The Tissue Engineering Laboratory integrates engineering principles with biological sciences to advance our knowledge of fundamental cellular processes and accelerate the development of innovative technologies that can have profound and direct applications in patient care. Neuromaterial engineering is a primary focus of our laboratory with the long-term goal of enhancing the quality of life for patients who have sustained traumatic injuries to their peripheral or central nervous system or who suffer from neurodegenerative diseases.
Injuries to the nervous system, whether peripheral or central, result in profound clinical deficits including motor paralysis, lack of protective sensibility and secondary complications such as tissue necrosis and infection. Even with the best technology and current microsurgical techniques available today, less than optimal results are achieved in the treatment of peripheral nerve injury. Understanding and advancing our knowledge of peripheral nerve repair may also ultimately provide clues to improve the management of spinal cord trauma.
The process of nerve regeneration is a complex interplay of cellular elements and molecules which can function both in contact guidance and tropism. Spanning gaps in divided nerves with conduits allow manipulation of this microenvironment. Previous work in in Lahey Hospital & Medical Center’s Tissue Engineering Laboratory demonstrated the enhancement of nerve regeneration with conduits constructed of molecules with piezoelectric properties and have demonstrated the application of electro-spinning technology in nerve regeneration.
Under the direction of Dr. David Bryan, the lab also demonstrated the necessity and role of Schwann cells in the microenvironment of a regenerating growth cone. Migrating from primarily the proximal and to a lesser degree from the distal cut end of the nerve, they provide a physical framework for regenerating growth cone and provide extracellular matrix proteins and specific adhesion molecules facilitating attachment and cell migration. They are also the source of stimulating factors mediated by the release of ligands important in growth and cell signaling. The beneficial effect of one ligand, human recombinant glial growth factor, results in enhanced axonal regeneration and establishment of a functional end point.
Using high- throughput reverse phase protein microarray technology, the Tissue Engineering Laboratory has also identified the spatiotemporal expression of multiple proteins involved in peripheral nerve regeneration. This work allows avenues of inquiry to manipulate the proteins of the nerve microenvironment with the goal of enhancing nerve regeneration.
The current focus of this lab is to investigate the effects of a new class of regulatory molecules, microRNA (miRNA). This family of molecules potentially represents the largest group of regulators in the genome. It is estimated that 60% of genes are regulated by miRNA. miRNA act to down- regulate protein expression through directly binding or degrading the mRNA that codes for a particular protein. They arise from introns of DNA as it is spiced in the nucleus. This class of molecules has potential clinical applications and synthetically produced mimics of some miRNA are currently being used in clinical trials.
David. J. Bryan, M.D., FACS, Director
Bryan DJ, AH Holway, KK Wang, AE Sylvia, DJ Trantolo, DL Wise, IC Summerhayes. Influence of glial growth factor and Schwann cells in a bioresorbable guidance channel on peripheral nerve regeneration, Tissue Engineering, 6: 129-138, 2000.
Bryan DJ, Tang JB, Holway AH, Rieger-Christ KM, Trantolo DJ, Wise DL, Summerhayes IC. Enhanced peripheral nerve regeneration elicited by cell-mediated events delivered via a bioresorbable PLGA guide. J Reconstr Microsurg, 19:125-34, 2003.
Bryan DJ, Tang JB, Doherty SA, Hile DD, Trantolo DJ, Wise DL, Summerhayes IC. Enhanced peripheral nerve regeneration through a poled bioresorbable poly(lactic-co-glycolic acid) guidance channel. J Neural Eng, 1: 91-8, 2004.
Manchio JV, Litchfield CR, Zeheb R, Bryan DJ. Evaluation of a novel reverse thermosensitive polymer for use in microvascular surgery. J Reconstr Microsurg, 25: 69-76, 2009.
Bryan DJ, Litchfield CR, Manchio JV, Logvinenko T, Holway AH, Austin J, Summerhayes IC, Rieger-Christ KM. Characterization of the Spatiotemporal Expression Profile of Key Proteins in Rat Sciatic Nerve Regeneration Using Reverse Phase Protein Arrays. Proteome Science, 10: 9, 2012.