Rotator cuff injury is a debilitating health concern that affects more than 40% of our aging population and costs the US economy $3 billion per year. For large, chronic tears, surgical intervention can improve clinical outcomes, but re-tear rates are reportedly as high as 94%. Several extracellular matrix (ECM) devices are commercially available to augment rotator cuff repairs, but none have yet demonstrated both the appropriate biological milieu and the sufficient mechanical strength for tendon augmentation. To address the critical need for such a scaffold, we propose to develop fascia ECM for rotator cuff augmentation, since it has mechanical, chemical, and structural properties similar to tendon. Furthermore, we propose to enrich fascia with high molecular weight hyaluronan (HA), a molecule well-known for its roles in wound healing and modulating inflammation. The long-term goal of our laboratory is to develop effective strategies for successful repair of large, chronic rotator cuff tears. The objective of this work is to engineer fascia for soft tissue repair by incorporating hyaluronan to modulate chronic inflammation without significantly reducing fascia's tendon-like mechanical properties. The central hypothesis is that hyaluronan treatment will decrease chronic inflammation and enhance host cell infiltration without significantly decreasing the time-zero or post- implantation mechanical properties of fascia. The rationale for engineering an HA enriched fascia scaffold is to ultimately improve clinical outcomes by providing the appropriate biological and mechanical environment to promote regeneration of a functional tendon-bone bridge. We will test our central hypothesis through the following specific aims: (1) develop a hyaluronan treatment of fascia, (2) evaluate the extent to which hyaluronan treated fascia modulates chronic inflammation, and (3) evaluate the extent to which hyaluronan treatment decreases the mechanical properties of fascia. Our approach is to develop a method to incorporate and immobilize hyaluronan into fascia ECM and to characterize HA content, distribution, and in vitro release. The chronic inflammatory response to HA treated fascia will be evaluated in a rat abdominal wall defect model by the identification and quantification of infiltrating inflammatory cells. The mechanical properties of treated fascia will be assessed at time zero and after four weeks implantation in a rat abdominal wall defect model.
Development of a hyaluronan treated fascia ECM scaffold would positively impact the repair of soft tissues, and in particular, torn rotator cuffs. Use of such a scaffold for rotator cuff augmentation could restore function of the tendon, alleviate patient pain, and consequently reduce medical costs and work-related losses.
|Chin, Likang; Calabro, Anthony; Walker, Esteban et al. (2012) Mechanical properties of tyramine substituted-hyaluronan enriched fascia extracellular matrix. J Biomed Mater Res A 100:786-93|
|Chin, Likang; Calabro, Anthony; Rodriguez, E Rene et al. (2011) Characterization of and host response to tyramine substituted-hyaluronan enriched fascia extracellular matrix. J Mater Sci Mater Med 22:1465-77|