Applying Tendon Structure and Function into Engineered 3D scaffolds

When the rotator cuff tendon tears, the balance between stability and mobility is disrupted, leading to disabilities and significantly reduced quality of life. Rotator cuff tendon tears are becoming increasingly common with almost half a million surgeries performed annually in the US. Surgical repair often yields unsatisfactory clinical outcomes due to poor healing capacity of native tissue, which often results in fibrotic scar tissue with impaired mechanical strength. Tissue engineering aims to address this issue by using biomaterials combined with stem cells to promote neo-tendon formation, aiding in the repair of healthy tendon tissue. However, current biomaterials frequently lack the necessary bioaugmentation for effective tendon repair. Synthetic scaffolds generally have low bioactivity, while biologic scaffolds often fail to provide adequate mechanical support during healing. Furthermore, tendon tears often occur at the tendon-to-bone interface, a specialized tissue with a continuous gradient from uncalcified tendon to calcified bone where the collagen fibers transition from highly aligned to randomly oriented fibers, which current biomaterials are unable to replicate. Thus, there is a critical need to improve biomaterials for tendon tissue engineering. 3D meltblowing (3DMB) is a novel high-throughput fabrication process that produces highly aligned fiber scaffolds, mimicking the collagen fiber structure of native tendon. However, to the best of our knowledge, 3DMB scaffolds have not been evaluated for this application. Therefore, the overall goal of this work is to advance tendon tissue engineering strategies and develop a biomaterial that can regenerate tendon tissue after injury. We explored 3DMB as a potential fabrication process for microfiber scaffolds in tendon tissue engineering. Then we incorporated mechanical stimulation to promote tendon matrix synthesis and to simulate in vivo responses. Finally, we aimed to stimulate development of the tendon-to-bone interface by encouraging trifunctional matrix synthesis through the combination of scaffold, tendon- and cartilage-derived matrix, and demineralized bone, providing stem cell substrates that guide differentiation into the various cell types of the native enthesis. Together, this body of work introduces translational strategies that advance the field of tendon tissue engineering and support the development of more effective treatments for tendon injuries.