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Mechanically-Conditioned Biphasic Composite Scaffolds to Augment Healing of Tendon-Bone Interface

Subramanian, Gayathri Gowri
http://orcid.org/0000-0002-0748-9721
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1500469300203445

Abstract Details

2017, Doctor of Philosophy, University of Toledo, Biomedical Engineering.
Rotator cuff injuries are very common among people over the age of 60, with more than 600,000 surgeries performed annually in the United States for rotator cuff repairs. However, in 20-80% of the cases, the repair fails due to re-rupture of the tendon at the tendon-bone insertion site. The complexity of the tendon tissue in terms of their structure, composition, and function at the tendon-to-bone interface demands for a combinatorial tissue-engineering approach in which cell maturation and function can be directed using bioactive proteins encapsulated within a biomaterial with appropriate material stiffness. Further, since tendons experience routine mechanical strains in their native environment, providing suitable mechanical cues to the engineered scaffold was considered important for the success of rotator cuff repair strategies. The objective of this dissertation was to synthesize and characterize a mechanically-conditioned biphasic composite collagen scaffold to enhance rotator cuff regeneration with (1) controlled delivery of adipose-derived stem cells (ASCs) and platelet-derived growth factor (PDGF) to augment and accelerate tendon healing, and (2) spatial material stiffness to promote gradient mineralization and matrix directionality at the tendon-bone interface. To this end, a mechanical loading bioreactor consisting of unique silicone loading chambers was designed that was capable of applying homogenous uniaxial tensile strains over 60% of the length of cell-encapsulated 3D collagen scaffolds. Uniaxial tensile mechanical loading at 2% strain with 0.1 Hz frequency was identified to be the appropriate loading modality to induce pure ASC tenogenic differentiation, along with enhanced matrix directionality and ECM gene expression within ASC-encapsulated 3D collagen scaffolds. Next, the poor protein retention and matrix stiffness properties of collagen were improved by synthesizing a composite collagen scaffold (PNCOL) interspersed with functionalized polycaprolactone (PCL) nanofibers. The PDGF-conjugated PNCOL scaffolds demonstrated controlled release of bioactive proteins (0.5% per day) under uniaxial tensile mechanical loading. Finally, the PDGF/ASC-encapsulated COL-PNCOL biphasic composite scaffold with gradient matrix stiffness was engineered and subjected to uniaxial tensile mechanical loading to mimic the tissue at the tendon-bone insertion point. Significantly, the COL-PNCOL biphasic scaffold demonstrated two major morphological and biochemical characteristics which is representative of the tendon-fibrocartilage region of the native tendon-bone interface tissue: (1) A gradient increase in mineral deposits and a gradient decrease in the matrix alignment. (2) Elevated tenogenic expression with COL region and higher chondrogenic expression within PNCOL region. This mechanically-conditioned PDGF/ASC-encapsulated COL-PNCOL biphasic scaffold is expected to provide sustained cells and growth factor delivery to induce tenogenic differentiation and ECM secretion, and promote gradient matrix mineralization and collagen alignment of the de novo tissue, thereby aiding and accelerating the natural tendon-bone interface healing process for functional regeneration of the rotator cuff.
Eda Yildirim-Ayan (Advisor)
298 p.
Biomedical Engineering; Biomedical Research
Tissue Engineering, Tendon, Collagen, Growth factor delivery, Enthesis, Mechanical loading, Uniaxial Tensile Strain Bioreactor, Adipose-derived Stem Cells, Polycaprolactone, Scaffold

Recommended Citations

Citations

  • Subramanian, G. G. (2017). Mechanically-Conditioned Biphasic Composite Scaffolds to Augment Healing of Tendon-Bone Interface [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1500469300203445

    APA Style (7th edition)

  • Subramanian, Gayathri. Mechanically-Conditioned Biphasic Composite Scaffolds to Augment Healing of Tendon-Bone Interface. 2017. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1500469300203445.

    MLA Style (8th edition)

  • Subramanian, Gayathri. "Mechanically-Conditioned Biphasic Composite Scaffolds to Augment Healing of Tendon-Bone Interface." Doctoral dissertation, University of Toledo, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1500469300203445

    Chicago Manual of Style (17th edition)

toledo1500469300203445
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© 2017, all rights reserved.
This open access ETD is published by University of Toledo and OhioLINK.