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ePaper created 2016-03-17, 15:06:18 | version 1.45.01
60 1 2 MEDICINE clickECM – AN INNOVATIVE BIOLOGICAL COATING FOR IMPLANTS Sybil Mara Ruff, Silke Keller, Günter Tovar, Monika Bach, Petra Kluger Optimized biocompatibility for implants Biomaterials are used in a wide range of applications in medical technology and orthopedics. They are designed to withstand the biomechanical stresses of the body; however, the biocompatibility of many biomaterials still requires optimi- zation [1]. Implants are often coated with biomaterials to im- prove their biocompatibility and assist in their integration into the body [2]. Conventional biomaterial coatings are attached to implants by a process called physisorption, which is a physi- cal interaction between the implant surface and the material. Despite the advantages of this type of surface coating, the stability requires improvement [2]. The aim of the clickECM project was to develop a stable biocompatible and biologically active implant coating with the human extracellular matrix (ECM). The ECM consists of a comple network of biomolecules, such as fibrous proteins, proteoglycans and glycosaminoglycans, as well as electrolytes, water and signaling molecules [3]. The ECM is instrumental in cellular processes such as cell motility, attachment, signal transduction and biomechanical stimuli [3]. Thanks to its uni ue and tissue-specific composition of biomolecules, the human ECM is the ideal biomaterial for coating implants. Covalent binding of clickECM to surfaces To create a covalent bond, meaning a strong chemical bond, between human M and an artificial surface, we developed a process to immobilize ECM via “click” reactions. Click reactions are efficient under physiological conditions, highly biocompatible, specific and selective even in the presence of the wide range of natural functional groups within the sur- rounding biomolecules. The first step in e uipping M with click groups is the generation of human ECM from primary cells. We performed Metabolic Oligosaccharide Engineering (MOE) in order to functionalize the ECM with azide groups during the in vitro culture of the cells (Fig. 1). Next, covalent attachment of the “clickECM” onto the substrate surfaces was achieved through the complementary click functionalization of the surfaces with an activated alkyne compound (dibenzocyclooctyne, DIBO). Due to the high ring strain of the used cyclooctyne compound, there is no cytotoxic copper catalyst necessary to drive the reaction forward. Stable and cell proliferation-inducing clickECM coating The successful introduction of the azide groups into the gly- can structures of the clickECM by the MOE was detected by a reaction with an alkyne-functional dye (Fig. 2). Histological and immunocytochemical staining confirmed that the isolated clickECM had a similar biological composition of human skin ECM (Fig. 3). Cell proliferation studies demonstrated that the covalent click M coating significantly increased cell prolifera- tion when compared to uncoated or DIBO functionalized glass substrates. clickECM had a comparable proliferation rate as unmodified M, which showed that the a ide modification had no effect on cell proliferation. Furthermore, the covalent immobilization of clickECM on DIBO functionalized material surfaces had a significantly increased level of coating stability than the conventional physisorbed coatings. 20 μm 12