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PubMed1996

Requirement of receptor-bound urokinase-type plasminogen activator for integrin alphavbeta5-directed cell migration.

The urokinase plasminogen activator (uPA) interacts with its cell surface receptor (uPAR), providing an inducible, localized cell surface proteolytic activity, thereby promoting cellular invasion. Evidence is provided for a novel function of cell surface-associated uPA.uPAR. Specifically, induction of cell surface expression of uPA. uPAR by growth factors or phorbol ester was necessary for vitronectin-dependent carcinoma cell migration, an event mediated by integrin alphavbeta5. Cell migration on vitronectin was blocked with either a soluble form of uPAR, an antibody that disrupts uPA binding to uPAR, or a monoclonal antibody to alphavbeta5. Moreover, plasminogen activator inhibitor type 2 blocked this migration event but did not affect adhesion, suggesting a direct role for uPA enzyme activity in this process and that migration but not adhesion of these cells is regulated by uPA.uPAR. Growth factor-mediated induction of uPA.uPAR on the carcinoma cell surface promotes a specific motility event mediated by integrin alphavbeta5, since cells transfected with the beta3 integrin subunit expressed alphavbeta3 and migrated on vitronectin independently of growth factors or uPA.uPAR expression. This relationship between alphavbeta5 and the uPA.uPAR system has significant implications for regulation of motility events associated with development, angiogenesis, and tumor metastasis.

Cell Movement↗
PubMed1997

Changing ligand specificities of alphavbeta1 and alphavbeta3 integrins by swapping a short diverse sequence of the beta subunit.

Integrins mediate signal transduction through interaction with multiple cellular or extracellular matrix ligands. Integrin alphavbeta3 recognizes fibrinogen, von Willebrand factor, and vitronectin, while alphavbeta1 does not. We studied the mechanisms for defining ligand specificity of these integrins by swapping the highly diverse sequences in the I domain-like structure of the beta1 and beta3 subunits. When the sequence CTSEQNC (residues 187-193) of beta1 is replaced with the corresponding CYDMKTTC sequence of beta3, the ligand specificity of alphavbeta1 is altered. The mutant (alphavbeta1-3-1), like alphavbeta3, recognizes fibrinogen, von Willebrand factor, and vitronectin (a gain-of-function effect). The alphavbeta1-3-1 mutant is recruited to focal contacts on fibrinogen and vitronectin, suggesting that the mutant transduces intracellular signals on adhesion. The reciprocal beta3-1-3 mutation blocks binding of alphavbeta3 to these multiple ligands and to LM609, a function-blocking anti-alphavbeta3 antibody. These results suggest that the highly divergent sequence is a key determinant of integrin ligand specificity. Also, the data support a recent hypothetical model of the I domain of beta, in which the sequence is located in the ligand binding site.

Amino Acid Sequence↗
PubMed1999

Cooperation between thrombospondin-1 type 1 repeat peptides and alpha(v)beta(3) integrin ligands to promote melanoma cell spreading and focal adhesion kinase phosphorylation.

CD47-binding sequences from the carboxyl-terminal domain of thrombospondin-1 (TSP1) are known to regulate activity of the alpha(v)beta(3) integrin (Gao, G., Lindberg, F. P., Dimitry, J. M., Brown, E. J., and Frazier, W. A. (1996) J. Cell Biol. 135, 533-544). Here we show that peptides from the type 1 repeats of TSP1 also stimulate alpha(v)beta(3) integrin function in melanoma cells. Addition of soluble peptide 246 (KRFKQDGGWSHWSPWSS) enhances spreading of A2058 melanoma cells on several alpha(v)beta(3) integrin ligands, including vitronectin, recombinant TSP1 fragments containing the Arg-Gly-Asp sequence, and native TSP1. This activity requires the Trp residues and is independent of CD36-binding sequences in the type 1 repeats. Recombinant type 1 repeats expressed as a glutathione S-transferase fusion protein also enhance spreading on vitronectin and TSP1. Activation of alpha(v)beta(3) integrin by the soluble peptide 246 stimulates organization of F-actin and increases tyrosine phosphorylation of focal adhesion kinase. In contrast, direct adhesion of melanoma cells on immobilized peptide 246 inhibits tyrosine phosphorylation of focal adhesion kinase. Stimulation of alpha(v)beta(3) integrin function by the type 1 repeat peptide differs from that induced by CD47-binding TSP1 peptides in that heparan sulfate proteoglycans are required and pertussis toxin does not inhibit the former activity. Thus, the type 1 repeats contain a second sequence of TSP1 that can enhance alpha(v)beta(3) integrin signaling, and these two sequences stimulate recognition of both vitronectin and TSP1 by the alpha(v)beta(3) integrin.

Amino Acid Sequence↗
PubMed2001

Down-regulation of integrin alpha(v)beta(3) expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes.

Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor alpha(v)beta(3) integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of alpha(v)beta(3) integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the alpha(v)beta(3) integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of alpha(v)beta(3) integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phenotype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the E1-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased alpha(v)beta(3) integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.

Adenoviridae↗
PubMed2004

Alphav-integrin utilization in human beta-cell adhesion, spreading, and motility.

The role of individual integrins in human beta-cell development and function is largely unknown. This study describes the contribution of alpha(v)-integrins to human beta-cell adhesion, spreading, and motility. Developmental differences in alpha(v)-integrin utilization are addressed by comparing the responses of adult and fetal beta-cells, and vitronectin is used as a substrate based on its unique pattern of expression in the developing pancreas. Fetal and adult beta-cells attached equally to vitronectin and integrin alpha(v)beta(5) was found to support the adhesion of both mature and immature beta-cell populations. Fetal beta-cells were also observed to spread and migrate on vitronectin, and integrin alpha(v)beta(1) was found to be essential for these responses. In contrast to their fetal counterparts, adult beta-cells failed to either spread or migrate and this deficit was associated with a marked down-regulation of alpha(v)beta(1) expression in adult islet preparations. The integrin alpha(v)beta(3) was not found to support significant beta-cell attachment or migration. Based on our findings, we conclude that integrins alpha(v)beta(5) and alpha(v)beta(1) are important mediators of human beta-cell adhesion and motility, respectively. By supporting fetal beta-cell migration, alpha(v)beta(1) could play an important role in early motile processes required for islet neogenesis.

Adult↗
PubMed1993

Molecular cloning of integrin-associated protein: an immunoglobulin family member with multiple membrane-spanning domains implicated in alpha v beta 3-dependent ligand binding.

Integrin Associated Protein (IAP) is a 50-kD membrane protein which copurifies with the integrin alpha v beta 3 from placenta and coimmunoprecipitates with beta 3 from platelets. IAP also is functionally associated with signal transduction from the Leukocyte Response Integrin. Using tryptic peptide sequence, human and murine IAP cDNAs have been isolated. The protein has an extracellular amino-terminal immunoglobulin domain that binds all monoclonal anti-IAP antibodies. The carboxy-terminal region is highly hydrophobic with three or five membrane-spanning segments and a short hydrophilic tail. Immunofluorescence microscopy suggests that this hydrophilic tail is located on the inside of the cytoplasmic membrane. Monoclonal anti-IAP antibody inhibits the binding of vitronectin-coated beads to alpha v beta 3 on human erythroleukemia cells, and polyclonal anti-IAP recognizes hamster IAP on CHO cells and inhibits vitronectin bead binding. When CHO cells are transfected with human IAP, monoclonal anti-human antibody completely inhibits vitronectin bead binding. These data suggest a model in which ligand binding by alpha v beta 3 is regulated by IAP.

Amino Acid Sequence↗
PubMed1994

Association of insulin receptor substrate-1 with integrins.

Insulin stimulation was found to promote association of the alpha v beta 3 integrin (a vitronectin receptor) with insulin receptor substrate-1 (IRS-1), an intracellular protein that mediates insulin signaling by binding other signaling molecules, including growth factor receptor-bound protein 2 (Grb2) and phosphatidylinositol-3' kinase. Insulin-treated cells expressing the alpha v beta 3 integrin showed 2.5 times more DNA synthesis when plated on vitronectin than on other substrates, whereas cells expressing another vitronectin receptor, alpha v beta 5, did not show this difference. The association between integrin and IRS-1 may be a mechanism for the synergistic action of growth factor and extracellular matrix receptors.

Amino Acid Sequence↗
PubMed2000

Human parechovirus 1 utilizes integrins alphavbeta3 and alphavbeta1 as receptors.

Human parechovirus 1 (HPEV1) displays an arginine-glycine-aspartic acid (RGD) motif in the VP1 capsid protein, suggesting integrins as candidate receptors for HPEV1. A panel of monoclonal antibodies (MAbs) specific for integrins alphavbeta3, alphavbeta1, and alphavbeta5, which have the ability to recognize the RGD motif, and also a MAb specific for integrin alpha2beta1, an integrin that does not recognize the RGD motif, were tested on A549 cells. Our results showed that integrin alphav-specific MAb reduced infectivity by 85%. To specify which alphav integrins the virus utilizes, we tested MAbs specific to integrins alphavbeta3 and alphavbeta1 which reduced infectivity significantly, while a MAb specific for integrin alphavbeta5, as well as the MAb specific for alpha2beta1, showed no reduction. When a combination of MAbs specific for integrins alphavbeta3 and alphavbeta1 were used, virus infectivity was almost completely inhibited; this shows that integrins alphavbeta3 and alphavbeta1 are utilized by the virus. We therefore proceeded to test whether alphav integrins' natural ligands fibronectin and vitronectin had an effect on HPEV1 infectivity. We found that vitronectin reduced significantly HPEV1 infectivity, whereas a combination of vitronectin and fibronectin abolished infection. To verify the use of integrins alphavbeta3 and alphavbeta1 as HPEV1 receptors, CHO cells transfected and expressing either integrin alphavbeta3 or integrin alphavbeta1 were used. It was shown that the virus could successfully infect these cells. However, in immunoprecipitation experiments using HPEV1 virions and allowing the virus to bind to solubilized A549 cell extract, we isolated and confirmed by Western blotting the alphavbeta3 heterodimer. In conclusion, we found that HPEV1 utilises both integrin alphavbeta3 and alphavbeta1 as receptors; however, in cells that express both integrins, HPEV1 may preferentially bind integrin alphavbeta3.

Animals↗
PubMed2001

Dual signaling by the alpha(v)beta(3)-integrin activates cytosolic PLA(2) in bovine pulmonary artery endothelial cells.

Vitronectin, which ligates the alpha(v)beta(3)-integrin, increases both lung capillary permeability and lung endothelial Ca(2+). In stable monolayers of bovine pulmonary artery endothelial cells (BPAECs) viewed with confocal microscopy, multimeric vitronectin aggregated the apically located alpha(v)beta(3)-integrin. This caused arachidonate release that was inhibited by pretreating the monolayers with the anti-alpha(v)beta(3) monoclonal antibody (MAb) LM609. No inhibition occurred in the presence of the isotypic MAb PIF6, which recognizes the integrin alpha(v)beta(5). Vitronectin also caused membrane translocation and phosphorylation of cytosolic phospholipase A(2) (cPLA(2)) as well as tyrosine phosphorylation of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 2. The cPLA(2) inhibitor arachidonyl trifluoromethylketone, the tyrosine kinase inhibitor genistein, and the MAPK kinase inhibitor PD-98059 all blocked the induced arachidonate release. PD-98059 did not inhibit the increase of cytosolic Ca(2+) or cPLA(2) translocation, although it blocked tyrosine phosphorylation of ERK2. Moreover, although the intracellular Ca(2+) chelator MAPTAM also inhibited arachidonate release, it did not inhibit tyrosine phosphorylation of ERK2. These findings indicate that ligation of apical alpha(v)beta(3) in BPAECs caused ERK2 activation and an increase of intracellular Ca(2+), both conjointly required for cPLA(2) activation and arachidonate release. This is the first instance of a tyrosine phosphorylation-initiated "two-hit" signaling pathway that regulates an integrin-induced proinflammatory response.

Animals↗
PubMed2002

Fibrillar collagen regulation of plasminogen activator inhibitor-1 is involved in altered smooth muscle cell migration.

OBJECTIVE: Vascular smooth muscle cells (SMCs) cultured on polymerized type I collagen fibrils are arrested in the G1 phase of the cell cycle, and their phenotypic markers and pattern of expressed genes are markedly altered. In this study, we examined polymerized collagen regulation of plasminogen activator inhibitor (PAI)-1 and its involvement in SMC migration. METHODS AND RESULTS: We demonstrate that secretion and cell surface accumulation of PAI-1 are suppressed in SMCs cultured on polymerized collagen compared with SMCs cultured on monomer collagen. SMCs replated on vitronectin after culture on monomer collagen result in PAI-1 accumulation at focal adhesions and colocalization with alpha(v)beta3 integrins. In contrast, polymerized collagen inhibits PAI-1 accumulation at focal adhesions when the SMCs are replated on vitronectin. Furthermore, for SMCs cultured on polymerized collagen, platelet-derived growth factor-stimulated migration on vitronectin is enhanced by PAI-1, with its function counteracted by urinary plasminogen activator. Finally, exogenous addition of PAI-1 appears to partly restore platelet-derived growth factor-stimulated alpha(v)beta3-dependent SMC migration that is specifically suppressed by polymerized collagen. CONCLUSIONS: Polymerized type I collagen fibrils dynamically regulate PAI-1, which may be involved in altered alpha(v)beta3 integrin-dependent SMC migration.

Cell Movement↗
PubMed2006

Syndecan-1 regulates alphavbeta5 integrin activity in B82L fibroblasts.

B82L mouse fibroblasts respond to fibronectin or vitronectin via a syndecan-1-mediated activation of the alphavbeta5 integrin. Cells attached to syndecan-1-specific antibody display only filopodial extension. However, the syndecan-anchored cells extend lamellipodia when the antibody-substratum is supplemented with serum, or low concentrations of adsorbed vitronectin or fibronectin, that are not sufficient to activate the integrin when plated alone. Integrin activation is blocked by treatment with (Arg-Gly-Asp)-containing peptides and function-blocking antibodies that target alphav integrins, as well as by siRNA-mediated silencing of beta5 integrin expression. In addition, alphavbeta5-mediated cell attachment and spreading on high concentrations of vitronectin is blocked by competition with recombinant syndecan-1 ectodomain core protein and by downregulation of mouse syndecan-1 expression by mouse-specific siRNA. Taking advantage of the species-specificity of the siRNA, rescue experiments in which human syndecan-1 constructs are expressed trace the activation site to the syndecan-1 ectodomain. Moreover, both full-length mouse and human syndecan-1 co-immunoprecipitate with the beta5 integrin subunit, but fail to do so if the syndecan is displaced by competition with soluble, recombinant syndecan-1 ectodomain. These results suggest that the ectodomain of the syndecan-1 core protein contains an active site that assembles into a complex with the alphavbeta5 integrin and regulates alphavbeta5 integrin activity.

Animals↗
PubMed1996

Regulation of cell migration by the integrin beta subunit ectodomain.

CS-1 melanoma cells transfected with cDNAs encoding either the beta 3 or beta 5 integrin subunit protein express alpha v beta 3 or alpha v beta 5, respectively, enabling them to adhere to vitronectin yet only alpha v beta 3 promotes cell spreading and migration on this substrate. Following exposure to insulin or insulin-like growth factor, alpha v beta 5-expressing CS-1 cells gain the ability to migrate on vitronectin. To identify structural regions in beta 3 or beta 5 that account for these distinct biological properties, CS-1 cells were transfected with one of two chimeric beta subunit proteins, in which the ecto- and cytoplasmic domains of beta 3 and beta 5 were exchanged (termed alpha v beta 3/5 or alpha v beta 5/3). Surprisingly, alpha v beta 3/5 expressing cells spread and migrate on vitronectin while cells expressing alpha v beta 5/3 do not unless they are exposed to cytokine. These findings suggest that the distinct migratory properties mediated by integrins alpha v beta 3 and alpha v beta 5 and their response to cytokine activation is determined by a sequence(s) within the ectodomain of the integrin beta subunit.

Animals↗
PubMed1998

The synergistic activity of alphavbeta3 integrin and PDGF receptor increases cell migration.

Integrins and growth factor receptors act synergistically to modulate cellular functions. The alphavbeta3 integrin and the platelet-derived growth factor receptor have both been shown to play a positive role in cell migration. We show here that a platelet derived growth factor-BB gradient stimulated migration of rat microvascular endothelial cells on vitronectin (9.2-fold increase compared to resting cells) in a alphavbeta3 and RGD-dependent manner. In contrast, this response was not observed on a beta1 integrin ligand, laminin; background levels of migration, in response to a platelet derived growth factor-BB gradient, were observed on this substrate or on bovine serum albumin (2.4- or 2.0-fold, respectively). Comparable results were obtained using NIH-3T3 cells. Platelet derived growth factor-BB did not change the cells' ability to adhere to vitronectin, nor did it stimulate a further increase in proliferation on vitronectin versus laminin. In addition, platelet derived growth factor-BB stimulation of NIH-3T3 cells did not alter the ability of alphavbeta3 to bind RGD immobilized on Sepharose. The alphavbeta3 integrin and the platelet derived growth factor receptor-beta associate in both microvascular endothelial cells and NIH-3T3 cells, since they coprecipitated using two different antibodies to either alphavbeta3 or to the platelet derived growth factor receptor-beta. In contrast, beta1 integrins did not coprecipitate with the platelet derived growth factor receptor-beta. These results point to a novel pathway, mediated by the synergistic activity of alphavbeta3 and the platelet derived growth factor receptor-beta, that regulates cell migration and, therefore, might play a role during neovessel formation and tissue infiltration.

3T3 Cells↗
PubMed2001

Potential synergies between matrix proteins and soluble factors on resorption and proteinase activities of rabbit bone cells.

Human growth hormone (GH) has recently been found to stimulate osteoclastic resorption, cysteine-proteinase and metalloproteinase activities (MMP-2 and MMP-9) in vitro via insulin-like growth factor-I (IGF-I) produced by stromal cells. The present study investigated the effects of two extracellular matrix components (vitronectin and type-I collagen) on hGH- and hIGF-1-stimulated osteoclastic resorption and proteinase activities in a rabbit bone cell model. After 4 days of rabbit bone cell culture on dentin slices with vitronectin coating, hGH and hIGF-1 stimulated bone resorption and hIGF-1 upmodulated cysteine-proteinase activities. MMP-2 expression (but not resorption, cathepsin or MMP-9 activities) was upmodulated by hGH and hIGF-1 on dentin slices coated with type I collagen as compared to those without coating. Then, vitronectin was synergistic with hIGF-1 in the regulation of cysteine-proteinase production whereas collagen showed synergy with hGH and hIGF-1 in the regulation of MMP-2 production. Anti-alphavbeta3 totally abolished the effects of hGH and hIGF-1 on metalloproteinase release, but had no influence on cathepsin release. The results suggest that cysteine-proteinase modulation is not mediated by alphavbeta3 integrin (strongly expressed on osteoclastic surface) whereas the resorption process and metalloproteinase modulation are clearly mediated by this integrin. Our finding about the collagen coating also suggests that hGH- and hIGF-1-stimulated MMP-2 activity are mediated, along with alphavbeta3 integrin, by another adhesion molecule.

Animals↗
PubMed1996

Dichotomy of astrocytoma migration and proliferation.

Astrocytomas often show high rates of local invasion that lead to local recurrence of the disease. Histologically, the most highly invasive astrocytoma cells are detected in isolation rather than as nests of tumor. Our study attempted to determine whether the migratory response to extracellular substrates influences the proliferative behavior of these highly invasive cells. The preferential and specific migratory response of human astrocytoma cells to extracellular matrix proteins was assessed by a microliter scale migration assay. Growth curve studies on protein ligands permissive (merosin) for cell migration indicated that the lag phase was protracted compared with cells seeded on non-permissive proteins (vitronectin). Once a certain cell density was reached, logarithmic proliferation was indistinguishable on the different proteins. The proliferation index of populations of cells migrating on merosin and vitronectin was measured by both BrdU incorporation and MIB-1 immunocytochemistry labeling. Cells seeded on vitronectin showed higher proliferation throughout the population than cells seeded on merosin. On merosin, the more migratory cells at the periphery were less proliferative than non-migratory cells in the central region of that population. The integrin-associated signal transduction protein, p125FAK, was heavily localized in the membrane of non-migrating cells and largely absent in migrating astrocytoma cells. We conclude that temporally, proliferation and migration are mutually exclusive behaviors. Cell density or non-permissive substrates that inhibit cell motility favor a more proliferative phenotype. Conversely, active migration suppresses cell proliferation.

Astrocytoma↗
PubMed1998

Apatite precipitation after incubation of biphasic calcium-phosphate ceramic in various solutions: influence of seed species and proteins.

The dissolution-precipitation process for calcium-phosphate ceramics in contact with biological fluid was studied by incubating blocks of biphasic calcium phosphate composed of hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) in different solutions: ionic simulated body fluid (SBF) without protein or SBF that contained various proteins and macromolecules separately (fibronectin, vitronectin, albumin, and poly-L-glutamic acid). Transmission electron microscopy studies revealed that apatite-precipitated microcrystals appeared around ceramic crystals as a result of secondary nucleation; microcrystals were in continuity with the lattice planes of the HA crystals but in a different direction from that of beta-TCP; the size of the precipitates was smaller when fibronectin, vitronectin, and poly-(L-glutamic acid) were present in SBF as compared to SBF without protein; and fibronectin and vitronectin initiated crystal nucleation in the void spaces between the ceramic crystals.

Apatites↗
PubMed1997

Effects of buffering intracellular free calcium on neutrophil migration through three-dimensional matrices.

Repeated transient increases in intracellular free calcium levels ([Ca2-]i) are required for polymorphonuclear neutrophil migration on two-dimensional surfaces coated with fibronectin or vitronectin. Cells in which [Ca2+]i is buffered with quin2 become stuck on these substrates. Neutrophils migrating through the extracellular matrix in vivo encounter these and other substrates in a three-dimensional architecture that may alter the spatial distribution of adhesion receptors in contact with the matrix. In this study, we used fluorescence confocal microscopy to obtain moving three-dimensional images of neutrophils migrating through a biological tissue (human amnion) in the presence and absence of [Ca2+]i-buffering with quin2. In the absence of buffering, [Ca2+]i transients similar to those seen in cells migrating in two-dimensions were observed. [Ca2+]i-buffered neutrophils were able to migrate into the matrix, but they became attached firmly to the substrate at the rear of the cell, resulting in a drastically elongated morphology. Immunofluorescence revealed that neutrophils adhered to regions of the matrix that contained fibronectin. RGD-containing peptides and antibodies that block integrin adhesion receptors for fibronectin and vitronectin were able to rescue the migration of quin2-treated cells through three-dimensional gels containing fibronectin and vitronectin. These data show that neutrophils migrating through physiologically relevant, three-dimensional matrices undergo repetitive increases in [Ca2+]i that are required for integrin-mediated detachment from the matrix.

Amnion↗
PubMed2005

Mechanism(s) of increased vascular cell adhesion on nanostructured poly(lactic-co-glycolic acid) films.

Studies have shown that poly(lactic-co-glycolic acid) (PLGA) films with nanometer surface features promote vascular endothelial and smooth muscle cell adhesion. The objective of this in vitro research was to begin to understand the mechanisms behind this observed increase in vascular cell adhesion. Results provided evidence that nanostructured PLGA adsorbed significantly more vitronectin and fibronectin from serum compared to conventional (or those not possessing nanometer surface features) PLGA. When separately preadsorbing both vitronectin and fibronectin, increased vascular smooth muscle and endothelial cell density was observed on nanostructured (compared to conventional) PLGA. Additionally, blocking of cell-binding epitopes of fibronectin and vitronectin significantly decreased vascular cell adhesion on nanostructured (compared to conventional) PLGA. For this reason, results of the present in vitro study demonstrated that cell adhesive proteins adsorbed in different quantities and altered bioactivity on nanostructured compared to conventional PLGA topographies, which (at least in part) may account for the documented increased vascular cell adhesion on nanostructured PLGA. In this manner, this study continues to provide evidence for the promise of nanostructured PLGA in vascular tissue engineering applications.

Absorbable Implants↗