Implantable medical devices are increasingly important in the practice of modern medicine. Unfortunately, almost all medical devices suffer to a different extent from adverse reactions, including inflammation, fibrosis, thrombosis and infection. To improve the safety and function of many types of medical implants, a major need exists for development of materials that evoked desired tissue responses. Because implant-associated protein adsorption and conformational changes thereafter have been shown to promote immune reactions, rigorous research efforts have been emphasized on the engineering of surface property (physical and chemical characteristics) to reduce protein adsorption and cell interactions and subsequently improve implant biocompatibility. This brief review is aimed to summarize the past efforts and our recent knowledge about the influence of surface functionality on protein:cell:biomaterial interactions. It is our belief that detailed understandings of bioactivity of surface functionality provide an easy, economic, and specific approach for the future rational design of implantable medical devices with desired tissue reactivity and, hopefully, wound healing capability.

Surface chemistry influences implant biocompatibility.

Hemocompatibility of blood-contacting biomaterials is one of the most important criteria for their successful in vivo applicability. Thus, extensive in vitro analyses according to ISO 10993-4 are required prior to clinical applications. In this review, we summarize essential aspects regarding the evaluation of the hemocompatibility of biomaterials and the required in vitro analyses for determining the blood compatibility. Static, agitated, or shear flow models are used to perform hemocompatibility studies. Before and after the incubation of the test material with fresh human blood, hemolysis, cell counts, and the activation of platelets, leukocytes, coagulation and complement system are analyzed. Furthermore, the surface of biomaterials are evaluated concerning attachment of blood cells, adsorption of proteins, and generation of thrombus and fibrin networks.

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Blood-Contacting Biomaterials : In Vitro Evaluation of the Hemocompatibility

A star-PEG-heparin hydrogel platform to aid cell replacement therapies for neurodegenerative diseases.

A wide range of biomedical devices is applied clinically in contact with blood. Tailoring the surface properties of the involved biomaterials is a common approach to enhance performance and to limit adverse reactions. This review summarizes current trends in coating technologies developed for that purpose. Inorganic coatings were shown to substantially improve the durability and inertness of biomaterials while a number of advanced polymer coatings were demonstrated to be very effective by targeting specific biochemical pathways. However, to fully utilize the power of these bioactive coatings safety issues need to be thoroughly addressed in future studies.

Current strategies towards hemocompatible coatings

Blood coagulation on biomaterials requires the combination of distinct activation processes

Maleic anhydride copolymers--a versatile platform for molecular biosurface engineering.

In vitro blood reactivity to hydroxylated and non-hydroxylated polymer surfaces.

Immobilization of an anticoagulant benzamidine derivative: effect of spacer arms and carrier hydrophobicity on thrombin binding.

Synthetic inhibitors of trypsin-like serine proteases were covalently immobilized to polymeric materials to passivate coagulation enzymes during blood contact. The inhibitory potency of a structurally simple and larger, more complex amidine derivatives was assessed against thrombin and factor Xa. After adsorption of serum albumin, the polymer films decorated with either one of the inhibitors were found to scavenge thrombin—with a higher affinity in the case of the larger inhibitor—but not factor Xa. Both inhibitor-containing coatings showed a significantly reduced thrombogenicity, coagulation activation, as well as complement activation when incubated with freshly drawn human whole blood in vitro. The authors conclude that the introduced principle offers a promising approach for hemocompatible materials for short term applications. Even rather simple inhibitors can be successfully employed for that purpose.

https://avs.scitation.org/doi/pdf/10.1116/1.2431753

Benzamidine-based coatings: Implication of inhibitor structure on the inhibition of coagulation enzymes in solution and in vitro hemocompatibility assessment

The invention relates to a modular coating system for bio-materials, used in medical products that are in direct contact with the blood Said coating system comprises a synthetic blood coagulation inhibitor layer, which is bonded to the bio-material surface by means of a flexible spacer layer, said bond between the spacer layer and the bio-material surface being covalent The blood coagulation inhibitor layer is configured from a substance with an A-B-C structure, where A is an amidino group or guanidino group, B is an alpha, beta, or para di-substituted phenyl ring or an alkyl chain and C is an amine (NH-), thiol (S-), alcohol (O-) or carboxylic acid group (CO-)

Marie-Françoise Gouzy

Papers

Maleic anhydride copolymers--a versatile platform for molecular biosurface engineering.

In vitro blood reactivity to hydroxylated and non-hydroxylated polymer surfaces.

Immobilization of an anticoagulant benzamidine derivative: effect of spacer arms and carrier hydrophobicity on thrombin binding.

Benzamidine-based coatings: Implication of inhibitor structure on the inhibition of coagulation enzymes in solution and in vitro hemocompatibility assessment

Modular coating system for bio-materials