Dissertation/Thesis Abstract

Tissue Engineering Strategies to Improve Tendon Healing and Insertion Site Integration
by Kinneberg, Kirsten Rose Carol, Ph.D., University of Cincinnati, 2011, 159; 3469920
Abstract (Summary)

Tendon and ligament tears and ruptures remain common and significant musculoskeletal injuries. Repairing these injuries continues to be a prominent challenge in orthopaedics and sports medicine. Despite advances in surgical techniques and procedures, traditional repair techniques maintain a high incidence of re-rupture. This has led some researchers to consider using tissue engineered constructs (TECs).

Previous studies in our laboratory have demonstrated that TEC stiffness at the time of surgery is positively correlated with repair tissue stiffness 12 weeks post-surgery. This correlation provided the rationale for implanting a soft tissue patellar tendon autograft (PTA) to repair a central-third defect in the rabbit patellar tendon (PT). The PTA was significantly stiffer than previous TECs and matched the stiffness of the normal central-third PT. Accordingly, we expected a significant improvement in repair tissue biomechanics relative to both natural healing (NH) and TEC repair. At 12 weeks, treatment with PTA improved repair tissue stiffness relative to NH. However, PTA and NH tissues did not differ in maximum force, modulus or maximum stress. Additionally, neither repair group regenerated normal zonal insertion sites.

To enhance integration at the tendon-to-bone insertion site, PTA repairs were 1) given up to 26 weeks to recover and 2) augmented at the patellar and tibial insertions with mesenchymal stem cell (MSC)-collagen gel biologic augmentations (BAs). The role of the native cell population in PTA healing was also tested by de-cellularizing the PTA at surgery. We found that osteotendinous integration improved with recovery time for both de-cellularized PTA (dcPTA) and PTA repairs. However, biomechanical properties were only affected by recovery time for dcPTA repairs. Despite the changes in biomechanical properties demonstrated by dcPTA repairs, biomechanical properties did not vary between dcPTA and PTA repairs at any time point. We also found that MSC-collagen gel BAs did not enhance osteotendinous integration or repair tissue biomechanical properties relative to PTA repairs at 12 weeks post-surgery.

Overall, the repair tissue biomechanics of our mechanically pre-conditioned MSC-collagen sponge TECs were approximately twice the biomechanical properties for both PTA repairs and NH. This result warranted additional experiments to further improve in vitro TEC stiffness and mRNA expression with the objective to enhance tendon healing. We investigated the effects of pore size, scaffold composition and mechanical pre-conditioning in vitro on MSC-collagen sponge TEC stiffness and mRNA expression levels for genes of interest. Our initial results indicated that for collagen sponge TECs, pore size did not affect linear stiffness and mechanical stimulation only enhanced stiffness when chondroitin-6-sulfate was incorporated into the collagen sponge.

The goals of my research were to 1) understand the effects of the resident cell population and healing time on PTA integration into bone, 2) develop a biologic augmentation that would improve tendon insertion site development, and 3) improve TEC-mediated PT healing. Future studies need to investigate the effects of combining biological and mechanical factors at the insertion site on PTA integration and also validate our in vitro-to-in vivo predictors for MSC-collagen sponge TEC repair using updated sponge materials.

Indexing (document details)
Advisor: Shearn, Jason T.
Commitee: Butler, David L., Kenter, Keith
School: University of Cincinnati
Department: Biomedical Engineering
School Location: United States -- Ohio
Source: DAI-B 72/11, Dissertation Abstracts International
Subjects: Biomedical engineering
Keywords: Autograft, Mesenchymal stem cell, Patellar tendon, Tissue engineering
Publication Number: 3469920
ISBN: 9781124863252
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