In a 4-year training/career development program for this investigator who has a strong background in biomaterials science and more recent clinical training in orthodontics, three specific aims are: (1) the development of further skills in tissue engineering involving a porous scaffold for ingrowth of tissues, extending previous experience and expertise in this area;(2) new capabilities in use of MAPC (multipotent adult progenitor cells) in tissue engineering of this type;and (3) clinical research skills based on longitudinal follow-up of patients treated for various types of dentofacail and craniofacial deformities. The overall longterm goal is to develop a replacement for both soft and hard tissue defects in the craniofacial complex (and elsewhere in the body). The short-term goal is to determine whether a biomimetic hydroxyapatite-gelatin (HAP-GEL) nanocomposite can serve as a load bearing scaffold to carry MAPC and grow bone. The training program is built around interaction with four mentors, related to each specific aim above, and participation in courses and seminars developed in the clinical scientist program at UNC. The mentors are Drs. Mitsuo Yamauchi (application of collagen cross-linkage in scaffold development for tissue engineering), Wei-Shou Hu (stem cell biology) and Leaf Huang (application of growth factors) and William Proffit (longitudinal studies of patients requiring orthognathic surgery for correction of dentofacial and craniofacial defects). Proposed work toward the short-term goal involves (1) cultivation of MAPC on a nanocomposite HAPGEL matrix so that MAPC differentiate into bone cells;(2) design of the HAP-GEL matrix to allow controlled release of growth factors to produce multiple lineages of MAPC differentiation and maximize penetration of MAPC into the matrix;and (3) design of the matrix to maximize the mechanical strength of the MAPCcarrying scaffold so that it could become a load-carrying graft. Preliminary data show promising interactions between osteoblasts and the HAP-GEL matrix, and it appears that this offers a highly favorable way to offer MAPC-based therapy. The significance of this work is that it can provide a new way to replace missing tissues in patients with congenital, developmental or trauma-induced deformities. With a graft material of this type, it should be possible to eliminate multiple surgeries in the treatment of critical-size cranial and facial defects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DE018695-04
Application #
8098914
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
King, Lynn M
Project Start
2008-08-01
Project End
2012-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$126,868
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Dentistry
Type
Schools of Dentistry
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Lee, Dong Joon; Park, Yonsil; Hu, Wei-Shou et al. (2016) Osteogenic Potential of Multipotent Adult Progenitor Cells for Calvaria Bone Regeneration. Adv Med 2016:2803081
Chiu, Chi-Kai; Lee, Dong Joon; Chen, Hsin et al. (2015) In-situ hybridization of calcium silicate and hydroxyapatite-gelatin nanocomposites enhances physical property and in vitro osteogenesis. J Mater Sci Mater Med 26:92
Lee, Dong Joon; Tseng, Henry C; Wong, Sing Wai et al. (2015) Dopaminergic effects on in vitro osteogenesis. Bone Res 3:15020
Lee, Dong Joon; Padilla, Ricardo; Zhang, He et al. (2014) Biological assessment of a calcium silicate incorporated hydroxyapatite-gelatin nanocomposite: a comparison to decellularized bone matrix. Biomed Res Int 2014:837524
Cox, Crystal; Nguyen, Tung; Koroluk, Lorne et al. (2014) In-vivo force decay of nickel-titanium closed-coil springs. Am J Orthod Dentofacial Orthop 145:505-13
Canales, Christopher; Larson, Matthew; Grauer, Dan et al. (2013) A novel biomechanical model assessing continuous orthodontic archwire activation. Am J Orthod Dentofacial Orthop 143:281-90
Ferreira, João R; Padilla, Ricardo; Urkasemsin, Ganokon et al. (2013) Titanium-enriched hydroxyapatite-gelatin scaffolds with osteogenically differentiated progenitor cell aggregates for calvaria bone regeneration. Tissue Eng Part A 19:1803-16
Ferreira, J R; Hirsch, M L; Zhang, L et al. (2013) Three-dimensional multipotent progenitor cell aggregates for expansion, osteogenic differentiation and 'in vivo' tracing with AAV vector serotype 6. Gene Ther 20:158-68
Kaku, Masaru; Komatsu, Yoshihiro; Mochida, Yoshiyuki et al. (2012) Identification and characterization of neural crest-derived cells in adult periodontal ligament of mice. Arch Oral Biol 57:1668-75
Dyke, Jason Christopher; Knight, Kelly Jane; Zhou, Huaxing et al. (2012) An Investigation of Siloxane Cross-linked Hydroxyapatite-Gelatin/Copolymer Composites for Potential Orthopedic Applications(). J Mater Chem 22:22888-22898

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