Biomolecule releasing adhesive for cell-mediated labral repair

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Summary The glenoid labrum is a fibrocartilaginous structure that lines the edge of the glenoid rim of the shoulder joint. Glenoid labral tears, or lesions, can occur in several distinct locations (anterior, superior, or posterior) with variable morphology (detachment from bone or intrasubstance) and have been associated with chronic shoulder pain and/or instability. While operative intervention is typically needed to re-attach the damaged labrum to the glenoid bone or to directly repair an intrasubstance tear of the labrum, recurrent shoulder instability and pain following surgical repair of the labrum has been reported to be as high as 30%. This continued disability following treatment is consistent with the poor healing capacity of the labrum. Current labral repair typically involves the use of anchors and sutures to restore stability of the labrum and shoulder, but rarely promotes actual regeneration of the injured labrum. Although cell therapy and tissue engineering approaches have been used to improve cartilage and bone healing, these approaches have not been explored to improve glenoid labrum healing. To address this deficiency in the treatment of glenoid labral injuries, it is essential to improve our knowledge of the process of labral tear associated tissue injury and to develop a new treatment method assisting in labral tissue regeneration and functional recovery. In our laboratory, substantial progress has been made on this front. Briefly, click-chemistry based adhesives have been synthesized and these adhesives possess good tissue attachment, cell/tissue compatibility, and in situ growth factor releasing property. Equally important, our studies have uncovered an abundant source of progenitor cells in human and rat labrum tissue, which can be recruited to the injured sites and stimulated to produce abundant extracellular matrix protein for accelerated labrum healing. When evaluated in an in vivo glenoid labrum tear rat model, the application of bioadhesive alone suffices to reduce 90% inflammatory cell infiltration and ~70% labral tissue erosion. By eliciting progenitor cell responses (recruitment, proliferation, and ECM production), the application of growth factor-releasing adhesive scaffold was found to enhance labral healing (with complete labral tear regeneration by 6 weeks vs. 50% labral degeneration/lost in no treatment control). These exciting findings support two hypotheses. First, an adhesive can be fabricated to serve as a scaffold matrix to bridge and seal the gap within the torn labrum, and preferentially recruit and stimulate endogenous labral progenitor cells to the injury site for repairing and regenerating damaged labral tissue. Second, labral tear injury mediated synovial inflammatory responses and infiltration of inflammatory cells in and around the tear site cause labral tissue erosion. These hypotheses will be investigated through 3- series of studies. The successful completion of the proposed work will significantly improve our understanding of labral tear-associated tissue damage and lead to the creation of a new treatment approach for promoting labrum regeneration complementing current surgical labral repair of torn labrum with suture anchor strategies.