Development of multicompartment biomaterials to modulate cellular environments for improved tendon-to-bone rotator cuff repair

Timmer, Kyle Benjamin

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https://hdl.handle.net/2142/129854 Copy

Description

Title

Development of multicompartment biomaterials to modulate cellular environments for improved tendon-to-bone rotator cuff repair

Author(s)

Timmer, Kyle Benjamin

Issue Date

2025-07-14

Director of Research (if dissertation) or Advisor (if thesis)

Harley, Brendan A

Doctoral Committee Chair(s)

Harley, Brendan A

Committee Member(s)

• Rogers, Simon A
• Kong, Hyunjoon
• Killian, Megan L

Department of Study

Chemical & Biomolecular Engr

Discipline

Chemical Engineering

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Enthesis
• Scaffold
• Triphasic
• Multicompartment
• Biomaterial

Abstract

Rotator cuff tears present a growing clinical challenge due to both the continual rise in the number of patients and the inability of current methods to facilitate regenerative healing, resulting in significant re-failure rates. Current surgical repair methods rely on the mechanical reattachment of the torn tendon back to the bone. However, these techniques fail to account for the crucial interfacial tissue that mechanically integrates highly dissimilar tendon and bone regions at the osteotendinous junction, known as the enthesis. Here, unmineralized and mineralized fibrocartilage regions provide a graded transition in structure between aligned tendon and unaligned bone, shielding the interface from detrimental concentrations of localized strain that could induce overall failure. Further, the tendon, unmineralized fibrocartilage, mineralized fibrocartilage, and bone contain unique populations of cells, giving rise to spatially distinct environments of small biomolecule signaling and cell-cell interaction. Given the complexity of this region and the current shortcomings in surgical repair, biomaterials strategies for regeneration of the enthesis offer a promising avenue for next-generation rotator cuff repair. Our lab has developed variations of collagen-glycosaminoglycan scaffolds that can guide mesenchymal stem cell behavior toward tenogenic or osteogenic lineages. Additionally, our lab has described designs for multicompartment scaffolds, incorporating these scaffold variants into a single material for use in tendon-to-bone enthesis regeneration. The most recent design utilizes a compliant, enzymatically cross-linked hydrogel that integrates aligned, non-mineralized tendon-specific and isotropic, mineralized bone-specific collagen scaffold compartments to form a triphasic scaffold. However, despite demonstrating preliminary mechanical promise, the biological implications of such a design were not considered. This thesis focuses on the development of a triphasic scaffold to guide region-specific osteotendinous cell behavior. We first evaluate cellular crosstalk between the individual compartments, establishing a biologically favorable hydrogel construct for use in the triphasic design and reinforcing the importance of all three scaffold compartments for a functional interfacial material. Next, we investigate the optimization of the interfacial hydrogel for improved mechanical compliance, material integration, and promotion of a fibrocartilaginous phenotype via chemical modification of the backbone polymer and selective incorporation of bioactive supplements. Finally, we extend our scope of biomaterials analysis to consider greater environmental complexity and outside stimuli through the incorporation of cyclic tensile loading and the development of a miniaturized multicompartment model for use with in vivo analysis. Altogether, this dissertation explores the development of materials for interfacial tissue engineering applications, establishing the importance of crosstalk between local cell populations and of cross-interaction between material, mechanical, and biological properties to demonstrate the importance of system-level consideration in biomaterial design.

Graduation Semester

2025-08

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/129854

Copyright and License Information

Copyright 2025 Kyle Timmer

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