Promoting Scarless Healing of Ruptured Tendons

Since tendon ruptures ultimately occur, we have been investigating mechanisms that drive scar formation of tendon healing in simple midsubstance punch injuries. We have been utilizing mouse genetic mutants and inbred strains, such as the naturally regenerative Murphy Roths Large (MRL/MpJ) mouse, to characterize the biomechanics of the adult regenerative environment. We have been investigating the contribution of the systemic environment and the local tendon environment in driving tendon regeneration. Our lab is determining how the structure and function of the MRL/MpJ ECM drive scarless healing in tendon. The ultimate goal of these studies is to provide a guide for interventions to restore the structure and the function of injured tendons.

Ongoing projects:

  1. The role of the systemic environment of MRL/MpJ in scarless tendon healing. We are evaluating the contribution of the systemic and the local tendon environment of the MRL/MpJ mouse to its improved tendon healing outcome. We are evaluating the healing response of MRL/MpJ tendons transplanted into normal-healer B6 environment and the healing response of B6 tendons transplanted into MRL/MpJ environment.
  2. The role of the local MRL/MpJ matrix in modulating tendon regeneration. We are evaluating the capacity of decellularized MRL/MpJ tendon derived matrix in re-programing cells from normal-healer tendons to behave like cells from regenerative tendons.
  3. The therapeutic potential of MRL/MpJ derived tendon matrix. We are assessing the utility of MRL/MpJ derived tendon matrix in promoting an improved healing outcome when introduced into normal-healer injured tendons.

Relevant publications:

  1. Paredes JJ, Pekmezian A, Andarawis-Puri N. MRL/MpJ tendon matrix derived therapeutic promotes improved healing outcomes in scar-mediated canonical tendon healing. J Orthop Res. 2020.
  2. George NG, Bell R, Paredes JJ, Taub PJ, Andarawis-Puri N. Superior mechanical recovery in male and female MRL/MpJ tendons is associated with a unique genetic profile. J Orthop Res. 2020.
  3. Paredes J, Marvin JC, Vaughn B, Andarawis-Puri N. Innate tissue properties drive improved tendon healing in MRL/MpJ and harnesses cues that enhance behavior of canonical healing cells. The FASEB Journal. 2020;00:1–16. Chosen as the cover for the journal
  4. Paredes J*, Shiovitz DA*, Andarawis-Puri N. Uncorrelated healing response of tendon and ear injuries in MRL highlight a role for the local tendon environment in driving scarless healing. Connect Tissue Res. 2018;59;1-11. *Contributed equally to this work.
  5. Paredes JJ, Andarawis-Puri N. Therapeutics for tendon regeneration: a multidisciplinary review of tendon research for improved healing. Ann N Y Acad Sci. 2016;1383(1):125-138.
  6. Sereysky JB, Flatow EL, Andarawis-Puri N. Musculoskeletal regeneration and its implications for the treatment of tendinopathy. Int J Exp Pathol. 2013;94(4):293-303.