Repair of bone defects using synthetic mimetics of collagenous extracellular matrices


We have engineered synthetic poly(ethylene glycol) (PEG)–based hydrogels as cell-ingrowth matrices for in situ bone regeneration. These networks contain a combination of pendant oligopeptide ligands for cell adhesion (RGDSP) and substrates for matrix metalloproteinase (MMP) as linkers between PEG chains. Primary human fibroblasts were shown to migrate within these matrices by integrin- and MMP-dependent mechanisms. Gels used to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) to the site of critical- sized defects in rat crania were completely infiltrated by cells and were remodeled into bony tissue within five weeks. Bone regeneration was dependent on the proteolytic sensitivity of the matrices and their architecture. The cell-mediated proteolytic invasiveness of the gels and entrapment of rhBMP-2 resulted in efficient and highly localized bone regeneration.

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Figure 1: Scheme for gel preparation.
Figure 2: Three-dimensional fibroblast migration.
Figure 3: rhBMP-2 release triggered by MMP activity.
Figure 4: Bone healing in rat calvaria.
Figure 5: Micro-CT imaging of bone healing.
Figure 6: Effect of gel architecture.


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Funding of this study was provided by the Swiss National Science Foundation (NFP46 grant 58681), the Swiss Federal Agency for Education and Science (01.0224), and the European Union Framework 5 Program (C5RD-CT-2000-00267). We thank A. Zisch and G. Raeber for helpful discussions.

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Correspondence to Jeffrey A. Hubbell.

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Competing interests

The materials employed in this study are the subject of patents that are held by the Swiss Federal Institute of Technology and the University of Zurich. These patents have been licensed by Kuros Biosurgery AG, in which the Swiss Federal Institute of Technology, the University of Zurich, and some of the authors hold equity, and by which some of the authors are employed as consultants.

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Lutolf, M., Weber, F., Schmoekel, H. et al. Repair of bone defects using synthetic mimetics of collagenous extracellular matrices. Nat Biotechnol 21, 513–518 (2003).

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