In Vitro and In Vivo Assessment of the Infection Resistance and Biocompatibility of Small-Molecule-Modified Polyurethane Biomaterials.

Bacterial intracellular nucleotide second messenger signaling is involved in biofilm formation and regulates biofilm development. Interference with the bacterial nucleotide second messenger signaling provides a novel approach to control biofilm formation and limit microbial infection in medical devices. In this study, we tethered small-molecule derivatives of 4-arylazo-3,5-diamino-1-pyrazole on polyurethane biomaterial surfaces and measured the biofilm resistance and initial biocompatibility of modified biomaterials in and settings.

Surfaces modified with small molecules that interfere with nucleotide signaling reduce Staphylococcus epidermidis biofilm and increase the efficacy of ciprofloxacin.

Staphylococcus epidermidis are common bacteria associated with biofilm related infections on implanted medical devices. Antibiotics are often used in combating such infections, but they may lose their efficacy in the presence of biofilms. Bacterial intracellular nucleotide second messenger signaling plays an important role in biofilm formation, and interference with the nucleotide signaling pathways provides a possible way to control biofilm formation and to increase biofilm susceptibility to antibiotic therapy.

Crosslinkable fluorophenoxy-substituted poly[bis(octafluoropentoxy) phosphazene] biomaterials with improved antimicrobial effect and hemocompatibility.

Biomaterial-associated microbial infection is one of the most frequent and severe complications associated with the use of biomaterials in medical devices. In previous studies, we developed new fluorinated polyphosphazenes, poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X-OFP), and demonstrated the inhibition of bacterial adhesion and biofilm formation, thereby controlling microbial infection. In this study, two additional fluorinated polyphosphazenes (PPs, defined as LS02 and LS03) with fluorophenoxy-substituted side groups, 4-fluorophenoxy and 4-(trifluoromethyl)phenoxy, respectively, based on X-OFP general structure, were synthesized and applied as coatings on stainless steel.

Biomedical applications of polyphosphazenes.

Ever since the pioneering research efforts on their utility in biomedicine, polyphosphazene polymers have witnessed enormous growth and expansion in several biomedical applications due to their unique properties. The development of this exceptional biodegradable system with extraordinary design flexibility, property tunability and neutral bioactivity could stimulate an unprecedented paradigm in biomaterial design. Thus, polyphosphazenes are, undoubtedly, the next-generation biomaterials.

In Vivo Evaluation of the Regenerative Capability of Glycylglycine Ethyl Ester-Substituted Polyphosphazene and Poly(lactic--glycolic acid) Blends: A Rabbit Critical-Sized Bone Defect Model.

In an effort to understand the biological capability of polyphosphazene-based polymers, three-dimensional biomimetic bone scaffolds were fabricated using the blends of poly[(glycine ethylglycinato)(phenylphenoxy)]phosphazene (PNGEGPhPh) and poly(lactic--glycolic acid) (PLGA), and an in vivo evaluation was performed in a rabbit critical-sized bone defect model. The matrices constructed from PNGEGPhPh-PLGA blends were surgically implanted into 15 mm critical-sized radial defects of the rabbits as structural templates for bone tissue regeneration. PLGA, which is the most commonly used synthetic bone graft substitute, was used as a control in this study.

Polyphosphazenes: Phosphorus in Inorganic-Organic Polymers.

Although the best-known examples of synthetic polymers are derived from carbon-based monomers, there exists another large and growing family of macromolecules based on the chemistry of phosphorus. These are the poly(organophosphazenes): polymers with a backbone of alternating phosphorus and nitrogen atoms and with two organic side groups attached to each phosphorus. The methods of synthesis of these polymers allow access to property combinations not found in all-organic counterparts, and this provides pathways to new materials that are important in biomedical research, energy generation and storage, aerospace materials, and numerous other specialized applications.

Inhibition of bacterial adhesion and biofilm formation by a textured fluorinated alkoxyphosphazene surface.

The utilization of biomaterials in implanted blood-contacting medical devices often induces a persistent problem of microbial infection, which results from bacterial adhesion and biofilm formation on the surface of biomaterials. In this research, we developed new fluorinated alkoxyphosphazene materials, specifically poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X-OFP), with improved mechanical properties, and further modified the surface topography with ordered pillars to improve the antibacterial properties. Three X-OFP materials, X-OFP, X-OFP X-OFP, with different crosslinking densities were synthesized, and textured films with patterns of 500/500/600 nm (diameter/spacing/height) were fabricated via a two stage soft lithography molding process.

A Regenerative Polymer Blend Composed of Glycylglycine ethyl ester-substituted Polyphosphazene and Poly (lactic-co-glycolic acid).

In the pursuit of continuous improvement in the area of biomaterial design, blends of mixed-substituent polyphosphazenes and poly (lactic acid-glycolic acid) (PLGA) were prepared, and their morphology of phase distributions for the first time was studied. The degradation mechanism and osteocompatibility of the blends were also evaluated for their use as regenerative materials. Poly [(ethyl phenylalanato)(glycine ethyl glycinato)phosphazene](PNEPAGEG) and poly [(glycine ethyl glycinato)(phenylphenoxy)phosphazene](PNGEGPhPh) were blended with PLGA at various weight ratios to yield different blends, namely PNEPAGEG-PLGA 25:75, PNEPAGEG-PLGA 50:50, PNGEGPhPh-PLGA 25:75, and PNGEGPhPh-PLGA 50:50.

Synthesis, Physicochemical Analysis, and Side Group Optimization of Degradable Dipeptide-Based Polyphosphazenes as Potential Regenerative Biomaterials.

We report the synthesis and physicochemical analysis of mixed-substituent dipeptide-based polyphosphazene polymers, poly[(glycineethylglycinato) (phenylphenoxy) phosphazene] (PNGEG PhPh ) and poly[(ethylphenylalanato) (glycineethylglycinato) phosphazene] (PNEPA GEG ), 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.

New cross-linkable poly[bis(octafluoropentoxy) phosphazene] biomaterials: Synthesis, surface characterization, bacterial adhesion, and plasma coagulation responses.

Biomaterial-associated microbial infection and thrombosis represent major issues to the success of long-term use of implantable blood-contacting medical devices. The development of new poly[bis(octafluoropentoxy) phosphazene (OFP) biomaterials provides new routes for combatting microbial infection and thrombosis. However, the limited mechanical properties of OFP to date render them unsuitable for application in medical devices and inhibit any attempts at subsequent surface topography modification.

Polyphosphazene polymers: The next generation of biomaterials for regenerative engineering and therapeutic drug delivery.

The demand for new biomaterials in several biomedical applications, such as regenerative engineering and drug delivery, has increased over the past two decades due to emerging technological advances in biomedicine. Degradable polymeric biomaterials continue to play a significant role as scaffolding materials and drug devices. Polyphosphazene platform is a subject of broad interest, as it presents an avenue for attaining versatile polymeric materials with excellent structure and property tunability, and high functional diversity.

Crystal structures of three hexakis-(fluoroar-yloxy)cyclo-triphosphazenes.

The syntheses and crystal structures of three cyclo-triphosphazenes, all with fluorinated ar-yloxy side groups that generate different steric characteristics, . hexa-kis-(penta-fluoro-phen-oxy)cyclo-triphosphazene, NP(OCF), , hexa-kis-[4-(tri-fluoro-methyl)-phen-oxy]cyclo-triphosphazene, NP[OCH(CF)], and hexa-kis-[3,5-bis(-tri-fluoro-methyl)-phen-oxy]cyclo-triphosphazene, NP[OCH(CF)] , are reported. Specifically, each phospho-rus atom bears either two penta-fluoro-phen-oxy, 4-tri-fluoro-methyl-phen-oxy, or 3,5-tri-fluoro-methyl-phen-oxy groups.

Generational Biodegradable and Regenerative Polyphosphazene Polymers and their Blends with Poly (lactic-co-glycolic acid).

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.

A new textured polyphosphazene biomaterial with improved blood coagulation and microbial infection responses.

Unlabelled: A new poly[bis(octafluoropentoxy) phosphazene] (OFP) was synthesized for the purpose of blood contacting medical devices. OFP was further either developed into crosslinkable polyphosphazene (X-OFP) or blended with polyurethane (PU) as the mixture (OFP/PU) for improvement of mechanical property of polyphosphazene polymers. All the materials were fabricated as smooth films or further textured with submicron pillars for the assay of antimicrobial and antithrombotic properties.

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering.

Unlabelled: 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.

Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering.

Rotator cuff (RC) tears represent a large proportion of musculoskeletal injuries attended to at the clinic and thereby make RC repair surgeries one of the most widely performed musculoskeletal procedures. Despite the high incidence rate of RC tears, operative treatments have provided minimal functional gains and suffer from high re-tear rates. The hypocellular nature of tendon tissue poses a limited capacity for regeneration.

Tunable, biodegradable gold nanoparticles as contrast agents for computed tomography and photoacoustic imaging.

Gold nanoparticles (AuNP) have been proposed for many applications in medicine. Although large AuNP (>5.5 nm) are desirable for their longer blood circulation and accumulation in diseased tissues, small AuNP (<5.

The expanding field of polyphosphazene high polymers.

The importance of phosphorus in polymer chemistry is illustrated by the growth of the broad field of polyphosphazene science. Several hundred high polymers are now known with a phosphorus-nitrogen backbone and combinations or more than 250 different organic side groups. The properties of these polymers depend on both the character of the inorganic backbone and the structure of the organic side groups.

Polyphosphazenes with Immobilized Dyes as Potential Color Filter Materials.

Red, green, and blue dye molecules were linked covalently to polyphosphazenes to generate soluble, film-forming materials appropriate for the formation of patterned tricolor filters for possible use in liquid crystalline and other display devices or in camera sensors. The monofunctional dyes (a red 1-[(E)-(4-nitrophenyl)diazenyl]-2-naphthol, a green tetraphenylporphyrin [5-(4-hydroxyphenyl)-10,15,20-tetraphenylporphyrin], and a toluidine blue dye) were employed as representative chromophores. The cosubstituents employed included 2,2,2-trifluoroethoxy with and without aryloxy groups or cyclopentanoxy groups.

Nanodisco balls: control over surface versus core loading of diagnostically active nanocrystals into polymer nanoparticles.

Nanoparticles of complex architectures can have unique properties. Self-assembly of spherical nanocrystals is a high yielding route to such systems. In this study, we report the self-assembly of a polymer and nanocrystals into aggregates, where the location of the nanocrystals can be controlled to be either at the surface or in the core.

Organophosphates as solvents for electrolytes in electrochemical devices.

A homologous series of fire-retardant oligoalkyleneoxy-phosphates was synthesized for evaluation as liquid or gel-type electrolyte media for dye-sensitized solar cells (DSSCs) and secondary lithium batteries. Unoptimized DSSC electrolyte formulations for DSSCs achieved ionic conductivities as high as 5.71 × 10(-3) S · cm(-1) and DSSC test-cell efficiencies up to 3.

Substituent exchange reactions of linear oligomeric aryloxyphosphazenes with sodium 2,2,2-trifluoroethoxide.

Side-group-exchange reactions have been studied for short-chain linear oligomeric phosphazenes, (RO)(4)P[N═P(OR(2))](n)OR (n = 6, 10, 20, and 40) as models for the corresponding linear high polymers (n ~ 15000). Specifically, the exchange behavior of oligomers where OR = OCH(2)CF(3), OC(6)H(5), OC(6)H(4)CHO-p, OC(6)H(4)CN-p, and OC(6)H(4)NO(2)-p with sodium trifluoroethoxide was examined. The ease of aryloxy group replacement by trifluoroethoxy increased with the electron-withdrawing character in the order OR = OC(6)H(5) ≪ OC(6)H(4)CHO-p < OC(6)H(4)CN-p < OC(6)H(4)NO(2)-p, but the reaction was efficient only if the phosphazene contained no more than 20 repeating units.

Polyphosphazene Elastomers, Gels, and Other Soft Materials.

Nearly all soft materials are based on organic polymer molecules. In other words they are derived from macromolecules constructed around the chemistry of carbon. Yet there are roughly 100 other elements in the periodic table that could in principle provide the building blocks for polymers and for soft materials.

Toward an iron(II) spin-crossover grafted phosphazene polymer.

Two new cyclotriphosphazene ligands with pendant 2,2':6',2″-terpyridine (Terpy) moieties, namely, (pentaphenoxy){4-[2,6-bis(2-pyridyl)]pyridoxy}cyclotriphosphazene (L(1)), (pentaphenoxy){4-[2,6-terpyridin-4-yl]phenoxy}cyclotriphosphazene (L(2)), and their respective polymeric analogues, L(1P) and L(2P), were synthesized. These ligands were used to form iron(II) complexes with an Fe(II)Terpy(2) core. Variable-temperature resonance Raman, UV-visible, and Mössbauer spectroscopies with magnetic measurements aided by density functional theory calculations were used to understand the physical characteristics of the complexes.

Polyphosphazene functionalized polyester fiber matrices for tendon tissue engineering: in vitro evaluation with human mesenchymal stem cells.

Poly[(ethyl alanato)(1)(p-methyl phenoxy)(1)] phosphazene (PNEA-mPh) was used to modify the surface of electrospun poly(ε-caprolactone) (PCL) nanofiber matrices having an average fiber diameter of 3000 ± 1700 nm for the purpose of tendon tissue engineering and augmentation. This study reports the effect of polyphosphazene surface functionalization on human mesenchymal stem cell (hMSC) adhesion, cell-construct infiltration, proliferation and tendon differentiation, as well as long term cellular construct mechanical properties. PCL fiber matrices functionalized with PNEA-mPh acquired a rougher surface morphology and led to enhanced cell adhesion as well as superior cell-construct infiltration when compared to smooth PCL fiber matrices.