Fiber-reinforced load-bearing soft tissues, including tendon, meniscus, and annulus fibrosus, have hierarchical structure and biochemical composition that enables in vivo mechanical function. These tissues are prone to degeneration and injury, with debilitating consequences, high costs, and limited therapeutic options. Although load-bearing tissues are classically described using idealized schematics showing an ordered prevailing fiber direction, these tissues are in fact highly inhomogeneous, with amorphous proteoglycan-rich structural micro-domains within an otherwise ordered collagen-rich fibrous tissue - they are not simply a schematic. The objective of this proposal is to investigate micro-level structure-function of native and engineered tissue by quantifying and modeling mechanics from the tissue to the cellular level, and evaluating the mechanistic impact of micro-level structure-function on mechanotransduction. This study will also recapitulate these natural and/or potentially diseased micro-environments in engineered tissues in order to develop controlled in vitro systems to evaluate altered mechanotransduction. Quantifying the size, mechanical inhomogeneity, and biological response among tissue micro-domains is important because this is the length scale that governs cell mechanotransduction, and therefore regulation of tissue homeostasis and disease progression. These studies will advance the field of regenerative medicine by addressing micromechanical mechanisms in tissue development, degeneration, and injury. Ultimately, this new understanding will direct therapeutic strategies for rehabilitatio, repair, and replacement to promote and preserve healthy mechanotransduction in fibrous load bearing tissues.
Load-bearing soft tissues, including tendon, meniscus, and annulus fibrosus, have a fiber-reinforced structure that enables mechanical function. These tissues are prone to degeneration and injury, with debilitating consequences, high costs, and limited therapeutic options. This proposal will investigate micro-level structure-function (?S/F) o native and engineered tissue by quantifying and modeling mechanics from the macroscopic to the cellular (micro-domain) level and evaluating the impact of ?S/F on cell mechanotransduction. These relationships are critical, as cell mechanotransduction and regulation of tissue homeostasis and disease progression occurs at this length scale. Ultimately, this new understanding will direct therapeutic strategies for rehabilitation, repair, and replacement to promote and preserve healthy mechanotransduction in fibrous load bearing tissues.
|Li, Qing; Qu, Feini; Han, Biao et al. (2017) Micromechanical anisotropy and heterogeneity of the meniscus extracellular matrix. Acta Biomater 54:356-366|
|Safa, Babak N; Meadows, Kyle D; Szczesny, Spencer E et al. (2017) Exposure to buffer solution alters tendon hydration and mechanics. J Biomech 61:18-25|
|Heo, Su-Jin; Szczesny, Spencer E; Kim, Dong Hwa et al. (2017) Expansion of mesenchymal stem cells on electrospun scaffolds maintains stemness, mechano-responsivity, and differentiation potential. J Orthop Res :|
|Szczesny, Spencer E; Fetchko, Kristen L; Dodge, George R et al. (2017) Evidence that interfibrillar load transfer in tendon is supported by small diameter fibrils and not extrafibrillar tissue components. J Orthop Res 35:2127-2134|
|Szczesny, Spencer E; Mauck, Robert L (2017) The Nuclear Option: Evidence Implicating the Cell Nucleus in Mechanotransduction. J Biomech Eng 139:|
|Peloquin, John M; Santare, Michael H; Elliott, Dawn M (2016) Advances in Quantification of Meniscus Tensile Mechanics Including Nonlinearity, Yield, and Failure. J Biomech Eng 138:021002|
|Heo, Su-Jin; Driscoll, Tristan P; Thorpe, Stephen D et al. (2016) Differentiation alters stem cell nuclear architecture, mechanics, and mechano-sensitivity. Elife 5:|
|Heo, Su-Jin; Han, Woojin M; Szczesny, Spencer E et al. (2016) Mechanically Induced Chromatin Condensation Requires Cellular Contractility in Mesenchymal Stem Cells. Biophys J 111:864-874|
|Peloquin, John M; Elliott, Dawn M (2016) A comparison of stress in cracked fibrous tissue specimens with varied crack location, loading, and orientation using finite element analysis. J Mech Behav Biomed Mater 57:260-8|
|Cote, Allison J; McLeod, Claire M; Farrell, Megan J et al. (2016) Single-cell differences in matrix gene expression do not predict matrix deposition. Nat Commun 7:10865|
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