Paul S. Engel

Injectable biodegradable polymer composites based on poly(propylene fumarate) crosslinked with poly(ethylene glycol)-dimethacrylate

New injectable, in situ crosslinkable biodegradable polymer composites were investigated consisting of poly(propylene fumarate) (PPF), poly(ethylene glycol)-dimethacrylate (PEG-DMA), and beta-tricalcium phosphate (beta-TCP). We examined the effects of the PEG-DMA/PPF double-bond ratio and beta-TCP content on the crosslinking characteristics of the composites including the maximum crosslinking temperature and the gel point, as well as the properties of the crosslinked composites such as the compressive strength and modulus, and the water-holding capacity. The maximum crosslinking temperature was constant averaging 39.7 degrees C for the composite formulations tested. The gel points varied from 8.0 +/- 1.0 to 12.6 +/- 2.5 min and were not affected by the relative amounts of PEG-DMA. The compressive strength at yield of PEG-DMA/PPF composites without beta-TCP increased from 5.9 +/- 1.0 to 11.2 +/- 2.2 MPa as the double-bond ratio of PEG-DMA/PPF increased from 0.38 to 1.88. An increase in compressive modulus was also observed from 30.2 +/- 3.5 to 58.4 +/- 6.2 MPa for the same range of the PEG-DMA/PPF double-bond ratio. Also, the addition of beta-TCP (33 wt%) enhanced the mechanical properties of all composites. The equilibrium water content of networks without beta-TCP increased from 21.7 +/- 0.2 to 30.6 +/- 0.2% for a double-bond ratio of PEG-DMA/PPF ranging from 0.38 to 1.88. However, the mechanical properties of the swollen composites under compression were smaller than the dry ones. These data demonstrate the feasibility of fabricating injectable biodegradable polymer composites with engineered mechanical properties for orthopedic tissue engineering.

Synthesis of biodegradable poly(propylene fumarate) networks with poly(propylene fumarate)-diacrylate macromers as crosslinking agents and characterization of their degradation products

Abstract New biodegradable poly(propylene fumarate)-based polymer networks have been prepared by radical polymerization using poly(propylene fumarate) (PPF) and poly(propylene fumarate)–diacrylate (PPF–DA) macromers. Two PPF–DAs were synthesized incorporating one (m=1) and two (m=2) fumarate units, and were employed in the synthesis of the polymer networks. The PPF/PPF–DA double bond ratio and the molecular weight of PPF–DA were varied to assess their effects on the mechanical properties of the resulting polymer networks as well as on their equilibrium water content. The compressive strength at fracture of PPF/PPF–DA (m=1) polymer networks increased from 11.2±1.8 to 66.2±5.5 MPa as the double bond ratio of PPF/PPF–DA (m=1) decreased from 4 to 0.5. An increase in compressive modulus was also observed from 19.4±1.8 to 340.2±30.7 MPa for the same range of the double bond ratio of PPF/PPF–DA. Increasing the molecular weight of PPF–DA (m=2) caused both the compressive strength at fracture and modulus of the corresponding polymer networks to increase to the ranges of 14.4±4.2 to 88.2±6.1 MPa and 28.0±2.4 to 480.4±35.9 MPa , respectively. Similarly, both were increased as the PPF/PPF–DA (m=2) double bond ratio decreased from 4 to 0.5. The PPF/PPF–DA crosslinked polymer networks showed negligible equilibrium water content for all 10 formulations tested in this study. The degradation reaction of the PPF/PPF–DA polymer networks under basic conditions was investigated. The degradation products were isolated and characterized by NMR and GC/MS as fumaric acid, propylene glycol, and poly(acrylic acid-co-fumaric acid) of weight average molecular weight of 5080. These data demonstrate that biodegradable PPF/PPF–DA polymer networks should have great potential as polymer scaffolds for orthopedic applications in tissue engineering.

Synthetic biodegradable polymers for orthopaedic applications.

Synthetic biodegradable polymers offer an alternative to the use of autografts, allografts, and nondegradable materials for bone replacement. They can be synthesized with tailored mechanical and degradative properties. They also can be processed to porous scaffolds with desired pore morphologic features conducive to tissue ingrowth. Moreover, functionalized polymers can modulate cellular function and induce tissue ingrowth. This review focuses on four classes of polymers that hold promise for orthopaedic applications: poly alpha-hydroxy esters, polyphosphazenes, polyanhydrides, and polypropylene fumarate crosslinked networks.

Synthesis and properties of photocross-linked poly(propylene fumarate) scaffolds

The photocross-linking of poly(propylene fumarate) (PPF) to form porous scaffolds for bone tissue engineering applications was investigated. PPF was cross-linked using the photoinitiator bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO) and exposure to 30 min of long wavelength ultraviolet (UV) light. The porous photocross-linked PPF scaffolds (6.5 mm diameter cylinders) were synthesized by including a NaCl porogen (70, 80, and 90 wt% at cross-linking) prior to photocross-linking. After UV exposure, the samples were placed in water to remove the soluble porogen, revealing the porous PPF scaffold. As porogen leaching has not been used often with cross-linked polymers, and even more rarely with photoinitiated cross-linking, a study of the efficacy of this strategy and the properties of the resulting material was required. Results show that the inclusion of a porogen does not significantly alter the photoinitiation process and the resulting scaffolds are homogeneously cross-linked throughout their diameter. It was also shown that porosity can be generally controlled by porogen content and that scaffolds synthesized with at least 80 wt% porogen possess an interconnected pore structure. Compressive mechanical testing showed scaffold strength to decrease with increasing porogen content. The strongest scaffolds with interconnected pores had an elastic modulus of 2.3 ± 0.5 MPa and compressive strength at 1% yield of 0.11 ± 0.02 MPa. This work has shown that a photocross-linking/porogen leaching technique is a viable method to form porous scaffolds from photoinitiated materials.

Kinetics of poly(propylene fumarate) synthesis by step polymerization of diethyl fumarate and propylene glycol using zinc chloride as a catalyst

Diethyl fumarate and propylene glycol were reacted in the presence of a zinc chloride catalyst to synthesize poly(propylene fumarate) (PPF) over a period of 12 hours. The kinetics of the transesterification polymerization at 130°C, 150°C, and 200°C were determined by gel permeation chromatography (GPC) analysis. The initial rate of polymerization at each temperature was quantified by calculating the rate of change of the number average molecular weight (Mn). At 200°C, gelation of the PPF occurred after 4 h. GPC analysis of the reaction showed that PPF synthesized at 150°C had a higher final Mn of 4600 (±190) and a higher weight average molecular weight of 10 500 (±760) than at 130°C (n = 3). The chemical structure of the PPF was verified by NMR and FT-IR analysis. This study demonstrated that the maximum Mn of PPF by a transesterification reaction is limited due to gelation of PPF at high temperature.

Characterization of partially saturated poly(propylene fumarate) for orthopaedic application

A partially saturated linear polyester based on poly(propylene fumarate) (PPF) was synthesized for potential application in filling skeletal defects. The synthesis was carried out according to a two-step reaction scheme. Propylene glycol and fumaryl chloride were first combined to form an intermediate fumaric diester. The intermediate was then subjected to a transesterification to form the PPF-based polymer. This method allowed for production of a polymer with a number average molecular weight up to 1500 and a polydispersity index of 2.8 and below. The polymeric backbone structure was investigated through the use of FTIR and NMR. Kinetic studies of the transesterification allowed mapping of the molecular weight increase with reaction time. The final product was also characterized by thermal and solubility analysis.

Computation of bond dissociation energies of substituted methanes with density functional theory

Abstract Density functional theory has been used to calculate bond dissociation energies of substituted methanes and radical stabilization energies obtained are compared to other systems.

Synthesis and Characterization of Injectable, Biodegradable, Phosphate-Containing, Chemically Cross-Linkable, Thermoresponsive Macromers for Bone Tissue Engineering

Novel, injectable, biodegradable macromer solutions that form hydrogels when elevated to physiologic temperature via a dual chemical and thermo-gelation were fabricated and characterized. A thermogelling, poly(N-isopropylacrylamide)-based macromer with pendant phosphate groups was synthesized and subsequently functionalized with chemically cross-linkable methacrylate groups via degradable phosphate ester bonds, yielding a dual-gelling macromer. These dual-gelling macromers were tuned to have transition temperatures between room temperature and physiologic temperature, allowing them to undergo instantaneous thermogelation as well as chemical gelation when elevated to physiologic temperature. Additionally, the chemical cross-linking of the hydrogels was shown to mitigate hydrogel syneresis, which commonly occurs when thermogelling materials are raised above their transition temperature. Finally, degradation of the phosphate ester bonds of the cross-linked hydrogels yielded macromers that were soluble at physiologic temperature. Further characterization of the hydrogels demonstrated minimal cytotoxicity of hydrogel leachables as well as in vitro calcification, making these novel, injectable macromers promising materials for use in bone tissue engineering.

Selective photochemical functionalization of surfactant-dispersed single wall carbon nanotubes in water.

Ultraviolet (UV) irradiation of single wall carbon nanotubes (SWCNTs) individually dispersed in surfactants leads to diameter and type-selective photohydroxylation of the nanotubes. Photohydroxylation of first semiconductor and then small diameter metallic SWCNTs was confirmed after 254 nm UV irradiation in acidic, neutral, and basic aqueous solutions at ambient and elevated temperatures. The increased oxygen content of the SWCNTs after UV irradiation, as detected by X-ray photoelectron spectroscopy, suggests that SWCNTs were hydroxylated by reaction with water. Attenuated total reflectance Fourier transform infrared analysis provides evidence of hydroxyl functional groups on their surface. This photochemical reaction is impeded by molecular oxygen and appears to involve a reactive intermediate generated in the vicinity of semiconducting SWCNTs. This represents a noncontaminating selective reaction in the liquid phase that uses an intrinsic property of the tubes.

Thermochemistry of nine diazenes (azo compounds)

Abstract Enthalpies of combustion of five diazenes and enthalpies of vaporization of nine diazenes have been measured. The experimental results yield values of the enthalpies of formation for the condensed and gaseous states of these compounds: di- n -propyldiazene; di- i -propyldiazene; di- t -butyldiazene; t -butyl(1,1,3,3-tetramethylbutyl)diazene; di(1,1,3,3-tetramethylbutyl)diazene; 1,1,3,3-tetramethyltrimethylenediazene; 1,1,4,4-tetramethyltetramethylenediazene; 2,3-diazabicyclo[2.2.1]heptene-2; and 1,4-dimethyl-2.3-diazabicyclo-[2.2.2]-octene-2.