Sliding contact loading enhances the tensile properties of mesenchymal stem cell-seeded hydrogels.
The primary goal of cartilage tissue engineering is to recapitulate the functional properties and structural features of native articular cartilage. While there has been some success in generating near-native compressive properties, the tensile properties of cell-seeded constructs remain poor, and key features of cartilage, including inhomogeneity and anisotropy, are generally absent in these engineered constructs. Therefore, in an attempt to instill these hallmark properties of cartilage in engineered cell-seeded constructs, we designed and characterized a novel sliding contact bioreactor to recapitulate the mechanical stimuli arising from physiologic joint loading (two contacting cartilage layers). Finite element modeling of this bioreactor system showed that tensile strains were direction-dependent, while both tensile strains and fluid motion were depth-dependent and highest in the region closest to the contact surface. Short-term sliding contact of mesenchymal stem cell (MSC)-seeded agarose improved chondrogenic gene expression in a manner dependent on both the axial strain applied and transforming growth factor-β supplementation. Using the optimized loading parameters derived from these short-term studies, long-term sliding contact was applied to MSC-seeded agarose constructs for 21 d. After 21 d, sliding contact significantly improved the tensile properties of MSC-seeded constructs and elicited alterations in type II collagen and proteoglycan accumulation as a function of depth; staining for these matrix molecules showed intense localization in the surface regions. These findings point to the potential of sliding contact to produce engineered cartilage constructs that begin to recapitulate the complex mechanical features of the native tissue.
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
Alice H
AH
Huang
Brendon M
BM
Baker
Gerard A
GA
Ateshian
Robert L
RL
Mauck
D053674:Aggrecans / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D016880:Anisotropy; D019149:Bioreactors; D002358:Cartilage, Articular / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D020100:Hydrogels; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D012685:Sepharose / Q000737:chemistry; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D053674:Aggrecans; D024042:Collagen Type I; D020100:Hydrogels; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D012685:Sepharose