Biomedical subjects

Seongbong Jo

Publications and source records attributed to Seongbong Jo.

10 recordsLinked to original sources

PubMed2006

Reverse thermal gelation of aliphatically modified biodegradable triblock copolymers.

A simple aliphatic modification demonstrated how to turn a water-soluble biodegradable triblock copolymer synthesized from PEG, L-lactide, and epsilon-caprolactone into a thermoreversible polymer of which aqueous solution underwent a sol-to-gel phase transition upon a mild temperature rise. Thermogelling behavior of the aliphatically modified polymer was dependent on the degree of aliphatic modification and polymer concentration. When the polymer solutions were subcutaneously injected into rats, immediate depot formation has been observed. The polymeric gel depots have lasted for two weeks in vivo. This aliphatically modified thermogelling polymer can find applications in drug delivery.

Animals↗

PubMed2006

Cholesteryl oligoarginine delivering vascular endothelial growth factor siRNA effectively inhibits tumor growth in colon adenocarcinoma.

Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic growth factor that is a primary stimulant of the development and maintenance of a vascular network in the vascularization of solid tumors. It has been reported that a blockade of VEGF-mediated angiogenesis is a powerful method for tumor regression. RNA interference represents a naturally occurring biological strategy for inhibition of gene expression. In mammalian systems, however, the in vivo application of small interfering RNA (siRNA) is severely limited by the instability and poor bioavailability of unmodified siRNA molecules. In this study, we tested the hypothesis that a hydrophobically modified protein transduction domain, cholesteryl oligo-d-arginine (Chol-R9), may stabilize and enhance tumor regression efficacy of the VEGF-targeting siRNA. The noncovalent complexation of a synthetic siRNA with Chol-R9 efficiently delivered siRNA into cells in vitro. Moreover, in a mouse model bearing a subcutaneous tumor, the local administration of complexed VEGF-targeting siRNA, but not of scrambled siRNA, led to the regression of the tumor. Hence, we propose a novel and simple system for the local in vivo application of siRNA through Chol-R9 for cancer therapy.

Adenocarcinoma↗

PubMed2004

Thermoreversible hydrogel scaffolds for articular cartilage engineering.

Articular cartilage has limited potential for repair. Current clinical treatments for articular cartilage damage often result in fibrocartilage and are associated with joint pain and stiffness. To address these concerns, researchers have turned to the engineering of cartilage grafts. Tissue engineering, an emerging field for the functional restoration of articular cartilage and other tissues, is based on the utilization of morphogens, scaffolds, and responding progenitor/stem cells. Because articular cartilage is a water-laden tissue and contains within its matrix hydrophilic proteoglycans, an engineered cartilage graft may be based on synthetic hydrogels to mimic these properties. To this end, we have developed a polymer system based on the hydrophilic copolymer poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)]. Solutions of this polymer are liquid below 25 degrees C and gel above 35 degrees C, allowing an aqueous solution containing cells at room temperature to form a hydrogel with encapsulated cells at physiological body temperature. The objective of this work was to determine the effects of the hydrogel components on the phenotype of encapsulated chondrocytes. Bovine articular chondrocytes were used as an experimental model. Results demonstrated that the components required for hydrogel fabrication did not significantly reduce the proteoglycan synthesis of chondrocytes, a phenotypic marker of chondrocyte function. In addition, chondrocyte viability, proteoglycan synthesis, and type II collagen synthesis within P(PF-co-EG) hydrogels were investigated. The addition of bone morphogenetic protein-7 increased chondrocyte proliferation with the P(PF-co-EG) hydrogels, but did not increase proteoglycan synthesis by the chondrocytes. These results indicate that the temperature-responsive P(PF-co-EG) hydrogels are suitable for chondrocyte delivery for articular cartilage repair.

Animals↗

PubMed2003

Biomimetic materials for tissue engineering.

The development of biomaterials for tissue engineering applications has recently focused on the design of biomimetic materials that are capable of eliciting specific cellular responses and directing new tissue formation mediated by biomolecular recognition, which can be manipulated by altering design parameters of the material. Biomolecular recognition of materials by cells has been achieved by surface and bulk modification of biomaterials via chemical or physical methods with bioactive molecules such as a native long chain of extracellular matrix (ECM) proteins as well as short peptide sequences derived from intact ECM proteins that can incur specific interactions with cell receptors. The biomimetic materials potentially mimic many roles of ECM in tissues. For example, biomimetic scaffolds can provide biological cues for cell-matrix interactions to promote tissue growth, and the incorporation of peptide sequences into materials can also make the material degradable by specific protease enzymes. This review discusses the surface and bulk modification of biomaterials with cell recognition molecules to design biomimetic materials for tissue engineering. The criteria to design biomimetic materials such as the concentration and spatial distribution of modified bioactive molecules are addressed. Recent advances for the development of biomimetic materials in bone, nerve, and cardiovascular tissue engineering are also summarized.

Amino Acid Sequence↗

PubMed2003

Crosslinking characteristics of and cell adhesion to an injectable poly(propylene fumarate-co-ethylene glycol) hydrogel using a water-soluble crosslinking system.

The crosslinking characteristics of an injectable poly(propylene fumarate-co-ethylene glycol) [P(PF-co-EG)]-based hydrogel were investigated. A water-soluble crosslinking system was used, consisting of poly(ethylene glycol) diacrylate (PEG-DA), ammonium persulfate (APS), and ascorbic acid (AA). The effects of PEG block length of the P(PF-co-EG), APS concentration, AA concentration, and PEG-DA concentration on equilibrium water content, sol fraction, onset of gelation, mechanical properties, and endothelial cell adhesion were studied. The equilibrium water content of the hydrogels ranged from 57.1 +/- 0.3 to 79.7 +/- 0.2% whereas the sol fraction ranged from 2.5 +/- 0.0 to 3.33 +/- 5.4%. The onset of gelation times varied from 1.1 +/- 0.1 to 4.3 +/- 0.2 min. For all hydrogel formulations, the tensile strength fell between 61.7 +/- 18.2 and 401.3 +/- 67.5 kPa and tensile moduli ranged from 0.4 +/- 0.0 to 3.3 +/- 0.3 MPa. Endothelial cells attached to the hydrogels in a range of 3.9 +/- 1.4 to 31.1 +/- 14.1% of cells seeded. These findings suggest that injectable poly(propylene fumarate-co-ethylene glycol) hydrogel formulations in conjunction with a novel water-soluble crosslinking system may be useful for in situ crosslinkable tissue-engineering applications.

Ammonium Sulfate↗

PubMed2002

Modulation of marrow stromal osteoblast adhesion on biomimetic oligo[poly(ethylene glycol) fumarate] hydrogels modified with Arg-Gly-Asp peptides and a poly(ethyleneglycol) spacer.

Novel oligo[poly(ethylene glycol) fumarate] (OPF) hydrogels functionalized with cell adhesion peptides were prepared, and the effects of incorporated peptide density and macromolecular structure of hydrogels on attachment and morphology of marrow stromal cells (MSCs) were evaluated. Poly(ethylene glycol) (PEG; number average molecular weight of 930, 2860, and 6090) was used to synthesize OPF. A model peptide, Gly-Arg-Gly-Asp (GRGD), was incorporated into OPF hydrogels after being coupled to acrylated PEG of molecular weight 3400. The increase of incorporated peptide concentration enhanced MSC attachment to OPF hydrogels of PEG of molecular weight of 930 and 2860. However, the number of attached MSCs to OPF hydrogels of PEG (molecular weight 6090) remained constant regardless of the peptide density. The length of PEG in OPF also influenced cell attachment. When 1 micromole peptide/g hydrogel was incorporated into the OPF hydrogels, the degree of cell attachment at 12 h relative to the initial seeding density was 93.9 +/- 5.9%, 64.7 +/- 8.2%, and 9.3 +/- 6.6% for OPF hydrogels prepared with PEG of molecular weights of 930, 2860, and 6090, respectively. However, the crosslinking density of hydrogels did not significantly affect cell attachment. The interaction was sequence specific, in that MSC attachment to GRGD-modified hydrogels was competitively inhibited when cells were incubated in the presence of 0.5 mM soluble GRGD before cell seeding. These results suggest that we can modulate MSC attachment to OPF hydrogels by altering the peptide density and the molecular structure of OPF hydrogels.

Animals↗

PubMed2002

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 degrees C, 150 degrees C, and 200 degrees 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 degrees C, gelation of the PPF occurred after 4 h. GPC analysis of the reaction showed that PPF synthesized at 150 degrees C had a higher final Mn of 4600 (+/- 190) and a higher weight average molecular weight of 10500 (+/- 760) than at 130 degrees 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.

Bone Cements↗

PubMedDate not supplied

Synthesis and characterization of triblock copolymers of methoxy poly(ethylene glycol) and poly(propylene fumarate).

Amphiphilic block copolymers were synthesized by transesterification of hydrophilic methoxy poly(ethylene glycol) (mPEG) and hydrophobic poly(propylene fumarate) (PPF) and characterized. Four block copolymers were synthesized with a 2:1 mPEG:PPF molar ratio and mPEGs of molecular weights 570, 800, 1960, and 5190 and PPF of molecular weight 1570 as determined by NMR. The copolymers synthesized with mPEG of molecular weights 570 and 800 had 1.9 and 1.8 mPEG blocks per copolymer, respectively, as measured by NMR, representing an ABA-type block copolymer. The number of mPEG blocks of the copolymer decreased with increasing mPEG block length to as low as 1.5 mPEG blocks for copolymer synthesized with mPEG of molecular weight 5190. At a concentration range of 5-25 wt % in phosphate-buffered saline, copolymers synthesized with mPEG molecular weights of 570 and 800 possessed lower critical solution temperatures (LCST) between 40 and 45 degrees C and between 55 and 60 degrees C, respectively. Aqueous solutions of copolymer synthesized with mPEG 570 and 800 also experienced thermoreversible gelation. The sol-gel transition temperature was dependent on the sodium chloride concentration as well as the mPEG block length. The copolymer synthesized from mPEG 570 had a transition temperature between 40 and 20 degrees C with salt concentrations between 1 and 10 wt %, while the sol-gel transition temperatures of the copolymer synthesized from mPEG molecular weight 800 were higher in the range 75-30 degrees C with salt concentrations between 1 and 15 wt %. These novel thermoreversible copolymers are the first biodegradable copolymers with unsaturated double bonds along their macromolecular chain that can undergo both physical and chemical gelation and hold great promise for drug delivery and tissue engineering applications.

Biocompatible Materials↗

PubMedDate not supplied

Synthesis of in situ cross-linkable macroporous biodegradable poly(propylene fumarate-co-ethylene glycol) hydrogels.

This study describes a synthesis method of biodegradable macroporous hydrogels suitable as in situ cross-linkable biomaterials. Macroporous hydrogels were based on poly(propylene fumarate-co-ethylene glycol) and prepared via coupled free radical and pore formation reactions. Cross-linking was initiated by a pair of redox initiators, ammonium persulfate and L-ascorbic acid. Pores were formed by the reaction between L-ascorbic acid and sodium bicarbonate, a basic component, which evolved carbon dioxide. Sol fraction of the hydrogels was varied from 0.06 +/- 0.01 to 0.64 +/- 0.01. A stereological approach was used to analyze the morphological properties of the macroporous hydrogels by relating the morphological properties of thin sections to the original three-dimensional macroporous hydrogel. Prepared macroporous hydrogels had porosities between 0.43 +/- 0.08 and 0.84 +/- 0.02 and surface area densities between 55 +/- 3 and 108 +/- 7 cm(-1). Sodium bicarbonate concentration had the greatest effect on both the porosity and surface area density. The effect of copolymer formulation on the porosity and surface area density was insignificant. From thin sections of the macroporous hydrogels, the profile size distributions were determined as an estimate of the pore size distribution. Two formulations synthesized with varying L-ascorbic acid concentration of 0.05 and 0.1 M had median profile sizes of 50-100 and 150-200 microm, respectively. This novel synthesis method allows for the in situ cross-linking of biodegradable macroporous hydrogels with morpholological properties suitable for consideration as an injectable tissue engineering scaffold.

Biodegradation, Environmental↗

PubMedDate not supplied

Synthesis and characterization of biodegradable cationic poly(propylene fumarate-co-ethylene glycol) copolymer hydrogels modified with agmatine for enhanced cell adhesion.

We synthesized positively charged biodegradable hydrogels by cross-linking of agmatine-modified poly(ethylene glycol)-tethered fumarate (Agm-PEGF) and poly(propylene fumarate-co-ethylene glycol) (P(PF-co-EG)) to investigate the effect of the guanidino groups of the agmatine on hydrogel swelling behavior and smooth muscle cell adhesion to the hydrogels. The weight swelling ratio of these hydrogels at pH 7.0 increased from 279 +/- 4 to 306 +/- 7% as the initial Agm-PEGF content increased from 0 to 200 mg/g of P(PF-co-EG), respectively. The diffusional exponents, n, during the initial phase of water uptake were independent of the initial Agm-PEGF content and were determined to be 0.66 +/- 0.08, 0.71 +/- 0.07, and 0.60 +/- 0.05 for respective initial Agm-PEGF contents of 0, 100, and 200 mg/g. The heat of fusion of water present in the hydrogels increased from 214 +/- 11 to 254 +/- 4 J/g as the initial Agm-PEGF content increased from 0 to 200 mg/g. The number of adherent smooth muscle cells increased dose-dependently from 15 +/- 6 to 75 +/- 7% of the initial seeding density as the initial Agm-PEGF content increased from 0 to 200 mg/g. These results suggest that the incorporation of the guanidino groups of agmatine into P(PF-co-EG) hydrogels increases the hydrogel free water content and the total water content of the hydrogels and also enhances cell adhesion to the hydrogels.

Agmatine↗