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Optimization of tyrosine-derived polycarbonate terpolymers for bone regeneration scaffolds
Descriptive
TitleInfo
Title
Optimization of tyrosine-derived polycarbonate terpolymers for bone regeneration scaffolds
Name
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NamePart
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Resurreccion-Magno
NamePart
(type = given)
Maria Hanshella C.
NamePart
(type = date)
1972-
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Maria Hanshella Magno
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(authority = RULIB)
author
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Kohn
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Joachim
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Joachim Kohn
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Advisory Committee
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chair
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Lee
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KiBum
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KiBum Lee
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Advisory Committee
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internal member
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Warmuth
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Ralf
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Ralf Warmuth
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Advisory Committee
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internal member
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Hollinger
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Jeffrey O
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Jeffrey O Hollinger
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Advisory Committee
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outside member
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Rutgers University
Role
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(authority = RULIB)
degree grantor
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Graduate School - New Brunswick
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school
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Text
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theses
OriginInfo
DateCreated
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2012
DateOther
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(type = degree)
2012-01
CopyrightDate
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2012
Place
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xx
Language
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eng
Subject
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Topic
Chemistry and Chemical Biology
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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ETD_3793
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electronic resource
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application/pdf
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text/xml
Extent
xx, 206 p. : ill.
Note
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Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Maria Hanshella C. Resurreccion-Magno
Abstract
(type = abstract)
Tyrosine-derived polycarbonates (TyrPC) are a versatile class of polymers highly
suitable for bone tissue engineering. Among the tyrosine-derived polycarbonates,
poly(DTE carbonate) has an FDA masterfile that documents its biocompatibility and nontoxicity and has shown potential utility in orthopedics due to its osteoconductive properties and strength. DTE stands for desaminotyrosyl-tyrosine ethyl ester and is the most commonly used tyrosine-derived monomer. However, in vitro degradation studies showed that poly(DTE carbonate) did not completely resorb even after four years of incubation in phosphate buffered saline. Thus for bone regeneration, which only requires a temporary implant until the bone heals, poly(DTE carbonate) would not be the best choice. The goal of the present research was to optimize a scaffold composition for bone regeneration that is based on desaminotyrosyl-tyrosine alkyl ester (DTR), desaminotyrosyl-tyrosine (DT) and poly(ethylene glycol) (PEG). Five areas of research were presented: (1) synthesis and characterization of a focused library of TyrPC terpolymers; (2) evaluation of the effects of how small changes on the composition affected the mechanism and kinetics of polymer degradation and erosion; (3) fabrication
of bioactive three-dimensional porous scaffold constructs for bone regeneration; (4)
assessment of osteogenic properties in vitro using pre-osteoblasts; and (5) evaluation of bone regeneration potential, with or without recombinant human bone morphogenetic protein-2 (rhBMP-2), in vivo using a critical sized defect (CSD) rabbit calvaria (cranium) model. Small changes in the composition, such as changing the R group of DTR from ethyl to methyl, varying the mole percentages of DT and PEG, and using a different PEG block length, affected the overall properties of these polymers. Porous scaffolds were prepared by a combination of solvent casting, porogen leaching and phase separation techniques. Calcium phosphate was coated on the surface post-fabrication. The scaffolds displayed (i) a bimodal pore architecture with micropores (< 20 μm) and macropores (200 – 400 μm), (ii) a highly interconnected and open pore structure, and (iii) a highly organized microstructure. These scaffolds supported robust cell attachment and promoted
osteogenic differentiation of pre-osteoblasts. This is the first report that a synthetic
polymeric scaffold either without a biological supplement or with a minimal dose of
rhBMP-2 induced comparable bone regeneration to a commercially available bone
substitute in a non-rodent CSD animal model.
suitable for bone tissue engineering. Among the tyrosine-derived polycarbonates,
poly(DTE carbonate) has an FDA masterfile that documents its biocompatibility and nontoxicity and has shown potential utility in orthopedics due to its osteoconductive properties and strength. DTE stands for desaminotyrosyl-tyrosine ethyl ester and is the most commonly used tyrosine-derived monomer. However, in vitro degradation studies showed that poly(DTE carbonate) did not completely resorb even after four years of incubation in phosphate buffered saline. Thus for bone regeneration, which only requires a temporary implant until the bone heals, poly(DTE carbonate) would not be the best choice. The goal of the present research was to optimize a scaffold composition for bone regeneration that is based on desaminotyrosyl-tyrosine alkyl ester (DTR), desaminotyrosyl-tyrosine (DT) and poly(ethylene glycol) (PEG). Five areas of research were presented: (1) synthesis and characterization of a focused library of TyrPC terpolymers; (2) evaluation of the effects of how small changes on the composition affected the mechanism and kinetics of polymer degradation and erosion; (3) fabrication
of bioactive three-dimensional porous scaffold constructs for bone regeneration; (4)
assessment of osteogenic properties in vitro using pre-osteoblasts; and (5) evaluation of bone regeneration potential, with or without recombinant human bone morphogenetic protein-2 (rhBMP-2), in vivo using a critical sized defect (CSD) rabbit calvaria (cranium) model. Small changes in the composition, such as changing the R group of DTR from ethyl to methyl, varying the mole percentages of DT and PEG, and using a different PEG block length, affected the overall properties of these polymers. Porous scaffolds were prepared by a combination of solvent casting, porogen leaching and phase separation techniques. Calcium phosphate was coated on the surface post-fabrication. The scaffolds displayed (i) a bimodal pore architecture with micropores (< 20 μm) and macropores (200 – 400 μm), (ii) a highly interconnected and open pore structure, and (iii) a highly organized microstructure. These scaffolds supported robust cell attachment and promoted
osteogenic differentiation of pre-osteoblasts. This is the first report that a synthetic
polymeric scaffold either without a biological supplement or with a minimal dose of
rhBMP-2 induced comparable bone regeneration to a commercially available bone
substitute in a non-rodent CSD animal model.
Subject
(authority = ETD-LCSH)
Topic
Bone regeneration
Subject
(authority = ETD-LCSH)
Topic
Polycarbonates
Subject
(authority = ETD-LCSH)
Topic
Polymers in medicine
Identifier
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http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064146
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Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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Identifier
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doi:10.7282/T3GM86BN
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Magno
GivenName
Maria Hanshella
Role
Copyright Holder
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Type
Permission or license
DateTime
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(point = start)
2012-01-06 01:13:01
AssociatedEntity
Name
Maria Hanshella Magno
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
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License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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2012-01-31
DateTime
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2012-08-01
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after August 1st, 2012.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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