Woo Sun Shim

Injectable In Situ–Forming pH/Thermo-Sensitive Hydrogel for Bone Tissue Engineering

We developed a novel pH- and thermo-sensitive hydrogel as a scaffold for autologous bone tissue engineering. We synthesized this polymer by adding pH-sensitive sulfamethazine oligomers (SMOs) to both ends of a thermo-sensitive poly(epsilon-caprolactone-co-lactide)-poly(ethylene glycol)-poly(epsilon-caprolactone-co-lactide) (PCLA-PEG-PCLA) block copolymer, yielding a pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer. The synthesized block copolymer solution rapidly formed a stable gel under physiological conditions (pH 7.4 and 37 degrees C), whereas it formed a sol at pH 8.0 and 37 degrees C, making it injectable. This pH/thermo-sensitive hydrogel exhibited high biocompatibility in a Dulbeccos modified Eagles medium extract test. Under physiological conditions, the hydrogel easily encapsulated human mesenchymal stem cells (hMSCs) and recombinant human bone morphogenetic protein-2 (rhBMP-2), with encapsulating efficiencies of about 90% and 85%, respectively. To assay for ectopic bone formation in vivo, we subcutaneously injected a polymer solution containing hMSCs and rhBMP-2 into the back of mice, after which we could observe hMSC differentiation for up to 7 weeks. Histological studies revealed mineralized tissue formation and high levels of alkaline phosphatase activity in the mineralized tissue. Therefore, this pH/thermo-sensitive SMO-PCLA-PEG-PCLA-SMO block copolymer demonstrated potential as an injectable scaffold for bone tissue engineering, with in situ formation capabilities.

Polypyrrole/thermally sensitive polyelectrolyte composite (I)

Abstract Polypyrrole (PPy) was prepared by electrochemical polymerization with the polyelectrolyte (PE) as a dopant. The PEs were copolymers of the water soluble polymers and 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS). The water soluble polymers were thermally sensitive poly( N -isopropyl acrylamide), P(NiPAAm) and thermally insensitive poly(acrylamide), P(AAm). The surface of PPy/PE film observed by SEM was smoother than that of PPy film doped with a monoelectrolyte. PPy/PE composites were fairly conductive, whose electrical conductivities measured by the four-probe method were in the range of 10 −1 to 10 −2 S/cm. The characteristics of cation and anion exchange during redox processes were investigated by applying potential from −0.8 to 0.5 V vs. an Ag/AgCl reference electrode to the PPy. The effect of temperature on the doping–dedoping behavior and mass change of PPy composites was investigated by potentiodynamic voltammetry and electrochemical quartz crystal microbalance (EQCM). The electrochemical activity of the PPy/PE gradually decreased with increasing temperature. PPy/P(NiPAAm/AMPS) showed much greater mass change with increasing temperature than PPy/P(AAm/AMPS), mainly because of a decrease in the degree of swelling of thermally sensitive moiety. This confirms that PPy/P(NiPAAm/AMPS) possesses temperature-dependent electrochemical activity, which indicates that it can be utilized for many attractive applications. The thermal volume transition temperature of PPy/P(NiPAAm/AMPS) was estimated from the slope change of mass decrease. The transition temperature of the oxidized state of PPy/P(NiPAAm/AMPS) was higher than that of the reduced state.

Electroactive and temperature‐sensitive hydrogel composites

The composites of the polypyrrole (PPy) and polyelectrolyte copolymers (PE) were prepared by electrochemical polymerization. The various compositions of the polyelectrolyte copolymers were used as a dopant, and were composed of copolymers of water-soluble polymers and 2-Acrylamido-2-methyl-1-propane sulfonic acid (AMPS). Thermally sensitive (N-isopropyl acrylamide, NiPAAm) and insensitive (acrylamide, AAm) polymers were used as the water-soluble polymer. The electrochemical activity and mass change during the redox process of the PPy composites were investigated by potentiodynamic voltametry and electrochemical quartz crystal microbalance (EQCM). The mass change during the redox process was mainly concerned with the cation in the electrolyte solution. When the electrochemical activity of the PPy was larger than the amount of the polyelectrolyte anion (AMPS), the insertion/expulsion of the monoanion (ClO - 4 ) into/from the PPy composite also occurred to ionically bond with the PPy in the redox process. The PPy/P(NiPAAm/AMPS) shows a significant mass decrease with increasing the temperature compared with the PPy/P(AAm/AMPS), The transition temperature of the PPy/P(NiPAAm/AMPS) is higher in the oxidized state than in the reduced state. The transition temperature of PPy composite increases with the composition of the hydrophilic electrolyte (AMPS).

pH-Induced Micellization of Biodegradable Block Copolymers Containing Sulfamethazine

AbstractpH-sensitive block copolymers were synthesized by coupling reaction of sulfamethazine and amphiphilic diblock copolymer, and their micellization-demicellization behavior was investigated. Sulfamethazine (SM), a derivative of sulfonamide, was introduced as a pH responsive moiety while methoxy poly(ethylene glycol)-poly(d,l-lactide) (MPEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactide-co-ε-caprolactone) (MPEG-PCLA) were used as biodegradable amphiphilic diblock copolymers. After the sulfamethazine was carboxylated by the reaction with succinic anhydride, the diblock copolymer was conjugated with sulfamethazine by coupling reaction in the presence of DCC. The critical micelle concentration (CMC) and mean diameter of the micelles were examined at various pH conditions through fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. For MPEG-PDLLA-SM and MPEG-PCLA-SM solutions, the pH-dependent micellization-demicellization was achieved within a narrow pH band, which was not observed in the MPEG-PDLLA and MPEG-PCLA solutions. The micelle showed a spherical morphology and had a very narrow size distribution. This pH-sensitive block copolymer shows potential as a site-targeted drug carrier.

Characterization of Poly(ethylene oxide)-b-Poly(L-lactide) Block Copolymer by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

A poly(ethylene oxide)-b-poly(L-lactide) diblock copolymer (PEO-b-PLLA) is characterized by matrixassisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and a block length distribution map is constructed. Although the MALDI-TOF mass spectrum of PEO-b-PLLA is very complicated, most of the polymer species were identified by isolating the overlapped isotope patterns and by fitting the overlapped peaks to the Schulz-Zimm distribution function. Reconstructed MALDI-TOF MS spectrum was nearly identical to the measured spectrum and this method shows its potential to be developed as an easy and fast analysis method of low molecular weight block copolymers.

pH-Induced Micellization of Sulfamethazine-Coupled MPEG-PCLA Block Copolymer

ConclusionsThe MPEG-PCLA-CSM-PCLA-MPEG block copolymer, with sulfamethazine as a pH-sensitive group, was synthesized, and the pH-sensitive micellization behavior was investigated. After coupling of the sulfamethazine with amphiphilic MPEG-PCLA block copolymer, the micellization-demicellization transition occurred at pH 6.0 and 2.6, due to the ionization of sulfonamide group and amine group, respectively. It is confirmed that the disassociation of micelle structure could be induced by the pH change, indicating that the targeted release would be possible. These micelles may be applicable to drug delivery system, diagnostic imaging as well as other potential applications.