Chondrocyte redifferentiation and construct mechanical property development in single-component photocrosslinkable hydrogels

J Biomed Mater Res A. 2014 Aug;102(8):2544-53. doi: 10.1002/jbm.a.34924. Epub 2013 Sep 2.

Abstract

Hydrogels are promising materials for cartilage repair, but the properties required for optimal functional outcomes are not yet known. In this study, we functionalized four materials that are commonly used in cartilage tissue engineering and evaluated them using in vitro cultures. Gelatin, hyaluronic acid, polyethylene glycol, and alginate were functionalized with methacrylic anhydride to make them photocrosslinkable. We found that the responses of encapsulated human chondrocytes were highly dependent on hydrogel type. Gelatin hydrogels supported cell proliferation and the deposition of a glycosaminoglycan rich matrix with significant mechanical functionality. However, cells had a dedifferentiated phenotype, with high expression of collagen type I. Chondrocytes showed the best redifferentiation in hyaluronic acid hydrogels, but the newly formed matrix was highly localized to the pericellular regions, and these gels degraded rapidly. Polyethylene glycol hydrogels, as a bioinert control, did not promote any strong responses. Alginate hydrogels did not support the deposition of new matrix, and the stiffness decreased during culture. The markedly different response of chondrocytes to these four photocrosslinkable hydrogels demonstrates the importance of material properties for chondrogenesis and extracellular matrix production, which are critical for effective cartilage repair.

Keywords: cartilage; chondrogenesis; hydrogels; photopolymerization; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Differentiation / drug effects*
  • Cell Differentiation / radiation effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Shape / drug effects
  • Cell Shape / radiation effects
  • Cells, Immobilized / cytology
  • Cells, Immobilized / drug effects
  • Cells, Immobilized / metabolism
  • Chondrocytes / cytology*
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / radiation effects
  • Compressive Strength / drug effects
  • Compressive Strength / radiation effects
  • Cross-Linking Reagents / pharmacology*
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / radiation effects
  • Female
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Glycosaminoglycans / metabolism
  • Humans
  • Hydrogels / pharmacology*
  • Light*
  • Mechanical Phenomena / drug effects*
  • Mechanical Phenomena / radiation effects
  • Tissue Scaffolds / chemistry*
  • X-Ray Microtomography

Substances

  • Cross-Linking Reagents
  • Glycosaminoglycans
  • Hydrogels