The influence of cyclic tensile strain on multi-compartment collagen-GAG scaffolds for tendon-bone junction repair

ABSTRACT

Background: Orthopedic injuries often occur at the interface between soft tissues and bone. The tendon-bone junction (TBJ) is a classic example of such an interface. Current clinical strategies for TBJ injuries prioritize mechanical reattachment over regeneration of the native interface, resulting in poor outcomes. The need to promote regenerative healing of spatially-graded tissues inspires our effort to develop new tissue engineering technologies that replicate features of the spatially-graded extracellular matrix and strain profiles across the native TBJ.

Materials and Methods: We recently described a biphasic collagen-glycosaminoglycan (CG) scaffold containing distinct compartment with divergent mineral content and structural alignment (isotropic vs. anisotropic) linked by a continuous interface zone to mimic structural and compositional features of the native TBJ.

Results: Here, we report application of cyclic tensile strain (CTS) to the scaffold via a bioreactor leads to non-uniform strain profiles across the spatially-graded scaffold. Further, combinations of CTS and matrix structural features promote rapid, spatially-distinct differentiation profiles of human bone marrow-derived mesenchymal stem cells (MSCs) down multiple osteotendinous lineages. CTS preferentially upregulates MSC activity and tenogenic differentiation in the anisotropic region of the scaffold. This work demonstrates a tissue engineering approach that couples instructive biomaterials with cyclic tensile stimuli to promote regenerative healing of orthopedic interfaces.

KEYWORDS:

• Collagen scaffold
• cyclic tensile strain
• bioreactor
• mechanotransduction
• tendon-bone junction

Acknowledgments

The authors would like to acknowledge the Carl R. Woese Institute for Genomic Biology Core Facilities for assistance with real-time PCR system and immunoblotting. This research was carried out in part at the Imaging Technology Group within the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. The authors would like to thank Scott Robinson and Cate Wallace for assistance with critical point drying and scanning electron microscopy. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R21 AR063331. We are grateful for funding from the NSF Graduate Research Fellowship DGE-1144245 (RSHC). Additional support was provided by the Chemical and Biomolecular Engineering Dept. and the Carl R. Woese Institute for Genomic Biology (BACH) at the University of Illinois at Urbana-Champaign.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

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Additional information

Funding

This work was supported by the Division of Graduate Education [1144245];National Institute of Arthritis and Musculoskeletal and Skin Diseases [R21 AR063331].