PMID- 23041782 OWN - NLM STAT- MEDLINE DCOM- 20130611 LR - 20211021 IS - 1878-7568 (Electronic) IS - 1742-7061 (Print) IS - 1742-7061 (Linking) VI - 9 IP - 1 DP - 2013 Jan TI - A chondroitinase-ABC and TGF-beta1 treatment regimen for enhancing the mechanical properties of tissue-engineered fibrocartilage. PG - 4626-34 LID - S1742-7061(12)00474-6 [pii] LID - 10.1016/j.actbio.2012.09.037 [doi] AB - The development of functionally equivalent fibrocartilage remains elusive despite efforts to engineer tissues such as knee meniscus, intervertebral disc and temporomandibular joint disc. Attempts to engineer these structures often fail to create tissues with mechanical properties on a par with native tissue, resulting in constructs unsuitable for clinical applications. The objective of this study was to engineer a spectrum of biomimetic fibrocartilages representative of the distinct functional properties found in native tissues. Using the self-assembly process, different co-cultures of meniscus cells and articular chondrocytes were seeded into agarose wells and treated with the catabolic agent chondroitinase-ABC (C-ABC) and the anabolic agent transforming growth factor-beta1 (TGF-beta1) via a two-factor (cell ratio and bioactive treatment), full factorial study design. Application of both C-ABC and TGF-beta1 resulted in a beneficial or positive increase in the collagen content of treated constructs compared to controls. Significant increases in both the collagen density and fiber diameter were also seen with this treatment, increasing these values by 32 and 15%, respectively, over control values. Mechanical testing found the combined bioactive treatment to synergistically increase the Young's modulus and ultimate tensile strength of the engineered fibrocartilages compared to controls, with values reaching the lower spectrum of those found in native tissues. Together, these data demonstrate that C-ABC and TGF-beta1 interact to develop a denser collagen matrix better able to withstand tensile loading. This study highlights a way to optimize the tensile properties of engineered fibrocartilage using a biochemical and a biophysical agent together to create distinct fibrocartilages with functional properties mimicking those of native tissue. CI - Copyright (c) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. FAU - MacBarb, Regina F AU - MacBarb RF AD - Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, USA. FAU - Makris, Eleftherios A AU - Makris EA FAU - Hu, Jerry C AU - Hu JC FAU - Athanasiou, Kyriacos A AU - Athanasiou KA LA - eng GR - R01 DE019666/DE/NIDCR NIH HHS/United States GR - T32 GM008799/GM/NIGMS NIH HHS/United States GR - R01 DEO19666/PHS HHS/United States GR - 5-T32-GM008799/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20121004 PL - England TA - Acta Biomater JT - Acta biomaterialia JID - 101233144 RN - 0 (Transforming Growth Factor beta1) RN - EC 4.2.2.20 (Chondroitin ABC Lyase) SB - IM MH - Animals MH - Biomechanical Phenomena MH - Cattle MH - Chondroitin ABC Lyase/*pharmacology MH - Coculture Techniques MH - *Fibrocartilage MH - Immunohistochemistry MH - Microscopy, Electron, Scanning MH - *Tissue Engineering MH - Transforming Growth Factor beta1/*pharmacology PMC - PMC3518537 MID - NIHMS412695 EDAT- 2012/10/09 06:00 MHDA- 2013/06/12 06:00 PMCR- 2014/01/01 CRDT- 2012/10/09 06:00 PHST- 2012/05/31 00:00 [received] PHST- 2012/08/24 00:00 [revised] PHST- 2012/09/27 00:00 [accepted] PHST- 2012/10/09 06:00 [entrez] PHST- 2012/10/09 06:00 [pubmed] PHST- 2013/06/12 06:00 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - S1742-7061(12)00474-6 [pii] AID - 10.1016/j.actbio.2012.09.037 [doi] PST - ppublish SO - Acta Biomater. 2013 Jan;9(1):4626-34. doi: 10.1016/j.actbio.2012.09.037. Epub 2012 Oct 4.