Emerging technologies – Advances in tissue engineering using mesenchymal stem cells and scaffolds in rotator cuff repair.

Austin Childress

Rotator cuff (RC) injuries are the most common cause of shoulder disability and pain in athletes and older adults, and the second most common musculoskeletal pathology behind lower back injury.1,2 Partial and full thickness tears to the RC are associated with pain and instability and if left untreated often result in osteoarthritis and/or a complete loss of function. It is estimated that full thickness RC tears are found in 13% of individuals in their 50s, 25% in their 60s, and 50% in their 80s.3  Surgical repair is often indicated for RC tears with complete healing of the tendon ranging from 1 – 2.5 years.2,4  Repaired tendon is less organized with an increased scar composition resulting in decreased overall mechanical strength and an increase probability of reinjury.4 The combination of tissue engineering with surgical repair has been suggested to stimulate stronger and more complete healing when compared to traditional methods.4-9 Tendon engineering therapies focus on Mesenchymal stem cells (MSC) due to their ability to differentiate into connective tissue.10 Engineered scaffolds are composed of biocompatible materials that support cell adhesin, cellular growth, the formation of three-dimensional tissue, and provide mechanical strength.6-9 Growth factors are involved in the activation and regulation of the cellular environmental response in tendon healing, and literature suggests that a 3D scaffold with sustained release of growth factors such as platelet-derived growth factor, transforming growth factor beta, vascular endothelial growth factor, insulin-like growth factor, and basic fibroblastic growth factor can provide the microenvironmental control needed to influence cell phenotype.6 Recent animal studies in rat and rabbit models have provided strong evidence suggesting that the use of MSCs with engineered scaffolds in conjunction with surgical repair improve the tendon to bone interface healing, collagen fiber alignment, increased rate a healing, and overall improved strength of the repaired tendon.6-9,11 The literature offers compelling evidence to suggest that the placement of scaffolds seeded with MSCs into the tendon repair site during surgical repair of RC tears may provide improved overall recovery and a reduction in reinjury for patients.

  1. Savin D, Meadows M, Verma N, Cole B. Rotator Cuff Healing: Improving Biology. Oper Tech Sports Med. 2017;25(1):34-40.
  2. Depres-Tremblay G, Chevrier A, Snow M, Hurtig MB, Rodeo S, Buschmann MD. Rotator cuff repair: a review of surgical techniques, animal models, and new technologies under development. J Shoulder Elbow Surg. 2016;25(12):2078-2085.
  3. Thomopoulos S, Parks WC, Rifkin DB, Derwin KA. Mechanisms of tendon injury and repair. J Orthop Res. 2015;33(6):832-839.
  4. Saether EE, Chamberlain CS, Leiferman EM, et al. Enhanced medial collateral ligament healing using mesenchymal stem cells: dosage effects on cellular response and cytokine profile. Stem Cell Rev. 2014;10(1):86-96.
  5. Adams SB, Jr., Thorpe MA, Parks BG, Aghazarian G, Allen E, Schon LC. Stem cell-bearing suture improves Achilles tendon healing in a rat model. Foot Ankle Int. 2014;35(3):293-299.
  6. Govoni M, Berardi AC, Muscari C, et al. (*) An Engineered Multiphase Three-Dimensional Microenvironment to Ensure the Controlled Delivery of Cyclic Strain and Human Growth Differentiation Factor 5 for the Tenogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells. Tissue Eng Part A. 2017;23(15-16):811-822.
  7. Peach MS, Ramos DM, James R, et al. Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering. PLoS One. 2017;12(4):e0174789.
  8. Tornero-Esteban P, Hoyas JA, Villafuertes E, et al. Efficacy of supraspinatus tendon repair using mesenchymal stem cells along with a collagen I scaffold. J Orthop Surg Res. 2015;10:124.
  9. Yokoya S, Mochizuki Y, Natsu K, Omae H, Nagata Y, Ochi M. Rotator cuff regeneration using a bioabsorbable material with bone marrow-derived mesenchymal stem cells in a rabbit model. Am J Sports Med. 2012;40(6):1259-1268.
  10. Berebichez-Fridman R, Gomez-Garcia R, Granados-Montiel J, et al. The Holy Grail of Orthopedic Surgery: Mesenchymal Stem Cells-Their Current Uses and Potential Applications. Stem Cells Int. 2017;2017:2638305.
  11. Sevivas N, Teixeira FG, Portugal R, et al. Mesenchymal Stem Cell Secretome Improves Tendon Cell Viability In Vitro and Tendon-Bone Healing In Vivo When a Tissue Engineering Strategy Is Used in a Rat Model of Chronic Massive Rotator Cuff Tear. Am J Sports Med. 2018;46(2):449-459.