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Role of Magnesium on Mineralization and Periosteal Differentiation

Hong, Dandan (2019) Role of Magnesium on Mineralization and Periosteal Differentiation. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Magnesium-based alloys have been fabricated into implants including the orthopedic fixation devices and endovascular stents. These metals not only fulfill the mechanical requirement in load bearing applications, they also degrade safely upon tissue healing. Their biocompatibility and osteoinductive potential have been evaluated in numerous studies. Our present study covers two topics involving magnesium, investigating 1) its osteogenic effect on periosteum and 2) surface mineralization triggered by its degradation process.
Our previous work showed that implantation of a magnesium-based device was associated with subperiosteal bone regeneration. In the present study, we harvested mouse and human periosteal cells, and exposed them to increased Mg2+ concentration. We found that the expression of osteogenic genes and proteins was cell- and concentration-dependent. We then electrospan magnesium metal nanopowder into PLGA nanofibers, and implanted in female and male rat calvaria defect with or without periosteum for one month. MicroCT and histology analyses showed greater new bone volume in magnesium+ periosteum group.
Magnesium degradation triggers calcium phosphate deposition on the metal surface. The mineral layer can potentially lead to ectopic calcification if the metal device is implanted in the soft tissue. We tested the feasibility of matrix Gla protein (MGP) to locally inhibit the mineralization. A secretory protein, MGP was shown to inhibit soft tissue calcification, especially in the vascular environment. To begin, we transfected MGP into mammalian cells, then exposed magnesium metals in medium containing MGP secreted by transfected cells. Results showed that significantly less minerals were deposited on metal surface when MGP was present. We then implanted magnesium rod, embedded in collagen scaffold seeded with stably transfected cells, intramuscularly in mouse. Analyses supported our in vitro results. Moreover, higher magnesium corrosion rate was observed from MGP group, indicating a protective role of the mineral layer.
The present study proves the direct osteogenic effect of Mg2+ on periosteal cells, and demonstrates the efficacy of a biomolecule to reduce mineralization on magnesium surface. Taken together, these findings suggest therapeutic potential of Mg-releasing scaffolds for cranial injury repair, and open a frontier for the design of medical devices.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Hong, Dandandah57@pitt.edudah57
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSfeir, Charlescsfeir@pitt.eduCSFEIR
Committee MemberBeniash, Eliaebeniash@pitt.eduEBENIASH
Committee MemberCui, Tracyxic11@pitt.eduxic11
Committee MemberWitte, Frankfrank.witte@charite.de
Date: 10 September 2019
Date Type: Publication
Defense Date: 15 April 2019
Approval Date: 10 September 2019
Submission Date: 5 July 2019
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 125
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Magnesium, Mineralization, Periosteal Differentiation, Matrix GLA Protein
Date Deposited: 10 Sep 2019 16:56
Last Modified: 10 Sep 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/37057

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