Synergistic and Additive Effects of Hydrostatic Pressure and Growth Factors on Tissue Formation
Open Access
- 4 June 2008
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 3 (6), e2341
- https://doi.org/10.1371/journal.pone.0002341
Abstract
Hydrostatic pressure (HP) is a significant factor in the function of many tissues, including cartilage, knee meniscus, temporomandibular joint disc, intervertebral disc, bone, bladder, and vasculature. Though studies have been performed in assessing the role of HP in tissue biochemistry, to the best of our knowledge, no studies have demonstrated enhanced mechanical properties from HP application in any tissue. The objective of this study was to determine the effects of hydrostatic pressure (HP), with and without growth factors, on the biomechanical and biochemical properties of engineered articular cartilage constructs, using a two-phased approach. In phase I, a 3×3 full-factorial design of HP magnitude (1, 5, 10 MPa) and frequency (0, 0.1, 1 Hz) was used, and the best two treatments were selected for use in phase II. Static HP at 5 MPa and 10 MPa resulted in significant 95% and 96% increases, respectively, in aggregate modulus (HA), with corresponding increases in GAG content. These regimens also resulted in significant 101% and 92% increases in Young's modulus (EY), with corresponding increases in collagen content. Phase II employed a 3×3 full-factorial design of HP (no HP, 5 MPa static, 10 MPa static) and growth factor application (no GF, BMP-2+IGF-I, TGF-β1). The combination of 10 MPa static HP and TGF-β1 treatment had an additive effect on both HA and EY, as well as a synergistic effect on collagen content. This group demonstrated a 164% increase in HA, a 231% increase in EY, an 85% increase in GAG/wet weight (WW), and a 173% increase in collagen/WW, relative to control. To our knowledge, this is the first study to demonstrate increases in the biomechanical properties of tissue from pure HP application, using a cartilage model. Furthermore, it is the only study to demonstrate additive or synergistic effects between HP and growth factors on tissue functional properties. These findings are exciting as coupling HP stimulation with growth factor application has allowed for the formation of tissue engineered constructs with biomechanical and biochemical properties spanning native tissue values.This publication has 55 references indexed in Scilit:
- Hydrostatic Pressure Differentially Regulates Outer and Inner Annulus Fibrosus Cell Matrix Production in 3D ScaffoldsAnnals of Biomedical Engineering, 2007
- Effects of confinement on the mechanical properties of self‐assembled articular cartilage constructs in the direction orthogonal to the confinement surfaceJournal of Orthopaedic Research, 2007
- Influence of extracellular osmolarity and mechanical stimulation on gene expression of intervertebral disc cellsJournal of Orthopaedic Research, 2007
- Cyclic Pressure Stimulates DNA Synthesis through the PI3K/Akt Signaling Pathway in Rat Bladder Smooth Muscle CellsAnnals of Biomedical Engineering, 2007
- Increased accumulation of superficial zone protein (SZP) in articular cartilage in response to bone morphogenetic protein‐7 and growth factorsJournal of Orthopaedic Research, 2006
- A novel method for assessing effects of hydrostatic fluid pressure on intracellular calcium: a study with bovine articular chondrocytesAmerican Journal of Physiology-Cell Physiology, 2005
- Effect of Low Oxygen Tension on Tissue-Engineered Cartilage Construct Development in the Concentric Cylinder BioreactorTissue Engineering, 2004
- Combining Chondrocytes and Smooth Muscle Cells to Engineer Hybrid Soft Tissue ConstructsTissue Engineering, 2000
- A function that relates protein synthetic rates to potassium activity in vivoJournal of Cellular Physiology, 1988
- Biphasic Creep and Stress Relaxation of Articular Cartilage in Compression: Theory and ExperimentsJournal of Biomechanical Engineering, 1980