|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Growth Factor Delivery Through Self-assembling Peptide Scaffolds. Clin Orthop Relat Res. 2011 Apr 19; Authors: Miller RE, Kopesky PW, Grodzinsky AJ BACKGROUND: The best strategy for delivering growth factors to cells for the purpose of cartilage tissue engineering remains an unmet challenge. Tethering biotinylated insulin-like growth factor-1 (bIGF-1) to the self-assembling peptide scaffold (RADA)(4) effectively delivers bioactive bIGF-1 to cardiac tissue. QUESTIONS/PURPOSES: We therefore asked whether: (1) soluble bIGF-1 could stimulate proteoglycan production by chondrocytes; (2) bIGF-1 could be adsorbed or tethered to the self-assembling peptide scaffold (KLDL)(3); (3) adsorbed or tethered bIGF-1 could stimulate proteoglycan production; and (4) transforming growth factor-β1 (TGF-β1) could be adsorbed or tethered and stimulate proteoglycan production by bone marrow stromal cells (BMSCs). METHODS: Chondrocytes or BMSCs were encapsulated in (KLDL)(3). The growth factors were (1) delivered solubly in the medium; (2) adsorbed to (KLDL)(3); or (3) tethered to (KLDL)(3) through biotin-streptavidin bonds. Fluorescently tagged streptavidin was used to determine IGF-1 kinetics; sGAG and DNA content was measured. RESULTS: Soluble bIGF-1 stimulated comparable sGAG accumulation as soluble IGF-1. Tethering IGF-1 to (KLDL)(3) increased retention of IGF-1 in (KLDL)(3) compared with adsorption, but neither method increased sGAG or DNA accumulation above control. Adsorbing TGF-β1 increased proteoglycan accumulation above control, but tethering did not affect sGAG levels. CONCLUSIONS: Although TGF-β1 can be effectively delivered by adsorption to (KLDL)(3), IGF-1 cannot. Additionally, although tethering these factors provided long-term sequestration, tethering did not stimulate proteoglycan production. CLINICAL RELEVANCE: Tethering growth factors to (KLDL)(3) results in long-term delivery, but tethering does not necessarily result in the same bioactivity as soluble delivery, indicating presentation of proteins is vital when considering a delivery strategy. PMID: 21503788 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Engineering Bi-layer Nanofibrous Conduits for Peripheral Nerve Regeneration. Tissue Eng Part C Methods. 2011 Apr 18; Authors: Zhu Y, Wang A, Patel S, Kurpinski K, Diao E, Bao X, Kwong G, Young WL, Li S Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. PMID: 21501089 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | High-efficiency cell seeding method by relatively hydrophobic culture strategy. J Biomed Mater Res B Appl Biomater. 2011 Apr 18; Authors: Hsieh CH, Kuo WT, Huang YC, Huang YY Cell adhesion efficiency is one of the key factors affecting the results of manufacturing tissue engineering constructs. High efficiency is required for seeding low proliferation cells onto scaffolds. In this study, we designed a strategy to improve the efficiency of cell adhesion using hydrophobic cell culture environment to enhance cells adhering to a scaffold. Cells have lower affinity to the surface of polydimethylsiloxane (PDMS) than tissue culture polystyrene (TCPS) plates. When cells were cultured with gelatin microspheres or chitosan films in a PDMS-coated plate instead of a normal TCPS plate, there was a significant increase in cell attachment efficiency. Cells cultured in the PDMS-coated system tended to selectively attach onto the gelatin microspheres or chitosan films, which are relatively more hydrophilic than the PDMS surface. However, minimal cell attachment on gelatin microspheres or chitosan films was observed when gelatin microspheres or chitosan films were placed in normal TCPS plate. Cell counting experiments with gelatin microspheres in the PDMS-coated system resulted in a cell attachment efficiency of 89.8% after 1 day of cultivation, whereas the cell attachment efficiency was less than 1% in normal TCPS plate. The results demonstrate that the method is easy to use and could be useful for fast cultivation of cell-scaffold constructs. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011. PMID: 21504053 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Current and future periodontal tissue engineering. Periodontol 2000. 2011 Jun;56(1):166-87 Authors: Izumi Y, Aoki A, Yamada Y, Kobayashi H, Iwata T, Akizuki T, Suda T, Nakamura S, Wara-Aswapati N, Ueda M, Ishikawa I PMID: 21501243 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Research progress of myocardial tissue engineering scaffold materials]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Mar;25(3):361-4 Authors: Fang Y, Liao B To review the current status and problems in the developing scaffolds for the myocardial tissue engineering application. PMID: 21500594 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Development and Characterization of a Full-Thickness Acellular Porcine Cornea Matrix for Tissue Engineering. Artif Organs. 2011 Apr 19; Authors: Du L, Wu X Our aim was to produce a natural, acellular matrix from porcine cornea for use as a scaffold in developing a tissue-engineered cornea replacement. Full-thickness, intact porcine corneas were decellularized by immersion in 0.5% (wt/vol) sodium dodecyl sulfate. The resulting acellular matrices were then characterized and examined specifically for completeness of the decellularization process. Histological analyses of decellularized corneal stromas showed that complete cell and α-Gal removal was achieved, while the major structural proteins including collagen type I and IV, laminin, and fibronectin were retained. DAPI staining did not detect any residual DNA within the matrix, and the DNA contents, which reflect the presence of cellular materials, were significantly diminished in the decellularized cornea. The collagen content of the decellularized cornea was well maintained compared with native tissues. Uniaxial tensile testing indicated that decellularization did not significantly compromise the ultimate tensile strength of the tissue (P > 0.05). In vitro cytotoxicity assays using rabbit corneal fibroblast cultures excluded the presence of soluble toxins in the biomaterial. In vivo implantation to rabbit interlamellar stromal pockets showed good biocompability. In summary, a full-thickness natural acellular matrix retaining the major structural components and strength of the cornea has been successfully developed. The matrix is biocompatible with cornea-derived cells and has potential for use in corneal transplantation and tissue-engineering applications. PMID: 21501189 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Self-degrading, MRI-detectable hydrogel sensors with picomolar target sensitivity. Magn Reson Med. 2010 Dec;64(6):1792-9 Authors: Colomb J, Louie K, Massia SP, Bennett KM Nanostructured hydrogels have been developed as synthetic tissues and scaffolds for cell and drug delivery, and as guides for tissue regeneration. A fundamental problem in the development of synthetic hydrogels is that implanted gel structure is difficult to monitor noninvasively. This work demonstrates that the aggregation of magnetic nanoparticles, attached to specific macromolecules in biological and synthetic hydrogels, can be controlled to detect changes in gel macromolecular structure with MRI. It is further shown that the gels can be made to self-degrade when they come into contact with a target molecule in as low as pM concentrations. The sensitivity of the gels to the target is finely controlled using an embedded zymogen cascade amplifier. These "MRI reporter gels" may serve as smart, responsive polymer implants, as tissue scaffolds to deliver drugs, or to detect specific pathogens in vivo. PMID: 20648680 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Aligned Hybrid Silk Scaffold for Enhanced Differentiation of Mesenchymal Stem Cells into Ligament Fibroblasts. Tissue Eng Part C Methods. 2011 Apr 18; Authors: Teh TK, Toh SL, Goh JC The concept of contact guidance utilizes the phenomenon of anchorage dependence of cells on the topography of seeded surfaces. It has been shown in previous studies that cells were guided to align along the topographical alignment of the seeding substrate and produced enhanced amounts of oriented extracellular matrix (ECM). In this study, we aimed to apply this concept to a three-dimensional full silk fibroin (SF) hybrid scaffold system, which comprised of knitted SF and aligned SF electrospun fibers (SFEFs), for ligament tissue engineering applications. Specifically, knitted SF, which contributed to the mechanical robustness of the system, was integrated with highly aligned SFEF mesh, which acted as the initial ECM to provide environmental cues for positive cellular response. Mesenchymal stem cells seeded on the aligned hybrid scaffolds were shown to be proliferative and aligned along the integrated aligned SFEF, forming oriented spindle-shaped morphology and produced an aligned ECM network. Expression and production of ligament-related proteins were also increased as compared to hybrid SF scaffolds with randomly arranged SFEFs, indicating differentiative cues for ligament fibroblasts present in the aligned hybrid SF scaffolds. Consequently, the tensile properties of cultured aligned constructs were significantly improved and superior to the counterpart with randomly arranged SFEF. These results thus show that the aligned hybrid scaffold system is promising for enhancing cell proliferation, differentiation, and function for ligament tissue engineering applications. PMID: 21501090 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biomaterial-mediated delivery of microenvironmental cues for repair and regeneration of articular cartilage. Mol Pharm. 2011 Apr 18; Authors: Toh WS, Spector M, Lee EH, Cao T Articular cartilage injuries are one of the most challenging problems in musculoskeletal medicine due to the poor intrinsic regenerative capacity of this tissue. The lack of efficient treatment modalities motivates research into tissue engineering - combining cells, biomaterials mimicking extracellular matrix (scaffolds) and microenvironmental signaling cues. The aim of this review is to focus on the use of biomaterials as delivery systems for microenvironmental cues in relation to their applications for treatment of cartilage defects. Latest advances in cartilage tissue engineering and regeneration are critically reviewed to demonstrate an outline of challenges toward biomaterial-based approaches of cartilage regeneration. PMID: 21500855 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Matrix Composition and Mechanics of Decellularized Lung Scaffolds. Cells Tissues Organs. 2011 Apr 18; Authors: Petersen TH, Calle EA, Colehour MB, Niklason LE The utility of decellularized native tissues for tissue engineering has been widely demonstrated. Here, we examine the production of decellularized lung scaffolds from native rodent lung using two different techniques, principally defined by use of either the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) or sodium dodecyl sulfate (SDS). All viable cellular material is removed, including at least 99% of DNA. Histochemical staining and mechanical testing indicate that collagen and elastin are retained in the decellularized matrices with CHAPS-based decellularization, while SDS-based decellularization leads to loss of collagen and decline in mechanical strength. Quantitative assays confirm that most collagen is retained with CHAPS treatment but that about 80% of collagen is lost with SDS treatment. In contrast, for both detergent methods, at least 60% of elastin content is lost along with about 95% of native proteoglycan content. Mechanical testing of the decellularized scaffolds indicates that they are mechanically similar to native lung using CHAPS decellularization, including retained tensile strength and elastic behavior, demonstrating the importance of collagen and elastin in lung mechanics. With SDS decellularization, the mechanical integrity of scaffolds is significantly diminished with some loss of elastic function as well. Finally, a simple theoretical model of peripheral lung matrix mechanics is consonant with our experimental findings. This work demonstrates the feasibility of producing a decellularized lung scaffold that can be used to study lung matrix biology and mechanics, independent of the effects of cellular components. PMID: 21502745 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Nuclear Mobility and Mitotic Chromosome Binding: Similarities between Pioneer Transcription Factor FoxA and Linker Histone H1. Cold Spring Harb Symp Quant Biol. 2011 Apr 18; Authors: Zaret KS, Caravaca JM, Tulin A, Sekiya T There exists a hierarchy by which transcription factors can engage their target sites in chromatin, in that a subset of factors can bind transcriptionally silent, nucleosomal DNA, whereas most factors cannot, and this hierarchy is reflected, at least in part, in the developmental function of the factors. For example, transcription factors possessing the Forkhead box (Fox) DNA-binding domain contain an overall fold resembling that of linker histone and thus are structured to bind DNA, site specifically, in a nucleosomal context. Where tested, Fox factors bind early in the developmental or physiological activation of target genes, thereby enabling the binding of other factors that cannot engage chromatin on their own. To investigate the basis for early chromatin binding, we have used fluorescence recovery after photobleaching (FRAP) to analyze the mobility, in the live cell nucleus, of FoxA factors in comparison to linker histone and other transcription factors. We have further analyzed the factors for their ability to bind to chromatin in mitosis and thereby serve as epigenetic marks. The results indicate that the "pioneer" features of FoxA factors involve various chromatin-binding parameters seen in linker histones and that distinguish the factors with respect to their regulatory and mechanistic functions. PMID: 21502411 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies. J Biomed Mater Res B Appl Biomater. 2011 Apr 18; Authors: Chang CC, Boland ED, Williams SK, Hoying JB Regenerative medicine seeks to repair or replace dysfunctional tissues with engineered biological or biohybrid systems. Current clinical regenerative models utilize simple uniform tissue constructs formed with cells cultured onto biocompatible scaffolds. Future regenerative therapies will require the fabrication of complex three-dimensional constructs containing multiple cell types and extracellular matrices. We believe bioprinting technologies will provide a key role in the design and construction of future engineered tissues for cell-based and regenerative therapies. This review describes the current state-of-the-art bioprinting technologies, focusing on direct-write bioprinting. We describe a number of process and device considerations for successful bioprinting of composite biohybrid constructs. In addition, we have provided baseline direct-write printing parameters for a hydrogel system (Pluronic F127) often used in cardiovascular applications. Direct-write dispensed lines (gels with viscosities ranging from 30 mPa s to greater than 600 × 10(6) mPa s) were measured following mechanical and pneumatic printing via three commercially available needle sizes (20 ga, 25 ga, and 30 ga). Example patterns containing microvascular cells and isolated microvessel fragments were also bioprinted into composite 3D structures. Cells and vessel fragments remained viable and maintained in vitro behavior after incorporation into biohybrid structures. Direct-write bioprinting of biologicals provides a unique method to design and fabricate complex, multicomponent 3D structures for experimental use. We hope our design insights and baseline parameter descriptions of direct-write bioprinting will provide a useful foundation for colleagues to incorporate this 3D fabrication method into future regenerative therapies. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011. PMID: 21504055 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Generation of PPARγ mono-allelic knockout pigs via zinc-finger nucleases and nuclear transfer cloning. Cell Res. 2011 Apr 19; Authors: Yang D, Yang H, Li W, Zhao B, Ouyang Z, Liu Z, Zhao Y, Fan N, Song J, Tian J, Li F, Zhang J, Chang L, Pei D, Chen YE, Lai L PMID: 21502977 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Characterizing accelerated capture of deoligomerized TNF within hemoadsorption beads used to treat sepsis. J Biomed Mater Res B Appl Biomater. 2011 Apr 18; Authors: Kimmel JD, Lacko CS, Delude RL, Federspiel WJ Sepsis is a systemic inflammatory response to infection, characterized by overexpression of cytokines in the circulating blood. Removal of cytokines and other inflammatory mediators from the blood may help attenuate systemic inflammation during sepsis and improve patient outcomes. In this work, we examined the dynamics of TNF capture within porous, polymeric sorbent beads used in a cytokine adsorption device. We sought to quantify how perturbation of TNF oligomeric structure accelerates TNF removal within the device. TNF was incubated with 10% DMSO for 24 h, which promoted complete monomerization of trimeric TNF, and accelerated TNF capture within the sorbent device compared with native TNF; removal halftime = 13.3 ± 1.5 min versus 112.8 ± 13.3 min, respectively. Intramolecular crosslinking stabilized the trimeric TNF structure and prevented DMSO monomerization. Results demonstrate that TNF is an unstable oligomeric molecule that can be dissociated into its smaller monomeric constituents to facilitate faster capture by hemoadsorption beads. Strategies to promote localized TNF deoligomerization at the sorbent surface may significantly accelerate TNF capture rates from the circulating blood using hemoadsorption as a treatment for sepsis. This concept could be extended to improve removal of other oligomeric molecules using size exclusion filtration materials for a variety of disease states. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011. PMID: 21504054 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stromal-derived factor-1[alpha] correlates with circulating endothelial progenitor cells and with acute lesion volume in stroke patients. Stroke. 2011 Mar;42(3):618-25 Authors: Bogoslovsky T, Spatz M, Chaudhry A, Maric D, Luby M, Frank J, Warach S, Endothelial progenitor cells (EPC) are important participants of neovascularization and are mobilized through signaling with stromal-derived factor (SDF-1α), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor, and stem cell factor. The association between EPC levels and these growth factors (GF) in acute stroke has not been previously established. We aimed to determine the association between EPC and these GF, and to elucidate a relationship between these GF and stroke severity in acute stroke patients. PMID: 21257825 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Defining the origins of Ras/p53-mediated squamous cell carcinoma. Proc Natl Acad Sci U S A. 2011 Apr 18; Authors: White AC, Tran K, Khuu J, Dang C, Cui Y, Binder SW, Lowry WE The precise identity of cancer cells of origin and the molecular events of tumor initiation in epidermal squamous cell carcinoma (SCC) are unknown. Here we show that malignancy potential is related to the developmental capacity of the initiating cancer cell in a genetically defined, intact, and inducible in vivo model. Specifically, these data demonstrate that SCCs can originate from inside the hair follicle stem cell (SC) niche or from immediate progenitors, whereas more developmentally restricted progeny, the transit amplifying (TA) cells, are unable to generate even benign tumors in the same genetic context. Using a temporal model of tumorigenesis in situ, we highlight the phenotypes of cancer progression from the hair follicle SC niche, including hyperplasia, epithelial to mesenchymal transition, and SCC formation. Furthermore, we provide insights into the inability of hair follicle TA cells to respond to tumorigenic stimuli. PMID: 21502519 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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