Our original NIDCR grant (DE018701) developed guided tissue regeneration (GTR) scaffolds for the reconstruction of periodontitis--?caused infrabony defects that employed a new non--?antibiotic based concept in biomaterials that, for the first time, promoted both a short--? and a long--?term immune response to a specific oral bacterial pathogen, Porphyromonas gingivalis (PG). Using a novel templating technology, we can fabricate polymer porous templated scaffolds (PTS) where every pore is the same size and pore interconnects are also uniform in size, with both parameters being adjustable. If the pore size is ~35?m, PTS show remarkable healing in numerous soft and hard tissues; independent of the polymer used. Given that our original project created PTS that successfully prevent bacterial infection, we now turn our attention in this renewal to defining the underlying mechanisms governing the tissue regeneration observed only in the 35?m PTS. Our transformative research will first prove and then second develop the heretical concept that other myeloid cells, i.e., th macrophage, can be engineered to trans--?differentiate into desired non--?myeloid lineages. Considering the population size of macrophage cells within humans, ease of access, and the ethical issues related to stem cell research, directing macrophage differentiation, rather than stem cells, could create whole new science paradigms and regenerative medicine technologies.

Public Health Relevance

Our original NIDCR grant (DE018701) developed guided tissue regeneration (GTR) scaffolds for the reconstruction of periodontitis--?caused infrabony defects that employed a new non--?antibiotic based concept in biomaterials that, for the first time, promoted both a short--? and a long--?term immune response to a specific oral bacterial pathogen, Porphyromonas gingivalis (PG). These anti--?infective porous scaffolds promote healing in any tissue through their ability to influence M polarization toward pro--?healing phenotypes and hypothetically further differentiate into non--? myeloid lineages (i.e., stem cell-?like behavior). Considering the population of M within humans, ease of access, and the ethical issues related to stem cell research, this project goal of directing M differentiation, rather than stem cells, could create a whole new science and a myriad of regenerative medicine technologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE018701-08
Application #
9209965
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lumelsky, Nadya L
Project Start
2008-08-15
Project End
2020-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
8
Fiscal Year
2017
Total Cost
$575,070
Indirect Cost
$192,570
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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