title: Degradation improves tissue formation in (un)loaded chondrocyte-laden hydrogels.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado-Boulder, ECCH 111, Campus Box 424, Boulder, CO 80309, USA.
authors.forename: Justine J
authors.initials: JJ
authors.lastname: Roberts
authors.forename: Garret D
authors.initials: GD
authors.lastname: Nicodemus
authors.forename: Eric C
authors.initials: EC
authors.lastname: Greenwald
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bryant
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000637:transplantation; D020219:Chondrogenesis; D003094:Collagen / Q000096:biosynthesis; D058575:Decorin / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D006025:Glycosaminoglycans / Q000096:biosynthesis; D020100:Hydrogels; D019344:Lactic Acid / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011509:Proteoglycans / Q000096:biosynthesis; D013314:Stress, Mechanical; D013997:Time Factors; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D000099249:Proteoglycan Link Protein
chemical_list: D003094:Collagen; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D020100:Hydrogels; D019344:Lactic Acid; D011092:Polyethylene Glycols; D011509:Proteoglycans; D000099249:Proteoglycan Link Protein