Abstract
Background
Photopolymerizable poly(ethylene glycol) (PEG) hydrogels offer a platform to deliver cells in vivo and support three-dimensional cell culture but should be designed to degrade in sync with neotissue development and endure the physiologic environment.
Questions/purposes
We asked whether (1) incorporation of degradation into PEG hydrogels facilitates tissue development comprised of essential cartilage macromolecules; (2) with early loading before pericellular matrix formation, the duration of load affects matrix production; and (3) dynamic loading in general influences macroscopic tissue development.
Methods
Primary bovine chondrocytes were encapsulated in hydrogels (n = 3 for each condition). The independent variables were hydrogel degradation (nondegrading PEG and degrading oligo(lactic acid)-b-PEG-b-oligo(lactic acid) [PEG-LA]), culture condition (free swelling, unconfined dynamic compressive loading applied intermittently for 1 or 4 weeks), and time (up to 28 days). The dependent variables were neotissue deposition through biochemical contents, immunohistochemistry, and compressive modulus.
Results
Degradation led to 2.3- and 2.9-fold greater glycosaminoglycan and collagen contents, respectively; macroscopic cartilage-like tissue formation comprised of aggrecan, collagen II and VI, link protein, and decorin; but decreased moduli. Loading, applied early or throughout culture, did not affect neotissue content in either hydrogel but affected neotissue spatial distribution in degrading hydrogels where 4 weeks of loading appeared to enhance hydrogel degradation resulting in tissue defects.
Conclusions
PEG-LA hydrogels led to macroscopic tissue development comprised of key cartilage macromolecules under loading, but hydrogel degradation requires further tuning.
Clinical Relevance
PEG-LA hydrogels have potential for delivering chondrocytes in vivo to replace damaged cartilage with a tissue-engineered native equivalent, overcoming many limitations associated with current clinical treatments.
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Acknowledgments
The antibodies developed by B. Caterson (link protein) and G. A. Pringle (decorin) used here were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the Department of Biology, University of Iowa, Iowa City, IA.
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The institution of the authors has received funding from the NIH/NIDCR (K22DE016608) and the NIH/NIAMS (R01AR053126); one of the authors (JJR) has received funding from the National Institute of Health’s Leadership Training in Pharmaceutical Biotechnology Program; two of the authors (JJR, GDN) have received funding from the Department of Education’s Graduate Assistantships in Areas of National Need (GAANN) fellowships.
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Roberts, J.J., Nicodemus, G.D., Greenwald, E.C. et al. Degradation Improves Tissue Formation in (Un)Loaded Chondrocyte-laden Hydrogels. Clin Orthop Relat Res 469, 2725–2734 (2011). https://doi.org/10.1007/s11999-011-1823-0
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DOI: https://doi.org/10.1007/s11999-011-1823-0