PMID- 22114714 OWN - NLM STAT- MEDLINE DCOM- 20120503 LR - 20240216 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 11 DP - 2011 TI - Tension-compression loading with chemical stimulation results in additive increases to functional properties of anatomic meniscal constructs. PG - e27857 LID - 10.1371/journal.pone.0027857 [doi] LID - e27857 AB - OBJECTIVE: This study aimed to improve the functional properties of anatomically-shaped meniscus constructs through simultaneous tension and compression mechanical stimulation in conjunction with chemical stimulation. METHODS: Scaffoldless meniscal constructs were subjected to simultaneous tension and compressive stimulation and chemical stimulation. The temporal aspect of mechanical loading was studied by employing two separate five day stimulation periods. Chemical stimulation consisted of the application of a catabolic GAG-depleting enzyme, chondroitinase ABC (C-ABC), and an anabolic growth factor, TGF-beta1. Mechanical and chemical stimulation combinations were studied through a full-factorial experimental design and assessed for histological, biochemical, and biomechanical properties following 4 wks of culture. RESULTS: Mechanical loading applied from days 10-14 resulted in significant increases in compressive, tensile, and biochemical properties of meniscal constructs. When mechanical and chemical stimuli were combined significant additive increases in collagen per wet weight (4-fold), compressive instantaneous (3-fold) and relaxation (2-fold) moduli, and tensile moduli in the circumferential (4-fold) and radial (6-fold) directions were obtained. CONCLUSIONS: This study demonstrates that a stimulation regimen of simultaneous tension and compression mechanical stimulation, C-ABC, and TGF-beta1 is able to create anatomic meniscus constructs replicating the compressive mechanical properties, and collagen and GAG content of native tissue. In addition, this study significantly advances meniscus tissue engineering by being the first to apply simultaneous tension and compression mechanical stimulation and observe enhancement of tensile and compressive properties following mechanical stimulation. FAU - Huey, Daniel J AU - Huey DJ AD - Department of Biomedical Engineering, University of California Davis, Davis, California, United States of America. FAU - Athanasiou, Kyriacos A AU - Athanasiou KA LA - eng GR - R01 AR047839/AR/NIAMS NIH HHS/United States GR - R01-AR-047839/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20111116 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Transforming Growth Factor beta1) RN - 9007-34-5 (Collagen) RN - EC 4.2.2.20 (Chondroitin ABC Lyase) SB - IM MH - Animals MH - Biomechanical Phenomena MH - Cattle MH - Cells, Cultured MH - Chondroitin ABC Lyase/*pharmacology MH - Collagen/metabolism MH - *Compressive Strength MH - Enzyme-Linked Immunosorbent Assay MH - Immunoenzyme Techniques MH - Menisci, Tibial/*drug effects/physiology MH - Stimulation, Chemical MH - *Tensile Strength MH - Tissue Engineering MH - Transforming Growth Factor beta1/*pharmacology PMC - PMC3218070 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2011/11/25 06:00 MHDA- 2012/05/04 06:00 PMCR- 2011/11/16 CRDT- 2011/11/25 06:00 PHST- 2011/06/15 00:00 [received] PHST- 2011/10/26 00:00 [accepted] PHST- 2011/11/25 06:00 [entrez] PHST- 2011/11/25 06:00 [pubmed] PHST- 2012/05/04 06:00 [medline] PHST- 2011/11/16 00:00 [pmc-release] AID - PONE-D-11-10874 [pii] AID - 10.1371/journal.pone.0027857 [doi] PST - ppublish SO - PLoS One. 2011;6(11):e27857. doi: 10.1371/journal.pone.0027857. Epub 2011 Nov 16.