Designing 3D photopolymer hydrogels to regulate biomechanical cues and tissue growth for cartilage tissue engineering.
OBJECTIVE
Synthetic hydrogels fabricated from photopolymerization are attractive for tissue engineering for their controlled macroscopic properties, the ability to incorporate biological functionalities, and cell encapsulation. The goal of the present study was to exploit the attractive features of synthetic hydrogels to elucidate the role of gel structure and chemistry in regulating biomechanical cues.


METHODS
Cartilage cells were encapsulated in poly(ethylene glycol) (PEG) hydrogels with different crosslinking densities. Cellular deformation was examined as a function of gel crosslinking. The effects of continuous versus intermittent dynamic loading regimens were examined. RGD, a cell adhesion peptide, was incorporated into PEG gels and subjected to mechanical loading. Chondrocyte morphology and activity was assessed by anabolic and catabolic ECM gene expression and matrix production by collagen and glycosaminoglycan production.


RESULTS
Cell deformation was mediated by gel crosslinking. In the absence of loading, anabolic activity was moderately upregulated while catabolic activity was significantly inhibited regardless of gel crosslinking. Dynamic loading enhanced anabolic activities, but continuous loading inhibited catabolic activity, while intermittent loading stimulated catabolic activity. RGD acted as a mechanoreceptor to influence tissue deposition.


CONCLUSIONS
We demonstrate the ability to regulate biomechanical cues through manipulations in the gel structure and chemistry and cartilage tissue engineering.
Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309-0424, USA. sbryant@colorado.edu
Stephanie J
SJ
Bryant
Garret D
GD
Nicodemus
Idalis
I
Villanueva
D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002417:Cattle; D048430:Cell Shape; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D020100:Hydrogels; D040542:Mechanotransduction, Cellular; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010777:Photochemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D013314:Stress, Mechanical; D013997:Time Factors; D023822:Tissue Engineering; D054457:Tissue Scaffolds
D003432:Cross-Linking Reagents; D006025:Glycosaminoglycans; D020100:Hydrogels; D009842:Oligopeptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D003094:Collagen