Bioactive Hydrogels Made from Step-Growth Derived PEG-Peptide Macromers

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dc.citation.firstpage3736en_US
dc.citation.issueNumber13en_US
dc.citation.journalTitleBiomaterialsen_US
dc.citation.lastpage3743en_US
dc.citation.volumeNumber31en_US
dc.contributor.authorMiller, Jordan S.en_US
dc.contributor.authorShen, Colette J.en_US
dc.contributor.authorLegant, Wesley R.en_US
dc.contributor.authorBaranski, Jan D.en_US
dc.contributor.authorBlakely, Brandon L.en_US
dc.contributor.authorChen, Christopher S.en_US
dc.date.accessioned2014-09-22T20:23:27Zen_US
dc.date.available2014-09-22T20:23:27Zen_US
dc.date.issued2010en_US
dc.description.abstractSynthetic hydrogels based on poly(ethylene glycol) (PEG) have been used as biomaterials for cell biology and tissue engineering investigations. Bioactive PEG-based gels have largely relied on heterobifunctional or multi-arm PEG precursors that can be difficult to synthesize and characterize or expensive to obtain. Here, we report an alternative strategy, which instead uses inexpensive and readily available PEG precursors to simplify reactant sourcing. This new approach provides a robust system in which to probe cellular interactions with the microenvironment. We used the step-growth polymerization of PEG diacrylate (PEGDA, 3400 Da) with bis-cysteine matrix metalloproteinase (MMP)-sensitive peptides via Michael-type addition to form biodegradable photoactive macromers of the form acrylate–PEG–(peptide–PEG)m-acrylate. The molecular weight (MW) of these macromers is controlled by the stoichiometry of the reaction, with a high proportion of resultant macromer species greater than 500 kDa. In addition, the polydispersity of these materials was nearly identical for three different MMP-sensitive peptide sequences subjected to the same reaction conditions. When photopolymerized into hydrogels, these high MW materials exhibit increased swelling and sensitivity to collagenase-mediated degradation as compared to previously published PEG hydrogel systems. Cell-adhesive acrylate–PEG–CGRGDS was synthesized similarly and its immobilization and stability in solid hydrogels was characterized with a modified Lowry assay. To illustrate the functional utility of this approach in a biological setting, we applied this system to develop materials that promote angiogenesis in an ex vivo aortic arch explant assay. We demonstrate the formation and invasion of new sprouts mediated by endothelial cells into the hydrogels from embedded embryonic chick aortic arches. Furthermore, we show that this capillary sprouting and three-dimensional migration of endothelial cells can be tuned by engineering the MMP-susceptibility of the hydrogels and the presence of functional immobilized adhesive ligands (CGRGDS vs. CGRGES peptide). The facile chemistry described and significant cellular responses observed suggest the usefulness of these materials in a variety of in vitro and ex vivo biologic investigations, and may aid in the design or refinement of material systems for a range of tissue engineering approaches.en_US
dc.identifier.citationMiller, Jordan S., Shen, Colette J., Legant, Wesley R., et al.. "Bioactive Hydrogels Made from Step-Growth Derived PEG-Peptide Macromers." <i>Biomaterials,</i> 31, no. 13 (2010) Elsevier: 3736-3743. http://dx.doi.org/10.1016/j.biomaterials.2010.01.058.en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.biomaterials.2010.01.058en_US
dc.identifier.urihttps://hdl.handle.net/1911/77217en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordpolyethylene glycolen_US
dc.subject.keywordhydrogelen_US
dc.subject.keywordpeptideen_US
dc.subject.keywordcell encapsulationen_US
dc.subject.keywordcell adhesionen_US
dc.subject.keywordcopolymeren_US
dc.titleBioactive Hydrogels Made from Step-Growth Derived PEG-Peptide Macromersen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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