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 ch...

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Bibliographic Details
Published in:Nature biotechnology 2003-05, Vol.21 (5), p.513-518
Main Authors: Hubbell, Jeffrey A, Lutolf, Matthias P, Weber, Franz E, Schmoekel, Hugo G, Schense, Jason C, Kohler, Thomas, Müller, Ralph
Format: Article
Language:English
Subjects:
Adhesion
Agriculture
Animals
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biomimetic Materials - chemical synthesis
Biotechnology
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins - pharmacology
Bone Regeneration - drug effects
Bone Substitutes - chemical synthesis
Bone Substitutes - pharmacology
Coated Materials, Biocompatible - chemical synthesis
Collagen - chemistry
Collagen - metabolism
Culture Techniques - instrumentation
Culture Techniques - methods
Extracellular Matrix
Fundamental and applied biological sciences. Psychology
Gels
Infusion Pumps, Implantable
Invasiveness
Life Sciences
Prostheses and Implants
Rats
Skull Fractures - pathology
Skull Fractures - surgery
Tissue Engineering - instrumentation
Tissue Engineering - methods
Transforming Growth Factor beta
Treatment Outcome
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Summary: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.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt818