Thursday, March 11, 2010

3/12 TE-RegenMed-StemCell feed

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Researchers characterize stem cell function
March 11, 2010 at 7:39 PM

 

Burnham's Snyder Receives $1.85 Million More Despite Faulty Application
March 11, 2010 at 5:23 PM

Directors of the California stem cell agency this morning, on a split vote, approved a $1.85 million increase in a grant to a Southern California scientist after he submitted a proposal that would violate the agency's rules against spending CIRM funds out-of-state.

Nineteen directors of those present voted in favor of the increase, although some expressed concern about the way in which the
 

Keynote speakers to focus on translating regenerative medicine science to the clinic
March 11, 2010 at 4:39 PM

 

CIRM Okays First Clinical Trial Round; $50 Million Earmarked
March 11, 2010 at 4:28 PM

Directors of the California stem cell agency this morning unanimously approved a $50 million foray – its first-ever -- into the financing of clinical trials.

The program appears likely to be of benefit to only a handful of organizations – particularly the three that have pluripotent proposals that are now on hold with the FDA. The names of the enterprises were not disclosed during the board
 

CIRM VP Salary Hike Move Delayed
March 11, 2010 at 2:16 PM

The directors of the California stem cell agency today put off action on a proposal that would have presumably increased the current $332,000 salary cap on the newly created position of vice president of research and development.

The deferral came on the same day that The Sacramento Bee carried a front page story that said California state workers received 4 percent less pay last year than in
 

HDL/Apolipoprotein A-I Binds to Macrophage-Derived Progranulin and Suppresses its Conversion into Proinflammatory Granulins.
March 11, 2010 at 1:59 PM

HDL/Apolipoprotein A-I Binds to Macrophage-Derived Progranulin and Suppresses its Conversion into Proinflammatory Granulins.

J Atheroscler Thromb. 2010 Mar 9;

Authors: Okura H, Yamashita S, Ohama T, Saga A, Yamamoto-Kakuta A, Hamada Y, Sougawa N, Ohyama R, Sawa Y, Matsuyama A

Aim: HDL has anti-inflammatory effects on macrophages, although the mechanism of action remains unclear. We hypothesized that HDL suppresses the conversion of macrophage-secreted factors into proinflammatory factors via binding, and tried to identify the factor that could form a complex with HDL and/or apolipoprotein (apo) A-I.Methods and Results: In conditioned media obtained from human monocyte-derived macrophages, we found an apo A-I binding protein and identified the protein as progranulin/proepithelin/acrogranin/PCDGF. Co-immunoprecipitation analysis showing that progranulin binds and forms a complex with apo A-I and the presence of progranulin in the HDL fraction in the sera indicated that progranilin is a novel apolipoprotein. Conditioned media of HEK293 cells transfected with progranulin augmented the expression of TNF-alpha and IL-1-beta on macrophages, but these effects of progranulin were inhibited by co-incubation with HDL or apo A-I. Anti-progranulin ! antibodies also reduced the expression of TNF-alpha and IL-1-beta on macrophages. Granulins as conversion products derived from progranilin increased TNF-alpha and IL-1-beta expression and the effects were not suppressed by HDL.Conclusions: Our results suggest that the anti-inflammatory effects of HDL on macrophages might be due to suppression of the conversion of progranulin into proinflammatory granulins by forming a complex.

PMID: 20215705 [PubMed - as supplied by publisher]

 

$62 Million Effort: First CIRM-financed Lab Opens at UC Davis
March 11, 2010 at 1:25 PM

The chairman of the California stem cell agency, Robert Klein, opened its board of directors meeting today by celebrating the opening of a $62 million UC Davis stem cell research center.

The facility, partially financed with a $20 million CIRM grant, was featured in a front page story in The Sacramento Bee yesterday. It is the first to open of a dozen labs that were partially funded by CIRM.
 

Entest BioMedical, Inc. Chairman & amp; CEO Addressed Shareholders on Its New Company Blog Site Regarding COPD and Immunotherapeutic Cancer Vaccine
March 11, 2010 at 12:17 PM

 

Live Coverage Today of CIRM Board Meeting
March 11, 2010 at 11:50 AM

We will be filing stories as warranted out of the CIRM directors meeting today from our post here in an Internet cafe in Manzanillo, Mexico.
 

Snyder Provides Additional Comment on Out-of-State Spending Proposal
March 11, 2010 at 11:33 AM

Evan Snyder of the Sanford-Burnham institute has emailed additional comment on his grant proposal, which this morning comes before the board of the California stem cell agency. His response came after we asked him yesterday: "How did you happen to propose spending CIRM money out of state? The agency clearly bans such actions and explicitly states that in its instructions to applicants."

Here
 

Multiple functionalities of polyelectrolyte multilayer films: new biomedical applications.
March 11, 2010 at 6:53 AM

Multiple functionalities of polyelectrolyte multilayer films: new biomedical applications.

Adv Mater. 2010 Jan 26;22(4):441-67

Authors: Boudou T, Crouzier T, Ren K, Blin G, Picart C

The design of advanced functional materials with nanometer- and micrometer-scale control over their properties is of considerable interest for both fundamental and applied studies because of the many potential applications for these materials in the fields of biomedical materials, tissue engineering, and regenerative medicine. The layer-by-layer deposition technique introduced in the early 1990s by Decher, Moehwald, and Lvov is a versatile technique, which has attracted an increasing number of researchers in recent years due to its wide range of advantages for biomedical applications: ease of preparation under "mild" conditions compatible with physiological media, capability of incorporating bioactive molecules, extra-cellular matrix components and biopolymers in the films, tunable mechanical properties, and spatio-temporal control over film organization. The last few years have seen a significant increase in reports exploring the possibilities offered by diffusin! g molecules into films to control their internal structures or design "reservoirs," as well as control their mechanical properties. Such properties, associated with the chemical properties of films, are particularly important for designing biomedical devices that contain bioactive molecules. In this review, we highlight recent work on designing and controlling film properties at the nanometer and micrometer scales with a view to developing new biomaterial coatings, tissue engineered constructs that could mimic in vivo cellular microenvironments, and stem cell "niches."

PMID: 20217734 [PubMed - in process]

 

Advances in biomimetic and nanostructured biohybrid materials.
March 11, 2010 at 6:53 AM

Advances in biomimetic and nanostructured biohybrid materials.

Adv Mater. 2010 Jan 19;22(3):323-36

Authors: Ruiz-Hitzky E, Darder M, Aranda P, Ariga K

The rapid increase of interest in the field of biohybrid and biomimetic materials that exhibit improved structural and functional properties is attracting more and more researchers from life science, materials science, and nanoscience. Concomitant results offer valuable opportunities for applications that involve disciplines dealing with engineering, biotechnology, medicine and pharmacy, agriculture, nanotechnology, and others. In the current contribution we collect recent illustrative examples of assemblies between materials of biological origin and inorganic solids of different characteristics (texture, structure, and particle size). We introduce here a general overview on strategies for the preparation and conformation of biohybrids, the synergistic effects that determine the final properties of these materials, and their diverse applications, which cover areas as different as tissue engineering, drug delivery systems, biosensing devices, biocatalysis, green na! nocomposites, etc.

PMID: 20217713 [PubMed - in process]

 

Controlling stem cell fate with material design.
March 11, 2010 at 6:53 AM

Controlling stem cell fate with material design.

Adv Mater. 2010 Jan 12;22(2):175-89

Authors: Marklein RA, Burdick JA

Advances in our understanding of stem cell interactions with their environment are leading to the development of new materials-based approaches to control stem cell behavior toward cellular culture and tissue regeneration applications. Materials can provide cues based on chemistry, mechanics, structure, and molecule delivery that control stem cell fate decisions and matrix formation. These approaches are helping to advance clinical translation of a range of stem cell types through better expansion techniques and scaffolding for use in tissue engineering approaches for the regeneration of many tissues. With this in mind, this progress report covers basic concepts and recent advances in the use of materials for manipulating stem cells.

PMID: 20217683 [PubMed - in process]

 

Biosensing and drug delivery at the microscale : novel devices for controlled and responsive drug delivery.
March 11, 2010 at 6:53 AM

Biosensing and drug delivery at the microscale : novel devices for controlled and responsive drug delivery.

Handb Exp Pharmacol. 2010;(197):87-112

Authors: Robitzki AA, Kurz R

An overall objective of pharmaceutical research is the controlled release or delivery of drugs at the biological target site in a therapeutically and pharmacodynamically optimal amount. In relation to "intelligent" drug delivery, several basic aspects are important, i.e., release of active pharmaceutical ingredients from the formulation, transport to and penetration across biological barriers, and subsequent biotransformation depending on a controlled release process. Future development of advanced and/or controlled drug releasing systems, e.g. polymeric or particulate drug targeting systems, nano-carbon tube related and/or nano-pillar based drug release, or electronically mediated molecule delivery, is expected to take advantage of progress in molecular cell biology, cell and tissue engineering, membrane nano-biophysics, and bioelectronic properties (Bramstedt et al. 2005; Gardner et al. 2006). In this chapter novel aspects of the development of innovative drug d! elivery systems described and are categorized into polymeric, lipid-based or electronically mediated delivery systems (De la Heras et al. 2004).

PMID: 20217527 [PubMed - in process]

 

Tensile Strain as a Regulator of Mesenchymal Stem Cell Osteogenesis.
March 11, 2010 at 6:53 AM

Tensile Strain as a Regulator of Mesenchymal Stem Cell Osteogenesis.

Ann Biomed Eng. 2010 Mar 9;

Authors: Kearney EM, Farrell E, Prendergast PJ, Campbell VA

A role for mechanical stimulation in the control of cell fate has been proposed and mechanical conditioning of mesenchymal stem cells (MSCs) is of interest in directing MSC behavior for tissue engineering applications. This study investigates strain-induced differentiation and proliferation of MSCs, and investigates the cellular mechanisms of mechanotransduction. MSCs were seeded onto a collagen-coated silicone substrate and exposed to cyclic tensile mechanical strain of 2.5% at 0.17 Hz for 1-14 days. To examine mechanotransduction, cells were strained in the presence of the stretch-activated cation channel (SACC) blocker, gadolinium chloride (GdCl(3)); the extracellular regulated kinase (ERK) inhibitor, U0126; the p38 inhibitor, SB203580; and the phosphatidylinosito1 3-kinase (PI3-kinase) inhibitor, LY294002. Following exposure to strain, the osteogenic markers Cbfalpha1, collagen type I, osteocalcin, and BMP2 were temporally expressed. Exposure to strain in the ! presence of GdCl(3) (10 muM) reduced the induction of collagen I expression, thus identifying a role for SACC, at least in part, as mechanosensors in strain-induced MSC differentiation. The strain-induced synthesis of BMP2 was found to be reduced by inhibitors of the kinases, ERK, p38, and PI3 kinase. Additionally, mechanical strain reduced the rate of MSC proliferation. The identification of the mechanical control of MSC proliferation and the molecular link between mechanical stimulation and osteogenic differentiation has consequences for regenerative medicine through the development of a functional tissue engineering approach.

PMID: 20217480 [PubMed - as supplied by publisher]

 

Physicochemical properties and cytotoxicities of Sr-containing biphasic calcium phosphate bone scaffolds.
March 11, 2010 at 6:53 AM

Physicochemical properties and cytotoxicities of Sr-containing biphasic calcium phosphate bone scaffolds.

J Mater Sci Mater Med. 2010 Mar 10;

Authors: Dagang G, Kewei X, Yaxiong L

This study demonstrates a new biomaterial system composed of Sr-containing hydroxyapatite (Sr-HA) and Sr-containing tricalcium phosphate (Sr-TCP), termed herein Sr-containing biphasic calcium phosphate (Sr-BCP). Furthermore, a series of new Sr-BCP porous scaffolds with tunable structure and properties has also been developed. These Sr-BCP scaffolds were obtained by in situ sintering of a series of composites formed by casting various Sr-containing calcium phosphate cement (Sr-CPC) into different rapid prototyping (RP) porous phenol formaldehyde resins, which acted as the negative moulds for controlling pore structures of the final scaffolds. Results show that the porous Sr-BCP scaffolds are composed of Sr-HA and Sr-TCP. The phase composition and the macro-structure of the Sr-BCP scaffold could be adjusted by controlling the processing parameters of the Sr-CPC pastes and the structure parameters of the RP negative mould, respectively. It is also found that both the! compressive strength (CS) and the dissolving rate of the Sr-BCP scaffold significantly vary with their phase composition and macropore percentage. In particular, the compressive strength achieves a maximum CS level of 9.20 +/- 1.30 MPa for the Sr-BCP scaffold with a Sr-HA/Sr-TCP weight ratio of 78:22, a macropore percentage of 30% (400-550 mum in size) and a total-porosity of 63.70%, significantly higher than that of the Sr-free BCP scaffold with similar porosity. All the extracts of the Sr-BCP scaffold exhibit no cytotoxicity. The current study shows that the incorporation of Sr plays an important role in positively improving the physicochemical properties of the BCP scaffold without introducing obvious cytotoxicity. It also reveals a potential clinical application for this material system as bone tissue engineering (BTE) scaffold.

PMID: 20217190 [PubMed - as supplied by publisher]

 

Rapid generation of biologically relevant hydrogels containing long-range chemical gradients.
March 11, 2010 at 6:53 AM

Rapid generation of biologically relevant hydrogels containing long-range chemical gradients.

Adv Funct Mater. 2010;20(1):131-137

Authors: He J, Du Y, Villa-Uribe JL, Hwang C, Li D, Khademhosseini A

Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue-mimetic constructs. Here we describe a simple and versatile method to rapidly generate materials containing centimeter-long gradients of chemical properties in a microfluidic channel. The formation of chemical gradient was initiated by a passive-pump-induced forward flow and further developed during an evaporation-induced backward flow. The gradient was spatially controlled by the backward flow time and the hydrogel material containing the gradient was synthesized via photopolymerization. Gradients of a cell-adhesion ligand, Arg-Gly-Asp-Ser (RGDS), was incorporated in the poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels to test the response of endothelial cells. The cells attached and spread along the hydrogel material in a manner consistent ! with the RGDS gradient profile. A hydrogel containing PEG-DA concentration gradient and constant RGDS concentration was also generated. The morphology of cells cultured on such hydrogel changed from round in the lower PEG-DA concentration regions to well-spread in the higher PEG-DA concentration regions. This approach is expected to be a valuable tool to investigate the cell-material interactions in a simple and high-throughput manner and to design graded biomimetic materials for tissue engineering applications.

PMID: 20216924 [PubMed - as supplied by publisher]

 

Evaluation of Nanostructural, Mechanical and Biological Properties of Collagen-Nanotube Composites.
March 11, 2010 at 6:53 AM

Evaluation of Nanostructural, Mechanical and Biological Properties of Collagen-Nanotube Composites.

IEEE Trans Nanobioscience. 2010 Mar 8;

Authors: Tan W, Twomey J, Guo D, Madhavan K, Li M

Collagen I is an essential structural and mechanical building block of various tissues, and it is often used as tissue engineering scaffolds. However, collagenbased constructs reconstituted in vitro often lack robust fiber structure, mechanical stability and molecule binding capability. To enhance these performances, the present study developed three-dimensional collagen-nanotube composite constructs with two types of functionalized carbon nanotubes, carboxylated nanotubes and covalently-functionalized nanotubes (CFNT). The influences of nanotube functionalization and loading concentration on the collagen fiber structure, mechanical property, biocompatibility and molecule binding were examined. Results revealed that surface modification and loading concentration of nanotubes determined the interactions between nanotubes and collagen fibrils, thus altering the structure and property of nanotube-collagen composites. Scanning electron microscopy and confocal microsco! py revealed that the incorporation of CFNT in collagen-based constructs was an effective means of restructuring collagen fibrils because CFNT strongly bound to collagen molecules inducing the formation of larger fibril bundles. However, increased nanotube loading concentration caused the formation of denser fibril network and larger aggregates. Static stress-strain tests under compression showed that the addition nanotube into collagen-based constructs did not significantly increase static compressive moduli. Creep/recovery testing under compression revealed that CFNT-collagen constructs showed improved mechanical stability under continuous loading. Testing with endothelial cells showed that biocompatibility was highly dependent on nanotube loading concentration. At a low loading level, CFNT-collagen showed higher endothelial coverage than the other tested constructs or materials. Additionally, CFNT-collagen showed capability of binding to other biomolecules to enhance the ! construct functionality. In conclusion, functionalized nanotub! e-collag en composites, particularly CFNT-collagen composites, could be promising materials which provide structural support showing bundled fibril structure, biocompatibility, multi-functionality and mechanical stability, but rigorous control over chemical modification, loading concentration and nanotube dispersion are needed.

PMID: 20215088 [PubMed - as supplied by publisher]

 

Fabrication of porous polysaccharide-based scaffolds using a combined freeze-drying/cross-linking process.
March 11, 2010 at 6:53 AM

Fabrication of porous polysaccharide-based scaffolds using a combined freeze-drying/cross-linking process.

Acta Biomater. 2010 Mar 4;

Authors: Autissier A, Visage CL, Pouzet C, Chaubet F, Letourneur D

Biocompatible three-dimensional porous scaffolds are of great interest for tissue engineering applications. We present here a novel combined freeze-drying/cross-linking process to prepare porous polysaccharide-based scaffolds. This process does not require organic solvent nor porogen agent. We unexpectedly found that cross-linking of biomacromolecules such as pullulan and dextran with sodium trimetaphosphate could be performed during a freeze-drying process. We evidenced that the freeze-drying pressures modulate the degree of porosity. High freeze-drying pressure scaffolds presented pores with a mean diameter of 55+/-4 microns and a porosity of 33%+/-12%, whereas low freeze-drying pressure scaffolds contained larger pores with a mean diameter of 243+/-14 microns and a porosity of 68%+/-3%. The porous scaffolds could be easily obtained at the desired shape and were stable in culture medium for weeks. In vitro, viable mesenchymal stem cells were found associated wit! h porous scaffolds in higher proportions than with non-porous scaffolds. Moreover, cells penetrated deeper into scaffolds with larger pores. This novel combined freeze-drying/cross-linking process of polysaccharides enabled the fabrication of biocompatible scaffolds with controlled porosity and architecture suitable for 3D in vitro culture and biomedical applications.

PMID: 20215057 [PubMed - as supplied by publisher]

 

Cellular cardiomyoplasty and cardiac tissue engineering for myocardial therapy.
March 11, 2010 at 6:53 AM

Cellular cardiomyoplasty and cardiac tissue engineering for myocardial therapy.

Adv Drug Deliv Rev. 2010 Mar 6;

Authors: Wang F, Guan J

Heart diseases, including myocardial infarction (MI) and congestive heart failure (CHF), have high mortality rates. Both MI and CHF are characterized by cardiac muscle damage caused by massive cardiomyocyte death and reduced cardiac function. Cellular therapy aimed at using cells to improve cardiac function and/or regenerate new myocardium, has been extensively investigated for cardiac repair. Two strategies have been currently taken for cellular transplantation, including in situ cellular cardiomyoplasty and cardiac tissue engineering. The in situ cellular cardiomyoplasty strategy delivers cells directly into the infarcted myocardium. A variety of cell types has been shown to be beneficial in cardiac repair. However, this strategy is limited in terms of cell retention, survival of the engrafted cells, cell differentiation, and integration of transplanted cells with host tissue. Cardiac tissue engineering is an alternate strategy to in situ cellular cardiomyoplast! y, which is designed to repair infarcted myocardium using cells, biomaterials and regulative factors (for example growth factors). There are currently various approaches for cardiac tissue engineering, such as, in situ delivering cells with injectable biomaterials into the infarcted myocardium, in vitro engineering of contractile tissue constructs followed by in vivo implantation, in vitro engineering of stem cell loaded tissue constructs for in vivo myocardium regeneration, and cell sheet tissue engineering. This review provides a comprehensive progress of in situ cellular cardiomyoplasty and cardiac tissue engineering for cardiac repair.

PMID: 20214939 [PubMed - as supplied by publisher]

 

Use of Tissue Engineering in Treatment of the Male Genitourinary Tract Abnormalities.
March 11, 2010 at 6:53 AM

Use of Tissue Engineering in Treatment of the Male Genitourinary Tract Abnormalities.

J Sex Med. 2010 Feb 25;

Authors: Fu Q, Cao YL

ABSTRACT Introduction. A variety of congenital and acquired male genitourinary tract abnormalities can lead to organ damage or tissue loss that requires surgical reconstruction. Traditional reconstructive methods do not produce consistent satisfactory structural or functional replacement and may damage the genitourinary tract. Tissue engineering provides a promising alternative for the treatment of these disorders. Aim. The aim of this article is to provide an update on clinical and experimental evidence concerning the application of tissue engineering to treatment of abnormalities in the male genitourinary tract system. Methods. A PubMed search was performed to retrieve relevant clinical and basic literature. Main Outcome Measures. The topics discussed in this review include the experimental and clinical application of tissue engineering for reconstruction of the urethra, penis, testis, and prostate. Results. Tissue engineering techniques can provide a plentiful ! source of healthy tissue for reconstructive purposes. Acellular matrix scaffold and seed cells are two key elements in tissue engineering. Proper employment of seed cells and scaffold material may result in synergistic effects. Moreover, new tissue engineering technologies are being transferred from the laboratory to clinical practice. Conclusions. Tissue engineering provides biological substitutes that can restore and maintain normal function in diseased and injured tissues, thus providing an effective technique for regeneration of the male genitourinary tract. Fu Q, and Cao Y. Use of tissue engineering in treatment of the male genitourinary tract abnormalities. J Sex Med **;**:**-**.

PMID: 20214721 [PubMed - as supplied by publisher]

 

Tissue-Engineered 3-D Tumor Models to Study Tumor Angiogenesis.
March 11, 2010 at 6:53 AM

Tissue-Engineered 3-D Tumor Models to Study Tumor Angiogenesis.

Tissue Eng Part A. 2010 Mar 9;

Authors: Verbridge SS, Chandler EM, Fischbach-Teschl C

Cell-microenvironment interactions play a critical role in the transformation of normal cells into cancer; however, the underlying mechanisms and effects are far from being well understood. Tissue Engineering provides innovative culture tools and strategies to study tumorigenesis under pathologically relevant culture conditions. Specifically, integration of biomaterials, scaffold fabrication, and micro/nano-fabrication techniques offers great promise to reveal the dynamic role of chemical, cell-cell, cell-extracellular matrix, and mechanical interactions in the pathogenesis of cancer. Due to the central importance of blood vessel formation in tumor growth, progression, and drug response, this review will discuss specific design parameters for the development of culture microenvironments to study tumor angiogenesis. Tumor Engineering approaches have the potential to revolutionize our understanding of cancer, provide new platforms for testing of anti-cancer drugs, a! nd may ultimately result in improved treatment strategies.

PMID: 20214471 [PubMed - as supplied by publisher]

 

Microfluidic culture models of tumor angiogenesis.
March 11, 2010 at 6:53 AM

Microfluidic culture models of tumor angiogenesis.

Tissue Eng Part A. 2010 Mar 9;

Authors: Fischbach-Teschl C, Stroock A

Blood vessels control all stages of tumor development and therapy by defining the physicochemical and cellular state of the tumor microenvironment. However, no pathologically relevant culture systems currently exist that recapitulate the associated cellular and convective mass transfer processes that are implicated in tumor angiogenesis. By integrating tissue engineering and microfluidic technologies it will be possible to develop tumor-mimetic culture environments with embedded microvascular structures. Utilization of these microfluidic tumor models will help reveal the importance of the transport of chemical and cellular factors in tumor angiogenesis, and provide a test bed that may ultimately improve current strategies to anti-angiogenic therapy.

PMID: 20214470 [PubMed - as supplied by publisher]

 

Enzymatically Crosslinked Dextran-tyramine Hydrogels as Injectable Scaffolds for Cartilage Tissue Engineering.
March 11, 2010 at 6:53 AM

Enzymatically Crosslinked Dextran-tyramine Hydrogels as Injectable Scaffolds for Cartilage Tissue Engineering.

Tissue Eng Part A. 2010 Mar 9;

Authors: Jin R, Moreirateixeira LS, Dijkstra P, Zhong Z, van Blitterswijk C, Karperien M, Feijen J

Enzymatic crosslinking of dextran-tyramine (Dex-TA) conjugates in the presence of horseradish peroxidase and hydrogen peroxide was successively applied in the preparation of hydrogels. Depending on the molecular weight of the dextran (Mn, GPC of 14000 or 31000 g/mol) and the degree of substitution (DS of 5, 10 or 15) with tyramine (TA) groups, the gelation times ranged from 20 s to 1 min. Hydrogels prepared from Dex31k -TA with a DS of 10 had storage moduli up to 60 kPa. Similar values were found when chondrocytes were incorporated into the hydrogels. Chondrocyte-seeded Dex-TA hydrogels were prepared at a molar ratio of H2O2/TA of 0.2 and cultured in a chondrocyte medium. A live-dead assay and a MTT assay revealed that almost all chondrocytes retained their viability after 2 weeks. SEM analysis showed that the encapsulated chondrocytes were capable of maintaining their round shape. Histology and immunofluorescent staining demonstrated the production of glycosamino! glycans (GAGs) and collagen type II after culturing for 14 and 21 days. Biochemical analysis showed that GAG accumulation increased with time inside Dex-TA hydrogels. Besides, GAG/DNA for Dex-TA hydrogels was higher than that for agarose at day 28. These results indicate that Dex-TA hydrogels are promising 3D scaffolds for cartilage tissue engineering applications.

PMID: 20214454 [PubMed - as supplied by publisher]

 

Constructing Kidney-like Tissues from Cells Based on Programs for Organ Development: Towards a Method of In Vitro Engineering of the Kidney.
March 11, 2010 at 6:53 AM

Constructing Kidney-like Tissues from Cells Based on Programs for Organ Development: Towards a Method of In Vitro Engineering of the Kidney.

Tissue Eng Part A. 2010 Mar 9;

Authors: Rosines E, Johkura K, Zhang X, Schmidt HJ, Decambre M, Bush KT, Nigam S

The plausibility of constructing vascularized 3-dimensional kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct, (WD), and the metanephric mesenchyme (MM). Isolated MMs were capable of inducing branching morphogenesis in WD tissue in recombination cultures, indicating that the isolated MM retains inductive capacity for cells other than the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells (UB and mIMCD cells) were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (mIMCD cells), supporting the view that the collecting system can be constructed from renal epithelial cells when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced! factors that stimulate branching morphogenesis, whereas another, RIMM-18, supported WD budding as a feeder layer. While engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, optimal macro and micro-patterning of kidney-like tissue is necessary for function of an organ assembled using a tissue engineering approach. To identify suitable conditions, 3D reconstructions of HoxB7-GFP mouse rudiments (E12) cultured on a filter or suspended in a collagen gel (type I or type IV), revealed that type IV collagen 3D culture supports the deepest tissue growth (600 +/- 8 mum) and the largest kidney volume (0.22 +/- 0.02 m! m3), and enabled the development of an umbrella-shaped collect! ing syst em such as occurs in vivo. Taken together with prior work (Rosines et al., 2007, Proc. Natl. Acad. Sci, USA, 104:20938; Steer et al., 2002, Kidney Int., 62:1958), these results support the plausibility of a developmental strategy for constructing vascularized 3D kidney-like tissues from recombinations of cultured renal progenitor cells.

PMID: 20214453 [PubMed - as supplied by publisher]

 

Implication of silk film RGD availability and surface roughness on cytoskeletal organization and proliferation of primary rat bone marrow cells.
March 11, 2010 at 6:53 AM

Implication of silk film RGD availability and surface roughness on cytoskeletal organization and proliferation of primary rat bone marrow cells.

Tissue Eng Part A. 2010 Mar 9;

Authors: Mandal BB, Das S, Chaudhury K, Kundu SC

In order to design and fabricate next-generation tissue engineering materials, the understanding of cell responses to material surfaces is required. Surface topography presents powerful cues for cells and can strongly influence cell morphology, adhesion and proliferation but the mechanisms mediating this cell response remain unclear. In this report, we have investigated the effects of nanoroughness assemblies of silk fibroin protein membranes and RGD sequences fabricated from two different silk fibroin sources, i.e. mulberry (Bombyx mori) and non-mulberry (Antheraea mylitta) on cytoskeletal organization, proliferation and viability using primary rat bone marrow cells. To vary surface roughness, silk fibroin substrates were treated with graded ethanol (50 - 100 % v/v) to produce nanoarchitectures in the range of 1- 12 nm height. The graded alcohol treatments have been found to produce nanoscale topographies of reproducible height in a much faster and cheaper way. T! he results showed no difference in cell proliferation within the same treatment groups for both silk types. Though, a change in cell response in terms of good cytoskeleton organization, actin development, cell spreading and strong binding to substratum using A. mylitta fibroin protein films having RGD sequences was observed. This finding provides the information that the nanoroughness affects cellular processes in a cell specific manner and may be helpful for the development of ''smart'' silk based biomaterials especially for directing cell differentiation and regenerative therapies.

PMID: 20214452 [PubMed - as supplied by publisher]

 

Experimental intervertebral disc regeneration with tissue engineered composite in a canine model.
March 11, 2010 at 6:53 AM

Experimental intervertebral disc regeneration with tissue engineered composite in a canine model.

Tissue Eng Part A. 2010 Mar 9;

Authors: Ruan D, Xin H, Zhang C, Wang C, Xu C, Li C, He Q

To construct PLGA scaffold-nucleus pulposus cells composite using tissue engineering methods and to investigate the in vivo performance of the composite in a canine model. Nucleus pulposus (NP) cells were isolated from the lumbar intervertebral discs of beagle dog. NP cells were cultured and expanded in vitro and seeded onto a 3-D porous poly (L-lactic-co-glycolic acid) (PLGA) scaffold. The composite was tested in 18 beagle dogs which were randomly divided into 3 groups: nucleotomy alone (A); nucleotomy with PLGA implantation(B), and nucleotomy with PLGA scaffold/NP cells composite implantation (C). X-ray and MRI scan were performed pre- and postoperatively. Evaluation of disc height, segment stability, biomechanics, and immunohistochemical analysis were performed. Dog NP cells could attach and showed proliferation activity within the PLGA scaffold in vitro and in vivo. The disc height, segmental stability and T2-weighted signal intensity on MRI were well preserve! d in group C dogs with engineered composite. PHK-26 positive cells were found within the area of the nucleus pulposus 8 weeks post operatively. The NP cell-PLGA scaffold composite can prevent or delay the degenerate process after nucleotomy in the canine model. This hybrid composite might be a promising construct for intervertebral disc regeneration.

PMID: 20214451 [PubMed - as supplied by publisher]

 

Beyond Cell Capture: Antibody-conjugation Improves Haemocompatibility for Vascular Tissue Engineering Applications.
March 11, 2010 at 6:53 AM

Beyond Cell Capture: Antibody-conjugation Improves Haemocompatibility for Vascular Tissue Engineering Applications.

Tissue Eng Part A. 2010 Mar 9;

Authors: Chong MS, Teoh SH, Teo EY, Zhang ZY, Lee CN, Koh SC, Choolani M, Chan J

Antibody conjugated surfaces are being studied for cardiovascular implant applications to capture Endothelial Progenitor Cells (EPCs) and promote endothelialisation. However, despite the large amount of literature on EPC capture efficiency, little effort has been made to understand acute blood responses to the modified surfaces. We hypothesise that CD34 antibody conjugation passivates surfaces against pro-coagulatory events,and thus improves haemocompatibility. To test this hypothesis, we subjected the modified films to haemocompatibility tests to evaluate contact activation, platelet adhesion and activation, as well as whole blood clotting response to the films. Here, we demonstrate the alteration of blood responses due to polyacrylic acid (PAAc) engraftment and subsequent antibody conjugation on biaxially stretched polycaprolactone (muXPCL) films. Compared to muXPCL, PAAc engrafted PCL (PCL-PAAc) and CD34 antibody conjugated films (PCL-PAAC-CD34) resulted in a 4! - 9 fold (p<0.001) reduced platelet activation. PCL-PAAc however resulted in an increased contact activation on thromboelastography, and a poorer blood compatibility index (BCI) assay (43.4+/-2.3 vs 60.9+/-2.5%, p<0.05). PCL-PAAC-CD34 on the other hand resulted in delayed clot formation (r=19.3+/-1.5, k=6.8+/-0.6 min), reduced platelet adhesion and activation, and yielded the highest BCI score, indicating least thrombogenicity (69.3+/-3.2%). Our results suggest that CD34 antibody conjugation significantly improved the haemocompatibility of PAAc-conjugated muXPCL.

PMID: 20214450 [PubMed - as supplied by publisher]

 

Tumor Engineering; the Other Face of Tissue Engineering.
March 11, 2010 at 6:53 AM

Tumor Engineering; the Other Face of Tissue Engineering.

Tissue Eng Part A. 2010 Mar 9;

Authors: Bissell M, Ghajar CM

Advances in Tissue Engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function of a given tissue. We believe the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of so-called 'tumor engineering'; that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physica! l scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment.

PMID: 20214448 [PubMed - as supplied by publisher]

 

Nanotechnology for bone materials.
March 11, 2010 at 6:53 AM

Related Articles

Nanotechnology for bone materials.

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009 May;1(3):336-51

Authors: Tran N, Webster TJ

It has been established that for orthopedic-related research, nanomaterials (materials defined as those with constituent dimensions less than 100 nm in at least one direction) have superior properties compared to conventional counterparts. This review summarizes studies that have demonstrated enhanced in vitro and in vivo osteoblast (bone-forming cells) functions (such as adhesion, proliferation, synthesis of bone-related proteins, and deposition of calcium-containing mineral) on nanostructured metals, ceramics, polymers, and composites thereof compared to currently used implants. These results strongly imply that nanomaterials may improve osseointegration, which is crucial for long-term implant efficacy. This review also focuses on novel drug-carrying magnetic nanoparticles designed to treat various bone diseases (such as osteoporosis). Although further investigation of the in vivo responses and toxicity of these novel nanomaterials pertinent for orthopedic appli! cations are needed, nanotechnology clearly has already demonstrated the ability to produce better bone implants and therefore should be further investigated.

PMID: 20049801 [PubMed - indexed for MEDLINE]

 

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