Bone fractures and defects result in more than 1.3 million surgical procedures each year in the United States. With current therapies, these fractures and defects can be restored to some degree, but far from an ideal solution. Although regenerative agents such as bone morphogenetic proteins (BMPs) have been shown to enhance bone formation when delivered to bone lesions in animal studies, results remain unpredictable for clinical applications. It is likely that the lack of an appropriate 3D scaffold that mimics the natural extracellular environment and supports bone regeneration is detrimental. It is also likely that inappropriate growth factor delivery (time, quantity, localization) confound the achievement of robust success. It is also likely that BMP alone is not sufficient but that additional factors and progenitor cells may be required in order to promote maximal bone regeneration. In addition, angiogenesis in parallel to tissue regeneration is critical to maintaining long-term viability and sustained function of regenerated tissues. Based on these analyses, we hypothesize that predictable and clinically relevant bone regeneration can be achieved by coordinating the biological activities (cells and regulating molecules) with structural cues (scaffold structures). We therefore propose a patient-specific, multi-scaled nano-fibrous scaffold for the delivery of bone marrow stromal cells (MSC) and multiple regenerative factors to engineer vascularized bone.
The specific aims are: SA 1. Design """"""""patient-specific"""""""" scaffolds with multi-scaled structures for bone regeneration. SA 2. Formulate NS to individually tune BMP? and bFGF release profiles in multi-scaled scaffolds in vitro; and determine the effects of scaffold structure, bFGF and BMP7 temporal release profiles on osteogenesis and angiogenesis in a mouse ectopic model. SA 3. Confirm that the multi-scaled and factor-releasing scaffolds (selected from Aims 1&2) afford a superior environment for vascularized bone regeneration in a rat critical defect model. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE017689-01A1
Application #
7259656
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lumelsky, Nadya L
Project Start
2007-03-01
Project End
2011-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
1
Fiscal Year
2007
Total Cost
$321,652
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
Gupte, Melanie J; Swanson, W Benton; Hu, Jiang et al. (2018) Pore size directs bone marrow stromal cell fate and tissue regeneration in nanofibrous macroporous scaffolds by mediating vascularization. Acta Biomater 82:1-11
Feng, Ganjun; Zhang, Zhanpeng; Dang, Ming et al. (2017) Injectable nanofibrous spongy microspheres for NR4A1 plasmid DNA transfection to reverse fibrotic degeneration and support disc regeneration. Biomaterials 131:86-97
Zhang, Xiaojin; Li, Yan; Chen, Y Eugene et al. (2016) Cell-free 3D scaffold with two-stage delivery of miRNA-26a to regenerate critical-sized bone defects. Nat Commun 7:10376
Guo, Baolin; Lei, Bo; Li, Peng et al. (2015) Functionalized scaffolds to enhance tissue regeneration. Regen Biomater 2:47-57
Zhang, Zhanpeng; Gupte, Melanie J; Jin, Xiaobing et al. (2015) Injectable Peptide Decorated Functional Nanofibrous Hollow Microspheres to Direct Stem Cell Differentiation and Tissue Regeneration. Adv Funct Mater 25:350-360
Zhang, Zhanpeng; Ma, Peter X (2015) From Nanofibrous Hollow Microspheres to Nanofibrous Hollow Discs and Nanofibrous Shells. Macromol Rapid Commun 36:1735-41
Kuang, Rong; Zhang, Zhanpeng; Jin, Xiaobing et al. (2015) Nanofibrous spongy microspheres enhance odontogenic differentiation of human dental pulp stem cells. Adv Healthc Mater 4:1993-2000
Xu, Haixing; Holzwarth, Jeremy M; Yan, Yuhua et al. (2014) Conductive PPY/PDLLA conduit for peripheral nerve regeneration. Biomaterials 35:225-35
He, Chuanglong; Jin, Xiaobing; Ma, Peter X (2014) Calcium phosphate deposition rate, structure and osteoconductivity on electrospun poly(l-lactic acid) matrix using electrodeposition or simulated body fluid incubation. Acta Biomater 10:419-27
BaoLin, Guo; Ma, Peter X (2014) Synthetic biodegradable functional polymers for tissue engineering: a brief review. Sci China Chem 57:490-500

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