Development of a biomaterial template for regeneration of the tendon-to-bone insertion

Sun Han Chang, Raul Agustin

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https://hdl.handle.net/2142/115506 Copy

Description

Title

Development of a biomaterial template for regeneration of the tendon-to-bone insertion

Author(s)

Sun Han Chang, Raul Agustin

Issue Date

2022-01-24

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

Harley, Brendan A

Doctoral Committee Chair(s)

Harley, Brendan A

Committee Member(s)

• Zhao, Huimin
• Rogers, Simon A
• Kersh, Mariana E

Department of Study

Chemical & Biomolecular Engr

Discipline

Chemical Engineering

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Biomaterials
• Tissue engineering

Abstract

The osteotendinous junction links tendon to bone via a continuous fibrocartilaginous interface (enthesis) that reduces interfacial strain and decreases the risk of failure between highly elastic tendon and 100-fold stiffer bone. Injuries at the osteotendinous junction are frequent due to the highly dynamic and load-bearing nature of the tissue, and occur in response to acute (e.g. overload) and degradative (e.g. aging) processes. The current standard of care for these injuries are surgical interventions that mechanically affix the torn tendon directly onto bone. However, poor post-operative healing due to formation of dense and mechanically inferior scar tissue rather than a native fibrocartilaginous enthesis results in high rates of tissue re-failure. Functional reintegration of the torn osteotendinous tissue requires regeneration of the compliant fibrocartilaginous interface. However, progress towards biomaterial-based regenerative strategies for healing of the tendon-to-bone enthesis is hampered by an inability for biomaterials to present spatially continuous interface zones or to overcome high levels of local strain that form at the interface between dissimilar tissues. This thesis describes a novel strategy to produce multi-tissue biomaterials incorporating three distinct phases: discrete osseous (bone) and tendinous (tendon) collagen-glycosaminoglycan (GAG) scaffolds linked by a compliant hydrogel interface. We report the ability to tune critical enthesis-mimetic properties of the hydrogel interface by varying the gelation rate and elasticity of the polymer network, which ultimately control the integration of tissue-phases at the interface and resultant local and bulk mechanical properties under tensile loading. While the adjacent collagen-GAG zones incorporate structural and chemical cues that have been shown to promote spatially-selective osteogenic and tenogenic behavior in human mesenchymal stem cells (hMSCs), this project identifies an interfacial hydrogel system with the potential to direct interface remodeling and regenerative potential. Future work aims to co-optimize these three phases to address local cell response while simultaneously imbuing tissue-relevant mechanical behavior, together forming a scaffold that recapitulates critical aspects of the osteotendinous junction for superior healing outcomes.

Graduation Semester

2022-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Raul Sun Han Chang

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