Combined Effects of Scaffold Stiffening and Mechanical Preconditioning Cycles on Construct Biomechanics, Gene Expression, and Tendon Repair Biomechanics
- 1 August 2009
- journal article
- research article
- Published by Mary Ann Liebert Inc in Tissue Engineering, Part A
- Vol. 15 (8), 2103-2111
- https://doi.org/10.1089/ten.tea.2008.0335
Abstract
Our group has previously reported that in vitro mechanical stimulation of tissue-engineered tendon constructs significantly increases both construct stiffness and the biomechanical properties of the repair tissue after surgery. When optimized using response surface methodology, our results indicate that a mechanical stimulus with three components (2.4% strain, 3000 cycles/day, and one cycle repetition) produced the highest in vitro linear stiffness. Such positive correlations between construct and repair stiffness after surgery suggest that enhancing structural stiffness before surgery could not only accelerate repair stiffness but also prevent premature failures in culture due to poor mechanical integrity. In this study, we examined the combined effects of scaffold crosslinking and subsequent mechanical stimulation on construct mechanics and biology. Autologous tissue-engineered constructs were created by seeding mesenchymal stem cells (MSCs) from 15 New Zealand white rabbits on type I collagen sponges that had undergone additional dehydrothermal crosslinking (termed ADHT in this manuscript). Both constructs from each rabbit were mechanically stimulated for 8 h/day for 12 consecutive days with half receiving 100 cycles/day and the other half receiving 3000 cycles/day. These paired MSC–collagen autologous constructs were then implanted in bilateral full-thickness, full-length defects in the central third of rabbit patellar tendons. Increasing the number of in vitro cycles/day delivered to the ADHT constructs in culture produced no differences in stiffness or gene expression and no changes in biomechanical properties or histology 12 weeks after surgery. Compared to MSC-based repairs from a previous study that received no additional treatment in culture, ADHT crosslinking of the scaffolds actually lowered the 12-week repair stiffness. Thus, while ADHT crosslinking may initially stiffen a construct in culture, this specific treatment also appears to mask any benefits of stimulation among repairs postsurgery. Our findings emphasize the importance of properly preconditioning a scaffold to better control/modulate MSC differentiation in vitro and to further enhance repair outcome in vivo.Keywords
This publication has 34 references indexed in Scilit:
- Improving Linear Stiffness of the Cell-Seeded Collagen Sponge Constructs by Varying the Components of the Mechanical StimulusTissue Engineering, Part A, 2008
- Mechanical Stimulation of Tendon Tissue Engineered Constructs: Effects on Construct Stiffness, Repair Biomechanics, and Their CorrelationJournal of Biomechanical Engineering, 2007
- Conjugation of extracellular matrix proteins to basal lamina analogs enhances keratinocyte attachmentJournal of Biomedical Materials Research Part A, 2006
- Effects of age on the repair ability of mesenchymal stem cells in rabbit tendonJournal of Orthopaedic Research, 2005
- Mesenchymal stem cells used for rabbit tendon repair can form ectopic bone and express alkaline phosphatase activity in constructsJournal of Orthopaedic Research, 2004
- Cell differentiation by mechanical stressThe FASEB Journal, 2001
- Use of mesenchymal stem cells in a collagen matrix for achilles tendon repairJournal of Orthopaedic Research, 1998
- Cell orientation response to cyclically deformed substrates: Experimental validation of a cell modelJournal of Biomechanics, 1995
- Temperature Dependent Behavior of the Canine Medial Collateral LigamentJournal of Biomechanical Engineering, 1987
- Effects of structure and strain measurement technique on the material properties of young human tendons and fasciaJournal of Biomechanics, 1984