Design of Tissue Engineering Scaffolds as Delivery Devices for Mechanical and Mechanically Modulated Signals
- 1 October 2007
- journal article
- research article
- Published by Mary Ann Liebert Inc in Tissue Engineering
- Vol. 13 (10), 2525-2538
- https://doi.org/10.1089/ten.2006.0443
Abstract
New approaches to tissue engineering aim to exploit endogenous strategies such as those occurring in prenatal development and recapitulated during postnatal healing. Defining tissue template specifications to mimic the environment of the condensed mesenchyme during development allows for exploitation of tissue scaffolds as delivery devices for extrinsic cues, including biochemical and mechanical signals, to drive the fate of mesenchymal stem cells seeded within. Although a variety of biochemical signals that modulate stem cell fate have been identified, the mechanical signals conducive to guiding pluripotent cells toward specific lineages are less well characterized. Furthermore, not only is spatial and temporal control of mechanical stimuli to cells challenging, but also tissue template geometries vary with time due to tissue ingrowth and/or scaffold degradation. Hence, a case study was carried out to analyze flow regimes in a testbed scaffold as a first step toward optimizing scaffold architecture. A pressure gradient was applied to produce local (nm-micron) flow fields conducive to migration, adhesion, proliferation, and differentiation of cells seeded within, as well as global flow parameters (micron-mm), including flow velocity and permeability, to enhance directed cell infiltration and augment mass transport. Iterative occlusion of flow channel dimensions was carried out to predict virtually the effect of temporal geometric variation (e.g., due to tissue development and growth) on delivery of local and global mechanical signals. Thereafter, insights from the case study were generalized to present an optimization scheme for future development of scaffolds to be implemented in vitro or in vivo. Although it is likely that manufacture and testing will be required to finalize design specifications, it is expected that the use of the rational design optimization will reduce the number of iterations required to determine final prototype geometries and flow conditions. As the range of mechanical signals conducive to guiding cell fate in situ is further elucidated, these refined design criteria can be integrated into the general optimization rubric, providing a technological platform to exploit nature's endogenous tissue engineering strategies for targeted tissue generation in the lab or the clinic.Keywords
This publication has 38 references indexed in Scilit:
- Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesisJournal of Thrombosis and Haemostasis, 2007
- Testing of a New One-Stage Bone-Transport Surgical Procedure Exploiting the Periosteum for the Repair of Long-Bone DefectsThe Journal of Bone & Joint Surgery, 2007
- Spatio–temporal VEGF and PDGF Delivery Patterns Blood Vessel Formation and MaturationPharmaceutical Research, 2006
- In vitro generated extracellular matrix and fluid shear stress synergistically enhance 3D osteoblastic differentiationProceedings of the National Academy of Sciences of the United States of America, 2006
- Adipose Tissue-Derived Mesenchymal Stem Cells Acquire Bone Cell-Like Responsiveness to Fluid Shear Stress on Osteogenic StimulationTissue Engineering, 2005
- Shear Stress Induces Endothelial Differentiation From a Murine Embryonic Mesenchymal Progenitor Cell LineArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- Bone Tissue Engineering Using Human Mesenchymal Stem Cells: Effects of Scaffold Material and Medium FlowAnnals of Biomedical Engineering, 2004
- Transforming growth factor β1 stimulates type II collagen expression in cultured periosteum-derived cellsJournal of Bone and Mineral Research, 1992
- Stimulation of chondrogenesis in limb bud mesoderm cells by recombinant human bone morphogenetic protein 2B (BMP-2B) and modulation by transforming growth factor ?1 and ?2*1Experimental Cell Research, 1991
- Effect of TGF-β1, TGF-β2, and bFGF on chick cartilage and muscle cell differentiationExperimental Cell Research, 1990