Biomedical subjects

T G van Kooten

Publications and source records attributed to T G van Kooten.

At least 19 recordsLinked to original sources

PubMed2006

A long-term in vitro biocompatibility study of a biodegradable polyurethane and its degradation products.

The biological safety of degradation products from degradable biomaterials is very important. In this study a new method is proposed to test the cytotoxicity of these degradation products with the aim to save time, laboratory animals, and research funds. A biodegradable polyurethane (PU) foam was subjected to this test method. The PU had soft segments of DL-lactide/epsilon-caprolactone and hard segments synthesized from butanediol and 1,4-butanediiosocyanate. Copolymer foams without urethane segments, consisting of DL-lactide/epsilon-caprolactone, were tested as well. Accumulated degradation products were collected by degrading the foams in distilled water at 60 degrees C up to 52 weeks. Cell-culture medium was prepared from powder medium with this water. In different tests the cytotoxicity of this medium was established. The first signs of cytotoxicity were observed after 3-5 weeks of degradation. This accounts for both materials and reestablishes the good short-term biocompatibility of these materials. The PU showed more toxicity toward the end stages of degradation in comparison with the copolymer. This is probably related to the accumulation of degradation products of the urethane segments. In the in vivo situation the degradation of the PU and the metabolism and excretion of degradation products may differ. Therefore, long-term in vivo studies will have to establish whether these in vitro results are representative for the in vivo behavior of the degrading PU.

Absorbable Implants↗

PubMed2005

Short-term in vitro and in vivo biocompatibility of a biodegradable polyurethane foam based on 1,4-butanediisocyanate.

In this study short-term in vitro and in vivo biocompatibility apects of a biodegradable polyurethane (PU) foam were evaluated. The PU consists of hard urethane segments and amorphous soft segments based on a copolyester of dl-lactide and epsilon-caprolactone. The urethane segments are of uniform length and synthesized with 1,4-butanediisocyanate. The foam has good mechanical properties and will be used for tissue regeneration applications. Degradation tests were carried out in a buffer solution for twelve weeks. Cytotoxicity was determined using extract and direct contact test methods with incubation periods varying form 24 to 72 h. The foam was implanted subcutaneously for one, four and twelve weeks and the tissue response to the material was histologically evaluated. In vitro, the mass loss was 3.4% after twelve weeks. In the cytotoxicity tests the PU caused no abnormal growth behaviour, nor morphological changes or inhibition in metabolic activity. The in vivo studies showed no toxic tissue response to the PU. Connective tissue ingrowth, accompanied by vascular ingrowth was complete at twelve weeks. In vivo degradation had started within four to twelve weeks. In conclusion, the PU shows a good in vitro and in vivo biocompatibility in these short-term experiments.

Absorbable Implants↗

PubMed2005

An animal model for oroantral communications: a pilot study with Göttingen minipigs.

A pilot study was performed to investigate whether the Göttingen minipig is a suitable animal model for creating and closing oroantral communications (OACs) and to test whether these defects can be closed with a biodegradable polyurethane (PU) foam. In three adult minipigs, an OAC was created on both sides of the maxilla. The left side was closed by a standard surgical buccal flap procedure, the right side by applying a PU foam. The pigs were killed after two weeks, one month and three months, respectively. Postmortem and histological examination showed that an OAC was created in only one of six cases. In the remaining cases, the infraorbital canal was perforated instead of the floor of the maxillary sinus. It was concluded that the Göttingen minipig is not a suitable animal model for OAC investigations. As a result, the closure of OACs with a biodegradable PU could not be evaluated.

Animals↗

PubMed2004

Promotion of fibroblast activity by coating with hydrophobins in the beta-sheet end state.

Hydrophobins such as SC3 and SC4 of Schizophyllum commune self-assemble into an amphipathic film at hydrophilic/hydrophobic interfaces. These proteins can thus change the nature of surfaces, which makes them attractive candidates to improve physio- and physico-chemical properties of implant surfaces. At a hydrophobic solid, assembly of the hydrophobin is arrested in an intermediate state, called the alpha-helical state. The conversion to the stable beta-sheet end state can be induced by treating the solid at elevated temperatures in the presence of detergent. We here show that SC3 and SC4 in the alpha-helical state homogeneously cover Teflon sheets when coating was performed at 20 degrees C. However, when the protein was adsorbed at 80 degrees C aggregates were shown to bind tightly to the adsorbed hydrophobin film. The transition to the beta-sheet state created pores of about 50 nm in the SC3 and SC4 coatings when coating was performed at 20 degrees C. Cell growth and morphology on SC4 coatings was better than on SC3. In case of both hydrophobins, fibroblast growth and morphology was not influenced by the coating temperature or the conformation of the protein. However, in contrast to the alpha-helical state, the beta-sheet state of both SC3 and SC4 hardly, if at all, affected mitochondrial activity.

Animals↗

PubMed2004

Animal models for tracheal research.

Tracheal research covers two main areas of interest: tracheal reconstruction and tracheal fixation. Tracheal reconstructions are aimed at rearranging or replacing parts of the tracheal tissue using implantation and transplantation techniques. The indications for tracheal reconstruction are numerous: obstructing tracheal tumors, trauma, post-intubation tissue reactions, etc. Although in the past years much progress has been made, none of the new developed techniques have resulted in clinical application at large scale. Tissue engineering is believed to be the technique to provide a solution for reconstruction of tracheal defects. Although developing functional tracheal tissue from different cultured cell types is still a challenge. Tracheal fixation research is relatively new in the field and concentrates on solving fixation-related problems for laryngectomized patients. In prosthetic voice rehabilitation tracheo-esophageal silicon rubber speech valves and tracheostoma valves are used. This is often accompanied by many complications. The animal models used for tracheal research vary widely and in most publications proper scientific arguments for animal selection are never mentioned. It showed that the choice on animal models is a multi-factorial process in which non-scientific arguments tend to play a key role. The aim of this study is to provide biomaterials scientists with information about tracheal research and the animal models used.

Animals↗

PubMed2004

The use of hydrophobins to functionalize surfaces.

The physiochemical nature of surfaces can be changed by small proteins which are secreted by filamentous fungi. These proteins, called hydrophobins, are characterized by the presence of eight conserved cysteine residues and a typical hydropathy pattern. Upon contact with a hydrophilic-hydrophobic interface they self-assemble into highly insoluble amphipathic membranes. As a result, hydrophobic surfaces become hydrophilic and vice versa. Genetic engineering of hydrophobins was used to study structure-function relationships. In addition, engineered hydrophobins were constructed to increase the biocompatibility of surfaces. The glycosylated N-terminal region of the mature SC3 hydrophobin was deleted and the cell-binding domain of human fibronectin was introduced at the N-terminus. The gross properties of the hydrophobins were not affected. However, the physiochemical properties of the hydrophilic side of the assembled protein did change. Growth of fibroblasts on Teflon could be improved by coating the solid with the engineered hydrophobins. Thus, by changing the N-terminal part of hydrophobins, the physiochemical nature of the hydrophilic side of the assembled form can be altered and a variety of new functionalities introduced. The fact that hydrophobins self-assemble at any hydrophilic-hydrophobic interface, irrespective of the chemical nature of the surface, therefore provides a generic approach to modify surfaces and make them interesting candidates for the use in various technical and medical applications.

Cell Proliferation↗

PubMed2002

Effect of biologically active coating on biocompatibility of Nitinol devices designed for the closure of intra-atrial communications.

Anti-thrombogenicity and rapid endothelialisation are prerequisites for the use of closure devices of intra-atrial communications in order to reduce the risk of cerebral embolism. The purpose of this study was therefore to assess the effect of bioactive coatings on biocompatibility of Nitinol coils designed for the closure of intra-atrial communications. Nitinol coils (n = 10, each) and flat Nitinol bands (n = 3, each) were treated by basic coating with poly(amino-p-xylylene-co-p-xylylene) and then coated with either heparin, r-hirudin or fibronectin. Anti-thrombogenicity was studied in vitro in a dynamic model with whole blood by partial thromboplastin time (PTT), platelet binding and thrombin generation, respectively, and cytotoxicity by hemolysis. Endothelialisation was studied on Nitinol bands with human umbilical venous endothelial cells (HUVEC) by 3-(4,5-dimethylthiazole-2yl)-2,5-triphenyl tetrazolium (MTT) assay and immnuofluorescence analysis of Ki67, vinculin, fibronectin and von Willebrand Factor. Uncoated or coated devices did not influence hemolysis and PTT. r-Hirudin (but not heparin) and fibronectin coating showed lower platelet binding than uncoated Nitinol (p < 0.005, respectively). Heparin and r-hirudin coating reduced thrombin formation (p < 0.05 versus Nitinol, respectively). HUVEC adhesion, proliferation, and matrix formation decreased in the order: fibronectin coating > uncoated Nitinol > r-hirudin coating > heparin coating > basic coating. MTT assay corroborated these findings. In conclusion, r-hirudin and fibronectin coating, by causing no acute cytotoxicity, decreasing thrombogenicity and increasing endothelialisation improve in vitro biocompatibility of Nitinol devices designed for the closure of intra-atrial communications.

Alloys↗

PubMed2002

Coating with genetic engineered hydrophobin promotes growth of fibroblasts on a hydrophobic solid.

Class I Hydrophobins self-assemble at hydrophilic-hydrophobic interfaces into a highly insoluble amphipathic film. Upon self-assembly of these fungal proteins hydrophobic solids turn hydrophilic, while hydrophilic materials can be made hydrophobic. Hydrophobins thus change the nature of a surface. This property makes them interesting candidates to improve physio- and physico-chemical properties of implant surfaces. We here show that growth of fibroblasts on Teflon can be improved by coating the solid with genetically engineered SC3 hydrophobin. Either deleting a stretch of 25 amino acids at the N-terminus of the mature hydrophobin (TrSC3) or fusing the RGD peptide to this end (RGD-SC3) improved growth of fibroblasts on the solid surface. In addition, we have shown that assembled SC3 and TrSC3 are not toxic when added to the medium of a cell culture of fibroblasts in amounts up to 125 microg ml(-1).

Amino Acid Sequence↗

PubMed2001

Western blotting as a method for studying cell-biomaterial interactions: the role of protein collection.

Research of cell-biomaterial interactions is building on knowledge and methods available in cell and molecular biology. Western blotting is one of the options to characterize protein expression in cell populations. Method transfer to biomaterial model systems is not trivial because of the structure that exists in many biomaterials, preventing the collection of cell lysate by mechanical means. In this technical report, we describe the influence of different protein collection methods in a model system for cell-biomaterial interactions, consisting of endothelial cells exposed to different stimuli. In particular, the influence of trypsinization before lysis, and handling complexity were determined. The results of this study indicate that many changes in proteins occur because of the intermediate enzymatic treatment, despite the use of ice-cold solutions and protease and tyrosine phosphatase inhibitors throughout the procedure. Protein degradation and slight depressions in molecular weight were observed. The enzymatic treatment induced a changed cell status associated with detachment from the substratum. Western blotting of lysates of cells obtained through enzymatic harvest therefore can only be used with internal controls for the assessment of artifacts introduced by trypsinization, or alternative methods should be sought.

Antigens, CD↗

PubMed2000

Cell-cycle control in cell-biomaterial interactions: expression of p53 and Ki67 in human umbilical vein endothelial cells in direct contact and extract testing of biomaterials.

Current biocompatibility testing involves the demonstration of cell proliferation, which is usually interpreted as a sign of positive biocompatibility when the materials sustain cell proliferation. As the field of biomaterials research is rapidly moving toward tissue-engineered devices and hybrid organs, control of cell function has become a main topic. Cell function, which involves specific differentiation pathways, cannot be separated from cell-cycle control. The study of cell-cycle control is an important extension of routine proliferation assays and has extensive roots in developmental and tumor biology. We studied the expression of the tumour suppressor gene p53 and the proliferation-associated antigen Ki67 of endothelial cells in response to biomaterial contact. Cells were seeded in six- or 24-well plates, in which one or three 12-mm-diameter biomaterial disks were laid down. After 48- and 72-h incubation periods, cells were processed for flow cytometry, immunofluorescence, or Western blotting. The following materials were used: titanium, NiCr alloy, and CoCr alloy. Cells were also exposed to 24-h (ISO-norm) extracts in 25-cm(2) culture flasks (600, 000 cells) for 24 and 48 h. For extract testing, serially diluted Ni-ion suspensions were also used. Human umbilical vein endothelial cells adhered to metal surfaces and started forming a monolayer within 3 days. Ki67 expression was positive in more than 60% after 2 days and decreased markedly after 3 days of adhesion. During this time cells developed focal contacts and produced a fibronectin matrix. p53 expression could be demonstrated with Western blotting and flow cytometry, but not with immunofluorescence. Differences due to both culturing time and material were found in expression patterns with both methods. Inverse correlations between Ki67 and p53 expression were detected, which are probably based on culture kinetics. The results indicate that expression of p53 and also Ki67 is clearly influenced by biomaterials in direct contact testing, despite the absence of obvious morphological differences. The p53 marker can be used for defining cell function in more detail, although the correlation with specific physiological function has still to be clarified.

Biocompatible Materials↗

PubMed1999

Focal adhesions and assessment of cytotoxicity.

Focal adhesions are highly ordered assemblies of transmembrane receptors, extracellular matrix proteins, and a large number of cytoplasmic proteins, including structural proteins, as well as tyrosine kinases, phosphatases, and their substrates. They are now accepted as a prime component of signal transduction. Because focal adhesions also play an important role in cell morphology and migration, it can be argued that their presence is indicative of healthy cells. This has been the reason for several research groups to conclude that biomaterials sustaining focal adhesion assembly are biocompatible. In this study we demonstrate that cells under cytotoxic stress may still be able to retain their focal adhesions. Human umbilical vein endothelial cells at passage 2 were exposed to nickel and zinc ion solutions ranging from 1 to 0.01 mM for 4 and 24 h. Cells were seeded on fibronectin precoated glass slides or in tissue culture quality 96-well plates. MTT conversion with 1 and 0.5 mM nickel and zinc was strongly depressed, indicating that these concentrations are cytotoxic. Proliferative activity was also affected by these concentrations. Cells exposed to zinc typically retracted and detached from the surface, whereas cells exposed to nickel remained on the surface without signs of retraction. Nevertheless, cells exposed to nickel were impaired to reach confluency, which was determined by cadherin-5 expression. All these data indicate that nickel ions at a sufficient concentration influence cells in a cytotoxic way. Despite this apparent cytotoxicity, focal adhesion distribution as visualized by immunofluorescence staining of vinculin was not affected. With zinc the morphological changes were accompanied by apparent fusion of focal adhesions during retraction and finally dissolution. These data indicate that the mere presence of focal adhesions does not allow a reliable statement about the functional status of a cell. On the other hand, when focal adhesions are affected it is an excellent monitor of disturbed cell function.

Cell Adhesion↗

PubMed1999

Cell adhesion to textured silicone surfaces: the influence of time of adhesion and texture on focal contact and fibronectin fibril formation.

Cell adhesion and spreading on biomaterials is a key issue in the study of cell-biomaterial interactions. With the development of new disciplines within biomaterials research such as tissue engineering and cellular therapy, information at molecular and structural levels is needed in order to conceive and design biomaterials that elicit specific, functional cell responses. In this study we determined the formation of focal adhesions and fibronectin fibrillar structures by human fibroblasts and human umbilical vein endothelial cells adhered to fibronectin-precoated, smooth, and textured silicones as a function of time. Textures consisted of parallel ridges and 0.5 mm deep grooves with a width of 2, 5, and 10 mm. In addition, pillar and well constructs were used. Cells assembled focal adhesions within the first 24 h of adhesion. Fibronectin production and assembly resulted in a dense fibrillar network at day 6. Initial focal adhesion density and size were dictated by the presence of the texture. Topography also influenced initial fibronectin deposition, although the differences did not result in apparent differences in fibronectin networks after 6 days of incubation. Without fibronectin preadsorption, cells did not proliferate on the silicone surfaces. Cells adhered to glass removed all the preabsorbed fibronectin, whereas on silicone they did not. The present study shows that different textures initially give rise to differences in focal contact and fibronectin fibril assembly. The effects of the small, initial in vitro differences on in vivo tissue biocompatibility remains to be studied.

Adult↗

PubMed1998

Mechanisms of cell activation by heavy metal ions.

Heavy metal ions can be released by corroding metallic implants into the surrounding tissue. When they enter blood vessels some of them are carried by proteins like albumin and can be taken up by endothelial cells lining the vessels. To study their involvement in the inflammatory response we investigated heavy metal ion induced effects in cultured human vascular endothelial cells (HUVECs). NiCl2 and CoCl2 upregulate, especially in concentrations of 1 mM, the expression of adhesion molecules (e.g., E-selectin and intercellular adhesion molecule-1), as well as the cytokines IL-6 and IL-8, as shown by enzyme immunoassay and Northern blot analysis. In addition, possible signal transduction mechanisms were elucidated. The HUVECs were treated with various selective inhibitory drugs followed by the incubation of metal ions before measuring the expression of the above-mentioned endothelial factors. Two protein kinase inhibitors (H-7 and H-8) strongly repressed Ni2+ and Co2+ enhanced expression, as did the phospholipase A2 inhibitor quinacrine. Other selective inhibitors of protein kinases C or A, or cGMP-dependent protein kinases, as well as calcium antagonists like 1,2-bis(2-aminophenoxy)ethan-N,N,N',N'-tetraacetic acid and 3,4,5-trimethoxybenzosaure 8-(diethylamino)-octylester and inhibitors of receptor mediated endocytosis (primary amines), had no influence. We showed that NiCl2 and CoCl2 activate the translocation of the transcription factor nuclear factor (NF)-kappaB into the cell nucleus and enhance its binding to a NF-kappaB consensus sequence as shown by mobility shift analysis. Furthermore, we demonstrated the activation of AP-1. Despite the repression of heavy metal induced adhesion molecule synthesis, we did not detect any inhibition of NF-kappaB translocation by H-7 or H-8. Therefore, it must be concluded that heavy metal ions like Ni2+ and Co2+ activate two or more signal transduction pathways in endothelial cells. We clearly showed that there is one pathway in which H-7 and H-8 sensitive protein kinases are involved and a second pathway leading to NF-kappaB activation, which is insensitive to H-7 and H-8. Our results demonstrate that heavy metal ions induce mechanisms of gene activation in endothelial cells as do proinflammatory mediators, indicating that corroding metal ion containing biomaterials can provoke inflammatory reactions by known, as well as by yet unknown, intracellular signaling pathways.

Base Sequence↗

PubMed1998

Influence of silicone (PDMS) surface texture on human skin fibroblast proliferation as determined by cell cycle analysis.

In vivo biocompatibility of soft-tissue implants is often hampered by development of capsules that eventually might contract and impair implant function. It has been shown that capsule formation can be significantly reduced by using materials with textured surface elements in the micron range. In this study the interaction of human fibroblasts with silicone surfaces was analyzed using cell cycle analysis. Silicone was textured with 2, 5, and 10 microns wide grooves (2MU, 5MU, 10MU, respectively) or kept smooth (SMT). Cell cycle analysis was performed after staining of cells with propidium iodide. Cells proliferated on the fibronectin-preadsorbed silicone, as demonstrated by increased coverage and occurrence of subpopulations in the S and G2/M phase of the cell cycle. Cells on SMT went faster into the S phase than cells on textured silicones. Cells on 10MU showed less proliferation than cells on 2MU and 5MU. Besides the basic percentages of cells in the different cycle phases, DNA profiles were also influenced by incubation time and texture, especially with respect to the presence of hypodiploid populations and asymmetry of the G0/G1 peak. Finally scatter characteristics were influenced. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay data did not reveal significant differences among the different samples. Fibronectin preadsorption of silicone only resulted in slightly higher MTT conversion. Cell cycle analysis proved to be a sensitive screening method for proliferation on the silicone surfaces and provided information beyond the normal G0/G1, S and G2/M subpopulations.

Biocompatible Materials↗

PubMed1998

Current trends in biocompatibility testing.

Biocompatibility remains the central theme for biomaterials applications in medicine. It is generally accepted that this term means not only absence of a cytotoxic effect but also positive effects in the sense of biofunctionality, i.e. promotion of biological processes which further the intended aim of the application of a biomaterial. The national and international standards for testing regimes represent a lowest common denominator for such applications and do not necessarily ensure that optimal function will be achieved. The authors' thesis is that biocompatibility testing has scope for extensive development with respect to biofunctionality. The present paper reviews current trends in the in vitro aspects of biocompatibility testing. As well as a critical appraisal of the recent literature, future trends are also stressed, which the authors regard as essential for a meaningful integration of a modern biological approach into new developments in the material sciences. These include the application of modern techniques of cell and molecular biology, the concepts of tissue remodelling, hybrid organ development and encapsulated cell technology.

Animals↗

PubMed1997

Physiology and cell biology of the endothelium: a dynamic interface for cell communication.

This manuscript presents a brief overview of the physiology and cell biology of the endothelium, which is the basis for understanding the role of endothelial cells in pathological processes as diverse as atherosclerosis, tumour intravasation and multiple organ failure. Following consideration of general aspects of endothelial function in regulating haemostasis, vascular tone and growth, special emphasis will be placed on endothelial regulation of the inflammatory response, which centres on the microcirculation. A particular role in inflammation is played by cell adhesion molecules (CAM), expressed both on endothelial and blood cells. Cell and molecular biological methods to investigate the expression of CAM in endothelial cells in vitro will be presented, as well as novel data, indicating that cytokine-induced up-regulation of CAM in the endothelium may involve signal transduction pathways other than those culminating in the activation of NF-kappa B. Finally, the phenomenon of angiogenesis will be briefly reviewed as a characteristic of endothelial cell activity of central importance to both physiology and pathology and new experimental data presented from an in vitro model to study the ability of individual endothelial cells to form vessel-like structures. In comparative studies to investigate the roles of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor, the dominant role of VEGF in the formation of capillary networks could be unequivocally demonstrated.

Animals↗

PubMed1996

Biomaterial-induced alterations of human neutrophils under fluid shear stress: scanning electron microscopical study in vitro.

Morphological changes of human polymorphonuclear neutrophils (PMN) adhering to hydrophilic (glass) and hydrophobic (FEP-Teflon, polyethylene, polypropylene) surfaces were studied in a parallel-plate flow chamber at the light and scanning electron microscopical levels. The PMN were exposed to a shear stress of 0.19 Pa (1.9 dynes cm-2) or were allowed to adhere without the stress component (static control) during 30 min for all four biomaterials. Observation by light microscopy was performed in situ in the flow chamber at 1, 5, 10, 15, 20, 25 and 30 min. The total number of adherent cells as a function of time and the activation status of the population on the basis of morphological criteria were determined. On the hydrophilic material adhesion of activated PMN was significantly higher (P < 0.05) than on the more hydrophobic surfaces. This effect was most pronounced for the adhesion of neutrophils to glass and polypropylene (PP). Polyethylene (PE) showed only minor adhesion rates. Scanning electron microscopy revealed details of cell shape changes and permitted a more precise classification of populations of neutrophils based on distinctive shapes. As PMN were exposed to shear stress on glass, the majority of cells exhibited surface veils, ridges and ruffles, suggesting a high level of cell migration. In this case, on polymeric surfaces the presence of filopodial networks (FEP-Teflon) and ameoboid cell shapes (PP and PE) was noted. The results suggest that a low shear stress, as well as various chemical and physical properties of biomaterial surfaces, are together responsible for differentiation of PMN populations on solid substrata.

Biocompatible Materials↗

PubMed1995

The influence of micro-topography on cellular response and the implications for silicone implants.

Tissue attachment to substratum surfaces is of central importance to the in vivo performance of prosthetic implant materials. It is not yet understood why connective tissue does not attach to the surface of silicone or any other polymeric material. Recently the authors have conclusively demonstrated that micro-range surface roughness modifies cellular responses in cell culture and modifies biocompatibility and tissue attachment in vivo significantly. In order to better understand the basic interactions between living cells or tissues on one hand and man-made substratum surfaces on the other hand, the germane literature is reviewed here. Cells adhere to substratum surfaces mainly through focal adhesions which are a complex of intracellular transmembrane and extracellular proteins. Adhesion is facilitated and modified by proteins adsorbed to the substratum surface. Protein adsorption in turn is modified by the underlying substratum surface properties including surface chemistry, charge, and free energy. When silicone and other polymeric implants having well-defined surface topographic features including pores, pillars, or grooves were implanted, the tissue response to these implants was strongly influenced by the dimensions of these features as well as by other geometric details. Highest biocompatibility along with tissue attachment was seen when topographic features had dimensions of 1-3 microns and a uniform distribution. Cell culture studies revealed that topographic features affect cellular alignment, direction of proliferation, cellular attachment, growth rate, metabolism, and cytoskeletal arrangement. Since discontinuities or curvatures associated with topographic features may represent local changes in surface free energy, it is hypothesized that these discontinuities trigger changes in protein adsorption, protein configuration, and cellular response.

Adsorption↗