On the blood compatibility of end-point immobilized heparin

Olsson, Per; Sánchez, Javier; Mollnes, Tom Eirik; Riesenfeld, Johan

doi:10.1163/156856200744192

Cited by 83 publications

(61 citation statements)

References 51 publications

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“…There is a need for such surfaces in biomimetic surface coatings for medical implants (33,34), environmental biosensors (35), and antibody arrays for early and precise disease diagnosis (36), all of which require functional (33,37) immobilized proteins. The capability of immobilizing the whole range of proteins expressed in a cell would enable "reverse phase" microarrays (38) to monitor disease progression through changes in protein expression.…”

Section: Resultsmentioning

confidence: 99%

“…The capability of immobilizing the whole range of proteins expressed in a cell would enable "reverse phase" microarrays (38) to monitor disease progression through changes in protein expression. "Cloaking" a prosthetic implant with a conformal coverage of selected bioactive proteins or peptide segments could be used to elicit an optimal local host response such as adherence of a target cell type (28,33,39,40). Used on implantable biomedical devices, such cloaked surfaces would make truly biomimetic implants that elicit optimum local cellular responses by means of a covalently immobilized functional protein layer derived from the patient's protein present at the site of the implant.…”

Section: Resultsmentioning

confidence: 99%

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Free radical functionalization of surfaces to prevent adverse responses to biomedical devices

Bilek

Bax

Kondyurin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

180

189

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Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surfaces do not induce denaturation of immobilized protein but exhibit a low binding affinity for protein. Here, we describe an energetic ion-assisted plasma process that can make any surface hydrophilic and at the same time enable it to covalently immobilize functional biological molecules. We show that the modification creates free radicals that migrate to the surface from a reservoir beneath. When they reach the surface, the radicals form covalent bonds with biomolecules. The kinetics and number densities of protein molecules in solution and free radicals in the reservoir control the time required to form a full protein monolayer that is covalently bound. The shelf life of the covalent binding capability is governed by the initial density of free radicals and the depth of the reservoir. We show that the high reactivity of the radicals renders the binding universal across all biological macromolecules. Because the free radical reservoir can be created on any solid material, this approach can be used in medical applications ranging from cardiovascular stents to heart-lung machines.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Free radical functionalization of surfaces to prevent adverse responses to biomedical devices

Bilek

Bax

Kondyurin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

180

189

View full text Add to dashboard Cite

show abstract

“…Heparin is a natural component of living tissues, present in the mast cells of connective tissues. 21,22 It is a polysaccharide of heterogeneous structure, belonging to the group of GAGs. The heavily sulfated polysaccharide is negatively charged and linear, consisting of repeating glucosamine and hexuronic acid residues.…”

Section: Discussionmentioning

confidence: 99%

Tissue Compatibility of Interfacial Polyelectrolyte Complexation Fibrous Scaffold: Evaluation of Blood Compatibility and Biocompatibility

Yim¹,

Liao²,

Leong³

2006

Tissue Engineering

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Interfacial polyelectrolyte complexation (PEC) fiber has been proposed as a biostructural unit and biological construct for tissue engineering applications, with its ability to incorporate proteins, drug molecules, DNA nanoparticles, and cells. In this study, we evaluated the biocompatibility and blood compatibility of PEC fiber in order to assess its potential for in vivo applications in tissue engineering. Although chitosan-alginate PEC fibrous scaffold was found to be thrombogenic, the blood compatibility of the scaffold could be significantly improved by incorporating a small amount of heparin in the polyelectrolyte solution during fiber formation. The platelet microparticle production and platelet adhesion on the chitosan-alginate-heparin fibrous scaffold were comparable to those on the resting control. In vitro cytotoxicity test showed that the scaffold was not toxic to human mesenchymal stem cells (hMSCs). In the in vivo biocompatibility test in rats, no acute inflammation was observed in the subcutaneously or intramuscularly implanted specimens. Good cell in-filtration and vascularization were observed after 2 months of implantations. Enhanced extracellular matrix (ECM) deposition was observed when hMSCs were cultured in the transforming growth factor-β3 (TGF-β3)-encapsulated PEC fibrous scaffold in vitro, or when the TGF-β3-encapsulated PEC was implanted intramuscularly in vivo. The results showed that this versatile PEC fibrous scaffold could be used in various tissue engineering applications for its good biocompatible and blood compatible properties.

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“…In addition, it has been used as a drug in humans for years. Inhibition of complement activation by polymer surfaces bearing heparin was obtained, especially when heparin was bound by one end [24,25]. Long-circulating and very low complement activating NPs were also obtained from block copolymers composed of heparin and acrylic polymers (Hep-PMMA) [26,27].…”

Section: Towards Biomimetic Strategiesmentioning

confidence: 99%

The Interactions between Blood and Polymeric Nanoparticles Depend on the Nature and Structure of the Hydrogel Covering the Surface

Labarre

2012

Polymers

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Polymeric surfaces in contact with blood in vivo are foreign bodies and are quickly isolated from blood by the non-specific defense systems. Nanoparticles (NP) used as drug carriers are normally quickly taken up by phagocytes and sequestered in liver and spleen to which they can deliver drugs. Long-circulating and/or low complement activating core-shell NPs can be obtained from PEO/PEG amphiphilic copolymers forming brush or loops on the surface. Core-shell NPs can also be obtained from polysaccharidic graft or block amphiphilic copolymers. Complement activation by the NPs and protein adsorption both depend on the structure, nature and molecular weight of the polysaccharide chains composing the shell. NPs showing low complement activation can be obtained if the polysaccharide on the surface is long and in a brush configuration. Fragile molecules such as hemoglobin or siRNA can be loaded and protected by appropriate brush shells without modifying the low complement activation properties.

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On the blood compatibility of end-point immobilized heparin

Cited by 83 publications

References 51 publications

Free radical functionalization of surfaces to prevent adverse responses to biomedical devices

Free radical functionalization of surfaces to prevent adverse responses to biomedical devices

Tissue Compatibility of Interfacial Polyelectrolyte Complexation Fibrous Scaffold: Evaluation of Blood Compatibility and Biocompatibility

The Interactions between Blood and Polymeric Nanoparticles Depend on the Nature and Structure of the Hydrogel Covering the Surface

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