TY - GEN
T1 - Designing polymers for the activation of, and selective resorption by, osteoclasts for bone regeneration
AU - Fung, Stephanie L.
AU - Martin, Daniel
AU - Mahat, Anisha
AU - Mishra, Prakhar
AU - Cohen, Jarrod
AU - Pashuck, E. Thomas
AU - Mao, Yong
AU - Moghe, Prabhas V.
AU - Merolli, Antonio
AU - Kohn, Joachim
N1 - Publisher Copyright: © 2019 Omnipress - All rights reserved.
PY - 2019
Y1 - 2019
N2 - Statement of Purpose: The majority of bone regeneration efforts focus on the production of bone by osteoblasts and osteocytes, while largely overlooking the other cell types in the wound environment. The overall goal of this project is to re-establish bone turnover by designing a biomaterial that specifically supports the activation of, and degradation by, osteoclasts. Peptides that are cleaved specifically by proteases are often used to crosslink hydrogels to promote cell-specific migration and to tether drugs to surfaces for improving targeting, but their use as sensitive linkages in a polymer backbone is largely unexplored. In this study, a two-pronged approach to designing biomaterials for osteoclast activation and resorption is explored. The first is the polymerization of a tyrosine-derived polymer with a cathepsin K-sensitive peptide in the backbone, which was designed to degrade specifically in the presence of osteoclasts. The second is the use of E1001(1k), a tyrosine polycarbonate that has shown promising results for bone regeneration in the past1. The ability of a material to support osteoclast activation and degradation is critical for re-establishing bone turnover and vascularization of the regenerated tissue, and it is advantageous to employ the cells physiologically responsible for resorption as a means of resorbing the supporting polymer during the regeneration process.
AB - Statement of Purpose: The majority of bone regeneration efforts focus on the production of bone by osteoblasts and osteocytes, while largely overlooking the other cell types in the wound environment. The overall goal of this project is to re-establish bone turnover by designing a biomaterial that specifically supports the activation of, and degradation by, osteoclasts. Peptides that are cleaved specifically by proteases are often used to crosslink hydrogels to promote cell-specific migration and to tether drugs to surfaces for improving targeting, but their use as sensitive linkages in a polymer backbone is largely unexplored. In this study, a two-pronged approach to designing biomaterials for osteoclast activation and resorption is explored. The first is the polymerization of a tyrosine-derived polymer with a cathepsin K-sensitive peptide in the backbone, which was designed to degrade specifically in the presence of osteoclasts. The second is the use of E1001(1k), a tyrosine polycarbonate that has shown promising results for bone regeneration in the past1. The ability of a material to support osteoclast activation and degradation is critical for re-establishing bone turnover and vascularization of the regenerated tissue, and it is advantageous to employ the cells physiologically responsible for resorption as a means of resorbing the supporting polymer during the regeneration process.
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M3 - Conference contribution
T3 - Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium
SP - 434
BT - Society for Biomaterials Annual Meeting and Exposition 2019
PB - Society for Biomaterials
T2 - 42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence
Y2 - 3 April 2019 through 6 April 2019
ER -