Development of siRNA Technology to Prevent Scar Formation in Tendon Repair.

摘要

Tendons are exquisite tissues that connect muscle to bone and couple muscle contraction to movement of the skeletal elements. The development of adhesions is a major complication associated with injury to muscles and tendons. Adhesions most commonly occur in intrasynovial locations and are common in Zone II flexor injuries of the hand (up to 30-40% of patients). Despite careful microscopic surgical approaches, optimal suture techniques and materials, and aggressive hand rehabilitation protocols tendon scarring/adhesions continues as an unsolved medical problem, particularly in severe in complex battlefield wounds. The scar tissues that form can severely compromise otherwise successful reconstructions of bone and other tissues. Continued outstanding progress has been made on our goal of establishing an innovative new method to prevent scar formation. This is based on the use of anti-sense oligonucleotides (ASOs) that target and inhibit the expression of TGF-beta1, Smad3, and CTGF (all members of the TGF-beta signaling pathway). Using an animal model of tendon injury and repair, biomechanical, histological, and gene expression analysis all show evidence of reduced scar formation while not impairing the strength of the tendon repair. This approach has tremendous relevance for translation to human studies to improve function in the injured soldier.