ORTHOPEDIC INTERFACE TISSUE ENGINEERING: BUILDING THE BRIDGE TO INTEGRATED MUSCULOSKELETAL TISSUE SYSTEMS - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 585

interface - specifi c markers in progenitor or stem cells, and demonstrate the effects
of heterotypic cellular interactions in regulating the maintenance of specifi c
cellular phenotypes at multi-tissue junctions. While the nature of the regulatory
molecules and the mechanism behind these interactions remains elusive, cell
communication is likely to be signifi cant for interface regeneration as well as
homeostasis (Jiang et al. 2007; Lu and Jiang 2006).

17.4 STRUCTURE-FUNCTION RELATIONSHIP AT THE INTERFACE

In addition to elucidating the mechanism of interface regeneration, understand-
ing the interface structure-function relationship will also be important for func-
tional scaffold design for interface tissue engineering. Butler et al. (Butler,
Goldstein, and Guilak 2000) proposed that, for functional tissue engineering, it is
critical to determine the material properties of the tissue to be replaced, as well as
to quantify the in vivo strains and stresses experienced by the native tissue. There-
fore, the structural and material properties of the insertion site must be character-
ized in order to re-engineer the functional interface between soft tissue and bone.
Moreover, the biomimetic design parameters can serve as outcome criteria for
determining the success of the tissue engineered interfaces.
The inherent multi-tissue organization and heterogeneity in matrix composi-
tion at the interface are likely related to the nature and distribution of the
mechanical stress experienced at the region. Knowledge of mechanical properties
of the insertion site has been largely derived from theoretical predictions (Matyas
et al. 1995; Thomopoulos et al. 2003). Thomopoulos et al. examined the variation
in biomechanical properties of the supraspinatus tendon-to-bone insertion in a
rodent model (Thomopoulos et al. 2003). Using the Quasi-Linear Viscoelastic
model (Fung 1972), the viscoelastic behavior of the tendon-to-bone insertion was
predicted to vary along the length of the tendon, with superior elastic and visco-
elastic properties predicted for the tendon - to - fi brocartilage transition compared
to the fi brocartilage - to - bone transition (Thomopoulos et al. 2003 ). These reports
strongly suggest that the matrix organization at the tendon-to-bone transition is
optimized to sustain both tensile and compressive stresses.
The direct measurement of interface mechanical properties has been diffi cult
due to the complexity and the relative small scale of the interface, in general
ranging from 100 m to 1 mm in length (Cooper and Misol 1970; Gao and Messner

1996; Wang, Mitroo, Chen, Lu, and Doty 2006; Woo and Buckwalter 1988).
Recently, using the novel functional imaging method of ultrasound elastography
(Konofagou and Ophir 2000), Spalazzi et al. conducted the fi rst experimental
determination of the strain distribution at the ACL-to-bone interface (Spalazzi,
Gallina, Fung-Kee-Fung, Konofagou, and Lu 2006). In this study, the tibio-
femoral joint was mounted on a material testing system and loaded in tension in
the tibial orientation while radiofrequency (RF) data were collected over time.
Axial elastograms between successive RF frames were then generated using
cross-correlation and recorrelation techniques. Elastography analyses revealed

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