| Preparation of chitosan scaffolds with a hierarchical porous structure.
January 22, 2010 at 10:56 PM
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| | Preparation of chitosan scaffolds with a hierarchical porous structure. J Biomed Mater Res B Appl Biomater. 2010 Jan 20; Authors: Ko YG, Kawazoe N, Tateishi T, Chen G Development of porous scaffolds with open surface pore structures is required for tissue engineering to deliver cells into the three-dimensional spaces in the scaffolds and improve cell distribution. This study demonstrated a new type of funnel-like chitosan sponge prepared using ice particulates as a template. The funnel-like chitosan sponges had a hierarchical bilayer porous structure of a surface layer and an interconnected bulk porous layer. The top surface porous layer consisted mainly of large open pores. The bulk porous layer was beneath the large surface pores and consisted of small pores that were connected with the large surface pores. The large surface pores were dependent on the shape, dimension, and density of the embossing ice particulates, while the bulk pores were dependent on the freezing temperature. The large open surface pores and interconnected bulk pores in the funnel-like chitosan sponges facilitated cell seeding and cell distribution from t! he surface into the inner bulk pores. Cells cultured in the funnel-like chitosan sponges showed high viability, high proliferation, and homogenous tissue formation. Such funnel-like chitosan sponges will be useful for tissue engineering. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20091925 [PubMed - as supplied by publisher] | | |
| Ceramic scaffolds produced by computer-assisted 3D printing and sintering: Characterization and biocompatibility investigations.
January 22, 2010 at 10:56 PM
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| | Ceramic scaffolds produced by computer-assisted 3D printing and sintering: Characterization and biocompatibility investigations. J Biomed Mater Res B Appl Biomater. 2010 Jan 20; Authors: Warnke PH, Seitz H, Warnke F, Becker ST, Sivananthan S, Sherry E, Liu Q, Wiltfang J, Douglas T Hydroxyapatite (HAP) and tricalcium phosphate (TCP) are two very common ceramic materials for bone replacement. However, in general HAP and TCP scaffolds are not tailored to the exact dimensions of the defect site and are mainly used as granules or beads. Some scaffolds are available as ordinary blocks, but cannot be customized for individual perfect fit. Using computer-assisted 3D printing, an emerging rapid prototyping technique, individual three-dimensional ceramic scaffolds can be built up from TCP or HAP powder layer by layer with subsequent sintering. These scaffolds have precise dimensions and highly defined and regular internal characteristics such as pore size. External shape and internal characteristics such as pore size can be fabricated using Computer Assisted Design (CAD) based on individual patient data. Thus, these scaffolds could be designed as perfect fit replacements to reconstruct the patient's skeleton. Before their use as bone replacement mate! rials in vivo, in vitro testing of these scaffolds is necessary. In this study, the behavior of human osteoblasts on HAP and TCP scaffolds was investigated. The commonly used bone replacement material BioOss(R) served as control. Biocompatibility was assessed by scanning electron microscopy (SEM), fluorescence microscopy after staining for cell vitality with fluorescin diacetate (FDA) and propidium iodide (PI) and the MTT, LDH, and WST biocompatibility tests. Both versions were colonised by human osteoblasts, however more cells were seen on HAP scaffolds than TCP scaffolds. Cell vitality staining and MTT, LDH, and WST tests showed superior biocompatibility of HAP scaffolds to BioOss(R), while BioOss(R) was more compatible than TCP. Further experiments are necessary to determine biocompatibility in vivo. Future modifications of 3D printed scaffolds offer advantageous features for Tissue Engineering. The integration of channels could allow for vascular and nerve ingrowth into! the scaffold. Also the complex shapes of convex and concave a! rticulat ing joint surfaces maybe realized with these rapid prototyping techniques. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20091914 [PubMed - as supplied by publisher] | | |
| Mechanical, permeability, and degradation properties of 3D designed poly(1,8 octanediol-co-citrate) scaffolds for soft tissue engineering.
January 22, 2010 at 10:56 PM
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| | Mechanical, permeability, and degradation properties of 3D designed poly(1,8 octanediol-co-citrate) scaffolds for soft tissue engineering. J Biomed Mater Res B Appl Biomater. 2010 Jan 20; Authors: Jeong CG, Hollister SJ Poly(1,8-octanediol-co-citric acid) (POC) is a synthetic biodegradable elastomer that can be processed into three-dimensional (3D) scaffolds for tissue engineering. We investigated the effect of designed porosity on the mechanical properties, permeability, and degradation profiles of the POC scaffolds. For mechanical properties, scaffold compressive data were fitted to a one-dimensional (1D) nonlinear elastic model, and solid tensile data were fitted to a Neohookean incompressible nonlinear elastic model. Chondrocytes were seeded on scaffolds to assess the biocompatibility of POC. Increased porosity was associated with increased degradation rate, increased permeability, and decreased mechanical stiffness, which also became less nonlinear. Scaffold characterization in this article will provide design guidance for POC scaffolds to meet the mechanical and biological parameters needed for engineering soft tissues such as cartilage. (c) 2010 Wiley Periodicals, Inc. J B! iomed Mater Res Part B: Appl Biomater, 2010. PMID: 20091910 [PubMed - as supplied by publisher] | | |
| Culture human mesenchymal stem cells with calcium phosphate cement scaffolds for bone repair.
January 22, 2010 at 10:56 PM
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| | Culture human mesenchymal stem cells with calcium phosphate cement scaffolds for bone repair. J Biomed Mater Res B Appl Biomater. 2010 Jan 20; Authors: Weir MD, Xu HH Because of its moldability and excellent osteoconductivity, calcium phosphate cement (CPC) is highly promising for craniofacial and orthopedic applications. The objectives of this study were to investigate the response of human mesenchymal stem cells (hMSCs) to a high-strength CPC-chitosan scaffold and to examine cell proliferation and osteogenic differentiation. hMSCs were seeded onto CPC-chitosan composite, CPC control, and tissue culture polystyrene (TCPS). Alkaline phosphatase activity (ALP) and mineralization of hMSCs were measured. CPC-chitosan had a flexural strength (mean +/- SD; n = 5) of (19.5 +/- 1.4) MPa, higher than (8.0 +/- 1.4) MPa of CPC control (p < 0.05). The percentage of live hMSCs on CPC-chitosan was (90.5 +/- 1.3)% at 8 days, matching (90.7 +/- 3.8)% of CPC control (p > 0.1). The CPC-chitosan surface area covered by the attached hMSCs increased from (51 +/- 11)% at 1 day to (90 +/- 4)% at 8 days (p < 0.05), matching those of CPC cont! rol (p > 0.1). Hence, the CPC strength was significantly increased via chitosan without compromising the hMSC response. At 8 days, there was a significant increase in ALP of cells in osteogenic media (10.99 +/- 0.93) [(mM pNpp/min)/(mug DNA)] versus control media (3.62 +/- 0.40) (p < 0.05). hMSCs in osteogenic media exhibited greater mineralization area of (47.5 +/- 19.7)% compared with (6.1 +/- 2.3)% in control medium on TCPS (p < 0.05). In conclusion, hMSCs showed excellent attachment and viability on the strong and tough CPC-chitosan scaffold, matching the hMSC response on CPC control. hMSCs were successfully differentiated down the osteogenic lineage. Hence, the strong, in situ hardening CPC-chitosan scaffold may be useful as a moderate load-bearing vehicle to deliver hMSCs for maxillofacial and orthopedic bone tissue engineering. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20091907 [PubMed - as supplied by publisher] | | |
| Poly(lactide-co-glycolide)/titania composite microsphere-sintered scaffolds for bone tissue engineering applications.
January 22, 2010 at 10:56 PM
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| | Poly(lactide-co-glycolide)/titania composite microsphere-sintered scaffolds for bone tissue engineering applications. J Biomed Mater Res B Appl Biomater. 2010 Jan 20; Authors: Wang Y, Shi X, Ren L, Yao Y, Zhang F, Wang DA The objective of this study was to synthesize and characterize novel three-dimensional porous scaffolds made of poly(lactic-co-glycolic acid) (PLGA)/nano-TiO(2)-particle composite microspheres for potential bone repair applications. The introduction of TiO(2) component has been proven capable of largely enhancing mechanical properties of PLGA/TiO(2) microsphere-sintered scaffold ("PLGA/TiO(2)-SMS"). In addition, composite nano-TiO(2) additives are capable of inducing an increased arrest of adhesive proteins from the environment, which benefits cell attachment onto the scaffolds. Osteoblast proliferation and maturation were evaluated by MTT assay, alkaline phosphatase (ALP) activity, and bony calcification assay. The results indicate that osteoblasts cultured on the composite scaffolds with different TiO(2) content (0, 0.1, and 0.3 g/1 g PLGA) display increased cell proliferation compared with pure PLGA scaffold. When cultured on composite scaffolds, osteoblasts al! so exhibit significantly enhanced ALP activity and higher calcium secretion, with respect to those on the pure PLGA scaffolds. Taken together, PLGA/TiO(2)-SMSs deserve attention utilizing for potential bone-repairing therapeutics. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20091906 [PubMed - as supplied by publisher] | | |
| Molecular biomimetics: GEPI-based biological routes to technology.
January 22, 2010 at 10:56 PM
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| | Molecular biomimetics: GEPI-based biological routes to technology. Biopolymers. 2010 Jan 20;94(1):78-94 Authors: Tamerler C, Khatayevich D, Gungormus M, Kacar T, Oren EE, Hnilova M, Sarikaya M In nature, the viability of biological systems is sustained via specific interactions among the tens of thousands of proteins, the major building blocks of organisms from the simplest single-celled to the most complex multicellular species. Biomolecule-material interaction is accomplished with molecular specificity and efficiency leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, Mother Nature developed molecular recognition by successive cycles of mutation and selection. Molecular specificity of probe-target interactions, e.g., ligand-receptor, antigen-antibody, is always based on specific peptide molecular recognition. Using biology as a guide, we can now understand, engineer, and control peptide-material interactions and exploit them as a new design tool for novel materials and systems. We adapted the protocols of combinatorially designed peptide libraries, via both cell surface or phage di! splay methods; using these we select short peptides with specificity to a variety of practical materials. These genetically engineered peptides for inorganics (GEPI) are then studied experimentally to establish their binding kinetics and surface stability. The bound peptide structure and conformations are interrogated both experimentally and via modeling, and self-assembly characteristics are tested via atomic force microscopy. We further engineer the peptide binding and assembly characteristics using a computational biomimetics approach where bioinformatics based peptide-sequence similarity analysis is developed to design higher generation function-specific peptides. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems in a wide-range of applications from tissue engineering, disease diagnostics, and therapeutics to various areas of nanotechnology where integration is required among inorganic, organic and! biological materials. Here, we describe lessons from biology ! with exa mples of protein-mediated functional biological materials, explain how novel peptides can be designed with specific affinity to inorganic solids using evolutionary engineering approaches, give examples of their potential utilizations in technology and medicine, and, finally, provide a summary of challenges and future prospects. (c) 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94:78-94, 2010.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com. PMID: 20091881 [PubMed - as supplied by publisher] | | |
| Self-assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials.
January 22, 2010 at 10:56 PM
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| | Self-assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials. Biopolymers. 2010 Jan 20;94(1):1-18 Authors: Cui H, Webber MJ, Stupp SI Peptide amphiphiles are a class of molecules that combine the structural features of amphiphilic surfactants with the functions of bioactive peptides and are known to assemble into a variety of nanostructures. A specific type of peptide amphiphiles are known to self-assemble into one-dimensional nanostructures under physiological conditions, predominantly nanofibers with a cylindrical geometry. The resultant nanostructures could be highly bioactive and are of great interest in many biomedical applications, including tissue engineering, regenerative medicine, and drug delivery. In this context, we highlight our strategies for using molecular self-assembly as a toolbox to produce peptide amphiphile nanostructures and materials and efforts to translate this technology into applications as therapeutics. We also review our recent progress in using these materials for treating spinal cord injury, inducing angiogenesis, and for hard tissue regeneration and replacement. (! c) 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94:1-18, 2010.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com. PMID: 20091874 [PubMed - as supplied by publisher] | | |
| Fibrillar peptide gels in biotechnology and biomedicine.
January 22, 2010 at 10:56 PM
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| | Fibrillar peptide gels in biotechnology and biomedicine. Biopolymers. 2010 Jan 20;94(1):49-59 Authors: Jung JP, Gasiorowski JZ, Collier JH Peptides, peptidomimetics, and peptide derivatives that self-assemble into fibrillar gels have received increasing interest as synthetic extracellular matrices for applications in 3D cell culture and regenerative medicine. Recently, several of these fibrillizing molecules have been functionalized with bioactive components and chemical features such as cell-binding ligands, degradable sequences, drug eluting compounds, and cross-linkable groups, thereby producing gels that can reliably display multiple factors simultaneously. This capacity for incorporating precise levels of many different biological and chemical factors is advantageous given the natural complexity of cell-matrix interactions that many current biomaterial strategies seek to mimic. In this review, recent efforts in the area of fibril-forming peptide materials are described, and advantages of biomaterials containing multiple modular elements are outlined. In addition, a few hurdles and open questions! surrounding fibrillar peptide gels are discussed, including issues of the materials' structural heterogeneity, challenges in fully characterizing the diversity of their self-assembled structures, and incomplete knowledge of how the materials are processed in vivo. (c) 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 49-59, 2010.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com. PMID: 20091870 [PubMed - as supplied by publisher] | | |
| Microporous cell-laden hydrogels for engineered tissue constructs.
January 22, 2010 at 10:56 PM
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| | Microporous cell-laden hydrogels for engineered tissue constructs. Biotechnol Bioeng. 2010 Jan 20; Authors: Park JH, Chung BG, Lee WG, Kim J, Brigham MD, Shim J, Lee S, Hwang C, Durmus NG, Demirci U, Khademhosseini A In this paper, we describe an approach to generate microporous cell-laden hydrogels for fabricating biomimetic tissue engineered constructs. Micropores at different length scales were fabricated in cell-laden hydrogels by micromolding fluidic channels and leaching sucrose crystals. Microengineered channels were created within cell-laden hydrogel precursors that contained agarose solution mixed with sucrose crystals. The rapid cooling of the agarose solution was used to gel the solution and form micropores in place of the sucrose crystals. The sucrose leaching process generated micropores that were homogeneously distributed within the gels, while enabling the direct immobilization of cells within the gels. We also characterized the physical, mechanical, and biological properties (i.e. microporosity, diffusivity, and cell viability) of cell-laden agarose gels as a function of engineered porosity. The microporosity was controlled from 0% to 40% and the diffusivity of! molecules in the porous agarose gels increased as compared to controls. Furthermore, the viability of human hepatocyte cells that were cultured in microporous agarose gels corresponded to the diffusion profile generated away from the microchannels. Based on their enhanced diffusive properties, microporous cell-laden hydrogels containing a microengineered fluidic channel could be a useful tool for generating tissue structures for regenerative medicine and drug discovery applications. (c) 2010 Wiley Periodicals, Inc. PMID: 20091766 [PubMed - as supplied by publisher] | | |
| Oxygen plasma-treated thermoresponsive polymer surfaces for cell sheet engineering.
January 22, 2010 at 10:56 PM
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| | Oxygen plasma-treated thermoresponsive polymer surfaces for cell sheet engineering. Biotechnol Bioeng. 2010 Jan 20; Authors: Shimizu K, Fujita H, Nagamori E Although cell sheet engineering is a potent and promising method for tissue engineering, an increase of mechanical strength of a cell sheet is needed for easy manipulation of it during transplantation or 3-D tissue fabrication. Previously, we developed a cell sheet-polymer film complex that had enough mechanical strength that can be manipulated even by tweezers (Fujita et al. 2009). We confirmed the polymer film involving a temperature sensitive polymer and extra cellular matrix (ECM) proteins could be removed by lowering temperature after transplantation, and its potential use in regenerative medicine was demonstrated. However, the use of ECM proteins conflicted with high stability in long-term storage and low cost. In the present study, to overcome these drawbacks, we employed the oxygen plasma treatment instead of using the ECM proteins. A cast and dried film of thermoresponsive poly-N-isopropylacrylamide (PNIPAAm) was fabricated and treated with high-intensity! oxygen plasma. The cells became possible to adhere to the oxygen plasma-treated PNIPAAm surface, whereas could not to the inherent surface of bulk PNIPAAm without treatment.Characterizations of the treated surface revealed the surface had high stability. The surface roughness, wettability, and composition were changed, depending on the plasma intensity. Interestingly, although bulk PNIPAAm layer had thermo-responsiveness and dissolved below lower critical solution temperature (LCST), it was found that the oxygen plasma-treated PNIPAAm surface lost its thermo-responsiveness and remained insoluble in water below LCST as a thin layer. Skeletal muscle C2C12 cells could be cultured on the oxygen plasma-treated PNIPAAm surface, a skeletal muscle cell sheet with the insoluble thin layer could be released in the medium, and thus the possibility of use of the cell sheet for transplantation was demonstrated. (c) 2010 Wiley Periodicals, Inc. PMID: 20091737 [PubMed - as supplied by publisher] | | |
| Moisture-cured silicone-urethanes-Candidate materials for tissue engineering: A biocompatibility study in vitro.
January 22, 2010 at 10:56 PM
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| | Moisture-cured silicone-urethanes-Candidate materials for tissue engineering: A biocompatibility study in vitro. J Biomed Mater Res A. 2010 Jan 20; Authors: Mrówka P, Kozakiewicz J, Jurkowska A, Sienkiewicz E, Przybylski J, Lewandowski Z, Przybylski J, Lewandowska-Szumieł M This study was performed to verify the response of human bone-derived cells (HBDCs) to moisture-cured silicone-urethanes (mcSUUs) in vitro, as the first step toward using them as scaffolds for bone tissue engineering. Good surgical handling, tissue cavity filling, stable mechanical properties, and potentially improved oxygen supply to cells after implantation justify the investigation of these nondegradable elastomers. A set of various mcSUUs were obtained by moisture-curing NCO-terminated prepolymers, synthesized from oligomeric siloxane diols of two different oligosiloxane chain lengths, and two different diisocyanates (MDI and IPDI), using two different NCO/OH molar ratios. Dibutyltindilaurate (DBTL) or N-dimethylethanolamine (N-met) served as catalysts. After 7 days of culture, cell number, viability, and alkaline phosphatase (ALP) activity were determined, and after 21 days, cell viability and collagen production were determined. Material characteristics sign! ificantly influenced the cell response. The mcSUUs prepared with DBTL (widely used in the syntheses of biomaterials) were cytotoxic. The MDI-based mcSUUs were significantly more favored by HBDCs than the IPDI-based ones in all performed tests. MDI-based material with low 2/1 NCO/OH and short chain length was the best support for cells, comparable with tissue-culture polystyrene (with ALP activity even higher). HBDCs cultured on porous scaffolds from this mcSUU produced a tissue-like structure in culture. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010. PMID: 20091705 [PubMed - as supplied by publisher] | | |
| Tailoring the mechanical properties of 3D-designed poly(glycerol sebacate) scaffolds for cartilage applications.
January 22, 2010 at 10:56 PM
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| | Tailoring the mechanical properties of 3D-designed poly(glycerol sebacate) scaffolds for cartilage applications. J Biomed Mater Res A. 2010 Jan 20; Authors: Kemppainen JM, Hollister SJ Matching tissue engineering scaffold modulus to that of native tissue is highly desirable. Effective scaffold modulus can be altered through changes in base material modulus and/or scaffold pore architecture. Because the latter may be restricted by tissue in-growth requirements, it is advantageous to be able to alter the base material modulus of a chosen scaffold material. Here, we show that the bulk modulus of poly(glycerol sebacate) (PGS) can be changed by varying molar ratios during prepolymer synthesis and by varying curing time. We go on to show that PGS can be used to create 3D designed scaffolds via solid freeform fabrication methods with modulus values that fall within the ranges of native articular cartilage equilibrium modulus. Furthermore, using base material modulus inputs, homogenization finite element analysis can effectively predict the tangent modulus of PGS scaffold designs, which provides a significant advantage for designing new cartilage regene! ration scaffolds. Lastly, we demonstrate that this relatively new biomedical material supports cartilaginous matrix production by chondrocytes in vitro. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010. PMID: 20091702 [PubMed - as supplied by publisher] | | |
| Familiarity and Prudence of the Japanese Public with Research into Induced Pluripotent Stem Cells, and Their Desire for its Proper Regulation.
January 22, 2010 at 10:56 PM
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| | Familiarity and Prudence of the Japanese Public with Research into Induced Pluripotent Stem Cells, and Their Desire for its Proper Regulation. Stem Cell Rev. 2010 Jan 22; Authors: Shineha R, Kawakami M, Kawakami K, Nagata M, Tada T, Kato K The lack of knowledge of current public attitudes towards basic research into induced pluripotent stem cells (iPSCs) is a serious problem when considering appropriate ways of governance regarding research and its clinical applications. We therefore conducted an internet-based survey to determine public opinion regarding the research and development of iPSCs and regenerative medicine (RM). A total of 14,908 valid responses were collected, which revealed that the Japanese public were familiar with the terms iPSCs and RM, and many of them had received information about iPSCs and RM through the television and newspapers. They also generally accepted the need for extra funding for research into iPSCs, but also decided to adopt a "wait and see" approach and thought that research and development of iPSCs and RM should be conducted under proper governance in accordance with an international regulatory framework. It will be necessary to discuss an internationally consisten! t regulatory system and effective mechanisms for information flow. PMID: 20091428 [PubMed - as supplied by publisher] | | |
| Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells.
January 22, 2010 at 10:56 PM
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| | Isolation, Characterization, Differentiation, and Application of Adipose-Derived Stem Cells. Adv Biochem Eng Biotechnol. 2010 Jan 21; Authors: Kuhbier JW, Weyand B, Radtke C, Vogt PM, Kasper C, Reimers K While bone marrow-derived mesenchymal stem cells are known and have been investigated for a long time, mesenchymal stem cells derived from the adipose tissue were identified as such by Zuk et al. in 2001. However, as subcutaneous fat tissue is a rich source which is much more easily accessible than bone marrow and thus can be reached by less invasive procedures, adipose-derived stem cells have moved into the research spotlight over the last 8 years.Isolation of stromal cell fractions involves centrifugation, digestion, and filtration, resulting in an adherent cell population containing mesenchymal stem cells; these can be subdivided by cell sorting and cultured under common conditions.They seem to have comparable properties to bone marrow-derived mesenchymal stem cells in their differentiation abilities as well as a favorable angiogenic and anti-inflammatory cytokine secretion profile and therefore have become widely used in tissue engineering and clinical regener! ative medicine. PMID: 20091288 [PubMed - as supplied by publisher] | | |
| Differentiation of Human Embryonic Stem Cells to Cardiomyocytes for In Vitro and In Vivo Applications.
January 22, 2010 at 10:56 PM
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| | Differentiation of Human Embryonic Stem Cells to Cardiomyocytes for In Vitro and In Vivo Applications. Stem Cell Rev. 2010 Jan 21; Authors: Vidarsson H, Hyllner J, Sartipy P The ability of human embryonic stem cells to differentiate into spontaneously contracting cardiomyocyte-like cells has attracted substantial interest from the scientific community over the last decade. From having been difficult to control, human cardiomyogenesis in vitro is now becoming a process which, to a certain extent, can be effectively manipulated and directed. Although much research remains, new and improved protocols for guiding pluripotent stem cells to the cardiomyocyte lineage are accumulating in the scientific literature. However, the stem cell derived cardiomyocytes described to date, generally resemble immature embryonic/fetal cardiomyocytes, and they are in some functional and structural aspects different from adult cardiomyocytes. Thus, a future challenge will be to design strategies that eventually may allow the cells to reach a higher degree of maturation in vitro. Nevertheless, the cells which can be prepared using current protocols still have! wide spread utility, and they have begun to find their way into the drug discovery platforms used in the pharmaceutical industry. In addition, stem cell derived cardiomyocytes and cardiac progenitors are anticipated to have a tremendous impact on how heart disease will be treated in the future. Here, we will discuss recent strategies for the generation of cardiomyocytes from human embryonic stem cells and recapitulate their features, as well as highlight some in vitro applications for the cells. Finally, opportunities in the area of cardiac regenerative medicine will be illustrated. PMID: 20091143 [PubMed - as supplied by publisher] | | |
| Promising New Sources for Pluripotent Stem Cells.
January 22, 2010 at 10:56 PM
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| | Promising New Sources for Pluripotent Stem Cells. Stem Cell Rev. 2009 Nov 29; Authors: Leeb C, Jurga M, McGuckin C, Moriggl R, Kenner L Recent findings have placed stem cell research at the forefront of biomedical sciences. Basic research on embryonic stem cells (ESCs) has contributed to our knowledge about the developmental potential and plasticity of stem cells. Furthermore, it has raised hope to use these cells as potential source for regenerative medicine and tissue replacement after injury or disease. Unfortunately, ESCs can also form tumors and they are ethically controversial because they originate from human embryos. This review summarizes findings and therapeutic applications of ESCs and their alternatives: adult stem cells and iPS cells. PMID: 20091142 [PubMed - as supplied by publisher] | | |
| A porous scaffold for bone tissue engineering/45S5 Bioglass((R)) derived porous scaffolds for co-culturing osteoblasts and endothelial cells.
January 22, 2010 at 10:56 PM
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| | A porous scaffold for bone tissue engineering/45S5 Bioglass((R)) derived porous scaffolds for co-culturing osteoblasts and endothelial cells. J Mater Sci Mater Med. 2009 Nov 29; Authors: Deb S, Mandegaran R, Di Silvio L One of the major factors in the therapeutic success of bone tissue engineered scaffolds is the ability of the construct to vascularise post implantation. One of the approaches for improving vascularisation within scaffolds has been to co-culture human umbilical vein endothelial cells (HUVECS) with human osteoblasts (HOBS), which may then promote vascularisation and facilitate tissue regeneration. However, in order to mimic a natural physiological niche it is vital that the scaffold is able to support and promote the proliferation of both cell types and thus become a viable tissue engineered construct. In this study we report the development of a porous bioactive glass-ceramic construct and examine the interaction with human umbilical vein endothelial cells (HUVEC's) and human osteoblast-like cell both in mono and co-culture. The study clearly demonstrated that the scaffolds were able to support both endothelial and human osteoblast cell proliferation both in mono ! and co-culture. A comparison of the proliferation response of HUVEC and HOB in mono-culture on the test scaffolds and the commercial porous hydroxyapatite was assessed over a 28 day period (4, 7, 14, 21 and 28 days), using alamar Blue(TM) assay. Proliferation of HOB cells seeded in the scaffolds was consistently shown to be above those observed on commercial HA scaffolds. PMID: 20091103 [PubMed - as supplied by publisher] | | |
| Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering.
January 22, 2010 at 10:56 PM
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| | Development and characterisation of a collagen nano-hydroxyapatite composite scaffold for bone tissue engineering. J Mater Sci Mater Med. 2009 Dec 20; Authors: Cunniffe GM, Dickson GR, Partap S, Stanton KT, O'Brien FJ Bone regeneration requires scaffolds that possess suitable mechanical and biological properties. This study sought to develop a novel collagen-nHA biocomposite scaffold via two new methods. Firstly a stable nHA suspension was produced and added to a collagen slurry (suspension method), and secondly, porous collagen scaffolds were immersed in nHA suspension after freeze-drying (immersion method). Significantly stronger constructs were produced using both methods compared to collagen only scaffolds, with a high porosity maintained (>98.9%). It was found that Coll-nHA composite scaffolds produced by the suspension method were up to 18 times stiffer than the collagen control (5.50 +/- 1.70 kPa vs. 0.30 +/- 0.09 kPa). The suspension method was also more reproducible, and the quantity of nHA incorporated could be varied with greater ease than with the immersion technique. In addition, Coll-nHA composites display excellent biological activity, demonstrating their pote! ntial as bone graft substitutes in orthopaedic regenerative medicine. PMID: 20091099 [PubMed - as supplied by publisher] | | |
| Embryonic porcine skin precursors can successfully develop into integrated skin without teratoma formation posttransplantation in nude mouse model.
January 22, 2010 at 10:56 PM
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| | Embryonic porcine skin precursors can successfully develop into integrated skin without teratoma formation posttransplantation in nude mouse model. PLoS One. 2010;5(1):e8717 Authors: Huang Z, Yang J, Luo G, Gan C, Cheng W, Yuan S, Peng X, Tan J, Wang X, Hu J, Yang S, Reisner Y, Ge L, Wei H, Cheng P, Wu J How to improve the wound healing quality of severe burn patients is still a challenge due to lack of skin appendages and rete ridges, no matter how much progress has been made in the fields of either stem cell or tissue engineering. We thus systematically studied the growth potential and differentiation capacity of porcine embryonic skin precursors. Implantation of embryonic skin precursors (PESPs) of different gestational ages in nude mice can generate the integrity skin, including epidermis, dermis and skin appendages, such as sweat gland, hair follicle, sebaceous gland, etc.. PESPs of embryonic day 42 possess the maximal growth potential, while, the safe window time of PESPs transplantation for prevention of teratoma risk is E56 or later. In conclusion, PESPs can form the 3 dimensional structures of skin with all necessary skin appendages. Our data strongly indicate that porcine embryonic skin precursors harvested from E56 of minipig may provide new hope for hi! gh-quality healing of extensive burns and traumas. PMID: 20090918 [PubMed - in process] | | |
| Pancreatic Islet Transplantation Using Vascularised Chambers Containing Nerve Growth Factor Ameliorates Hyperglycaemia in Diabetic Mice.
January 22, 2010 at 10:56 PM
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| | Pancreatic Islet Transplantation Using Vascularised Chambers Containing Nerve Growth Factor Ameliorates Hyperglycaemia in Diabetic Mice. Cells Tissues Organs. 2010 Jan 14; Authors: Hussey AJ, Winardi M, Wilson J, Forster N, Morrison WA, Penington AJ, Knight KR, Feeney SJ Intraportal islet transplantation has shown initial promise for the treatment of type 1 diabetes. However, the portal vein site is associated with complications such as thrombosis and hepatic steatosis, leading to transplant failure. The aims of this study were to (1) test the feasibility of an alternative islet transplantation method that utilises a FDA-approved gelatin sponge as a novel islet carrier and (2) assess if exogenous addition of nerve growth factor (NGF) has any additional beneficial effects on graft performance in diabetic mice. Mice were rendered diabetic by a single intraperitoneal injection of streptozotocin. Five hundred syngeneic islets were seeded onto a Gelitaspon(R) disc in the presence or absence of NGF, and placed into a silicone chamber surrounding the femoral neurovascular pedicle. Islet function was assessed by weekly monitoring of blood glucose levels and an intraperitoneal glucose tolerance test performed at the end of the study. Chamb! ers were harvested for further histological analysis. Four of five mice transplanted with islets seeded onto Gelitaspon with NGF showed a significant reduction in blood glucose levels by 4 weeks after transplantation, and demonstrated a response similar to non-diabetic mice when tested with an intraperitoneal glucose tolerance test. Chamber tissue from this group contained islets with insulin-producing beta cells adjacent to the vascular pedicle. Islets seeded onto Gelitaspon with NGF and sited on femoral vessels using a tissue-engineering chamber offer an alternative method for islet transplantation in diabetic mice. This may have potential as a method for clinical islet transplantation. PMID: 20090306 [PubMed - as supplied by publisher] | | |
| Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges.
January 22, 2010 at 10:56 PM
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| | Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges. J Genet. 2009 Dec;88(4):417-24 Authors: Jin ZB, Okamoto S, Mandai M, Takahashi M Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are the prodominant causes of human blindness in the world; however, these diseases are difficult to treat. Currently, knowledge on the mechanisms of these diseases is still very limited and no radical drugs are available. Induced pluripotent stem (iPS) cells are an innovative technology that turns somatic cells into embryonic stem (ES)-like cells with pluripotent potential via the exogenous expression of several key genes. It can be used as an unlimited source for cell differentiation or tissue engineering, either of which is a promising therapy for human degenerative diseases. Induced pluripotent cells are both an unlimited source for retinal regeneration and an expectant tool for pharmaprojects and developmental or disease modelling. In this review, we try to summarize the advancement of iPS-based technologies and the potential utility for retinal degenerative di! seases. We also discuss the challenges of using this technology in the retinology field. PMID: 20090205 [PubMed - in process] | | |
| Globular Adiponectin as a Complete Mesoangioblast Regulator: Role in Proliferation, Survival, Motility, and Skeletal Muscle Differentiation.
January 22, 2010 at 10:56 PM
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| | Globular Adiponectin as a Complete Mesoangioblast Regulator: Role in Proliferation, Survival, Motility, and Skeletal Muscle Differentiation. Mol Biol Cell. 2010 Jan 20; Authors: Fiaschi T, Tedesco FS, Giannoni E, Diaz-Manera J, Parri M, Cossu G, Chiarugi P Monitoring Editor: Carl-Henrik Heldin Mesoangioblasts are progenitor endowed with multipotent mesoderm differentiation ability. Despite the promising results obtained with mesoangioblast transplantation in muscle dystrophy, an improvement of their efficient engrafting and survival within damaged muscles, as well as their ex-vivo activation/expansion and commitment toward myogenic lineage, is highly needed and should greatly increase their therapeutic potential. We show that globular adiponectin, an adipokine endowed with metabolic and differentiating functions for muscles, regulates vital cues of mesoangioblast cell biology. The adipokine drives mesoangioblasts to entry cell cycle and strongly counteracts the apoptotic process triggered by growth factor withdrawal, thereby serving as an activating and prosurvival stem cell factor. In addition, adiponectin provides a specific protection against anoikis, the apoptotic death due to lack of anchorage to extracellular ! matrix, suggesting a key protective role for these nonresident stem cells after systemic injection. Finally, adiponectin behaves as a chemo-attractive factor toward mature myotubes and stimulates their differentiation toward the skeletal muscle lineage, serving as a positive regulator in mesoangioblast homing to injured/diseased muscles. We conclude that adiponectin exerts several advantageous effects on mesoangioblasts, potentially valuable to improve their efficacy in cell based therapies of diseased muscles. PMID: 20089845 [PubMed - as supplied by publisher] | | |
| Differentiation of Bone Marrow Stromal Cells into Osteoblasts in a Self-assembling Peptide Hydrogel: In Vitro and In Vivo Studies.
January 22, 2010 at 10:56 PM
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| | Differentiation of Bone Marrow Stromal Cells into Osteoblasts in a Self-assembling Peptide Hydrogel: In Vitro and In Vivo Studies. J Biomater Appl. 2010 Jan 20; Authors: Ozeki M, Kuroda S, Kon K, Kasugai S A prerequisite of tissue engineering approaches with regard to autograft is a suitable scaffold that can harbor cells and signals. Conventionally, such scaffolds have been prepared as 3D scaffolds prefabricated from synthetic or natural biomaterials. RAD16 has been introduced as a new biomaterial, where synthetic peptides self-assemble to form a hydrogel. In this study, RAD16 was examined in terms of osteogenic efficacy and feasibility of ectopic mineralization.Two hundred and seventy-one RAD16 was cocultured with 1 x 10(6) bone marrow cells from the femurs of 6-week-old Wistar male rats in alpha minimum essential medium supplemented with or without dexamethasone. Second, the same volume of the RAD16 construct hosting the cells with or without hydroxyapatite (HA) particles was treated in the dexamethasone medium as well, prepared in a Teflon tube, and implanted subcutaneously. Cell proliferation was prominent in the RAD16 coculture with dexamethasone at 1 week and! significantly decreased by 2 weeks, whereas the other combinations remained or inclined, and their osteogenic differentiation was accelerated up to 2 weeks, as seen in increasing alkaline phosphatase (ALP) activity and mRNAs of ALP, OPN, and OCN. The RAD16 implant prepared with HA particles allowed more osteoblast-like cells and blood cells to grow inside, which was accompanied by elevating OPN gene expression and the stronger peak of VEGF gene expression at 2 weeks. Furthermore, more OPN mRNA signal was detected around the RAD16 containing HA particles by 4 weeks. On the other hand, the RAD16 alone represented lower expression of OPN gene. During the experiment, however, no ectopic mineralization was observed in both groups. Conclusively, it was suggested that the RAD16 showed feasibility of serving as a matrix for osteogenic differentiation of cocultured bone marrow cells in vitro and in vivo. Proceeding of exploration and modification of RAD16 are continuously required ! for cell-based tissue engineering. PMID: 20089608 [PubMed - as supplied by publisher] | | |
| The Mighty Mice Prove Pluripotency for iPSCs.
January 22, 2010 at 10:56 PM
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| | The Mighty Mice Prove Pluripotency for iPSCs. J Mol Cell Biol. 2010 Jan 20; Authors: Pei D By injecting induced pluripotent stem cells (iPSCs) into tetraploid blastocysts to generate live pups, two groups in China demonstrated that the injected cells are as pluripotent as embryonic stem cells, i.e. capable of giving rise to every cell in the newborn mice. This achievement validates iPS technology for regenerative medicine. PMID: 20089535 [PubMed - as supplied by publisher] | | |
| A bFGF-releasing silk/PLGA-based biohybrid scaffold for ligament/tendon tissue engineering using mesenchymal progenitor cells.
January 22, 2010 at 10:56 PM
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| | A bFGF-releasing silk/PLGA-based biohybrid scaffold for ligament/tendon tissue engineering using mesenchymal progenitor cells. Biomaterials. 2010 Jan 18; Authors: Sahoo S, Toh SL, Goh JC An ideal scaffold that provides a combination of suitable mechanical properties along with biological signals is required for successful ligament/tendon regeneration in mesenchymal stem cell-based tissue engineering strategies. Among the various fibre-based scaffolds that have been used, hybrid fibrous scaffolds comprising both microfibres and nanofibres have been recently shown to be particularly promising. This study developed a biohybrid fibrous scaffold system by coating bioactive bFGF-releasing ultrafine PLGA fibres over mechanically robust slowly-degrading degummed knitted microfibrous silk scaffolds. On the ECM-like biomimetic architecture of ultrafine fibres, sustained release of bFGF mimicked the ECM in function, initially stimulating mesenchymal progenitor cell (MPC) proliferation, and subsequently, their tenogeneic differentiation. The biohybrid scaffold system not only facilitated MPC attachment and promoted cell proliferation, with cells growing both ! on ultrafine PLGA fibres and silk microfibres, but also stimulated tenogeneic differentiation of seeded MPCs. Upregulated gene expression of ligament/tendon-specific ECM proteins and increased collagen production likely contributed to enhancing mechanical properties of the constructs, generating a ligament/tendon analogue that has the potential to be used to repair injured ligaments/tendons. PMID: 20089300 [PubMed - as supplied by publisher] | | |
| ON MORAL INCOHERENCE AND HIDDEN BATTLES: STEM CELL RESEARCH IN ARGENTINA.
January 22, 2010 at 10:56 PM
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| | ON MORAL INCOHERENCE AND HIDDEN BATTLES: STEM CELL RESEARCH IN ARGENTINA. Dev World Bioeth. 2010 Jan 18; Authors: Luna F, Salles A ABSTRACT In this article, the authors focus on Argentina's activity in the developing field of regenerative medicine, specifically stem cell research. They take as a starting point a recent article by Shawn Harmon (published in this journal) who argues that attempts to regulate the practice in Argentina are morally incoherent. The authors try to show first, that there is no such 'attempt to legislate' on stem cell research in Argentina and this is due to a number of reasons that they explain. Second, by examining the role played by different values, conflicting legal and moral views, and the influence of various actors, they attempt to show that the legislative silence regarding stem cell research may not necessarily be a manifestation of a legal/moral disconnection but rather a survival strategy for navigating the long and heated battle on the moral status of the embryo and the kind of treatment it deserves. PMID: 20089053 [PubMed - as supplied by publisher] | | |
| Stem Cells: An Overview of the Current Status of Therapies for Central and Peripheral Nervous System Diseases.
January 22, 2010 at 10:56 PM
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| | Stem Cells: An Overview of the Current Status of Therapies for Central and Peripheral Nervous System Diseases. Curr Med Chem. 2010 Jan 21; Authors: Orlacchio A, Bernardi G, Orlacchio A, Martino S In regenerative medicine, stem cells are currently considered ideal candidates for the treatment of diseases and injuries of the nervous system, for which, at present, there are no effective treatments. Promising results have been shown by clinical trials for neurodegenerative diseases such as Parkinson's diseases, but also for demyelinising disorders and traumatic lesions of the brain and spinal cord. The proof-of-principle is that the replacement of damaged cells and the restoration of function can be accomplished by the transplantation of embryonic or adult stem cells. Advancements in stem cell biology were recently propelled by the ability to generate induced pluripotent stem (iPS) cells from fibroblasts of several neurodegenerative diseases (e.g. Parkinson's and Huntington's diseases, Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy). In this review, we discuss the molecular basis of stem cell therapy and the advancement of research on regenerative m! edicine for diseases and injuries of the nervous system. PMID: 20088765 [PubMed - as supplied by publisher] | | |
| Gene-delivery systems for iPS cell generation.
January 22, 2010 at 10:56 PM
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| | Gene-delivery systems for iPS cell generation. Expert Opin Biol Ther. 2010 Feb;10(2):231-42 Authors: Shao L, Wu WS IMPORTANCE OF THE FIELD: Induced pluripotent stem (iPS) cells offer extraordinary promise for regenerative medicine applications, and provide new opportunities for use in disease modeling, drug screening and drug toxicology. AREAS COVED IN THIS REVIEW: iPS cell technology is still in its infancy. In this review article, we present a comprehensive survey of reprogramming approaches focusing on gene-delivery systems used for generation of iPS cells from somatic cells, categorize gene-delivery vectors, and discuss their advantages and limitations for somatic cell reprogramming. We include pertinent literature published between 2006 and the present. WHAT THE READER WILL GAIN: Although iPS cell technology has been improved via the use of various gene-delivery vectors, it still suffers from either low reprogramming efficiency or too many genomic modification steps. Extensive work is still required to improve current vectors or explore new vectors for effectively reprogr! amming human somatic cells into iPS cells, with or without minimal genomic modification steps. TAKE HOME MESSAGE: A single non-integrating reprogramming vector system with high reprogramming efficiency is probably essential for generation of clinically translatable human iPS cells. PMID: 20088717 [PubMed - in process] | | |
| Effect of varied ionic calcium on human adipose-derived stem cell mineralization.
January 22, 2010 at 10:56 PM
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| | Effect of varied ionic calcium on human adipose-derived stem cell mineralization. Tissue Eng Part A. 2010 Jan 20; Authors: McCullen S, Zhan J, Onorato M, Bernacki S, Loboa E Human adipose-derived stem cells (hASCs) are a relatively abundant and accessible stem cell source with multilineage differentiation capability and have great potential for bone tissue engineering applications. The success of bone tissue engineering is intimately linked with the production of a mineralized matrix that mimics the natural mineral present within native bone. In this study, we examined the effects of ionic calcium levels of 1.8 (normal concentration in cell culture medium), 8, and 16 mM on hASCs seeded in both 2D monolayer and 3D electrospun scaffolds and cultured in either complete growth (CGM) or osteogenic differentiation medium (ODM).. The impact of calcium supplementation on hASC viability, proliferation, and mineral deposition were determined. Human ASCs remained viable for all experimental treatments. Human ASC proliferation increased with the addition of 8 mM Ca2+ CGM, but decreased for the 16 mM Ca2+ CGM treatment. Materials deposited by hASC! s were analyzed using four techniques: 1) histological staining with Alizarin Red S, 2) calcium quantification, 3) Fourier transform infrared spectroscopy (FTIR), and 4) wide angle x-ray diffraction (XRD). Mineral deposition was significantly enhanced under both growth and osteogenic medium conditions by increasing extracellular Ca2+. The greatest mineral deposition occurred in the osteogenic differentiating medium 8 mM Ca2+ treatment group. FTIR analysis indicated that elevated calcium concentrations of 8 mM Ca2+ significantly increased both PO4 amount and PO4 to protein ratio for ODM. X-ray diffraction indicated that mineral produced with elevated Ca2+ in both complete growth and osteogenic differentiating medium had a crystalline structure characteristic of hydroxyapatite. Ionic calcium should be considered a potent regulator in hASC mineralization and could serve as a potential treatment for inducing prompt ossification of hASC-seeded scaffolds for bone tissue engineeri! ng prior to implantation. PMID: 20088702 [PubMed - as supplied by publisher] | | |
| Enhanced biomineralization in osteoblasts on a novel electrospun biocomposite nanofibrous substrate of hydroxyapatite/collagen/chitosan.
January 22, 2010 at 10:56 PM
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| | Enhanced biomineralization in osteoblasts on a novel electrospun biocomposite nanofibrous substrate of hydroxyapatite/collagen/chitosan. Tissue Eng Part A. 2010 Jan 20; Authors: Zhang Y, Jayarama Reddy V, Wong SY, Li X, Su B, Ramakrishna S, Lim CT Electrospun chitosan-based hydroxyapatite/chitosan (HAp/CTS) biocomposite nanofibers for bone tissue engineering could afford a close biomimicry to the fibrous nanostructure and constituents of the hierarchically organized natural bone, but their biological performance is somewhat deficient compared to the hydroxyapatite/collagen biocomposite system. This necessitates doping the electrospun HAp/CTS hybrid with the bioactive component of collagen (Col). We show herein that Col doped HAp/CTS biocomposite (i.e., HAp/Col/CTS) containing 27.8 wt% of HAp nanoparticles, 7.2 wt% of Col, and 57.8 wt% of CTS, can be successfully electrospun into nanofibrous form through using small amount (7.2 wt%) of ultrahigh molecular weight poly(ethylene oxide) as the fiber forming additive. Morphology, structure, composition, and mechanical properties of the electrospun HAp/Col/CTS scaffolds were examined by FESEM and AFM, XRD, FTIR, and tensile tests, respectively. Human fetal osteobl! asts on the nanofibrous HAp/Col/CTS scaffolds were cultured for up to 15 days to assess the cell-scaffold interaction and biomineralization effect. In comparison with different controls, significant increments in osteoblast proliferation, alkaline phosphatase expression, and mineral deposition were observed. Results obtained thus highlight that introduction of collagen can significantly enhance the biological performance of osteoblasts on the chitosan-based nanofibrous substrates, and suggest that current electrospun HAp/Col/CTS biocomposite, as a highly biomimetic and bioactive nanofibrous structure, may be one of the most attractive candidates for various osteoregeneration related applications. PMID: 20088700 [PubMed - as supplied by publisher] | | |
| Tensile Loading Modulates BMSC Differentiation and the Development of Engineered Fibrocartilage Constructs.
January 22, 2010 at 10:56 PM
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| | Tensile Loading Modulates BMSC Differentiation and the Development of Engineered Fibrocartilage Constructs. Tissue Eng Part A. 2010 Jan 20; Authors: Connelly JT, Vanderploeg EJ, Mouw JK, Wilson C, Levenston ME Mesenchymal progenitors such as bone marrow stromal cells (BMSCs) are an attractive cell source for fibrocartilage tissue engineering, but the types or combinations of signals required to promote fibrochondrocyte-specific differentiation remain unclear. The present study investigated the influences of cyclic tensile loading on the chondrogenesis of BMSCs and the development of engineered fibrocartilage. Cyclic tensile displacements (10%, 1Hz) were applied to BMSC seeded fibrin constructs for short (24 h) or extended (1-2 weeks) periods using a custom loading system. At early stages of chondrogenesis, 24 h of cyclic tension stimulated both protein and proteoglycan synthesis, but at later stages, tension increased protein synthesis only. One week of intermittent cyclic tension significantly increased the total sulfated glycosaminoglycan (sGAG) and collagen contents in the constructs, but these differences were lost after two weeks of loading. Constraining the gels d! uring the extended culture periods prevented contraction of the fibrin matrix, aligned collagen fibers, and increased sGAG release to the media. Cyclic tension specifically stimulated collagen I mRNA expression and protein synthesis, but had no effect on collagen II, aggrecan, or osteocalcin mRNA levels. Overall, these studies suggest that the combination of chondrogenic stimuli and tensile loading promotes fibrochondrocyte-like differentiation of BMSCs and has the potential to direct fibrocartilage development in vitro. PMID: 20088686 [PubMed - as supplied by publisher] | | |
| Freshly isolated stromal cells from the infrapatellar fat pad are suitable for a one-step surgical procedure to regenerate cartilage tissue.
January 22, 2010 at 10:56 PM
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| | Freshly isolated stromal cells from the infrapatellar fat pad are suitable for a one-step surgical procedure to regenerate cartilage tissue. Cytotherapy. 2009;11(8):1052-64 Authors: Jurgens WJ, van Dijk A, Doulabi BZ, Niessen FB, Ritt MJ, van Milligen FJ, Helder MN BACKGROUND AIMS: Stem cell therapies are being evaluated as promising alternatives for cartilage regeneration. We investigated whether stromal vascular fraction cells (SVF) from the infrapatellar (Hoffa) fat pad are suitable for a one-step surgical procedure to treat focal cartilage defects. METHODS: SVF was harvested from patients undergoing knee arthroplasty (n = 53). Colony-forming unit (CFU) assays, growth kinetics and surface marker profiles were determined, and the chondrogenic differentiation capacity of freshly isolated SVF was assessed after seeding in three-dimensional poly (L-lactic-co-epsilon-caprolactone) scaffolds. RESULTS: SVF yield per fat pad varied between 0.55 and 16 x 10(6) cells. CFU frequency and population doubling time were 2.6 +/- 0.6% and +/-2 days, respectively. Surface marker profiles matched those of subcutaneous-derived adipose-derived stem cells (ASC). CFU from Hoffa SVF showed differentiation toward osteogenic and adipogenic lineage! s. Cartilage differentiation was confirmed by up-regulation of the cartilage genes sox9, aggrecan, collagen type II and cartilage oligomeric matrix protein (COMP), collagen II immunostaining, Alcian Blue staining and glycosaminoglycan production. Compared with passaged cells, SVF showed at least similar chondrogenic potential. CONCLUSIONS: This study demonstrates that SVF cells from the infrapatellar fat pad are suitable for future application in a one-step surgical procedure to regenerate cartilage tissue. SVF shows similar favorable characteristics as cultured ASC, and chondrogenic differentiation even appears to be slightly better. However, because of variable harvesting volumes and yields, SVF from the infrapatellar fat pad might only be applicable for treatment of small focal cartilage defects, whereas for larger osteoarthritic defects subcutaneous adipose tissue depot would be preferable. PMID: 19929469 [PubMed - indexed for MEDLINE] | | |
| Medical applications of nanoparticles and nanomaterials.
January 22, 2010 at 10:56 PM
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| | Medical applications of nanoparticles and nanomaterials. Stud Health Technol Inform. 2009;149:257-83 Authors: Burgess R Current clinical diagnostics and therapeutics platforms are often limited by borderline sensitivity or efficacy levels. These limitations result from low or minimal specificity for the intended target cell or organ, span a multitude of physiological disorders and result in nominal success rates for diagnosis or treatment in many cases. Diagnosis and treatment of diseases such as cancer or viral infections require next generation medical methods. Nanotechnology has the potential to significantly address diagnostics and therapeutics sensitivity and resulting unwanted side effects by providing extremely precise reagents and tools that allow for unparalleled detection and treatment at the clinical level. This is accomplished through extremely controlled nanofabrication methodologies which result in the generation of molecularly defined nanoscale materials and devices that harbor known physical properties unique to each material in question and useful for particular me! dical applications. The further precise targeting of these materials to specific sites within the body allows for an added layer of accuracy and potency. Research in this area is quickly advancing to the point of providing a comprehensive portfolio of nanotechnology-based diagnostic and therapeutic platforms that will be unparalleled in sensitivity, specificity and elimination of unwanted side effects. PMID: 19745487 [PubMed - indexed for MEDLINE] | | |
| Future approaches to organ regeneration: microscale environments, stem cell engineering, and self-assembly of living tissues.
January 22, 2010 at 10:56 PM
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| | Future approaches to organ regeneration: microscale environments, stem cell engineering, and self-assembly of living tissues. Stud Health Technol Inform. 2009;149:214-35 Authors: Hacking SA, Kachouie NN, Lee WG, Khademhosseini A A promising means to address the limited supply of donor tissue is through the generation of artificial organs consisting of cells and materials. Progress towards this goal is limited by three main obstacles namely the generation of a sufficient number of cells specific to the organ, the arrangement of these cells in a functional tissue architecture and the delivery of nutrients and removal of waste from the tissue mass. This chapter describes the emerging approaches that may be achieved by the control of stem cell differentiation, control of the local tissue environment on the microscale, and the generation of complex structures containing multiple cell types. PMID: 19745484 [PubMed - indexed for MEDLINE] | | |
| Controlling cellular uptake by surface chemistry, size, and surface topology at the nanoscale.
January 22, 2010 at 10:56 PM
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| | Controlling cellular uptake by surface chemistry, size, and surface topology at the nanoscale. Small. 2009 Nov;5(21):2424-32 Authors: Massignani M, LoPresti C, Blanazs A, Madsen J, Armes SP, Lewis AL, Battaglia G Cell cytosol and the different subcellular organelles house the most important biochemical processes that control cell functions. Effective delivery of bioactive agents within cells is expected to have an enormous impact on both gene therapy and the future development of new therapeutic and/or diagnostic strategies based on single-cell-bioactive-agent interactions. Herein a biomimetic nanovector is reported that is able to enter cells, escape from the complex endocytic pathway, and efficiently deliver actives within clinically relevant cells without perturbing their metabolic activity. This nanovector is based on the pH-controlled self-assembly of amphiphilic copolymers into nanometer-sized vesicles (or polymersomes). The cellular-uptake kinetics can be regulated by controlling the surface chemistry, the polymersome size, and the polymersome surface topology. The latter is controlled by the extent of polymer-polymer phase separation within the external envelope of! the polymersome. PMID: 19634187 [PubMed - indexed for MEDLINE] | | |
| Pulmonary responses to polyhydroxylated fullerenols, C(60)(OH)(x).
January 22, 2010 at 10:56 PM
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| | Pulmonary responses to polyhydroxylated fullerenols, C(60)(OH)(x). J Appl Toxicol. 2009 Oct;29(7):578-84 Authors: Xu JY, Han K, Li SX, Cheng JS, Xu GT, Li WX, Li QN Although many scientists have been attracted by polyhydroxylated fullerenols for their radical-scavenging and antioxidant ability in vivo and in vitro and their potential use as a drug or for drug delivery, there is little information on their pulmonary toxicological properties. The aim of this study was to investigate the effect of polyhydroxylated derivatives of fullerene on Sprague-Dawley rats after intratracheal instillation. Polyhydroxylated fullerenols [C(60)(OH)(x), x = 22, 24] were administered intratracheally (1, 5 or 10 mg per rat). Following 3-day exposures, the lungs of the rats were assessed using bronchoalveolar lavage fluid biomarkers and a pathological evaluation of lung tissue. Exposures to 1 mg per rat did not induce adverse pulmonary toxicity, while the two other doses induced cell injury effect, oxidative/nitrosative stress and inflammation, showing that C(60)(OH)(x) produced responses in a dose-dependent manner. The dosage of C(60)(OH)(x) reta! ined in lung and the ensuing aggregation might be the main factor in the process. Our results might shed light on the possible use of C(60)(OH)(x) as an inhaled drug. PMID: 19484703 [PubMed - indexed for MEDLINE] | | |
| [Immuno-suppressive effects on T cells mediated by mesenchymal stem cells from patients with myelodysplastic syndrome]
January 22, 2010 at 10:56 PM
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| | [Immuno-suppressive effects on T cells mediated by mesenchymal stem cells from patients with myelodysplastic syndrome] Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Apr;16(2):299-304 Authors: Liu LH, Chen H, Chen B, Sun Z, Ye LP, Shi B, Jin JG, Zhao CH The study was aimed to compare the effects of T-cell suppression mediated by mesenchymal stem cells (MSC) from normal individuals and myelodysplastic syndromes (MDS) patients. MSC were cultured from the bone marrow of 12 healthy volunteers and 12 MDS patients, the morphology, surface markers and expression of several cytokines of MSC from normal individuals and MDS patients were compared, and the effects of T-cell suppression were tested in the following assays: phytohemaglutinin (PHA)-primed cultures, mixed lymphocyte reaction (MLR), cell cycle of T-cell after PHA-primed cultures and apoptosis of T-cell as well. The results showed that the MSC from normal individuals and MDS patients were similar in morphology, proliferation and surface markers. The suppressions of T-cell proliferation induced by PHA and alloantigens mediated by MDS-MSC were significantly lower than that of normal MSC. More T-cells were arrested in G0/G1 phase by normal MSC, while the effects wer! e deficient by MDS-MSC. The suppression of T-cell activation mediated by MDS-MSC was also lower than that of normal MSC, but suppression effect on T-cell apoptosis increased. The cytokines TGF-beta1, 3, FasL expressed by MDS-MSC were reduced as compared with normal MSC, but TGF-beta2 expression increased in MDS-MSC. It is concluded that although the morphology, proliferation and cell surface markers of MDS-MSC are normal, the T-cell suppression mediated by MDS-MSC is deficient as compared with normal controls. Whether these abnormalities are relevant to the pathogenesis of aplastic anemia remains to be determined. PMID: 18426653 [PubMed - indexed for MEDLINE] | | |
| A biohybrid artificial lung prototype with active mixing of endothelialized microporous hollow fibers.
January 22, 2010 at 4:56 PM
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| | A biohybrid artificial lung prototype with active mixing of endothelialized microporous hollow fibers. Biotechnol Bioeng. 2010 Jan 20; Authors: Polk AA, Maul TM, McKeel DT, Snyder TA, Lehocky CA, Pitt B, Stolz DB, Federspiel WJ, Wagner WR Acute respiratory distress syndrome (ARDS) affects nearly 150,000 patients per year in the US, and is associated with high mortality ( approximately 40%) and suboptimal options for patient care. Mechanical ventilation and extracorporeal membrane oxygenation are limited to short-term use due to ventilator-induced lung injury and poor biocompatibility, respectively. In this report, we describe the development of a biohybrid lung prototype, employing a rotating endothelialized microporous hollow fiber (MHF) bundle to improve blood biocompatibility while MHF mixing could contribute to gas transfer efficiency. MHFs were surface modified with radio frequency glow discharge (RFGD) and protein adsorption to promote endothelial cell (EC) attachment and growth. The MHF bundles were placed in the biohybrid lung prototype and rotated up to 1500 revolutions per minute (RPM) using speed ramping protocols to condition ECs to remain adherent on the fibers. Oxygen transfer, thromb! otic deposition, and EC p-selectin expression were evaluated as indicators of biohybrid lung functionality and biocompatibility. A fixed aliquot of blood in contact with MHF bundles rotated at either 250 or 750 RPM reached saturating pO(2) levels more quickly with increased RPM, supporting the concept that fiber rotation would positively contribute to oxygen transfer. The presence of ECs had no effect on the rate of oxygen transfer at lower fiber RPM, but did provide some resistance with increased RPM when the overall rate of mass transfer was higher due to active mixing. RFGD followed by fibronectin adsorption on MHFs facilitated near confluent EC coverage with minimal p-selectin expression under both normoxic and hyperoxic conditions. Indeed, even subconfluent EC coverage on MHFs significantly reduced thrombotic deposition adding further support that endothelialization enhances, blood biocompatibility. Overall these findings demonstrate a proof-of-concept that a rotating ! endothelialized MHF bundle enhances gas transfer and biocompat! ibility, potentially producing safer, more efficient artificial lungs. (c) 2010 Wiley Periodicals, Inc. PMID: 20091735 [PubMed - as supplied by publisher] | | | |
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