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Harry R. Allcock - One of the best experts on this subject based on the ideXlab platform.

  • Generational Biodegradable and Regenerative Polyphosphazene Polymers and their Blends with Poly (lactic-co-glycolic acid).
    Progress in polymer science, 2019
    Co-Authors: Kenneth S. Ogueri, Harry R. Allcock, Cato T. Laurencin
    Abstract:

    Abstract New fields such as regenerative engineering have driven the design of advanced biomaterials with a wide range of properties. Regenerative engineering is a multidisciplinary approach that integrates the fields of advanced materials science and engineering, stem cell science, physics, developmental biology, and clinical translation for the regeneration of complex tissues. The complexity and demands of this innovative approach have motivated the synthesis of new polymeric materials that can be customized to meet application-specific needs. Polyphosphazene polymers represent this fundamental change and are gaining renewed interest as biomaterials due to their outstanding synthetic flexibility, neutral bioactivity (buffering degradation products), and tunable properties across the range. Polyphosphazenes are a unique class of polymers composed of an inorganic backbone with alternating phosphorus and nitrogen atoms. Each phosphorus atom bears two substituents, with a wide variety of side groups available for property optimization. Polyphosphazenes have been investigated as potential biomaterials for regenerative engineering. Polyphosphazenes for use in regenerative applications have evolved as a class to include different generations of degradable polymers. The first generation of Polyphosphazenes for tissue regeneration entailed the use of hydrolytically active side groups such as imidazole, lactate, glycolate, glucosyl, or glyceryl groups. These side groups were selected based on their ability to sensitize the polymer backbone to hydrolysis, which allowed them to break down into non-toxic small molecules that could be metabolized or excreted. The second generation of degradable Polyphosphazenes developed consisted of polymers with amino acid ester side groups. When blended with poly (lactic acid-co-glycolic acid) (PLGA), the feasibility of neutralizing acidic degradation products of PLGA was demonstrated. The blends formed were mostly partially miscible. The desire to improve miscibility led to the design of the third generation of degradable Polyphosphazenes by incorporating dipeptide side groups which impart significant hydrogen bonding capability to the polymer for the formation of completely miscible polyphosphazene-PLGA blends. Blend system of the dipeptide-based Polyphosphazenes and PLGA exhibit a unique degradation behavior that allows the formation of interconnected porous structures upon degradation. These inherent pore-forming properties have distinguished degradable Polyphosphazenes as a potentially important class of biomaterials for further study. The design considerations and strategies for the different generations of degradable Polyphosphazenes and future directions are discussed.

  • synthesis physicochemical analysis and side group optimization of degradable dipeptide based Polyphosphazenes as potential regenerative biomaterials
    ACS Applied Polymer Materials, 2019
    Co-Authors: Harry R. Allcock, Kenneth S. Ogueri, Jorge Escobar L. Ivirico, Riley H. Blumenfield, Cato T. Laurencin
    Abstract:

    We report the synthesis and physicochemical analysis of mixed-substituent dipeptide-based polyphosphazene polymers, poly[(glycineethylglycinato) x (phenylphenoxy) y phosphazene] (PNGEG x PhPh y ) and poly[(ethylphenylalanato) x (glycineethylglycinato) y phosphazene] (PNEPA x GEG y ), using glycylglycine ethyl ester (GEG) as the primary substituent side group and cosubstituting with phenylphenol (PhPh) and phenylalanine ethyl ester (EPA), respectively. The suitability of the cosubstituted Polyphosphazenes to regenerative engineering was evaluated. The physicochemical evaluation revealed that the molecular weights, glass transition temperatures, hydrophilicity, and mechanical properties could be modulated by varying the compositions of the side groups to obtain a variety of properties. The PNEPA25GEG75 and PNGEG75PhPh25 polymers exhibited the most promising physicochemical properties. These two polymers were further subjected to in vitro hydrolysis and cell proliferation studies using poly(lactic-co-glycolic acid) (PLAGA) as a control. The hydrolysis experiments revealed that the two polymers hydrolyzed to near-neutral pH media (~5.3 to 7.0) in a relatively slow fashion, whereas a pH value as low as 2.2 was obtained for the PLAGA media over 12 weeks of degradation study. Furthermore, the two polymers showed continuous MC3T3 cell proliferation and growth in comparison to PLAGA over a 21-day culture period. These findings establish that cosubstitution of different side groups of Polyphosphazenes and exploitation of the hydrogen-bonding capacity of peptide bonds in GEG offer a flexible tool that can be employed to make new and fascinating polymeric biomaterials with different and tailored properties that can suit different regenerative needs.

  • Synthesis, Physicochemical Analysis, and Side Group Optimization of Degradable Dipeptide-Based Polyphosphazenes as Potential Regenerative Biomaterials
    2019
    Co-Authors: Kenneth S. Ogueri, Harry R. Allcock, Jorge Escobar L. Ivirico, Riley H. Blumenfield, Cato T. Laurencin
    Abstract:

    We report the synthesis and physicochemical analysis of mixed-substituent dipeptide-based polyphosphazene polymers, poly­[(glycine­ethylglycinato)x(phenyl­phenoxy)y­phosphazene] (PNGEGxPhPhy) and poly­[(ethylphenyl­alanato)x(glycine­ethylglycinato)y­phosphazene] (PNEPAxGEGy), using glycylglycine ethyl ester (GEG) as the primary substituent side group and cosubstituting with phenylphenol (PhPh) and phenylalanine ethyl ester (EPA), respectively. The suitability of the cosubstituted Polyphosphazenes to regenerative engineering was evaluated. The physicochemical evaluation revealed that the molecular weights, glass transition temperatures, hydrophilicity, and mechanical properties could be modulated by varying the compositions of the side groups to obtain a variety of properties. The PNEPA25GEG75 and PNGEG75PhPh25 polymers exhibited the most promising physicochemical properties. These two polymers were further subjected to in vitro hydrolysis and cell proliferation studies using poly­(lactic-co-glycolic acid) (PLAGA) as a control. The hydrolysis experiments revealed that the two polymers hydrolyzed to near-neutral pH media (∼5.3 to 7.0) in a relatively slow fashion, whereas a pH value as low as 2.2 was obtained for the PLAGA media over 12 weeks of degradation study. Furthermore, the two polymers showed continuous MC3T3 cell proliferation and growth in comparison to PLAGA over a 21-day culture period. These findings establish that cosubstitution of different side groups of Polyphosphazenes and exploitation of the hydrogen-bonding capacity of peptide bonds in GEG offer a flexible tool that can be employed to make new and fascinating polymeric biomaterials with different and tailored properties that can suit different regenerative needs

  • Polyphosphazenes and cyclotriphosphazenes with propeller like tetraphenylethyleneoxy side groups tuning mechanical and optoelectronic properties
    Macromolecules, 2018
    Co-Authors: Yi Ren, Dingying Shan, Kai Yang, Cuiyan Tong, Harry R. Allcock
    Abstract:

    A new class of polyphosphazene elastomers has been synthesized that combines a −P═N– backbone with both 2,2,2-trifluoroethoxy and tetraphenylethyleneoxy (TPEO) side groups. The polymer syntheses and photoproperties were first modeled using small molecule cyclic phosphazenes, and these were then applied to the high polymers. The TPEO groups confer useful mechanical and photophysical properties on the polymers. Thus, those Polyphosphazenes with the more rigid bidentate TPEO side groups have higher fluorescence quantum yields than counterparts with monodentate TPEO groups. Different TPEO substituents also allow tuning of the side-group interactions to modify the elastomeric properties of the polymers. For example, the two-dimensional TPEO unit is a stronger physical cross-linker than the comparable cross-linkers used in earlier polyphosphazene elastomers. Thus, the elastomeric polymers containing the two-dimensional TPEO exhibit greatly improved mechanical properties compared to the previous ones. Moreover, ...

  • Molecular Engineering of Polyphosphazenes and SWNT Hybrids with Potential Applications as Electronic Materials
    2018
    Co-Authors: Yi Ren, Harry R. Allcock
    Abstract:

    Polymer/single-walled carbon nanotube (SWNT) hybrids are promising candidates in applications such as flexible and stretchable electronics. In this contribution, we have examined structure–property relationships for constructing new polyphosphazene–SWNT hybrids. UV–vis and Raman spectroscopy studies revealed that the unique PN backbone enables strong intermolecular donor–acceptor interactions between the polymer and SNWTs. Furthermore, the polymeric backbone and the environment at the P-centers collectively play important roles in the formation of the hybrids. For polymers with shorter alkoxy substituents, the donor–acceptor interactions between the PN backbone and SWNTs play a crucial role in stabilizing the hybrid complexes, but for polymers with longer alkoxy substituents, the CH−π interactions and steric hindrance between the alkyl side chains and SWNTs counterbalance each other and control the stability of the hybrid complexes. Furthermore, the presence of fluorine and oxygen atoms is detrimental to the stability of the hybrid complexes. New cross-linkable Polyphosphazenes with anthracene side units were also synthesized. When photo-cross-linked, these polyphosphazene/SWNT hybrids showed elastomeric characteristics and electronic properties that are promising for future applications

Cato T. Laurencin - One of the best experts on this subject based on the ideXlab platform.

  • Generational Biodegradable and Regenerative Polyphosphazene Polymers and their Blends with Poly (lactic-co-glycolic acid).
    Progress in polymer science, 2019
    Co-Authors: Kenneth S. Ogueri, Harry R. Allcock, Cato T. Laurencin
    Abstract:

    Abstract New fields such as regenerative engineering have driven the design of advanced biomaterials with a wide range of properties. Regenerative engineering is a multidisciplinary approach that integrates the fields of advanced materials science and engineering, stem cell science, physics, developmental biology, and clinical translation for the regeneration of complex tissues. The complexity and demands of this innovative approach have motivated the synthesis of new polymeric materials that can be customized to meet application-specific needs. Polyphosphazene polymers represent this fundamental change and are gaining renewed interest as biomaterials due to their outstanding synthetic flexibility, neutral bioactivity (buffering degradation products), and tunable properties across the range. Polyphosphazenes are a unique class of polymers composed of an inorganic backbone with alternating phosphorus and nitrogen atoms. Each phosphorus atom bears two substituents, with a wide variety of side groups available for property optimization. Polyphosphazenes have been investigated as potential biomaterials for regenerative engineering. Polyphosphazenes for use in regenerative applications have evolved as a class to include different generations of degradable polymers. The first generation of Polyphosphazenes for tissue regeneration entailed the use of hydrolytically active side groups such as imidazole, lactate, glycolate, glucosyl, or glyceryl groups. These side groups were selected based on their ability to sensitize the polymer backbone to hydrolysis, which allowed them to break down into non-toxic small molecules that could be metabolized or excreted. The second generation of degradable Polyphosphazenes developed consisted of polymers with amino acid ester side groups. When blended with poly (lactic acid-co-glycolic acid) (PLGA), the feasibility of neutralizing acidic degradation products of PLGA was demonstrated. The blends formed were mostly partially miscible. The desire to improve miscibility led to the design of the third generation of degradable Polyphosphazenes by incorporating dipeptide side groups which impart significant hydrogen bonding capability to the polymer for the formation of completely miscible polyphosphazene-PLGA blends. Blend system of the dipeptide-based Polyphosphazenes and PLGA exhibit a unique degradation behavior that allows the formation of interconnected porous structures upon degradation. These inherent pore-forming properties have distinguished degradable Polyphosphazenes as a potentially important class of biomaterials for further study. The design considerations and strategies for the different generations of degradable Polyphosphazenes and future directions are discussed.

  • synthesis physicochemical analysis and side group optimization of degradable dipeptide based Polyphosphazenes as potential regenerative biomaterials
    ACS Applied Polymer Materials, 2019
    Co-Authors: Harry R. Allcock, Kenneth S. Ogueri, Jorge Escobar L. Ivirico, Riley H. Blumenfield, Cato T. Laurencin
    Abstract:

    We report the synthesis and physicochemical analysis of mixed-substituent dipeptide-based polyphosphazene polymers, poly[(glycineethylglycinato) x (phenylphenoxy) y phosphazene] (PNGEG x PhPh y ) and poly[(ethylphenylalanato) x (glycineethylglycinato) y phosphazene] (PNEPA x GEG y ), using glycylglycine ethyl ester (GEG) as the primary substituent side group and cosubstituting with phenylphenol (PhPh) and phenylalanine ethyl ester (EPA), respectively. The suitability of the cosubstituted Polyphosphazenes to regenerative engineering was evaluated. The physicochemical evaluation revealed that the molecular weights, glass transition temperatures, hydrophilicity, and mechanical properties could be modulated by varying the compositions of the side groups to obtain a variety of properties. The PNEPA25GEG75 and PNGEG75PhPh25 polymers exhibited the most promising physicochemical properties. These two polymers were further subjected to in vitro hydrolysis and cell proliferation studies using poly(lactic-co-glycolic acid) (PLAGA) as a control. The hydrolysis experiments revealed that the two polymers hydrolyzed to near-neutral pH media (~5.3 to 7.0) in a relatively slow fashion, whereas a pH value as low as 2.2 was obtained for the PLAGA media over 12 weeks of degradation study. Furthermore, the two polymers showed continuous MC3T3 cell proliferation and growth in comparison to PLAGA over a 21-day culture period. These findings establish that cosubstitution of different side groups of Polyphosphazenes and exploitation of the hydrogen-bonding capacity of peptide bonds in GEG offer a flexible tool that can be employed to make new and fascinating polymeric biomaterials with different and tailored properties that can suit different regenerative needs.

  • Synthesis, Physicochemical Analysis, and Side Group Optimization of Degradable Dipeptide-Based Polyphosphazenes as Potential Regenerative Biomaterials
    2019
    Co-Authors: Kenneth S. Ogueri, Harry R. Allcock, Jorge Escobar L. Ivirico, Riley H. Blumenfield, Cato T. Laurencin
    Abstract:

    We report the synthesis and physicochemical analysis of mixed-substituent dipeptide-based polyphosphazene polymers, poly­[(glycine­ethylglycinato)x(phenyl­phenoxy)y­phosphazene] (PNGEGxPhPhy) and poly­[(ethylphenyl­alanato)x(glycine­ethylglycinato)y­phosphazene] (PNEPAxGEGy), using glycylglycine ethyl ester (GEG) as the primary substituent side group and cosubstituting with phenylphenol (PhPh) and phenylalanine ethyl ester (EPA), respectively. The suitability of the cosubstituted Polyphosphazenes to regenerative engineering was evaluated. The physicochemical evaluation revealed that the molecular weights, glass transition temperatures, hydrophilicity, and mechanical properties could be modulated by varying the compositions of the side groups to obtain a variety of properties. The PNEPA25GEG75 and PNGEG75PhPh25 polymers exhibited the most promising physicochemical properties. These two polymers were further subjected to in vitro hydrolysis and cell proliferation studies using poly­(lactic-co-glycolic acid) (PLAGA) as a control. The hydrolysis experiments revealed that the two polymers hydrolyzed to near-neutral pH media (∼5.3 to 7.0) in a relatively slow fashion, whereas a pH value as low as 2.2 was obtained for the PLAGA media over 12 weeks of degradation study. Furthermore, the two polymers showed continuous MC3T3 cell proliferation and growth in comparison to PLAGA over a 21-day culture period. These findings establish that cosubstitution of different side groups of Polyphosphazenes and exploitation of the hydrogen-bonding capacity of peptide bonds in GEG offer a flexible tool that can be employed to make new and fascinating polymeric biomaterials with different and tailored properties that can suit different regenerative needs

  • Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering
    Regenerative Engineering and Translational Medicine, 2017
    Co-Authors: Kenneth S. Ogueri, Lakshmi S. Nair, Harry R. Allcock, Jorge L. Escobar Ivirico, Cato T. Laurencin
    Abstract:

    The occurrence of musculoskeletal tissue injury or disease and the subsequent functional impairment is at an alarming rate. It continues to be one of the most challenging problems in the human health care. Regenerative engineering offers a promising transdisciplinary strategy for tissues regeneration based on the convergence of tissue engineering, advanced materials science, stem cell science, developmental biology, and clinical translation. Biomaterials are emerging as extracellular-mimicking matrices designed to provide instructive cues to control cell behavior and ultimately be applied as therapies to regenerate damaged tissues. Biodegradable polymers constitute an attractive class of biomaterials for the development of scaffolds due to their flexibility in chemistry and the ability to be excreted or resorbed by the body. Herein, the focus will be on biodegradable polyphosphazene-based blend systems. The synthetic flexibility of polyphosphazene, combined with the unique inorganic backbone, has provided a springboard for more research and subsequent development of numerous novel materials that are capable of forming miscible blends with poly(lactide-co-glycolide) (PLAGA). Laurencin and co-workers have demonstrated the exploitation of the synthetic flexibility of polyphosphazene that will allow the design of novel polymers, which can form miscible blends with PLAGA for biomedical applications. These novel blends, due to their well-tuned biodegradability, and mechanical and biological properties coupled with the buffering capacity of the degradation products, constitute ideal materials for regeneration of various musculoskeletal tissues. Lay Summary Regenerative engineering aims to regenerate complex tissues to address the clinical challenge of organ damage. Tissue engineering has largely focused on the restoration and repair of individual tissues and organs, but over the past 25 years, scientific, engineering, and medical advances have led to the introduction of this new approach which involves the regeneration of complex tissues and biological systems such as a knee or a whole limb. While a number of excellent advanced biomaterials have been developed, the choice of biomaterials, however, has increased over the past years to include polymers that can be designed with a range of mechanical properties, degradation rates, and chemical functionality. The Polyphosphazenes are one good example. Their chemical versatility and hydrogen bonding capability encourages blending with other biologically relevant polymers. The further development of polyphosphazene-based blends will present a wide spectrum of advanced biomaterials that can be used as scaffolds for regenerative engineering as well as other biomedical applications.

  • Chapter 11 – Polyphosphazenes
    Natural and Synthetic Biomedical Polymers, 2014
    Co-Authors: Roshan James, Sangamesh G. Kumbar, Meng Deng, Cato T. Laurencin
    Abstract:

    Polyphosphazenes consist of an inorganic backbone of alternating phosphorous and nitrogen atoms form a unique class of synthetic materials with vast potential for biomedical applications. Through studies conducted by our group and other researchers, one can effectively control polymer properties by modulating the side group chemistry. This approach has enabled the generation of a biomaterial library detailing tunable physical, chemical, and biological properties. Biodegradable Polyphosphazenes undergo controlled degradation producing nontoxic and neutral pH degradation products. These polymers have excellent buffering capacity due to the simultaneous production of phosphates and ammonia during polyphosphazene degradation. This chapter focuses on the synthesis of biodegradable Polyphosphazenes, their degradation characteristics, their biocompatibility, and their application for tissue regeneration and as drug delivery matrices.

Alexander K. Andrianov - One of the best experts on this subject based on the ideXlab platform.

  • protein loaded soluble and nanoparticulate formulations of ionic Polyphosphazenes and their interactions on molecular and cellular levels
    Materials Science and Engineering: C, 2020
    Co-Authors: Alexander K. Andrianov, Alexander Marin, Joseph Deng, Thomas R. Fuerst
    Abstract:

    Abstract Nanoparticulate and water-soluble formulations of ionic Polyphosphazenes and protein cargo - lysozyme (LYZ) were prepared by their self-assembly in aqueous solutions at near physiological pH (pH 7.4) in the presence and absence of an ionic cross-linker – spermine tetrahydrochloride. Efficiency of LYZ encapsulation, physico-chemical characteristics of formulations, and the effect of reaction parameters were investigated using asymmetric flow field flow fractionation (AF4) and dynamic light scattering (DLS) methods. The effect of both polymer formulations on encapsulated LYZ was evaluated using soluble oligosaccharide substrate, whereas their ability to present the protein to cellular surfaces was assessed by measuring enzymatic activity of encapsulated LYZ against Micrococcus lysodeikticus cells. It was found that both soluble and cross-linked polymer matrices reduce lysis of bacterial cells by LYZ, whereas activity of encapsulated protein against oligosaccharide substrate remained practically unchanged indicating no adverse effect of polyphosphazene on protein integrity. Moreover, nanoparticulate formulations display distinctly different behavior in cellular assays when compared to their soluble counterparts. LYZ encapsulated in polyphosphazene nanoparticles shows approximately 2.5-fold higher activity in its ability to lyse cells as compared with water-soluble LYZ-PCPP formulations. A new approach to PEGylation of polyphosphazene nanoparticles was also developed. The method utilizes a new ionic polyphosphazene derivative, which contains graft (polyethylene glycol) chains. PEGylation allows for an improved control over the size of nanoparticles and broader modulation of their cross-linking density, while still permitting for protein presentation to cellular substrates.

  • Biocompatible Nanocoatings of Fluorinated Polyphosphazenes through Aqueous Assembly.
    ACS applied materials & interfaces, 2018
    Co-Authors: Victor Selin, Alexander K. Andrianov, Alexander Marin, Victoria Albright, John F. Ankner, Svetlana A. Sukhishvili
    Abstract:

    Nonionic fluorinated Polyphosphazenes, such as poly[bis(trifluoroethoxy)phosphazene] (PTFEP), display superb biocompatibility, yet their deposition to surfaces has been limited to solution casting from organic solvents or thermal molding. Herein, hydrophobic coatings of fluorinated Polyphosphazenes are demonstrated through controlled deposition of ionic fluorinated Polyphosphazenes (iFPs) from aqueous solutions using the layer-by-layer (LbL) technique. Specifically, the assemblies included poly[(carboxylatophenoxy)(trifluoroethoxy)phosphazenes] with varied content of fluorine atoms as iFPs (or poly[bis(carboxyphenoxy)phosphazene] (PCPP) as a control nonfluorinated polyphosphazene) and a variety of polycations. Hydrophobic interactions largely contributed to the formation of LbL films of iFPs with polycations, leading to linear growth and extremely low water uptake. Hydrophobicity-enhanced ionic pairing within iFP/BPEI assemblies gave rise to large-amplitude oscillations in surface wettability as a functio...

  • Hydrolytically Degradable PEGylated Polyelectrolyte Nanocomplexes for Protein Delivery
    2018
    Co-Authors: Alexander K. Andrianov, Alexander Marin, Andre P Martinez, Jacob L. Weidman, Thomas R. Fuerst
    Abstract:

    Novel oppositely charged polyphosphazene polyelectrolytes containing grafted poly­(ethylene glycol) (PEG) chains were synthesized as modular components for the assembly of biodegradable PEGylated protein delivery vehicles. These macromolecular counterparts, which contained either carboxylic acid or tertiary amino groups, were then formulated at near physiological conditions into supramolecular assemblies of nanoscale level, below 100 nm. Nanocomplexes with electroneutral surface charge, as assessed by zeta potential measurements, were stable in aqueous solutions, which suggests their compact polyelectrolyte complex “core”–hydrophilic PEG “shell” structure. Investigation of PEGylated polyphosphazene nanocomplexes as agents for noncovalent PEGylation of the therapeutic protein l-asparaginase (L-ASP) in vitro demonstrated their ability to dramatically reduce protein antigenicity, as measured by antibody binding using enzyme linked immunosorbent assay (ELISA). Encapsulation in nanocomplexes did not affect enzymatic activity of L-ASP, but improved its thermal stability and proteolytic resistance. Gel permeation chromatography (GPC) experiments revealed that all synthesized Polyphosphazenes exhibited composition controlled hydrolytic degradability in aqueous solutions at neutral pH and showed greater stability at lower temperatures. Overall, novel hydrolytically degradable polyphosphazene polyelectrolytes capable of spontaneous self-assembly into PEGylated nanoparticulates in aqueous solutions can potentially enable a simple and effective approach to modifying therapeutic proteins without the need for their covalent modification

  • Biocompatible Nanocoatings of Fluorinated Polyphosphazenes through Aqueous Assembly
    2018
    Co-Authors: Victor Selin, Alexander K. Andrianov, Alexander Marin, Victoria Albright, John F. Ankner, Svetlana A. Sukhishvili
    Abstract:

    Nonionic fluorinated Polyphosphazenes, such as poly­[bis­(trifluoroethoxy)­phosphazene] (PTFEP), display superb biocompatibility, yet their deposition to surfaces has been limited to solution casting from organic solvents or thermal molding. Herein, hydrophobic coatings of fluorinated Polyphosphazenes are demonstrated through controlled deposition of ionic fluorinated Polyphosphazenes (iFPs) from aqueous solutions using the layer-by-layer (LbL) technique. Specifically, the assemblies included poly­[(carboxylatophenoxy)­(trifluoroethoxy)­phosphazenes] with varied content of fluorine atoms as iFPs (or poly­[bis­(carboxyphenoxy)­phosphazene] (PCPP) as a control nonfluorinated polyphosphazene) and a variety of polycations. Hydrophobic interactions largely contributed to the formation of LbL films of iFPs with polycations, leading to linear growth and extremely low water uptake. Hydrophobicity-enhanced ionic pairing within iFP/BPEI assemblies gave rise to large-amplitude oscillations in surface wettability as a function of capping layer, which were the largest for the most fluorinated iFP, while control PCPP/polycation systems remained hydrophilic regardless of the film top layer. Neutron reflectometry (NR) studies indicated superior layering and persistence of such layering in salt solution for iFP/BPEI films as compared to control PCPP/polycation systems. Hydrophobicity of iFP-capped LbL coatings could be further enhanced by using a highly porous polyester surgical felt rather than planar substrates for film deposition. Importantly, iFP/polycation coatings displayed biocompatibility which was similar to or superior to that of solution-cast coatings of a clinically validated material (PTFEP), as demonstrated by the hemolysis of the whole blood and protein adsorption studies

  • biodegradable smart Polyphosphazenes with intrinsic multifunctionality as intracellular protein delivery vehicles
    Biomacromolecules, 2017
    Co-Authors: Andre P Martinez, Thomas R. Fuerst, Bareera Qamar, Silvia Muro, Alexander K. Andrianov
    Abstract:

    A series of biodegradable drug delivery polymers with intrinsic multifunctionality have been designed and synthesized utilizing a polyphosphazene macromolecular engineering approach. Novel water-soluble polymers, which contain carboxylic acid and pyrrolidone moieties attached to an inorganic phosphorus–nitrogen backbone, were characterized by a suite of physicochemical methods to confirm their structure, composition, and molecular sizes. All synthesized Polyphosphazenes displayed composition-dependent hydrolytic degradability in aqueous solutions at neutral pH. Their formulations were stable at lower temperatures, potentially indicating adequate shelf life, but were characterized by accelerated degradation kinetics at elevated temperatures, including 37 °C. It was found that synthesized Polyphosphazenes are capable of environmentally triggered self-assembly to produce nanoparticles with narrow polydispersity in the size range of 150–700 nm. Protein loading capacity of copolymers has been validated via the...

Lakshmi S. Nair - One of the best experts on this subject based on the ideXlab platform.

  • Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering
    Regenerative Engineering and Translational Medicine, 2017
    Co-Authors: Kenneth S. Ogueri, Lakshmi S. Nair, Harry R. Allcock, Jorge L. Escobar Ivirico, Cato T. Laurencin
    Abstract:

    The occurrence of musculoskeletal tissue injury or disease and the subsequent functional impairment is at an alarming rate. It continues to be one of the most challenging problems in the human health care. Regenerative engineering offers a promising transdisciplinary strategy for tissues regeneration based on the convergence of tissue engineering, advanced materials science, stem cell science, developmental biology, and clinical translation. Biomaterials are emerging as extracellular-mimicking matrices designed to provide instructive cues to control cell behavior and ultimately be applied as therapies to regenerate damaged tissues. Biodegradable polymers constitute an attractive class of biomaterials for the development of scaffolds due to their flexibility in chemistry and the ability to be excreted or resorbed by the body. Herein, the focus will be on biodegradable polyphosphazene-based blend systems. The synthetic flexibility of polyphosphazene, combined with the unique inorganic backbone, has provided a springboard for more research and subsequent development of numerous novel materials that are capable of forming miscible blends with poly(lactide-co-glycolide) (PLAGA). Laurencin and co-workers have demonstrated the exploitation of the synthetic flexibility of polyphosphazene that will allow the design of novel polymers, which can form miscible blends with PLAGA for biomedical applications. These novel blends, due to their well-tuned biodegradability, and mechanical and biological properties coupled with the buffering capacity of the degradation products, constitute ideal materials for regeneration of various musculoskeletal tissues. Lay Summary Regenerative engineering aims to regenerate complex tissues to address the clinical challenge of organ damage. Tissue engineering has largely focused on the restoration and repair of individual tissues and organs, but over the past 25 years, scientific, engineering, and medical advances have led to the introduction of this new approach which involves the regeneration of complex tissues and biological systems such as a knee or a whole limb. While a number of excellent advanced biomaterials have been developed, the choice of biomaterials, however, has increased over the past years to include polymers that can be designed with a range of mechanical properties, degradation rates, and chemical functionality. The Polyphosphazenes are one good example. Their chemical versatility and hydrogen bonding capability encourages blending with other biologically relevant polymers. The further development of polyphosphazene-based blends will present a wide spectrum of advanced biomaterials that can be used as scaffolds for regenerative engineering as well as other biomedical applications.

  • mechanical properties and osteocompatibility of novel biodegradable alanine based Polyphosphazenes side group effects
    Acta Biomaterialia, 2010
    Co-Authors: Swaminathan Sethuraman, Lakshmi S. Nair, Anurima Singh, Nick R. Krogman, Yaser E. Greish, Harry R. Allcock, Saadiq F Elamin, My Tien N Nguyen, Paul W. Brown
    Abstract:

    The versatility of polymers for tissue regeneration lies in the feasibility to modulate the physical and biological properties by varying the side groups grafted to the polymers. Biodegradable Polyphosphazenes are high-molecular-weight polymers with alternating nitrogen and phosphorus atoms in the backbone. This study is the first of its kind to systematically investigate the effect of side group structure on the compressive strength of novel biodegradable polyphosphazene based polymers as potential materials for tissue regeneration. The alanine polyphosphazene based polymers, poly(bis(ethyl alanato) phosphazene) (PNEA), poly((50% ethyl alanato) (50% methyl phenoxy) phosphazene) (PNEA(50)mPh(50)), poly((50% ethyl alanato) (50% phenyl phenoxy) phosphazene) (PNEA(50)PhPh(50)) were investigated to demonstrate their mechanical properties and osteocompatibility. Results of mechanical testing studies demonstrated that the nature and the ratio of the pendent groups attached to the polymer backbone play a significant role in determining the mechanical properties of the resulting polymer. The compressive strength of PNEA(50)PhPh(50) was significantly higher than poly(lactide-co-glycolide) (85:15 PLAGA) (p<0.05). Additional studies evaluated the cellular response and gene expression of primary rat osteoblast cells on PNEA, PNEA(50)mPh(50) and PNEA(50)PhPh(50) films as candidates for bone tissue engineering applications. Results of the in vitro osteocompatibility evaluation demonstrated that cells adhere, proliferate, and maintain their phenotype when seeded directly on the surface of PNEA, PNEA(50)mPh(50), and PNEA(50)PhPh(50). Moreover, cells on the surface of the polymers expressed type I collagen, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein, which are characteristic genes for osteoblast maturation, differentiation, and mineralization.

  • hydrogen bonding in blends of polyesters with dipeptide containing Polyphosphazenes
    Journal of Applied Polymer Science, 2010
    Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Nhu Q Nguyen, Harry R. Allcock
    Abstract:

    New biomedically erodible polymer composites were investigated. Polyphosphazenes containing the dipeptide side groups alanyl–glycine ethyl ester, valinyl–glycine ethyl ester, and phenylalanyl–glycine ethyl ester were blended with poly(lactide-co-glycolide) (PLGA) with lactic to glycolic acid ratios of 50 : 50 [PLGA (50 : 50)] and 85 : 15 [PLGA (85 : 15)] with solution-phase techniques. Each dipeptide ethyl ester side group contains two NH protons that are capable of hydrogen bonding with the carbonyl functions of PLGA. Polyphosphazenes that contain only the dipeptide ethyl ester groups are insoluble in organic solvents and are thus unsuitable for solution-phase composite formation. To ensure solubility during and after synthesis, cosubstituted polymers with both dipeptide ethyl ester and glycine or alanine ethyl ester side groups were used. Solution casting or electrospinning was used to fabricate polymer blend matrices with different ratios of polyphosphazene to polyester, and their miscibilities were estimated with differential scanning calorimetry and scanning electron microscopy techniques. Polyphosphazenes with alanyl–glycine ethyl ester side groups plus the second cosubstituent were completely miscible with PLGA (50 : 50) and PLGA (85 : 15) when processed via solution-casting techniques. This suggests that the hydrogen-bonding protons in alanyl–glycine ethyl ester have access to the oxygen atoms of the carbonyl units in PLGA. However, when the same pair of polymers was electrospun from solution, the polymers proved to be immiscible. Solution-cast miscible polymer blends were obtained from PLGA (50 : 50) plus the polyphosphazene that was cosubstituted with valinyl–glycine ethyl ester and glycine ethyl ester side groups. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

  • Hydrogen bonding in blends of polyesters with dipeptide‐containing Polyphosphazenes
    Journal of Applied Polymer Science, 2010
    Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Nhu Q Nguyen, Harry R. Allcock
    Abstract:

    New biomedically erodible polymer composites were investigated. Polyphosphazenes containing the dipeptide side groups alanyl–glycine ethyl ester, valinyl–glycine ethyl ester, and phenylalanyl–glycine ethyl ester were blended with poly(lactide-co-glycolide) (PLGA) with lactic to glycolic acid ratios of 50 : 50 [PLGA (50 : 50)] and 85 : 15 [PLGA (85 : 15)] with solution-phase techniques. Each dipeptide ethyl ester side group contains two NH protons that are capable of hydrogen bonding with the carbonyl functions of PLGA. Polyphosphazenes that contain only the dipeptide ethyl ester groups are insoluble in organic solvents and are thus unsuitable for solution-phase composite formation. To ensure solubility during and after synthesis, cosubstituted polymers with both dipeptide ethyl ester and glycine or alanine ethyl ester side groups were used. Solution casting or electrospinning was used to fabricate polymer blend matrices with different ratios of polyphosphazene to polyester, and their miscibilities were estimated with differential scanning calorimetry and scanning electron microscopy techniques. Polyphosphazenes with alanyl–glycine ethyl ester side groups plus the second cosubstituent were completely miscible with PLGA (50 : 50) and PLGA (85 : 15) when processed via solution-casting techniques. This suggests that the hydrogen-bonding protons in alanyl–glycine ethyl ester have access to the oxygen atoms of the carbonyl units in PLGA. However, when the same pair of polymers was electrospun from solution, the polymers proved to be immiscible. Solution-cast miscible polymer blends were obtained from PLGA (50 : 50) plus the polyphosphazene that was cosubstituted with valinyl–glycine ethyl ester and glycine ethyl ester side groups. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

  • The influence of side group modification in Polyphosphazenes on hydrolysis and cell adhesion of blends with PLGA.
    Biomaterials, 2009
    Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Meng Deng, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Harry R. Allcock
    Abstract:

    Abstract Polyphosphazenes have been synthesized with tris(hydroxymethyl)amino methane (THAM) side groups and with co-substituents glycine ethyl ester and alanine ethyl ester. The THAM side group was linked to the polyphosphazene backbone via the amino function. The three pendent hydroxyl functions on each THAM side group were utilized for hydrogen bonding association with poly(glycolic–lactic acid) (PLGA). Co-substitution of the polyphosphazene with both THAM and glycine or alanine ethyl esters was employed to avoid the insolubility of the single-substituent THAM-substituted Polyphosphazenes. Both poly[(tris(hydroxymethyl)aminomethane)(ethyl glycinato)phosphazene] and poly[(tris(hydroxymethyl)aminomethane)(ethyl alanato)phosphazene] (1:1 ratio of side groups) were blended with PLGA (50:50) or PLGA (85:15). DSC analysis indicated miscible blend formation, irrespective of the detailed molecular structure of the polyphosphazene or the composition of PLGA in the blend. Hydrolysis studies of the polyphosphazene:PLGA (50:50) blends indicated that the PLGA component hydrolyzed more rapidly than the polyphosphazene. Primary osteoblast cell studies showed good cell adhesion to the polymer blends during 14 days, but subsequent limited cell spreading due to increased surface roughness as the two polymers eroded at different rates.

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  • mechanical properties and osteocompatibility of novel biodegradable alanine based Polyphosphazenes side group effects
    Acta Biomaterialia, 2010
    Co-Authors: Swaminathan Sethuraman, Lakshmi S. Nair, Anurima Singh, Nick R. Krogman, Yaser E. Greish, Harry R. Allcock, Saadiq F Elamin, My Tien N Nguyen, Paul W. Brown
    Abstract:

    The versatility of polymers for tissue regeneration lies in the feasibility to modulate the physical and biological properties by varying the side groups grafted to the polymers. Biodegradable Polyphosphazenes are high-molecular-weight polymers with alternating nitrogen and phosphorus atoms in the backbone. This study is the first of its kind to systematically investigate the effect of side group structure on the compressive strength of novel biodegradable polyphosphazene based polymers as potential materials for tissue regeneration. The alanine polyphosphazene based polymers, poly(bis(ethyl alanato) phosphazene) (PNEA), poly((50% ethyl alanato) (50% methyl phenoxy) phosphazene) (PNEA(50)mPh(50)), poly((50% ethyl alanato) (50% phenyl phenoxy) phosphazene) (PNEA(50)PhPh(50)) were investigated to demonstrate their mechanical properties and osteocompatibility. Results of mechanical testing studies demonstrated that the nature and the ratio of the pendent groups attached to the polymer backbone play a significant role in determining the mechanical properties of the resulting polymer. The compressive strength of PNEA(50)PhPh(50) was significantly higher than poly(lactide-co-glycolide) (85:15 PLAGA) (p<0.05). Additional studies evaluated the cellular response and gene expression of primary rat osteoblast cells on PNEA, PNEA(50)mPh(50) and PNEA(50)PhPh(50) films as candidates for bone tissue engineering applications. Results of the in vitro osteocompatibility evaluation demonstrated that cells adhere, proliferate, and maintain their phenotype when seeded directly on the surface of PNEA, PNEA(50)mPh(50), and PNEA(50)PhPh(50). Moreover, cells on the surface of the polymers expressed type I collagen, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein, which are characteristic genes for osteoblast maturation, differentiation, and mineralization.

  • hydrogen bonding in blends of polyesters with dipeptide containing Polyphosphazenes
    Journal of Applied Polymer Science, 2010
    Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Nhu Q Nguyen, Harry R. Allcock
    Abstract:

    New biomedically erodible polymer composites were investigated. Polyphosphazenes containing the dipeptide side groups alanyl–glycine ethyl ester, valinyl–glycine ethyl ester, and phenylalanyl–glycine ethyl ester were blended with poly(lactide-co-glycolide) (PLGA) with lactic to glycolic acid ratios of 50 : 50 [PLGA (50 : 50)] and 85 : 15 [PLGA (85 : 15)] with solution-phase techniques. Each dipeptide ethyl ester side group contains two NH protons that are capable of hydrogen bonding with the carbonyl functions of PLGA. Polyphosphazenes that contain only the dipeptide ethyl ester groups are insoluble in organic solvents and are thus unsuitable for solution-phase composite formation. To ensure solubility during and after synthesis, cosubstituted polymers with both dipeptide ethyl ester and glycine or alanine ethyl ester side groups were used. Solution casting or electrospinning was used to fabricate polymer blend matrices with different ratios of polyphosphazene to polyester, and their miscibilities were estimated with differential scanning calorimetry and scanning electron microscopy techniques. Polyphosphazenes with alanyl–glycine ethyl ester side groups plus the second cosubstituent were completely miscible with PLGA (50 : 50) and PLGA (85 : 15) when processed via solution-casting techniques. This suggests that the hydrogen-bonding protons in alanyl–glycine ethyl ester have access to the oxygen atoms of the carbonyl units in PLGA. However, when the same pair of polymers was electrospun from solution, the polymers proved to be immiscible. Solution-cast miscible polymer blends were obtained from PLGA (50 : 50) plus the polyphosphazene that was cosubstituted with valinyl–glycine ethyl ester and glycine ethyl ester side groups. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

  • Hydrogen bonding in blends of polyesters with dipeptide‐containing Polyphosphazenes
    Journal of Applied Polymer Science, 2010
    Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Nhu Q Nguyen, Harry R. Allcock
    Abstract:

    New biomedically erodible polymer composites were investigated. Polyphosphazenes containing the dipeptide side groups alanyl–glycine ethyl ester, valinyl–glycine ethyl ester, and phenylalanyl–glycine ethyl ester were blended with poly(lactide-co-glycolide) (PLGA) with lactic to glycolic acid ratios of 50 : 50 [PLGA (50 : 50)] and 85 : 15 [PLGA (85 : 15)] with solution-phase techniques. Each dipeptide ethyl ester side group contains two NH protons that are capable of hydrogen bonding with the carbonyl functions of PLGA. Polyphosphazenes that contain only the dipeptide ethyl ester groups are insoluble in organic solvents and are thus unsuitable for solution-phase composite formation. To ensure solubility during and after synthesis, cosubstituted polymers with both dipeptide ethyl ester and glycine or alanine ethyl ester side groups were used. Solution casting or electrospinning was used to fabricate polymer blend matrices with different ratios of polyphosphazene to polyester, and their miscibilities were estimated with differential scanning calorimetry and scanning electron microscopy techniques. Polyphosphazenes with alanyl–glycine ethyl ester side groups plus the second cosubstituent were completely miscible with PLGA (50 : 50) and PLGA (85 : 15) when processed via solution-casting techniques. This suggests that the hydrogen-bonding protons in alanyl–glycine ethyl ester have access to the oxygen atoms of the carbonyl units in PLGA. However, when the same pair of polymers was electrospun from solution, the polymers proved to be immiscible. Solution-cast miscible polymer blends were obtained from PLGA (50 : 50) plus the polyphosphazene that was cosubstituted with valinyl–glycine ethyl ester and glycine ethyl ester side groups. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

  • The influence of side group modification in Polyphosphazenes on hydrolysis and cell adhesion of blends with PLGA.
    Biomaterials, 2009
    Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Meng Deng, Arlin L. Weikel, Katherine A. Kristhart, Syam P. Nukavarapu, Harry R. Allcock
    Abstract:

    Abstract Polyphosphazenes have been synthesized with tris(hydroxymethyl)amino methane (THAM) side groups and with co-substituents glycine ethyl ester and alanine ethyl ester. The THAM side group was linked to the polyphosphazene backbone via the amino function. The three pendent hydroxyl functions on each THAM side group were utilized for hydrogen bonding association with poly(glycolic–lactic acid) (PLGA). Co-substitution of the polyphosphazene with both THAM and glycine or alanine ethyl esters was employed to avoid the insolubility of the single-substituent THAM-substituted Polyphosphazenes. Both poly[(tris(hydroxymethyl)aminomethane)(ethyl glycinato)phosphazene] and poly[(tris(hydroxymethyl)aminomethane)(ethyl alanato)phosphazene] (1:1 ratio of side groups) were blended with PLGA (50:50) or PLGA (85:15). DSC analysis indicated miscible blend formation, irrespective of the detailed molecular structure of the polyphosphazene or the composition of PLGA in the blend. Hydrolysis studies of the polyphosphazene:PLGA (50:50) blends indicated that the PLGA component hydrolyzed more rapidly than the polyphosphazene. Primary osteoblast cell studies showed good cell adhesion to the polymer blends during 14 days, but subsequent limited cell spreading due to increased surface roughness as the two polymers eroded at different rates.

  • synthesis and characterization of new biomedical polymers serine and threonine containing Polyphosphazenes and poly l lactic acid grafted copolymers
    Macromolecules, 2008
    Co-Authors: Nick R. Krogman, Lakshmi S. Nair, Cato T. Laurencin, Arlin L. Weikel, Nhu Q Nguyen, Harry R. Allcock
    Abstract:

    Polyphosphazenes that contain serine and threonine side groups have been synthesized by the macromolecular substitution technique, and their structure and properties were determined. Serine and threonine have two different sites for covalent linkage to the polyphosphazene backbone. For one series of polymers, serine ethyl ester and threonine ethyl ester units were linked to the polyphosphazene skeleton via the N-terminus. The free hydroxyl groups on each side group were then used to graft poly(l-lactide). Graft densities of 1:0.5, 1:2, and 1:4 grafts per repeat unit were controlled through the stoichiometric ratios of sodium naphthalenide to polyphosphazene side groups during the synthetic procedures. For the second series of macromolecules, the hydroxyl function of serine or threonine was used as the site for covalent attachment to the polyphosphazene backbone, a process that required protection of both the N- and C-termini. Secondary reactions to remove the protective groups then yielded side units with...