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Molecular engineering of supramolecular scaffold coatings that can reduce static platelet adhesion.

ABSTRACT: Novel supramolecular coatings that make use of low-molecular weight ditopic monomers with guanine end groups are studied using fluid tapping AFM. These molecules assemble on highly oriented pyrolytic graphite (HOPG) from aqueous solutions to form nanosized banding structures whose sizes can be systematically tuned at the nanoscale by tailoring the molecular structure of the monomers. The nature of the self-assembly in these systems has been studied through a combination of the self-assembly of structural derivatives and molecular modeling. Furthermore, we introduce the concept of using these molecular assemblies as scaffolds to organize functional groups on the surface. As a first demonstration of this concept, scaffold monomers that contain a monomethyl triethyleneglycol branch were used to organize these "functional" units on a HOPG surface. These supramolecular grafted assemblies have been shown to be stable at biologically relevant temperatures and even have the ability to significantly reduce static platelet adhesion.

SUBMITTER: Kumar AM

PROVIDER: S-EPMC2536642 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Molecular engineering of supramolecular scaffold coatings that can reduce static platelet adhesion.

Kumar Aryavarta M S AM Sivakova Sona S Fox Justin D JD Green Jennifer E JE Marchant Roger E RE Rowan Stuart J SJ

Journal of the American Chemical Society 20080105 4

Novel supramolecular coatings that make use of low-molecular weight ditopic monomers with guanine end groups are studied using fluid tapping AFM. These molecules assemble on highly oriented pyrolytic graphite (HOPG) from aqueous solutions to form nanosized banding structures whose sizes can be systematically tuned at the nanoscale by tailoring the molecular structure of the monomers. The nature of the self-assembly in these systems has been studied through a combination of the self-assembly of s ...[more]

PMID: 18177047

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Project description:BACKGROUND: Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA) and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays. This study aimed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel. The adhesion assay measures several aspects of platelet adhesion simultaneously, which increases the probability of finding conditions sensitive for anti-platelet treatment. METHODS: With a randomised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome. Also, 29 matched healthy controls were included to evaluate intra-individual variability over time. Platelet function was measured by flow cytometry, serum thromboxane B2 (TXB2)-levels and by static platelet adhesion to different protein surfaces. The results were subjected to Principal Component Analysis followed by ANOVA, t-tests and linear regression analysis. RESULTS: The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity. Adenosine 5'-diphosphate (ADP)-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA. Flow cytometric measurements showed the same pattern (r2 = 0.49). In opposite, TXB2-levels decreased with ASA compared to clopidogrel. Serum TXB2 and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively. Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN-induced activation measured by flow cytometry were lower for clopidogrel compared to ASA. Furthermore, adhesion to collagen was lower for ASA and clopidogrel combined compared with either drug alone. CONCLUSION: The indirect pharmacodynamic measures of the effects of ASA and clopidogrel might be used together with ADP-induced activation and serum TXB2 for evaluation of anti-platelet treatment. This should be further evaluated in future clinical studies where screening opportunities with the adhesion assay will be optimised towards increased sensitivity to anti-platelet treatment.

Project description:Infection is the major cause of morbidity after breast implant surgery. Biodegradable medical-grade polycaprolactone (mPCL) scaffolds designed and rooted in evidence-based research offer a promising alternative to overcome the limitations of routinely used silicone implants for breast reconstruction. Nevertheless, as with any implant, biodegradable scaffolds are susceptible to bacterial infection too, especially as bacteria can rapidly colonize the biomaterial surface and form biofilms. Biofilm-related infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation of surrounding tissue. To date, no clinical solution that allows to efficiently prevent bacterial infection while promoting correct implant integration, has been developed. In this study, we demonstrated for the first time, to our knowledge that the physical immobilization of 1 and 5% human serum albumin (HSA) onto the surface of 3D printed macro- and microporous mPCL scaffolds, resulted in a reduction of Staphylococcus aureus colonization by 71.7 ± 13.6% and 54.3 ± 12.8%, respectively. Notably, when treatment of scaffolds with HSA was followed by tannic acid (TA) crosslinking/stabilization, uniform and stable coatings with improved antibacterial activity were obtained. The HSA/TA-coated scaffolds were shown to be stable when incubated at physiological conditions in cell culture media for 7 days. Moreover, they were capable of inhibiting the growth of S. aureus and Pseudomonas aeruginosa, two most commonly found bacteria in breast implant infections. Most importantly, 1%HSA/10%TA- and 5%HSA/1%TA-coated scaffolds were able to reduce S. aureus colonization on the mPCL surface, by 99.8 ± 0.1% and 98.8 ± 0.6%, respectively, in comparison to the non-coated control specimens. This system offers a new biomaterial strategy to effectively translate the prevention of biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.

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Molecular engineering of supramolecular scaffold coatings that can reduce static platelet adhesion.

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Molecular engineering of supramolecular scaffold coatings that can reduce static platelet adhesion.

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