Repair of tooth-supporting structures destroyed by the chronic inflammatory disease periodontitis is a major goal of oral reconstructive therapy. We propose to develop a novel scaffolding system that can deliver regenerative agents to periodontal defects. This system consists of a nano-fibrous polymer scaffold modified with bone mineral-mimicking apatite containing microspheres for delivery of bioactive molecules such as bone morphogenetic protein-7 (BMP-7). It is anticipated that this scaffolding/factor delivery system will promote periodontal regeneration at the defect site by providing an environment for enhancing adhesion, migration, and differentiation of putative cells such as osteoblasts, cementoblasts, and periodontal ligament (PDL) fibroblasts. Moreover, this scaffolding delivery system will allow for permeation of nutrients, metabolites, and signaling molecules required for three dimensional (3D) tissue neogenesis. This exploratory research project will focus on development of the scaffolding/factor delivery system and on testing the feasibility of this novel method for use in treatment of periodontal defects. The following specific aims are designed to generate preliminary data to determine the strength of this approach for periodontal tissue engineering.
Specific Aim 1. Design nano-fibrous scaffolds with interconnected spherical macropores and modified with bone mineral-like apatite.
Specific Aim 2. Integrate microspheres containing BMP-7 into nano-fibrous scaffolds and evaluate the bioactivity and release kinetics of BMP-7 in vitro. Accomplishing these specific aims will generate critical preliminary data and provide vital information as to the appropriate scaffolding/factor delivery system for use in designing optimal periodontal regenerative therapies. This knowledge will enable us to develop a predictable biomimetic scaffold for in vivo application and will be the basis for our planned R01 investigation. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DE014755-02
Application #
6726927
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Kousvelari, Eleni
Project Start
2003-04-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2006-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$153,000
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
Zhang, Zhanpeng; Hu, Jiang; Ma, Peter X (2012) Nanofiber-based delivery of bioactive agents and stem cells to bone sites. Adv Drug Deliv Rev 64:1129-41
Hu, Jiang; Ma, Peter X (2011) Nano-fibrous tissue engineering scaffolds capable of growth factor delivery. Pharm Res 28:1273-81
Holzwarth, Jeremy M; Ma, Peter X (2011) Biomimetic nanofibrous scaffolds for bone tissue engineering. Biomaterials 32:9622-9
Wei, Guobao; Ma, Peter X (2009) Partially nanofibrous architecture of 3D tissue engineering scaffolds. Biomaterials 30:6426-34
Smith, Laura A; Liu, Xiaohua; Ma, Peter X (2008) Tissue Engineering with Nano-Fibrous Scaffolds. Soft Matter 4:2144-2149
Jin, Qiming; Wei, Guobao; Lin, Zhao et al. (2008) Nanofibrous scaffolds incorporating PDGF-BB microspheres induce chemokine expression and tissue neogenesis in vivo. PLoS One 3:e1729
Ma, Peter X (2008) Biomimetic materials for tissue engineering. Adv Drug Deliv Rev 60:184-98
Wei, Guobao; Jin, Qiming; Giannobile, William V et al. (2007) The enhancement of osteogenesis by nano-fibrous scaffolds incorporating rhBMP-7 nanospheres. Biomaterials 28:2087-96
Hou, Sijian; McCauley, Laurie K; Ma, Peter X (2007) Synthesis and erosion properties of PEG-containing polyanhydrides. Macromol Biosci 7:620-8
Chen, Victor J; Ma, Peter X (2006) The effect of surface area on the degradation rate of nano-fibrous poly(L-lactic acid) foams. Biomaterials 27:3708-15

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