Reconstruction of orofacial defects represents a major clinical challenge. Existing treatments have limitations and lack predictability, necessitating development of new strategies to heal orofacial tissues. One new approach is to regenerate the tissue(s) of interest by seeding autogenous cells into a biomaterial which supports and may even provide cues for the cells, allowing them to grow, differentiate and secrete new extracellular matrix. Towards this end, we have developed in vitro culture methods in which human bone marrow stromal cells are expanded, and demonstrated that these cells are capable of forming new bone in vivo. The formation of bone from progenitor cells is, however, variable, especially if human cells are used, and is controlled by a number of factors in the cells' microenvironment, including the supporting biomaterial. We therefore seek to establish material parameters that could enhance bone cell function in vitro and in vivo. The global hypothesis is that bone-like mineral/organic hybrids that are co-precipitated onto scaffolds used for BMSC transplantation can be used by the cells to restructure a mineralized extracellular matrix of increased volume and structural integrity, thereby enhancing bone formation by the transplanted cells. Results from our and other laboratories support this hypothesis, which is tested by synthesizing 3 classes of organic/inorganic hybrid materials: organic templates whose surface self-assembles into a biological apatite via the co-precipitation of a mineral/poly amino acid hybrid layer; organic templates whose surface includes cell adhesion molecules co-adsorbed with a mineral phase; and incorporation of growth factors into the self-assembled mineral layer such that the biomineral serves as a controlled delivery vehicle. For each of these biomimetic strategies, we test the hypothesis that co-precipitation of organic and inorganic phases onto scaffold pore surfaces leads to increased osteoblast invasion and osteoconductivity and that the rate and extent of BMSC differentiation toward an osteoblast phenotype in-vitro and in-vivo are regulated by the type and concentration of the organic phase within the mineral. The results of these studies may lead to biomaterials that modulate bone formation by progenitor cells. This approach has implications for cell transplantation, but may also have impact on the differentiation of host cells if used as an inductive approach to tissue engineering.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE015411-04
Application #
7075373
Study Section
Special Emphasis Panel (ZDE1-PZ (37))
Program Officer
Lumelsky, Nadya L
Project Start
2003-08-01
Project End
2008-05-31
Budget Start
2006-06-01
Budget End
2008-05-31
Support Year
4
Fiscal Year
2006
Total Cost
$288,458
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Biology
Type
Schools of Dentistry
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Ramaraju, Harsha; Miller, Sharon J; Kohn, David H (2017) Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials. Biomaterials 134:1-12
Ramaswamy, Janani; Nam, Hwa Kyung; Ramaraju, Harsha et al. (2015) Inhibition of osteoblast mineralization by phosphorylated phage-derived apatite-specific peptide. Biomaterials 73:120-30
Ramaraju, Harsha; Miller, Sharon J; Kohn, David H (2014) Dual-functioning phage-derived peptides encourage human bone marrow cell-specific attachment to mineralized biomaterials. Connect Tissue Res 55 Suppl 1:160-3
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Luong, Linh N; Ramaswamy, Janani; Kohn, David H (2012) Effects of osteogenic growth factors on bone marrow stromal cell differentiation in a mineral-based delivery system. Biomaterials 33:283-94
Rossello, Ricardo A; H, David (2010) Cell communication and tissue engineering. Commun Integr Biol 3:53-6
Addison, William N; Miller, Sharon J; Ramaswamy, Janani et al. (2010) Phosphorylation-dependent mineral-type specificity for apatite-binding peptide sequences. Biomaterials 31:9422-30
Luong, Linh N; McFalls, Kristen M; Kohn, David H (2009) Gene delivery via DNA incorporation within a biomimetic apatite coating. Biomaterials 30:6996-7004
Scheller, E L; Krebsbach, P H; Kohn, D H (2009) Tissue engineering: state of the art in oral rehabilitation. J Oral Rehabil 36:368-89
Segvich, Sharon J; Smith, Hayes C; Kohn, David H (2009) The adsorption of preferential binding peptides to apatite-based materials. Biomaterials 30:1287-98

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