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PLoS One. 2017 Apr 3;12(4):e0174789. doi: 10.1371/journal.pone.0174789. eCollection 2017.

Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering.

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Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, Farmington, Connecticut, United States of America.
Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, Connecticut, United States of America.
Department of Materials Science & Engineering, University of Connecticut, Storrs, Connecticut, United States of America.
Department of Chemistry, the Pennsylvania State University, University Park, Pennsylvania, United States of America.
Analytical Microscopy Laboratory, Hospital for Special Surgery, New York, NY, United States of America.


Rotator cuff (RC) tears represent a large proportion of musculoskeletal injuries attended to at the clinic and thereby make RC repair surgeries one of the most widely performed musculoskeletal procedures. Despite the high incidence rate of RC tears, operative treatments have provided minimal functional gains and suffer from high re-tear rates. The hypocellular nature of tendon tissue poses a limited capacity for regeneration. In recent years, great strides have been made in the area of tendonogenesis and differentiation towards tendon cells due to a greater understanding of the tendon stem cell niche, development of advanced materials, improved scaffold fabrication techniques, and delineation of the phenotype development process. Though in vitro models for tendonogenesis have shown promising results, in vivo models have been less successful. The present work investigates structured matrices mimicking the tendon microenvironment as cell delivery vehicles in a rat RC tear model. RC injuries augmented with a matrix delivering rat mesenchymal stem cells (rMSCs) showed enhanced regeneration over suture repair alone or repair with augmentation, at 6 and 12-weeks post-surgery. The local delivery of rMSCs led to increased mechanical properties and improved tissue morphology. We hypothesize that the mesenchymal stem cells function to modulate the local immune and bioactivity environment through autocrine/paracrine and/or cell homing mechanisms. This study provides evidence for improved tendon healing with biomimetic matrices and delivered MSCs with the potential for translation to larger, clinical animal models. The enhanced regenerative healing response with stem cell delivering biomimetic matrices may represent a new treatment paradigm for massive RC tendon tears.

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