Singh, Satish
(2015)
Fundamental Study of Cationic Doped Calcium Phosphate Scaffolds and Coatings for Bone Tissue Engineering.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Calcium phosphates (CaPs) are widely studied as scaffolds for hard tissue regeneration due to their similar composition to the inorganic component of native mineralized tissues. Unfortunately, their poor mechanical properties and the limited dissolution of hydroxyapatite (HA), the most ubiquitous CaP in bone tissue engineering, restricts their application to the treatment of non-load bearing defects. In order to improve patient outcomes, a major emphasis has been placed on the controlled delivery of growth factors, such as bone morphogenic proteins (BMPs), from CaPs, to accelerate regeneration and recruit cells capable of resorbing HA. However, the added expense, poor shelf life, and the unknown side effects of treatment with increased amounts of growth factors are the major limitations of this approach.
In an attempt to reduce the requirement to deliver increased amounts of growth factors, more resorbable CaP phases, such as β-tricalcium phosphate (β-TCP), have been studied. Recent work has shown that scaffolds prepared with β-TCP may be at least equally capable of inducing in vivo bone regeneration in comparison to autologous bone grafts and BMP-2, delivered from a collagen sponge. This favorable response is believed to be due to the capability of β-TCP to degrade in a more clinically relevant time frame, similar to the rate at which native tissues are regenerated, and release bioactive Ca2+ and PO43- ions in close proximity to the defect site.
In addition to Ca2+ and PO43-, mineralized tissues are composed of several other elements which play a key role in regulating their structure and function. Therefore, in the current work the influence of ionic substitutions using two biologically relevant cations, Mg2+ and Sr2+, in CaPs on their physicochemical and biological properties was studied. It was hypothesized that β-TCP scaffolds prepared with various amounts of Mg2+ and Sr2+ would provide microenvironments suitable for promoting osteogenic differentiation in comparison to commercially available β-TCP. In addition to bulk scaffolds, cationic substituted β-TCP was explored as a bioactive coating on a biodegradable metallic substrate. The influence of coating composition and structure on corrosion protection and cytocompatibility was assessed. Finally, the influence of cationic substitution on the physicochemical properties and cytocompatibility of an injectable self-setting HA cement was also evaluated.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
29 January 2015 |
| Date Type: |
Publication |
| Defense Date: |
20 June 2014 |
| Approval Date: |
29 January 2015 |
| Submission Date: |
16 June 2014 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
341 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Chemical Engineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Calcium phosphate, biodegradable metals, osteogenic differentiation, human mesenchymal stem cells |
| Date Deposited: |
29 Jan 2016 06:00 |
| Last Modified: |
19 Dec 2016 14:41 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/21895 |
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