Dual Phase Engineered Tissue for Enhanced Bone Formation.
dc.contributor.author | Rao, Rameshwar | en_US |
dc.date.accessioned | 2013-09-24T16:01:09Z | |
dc.date.available | NO_RESTRICTION | en_US |
dc.date.available | 2013-09-24T16:01:09Z | |
dc.date.issued | 2013 | en_US |
dc.date.submitted | 2013 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/99786 | |
dc.description.abstract | Large bone defects are a significant clinical problem in the United States and worldwide. “Non-unions” are fractures that fail to heal due to a lack of blood supply to the defect site. In our approach to bone regeneration, we create modular engineered tissues (“microbeads”) designed to form bone, and combine them with a surrounding vascularizing tissue to generate a dual-phase injectable matrix for enhanced bone formation. In the first Aim, human bone marrow mesenchymal stem cells (bmMSC) or human adipose stem cells (AdSC) were embedded in collagen/fibrin (COL/FIB) or collagen/fibrin/hydroxyapatite (COL/FIB/HA) microbeads. Both cell types mineralized microbeads, indicating differentiation towards the osteogenic lineage. The second Aim used a co-culture model of bmMSC and human umbilical vein endothelial cells in COL/FIB composite hydrogels to create a vasculogenic matrix. Cell ratio and matrix composition were varied in a systematic manner. Vascular network formation increased in vitro with increasing fibrin content in composite materials, although the 40/60 COL/FIB and pure fibrin materials exhibited similar responses. Hydroxyapatite (HA) was found to recover endothelial network formation in unconstrained hydrogels. Over 7 days of dorsal subcutaneous implantation in nude mice, these matrices exhibited increasing neovascularization, though there was no significant effect of HA. The final Aim combined osteogenic microbeads with a surrounding vasculogenic matrix to evaluate the effect of this dual-phase tissue in vivo. Both vasculogenesis and osteogenesis were examined in a subcutaneous bone formation model in the mouse at 4 and 8 weeks. Blood flow measured by Doppler imaging was not significantly different between any conditions at any time point, except at 8 weeks where the vasculogenic matrix alone was lower than all other groups. Micro-computed tomography of ectopic bone demonstrated significantly higher bone volume in the osteogenic microbead condition at 4 weeks and both the blank and osteogenic microbead conditions at 8 weeks, compared to the dual osteogenic/vasculogenic condition. These data suggest an inhibitory effect of the vasculogenic component on bone formation in the non-ischemic model. Dual-phase implants may be more effective in ischemic orthotopic bone regeneration models, and these results demonstrate that such constructs can be designed, fabricated, and delivered for therapeutic use. | en_US |
dc.language.iso | en_US | en_US |
dc.subject | Tissue Engineering | en_US |
dc.subject | Biomaterials | en_US |
dc.subject | Orthopedics | en_US |
dc.subject | Vascularization | en_US |
dc.subject | Cell Therapy | en_US |
dc.subject | Stem Cells | en_US |
dc.title | Dual Phase Engineered Tissue for Enhanced Bone Formation. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Biomedical Engineering | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.contributor.committeemember | Stegemann, Jan Philip | en_US |
dc.contributor.committeemember | Krebsbach, Paul | en_US |
dc.contributor.committeemember | Kohn, David H. | en_US |
dc.contributor.committeemember | Putnam, Andrew James | en_US |
dc.subject.hlbsecondlevel | Biomedical Engineering | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/99786/1/ramrao_1.pdf | |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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