Genipin crosslinker releasing sutures for improving the mechanical/repair strength of damaged connective tissue

Abstract

The most common mode of surgical repair of ruptured tendons and ligaments involves the use of sutures for reattachment. However, there is a high incidence of rerupture and repair failure due to pulling out of the suture material from the damaged connective tissue. The main goal of this research was to achieve a localized delivery of crosslinking agent genipin (GP) from rapid-release biodegradable coatings on sutures, for strengthening the repair of ruptured connective tissue. Our hypothesis is that GP released from the suture coating will lead to exogenous crosslinking of native connective tissue resulting in beneficial effects on clinically relevant mechanical parameters such as tear resistance, tissue strength, and energy required to rupture the tissue (toughness). Sutures were successfully coated with a biodegradable polymer layer loaded with the crosslinking agent genipin, without compromising the mechanical properties of the suture. The rapid-release of genipin was achieved under both in vitro and ex vivo conditions. Exogenous crosslinking using these genipin releasing sutures was demonstrated using equine tendons. The tendons treated with genipin releasing sutures showed significant improvement in failure load, energy required for pull-out failure, and stiffness. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2199-2205, 2017.

Regeneration of skeletal system with genipin crosslinked biomaterials

“…Hence, genipin-coated suture lines are more suitable for repairing tendon injuries involving trauma rather than age-related tendon degeneration. 90…”

Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study

“…This increase was attained when the healthy ovine infraspinatus tendon was incubated for 24 hours in a relatively high concentration solution of genipin (20 mmol/L)—an approach that results in substantial unintended crosslinking of the surrounding tissue. Using the suture as a delivery vehicle is easily applicable and has been shown to be compatible with genipin use [38]. We refined this approach, demonstrating that it can be potentially relevant for a clinical application to improve mechanical suture performance while minimizing unintended tissue crosslinking.…”

“…Suture coating was prepared according to the description of Sundararaj et al [38]. The formula consists of a genipin-cosolvent solution with dimethyl sulfoxide (Sigma-Aldrich, St Louis, MO, USA) and acetone (50:50 v/v).…”

“…High-strength braided polyethylene suture (ORTHOCORD ® USP #2; DePuy Synthes, New Brunswick, NJ, USA) was submerged in the coating solution for 10 minutes. In modification of the protocol proposed by Sundararaj et al [38], soaked sutures were not air-dried but vacuum-dried for 2 hours to ensure complete evaporation of the solvent.…”

“…In that study, sheep infraspinatus tendons were incubated in a 20-mmol/L genipin solution for 24 hours; this process increased the maximum suture pullout force of a single suture stitch by 30%. Preliminary work has shown that embedding the crosslinking agent in the suture may enhance tissue delivery [38], although the utility of this approach for arthroscopic repair of torn tendons with underlying tissue degeneration remains uninvestigated, to the best of our knowledge [38]. The aim of the current investigation was to assess the potential of a genipin-releasing suture to augment suture retention strength using a simple stitch configuration in healthy and degenerative tissues, whereby tendon degeneration was modeled through collagenase injection to disrupt the collagen matrix [7, 14, 27, 43].…”