Matrix metalloproteinase 9 (MMP-9) mediated release of MMP-9 resistant stromal cell-derived factor 1α (SDF-1α) from surface modified polymer films

ACS Appl Mater Interfaces. 2014 Apr 23;6(8):5891-9. doi: 10.1021/am500794q. Epub 2014 Apr 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement
  • Chemokine CXCL12 / chemistry*
  • Chemokine CXCL12 / metabolism
  • Coated Materials, Biocompatible / chemistry*
  • Coated Materials, Biocompatible / metabolism
  • Humans
  • Matrix Metalloproteinase 9 / chemistry
  • Matrix Metalloproteinase 9 / metabolism*
  • Polymers / chemistry*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism


  • Chemokine CXCL12
  • Coated Materials, Biocompatible
  • Polymers
  • Matrix Metalloproteinase 9