bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situ crosslinkable heparin‐containing poly(ethylene glycol) hydrogels for sustained anticoagulant release
Authors: Baldwin Aaron D. , Robinson Karyn G. , Militar Jaimee L. , Derby Christopher D. , Kiick Kristi L. , Akins Robert E. 
Published: May 2012

AbstractLow‐molecular weight heparin (LMWH) is widely used in anticoagulation therapies and for the prevention of thrombosis. LMWH is administered by subcutaneous injection usually once or twice per day. This frequent and invasive delivery modality leads to compliance issues for individuals on prolonged therapeutic courses, particularly pediatric patients. Here, we report a long‐term delivery method for LMWH via subcutaneous injection of long‐lasting hydrogels. LMWH is modified with reactive maleimide groups so that it can be crosslinked into continuous networks with four‐arm thiolated poly(ethylene glycol) (PEG‐SH). Maleimide‐modified LMWH (Mal‐LMWH) retains bioactivity as indicated by prolonged coagulation time. Hydrogels comprising PEG‐SH and Mal‐LMWH degrade via hydrolysis, releasing bioactive LMWH by first‐order kinetics with little initial burst release. Separately dissolved Mal‐LMWH and PEG‐SH solutions were co‐injected subcutaneously in New Zealand White rabbits. The injected solutions successfully formed hydrogels in situ and released LMWH as measured via chromogenic assays on plasma samples, with accumulation of LMWH occurring at day 2 and rising to near‐therapeutic dose equivalency by day 5. These results demonstrate the feasibility of using LMWH‐containing, crosslinked hydrogels for sustained and controlled release of anticoagulants. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
In vitro and in vivo toxicity of rinsed and aged nanocellulose–polypyrrole composites
Authors: Ferraz Natalia , Strømme Maria , Fellström Bengt , Pradhan Sulena , Nyholm Leif , Mihranyan Albert 
Published: May 2012

AbstractNovel composites of nanocellulose and the conducting polymer polypyrrole (PPy) are herein suggested as potential candidates for active ion‐extraction membranes in electrochemically controlled hemodialysis. This study has defined processing parameters to obtain a biocompatible nanocellulose‐PPy composite, and for the first time, the effect of the composite aging on cell viability has been studied. The influence of rinsing and extraction process steps, as well as aging under different conditions (i.e. in air, at –20°C and in argon), on the electroactivity and cytotoxicity of a PPy‐nanocellulose composite has been investigated. The biocompatibility evaluation was based on indirect toxicity assays with fibroblasts and monocyte cell lines and an acute toxicity test in mice, while the electroactivity was evaluated by cyclic voltammetry experiments. The as‐prepared composite did not induce any cytotoxic response in vitro or in vivo. Extensive rinsing and 48 h incubation in biological buffer previous to the preparation of the culture medium extracts were, however, necessary to obtain a noncytotoxic composite. The as‐prepared composite was also found to exhibit acceptable electrochemical performance, which was retained upon 4 weeks storage in argon atmosphere. It was shown that aging of the composite had a negative effect on biocompatibility, regardless of the storage condition. Thus, to allow for longtime storage of electroactive nanocellulose‐PPy hemodialysis membranes, the degradation of PPy upon storage must be controlled. The present results show that the biocompatibility of PPy composites depends on the rinsing and pretreatment of the composite material as well as the aging of the material. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Orthopedic implant cobalt‐alloy particles produce greater toxicity and inflammatory cytokines than titanium alloy and zirconium alloy‐based particlesin vitro, in human osteoblasts, fibroblasts, and macrophages
Authors: Dalal Ali , Pawar Vivek , McAllister Kyron , Weaver Carolyn , Hallab Nadim J. 
Published: May 2012

AbstractThe performance of total joint arthroplasty (TJA) depends on the size/shape, material, and amounts of implant debris. Much remains unknown in terms of which types of debris are most reactive. We compared the responses of human periimplant cells, osteoblasts, fibroblasts, and macrophages, exposed to particles of different metal‐based particles (i.e., cobalt‐chromium‐molybdenum (CoCrMo) alloy, titanium (Ti) alloy, zirconium (Zr) oxide, and Zr alloy. CoCrMo‐alloy particles were by far the most toxic (p< 0.05) and decreased viability and proliferation of human osteoblasts, fibroblasts, and macrophages by >50% at a dose of only 50 particles per cell. All particle types induced the production of interleukin (IL)‐6, tumor necrosis factor (TNF)‐α, and IL‐8 by osteoblasts, fibroblasts, and monocytes/macrophages. However, the greatest cytokine responses of macrophages were to CoCrMo alloy (TNF‐α and IL‐8) and Ti alloy (IL‐1β). Likewise, the greatest responses of fibroblasts and osteoblasts were to CoCrMo alloy (IL‐6 and TNF‐α) (i.e., IL‐6 300 pg/mL; 30‐fold max, TNF‐α 150 pg/mL; 15‐fold max) versus controls. For macrophages, CoCrMo particles induced IL‐8 (> 2000 pg/mL; approx 100‐fold max) above controls and were also significantly elevated above levels produced by Zr‐based particles. Submicron sized (0.2‐0.9 μm) Zr‐based particles (originally presumed to be more reactive) induced less toxicity and inflammatory responses when compared with larger (approx 1 μm) CoCrMo‐alloy and Ti‐alloy particles. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Augmenting the articular cartilage‐implant interface: Functionalizing with a collagen adhesion protein
Authors: Allon Aliza A. , Ng Kenneth W. , Hammoud Sommer , Russell Brooke H. , Jones Casey M. , Rivera Jose J. , Schwartz Jeffrey , Hook Magnus , Maher Suzzane A. 
Published: May 2012

AbstractThe lack of integration between implants and articular cartilage is an unsolved problem that negatively impacts the development of treatments for focal cartilage defects. Many approaches attempt to increase the number of matrix‐producing cells that can migrate to the interface, which may help to reinforce the boundary over time but does not address the problems associated with an initially unstable interface. The objective of this study was to develop a bioadhesive implant to create an immediate bond with the extracellular matrix components of articular cartilage. We hypothesized that implant‐bound collagen adhesion protein (CNA) would increase the interfacial strength between a poly(vinly alcohol) implant and an articular cartilage immediately after implantation, without preventing cell migration into the implant. By way of a series of in vitro immunohistochemical and mechanical experiments, we demonstrated that (i) free CNA can bind to articular cartilage, (ii) implant‐bound CNA can bind to collagen type II and (iii) implants functionalized with CNA result in a fourfold increase in interfacial strength with cartilage relative to untreated implants at day zero. Of note, the interfacial strength significantly decreased after 21 days in culture, which may be an indication that the protein itself has lost its effectiveness. Our data suggest that functionalizing scaffolds with CNA may be a viable approach toward creating an initially stable interface between scaffolds and articular cartilage. Further efforts are required to ensure long‐term interface stability. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Compositional dependence of hematopoietic stem cells expansion on bioceramic composite scaffolds for bone tissue engineering
Authors: Mishra Sarika , Rajyalakshmi A. , Balasubramanian K. 
Published: May 2012

AbstractBioceramics are although well known for their osteoinductive and osseointegrative properties in bone tissue regeneration, yet, they are inappropriate for load bearing applications due to inadequate mechanical strength. In this article, the authors report the expansion of hematopoietic stem cells (HSCs) on as‐synthesized composite scaffolds from hydroxyapatite and β‐tricalcium phosphate for bone tissue engineering, in an adequate load‐bearing application. The physical, structural, and mechanical properties of the composite scaffolds have been examined and correlated with the in vitro adhesion pattern of HSCs. The results indicated that the response of HSCs varies with change in the stoichiometry of composite scaffolds. The H2T2 scaffolds have exhibited the highest expansion of CD34+ cells and long‐term culture initiating cells when compared with other stoichiometries. The results suggest that H2T2 composite can be a potential strategic bone‐graft substitute in contrast with monolithic bioceramics, serving a dual role of bioresorbability and enhanced load‐bearing capacity. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2483–2491, 2012.
Tissue engineering of ureteral grafts by seeding urothelial differentiated hADSCs onto biodegradable ureteral scaffolds
Authors: Shi Jian‐Guo , Fu Wei‐Jun , Wang Xiao‐Xiong , Xu Yong‐De , Li Gang , Hong Bao‐Fa , Wang Yan , Du Zhi‐Yan , Zhang Xu 
Published: May 2012

AbstractThe study is aimed to evaluate the differentiation potential of human adipose‐derived stem cells (hADSCs) into urothelial lineage, and to assess possibility of constructing ureteral grafts using the differentiated hADSCs and a novel polylactic acid (PLA)/collagen scaffolds. HADSCs were indirectly cocultured with urothelial cells in a transwell coculture system for urothelial differentiation. After 14 days coculturing, differentiation was evaluated by detecting urothelial lineage markers (cytokeratin‐18 and uroplakin 2) in mRNA and protein level. Then the differentiated hADSCs were seeded onto PLA/collagen ureteral scaffolds and culturedin vitrofor 1 week. The biocompatibility of the scaffolds was tested by scanning electron microscopy (SEM) and MTT analysis. At last, the cell/scafflod grafts were subcutaneously implanted into 4‐week‐old female athymic mice for 14 days. The results demonstrated that the hADSCs could be efficiently induced into urothelial lineage by indirect coculture. The differentiated cells seeded onto the PLA/collagen ureteral scaffolds survived up to 7 days and maintained proliferationin vitro, which indicated that the scaffolds displayed good biocompatibility.In vivostudy showed that the differentiated cells in the grafts survived, formed multiple layers on the scaffolds and expressed urothelial lineage markers. In conclusion, hADSCs may serve as an alternative cell resource in cell‐based tissue engineering for ureteral reconstruction. These cells could be employed to construct a model of ureteral engineering grafts and be effectively appliedin vivo, which could be a new strategy on ureteral replacement with applicable potential in clinical research. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:2612–2622, 2012.
Titanium surfaces with nanotopography modulate cytokine production in cultured human gingival fibroblasts
Authors: Schwartz‐Filho Humberto Osvaldo , Morandini Ana Carolina Faria , Ramos‐Junior Erivan Schnaider , Jimbo Ryo , Santos Carlos Ferreira , Marcantonio Elcio , Wennerberg Ann , Marcantonio Rosemary Adriana Chiérici 
Published: May 2012

AbstractImplant topography is an important factor that influences many cell types. To understand the role of topography in the inflammatory events, we evaluated the response of human gingival fibroblasts (HGFs) by the release pattern of cytokines. HGFs were cultured on Ti discs for 24 and 48 h. Four different surface treatments were used: machining method (turned), blasting followed by an acid‐etching method (BAE), oxidative nanopatterning (ON) method, and an association of blasting followed by an acid‐etching plus oxidative nanopatterning (BAE+ON) method. Extracellular levels of IL‐6, IL‐8, transforming growth factor beta (TGF‐β), IL‐4, and IL‐10 were measured by enzyme‐linked immunosorbant assay. Increased levels of IL‐6 and IL‐8 were observed in all surfaces after 24 h which decreased after 48 h. BAE, ON, and BAE+ON surfaces showed a reduction in IL‐6 levels compared with the turned after 48 h (p < 0.05). On one hand, IL‐8 production was lower in BAE+ON in comparison to the turned surface (p < 0.05). On the other hand, IL‐4 showed increased levels with 48 h, which were significantly different between turned, BAE, and ON surfaces, but not with BAE+ON. Additionally, TGF‐β and IL‐10 production were not detected. This study indicates that nanotopography might be important in the modulation of the inflammatory response in cultured HGFs. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2629–2636, 2012.
Optimizing siRNA efficacy through alteration in the target cell‐adhesion substrate interaction
Authors: Khormaee Sariah , Ali Omar A. , Chodosh James , Mooney David J. 
Published: May 2012

AbstractThe clinical potential of short interfering RNA (siRNA) based therapeutics remains hindered by the challenge of delivering enough siRNA into the cytoplasm to yield a clinically relevant effect. Although much research has focused on optimizing delivery vehicles for this class of molecules, considerably less is known about the microenvironmental influences on the response of target cells to siRNA. The substrate to which cells adhere is one component of the microenvironment that can modulate cellular behavior. Here, we tested the hypothesis that modulating the properties of cellular adhesion substrates can alter siRNA efficacy. Specifically, cationic lipid complexed siRNA particles were applied to U251 cells seeded on alginate hydrogel surfaces with systematic variation in elastic modulus and integrin ligand arginine‐glycine‐aspartate (RGD) peptide density. These experiments revealed no change in siRNA‐mediated eGFP knockdown over the elastic modulus range tested (53–133 kPa). However, an eightfold increase in RGD content of the alginate growth substrate resulted in an increase in siRNA knockdown efficacy from 25 ± 12% to 52 ± 10%, a more than twofold increase in silencing. Our results identify control of the cell‐adhesion substrate interaction as a modulator of siRNA protein silencing efficacy. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2637–2643, 2012.
Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and CXCL2 in ovarian and endometrial cancer cells
Authors: Kavandi Leyla , Collier Michael A. , Nguyen Huyen , Syed Viqar 
Published: May 2012

AbstractCytokines/chemokines are key players in cancer‐related inflammation. Increasing evidence suggests that chemokines produced by tumor cells are the mediators of metastasis. Thus, agents that can downregulate chemokines expression have potential against cancer metastasis. We have previously shown inhibition of ovarian and endometrial cancer cell growth with progesterone and calcitriol. In the present study, we evaluated the effect of these two agents on the expression of inflammatory genes. Using a RT‐PCR array of inflammatory cytokines/chemokines and their receptors, we found a marked attenuation of CXCL1 and CXCL2 (GRO‐α and ‐β) in cancer cells by both treatments. Knockdown of NFκB resulted in a reduced expression of CXCL1 and CXCL2 and the inhibitory effect of progesterone and calcitriol on the expression of chemokines was abrogated in NFκB‐silenced cancer cells. Silencing of IκBα increased the expression of CXCL1 and CXCL2 in cancer cells, which can be attributed to the increased activation of NFκB‐p65, caused by the lack of its inhibitor. Progesterone and calcitriol‐induced inhibition was abolished in IκBα‐knockdown cells. Our results demonstrate that suppression of IκBα phosphorylation by progesterone and calcitriol contributes to the reduced expression of CXCL1 and CXCL2. Downregulation of CXCL1 and CXCL2 was associated with a marked inhibition of metastasis‐promoting genes. Overall, our results indicate that progesterone and calcitriol inhibit IκBα phosphorylation, NFκB activation, and the expression of NFκB regulated metastasis promoting genes. These results provide attractive data for the possible use of progesterone and calcitriol in the management of endometrial and ovarian tumors. J. Cell. Biochem. 113: 3143–3152, 2012. © 2012 Wiley Periodicals, Inc.
Comparative cellular and molecular analyses of pooled bone marrow multipotent mesenchymal stromal cells during continuous passaging and after successive cryopreservation
Authors: Mamidi Murali Krishna , Nathan Kavitha Ganesan , Singh Gurbind , Thrichelvam Saratha Thevi , Mohd Yusof Nurul Ain Nasim , Fakharuzi Noor Atiqah , Zakaria Zubaidah , Bhonde Ramesh , Das Anjan Kumar , Majumdar Anish Sen 
Published: May 2012

AbstractThe clinical application of human bone marrow derived multipotent mesenchymal stromal cells (MSC) requires expansion, cryopreservation, and transportation from the laboratory to the site of cell implantation. The cryopreservation and thawing process of MSCs may have important effects on the viability, growth characteristics and functionality of these cells both in vitro and in vivo. More importantly, MSCs after two rounds of cryopreservation have not been as well characterized as fresh MSCs from the transplantation perspective. The objective of this study was to determine if the effect of successive cryopreservation of pooled MSCs during the exponential growth phase could impair their morphology, phenotype, gene expression, and differentiation capabilities. MSCs cryopreserved at passage 3 (cell bank) were thawed and expanded up to passage 4 and cryopreserved for the second time. These cells (passive) were then thawed and cultured up to passage 6, and, at each passage MSCs were characterized. As control, pooled passage 3 cells (active) after one round of cryopreservation were taken all the way to passage 6 without cryopreservation. We determined the growth rate of MSCs for both culture conditions in terms of population doubling number (PDN) and population doubling time (PDT). Gene expression profiles for pluripotency markers and tissue specific markers corresponding to neuroectoderm, mesoderm and endoderm lineages were also analyzed for active and passive cultures of MSC. The results show that in both culture conditions, MSCs exhibited similar growth properties, phenotypes and gene expression patterns as well as similar differentiation potential to osteo‐, chondro‐, and adipo‐lineages in vitro. To conclude, it appears that successive or multiple rounds of cryopreservation of MSCs did not alter the fundamental characteristics of these cells and may be used for clinical therapy. J. Cell. Biochem. 113: 3153–3164, 2012. © 2012 Wiley Periodicals, Inc.
Nestin protects mouse podocytes against high glucose‐induced apoptosis by a Cdk5‐dependent mechanism
Authors: Liu Wei , Zhang Yue , Hao Jun , Liu Shuxia , Liu Qingjuan , Zhao Song , Shi Yonghong , Duan Huijun 
Published: May 2012

AbstractPodocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate hyperglycemia‐induced podocyte apoptosis remain poorly understood. Recent findings indicate that the disruption of the cytoskeleton is related to the podocyte apoptosis. In the present study, we investigated the involvement of nestin, an important cytoskeleton‐associated class VI intermediate filament (IF) protein, in the high glucose (HG)‐induced podocyte apoptosis. Our data showed that HG decreased the expression level of nestin, either mRNA or protein, in a time‐dependent manner in cultured podocytes. Also, through knockdown of nestin expression by miRNA interference, the HG‐induced podocyte apoptotic rate was significantly increased. The expression of cleaved caspase‐3 was also markedly elevated. Considering that nestin is a substrate of cyclin‐dependent kinase 5 (Cdk5), we further assessed the expression of Cdk5 in HG‐treated podocytes. The results showed that HG stimulation increased the protein and mRNA expression of Cdk5 in a time‐dependent manner in cultured mouse podocytes. The protein activator of Cdk5, p35, was also increased in a time‐dependent manner by HG stimulation, and downregulation of Cdk5 by miRNA interference attenuated the nestin reduction in HG‐treated podocytes; the HG‐induced podocyte apoptosis, the increased cleaved caspase‐3 expression and the Bax/Bcl‐2 ratio were all effectively attenuated. These data suggested that nestin, which is dependent on Cdk5 regulation, plays a cytoprotective role in HG‐induced podocyte apoptosis. J. Cell. Biochem. 113: 3186–3196, 2012. © 2012 Wiley Periodicals, Inc.
Silicate modulates the cross‐talk between osteoblasts (SaOS‐2) and osteoclasts (RAW 264.7 cells): Inhibition of osteoclast growth and differentiation
Authors: Schröder H.C. , Wang X.H. , Wiens M. , Diehl‐Seifert B. , Kropf K. , Schloßmacher U. , Müller W.E.G. 
Published: May 2012

AbstractIt has been shown that inorganic monomeric and polymeric silica/silicate, in the presence of the biomineralization cocktail, increases the expression of osteoprotegerin (OPG) in osteogenic SaOS‐2 sarcoma cells in vitro. In contrast, silicate does not affect the steady‐state gene expression level of the osteoclastogenic ligand receptor activator of NF‐κB ligand (RANKL). In turn it can be expected that the concentration ratio of the mediators OPG/RANKL increases in the presence of silicate. In addition, silicate enhances the growth potential of SaOS‐2 cells in vitro, while it causes no effect on RAW 264.7 cells within a concentration range of 10–100 µM. Applying a co‐cultivation assay system, using SaOS‐2 cells and RAW 264.7 cells, it is shown that in the presence of 10 µM silicate the number of RAW 264.7 cells in general, and the number of TRAP+ RAW 264.7 cells in particular markedly decreases. The SaOS‐2 cells retain their capacity of differential gene expression of OPG and RANKL in favor of OPG after exposure to silicate. It is concluded that after exposure of the cells to silicate a factor(s) is released from SaOS‐2 cells that causes a significant inhibition of osteoclastogenesis of RAW 264.7 cells. It is assumed that it is an increased secretion of the cytokine OPG that is primarily involved in the reduction of the osteoclastogenesis of the RAW 264.7 cells. It is proposed that silicate might have the potential to stimulate osteogenesis in vivo and perhaps to ameliorate osteoporotic disorders. J. Cell. Biochem. 113: 3197–3206, 2012. © 2012 Wiley Periodicals, Inc.