Polyphosphazene Dissertation Allcock

A novel biodegradable polymer blend was developed for potential biomedical applications. A 50:50 poly(lactide-co-glycolide) (PLAGA) was blended in a 50:50 ratio with the followiing polyphosphazenes (PPHOS): poly[(25% ethyl glycinato)(75% p-methylphenoxy)phosphazene[, poly[(50% ethyl glycinato)(50% p-methylphenoxy)phosphazene], and poly[(75% ethyl glycinato)(25% p-methylphenoxy)phosphazene] to obtain Blends A, B, and C, respectively, using a mutual solvent technique. The miscibility of these blends was determined by measuring their glass transition temperature (Tg) using differential scanning calorimetry. After fabrication using a casting technique, the degradation of the matrices was examined. Differential scanning calorimetry showed one glass transition temperature for each blend which was between the Tg's of their respective parent polymers indicating miscibility of the blends. Surface analysis by scanning electron microscopy showed the matrices to have smooth uniform surfaces. Degradation studies showed near-zero order degradation kinetics for the blends with Blends A and B losing 10% of their mass after two weeks and Blend C degrading more rapidly (30% mass loss during the same period). These findings suggest that these novel biodegradable PLAGA/PPHOS blends may be useful for biomedical purposes.

Design And Synthesis Of Polyphosphazenes:hard Tissue Scaffolding Biomaterials And Physically Crosslinked Elastomers

Modzelewski, Tomasz
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
June 04, 2015
Committee Members:
  • Harry R Allcock, Dissertation Advisor
  • Alexander Thomas Radosevich, Committee Member
  • Benjamin James Lear, Committee Member
  • James Patrick Runt, Committee Member
  • Polymer
  • Polyphosphazene
  • Hard Tissue Engineering Scaffold
  • Fluorinated Elastomers
The work in this thesis is divided into two main parts. The first part examines the synthesis and characterization of polyphosphazenes as potential scaffolding materials usable for hard tissue repair. The goal of this work was to design polymers containing acidic functional groups in an attempt to encourage the deposition of calcium hydroxyapatite when the polymer is exposed to simulated body fluids. The second part examines the development of a new polymeric architecture which generates elastomeric properties without the use of traditional covalent or physical crosslinks. The goal was to examine the effects of this new architecture on the physical and mechanical properties of the final polymers. While the two main foci are very disparate, they are connected by the fundamental quest to explore and expand the potential application of polyphosphazenes. Chapter 1 provides a general background for the two main focus areas mentioned above. More specifically: a brief explanation is provided of the necessary physical and chemical properties of a suitable hard tissue engineering scaffolding substrate, and the basis of those requirements; together with an examination of the traditional ways in which elastomeric properties are introduced into a polymeric sample. In addition, the chemistry and selected applications of polyphosphazenes are also introduced. Chapter 2 details the design and synthesis of polyphosphazenes bearing phosphonic acid and phosphoester side groups using two different routes. The first route utilized a linker unit which was functionalized with phosphoesters prior to its attachment to the polyphosphazene backbone, while the second route involved attachment of the same linking group to the polyphosphazene backbone before the introduction of the phosphoester moieties. In both cases, the samples were treated with iodotrimethylsilane to cleave the ester bonds and afford the parent phosphonic acid. Both routes proved successful. However, varying difficulties were encountered for each route. The attachment of a phosphonated side group allowed the synthesis of final polymers with a higher total concentration of phosphonate groups. However, due to insolubility issues encountered during the deesterification, only a portion of the ester groups were cleaved. This resulted in a decreased concentration of acidic groups along the polymeric backbone. These solubility issues were not encountered for the second route, in which the linker group was phosphonated after attachment to the polymer backbone, resulting in complete removal of the ester groups. However, due to a decreased efficiency of the phosphonation step, not all of the linker groups could be functionalized, and this limited the total phosphonic acid content along the polymer chain. The author was responsible for the synthetic work associated with the prior-side-group assembly route, while the post¬-side-groups assembly work was performed by Dr. Nicole Morozowich. The manuscript is published in Macromolecules (year 2012, volume 45, pages 7684 – 7691). In Chapter 3 we examine the ability of the phosphonic acid functionalized polyphosphazenes described in Chapter 2 to mineralize calcium hydroxyapatite when exposed to simulated body fluid, which has the same ion concentration as human blood plasma. Scanning electron microscopy studies revealed that those polymers which were synthesized by phosphonation of the linker group after its attachment to the polymer backbone had a higher degree of inorganic deposition along the surface. However, these polymers had a lowed overall concentration of phosphonate groups per polymer chain. The inability to fully remove the ester protecting groups proved to be a key driving force for this increased activity. In addition, Time of Flight Secondary Ion Mass Spectroscopy (ToF-SIMS) analysis was utilized along with X-ray scattering to provide confirmation that the deposited phase was calcium hydroxyapatite, the natural mineral of bone. The author was responsible for the synthesis of the polymers in collaboration with Dr. Nichole Morozowich. The ToF-SIMS analysis was performed by Dr. Jordan Lerach and Dr. Lauren Jackson working in the lab of Dr. Nicholas Winograd. The manuscript is published in RSC Advances (year 2014, volume 4, pages 19680 – 19689). Chapter 4 describes the development of a family of carboxylic acid functionalized polyphosphazenes and the examination of their ability to mineralize calcium hydroxyapatite when exposed to simulated body fluids. The acid moieties in this system are introduced by the incorporation of the allyl esters of β-alanine or γ-amino butyric acid, followed by deesterification to afford the parent carboxylic acid. These samples show a significant increase in their ability to nucleate the growth of calcium hydroxyapatite along their surface, with the best sample doubling in mass within 4 weeks, which is a major improvement over the phosphonic acid functionalized samples described in Chapter 3. The author was helped by Ian Hotham with the synthesis and testing of the polymers. The manuscript is published in Journal of Applied Polymer Science (year 2015, volume 132, DOI: 10.1002/APP.41741) Chapter 5 contains an account of a new polymer architecture which imparts elastomeric properties without the use of traditional covalent or physical crosslinks. The polymers were synthesized with sterically bulky cyclotriphosphazene side groups linked directly to the polyphosphazene backbone using a hydroquinone linker. The geometry of the linking unit, as well as the large bulk of the side groups themselves, allowed the cyclotriphosphazene units to protrude away from the polymer backbone in a manner similar to the oars on a Viking long ship. This allowed them to interact physically with the “oars” on adjacent polymer chains, and lock the chains in place, similar to the way in which the oars on one ship will interdigitate with the oars of another ship if they get too close. These interactions allow the polymers to undergo extensive elongation before breaking (≥ 1,600 % of their original length) and the ability to recover up to 90% of the elongation when extended to high strain (up to 1,000 % of their original length). The manuscript is published in Macromolecules (year 2014, volume 47, pages 6776 – 6782). Chapter 6 expands the chemistry of the non-traditional elastomers described in Chapter 5. Specifically, the substituent groups on the cyclotriphosphazene groups are changed from 2,2,2-trifluoroethoxy to phenoxy, while the remaining chlorine atoms along the polymer backbone are still replaced with 2,2,2-trifluoroethoxide. The new polymers are shown to have better mechanical properties then the polymers described in Chapter 5. This change is attributed to the increased ability of the cyclotriphosphazene side groups to interact via π-π interactions through the presence of the phenoxy substituents. The ability to tune the final mechanical properties by simply changing the chemical nature on the cyclotriphosphazene groups provides an easy route to tailor the mechanical properties based on the final application. The author was helped by Emily Wilts with the synthesis of the polymers. The intended target journal for submission is Macromolecules. Chapter 7 describes a further extension of the ideas in Chapters 5 and 6. Specifically it involves the synthesis and mechanical testing of polyphosphazenes bearing oligo-p-phenylene groups co-substituted with 2,2,2-trifluoroethoxide. The oligo-phenylene groups are incorporated to act as variable length cross-linking moieties to further expand the new family of non-traditional polyphosphazene elastomers. The mechanical and physical properties of these polymers reveal a strong dependence on both the length and concentration of the oligo-phenylene minor co-substituent groups. In order to better understand the role that the aryloxy side groups play, the samples were examined using Small Angle X-Ray Scattering (SAXS). These studies showed that, once the side groups were long enough, they are able to interact and cause a phase separation. This results in an improvement in the mechanical properties of the final polymers. The author was responsible for all synthesis and mechanical testing. The SAXS data acquisition was performed by Nichole Wonderling, with the data analysis helped by Dr. James Runt. The intended target journal for submission is Macromolecules.

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