Degradation improves tissue formation in (un)loaded chondrocyte-laden hydrogels.
Clin Orthop Relat Res
; 469(10): 2725-34, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21347817
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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Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
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Ácido Láctico
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Condrócitos
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Hidrogéis
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Condrogênese
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Engenharia Tecidual
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Matriz Extracelular
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Alicerces Teciduais
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article