Design and Development of Novel Biocompatible and Mechanically Competent Polyphosphazene-based Blends for Bone Tissue Regeneration
Digital Document
Document
Handle |
Handle
http://hdl.handle.net/11134/20002:860668651
|
||||||
---|---|---|---|---|---|---|---|
Persons |
Persons
Creator (cre): Ogueri, Kenneth
Major Advisor (mja): Laurencin, Cato T.
Associate Advisor (asa): Allcock, Harry R.
Associate Advisor (asa): Nair, Lakshmi S.
Associate Advisor (asa): Khan, Yusuf
|
||||||
Title |
Title
Title
Design and Development of Novel Biocompatible and Mechanically Competent Polyphosphazene-based Blends for Bone Tissue Regeneration
|
||||||
Origin Information |
Origin Information
|
||||||
Parent Item |
Parent Item
|
||||||
Resource Type |
Resource Type
|
||||||
Digital Origin |
Digital Origin
born digital
|
||||||
Description |
Description
The goal of this dissertation is focused on the design and development of polyphosphazene biomaterials with ideal physicochemical and biological properties for regenerative engineering. This goal was achieved through four specific aims. In specific aim 1, the study began with the investigation of the relationships between the composition (defined by the chemical characteristics and ratios of the side groups used in the nucleophilic macromolecular cosubstitution), the structure (the atomistic and molecular arrangements of the side groups along the inorganic nitrogen-phosphorus backbone), and the physicochemical and biological properties of the polyphosphazene polymers. The design strategy narrowly focused on designing dipeptide-based polyphosphazenes with co-substituents such as phenylalanine ethyl ester and phenylphenoxy moieties at different ratios. Results revealed that the combinations with 75% composition of glycylglycine ethyl ester in both sets of polymers showed the most promising traits in terms of physicochemical properties. In specific aims 2 and 3, polyphosphazene-PLGA blends containing two different mixed-substituted polyphosphazenes (PNEPA25GEG75 and PNGEG75PhPh25) were designed, and the effects of the molecular interactions within the component polymers on the physicochemical properties and degradation kinetics were evaluated. The intermolecular and intramolecular hydrogen bonding interactions were influential compatibilizing factors in the blends as they determined the miscibility, phase distribution morphology, and erosion mechanism of the blends. The blends exhibited intrinsic pore-forming tendencies upon degradation, and presented 3D porous structures with sufficient interconnectivity. This erosion mechanism is quite distinct from that exhibited by any biodegradable systems currently available in the market. The blends were able to maintain near-neutral pH values during degradation in PBS as polyphosphazene degradation products neutralized that of the pristine PLGA. In vitro studies illustrated that cell growth and infiltration were well promoted on these promising matrices. Finally, the regenerative capability of the novel polyphosphazene-PLGA system was demonstrated in specific aim 4 using a critical-sized bone defect rabbit model. Radiological and histological analyses indicated that the newly designed matrices positively impacted new bone formation. Overall, this study shows that polyphosphazenes can present a flexible and useful platform for manipulating biomaterial properties at the molecular level and adapting them to specific regenerative engineering applications.
|
||||||
Genre |
Genre
|
||||||
Organizations |
Organizations
Degree granting institution (dgg): University of Connecticut
|
||||||
Held By | |||||||
Rights Statement |
Rights Statement
|
||||||
Note |
Note
|
||||||
Degree Name |
Degree Name
Doctor of Philosophy
|
||||||
Degree Level |
Degree Level
Doctoral
|
||||||
Degree Discipline |
Degree Discipline
Materials Science and Engineering
|
||||||
Local Identifier |
Local Identifier
S_17386854
|