title: Matrix metalloproteinase 9 (MMP-9) mediated release of MMP-9 resistant stromal cell-derived factor 1α (SDF-1α) from surface modified polymer films.
abstract: Preparation of smart materials by coatings of established surfaces with biomolecules will lead to the next generation of functionalized biomaterials. Rejection of implants is still a major problem in medical applications but masking the implant material with protein coatings is a promising approach. These layers not only disguise the material but also equip it with a certain biological function. The anti-inflammatory chemokine stromal cell-derived factor 1α (SDF-1α) is well suited to take over this function, because it efficiently attracts stem cells and promotes their differentiation and proliferation. At least the initial stem cell homing requires the formation of a concentration gradient. Thus, a reliable and robust release mechanism of SDF-1α from the material is essential. Several proteases, most notably matrix metalloproteinases, are upregulated during inflammation, which, in principle, can be exploited for a tightly controlled release of SDF-1α. Herein, we present the covalent immobilization of M-[S4V]-SDF-1α on novel biodegradable polymer films, which consist of heterobifunctional poly(ethylene glycol) and oligolactide-based functionalized macromers. A peptidic linker with a trimeric matrix metalloproteinase 9 (MMP-9) cleavage site (MCS) was used as connection and the linkage between the three components was achieved by combination of expressed protein ligation and Cu(I) catalyzed azide/alkyne cycloaddition. The MCS was used for MMP-9 mediated release of M-[S4V]-SDF-1α from the biomaterial and the released SDF-1α derivative was biologically active and induced strong cell migration, which demonstrates the great potential of this system.
authors.affiliation: Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, Universität Leipzig , Brüderstraße 34, 04103 Leipzig, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Steinhagen
authors.forename: Peter-Georg
authors.initials: PG
authors.lastname: Hoffmeister
authors.forename: Karoline
authors.initials: K
authors.lastname: Nordsieck
authors.forename: Rudi
authors.initials: R
authors.lastname: Hötzel
authors.forename: Lars
authors.initials: L
authors.lastname: Baumann
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hacker
authors.forename: Michaela
authors.initials: M
authors.lastname: Schulz-Siegmund
authors.forename: Annette G
authors.initials: AG
authors.lastname: Beck-Sickinger
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000737:chemistry* / Q000378:metabolism; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D020099:Coated Materials, Biocompatible; D011108:Polymers; D020780:Matrix Metalloproteinase 9