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Translational Grant Awards

Year 7


Grant # 1

Adhesive sutures for enhanced flexor tendon repair.

PI: Richard Gelberman, MD

 

Specific Aims

While modern repair techniques are sufficient to hold together many tissues, tendon and ligament repairs have elongation and rupture rates as high as 94% for rotator cuff1–5 and 48% for flexor tendon6–9. These repair failures lead to reoperations, worsening injuries, and even permanent disability10. Musculoskeletal tissue reconstructions such as tendon or ligament repair demand high biomechanical strength to accommodate activities of daily living without risking rupture. Improved orthopaedic surgical repair mechanics facilitate improved tissue healing and regained function. Unfortunately, surgical suturing is a crude mechanical solution. Sutures are in tension along their length, but the load is predominantly transferred to the surrounding tissue where sutures bend at anchor points (Figure 1).

High stress concentrations at these anchor points lead to repair failure11,12. Improved repair schemes would minimize stress concentrations and increase repair strength, reducing rupture and gap formation between the repaired tissues6,7.

Here, we propose to improve surgical repair outcomes using adhesive-coated sutures to distribute load transfer over the sutures’ length. This technology fundamentally changes how sutures function mechanically, but does not require any change in surgical suturing technique. Our hypothesis is that modified surgical sutures incorporating a mechanically optimized, adhesive biomaterial that binds tissue along the suture’s length will reduce stress concentrations and better distribute load, thereby improving load tolerance of repaired tendons. To test this hypothesis, we will evaluate sutures coated with our novel adhesive biomaterials for (1) biocompatibility and (2) effectiveness in a large animal surgical model. These adhesive biomaterials are developed from biocompatible components specifically to have desirable material and mechanical properties defined by our mechanical model of adhesive-coated sutures within flexor digitorum profundus tendon13.

Aim 1: Evaluate biocompatibility of adhesive biomaterials. We will assess cell- and tissue-level responses to the novel bioadhesives using an in vitro canine tendon fibroblast culture model14–16 and an in vivo murine subcutaneous implantation model. Bioadhesives will be tested individually and in conjunction with sutures to assess reactions of tendon fibroblasts to the adhesiveinfluenced environment. These outcomes will be measured by histologic responses and changes in gene expression over time, e.g., for inflammation, proliferation, matrix synthesis14–16. We hypothesize that biomaterial-based adhesives will have substantially better biocompatibility than synthetic adhesives such as cyanoacrylates.

Aim 2: Determine efficacy of adhesive sutures for improved outcomes after in vivo tendon repairs. Bioadhesive-coated sutures with desirable ex vivo mechanical properties in a clinical repair setting and appropriate biocompatibility will be tested surgically using an in vivo canine flexor digitorum profundus (FDP) tendon repair model7,14–20. This clinically relevant animal model allows assessment of surgical outcomes, including inflammatory reaction around the repair, repair strength, resilience, and resistance to gap formation between the repaired tissues. The PI of this proposal, Dr. Gelberman, will perform all repairs following standard clinical practice to ensure relatability and translatability to the clinical situation for tendon repairs.