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CD62, thromboxane B2, and beta-thromboglobulin: a comparison between different markers of platelet activation after contact with biomaterials
Cenni, E., D. Granchi, et al. (1997), J Biomed Mater Res 36(3): 289-94.
Abstract: The authors examined the modifications of some markers of platelet activation after contact with biomaterials. Glycoprotein GMP-140 (CD62) was evaluated by flow cytometry; beta-thromboglobulin (beta-TG) and thromboxane B2 (TXB2) were determined by radioimmunoassay. Polyethylene terephthalate (PET) induced a remarkable platelet adhesion and a significant increase in beta-TG and TXB2, with no increase in CD62 on the nonadherent platelets. Pyrolytic carbon-coated PET (PC) did not induce platelet adhesion after 15 min of contact, but a significant increase in CD62 was detected. After 30 min a significant increase in platelet adhesion as well as the release of beta-TG and TXB2 were noted. The increase was lower than that observed for uncoated PET, and after 30 min of contact with PC the increase no longer was observed.

Cefepime and continuous renal replacement therapy (CRRT): in vitro permeability of two CRRT membranes and pharmacokinetics in four critically ill patients
Isla, A., A. R. Gascon, et al. (2005), Clin Ther 27(5): 599-608.
Abstract: BACKGROUND: Cefepime is a fourth-generation cephalosporin with a broad spectrum of antimicrobial activity against gram-positive and gram-negative micro-organisms. It is a useful option for treating infections in critically ill patients in intensive care due to its high degree of activity and its tolerability. OBJECTIVE: The aim of this study was to characterize in vitro the permeability to cefepime of 2 membranes frequently used in continuous renal replacement therapies (CRRTs). An in vivo study was also carried out to determine the pharmacokinetics of cefepime in critically ill patients undergoing CRRT. METHODS: In vitro procedures were conducted in 3 different fluids using polyacrylonitrile (AN69) or polysulfone (PS) membranes. Continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) were simulated. Four male patients undergoing CVVH or continuous venovenous hemodiafiltration, who received 2000 mg of cefepime intravenously every 8 hours, entered the in vivo study. Prefilter and ultrafiltrate samples were collected, and concentrations of cefepime were measured using high-performance liquid chromatography. The sieving coefficient (Sc), defined as the fraction of drug eliminated across the membrane, and the saturation coefficient (Sa), defined as the fraction of drug diffused through the membrane to the dialysate fluid, were analyzed. Pharmacokinetic parameters were determined according to a noncompartmental analysis. RESULTS: The patients ranged in age from 18 to 75 years and weighed from 65 to 80 kg. By analyzing Sc and Sa values in the in vitro procedures, no differences were detected in the permeability of AN69 or PS membranes to cefepime in CVVH or CVVHD. Sc/Sa values were between 0.93 and 1.03 in Ringer's lactate and in bovine albumin-containing Ringer's lactate samples, but Sc/Sa values were lower in plasma samples (0.82-0.95). In the in vivo portion of the study, the patients' mean (SD) Sc/Sa value was 0.76 (0.21) and correlated well with the fraction unbound to proteins (0.79 [0.09]). Clearance by CRRT (mean [SD]) was 29.0 (16.8)% of the total clearance. Serum elimination t(1/2) was 4.6 (0.9) hours, and the volume of distribution at steady state was 0.6 (0.3) L/kg (mean [SD] values). CONCLUSIONS: Cefepime was significantly removed by CRRT. No significant differences were found in the Sc or Sa of cefepime between AN69 and PS membranes used in the CVVH or CVVHD procedures. The clearance of cefepime by CRRT must be considered when dosing critically ill patients.

Cell adhesion ability of artificial extracellular matrix proteins containing a long repetitive Arg-Gly-Asp sequence
Kurihara, H. and T. Nagamune (2005), J Biosci Bioeng 100(1): 82-7.
Abstract: We generated recombinant artificial extracellular matrix (ECM) proteins containing repetitive Arg-Gly-Asp (RGD) sequences: double (RGD2), 21 (RGD21) and 43 (RGD43) repeats of RGD. RGD43-coated glass slides promoted fibroblast NIH3T3 cell adhesion and spreading on the surface. Since actin stress fibers and focal contacts were also observed in cells adhering on RGD43-coated glass slides, it was suggested that the RGD peptides in RGD43 transmitted an adhesion signal via integrins and promoted cell adhesion. We coated recombinant ECM proteins, each containing repetitive RGD domains, on polystyrene plates and investigated the effects of RGD length on the cell adhesion ability using three different cell lines, namely, fibroblast NIH3T3, HeLa cancer and neuronal PC12 cell lines. The results indicated that RGD43 had a cell adhesion ability superior to those of natural extracellular matrix proteins, fibronectin and laminin, although the effects of RGD repeat length on the cell adhesion ability depended on the cell line. As an artificial three-dimensional scaffold for cell cultivation, we also prepared an RGD43 hydrogel by a cross-linking reaction using glutaraldehyde. On the RGD43 hydrogel scaffold, fibroblast cells also successfully adhered under serum-free conditions.

Cell adhesion to acrylic intraocular lens associated with lens surface properties
Tanaka, T., M. Shigeta, et al. (2005), J Cataract Refract Surg 31(8): 1648-51.
Abstract: PURPOSE: To examine the number cells adhering to acrylic intraocular lenses (IOLs) having different degrees of surface roughness and acrylic IOLs having different contact angles. SETTING: Department of Ophthalmology, Tokyo Medical University Hospital, Tokyo, Japan. METHODS: In this study, VA-60 CB acrylic IOLs were used. After different durations of polishing of the optics, the roughness values of the lenses were set at 10.0 nm, 2.5 nm, and 0.7 nm. Intraocular lenses were also chemically coated to achieve angles of contact of 100 degrees and 57.5 degrees, with untreated IOLs having a 93.5-degree angle of contact. Intraocular lenses were cultured for 96 hours in 1 x 10(7) spleen cells/mL of developed experimental autoimmune uveoretinitis, and the number of cells adhering to the IOLs was counted. RESULTS: Fewer cells adhered to the optics of IOLs with lower roughness values, and fewer cells adhered to the IOL surface with increased contact angles. CONCLUSION: Hydrophobic optics with small roughness values of acrylic IOLs may reduce the number of adherent cells and escaped the unexpected inflammatory cell reaction associated with intraocular inflammation in the eye.

Cell adhesion to biomaterials. The role of several extracellular matrix components in the attachment of non-transformed fibroblasts and parenchymal cells
Jauregui, H. O. (1987), ASAIO Trans 33(2): 66-74.
Abstract: This presentation has covered, in part, the subject of fibroblasts or parenchymal cell adhesion to biomaterials and the manipulation of biomaterial surfaces by appropriate biologic coatings from the viewpoint of the biologist. A tissue culture laboratory with good biochemical instrumentation can contribute greatly to the understanding of biomaterial-cell interactions. Such a laboratory cannot only test the toxicity of polymers, but can also proceed with systematic investigations of the role of synthetic and biologic substrates in favoring non-transformed cell attachment, improving cell spreading, and prolonging the life in vitro of normal cell constituents from a diversity of human tissues or organs. Yet, there are certain questions about the biomaterial-tissue interactions that will only be answered by in vivo experiments, since in vitro data may or may not predict the in vivo attachment of a particular cell in a highly protein-competitive environment. One important, albeit neglected, fact is that the early deposition of a protein/glycoprotein/lipid layer from serum, plasma, or peritoneal fluid will modify any synthetic surface introduced into the body. Baier called this early step "interface conversion," and it is quite clear that the shape, surface contamination, and physiochemical properties of the synthetic substratum triggers many events that take place during this "interface conversion." Many investigators have tried to explain cell behavior in vitro by manipulating polymer surface charges, hydrophilicity/hydrophobicity, physical and chemical anisotropy, and/or substrate contractility. We believe that new biomaterial surface coatings will be available as soon as new methods of extraction from biomatrices or extracellular matrices become more familiar. These new coatings will probably promote attachment in more specific terms.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell adhesion to biomaterials: correlations between surface charge, surface roughness, adsorbed protein, and cell morphology
Hallab, N. J., K. J. Bundy, et al. (1995), J Long Term Eff Med Implants 5(3): 209-31.
Abstract: Adhesion of cells to a biomaterial surface can be a major factor mediating its biocompatibility. In this investigation, jet impingement techniques were used to quantify strength of cellular adhesion to various material surfaces. The metals tested: HS25 (a cobalt-based alloy similar to F75), 316L stainless steel, Ti-6Al-4V, and commercially pure tantalum, exhibited nearly a fivefold increase in adhesion strength above that characteristic of the polymeric materials tested (PTFE, silicone rubber, and HDPE). The present study examines physical and biological factors that might influence fibroblast adhesion to the biomaterial surface. The relation between surface charge and cellular adhesion was investigated in a controlled manner by measuring adhesion strength over a range of charge densities. The cells showed charge and electrical potential-dependent adhesion maxima, suggesting that surface alloying for optimum adherence may be possible. In a preliminary series of experiments adsorbed serum protein layers on a series of materials of differing adherence were investigated using gel electrophoresis to assess protein composition. Analysis of adsorbed proteins revealed little difference in relative abundance or total adsorption quantity. SEM micrographs of cells on Ti-6Al-4V and silicone rubber (high and low adhesion materials, respectively) demonstrated differences in cell morphology and cell density.

Cell attachment to laser-induced AAm- and HEMA-grafted ethylene-propylene rubber as biomaterial: in vivo study
Mirzadeh, H., A. A. Katbab, et al. (1995), Biomaterials 16(8): 641-8.
Abstract: With the purpose of improved tissue compatibility, ethylene-propylene rubber (EPR)-based vulcanizates have been surface grafted with acrylamide (AAm) and 2-hydroxyethyl methacrylate (HEMA) using CO2-pulsed laser as excitation source. Grafted surfaces were characterized by performing scanning electron microscopy combined with energy dispersive X-ray analysis and attenuated total reflectance infrared spectroscopy to study the surface morphology and grafting. Surface hydrophilicity (measured by water drop contact angle) increased for the grafted samples. Fractal type of morphology is formed by the grafted poly(AAm) and poly(HEMA) chains on the surface of EPR, which provides both hydrophilic and hydrophobic sites. In vivo tissue compatibility was assessed by implanting test samples in the deep intramuscular and peritoneal layers of rabbits. After 8 weeks of implantation, comparative results indicate that the adhesion of macrophages to EPR samples modified with AAm and HEMA, with no respiratory burst and cellular damage, is significantly lower than their adhesion on unmodified surfaces which show an activated state of the attached macrophages. Also, no acute or chronic inflammatory reaction was observed at the site of implantation and a thinner fibrous tissue capsule formed around the modified samples, whereas foreign body giant cells adhered to unmodified EPR.

Cell engineering biointerface focusing on cytocompatibility using phospholipid polymer with an isomeric oligo(lactic acid) segment
Watanabe, J. and K. Ishihara (2005), Biomacromolecules 6(3): 1797-802.
Abstract: Initial contact between a biological environment and a biomaterial ultimately decides the in vivo performance. Therefore, the fabrication of a delicate biointerface is important because it can be utilized as a platform for novel biomaterials. For the preparation of advanced biomedical devices such as biochips, nanoparticles, and cell engineering devices, the surface properties may be modified by the design of polymeric biomaterials. Anomalous phospholipid polymers with an isomeric oligo(lactic acid) segment were designed and evaluated as a biointerface. The phospholipid polymer containing 2-methacryloyloxyethyl phosphorylcholine was easily copolymerized with isomeric oligo(lactic acid) macromonomers, and the obtained polymer could easily form thin coating membranes as biointerfaces. The oligo(lactic acid) involves three kinds of isomers: dl-, d-, and l-forms. The favorable characteristic on the surface provides regulation of cell-material interactions on the biointerface. The oligo(lactic acid) segment could form hydrophobic domains, which were considered to be located on the interface, to enhance protein adsorption and cell adhesion. The most favorable characteristics on the biointerface were dual functions of cytocompatibility by the phospholipid polymer and cell adhesion property by the oligo(lactic acid) segment. In this study, we focused on the biological responses such as protein adsorption and cell adhesion by change in the oligo(lactic acid) component. The cell viability on the confluent stage was evaluated in terms of metabolic activity.

Cell microarrays on photochemically modified polytetrafluoroethylene
Mikulikova, R., S. Moritz, et al. (2005), Biomaterials 26(27): 5572-80.
Abstract: We studied the adhesion, proliferation, and viability of human umbilical vein endothelial cells (HUVEC) and human embryonic kidney cells (HEK) on modified spots at polytetrafluoroethylene (PTFE) surfaces. The viability of the cells was assessed using an aqueous non-radioactive cell proliferation assay. Round spots with a diameter of 100 microm were modified by exposure to the ultraviolet (UV) light of a Xe(2)(*)-excimer lamp at a wavelength of 172 nm in an ammonia atmosphere employing a contact mask. The spots were arranged in a quadratic pattern with 300 microm center-to-center spot distances. With optimized degree of modification, the cells adhered to the modified spots with a high degree of selectivity (70-90%). The adhered cells on the spots proliferated. This resulted in a significant increase in the number of adhering HUVECS or HEK cells after seeding and in the formation of confluent cell clusters after 3-4 days. With higher start seeding density, these clusters were not only confined to the modified spots but extended several micrometer to the neighborhood. The high potential of the cell microarrays for gene analysis in living cells was demonstrated with HEK cells transfected by yellow fluorescent protein (YFP).

Cell processing engineering for ex-vivo expansion of hematopoietic cells
Takagi, M. (2005), J Biosci Bioeng 99(3): 189-96.
Abstract: The cell processing engineering for ex vivo expansion of hematopoietic cells is reviewed. All hematopoietic cells of different lineages and/or at various stages of differentiation are derived from the same precursor, pluripotent hematopoietic stem cells. Bone marrow stromal cells promote and regulate the self-renewal, commitment, differentiation, and proliferation of stem cells and progenitors through their secreted extracellular matrices and cytokine environment in the hematopoietic microenvironment. Although stroma-mediated hematopoiesis has been studied in vitro using the Dexter culture system in tissue culture flasks, hematopoiesis in the Dexter culture system is almost limited to a granulocyte lineage and the system could not expand primitive cells. The addition of large amounts of cytokines to the culture of hematopoietic cells enabled their expansion, but is too expensive. Some clonal stromal cell lines have been established from the Dexter culture of murine bone marrow cells in order to simplify and stimulate the ex vivo expansion of hematopoietic cells. In order to solve the problem regarding the usage of exogeneic stromal cell lines, a novel membrane-separated coculture system, in which stromal cells adhere onto the lower surface of a porous membrane and hematopoietic cells are incubated on the upper surface of the membrane, was proposed. In order to mimic the contact between stromal and hematopoietic cells in vivo in the bone marrow, several types of three-dimensional (3-D) culture of hematopoietic cells were developed. The 3-D coculture of hematopoietic cells with spatial development of stromal cells in nonwoven fabrics enabled the expansion of progenitors without cytokine addition. Progenitors in cord blood mononucleated cells were also successfully expanded without the addition in the 3-D coculture with primary human bone marrow stromal cells in 3-D. Heparin addition to the 3-D coculture and coating the nonwoven fabrics with N-(O-beta-(6-O-sulfogalactopyranosyl)-6-oxyhexyl)-3,5-bis(dodecyloxy)-benz amide further increased the number of progenitors.

Cell reactions with biomaterials: the microscopies
Curtis, A. S. (2001), Eur Cell Mater 1: 59-65.
Abstract: The methods and results of optical microscopy that can be used to observe cell reactions to biomaterials are Interference Reflection Microscopy (IRM), Total Internal Reflection Fluorescence Microscopy (TIRFM), Surface Plasmon Resonance Microscopy (SPRM) and Forster Resonance Energy Transfer Microscopy (FRETM) and Standing Wave Fluorescence Microscopy. The last three are new developments, which have not yet been fully perfected. TIRFM and SPRM are evanescent wave methods. The physics of these methods depend upon optical phenomena at interfaces. All these methods give information on the dimensions of the gap between cell and the substratum to which it is adhering and thus are especially suited to work with biomaterials. IRM and FRETM can be used on opaque surfaces though image interpretation is especially difficult for IRM on a reflecting opaque surface. These methods are compared with several electron microscopical methods for studying cell adhesion to substrata. These methods all yield fairly consistent results and show that the cell to substratum distance on many materials is in the range 5 to 30 nm. The area of contact relative to the total projected area of the cell may vary from a few per cent to close to 100% depending on the cell type and substratum. These methods show that those discrete contact areas well known as focal contacts are frequently present. The results of FRETM suggest that the separation from the substratum even in a focal contact is about 5 nm.

Cell responses to biomaterials. I: Adhesion and growth of vascular endothelial cells on poly(hydroxyethyl methacrylate) following surface modification by hydrolytic etching
McAuslan, B. R. and G. Johnson (1987), J Biomed Mater Res 21(7): 921-35.
Abstract: Hydrogels of poly(hydroxyethyl methacrylate) (polyHEMA) homopolymer do not normally support the attachment and growth of mammalian cells. By altering the surface it has been possible to dramatically change this cell-substratum interaction so that vascular endothelial cells can attach and completely populate a polyHEMA surface. While this can be achieved by copolymerisation of polyHEMA with methacrylic acid or diethylaminoethyl methacrylate, it is most conveniently achieved by brief treatment of polyHEMA hydrogel with concentrated sulphuric acid. The resultant creation of surface-COOH groups, revealed by electron spectroscopy for chemical analysis, is consistent with the hydrolytic formation of methacrylic acid on the surface layer. Surface--COOH groups created by treatment with chloric or hydrofluoric acids were not effective. Following sulfuric acid treatment, cell adhesion and growth on polyHEMA hydrogel were better than on Teflon and approached those attained on glow-discharge-treated polystyrene. The capacity of acid-treated polyHEMA to adsorb albumin or fibronectin was of the order of 100-fold or 10-fold lower respectively than either polystyrene, Teflon, or segmented polyurethane. Hydrolytic "etching" in this way is proposed as an efficient means of expanding the use of polyHEMA hydrogel as a biomaterial without modifying the overall physicochemical properties of the bulk of the material.

Cell responses to biomaterials. II: Endothelial cell adhesion and growth on perfluorosulfonic acid
McAuslan, B. R., G. Johnson, et al. (1988), J Biomed Mater Res 22(11): 963-76.
Abstract: We report here the use of perfluorosulfonic acid (Nafion) as a substratum for the growth of bovine aortal endothelial cells. This support which can be generated in a number of forms is at least as efficient in maintaining the growth of endothelial and other cell types as tissue culture grade polystyrene (TCP) and represents an advance in this regard over polytetrafluoroethylene (Teflon). The mechanism underlying the different cell attachment capacities of these three polymers is not readily related to their different protein binding patterns. While Nafion adsorbs more total protein from serum than Teflon or TCP, it adsorbs relatively less of the major cell adhesive proteins, vitronectin and fibronectin, than does Teflon. Both Nafion and Teflon had comparable but low thrombogenic potential by in vitro tests. Teflon or expanded Teflon (Gore-tex) coated with a thin film of Nafion assumes the cell supportive characteristics of Nafion and hence the modification of these surfaces by the induction of a stable bond between Teflon (in various forms) and Nafion may provide a composite vascular graft material which has all the desirable qualities of both materials.

Cell separation between mesenchymal progenitor cells through porous polymeric membranes
Higuchi, A., Y. Shindo, et al. (2005), J Biomed Mater Res B Appl Biomater 74(1): 511-9.
Abstract: This study investigates the separation of two types of marrow stromal cells, KUSA-A1 osteoblasts and H-1/A preadipocytes, by filtration through various porous polymeric membranes. It was found that KUSA-A1 permeates better than H-1/A cells through 12-microm polyurethane foaming membranes. This appears to be due to the relatively smaller cell size of KUSA-A1 cells. In addition, when feed solutions containing suspensions of either cell type or a mixture of the two were used, the permeation ratio was relatively low (< 6%) through polyurethane and surface-modified polyurethane foaming membranes. It was also found that there was some degree of separation between KUSA-A1 and H-1/A cells (separation factor = 1.8) with nylon-net filter membranes, but no separation was obtained when filters made of nonwoven fabrics or silk screens were used. This ability of the nylon-net filter membranes to separate the two cell types was due to a sieving effect that results from an optimal pore size. Finally, permeation of a solution of human serum albumin through the membrane following filtration of the cells did not result in a separation of cells in the recovery solution.

Cell sheet detachment affects the extracellular matrix: a surface science study comparing thermal liftoff, enzymatic, and mechanical methods
Canavan, H. E., X. Cheng, et al. (2005), J Biomed Mater Res A 75(1): 1-13.
Abstract: This work compares the removal of bovine aortic endothelial cell (BAEC) monolayers via 1) low-temperature liftoff from a "smart polymer," plasma polymerized poly(N-isopropyl acrylamide) (ppNIPAM), 2) enzymatic digestion, and 3) mechanical dissociation from ppNIPAM surfaces. We examine the surfaces after cell removal by using X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), immunostaining, and cell adhesion assay. Immunoassay results indicate that low-temperature liftoff nondestructively harvests the cell sheet and most of the underlying extracellular matrix (ECM), whereas enzymatic digestion and mechanical dissociation are damaging to both the cells and ECM. XPS results indicate that amide and alcohol groups attributed to proteins in the ECM are present on postliftoff surfaces. Principal component analysis (PCA) of ToF-SIMS data indicates that molecular ion fragments of amino acids are present on postliftoff surfaces. Finally, a cell adhesion assay seeding new cells on surfaces from which an initial layer of cells was removed via each of the three methods indicates that liftoff and mechanical dissociation leave behind surfaces that better promote cell adhesion. We conclude that the removal of BAEC cells via low-temperature liftoff from ppNIPAM-treated surfaces is less damaging to the ECM proteins remaining at the surface than the other methods.

Cell sheet engineering: recreating tissues without biodegradable scaffolds
Yang, J., M. Yamato, et al. (2005), Biomaterials 26(33): 6415-22.
Abstract: While tissue engineering has long been thought to possess enormous potential, conventional applications using biodegradable scaffolds have limited the field's progress, demonstrating a need for new methods. We have previously developed cell sheet engineering using temperature-responsive culture dishes in order to avoid traditional tissue engineering approaches, and their related shortcomings. Using temperature-responsive dishes, cultured cells can be harvested as intact sheets by simple temperature changes, thereby avoiding the use of proteolytic enzymes. Cell sheet engineering therefore allows for tissue regeneration by either direct transplantation of cell sheets to host tissues or the creation of three-dimensional structures via the layering of individual cell sheets. By avoiding the use of any additional materials such as carrier substrates or scaffolds, the complications associated with traditional tissue engineering approaches such as host inflammatory responses to implanted polymer materials, can be avoided. Cell sheet engineering thus presents several significant advantages and can overcome many of the problems that have previously restricted tissue engineering with biodegradable scaffolds.

Cell sorting by one gravity SPLITT fractionation
Benincasa, M. A., L. R. Moore, et al. (2005), Anal Chem 77(16): 5294-301.
Abstract: The need for innovative separative techniques suitable for the fractionation of biomaterials prompted this investigation into the performance of the gravitational split-flow thin channel (G-SPLITT) system as a cell sorter. The rigorous mathematical description of the separation mechanism allows achievement of fast separation of several million myeloma cells from healthy splenocytes using flow conditions calculated from theory. Separation in G-SPLITT is based on differences in sedimentation rate. For accurate prediction of the optimal working conditions, this parameter was directly measured by cell tracking velocimetry rather than relying on a measure of diameter (by Multisizer) and an assumed density for each cell population. We also discuss the influence of different flow conditions on the effectiveness of separation.

Cell traction forces on soft biomaterials. I. Microrheology of type I collagen gels
Velegol, D. and F. Lanni (2001), Biophys J 81(3): 1786-92.
Abstract: A laser-trap microrheometry technique was used to determine the local shear moduli of Type I collagen gels. Embedded 2.1 microm polystyrene latex particles were displaced 10-100 nm using a near-infrared laser trap with a trap constant of 0.0001 N/m. The trap was oscillated transversely +/- 200 nm using a refractive glass plate mounted on a galvanometric scanner. The displacement of the microspheres was in phase with the movement of the laser trap at frequencies less than 1 rad/s, indicating that at least locally, the gels behaved as elastic media. The local shear modulus was measured at various positions throughout the gel, and, for gels at 2.3 mg/mL and 37 degrees C, values ranged from G = 3 to 80 Pa. The average shear modulus G = 55 Pa, which compares well with measurements from parallel plate rheometry.

Cell type-specific response to growth on soft materials
Georges, P. C. and P. A. Janmey (2005), J Appl Physiol 98(4): 1547-53.
Abstract: Many cell types respond to forces as acutely as they do to chemical stimuli, but the mechanisms by which cells sense mechanical stimuli and how these factors alter cellular structure and function in vivo are far less explored than those triggered by chemical ligands. Forces arise both from effects outside the cell and from mechanochemical reactions within the cell that generate stresses on the surface to which the cells adhere. Several recent reviews have summarized how externally applied forces may trigger a cellular response (Silver FH and Siperko LM. Crit Rev Biomed Eng 31: 255-331, 2003; Estes BT, Gimble JM, and Guilak F. Curr Top Dev Biol 60: 91-126, 2004; Janmey PA and Weitz DA. Trends Biochem Sci 29: 364-370, 2004). The purpose of this review is to examine the information available in the current literature describing the relationship between a cell and the rigidity of the matrix on which it resides. We will review recent studies and techniques that focus on substrate compliance as a major variable in cell culture studies. We will discuss the specificity of cell response to stiffness and discuss how this may be important in particular tissue systems. We will attempt to link the mechanoresponse to real pathological states and speculate on the possible biological significance of mechanosensing.

Cell viability of chitosan-containing semi-interpenetrated hydrogels based on PCL-PEG-PCL diacrylate macromer
Zhu, A. P. and M. B. Chan-Park (2005), J Biomater Sci Polym Ed 16(3): 301-16.
Abstract: Chitosan-modified biodegradable hydrogels were prepared by UV irradiation of solutions in mild aqueous acidic media of poly(caprolactone)-co-poly(ethylene glycol)-co-poly(caprolactone) diacrylate (PCL-PEG-PCL-DA) and chitosan. Hydrogels obtained were characterized using FT-IR, DSC, TGA and XPS. FT-IR, TGA and DSC revealed the semi-interpenetrating polymer network structure formed in the hydrogel. Though the water swelling degree of these chitosan-modified hydrogels was substantial in the range of 322-539%, it was found that fibroblasts could still attach, spread and grow on them; this is in contrast to the commonly investigated PEG-diacrylate hydrogel. The MTT assay demonstrated that cells could grow better on 3 or 6% chitosan-modified hydrogel than unmodified PCL-PEG-PCL-DA hydrogels or low-content (1%) chitosan-modified PCL-PEG-PCL-DA hydrogel. Increased chitosan content resulted in increased cell interaction and also decreased water swelling, both of which results in increased cell attachment and spread.


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