Converging biomechanical and biophysical approaches toward ligament and tendon regeneration

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The overall goal of my research program is leverage biofabrication, bioengineering and biophysical approaches to drive human mesenchymal stem cell differentiation towards ligament and tendon for tissue engineering. Tendon and ligament injuries account for approximately 50% of the 33 million musculoskeletal injuries reported in the United States. These tissues have limited self-healing capacities, and the current gold-standard of autografts have high failure rates, showing the need for improved repair strategies. Tendon tissue engineering aims to provide alternative to autografts by providing a biocompatible material to act as a scaffold for cell remodelling in vitro or in vivo to fabricate a tendon-like tissue. However, the most suitable cell type, scaffold design and biomaterial remain to be determined for optimal tendon-like tissue growth. Mesenchymal stem cells (MSCs) are multipotent and self-renewing cells, which have shown great potential within regenerative medicine. Although the optimal type of MSCs for ligament repair remains to be identified. Furthermore, ligament/tendon tissues require mechanical stimulation for extracellular matrix gene expression, yet it remains unlcear whether tissue engineered ligament constructs could benefit from mechanical activation. To successfully promote cell differentiation and matrix deposition for tendon/ligament healing, we propose that MSCs or MSC-seeded scaffolds should undergo mechanoactivation and cellular alignemnt for optimal cell signaling and gene expression. We will apply novel 3D printing technologies to generate unique geometric scaffolds with biophysical and topographical properties not achievable in other platforms. Our group has been at the forefront of biofabrication for tissue engineering and in vitro human tissue modeling applications. We also have extensive expertise in mechanical/dynamic culture of primary human cells using unique cell cutlure platforms. These approaches will be applied in the following aims: Objectives: 1) Asses impact of nanopatterned 3D printed scaffolds on stem cell seeding, and tendon/ligament differentiation. 2) Determine the effects of mechanically dynamic 2D cell culture on priming stem cells for tendon and ligament differentiation. 3) Determine impact of long term mechanically active bioreactor culture on tendon matrix depostion and remodeling. Multidisciplinary approaches including biomaterials science, bioengineering, and cell biology expertise are used to generate a unique technology platform for tissue modeling and tissue engineering. The availability of such biofabricaton technology will directly allow for rapid scaffold design testing and better understanding of how biophysics and mechanics can drive ligament cell differentiation. Finally, this research program may open up avenues to intellectual properties, commercialization and interactions with industry partners.