Measuring spatially varying elastic modulus of multi-compartment 3D collagen scaffold using indentation

Collagen Scaffold;Multi-compartment;Indentation;tendon-to-bone junctions (TBJ)

Altahhan, Khaldoon N

关键词: Collagen Scaffold;    Multi-compartment;    Indentation;    tendon-to-bone junctions (TBJ);   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/78489/ALTAHHAN-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Collagen scaffolds with discrete mineralized and non-mineralized regions that are joined by a continuous interface offer great potential for generating a platform with spatially variant stiffness.Once such platforms are seeded with cells, they have been shown to significantly influence cell behavior and differentiation.Accurate elastic modulus measurements of theses scaffolds will greatly influence their ability to engineer tissues with varying degrees of stiffness such as tendon-to-bone junctions (TBJ). This thesis presents a novel indentation method as an accurate measurement technique for estimating the intrinsic elastic modulus in 3-D thin-layer collagen scaffolds with varying degrees of stiffness.Indentation techniques are widely used to characterize the mechanical properties of biological materials.These methods have received considerable attention during the last 20 years because of their simplicity and low cost, but they are challenging to implement. The challenge is to interpret the intrinsic mechanical properties from force-displacement data when studying very soft polymeric media with a volume on the order of a milliliter.It is especially challenging to estimate the elastic modulus of thin-layer scaffolds when the stiffness varies spatially.In this work we use the hydrated indentation method (w/o surface adhesion) to measure the elastic modulus for very soft (<1kPa) polymeric media and for thin-layer 3-D collagen scaffolds.We build confidence in our approach by first validating the indentation measurements using an elastic hydro-polymer (gelatin gels) through comparisons with other quasi-static indentation methods (i.e., using surface adhesion) and with dynamic shear-wave imaging estimates. We then show our modulus measurements can be biased because of coupling with sample boundaries.Finally, we develop a novel inverse approach for correcting the indentation measurement bias near continuously-varying interfaces between mineralized and non-mineralized regions.For this approach we developed a shift-varying Gaussian filter that we used to uncouple the spread in the applied indenter force from the material interface.We established the correction filter using FEA simulation data where indenter is serially applied across a step interface.We argued that due to system linearity the correction filter should apply equally to a step or ramp interface.Intrinsic values of elastic modulus at and near the interface where obtained by solving the inverse problem the correction filter was found.We then tested our technique using FE models for a range of scaffold-like stiffnesses and interface shapes to evaluate the impact of interface width and indenter size on the inverse solution. Our approach significantly reduced indentation measurement bias near step interfaces by more than 60% when using a 2.5 mm-diameter hemispherical indenter.The improvement was more than 35% for a ramp interface using the same indenter size.These improvements are beneficial as a tight control over scaffold mechanical properties is essential for their success in the development of TBJ. The TBJ stiffness changes two orders of magnitude from relatively compliant tendon to bone over a relatively narrow interface region (600-400 µm).Therefore, accurate elastic modulus measurements of theses scaffolds will greatly improve their manufacturing process, and ability to provide a standardized framework for both in vitro interactions between cells and scaffolds and in vivo tissue engineering studies