title: Tissue engineering of cartilage using a mechanobioreactor exerting simultaneous mechanical shear and compression to simulate the rolling action of articular joints.
abstract: The effect of dynamic mechanical shear and compression on the synthesis of human tissue-engineered cartilage was investigated using a mechanobioreactor capable of simulating the rolling action of articular joints in a mixed fluid environment. Human chondrocytes seeded into polyglycolic acid (PGA) mesh or PGA-alginate scaffolds were precultured in shaking T-flasks or recirculation perfusion bioreactors for 2.5 or 4 weeks prior to mechanical stimulation in the mechanobioreactor. Constructs were subjected to intermittent unconfined shear and compressive loading at a frequency of 0.05 Hz using a peak-to-peak compressive strain amplitude of 2.2% superimposed on a static axial compressive strain of 6.5%. The mechanical treatment was carried out for up to 2.5 weeks using a loading regime of 10 min duration each day with the direction of the shear forces reversed after 5 min and release of all loading at the end of the daily treatment period. Compared with shaking T-flasks and mechanobioreactor control cultures without loading, mechanical treatment improved the amount and quality of cartilage produced. On a per cell basis, synthesis of both major structural components of cartilage, glycosaminoglycan (GAG) and collagen type II, was enhanced substantially by up to 5.3- and 10-fold, respectively, depending on the scaffold type and seeding cell density. Levels of collagen type II as a percentage of total collagen were also increased after mechanical treatment by up to 3.4-fold in PGA constructs. Mechanical treatment had a less pronounced effect on the composition of constructs precultured in perfusion bioreactors compared with perfusion culture controls. This work demonstrates that the quality of tissue-engineered cartilage can be enhanced significantly by application of simultaneous dynamic mechanical shear and compression, with the greatest benefits evident for synthesis of collagen type II.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW, Australia.
authors.forename: Kifah
authors.initials: K
authors.lastname: Shahin
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Doran
mesh_terms: D000464:Alginates; D061249:Batch Cell Culture Techniques / Q000295:instrumentation*; D001696:Biomechanical Phenomena; D019149:Bioreactors; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D024043:Collagen Type II / Q000096:biosynthesis; D019245:Compressive Strength; D004867:Equipment Design; D020723:Glucuronic Acid; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006132:Growth Plate / Q000166:cytology* / Q000196:embryology; D006603:Hexuronic Acids; D006801:Humans; D007596:Joints / Q000502:physiology*; D010477:Perfusion; D011100:Polyglycolic Acid; D011312:Pressure; D033081:Shear Strength; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds; D016474:Weight-Bearing
chemical_list: D000464:Alginates; D024043:Collagen Type II; D006025:Glycosaminoglycans; D006603:Hexuronic Acids; D011100:Polyglycolic Acid; D020723:Glucuronic Acid