Session: Rising Stars of Mechanical Engineering Celebration & Showcase

Paper Number: 148590

148590 - Unraveling Cellular Disease Mechanisms Through Mechanobiology: Bridging Basic Science and Translational Medicine 

This Faculty Early Career Development (CAREER) grant focuses on elucidating the molecular mechanisms associated with the development of osteoarthritis (OA), the type of arthritis we get with age or injury. Although mechanical force is well known to be a key contributing factor to the development of OA, substantial gaps remain in our understanding of the mechanisms by which chondrocytes, i.e., the cells in the cartilage, convert mechanical forces into biological behaviors that advance or prevent OA. This project will elucidate molecular mechanisms by which articular chondrocytes determine cartilage tissue health via integrin-mediated mechanotransduction – i.e., the relation of mechanical inputs to biological outputs mediated through the transmission of forces across specific mechanoreceptors that connect the fibrous environment outside the cell with the structural components inside the cell. This research will have a significant impact on tissue engineering and OA-related healthcare by identifying mechanisms of chondrocyte mechanotransduction that may be promising targets for future biomechanical or pharmaceutical interventions to prevent or reverse OA. The research from this project is also being integrated into an educational and outreach program based on graduate and undergraduate curriculum development, promotion of graduate and undergraduate research opportunities, and K-12 and underrepresented minority outreach through the development of educational story books and hands-on summer camp activities.

The specific goal of the research is to determine the integrin-mediated mechanotransduction mechanisms by which articular chondrocytes regulate cartilage homeostasis, and thus to advance understanding of the pathogenesis of osteoarthritis. The research objectives include: (1) establishing a baseline catabolic threshold for tensile force applied to chondrocyte integrins, (2) determining the degree to which actin dynamics drives chondrocyte preference for dynamic force, and (3) establishing surface glycoproteins as modulators of chondrocyte integrin tension dynamics via application of prestress. The following fundamental questions are being investigated: (i) at what level of force do the prior studies that established a switch from anabolic to catabolic outcomes with increasing force translate when applied to specific chondrocyte integrins; (ii) does the motion of the actin cytoskeleton impart regulate chondrocyte mechanotransduction by imparting dynamic forces on chondrocyte integrins; and (iii) will characterizing surface glycoprotein profiles be critical to the success of any future integrin-targeted biomechanical treatments of OA. The overarching focus will be on leveraging mechanical concepts developed initially for civil and mechanical engineering to investigate mechanisms of outside-in mechanotransduction, inside-out mechanotransduction, and molecular tensegrity to obtain a better understanding of integrin-mediated mechanotransduction in articular chondrocytes. Education and outreach components integrate research results into graduate and undergraduate coursework and research opportunities, storybooks introducing Native American elementary students to principles of cellular mechanobiology, and hands-on summer camp activities for middle and high school students. This project will allow the PI to advance the knowledge base in cellular vibrational analysis, molecular tensegrity, and cellular mechanobiology and establish his long-term career at the intersection of nanoscience, nanoengineering, and biomedical engineering.

Also presented are applied research efforts of the PI focused on engineering microphysiological systems (MPSs, aka organs on a chip). This work leverages mechanobiological and biophysical tissue engineering approaches to develop biomimetic in vitro disease models. Results are presented on a groundbreaking biphasic nanocomposite micropatterned thin film cell culture platform known as the CellWell. This model for articular cartilage enables the long-term differentiation of chondrocytes in vitro, marking a pivotal milestone in the pursuit of innovative disease-modifying therapies. Efforts are underway to extend the principles behind the CellWell into the development of a biomimetic MPS for use in mechanistic OA pathogenesis studies and drug screening, with key results of that development presented here. Our MPS platform mirrors human joint complexity, from the macro- to the nano-scale, offering the potential to revolutionize drug efficacy prediction, mitigate translational risks, and reduce drug development time and resources.

Presenting Author: Scott Wood University of New England

Presenting Author Biography: Dr. Wood received a B.S. in Mechanical Engineering from Texas Tech University in 2005, and Ph.D. in Bioengineering from Clemson in 2011. After completing postdoctoral fellowships in Cell and Molecular Biology at the medical schools of Wake Forest University and the University of North Carolina, he joined the faculty of the Nanoscience & Biomedical Engineering department at the South Dakota School of Mines and Technology in 2016. More recently, in the Fall of 2024, he moved to the University of New England in Maine, where is the new Director of the Portland Laboratory for Biotechnology and Health Sciences. He is also the Founder and Chief Technology Officer (CTO) of CellField Technologies LLC, through which he is working to commercialize innovative drug screening solutions using various technologies and principles developed through his academic research.

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