Yidan Chen

Bioengineering PhD Defense Presentation

Date: October 29th, 2025

Time: 9:00 AM to 11:00 AM

Location: J. Erskine Love Building 295 (Large) Conference Room

Meeting link: https://gatech.zoom.us/j/97047305062?pwd=etBZorvI2E91jblcL8ERQY8gbMvLfl.1

Advisor: Younan Xia, PhD (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology)

Committee Members:

Stavros Thomopoulos, PhD (Department of Orthopedic Surgery & Biomedical Engineering, Columbia University)

Yuhang Hu, PhD (Woodruff School of Mechanical Engineering, Georgia Institute of Technology)

Johnna Temenoff, PhD (Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology)

Vladimir Tsukruk, PhD (School of Materials Science and Engineering, Georgia Institute of Technology)

Design and Fabrication of Novel Scaffolding Materials to Enhance Orthopedic Tissue Repair

Musculoskeletal injuries result in nearly 30 billion dollars of cost annually in the United States. Those affecting tendons and ligaments, including transections of intrasynovial flexor tendons of the hand and rotator cuff tears of the shoulder, are prevalent and typically result in significant pain and disability. Although advances have been made in surgical techniques and rehabilitation methods, the outcomes of tendon and tendon-to-bone insertion repair remain poor. For instance, current approaches often fail to restore hand function after flexor tendon injury due to poor healing that leads to gapping, repair-site failure, and motion-limiting adhesions, frequently requiring additional surgeries. For the more intricate tendon-to-bone repair, failure rates range from 20-94%, depending on the extent of the injury and the patient’s age. Tissue engineering strategies, including rationally-designed scaffolds, delivery of bioactive molecules, cell-based therapy, or a combination of these, offer promising routes to enhance musculoskeletal repair. In this dissertation, I focused on the first two aspects, tuning scaffold composition, stiffness, and topography, and delivering specific biochemical cues to the injury site to facilitate repair. With an initial focus on the tendon itself, I first designed a delivery system to address the specific challenges of intrasynovial flexor tendon injuries. The clinical success of the repair depends on reconciling the contrasting goals of suppressing matrix formation at the tendon surface while promoting it within the repair site. To address this clinical need, a targeted drug delivery film was developed with controlled bi-directional and bi-temporal release to concurrently modulate inflammation and promote matrix remodeling. Next, my focus shifted to the tendon-to-bone insertion site, where repair often fails due to the challenge of recreating the native transitional tissue of the tendon enthesis. Effective tendon-to-bone attachment critically depends on the spatially-graded composition and hierarchical structure of the extracellular matrix and a unique population of cells with a phenotypic gradient. Therefore, a promising strategy to address this clinical challenge involves the use of biomimetic scaffolds to promote the regeneration of a functionally-graded enthesis. To this end, scaffolds were engineered with a well-controlled mineral gradient and optimized interdigitation geometry using spin-coating followed by laser machining. Building on this design, an additional developmentally-inspired cue, hedgehog agonist, was incorporated into the scaffold to further guide the formation of a cell phenotype gradient across the scaffold, thereby more comprehensively mimicking the cellular phenotypes in native enthesis.