by computerized scaffolds, which were dynamically integrated into the learning process and took a structuring or problematizing form. In an experimental design the two…

  20. Scaffolding Mathematical Modelling with a Solution Plan

    ERIC Educational Resources Information Center

    Schukajlow, Stanislaw; Kolter, Jana; Blum, Werner

    2015-01-01

    In the study presented in this paper, we examined the possibility to scaffold mathematical modelling with strategies. The strategies were prompted using an instrument called "solution plan" as a scaffold. The effects of this step by step instrument on mathematical modelling competency and on self-reported strategies were tested using…

  1. Understanding Literacy Teacher Educators' Use of Scaffolding

    ERIC Educational Resources Information Center

    Many, Joyce E.; Aoulou, Eudes

    2014-01-01

    This inquiry examined four literacy teacher educators' perspectives and practices as related to scaffolding by using document analysis (i.e. syllabus), observations, and interviews. Findings indicated these teacher educators used scaffolding to develop preservice teachers' dispositions, strategies, and conceptual understandings. Faculty used…

  2. Cell colonization in degradable 3D porous matrices

    PubMed Central

    Lawrence, Benjamin J

    2008-01-01

    Cell colonization is an important in a wide variety of biological processes and applications including vascularization, wound healing, tissue engineering, stem cell differentiation and biosensors. During colonization porous 3D structures are used to support and guide the ingrowth of cells into the matrix. In this review, we summarize our understanding of various factors affecting cell colonization in three-dimensional environment. The structural, biological and degradation properties of the matrix all play key roles during colonization. Further, specific scaffold properties such as porosity, pore size, fiber thickness, topography and scaffold stiffness as well as important cell material interactions such as cell adhesion and mechanotransduction also influence colonization. PMID:19262124

  3. Cell culture and characterization of cross-linked poly(vinyl alcohol)-g-starch 3D scaffold for tissue engineering.

    PubMed

    Hsieh, Wen-Chuan; Liau, Jiun-Jia

    2013-10-15

    The research goal of this experiment is chemically to cross-link poly(vinyl alcohol) (PVA) and starch to form a 3D scaffold that is effective water absorbent, has a stable structure, and supports cell growth. PVA and starch can be chemically cross-linked to form a PVA-g-starch 3D scaffold polymer, as observed by Fourier transform infrared spectroscopy (FTIR), with an absorbency of up to 800%. Tensile testing reveals that, as the amount of starch increases, the strength of the 3D scaffold strength reaches 4×10(-2) MPa. Scanning electron microscope (SEM) observations of the material reveal that the 3D scaffold is highly porous formed using a homogenizer at 500 rpm. In an enzymatic degradation, the 3D scaffold was degraded by various enzymes at a rate of up to approximately 30-60% in 28 days. In vitro tests revealed that cells proliferate and grow in the 3D scaffold material. Energy dispersive spectrometer (EDS) analysis further verified that the bio-compatibility of this scaffold. PMID:23987384

  4. Silk scaffolds for musculoskeletal tissue engineering

    PubMed Central

    Yao, Danyu

    2015-01-01

    The musculoskeletal system, which includes bone, cartilage, tendon/ligament, and skeletal muscle, is becoming the targets for tissue engineering because of the high need for their repair and regeneration. Numerous factors would affect the use of musculoskeletal tissue engineering for tissue regeneration ranging from cells used for scaffold seeding to the manufacture and structures of materials. The essential function of the scaffolds is to convey growth factors as well as cells to the target site to aid the regeneration of the injury. Among the variety of biomaterials used in scaffold engineering, silk fibroin is recognized as an ideal material for its impressive cytocompatibility, slow biodegradability, and excellent mechanical properties. The current review describes the advances made in the fabrication of silk fibroin scaffolds with different forms such as films, particles, electrospun fibers, hydrogels, three-dimensional porous scaffolds, and their applications in the regeneration of musculoskeletal tissues. PMID:26445979

  5. Thermally drawn fibers as nerve guidance scaffolds.

    PubMed

    Koppes, Ryan A; Park, Seongjun; Hood, Tiffany; Jia, Xiaoting; Abdolrahim Poorheravi, Negin; Achyuta, Anilkumar Harapanahalli; Fink, Yoel; Anikeeva, Polina

    2016-03-01

    Synthetic neural scaffolds hold promise to eventually replace nerve autografts for tissue repair following peripheral nerve injury. Despite substantial evidence for the influence of scaffold geometry and dimensions on the rate of axonal growth, systematic evaluation of these parameters remains a challenge due to limitations in materials processing. We have employed fiber drawing to engineer a wide spectrum of polymer-based neural scaffolds with varied geometries and core sizes. Using isolated whole dorsal root ganglia as an in vitro model system we have identified key features enhancing nerve growth within these fiber scaffolds. Our approach enabled straightforward integration of microscopic topography at the scale of nerve fascicles within the scaffold cores, which led to accelerated Schwann cell migration, as well as neurite growth and alignment. Our findings indicate that fiber drawing provides a scalable and versatile strategy for producing nerve guidance channels capable of controlling direction and accelerating the rate of axonal growth. PMID:26717246

  6. Thermally drawn fibers as nerve guidance scaffolds.

    PubMed

    Koppes, Ryan A; Park, Seongjun; Hood, Tiffany; Jia, Xiaoting; Abdolrahim Poorheravi, Negin; Achyuta, Anilkumar Harapanahalli; Fink, Yoel; Anikeeva, Polina

    2016-03-01

    Synthetic neural scaffolds hold promise to eventually replace nerve autografts for tissue repair following peripheral nerve injury. Despite substantial evidence for the influence of scaffold geometry and dimensions on the rate of axonal growth, systematic evaluation of these parameters remains a challenge due to limitations in materials processing. We have employed fiber drawing to engineer a wide spectrum of polymer-based neural scaffolds with varied geometries and core sizes. Using isolated whole dorsal root ganglia as an in vitro model system we have identified key features enhancing nerve growth within these fiber scaffolds. Our approach enabled straightforward integration of microscopic topography at the scale of nerve fascicles within the scaffold cores, which led to accelerated Schwann cell migration, as well as neurite growth and alignment. Our findings indicate that fiber drawing provides a scalable and versatile strategy for producing nerve guidance channels capable of controlling direction and accelerating the rate of axonal growth.

  7. Functional Electrospun Nanofibrous Scaffolds for Biomedical Applications

    PubMed Central

    Liang, Dehai; Hsiao, Benjamin S.; Chu, Benjamin

    2009-01-01

    Functional nanofibrous scaffolds produced by electrospinning have great potential in many biomedical applications, such as tissue engineering, wound dressing, enzyme immobilization and drug (gene) delivery. For a specific successful application, the chemical, physical and biological properties of electrospun scaffolds should be adjusted to match the environment by using a combination of multi-component compositions and fabrication techniques where electrospinning has often become a pivotal tool. The property of the nanofibrous scaffold can be further improved with innovative development in electrospinning processes, such as two-component electrospinning and in-situ mixing electrospinning. Post modifications of electrospun membranes also provide effective means to render the electrospun scaffolds with controlled anisotropy and porosity. In this review, we review the materials, techniques and post modification methods to functionalize electrospun nanofibrous scaffolds suitable for biomedical applications. PMID:17884240

  8. Silk scaffolds for musculoskeletal tissue engineering.

    PubMed

    Yao, Danyu; Liu, Haifeng; Fan, Yubo

    2016-02-01

    The musculoskeletal system, which includes bone, cartilage, tendon/ligament, and skeletal muscle, is becoming the targets for tissue engineering because of the high need for their repair and regeneration. Numerous factors would affect the use of musculoskeletal tissue engineering for tissue regeneration ranging from cells used for scaffold seeding to the manufacture and structures of materials. The essential function of the scaffolds is to convey growth factors as well as cells to the target site to aid the regeneration of the injury. Among the variety of biomaterials used in scaffold engineering, silk fibroin is recognized as an ideal material for its impressive cytocompatibility, slow biodegradability, and excellent mechanical properties. The current review describes the advances made in the fabrication of silk fibroin scaffolds with different forms such as films, particles, electrospun fibers, hydrogels, three-dimensional porous scaffolds, and their applications in the regeneration of musculoskeletal tissues.

  9. Electrophoretic deposition of porous hydroxyapatite scaffold.

    PubMed

    Ma, J; Wang, C; Peng, K W

    2003-09-01

    Bioactive porous hydroxyapatite (HA) scaffold was fabricated using electrophoretic deposition (EPD) technique in the present work. Bulk HA scaffold was achieved by repeated deposition. The green scaffold was sintered at 1200 degrees C to 82% of the theoretical density. Scanning electron microscopy examination and mercury porosimetry measurement have shown that the porosity remains interconnected and a range of pore size from several microns to hundreds of microns was obtained. X-ray diffraction analysis was performed and confirmed that there is no HA decomposition during the sintering process. Mechanical characterization has also shown that the EPD scaffold possesses excellent properties. Cell culturing experiment was carried out and the result shows that the scaffold bioactivity is not only dependent on the interconnectivity of the pores, but also the pore size.

  10. Proton transfer in organic scaffolds

    NASA Astrophysics Data System (ADS)

    Basak, Dipankar

    This dissertation focuses on the fundamental understanding of the proton transfer process and translating the knowledge into design/development of new organic materials for efficient non-aqueous proton transport. For example, what controls the shuttling of a proton between two basic sites? a) Distance between two groups? or b) the basicity? c) What is the impact of protonation on molecular conformation when the basic sites are attached to rigid scaffolds? For this purpose, we developed several tunable proton sponges and studied proton transfer in these scaffolds theoretically as well as experimentally. Next we moved our attention to understand long-range proton conduction or proton transport. We introduced liquid crystalline (LC) proton conductor based on triphenylene molecule and established that activation energy barrier for proton transport is lower in the LC phase compared to the crystalline phase. Furthermore, we investigated the impact of several critical factors: the choice of the proton transferring groups, mobility of the charge carriers, intrinsic vs. extrinsic charge carrier concentrations and the molecular architectures on long-range proton transport. The outcome of this research will lead to a deeper understanding of non-aqueous proton transfer process and aid the design of next generation proton exchange membrane (PEM) for fuel cell.

  11. Scaffolds from alternating block polyurethanes of poly(ɛ-caprolactone) and poly(ethylene glycol) with stimulation and guidance of nerve growth and better nerve repair than autograft.

    PubMed

    Niu, Yuqing; Li, Linjing; Chen, Kevin C; Chen, Feiran; Liu, Xiangyu; Ye, Jianfu; Li, Wei; Xu, Kaitian

    2015-07-01

    Nerve repair scaffolds from novel alternating block polyurethanes (PUCL-alt-PEG) based on PCL and PEG without additional growth factors or proteins were prepared by a particle leaching method. The scaffolds have pore size 10-20 µm and porosity 92%. Mechanical tests showed that the polyurethane scaffolds have maximum loads of 5.97 ± 0.35 N and maximal stresses of 8.84 ± 0.5 MPa. Histocompatiblity of the nerve repair scaffolds was tested in a SD rat model for peripheral nerve defect treatment. Two types of treatments including PUCL-alt-PEG scaffolds and autografts were compared in rat model. After 32 weeks, bridging of a 12 mm defect gap by the regenerated nerve was observed in all rats. The nerve regeneration was systematically characterized by sciatic function index (SFI), electrophysiology, histological assessment including HE staining, immunohistochemistry, ammonia sliver staining, Masson's trichrome staining and TEM observation. Results revealed that nerve repair scaffolds from PUCL-alt-PEG exhibit better regeneration effects compared to autografts. Electrophysiological recovery was seen in 90% and 87% of rats in PUCL-alt-PEG and autograft groups respectively. Biodegradation in vitro and in vivo shows good degradation match of PUCL-alt-PEG scaffolds with nerve regeneration. It demonstrates that plain nerve repair scaffolds from PUCL-alt-PEG biomaterials can achieve peripheral nerve regeneration satisfactorily.

  12. Mechanical properties and drug release behavior of PCL/zein coated 45S5 bioactive glass scaffolds for bone tissue engineering application.

    PubMed

    Fereshteh, Zeinab; Nooeaid, Patcharakamon; Fathi, Mohammadhossein; Bagri, Akbar; Boccaccini, Aldo R

    2015-09-01

    This article presents data related to the research article entitled "The effect of coating type on mechanical properties and controlled drug release of PCL/zein coated 45S5 bioactive glass scaffolds for bone tissue engineering" [1]. We provide data on mechanical properties, in vitro bioactivity and drug release of bioactive glass (BG) scaffolds coated by poly (ε-caprolactone) (PCL) and zein used as a controlled release device for tetracycline hydrochloride (TCH). By coating the BG scaffolds with PCL or PCL/zein blend the mechanical properties of the scaffolds were substantially improved, i.e., the compressive strength increased from 0.004±0.001 MPa (uncoated BG scaffolds) to 0.15±0.02 MPa (PCL/zein coated BG scaffolds). A dense bone-like apatite layer formed on the surface of PCL/zein coated scaffolds immersed for 14 days in simulated body fluid (SBF). The data describe control of drug release and in vitro degradation behavior of coating by engineering the concentration of zein. Thus, the developed scaffolds exhibit attractive properties for application in bone tissue engineering research.

  13. Polysaccharide Degradation

    NASA Astrophysics Data System (ADS)

    Stone, Bruce A.; Svensson, Birte; Collins, Michelle E.; Rastall, Robert A.

    An overview of current and potential enzymes used to degrade polysaccharides is presented. Such depolymerases are comprised of glycoside hydrolases, glycosyl transferases, phosphorylases and lyases, and their classification, active sites and action patterns are discussed. Additionally, the mechanisms that these enzymes use to cleave glycosidic linkages is reviewed as are inhibitors of depolymerase activity; reagents which react with amino acid residues, glycoside derivatives, transition state inhibitors and proteinaceous inhibitors. The characterization of various enzymes of microbial, animal or plant origin has led to their widespread use in the production of important oligosaccharides which can be incorporated into food stuffs. Sources of polysaccharides of particular interest in this chapter are those from plants and include inulin, dextran, xylan and pectin, as their hydrolysis products are purported to be functional foods in the context of gastrointestinal health. An alternative use of degraded polysaccharides is in the treatment of disease. The possibility exists to treat bacterial exopolysaccharide with lyases from bacteriophage to produce oligosaccharides exhibiting bioactive sequences. Although this area is currently in its infancy the knowledge is available to investigate further.

  14. 54. West elevation of portion of elevated Mainline structure (Section ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    54. West elevation of portion of elevated Mainline structure (Section F-5) over Washington Street - looking East - at the corner of Bray Street. - Boston Elevated Railway, Elevated Mainline, Washington Street, Boston, Suffolk County, MA

  15. 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.

  16. 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.

  17. Full-course inhibition of biodegradation-induced inflammation in fibrous scaffold by loading enzyme-sensitive prodrug.

    PubMed

    Pan, Guoqing; Liu, Shen; Zhao, Xin; Zhao, Jingwen; Fan, Cunyi; Cui, Wenguo

    2015-06-01

    Biodegradation-induced inflammation in biodegradable scaffold materials is a critical problem to be addressed due to its potential inducement to tissue necrosis, granulomas, or tumor genesis. Here, a facile strategy for on-demand release of anti-inflammatory drugs and full-course inhibition of degradation-induced inflammation was demonstrated by simply loading an esterase-sensitive prodrug into a fibrous scaffold. In this study, drug release from the prodrug-loaded scaffolds showed an enzyme-triggered release process, which led to an initial moderate release of anti-inflammatory drugs and a later-stage degradation-synchronized drug release. This unique release kinetics ingeniously achieved on-demand drug therapy and efficient inhibition of inflammation throughout the biodegradation in vivo. More importantly, the prodrug-loaded scaffolds prepared with different biodegradable polymers (i.e., different biodegradation rates) all showed drug release kinetics that matched to the biodegradation rates and full-course inhibition of inflammation in vivo. Therefore, this method offered a general approach for on-demand release of anti-inflammatory drugs and efficient inhibition of inflammation throughout the biodegradation of different polymeric scaffolds. In addition, the release kinetics in our system showed potentials for "batch release" of multiple drugs in combination therapies as well as provided a feasible hint for the drug therapies of some other symptoms caused by in vivo biodegradation.

  18. 30 CFR 57.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Scaffolds and working platforms. 57.11027... and Escapeways Travelways-Surface Only § 57.11027 Scaffolds and working platforms. Scaffolds and... condition. Floorboards shall be laid properly and the scaffolds and working platform shall not be...

  19. 30 CFR 57.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Scaffolds and working platforms. 57.11027... and Escapeways Travelways-Surface Only § 57.11027 Scaffolds and working platforms. Scaffolds and... condition. Floorboards shall be laid properly and the scaffolds and working platform shall not be...

  20. 30 CFR 56.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Scaffolds and working platforms. 56.11027... § 56.11027 Scaffolds and working platforms. Scaffolds and working platforms shall be of substantial... and the scaffolds and working platforms shall not be overloaded. Working platforms shall be...

  1. 30 CFR 56.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Scaffolds and working platforms. 56.11027... § 56.11027 Scaffolds and working platforms. Scaffolds and working platforms shall be of substantial... and the scaffolds and working platforms shall not be overloaded. Working platforms shall be...

  2. 30 CFR 56.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Scaffolds and working platforms. 56.11027... § 56.11027 Scaffolds and working platforms. Scaffolds and working platforms shall be of substantial... and the scaffolds and working platforms shall not be overloaded. Working platforms shall be...

  3. 30 CFR 57.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Scaffolds and working platforms. 57.11027... and Escapeways Travelways-Surface Only § 57.11027 Scaffolds and working platforms. Scaffolds and... condition. Floorboards shall be laid properly and the scaffolds and working platform shall not be...

  4. 30 CFR 57.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Scaffolds and working platforms. 57.11027... and Escapeways Travelways-Surface Only § 57.11027 Scaffolds and working platforms. Scaffolds and... condition. Floorboards shall be laid properly and the scaffolds and working platform shall not be...

  5. 30 CFR 56.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Scaffolds and working platforms. 56.11027... § 56.11027 Scaffolds and working platforms. Scaffolds and working platforms shall be of substantial... and the scaffolds and working platforms shall not be overloaded. Working platforms shall be...

  6. 30 CFR 56.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Scaffolds and working platforms. 56.11027... § 56.11027 Scaffolds and working platforms. Scaffolds and working platforms shall be of substantial... and the scaffolds and working platforms shall not be overloaded. Working platforms shall be...

  7. 30 CFR 57.11027 - Scaffolds and working platforms.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Scaffolds and working platforms. 57.11027... and Escapeways Travelways-Surface Only § 57.11027 Scaffolds and working platforms. Scaffolds and... condition. Floorboards shall be laid properly and the scaffolds and working platform shall not be...

  8. Scaffolds in vascular regeneration: current status

    PubMed Central

    Thottappillil, Neelima; Nair, Prabha D

    2015-01-01

    An ideal vascular substitute, especially in <6 mm diameter applications, is a major clinical essentiality in blood vessel replacement surgery. Blood vessels are structurally complex and functionally dynamic tissue, with minimal regeneration potential. These have composite extracellular matrix (ECM) and arrangement. The interplay between ECM components and tissue specific cells gives blood vessels their specialized functional attributes. The core of vascular tissue engineering and regeneration relies on the challenges in creating vascular conduits that match native vessels and adequately regenerate in vivo. Out of numerous vascular regeneration concerns, the relevance of ECM emphasizes much attention toward appropriate choice of scaffold material and further scaffold development strategies. The review is intended to be focused on the various approaches of scaffold materials currently in use in vascular regeneration and current state of the art. Scaffold of choice in vascular tissue engineering ranges from natural to synthetic, decellularized, and even scaffold free approach. The applicability of tubular scaffold for in vivo vascular regeneration is under active investigation. A patent conduit with an ample endothelial luminal layer that can regenerate in vivo remains an unanswered query in the field of small diameter vascular tissue engineering. Besides, scaffolds developed for vascular regeneration, should aim at providing functional substitutes for use in a regenerative approach from the laboratory bench to patient bedside. PMID:25632236

  9. Scaffold devices for rotator cuff repair.

    PubMed

    Ricchetti, Eric T; Aurora, Amit; Iannotti, Joseph P; Derwin, Kathleen A

    2012-02-01

    Rotator cuff tears affect 40% or more of those aged older than 60 years, and repair failure rates of 20% to 70% remain a significant clinical challenge. Hence, there is a need for repair strategies that can augment the repair by mechanically reinforcing it, while at the same time biologically enhancing the intrinsic healing potential of the tendon. Tissue engineering strategies to improve rotator cuff repair healing include the use of scaffolds, growth factors, and cell seeding, or a combination of these approaches. Currently, scaffolds derived from mammalian extracellular matrix, synthetic polymers, and a combination thereof, have been cleared by the U.S. Food and Drug Administration and are marketed as medical devices for rotator cuff repair in humans. Despite the growing clinical use of scaffold devices for rotator cuff repair, there are numerous questions related to their indication, surgical application, safety, mechanism of action, and efficacy that remain to be clarified or addressed. This article reviews the current basic science and clinical understanding of commercially available synthetic and extracellular matrix scaffolds for rotator cuff repair. Our review will emphasize the host response and scaffold remodeling, mechanical and suture-retention properties, and preclinical and clinical studies on the use of these scaffolds for rotator cuff repair. We will discuss the implications of these data on the future directions for use of these scaffolds in tendon repair procedures.

  10. Biomimetic nanofibrous scaffolds for bone tissue engineering

    PubMed Central

    Holzwarth, Jeremy M.; Ma, Peter X.

    2011-01-01

    Bone tissue engineering is a highly interdisciplinary field that seeks to tackle the most challenging bone-related clinical issues. The major components of bone tissue engineering are the scaffold, cells, and growth factors. This review will focus on the scaffold and recent advancements in developing scaffolds that can mimic the natural extracellular matrix of bone. Specifically, these novel scaffolds mirror the nanofibrous collagen network that comprises the majority of the non-mineral portion of bone matrix. Using two main fabrication techniques, electrospinning and thermally-induced phase separation, and incorporating bone-like minerals, such as hydroxyapatite, composite nanofibrous scaffolds can improve cell adhesion, stem cell differentiation, and tissue formation. This review will cover the two main processing techniques and how they are being applied to fabricate scaffolds for bone tissue engineering. It will then cover how these scaffolds can enhance the osteogenic capabilities of a variety of cell types and survey the ability of the constructs to support the growth of clinically relevant bone tissue. PMID:21944829

  11. Effects of sterilisation method on surface topography and in-vitro cell behaviour of electrostatically spun scaffolds.

    PubMed

    Andrews, Kirstie D; Hunt, John A; Black, Richard A

    2007-02-01

    Electrostatic spinning is a potentially significant technique for scaffold production within the field of tissue engineering; however, the effect of sterilisation upon these structures is not known. This research investigated the extent of any topographical alteration to electrostatically spun scaffolds post-production through sterilisation, and examined any subsequent effect on contacting cells. Scaffolds made from Tecoflex SG-80A polyurethane were sterilised using ethylene oxide and UV-ozone. Scaffold topography was characterized in terms of inter-fibre separation (ifs), fibre diameter (f.dia) and surface roughness. Cell culture was performed over 7 days with both mouse L929 and human embryonic lung fibroblasts, the results of which were assessed using SEM, image analysis and confocal microscopy. Sterilisation by UV-ozone and ethylene oxide decreased ifs and increased f.dia; surface roughness was decreased by UV-ozone but increased by ethylene oxide. Possible mechanisms to explain these observations are discussed, namely photo-oxidative degradation in the case of UV-ozone and process-induced changes in surface roughness. UV-ozone sterilised scaffolds showed greater cell coverage than those treated with ethylene oxide, but lower coverage than all the controls. Changes in cell attachment and morphology were thought to be due to the changes in topography brought about by the sterilisation process. We conclude that surface modification by sterilisation could prove to be a useful tool at the final stage of scaffold production to enhance cell contact, phenotype or function.

  12. Three-dimensional zinc incorporated borosilicate bioactive glass scaffolds for rodent critical-sized calvarial defects repair and regeneration.

    PubMed

    Wang, Hui; Zhao, Shichang; Xiao, Wei; Cui, Xu; Huang, Wenhai; Rahaman, Mohamed N; Zhang, Changqing; Wang, Deping

    2015-06-01

    The biomaterials with high osteogenic ability are being intensively investigated. In this study, we evaluated the bioactivity and osteogenesis of BG-Zn scaffolds in vitro and in vivo with a rodent calvarial defects model. Zinc containing borosilicate bioactive glass was prepared by doping glass with 1.5, 5 and 10 wt.% ZnO (denoted as BG-1.5Zn, BG-5Zn and BG-10Zn, respectively). When immersed in simulated body fluid, dopant ZnO retarded the degradation process, but did not affect the formation of hydroxyapatite (HA) after long-period soaking. BG-Zn scaffolds showed controlled release of Zn ions into the medium for over 8 weeks. Human bone marrow derived stem cells (hBMSCs) attached well on the BG-1.5Zn and BG-5Zn scaffolds, which exhibited no cytotoxicity to hBMSCs. In addition, the alkaline phosphatase activity of the hBMSCs increased with increasing dopant amount in the glass, while the BG-10Zn group showed over-dose of Zn. Furthermore, when implanted in rat calvarial defects for 8 weeks, the BG-5Zn scaffolds showed a significantly better capacity to regenerate bone tissue compared to the non-doping scaffolds. Generally, these results showed the BG-Zn scaffolds with high osteogenic capacity will be promising candidates using in bone tissue repair and regeneration.

  13. Constitution and in vivo test of micro-porous tubular scaffold for esophageal tissue engineering.

    PubMed

    Hou, Lei; Jin, Jiachang; Lv, Jingjing; Chen, Ling; Zhu, Yabin; Liu, Xingyu

    2015-11-01

    Current clinical techniques in treating long-gap esophageal defects often lead to complications and high morbidity. Aiming at long-gap synthetic esophageal substitute, we had synthesized a biodegradable copolymer, poly(L-lactide-co-caprolactone) (PLLC), with low glass transition temperature. In this work, we developed a tubular PLLC porous scaffold using a self-designed tubular mold and thermal induced phase separation (TIPS) method. In order to enhance the interaction between tissue and scaffold, fibrin, a natural fibrous protein derived from blood fibrinogen, was coated on the scaffold circumferential surface. The fibrin density was measured to be 1.23 ± 0.04 mg/cm(2). Primary epithelial cell culture demonstrated the improved in vitro biocompatibility. In animal study with partial scaffold implantation, in situ mucosa regeneration was observed along the degradation of the scaffold. These indicate that fibrin incorporated PLLC scaffold can greatly improve epithelial regeneration in esophagus repair, therefore serve as a good candidate for long-term evaluation of post-implantation at excision site.

  14. The National Map - Elevation

    USGS Publications Warehouse

    Gesch, Dean; Evans, Gayla; Mauck, James; Hutchinson, John; Carswell, William J.

    2009-01-01

    The National Elevation Dataset (NED) is the primary elevation data product produced and distributed by the USGS. The NED provides seamless raster elevation data of the conterminous United States, Alaska, Hawaii, and the island territories. The NED is derived from diverse source data sets that are processed to a specification with a consistent resolution, coordinate system, elevation units, and horizontal and vertical datums. The NED is the logical result of the maturation of the long-standing USGS elevation program, which for many years concentrated on production of topographic map quadrangle-based digital elevation models. The NED serves as the elevation layer of The National Map, and provides basic elevation information for earth science studies and mapping applications in the United States. The NED is a multi-resolution dataset that is updated bimonthly to integrate newly available, improved elevation source data. NED data are available nationally at grid spacings of 1 arc-second (approximately 30 meters) for the conterminous United States, and at 1/3 and 1/9 arc-seconds (approximately 10 and 3 meters, respectively) for parts of the United States. Most of the NED for Alaska is available at 2-arc-second (about 60 meters) grid spacing, where only lower resolution source data exist. Part of Alaska is available at the 1/3-arc-second resolution, and plans are in development for a significant upgrade in elevation data coverage of the State over the next 5 years. Specifications for the NED include the following: *Coordinate system: Geographic (decimal degrees of latitude and longitude), *Horizontal datum: North American Datum of 1983 (NAD 83), *Vertical datum: North American Vertical Datum of 1988 (NAVD 88) over the conterminous United States and varies in other areas, and *Elevation units: Decimal meters.

  15. In vitro evaluation of bi-layer silk fibroin scaffolds for gastrointestinal tissue engineering

    PubMed Central

    Franck, Debra; Chung, Yeun Goo; Coburn, Jeannine; Kaplan, David L; Estrada, Carlos R

    2014-01-01

    Silk fibroin scaffolds were investigated for their ability to support attachment, proliferation, and differentiation of human gastrointestinal epithelial and smooth muscle cell lines in order to ascertain their potential for tissue engineering. A bi-layer silk fibroin matrix composed of a porous silk fibroin foam annealed to a homogeneous silk fibroin film was evaluated in parallel with small intestinal submucosa scaffolds. AlamarBlue analysis revealed that silk fibroin scaffolds supported significantly higher levels of small intestinal smooth muscle cell, colon smooth muscle cell, and esophageal smooth muscle cell attachment in comparison to small intestinal submucosa. Following 7 days of culture, relative numbers of each smooth muscle cell population maintained on both scaffold groups were significantly elevated over respective 1-day levels—indicative of cell proliferation. Real-time reverse transcription polymerase chain reaction and immunohistochemical analyses demonstrated that both silk fibroin and small intestinal submucosa scaffolds were permissive for contractile differentiation of small intestinal smooth muscle cell, colon smooth muscle cell, esophageal smooth muscle cell as determined by significant upregulation of α-smooth muscle actin and SM22α messenger RNA and protein expression levels following transforming growth factor-β1 stimulation. AlamarBlue analysis demonstrated that both matrix groups supported similar degrees of attachment and proliferation of gastrointestinal epithelial cell lines including colonic T84 cells and esophageal epithelial cells. Following 14 days of culture on both matrices, spontaneous differentiation of T84 cells toward an enterocyte lineage was confirmed by expression of brush border enzymes, lactase, and maltase, as determined by real-time reverse transcription polymerase chain reaction and immunohistochemical analyses. In contrast to small intestinal submucosa scaffolds, silk fibroin scaffolds supported

  16. Electrospinning of Bioinspired Polymer Scaffolds.

    PubMed

    Araujo, Jose V; Carvalho, Pedro P; Best, Serena M

    2015-01-01

    Electrospinning is a technique used in the production of polymer nanofibre meshes. The use of biodegradable and biocompatible polymers to produce nanofibres that closely mimic the extracellular matrix (ECM) of different tissues has opened a wide range of possibilities for the application of electrospinning in Tissue Engineering. It is believed that nano-features (such as voids and surface cues) present in nanofibre mesh scaffolds, combined with the chemical composition of the fibres, can stimulate cell attachment, growth and differentiation. Despite the widespread use of electrospun nanofibres in tissue engineering, the present chapter will focus on the advances made in the utilisation of these materials in bone, cartilage and tooth related applications. Several aspects will be taken into consideration, namely the choice of polymers, the surface modification of the nanofibres in order to achieve mineralisation, and also the biological application of such materials. PMID:26545743

  17. Cell penetration to nanofibrous scaffolds

    PubMed Central

    Rampichová, Michala; Buzgo, Matej; Chvojka, Jiří; Prosecká, Eva; Kofroňová, Olga; Amler, Evžen

    2014-01-01

    Cell infiltration is a critical parameter for the successful development of 3D matrices for tissue engineering. Application of electrospun nanofibers in tissue engineering has recently attracted much attention. Notwithstanding several of their advantages, small pore size and small thickness of the electrospun layer limit their application for development of 3D scaffolds. Several methods for the pore size and/or electrospun layer thickness increase have been recently developed. Nevertheless, tissue engineering still needs emerging of either novel nanofiber-enriched composites or new techniques for 3D nanofiber fabrication. Forcespinning® seems to be a promising alternative. The potential of the Forcespinning® method is illustrated in preliminary experiment with mesenchymal stem cells. PMID:24429388

  18. Electrospinning of Bioinspired Polymer Scaffolds.

    PubMed

    Araujo, Jose V; Carvalho, Pedro P; Best, Serena M

    2015-01-01

    Electrospinning is a technique used in the production of polymer nanofibre meshes. The use of biodegradable and biocompatible polymers to produce nanofibres that closely mimic the extracellular matrix (ECM) of different tissues has opened a wide range of possibilities for the application of electrospinning in Tissue Engineering. It is believed that nano-features (such as voids and surface cues) present in nanofibre mesh scaffolds, combined with the chemical composition of the fibres, can stimulate cell attachment, growth and differentiation. Despite the widespread use of electrospun nanofibres in tissue engineering, the present chapter will focus on the advances made in the utilisation of these materials in bone, cartilage and tooth related applications. Several aspects will be taken into consideration, namely the choice of polymers, the surface modification of the nanofibres in order to achieve mineralisation, and also the biological application of such materials.

  19. Ionic solutes impact collagen scaffold bioactivity.

    PubMed

    Pawelec, K M; Husmann, A; Wardale, R J; Best, S M; Cameron, R E

    2015-02-01

    The structure of ice-templated collagen scaffolds is sensitive to many factors. By adding 0.5 wt% of sodium chloride or sucrose to collagen slurries, scaffold structure could be tuned through changes in ice growth kinetics and interactions of the solute and collagen. With ionic solutes (sodium chloride) the entanglements of the collagen molecule decreased, leading to fibrous scaffolds with increased pore size and decreased attachment of chondrocytes. With non-ionic solutes (sucrose) ice growth was slowed, leading to significantly reduced pore size and up-regulated cell attachment. This highlights the large changes in structure and biological function stimulated by solutes in ice-templating systems. PMID:25649518

  20. Using glucosamine to improve the properties of photocrosslinked gelatin scaffolds.

    PubMed

    Suo, Hairui; Xu, Kedi; Zheng, Xiaoxiang

    2015-02-01

    The use of hydrogel-based cell transport scaffolds holds great promise in regenerative medicine, such as treating osteoarthritis. Gelatin and glucosamine are the ideal materials to be used in the hydrogel scaffolds for cartilage regeneration for they could act as compositions of cartilage. To overcome the weak strength of traditional gelatin hydrogels and down-regulate cell toxicity of glucosamine, gelatin and glucosamine molecules were grafted with acrylate groups and covalently crosslinked under photo-radiation to form hydrogels. Hydrogels with tuning physiochemical properties were produced according to different proportions of methacrylate gelatin (GelMA) and N-acryloyl glucosamine (AGA). The process of photocrosslinking was elaborated, and the hypothesis of increasing AGA concentration leading to higher strength of hydrogels was corroborated by testing rheological property and scanning micro-morphological features. A serial of properties, including smaller swelling ratio, lower gelatin dissolution and slower degradation of GelMA/AGA hydrogels with higher AGA concentration further proved our hypothesis. Moreover, AGA molecules showed less cytotoxicity than unmodified glucosamine molecules and the incorporation of AGA molecules in GelMA/AGA hydrogels upregulated cell adhesion and spreading on the hydrogel surface. All of these results indicated that addition of AGA molecules could significantly alter the physiochemical properties of GelMA/AGA hydrogels, which may have broad application prospects in the future.

  1. Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration

    PubMed Central

    Zhang, Xingdi; Zeng, Deliang; Li, Nan; Wen, Jin; Jiang, Xinquan; Liu, Changsheng; Li, Yongsheng

    2016-01-01

    Mesoporous bioactive glass (MBG), which possesses excellent bioactivity, biocompatibility and osteoconductivity, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with high compressive strength for applications in bone regeneration; this difficulty has greatly hindered its development and use. To solve this problem, a simple powder processing technique has been successfully developed to fabricate a novel type of MBG scaffold (MBGS). Furthermore, amino or carboxylic groups could be successfully grafted onto MBGSs (denoted as N-MBGS and C-MBGS, respectively) through a post-grafting process. It was revealed that both MBGS and the functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bMSCs. Due to its positively charged surface, N-MBGS presented the highest in vitro osteogenic capability of the three samples. Moreover, in vivo testing results demonstrated that N-MBGS could promote higher levels of bone regeneration compared with MBGS and C-MBGS. In addition to its surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in promoting bone regeneration. These findings indicate that MBGSs are promising materials with potential practical applications in bone regeneration, which can be successfully fabricated by combining a powder processing technique and post-grafting process. PMID:26763311

  2. Nanofibrous poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate) scaffolds provide a functional microenvironment for cartilage repair.

    PubMed

    Ching, Kuan Y; Andriotis, Orestis G; Li, Siwei; Basnett, Pooja; Su, Bo; Roy, Ipsita; Tare, Rahul S; Sengers, Bram G; Stolz, Martin

    2016-07-01

    Articular cartilage defects, when repaired ineffectively, often lead to further deterioration of the tissue, secondary osteoarthritis and, ultimately, jo