Helen Lu's tissue engineering approach to rotator cuff repair

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Human rotator cuff tendon fibroblasts (green) are on aligned nanofibers (purple) --Testing the potential of a nanofiber-based device to enable biological healing between tendon and bone post rotator cuff surgery. Photo Credit: Helen Lu/Columbia Engineering

Helen H. Lu, professor of biomedical engineering at Columbia Engineering, has won a three-year $1.125 million Translational Research Award grant from the Department of Defense's Congressionally Directed Medical Research Programs for her research on tendon-to-bone integration for rotator cuff repair. Lu is collaborating with William Levine, chairman and Frank E. Stinchfield Professor of Orthopedic Surgery at Columbia University Medical Center. The funding, part of the DoD's Orthopaedic Research Program, will support preclinical trials to test the potential of a nanofiber-based device to enable biological healing between tendon and bone post rotator cuff surgery.

"This is the culmination of our decade-long, interdisciplinary collaboration on integrative rotator cuff repair," Lu says. "What is truly exciting is that the work planned in this new project will bring our novel technology another major step closer to clinical realization."

Rotator cuff tears represent the most common shoulder injury, with more than 600,000 repair procedures performed annually in the U.S. Among military personnel, the incidence of shoulder injuries is more than twice that of the general population. The rotator cuff tendon-to-bone insertion is often the site of injury when the cuff tendon tears. Current repair aims to surgically reconnect the torn tendon to the humerus. However mechanical fixation of the tendon fail to promote its integration with bone, and this inability contributes significantly to the high re-tear rate following cuff surgery.

"So there is a large unmet clinical demand for integrative technologies for rotator cuff repair," Levine observes. To address this problem, Lu, Levine, and their students developed an innovative approach that centers on the regeneration of the tendon-to-bone interface through the design of a biomimetic nanofiber scaffold coupled with controlled stem cell differentiation.

Current clinically available strategies, such as graft patches, provide initial stability to tendons, but ultimately they lack the mechanical integrity and structural make-up necessary for tendon-bone healing. These disadvantages have significantly limited their clinical use.

In contrast, the bioinspired technology developed by Lu and Levine is based on organized nanofibers (aligned and parallel to each other) that enable the integrative repair of rotator cuff tears by targeting the regeneration of the layered tendon-to-bone interface.

"Given that the predominant reason for repair failure and requisite revision surgery is the lack of functional tendon-to-bone integration, our new approach represents a paradigm shift and will improve how tendons are repaired clinically," Levine notes.

Building upon their projects funded by the National Institutes of Health, the New York Stem Cell Foundation, and Wallace H. Coulter-Columbia Partnership, the researchers are planning a series of studies in the DoD grant to expedite tendon-to-bone healing by using the scaffold to harness the regenerative potential of stem cells and growth factor delivery.

Completion of these studies will accelerate the development of a new generation of soft tissue fixation devices for use in both sports medicine and the treatment of degenerative joint diseases, which, says Lu, is "great news for athletes and non-athletes alike. Being able to functionally integrate different tissues such as tendon and bone will lay the foundation for the formation of composite tissue systems and ultimately, pave the way for total limb regeneration."

Read more at: https://www.eurekalert.org/pub_releases/2015-12/cuso-phl121515.php

Published November 7, 2017