Tissue Engineering and Drug Delivery Approaches for Bone Regeneration
Abstract
The Therapeutic Biomaterials Laboratory at the University of Rochester focuses on the development of polymer therapeutics for orthopaedic tissue engineering and drug delivery applications. There are myriad diseases of the skeleton that require regenerative approaches including bone grafts, osteoporosis, or delayed union or nonunion fractures. Specifically, in the case of allograft procedures, which are the ‘gold standard’ for massive bone defects, there exists a 60% failure rate within 10 years of implantation due to poor graft-host integration and microcrack propagation.Unlike allografts, autografts fully heal and integrate, mediated by the periosteum, a thin layer of osteogenic tissue surrounding bone.
Our efforts are two-fold to augment allograft healing: developing (1) cell transplantation approaches to recreate the periosteum and (2) targeted drug delivery systems to promote native periosteal cell recruitment and expansion to coordinate graft revitalization.
We have pioneered transplantation of mesenchymal stem cells (MSCs) within degradable hydrogels surrounding allografts as a tissue-engineered periosteum. In this approach, MSCs augment graft healing, as measured via increased graft vascularization (∼2.4-fold), endochondral bone formation (∼2.8-fold), and biomechanical strength (1.8-fold), as compared to untreated allografts. However, graft remodeling is slow compared to autografts, likely due to phenotypic differences of the PCs versus MSCs. Considering additional challenges associated with cell therapies, in parallel, we have developed a novel bone resorption site-targeted polymer therapeutic platform to promote PC recruitment and expansion.
We have shown that biodistribution of drug carriers after systemic administration can be dramatically altered to favor delivery to remodeling bone tissue through the incorporation of peptides that bind specifically to tartrate resistant acid phosphatase (TRAP), a protein deposited by osteoclast during the resorption phase of bone remodeling. Taken together, this work strives to advance our understanding of how the periosteum coordinates allograft healing and the design of regenerative strategies to recapitulate periosteal mediated healing.
About Danielle Benoit
Danielle Benoit is Associate Professor within the Department of Biomedical Engineering with appointments also in Chemical Engineering and the Center for Musculoskeletal Research at the University of Rochester. She directs the Therapeutic Biomaterials Laboratory, which specializes in the rational design of polymeric materials for regenerative medicine and drug delivery applications. Her work has provided insights into the translation of tissue engineering strategies for bone allograft repair, development of pH-responsive nanoparticles for nucleic acid and small molecule drug delivery, and novel targeting strategies for bone-specific delivery of therapeutics.
Prof. Benoit has received numerous awards for her research program including the 2015 Young Innovator Award in Cellular and Molecular Bioengineering, an NSF CAREER Award, and Alex’s Lemonade Stand Young Investigator Award.
Prof. Benoit received her undergraduate degree in Biological Engineering from the University of Maine and M.S. and Ph.D. in Chemical Engineering from the University of Colorado, where she was mentored by Dr. Kristi Anseth. She then trained at the University of Washington where she was a Damon Runyon Cancer Research Foundation Postdoctoral Fellow, working with Drs. Patrick Stayton and Allan Hoffman. Prof. Benoit joined the faculty at the University of Rochester in 2010.