Tissue adhesive can potentially reduce complications associated with mechanical perforating devices (e.g., sutures, tacks, and staples), which include tissue trauma, chronic pain and discomfort, and localized stress concentrations that lead to failure of the repair. In the previous R15 award, we incorporated biodegradable, silica-based nanoparticles to simultaneous enhance the adhesive properties and in vivo cellular infiltration capability of a synthetic, bioinert polyethylene glycol-based adhesive. In this renewa, we seek to build on these findings to design an adhesive-coated biologic scaffold with adhesive performance, degradation behavior, and cellular responses tailored at repairing Achilles tendons. The Achilles tendon is the most frequently ruptured tendon, with an estimated 225,000 ruptures and 50,000 repairs of these ruptures occurring annually in the US. Tendon ruptures, both acute and chronic (neglected), can dramatically affect a patient's quality of life, and requir a prolonged period of recovery before returning to pre-injury activity levels. The current standard of care (i.e., suture primary repair) is rarely completely successful. Re-rupture of suture repaire tendon and chronic pain are common complications of tendon repair. There are three main objectives to this proposal. Objective 1: effectively and efficiently optimize adhesive performance and degradation characteristics using Robust Design experiment and magnetoelastic sensor, respectively. Objective 2: in vitro cell culture experiments to demonstrate the adhesive's ability to support tendon healing as measured by tenocyte viability, proliferation activity, phenotypic expression of transcript factor scleraxis, collagen matrix deposition, and cell attachment and infiltration. Objective 3: demonstrate the adhesive's ability to repair transected Achilles tendon through ex vivo biomechanical testing and a rat tendon repair model. The central hypothesize of this proposal is that an adhesive with the ideal combination of postsurgical fixation strength and fast tissue integration will outperform suture repair during the early phases of healing, as measured by mechanical properties and degree of lengthening of the repaired tendon. Successful completion of the proposed work will lead to a follow-on project aimed at repairing Achilles tendon in a confirmatory ovine model. Additionally, the adhesive will be tailored for repairing other soft tissues (e.g., ligament repair, hernia repai, pelvic floor repair) or interfacial tissues (e.g., rotator cuff repair). Renewing this AREA award wll continue to provide the PI with resources to train undergraduate and graduate students, strengthen the biomedical research capability at Michigan Technological University, obtain data for future NIH funding, and build a nationally-recognized graduate program.
Tissue adhesives play an important role in wound closure, tissue repair, implant fixation, simplifying complex surgical procedures, reducing surgical time, and can potentially alleviate pain associated with traditional mechanical perforating devices (i.e. suture, staples, and tacks). However, due to stringent design requirements such as water-resistant adhesion, biocompatibility, and degradability, successful tissue adhesives have been difficult to engineer. Current proposal seeks to develop biomimetic tissue adhesive with improved adhesive strength and bioactivity for the repair of soft connective tissues.
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