Lucas Lu, PhD

University of Delaware

A Biomimetic Heterogeneous Synthetic Matrices for TMJ Condylar Cartilage Repair

Dr. X. Lucas Lu received his PhD in Biomedical Engineering from Columbia University with distinction in 2007. He is currently an Assistant Professor of Mechanical Engineering at the University of Delaware with a joint appointment in the Biomedical Engineering program and the Biomechanics and Movement Science program. The primary focus of Dr. Lu’s current research is cartilage tissue engineering and the prevention, treatment and rehabilitation of osteoarthritis. His research is funded by the Department of Defense, National Institutes of Health, the National Science Foundation, and the Musculoskeletal Transplant Foundation.

Abstract:

Temporamandibular joint (TMJ) disorders affect over 10 million Americans and are often caused by osteoarthritis (OA) or “internal derangement” of the joint. TMJ disorders pose a significant challenge in maxillofacial surgery. Here, we propose a matrix-guided, tissue engineering approach for the repair and regeneration of TMJ condylar cartilage. Our approach relies on the development of a multilayered synthetic matrix that recapitulates the anisotropic feature and the tension-compression nonlinearity. We will create a composite matrix consisting of a bottom, hyaluronan (HA)-based gel layer with spatial gradient of biochemical cues, and a top fibrous layer, de novo designed to mimic the structure and function of type I collagen. Mesenchymal stem cells residing in the matrix will receive signals from the matrix to undergo programmed differentiation in a spatial fashion. The potential of the synthetic matrix in cartilage repair will be tested in an in vitro culture system, as a TMJ osteochondral explant with physiologically relevant mechanical loading, for the generation of new cartilage tissue at the lesion site. We expect that the engineered tissue will exhibit a defined layered and zonal structure and integrate with the host tissue to fulfill the mechanical requirements of daily TMJ activities. This project represents the first effort to fabricate a biomimetic scaffold for TMJ condylar cartilage repair by replicating the unique multilayered structure found in the native tissue. The new synthetic matrix also provides a powerful in vitro platform to study the mechnobiology of TMJ chondrocytes and the developmental biology of condylar cartilage.

Publications:

Han, Z.; Trout, W. S.; Liu, S.; Andrade, G. A.; Hudson, D. A.; Scinto, S. L.; Dicker, K. T.; Li, Y.; Lazouski, N.; Rosenthal, J.; Thorpe, C; Jia, X.; Fox, J. M. “Rapid Bioorthogonal Chemistry Turn–on through Enzymatic or Long Wavelength Photocatalytic Activation of Tetrazine Ligation”, J. Am. Chem. Soc. 2016, 38, 5978–5983.   Full Text

Ravikrishnan, A.; Ozdemir, T.; Bah, M.; Baskerville, K. A.; Shah, S. I.; Ayyappan, R. K.; Jia, X. “Regulation of Epithelial–to–Mesenchymal Transition Using Biomimetic Fibrous Scaffolds” ACS Appl. Mater. Interfaces 2016, DOI: 10.1021/acsami.6b05646. Full Text

Ruggiero L, Zimmerman BK, Park M, Han L, Wang L, Burris DL, Lu XL. Roles of the Fibrous Superficial Zone in the Mechanical Behavior of TMJ Condylar Cartilage. Annals of biomedical engineering. 2015; PMID: 25893511  Abstract