Date of Award
Master of Science (MS)
Jeremy Mercuri, PhD, Committee Chair
Agneta Simionescu, PhD
Richard Hawkins, MD
Injury and degeneration of rotator cuff tendons are frequent causes of shoulder disability globally, commonly affecting athletes and the elderly. Annually, there are approximately 250,000 surgeries related to the rotator cuff performed in the United States.1 With rotator cuff tears being the largest cause of rotator cuff surgery, between 10% and 40% of all rotator cuff tears are classified as massive, extending over 5 cm in length. 2,3,4,5,6 The success rate of massive rotator cuff tear repair is variable, with re-tear rates ranging from 38% to 90% depending on factors such as patient age, tear chronicity, and overall tissue quality.7,8,9,10 A primary factor causing failure is poor tissue quality due to poor tissue regeneration by sparse and inactive resident tenocytes.11 Current repair approaches (biceps tenotomy/tenodesis, muscle-tendon transfer, and biologic tissue grafts) suffer from shortcomings because they do not address tissue quality nor do they attempt to regenerate damaged tendon.12,13,14,15,16,17,18,19 Therefore, it would be advantageous to develop a therapy that can cause tissue regeneration by addressing the issues of tenocyte inactivity and poor tissue quality. Our proposed approach for massive RC repair utilizes autologous adipose derived stem cells (hADSC) and an autologous tendon graft scaffold to biologically augment suture repair by delivering stem cells and promoting their differentiation. This approach aims to improve the quality of naturally formed matrix at the repair site over time through integration of the scaffold with the damaged tendon. This method can be performed entirely at the point of care, reducing additional processing time, external expansion of cells, and tissue contamination. Herein, we propose to address proof of concept studies illustrating the following: 1) the ability to reliably form macro-porous (meshed) scaffolds from a tendon source. 2) The viability of tenocytes within scaffolds. 3) The mechanical properties of the scaffold. 4) The ideal autologous tenocyte source for differentiation of hADSCs. 5) The ability of the scaffold-stem cell construct to integrate with underlying tissue. Results presented illustrate our ability to fabricate a macro-porous tendon scaffold of 187% expansion and the properties of said scaffolds. Once scaffold fabrication was established, the properties were assessed. When tendons were meshed to fabricate a tendon graft scaffold cell viability was decreased by 30%, elastic modulus was decreased by 32.45 MPa, and ultimate tensile stress was decreased by 1.82 MPa. The ideal tendon source for fabrication of tendon graft scaffolds was determined to be semitendinosus tendon over long head biceps tendon via hADSC differentiation profile. Lastly, in order to determine if the scaffolds would improve the underlying tendon quality, the integration of the proposed construct was illustrated in vitro.
Welch, Alison, "Proof of Concept Studies for Point of Care Rotator Cuff Tissue Engineering" (2016). All Theses. 2397.