Biomedical subjects

Oju Jeon

Publications and source records attributed to Oju Jeon.

10 recordsLinked to original sources

PubMed2007

Controlled release of nerve growth factor from fibrin gel.

Nerve growth factor (NGF) is known to promote the axonal regeneration in injured nerve system. Delivery of NGF for a long period in a controlled manner may enhance the regeneration efficacy. In this study, we investigated whether NGF can be released from fibrin gel for a long period in a controlled manner. We also investigated whether sustained delivery of NGF using fibrin gel can enhance the efficacy of NGF in vitro. The addition of heparin to fibrin gel decreased the rate of NGF release from the fibrin gel. As the concentrations of thrombin and fibrinogen in fibrin gel increased, the NGF release rate decreased significantly, and the initial release burst decreased. NGF was released for up to 14 days in vitro. The bioactivity of NGF released from fibrin gel was assessed by morphological changes of pheochromocytoma (PC12) cells cultured in the presence of NGF-containing fibrin gel. NGF released from fibrin gel exhibited significantly higher degrees of PC12 cell viability and differentiation than NGF added in a free form daily into the culture medium. This study demonstrates that fibrin gel can release NGF in a sustained, controlled manner and in a bioactive form.

Animals↗

PubMed2007

The effect of microsphere degradation rate on the efficacy of polymeric microspheres as bulking agents: an 18-month follow-up study.

The injection of bulking substances has been proposed as a new therapy to treat urinary incontinence and vesicoureteral reflux. Our previous study demonstrated that poly(lactic-co-glycolic acid) (PLGA) microspheres have the potential to serve as a bulking agent for urological injection therapies. Hybrid tissues exhibiting a bulking effect were formed in vivo by PLGA microsphere injection, but long-term volume stability was not proven. In this study, we hypothesized that the biodegradation rate of the bulking substance (polymer microspheres) would affect the duration of volume conservation of the induced hybrid tissue. To test this hypothesis, rapidly degrading 75:25 PLGA microspheres and slowly degrading poly(L-lactic acid) (PLLA) microspheres were used as injectable bulking agents for the injection therapy. In vitro degradation tests showed that the mass losses of PLLA and PLGA were 16 and 96% of the initial masses, respectively, at 30 weeks. PLLA and PLGA microspheres were injected into the subcutaneous dorsum of mice. Both types of microspheres were easily injectable through 24-gauge needles. Histological examinations at various time points indicated that host cells from the surrounding tissues migrated to the spaces between both types of injected microspheres and formed new hybrid tissue structures. Lymphocyte migration was noted around the implanted PLGA and PLLA microspheres, but the inflammatory reaction diminished with time. Importantly, the volume of the PLLA hybrid tissues slowly decreased to 52% of the initial volume at 12 months and maintained that volume until 18 months, whereas the volume of the PLGA hybrid tissues rapidly decreased to 22% at 6 months, and the PLGA hybrid tissues disappeared at 11 months. These results show that the biodegradation rate of the bulking substance may be useful for controlling the duration of volume conservation of the induced hybrid tissue.

Animals↗

PubMed2006

Effects of cardiac patches engineered with bone marrow-derived mononuclear cells and PGCL scaffolds in a rat myocardial infarction model.

Little is known about the cardioprotective effects against heart failure (HF), the effects on differentiation of bone marrow-derived mononuclear cell (BMMNC), and the biocompatibility of BMMNC-seeded biodegradable poly-glycolide-co-caprolactone (PGCL) scaffolds in a myocardial infarction (MI) animal model. This study hypothesized that implantation of a BMMNC-seeded PGCL scaffold into the epicardial surface in a rat MI model would be biocompatible, induce BMMNC migration into infarcted myocardium, and effectively improve left ventricular (LV) systolic dysfunction. One week after the implantation of a BMMNC-seeded PGCL scaffold, BMMMC showed migration into the epicardial region. Four weeks after implantation, augmented neovascularization was observed in infarcted areas and in infarct border zones. Some BMMNCs exhibited the presence of alpha-MHC and troponin I, markers of differentiation into cardiomyocytes. In echocardiographic examinations, BMMNC-seeded PGCL scaffold and non-cell-seeded simple PGCL scaffold groups effectively reduced progressive LV dilatation and preserved LV systolic function as compared to control rat MI groups. Thus, BMMNC-seeded PGCL scaffolding influences BMMNC migration, differentiation to cardiomyocytes, and induction of neovascularization, ultimately effectively lessening LV remodeling and progressive LV systolic dysfunction. PGCL scaffolding can be considered as an effective treatment alternative in MI-induced advanced HF.

Animals↗

PubMed2006

Preliminary experience with tissue engineering of a venous vascular patch by using bone marrow-derived cells and a hybrid biodegradable polymer scaffold.

OBJECTIVE: Currently available synthetic polymer vascular patches used in cardiovascular surgery have shown serious shortcomings, including thrombosis, calcification, infection, and lack of growth potential. These problems may be avoided by vascular patches tissue-engineered with autologous stem cells and biodegradable polymeric materials. The objective of this study was to develop a tissue-engineered vascular patch by using autologous bone marrow-derived cells (BMCs) and a hybrid biodegradable polymer scaffold. METHODS: Hybrid biodegradable polymer scaffolds were fabricated from poly(lactide-co-epsilon-caprolactone) (PLCL) copolymer reinforced with poly(glycolic acid) (PGA) fibers. Canine bone marrow mononuclear cells were induced in vitro to differentiate into vascular smooth muscle cells and endothelial cells. Tissue-engineered vascular patches (15 mm wide x 30 mm long) were fabricated by seeding vascular cells onto PGA/PLCL scaffolds and implanted into the inferior vena cava of bone marrow donor dogs. RESULTS: Compared with PLCL scaffolds, PGA/PLCL scaffolds exhibited tensile mechanical properties more similar to those of dog inferior vena cava. Eight weeks after implantation of vascular patches tissue-engineered with BMCs and PGA/PLCL scaffolds, the vascular patches remained patent with no sign of thrombosis, stenosis, or dilatation. Histological, immunohistochemical, and scanning electron microscopic analyses of the retrieved vascular patches revealed regeneration of endothelium and smooth muscle, as well as the presence of collagen. Calcium deposition on tissue-engineered vascular patches was not significantly different from that on native blood vessels. Immunofluorescent double staining confirmed that implanted BMCs survived after implantation and contributed to regeneration of endothelium and vascular smooth muscle in the implanted vascular patches. CONCLUSIONS: This study demonstrates that vascular patches can be tissue-engineered with autologous BMCs and hybrid biodegradable polymer scaffolds.

Absorbable Implants↗

PubMed2006

Combined sustained delivery of basic fibroblast growth factor and administration of granulocyte colony-stimulating factor: synergistic effect on angiogenesis in mouse ischemic limbs.

PURPOSE: To investigate whether the efficacy of a single angiogenic therapy (sustained delivery of basic fibroblast growth factor [bFGF] or administration of granulocyte colony-stimulating factor [G-CSF]) can be enhanced further by combining the therapies. METHODS: One day after surgical induction of hind-limb ischemia, groups of 6 mice were randomized to receive either no treatment, sustained delivery (SD) of bFGF, endothelial progenitor cell (EPC) mobilization with G-CSF administration, or a combination of bFGF SD + G-CSF administration. RESULTS: G-CSF administration increased significantly (p < 0.05) the number of EPC lineages (CD34 + /AC133 + cells) in both peripheral blood and bone marrow compared to no G-CSF administration. The bFGF SD and G-CSF administration individually increased the capillary and arteriole densities significantly versus no treatment (capillary density: 659 +/- 48/mm2 and 385 +/- 59/mm2, respectively, versus 280 +/- 28/mm2; p < 0.05; arteriole density: 34 +/- 9/mm2 and 41 +/- 6/mm2, respectively, versus 15 +/- 2/mm2; p<0.05). Importantly, bFGF SD + G-CSF further increased the capillary and arteriole densities compared to either strategy alone (capillary density: 786 +/- 40/mm2 versus 659 +/- 48/mm2 and 385 +/- 59/mm2, respectively, p < 0.05; arteriole density: 55 +/- 10/mm2 versus 34 +/- 9/mm2 and 41 +/- 6/mm2, respectively, p < 0.05). CONCLUSION: This study demonstrates that the combined therapy of sustained bFGF delivery and G-CSF administration potentiates the angiogenic efficacy of either single therapy in mouse hind-limb ischemia models.

Animals↗

PubMed2005

Poly(lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering.

Biodegradable polymer/bioceramic composite scaffolds can overcome the limitations of conventional ceramic bone substitutes such as brittleness and difficulty in shaping. However, conventional methods for fabricating polymer/bioceramic composite scaffolds often use organic solvents (e.g., the solvent casting and particulate leaching (SC/PL) method), which might be harmful to cells or tissues. Furthermore, the polymer solutions may coat the ceramics and hinder their exposure to the scaffold surface, which may decrease the likelihood that the seeded osteogenic cells will make contact with the bioactive ceramics. In this study, a novel method for fabricating a polymer/nano-bioceramic composite scaffold with high exposure of the bioceramics to the scaffold surface was developed for efficient bone tissue engineering. Poly(D,L-lactic-co-glycolic acid)/nano-hydroxyapatite (PLGA/HA) composite scaffolds were fabricated by the gas forming and particulate leaching (GF/PL) method without the use of organic solvents. The GF/PL method exposed HA nanoparticles at the scaffold surface significantly more than the conventional SC/PL method does. The GF/PL scaffolds showed interconnected porous structures without a skin layer and exhibited superior enhanced mechanical properties to those of scaffolds fabricated by the SC/PL method. Both types of scaffolds were seeded with rat calvarial osteoblasts and cultured in vitro or were subcutaneously implanted into athymic mice for eight weeks. The GF/PL scaffolds exhibited significantly higher cell growth, alkaline phosphatase activity, and mineralization compared to the SC/PL scaffolds in vitro. Histological analyses and calcium content quantification of the regenerated tissues five and eight weeks after implantation showed that bone formation was more extensive on the GF/PL scaffolds than on the SC/PL scaffolds. Compared to the SC/PL scaffolds, the enhanced bone formation on the GF/PL scaffolds may have resulted from the higher exposure of HA nanoparticles at the scaffold surface, which allowed for direct contact with the transplanted cells and stimulated the cell proliferation and osteogenic differentiation. These results show that the biodegradable polymer/bioceramic composite scaffolds fabricated by the novel GF/PL method enhance bone regeneration compared with those fabricated by the conventional SC/PL method.

Alkaline Phosphatase↗

PubMed2005

Synergistic effect of sustained delivery of basic fibroblast growth factor and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs.

Combined angiogenic therapies may be superior to single angiogenic therapy for treatment of limb ischemia. First, we investigated whether the angiogenic efficacy of basic fibroblast growth factor (bFGF) administration and bone marrow-derived mononuclear cell (BMMNC) transplantation can be enhanced by sustained delivery (SD) of bFGF and BMMNC transplantation using a matrix, respectively, in mouse ischemic limbs. Next, we investigated whether the angiogenic efficacy of combination of two angiogenic strategies is superior to either strategy alone. One day after surgical induction of mouse hindlimb ischemia, mice were randomized to receive either no treatment, daily injection (DI) of bFGF, SD of bFGF, BMMNC transplantation using culture medium, BMMNC transplantation using fibrin matrix (FM), or combination of SD of bFGF with BMMNC transplantation using FM. The SD of bFGF significantly increased the microvessel density, compared with DI of bFGF (659+/-48/mm2 versus 522+/-39/mm2, p<0.05). BMMNC transplantation using FM significantly increased the microvessel density, compared with BMMNC transplantation using culture medium (523+/-103/mm2 versus 415+/-75/mm2, p<0.05). Importantly, combination of bFGF sustained release with BMMNC transplantation using FM further increased the densities of microvessels and arterioles, compared to either strategy alone (p<0.05). The SD method of angiogenic protein and cell transplantation using matrix potentiate the angiogenic efficacy of bFGF and BMMNC transplantation, respectively, for limb ischemia. In addition, the combined therapy of SD of bFGF and BMMNC transplantation synergistically enhances angiogenesis in mouse ischemic limb, compared to each separate therapy.

Animals↗

PubMed2005

Long-term and zero-order release of basic fibroblast growth factor from heparin-conjugated poly(L-lactide-co-glycolide) nanospheres and fibrin gel.

Controlled long-term delivery of basic fibroblast growth factor (bFGF) could be used as an angiogenesis therapy. In this study, novel heparin-conjugated poly(L-lactide-co-glycolide) (PLGA) nanospheres (HCPNs) were developed for long-term, zero-order delivery of bFGF. HCPNs were prepared by using a coupling reaction between amino-terminated PLGA nanospheres and heparin in the presence of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide. The amount of heparin conjugated to the PLGA nanospheres was increased up to 29-fold by using nanospheres made from lower molecular weight PLGA, or star-shaped PLGA, as compared to nanospheres made from higher molecular weight PLGA, or linear PLGA. The release of bFGF from HCPNs was sustained for 3 weeks with no initial burst release. The bFGF release period was increased to more than 4 weeks using a delivery system of HCPNs suspended in fibrin gel. The release was nearly zero order. The rate of bFGF release from HCPNs in fibrin gel was controlled by the fibrinogen concentration in the fibrin gel. As the fibrinogen concentration increased, the bFGF release rate decreased. The bioactivity of bFGF released from HCPNs in fibrin gel was assessed using human umbilical vein endothelial cell (HUVEC) culture. bFGF released from HCPNs in fibrin gel exhibited HUVEC growth for 15 days, similar to that of cultures to which bFGF in free form was added daily, suggesting that the delivery system of HCPNs in fibrin gel can release bFGF in a bioactive form for a long period. The therapeutic potential of bFGF delivery using HCPNs in fibrin gel was investigated in a mouse limb ischemia model. Immunohistological analysis of mouse ischemic limbs indicated that the microvessel density was much higher in the ischemic limbs treated with bFGF delivery using HCPNs in fibrin gel than in the ischemic limbs treated with daily injections of bFGF or with bFGF delivery using fibrin gel. This study shows that a bFGF delivery system using HCPNs in fibrin gel exhibits controllable, long-term, zero-order release of bFGF and potentiates the angiogenic efficacy of bFGF administration.

Animals↗

PubMed2005

Control of basic fibroblast growth factor release from fibrin gel with heparin and concentrations of fibrinogen and thrombin.

Basic fibroblast growth factor (bFGF) has been known to stimulate the regeneration of a number of tissues including cartilage, nerve, skin, liver, and blood vessel. Delivery of bFGF for a long period in a controlled manner would enhance stimulative effects. The purpose of the present study is to test the hypothesis that the kinetics of bFGF release from fibrin gels could be controlled with heparin and concentrations of fibrinogen and thrombin. The kinetics of bFGF release from fibrin gels with various concentrations of fibrinogen, thrombin, and heparin was determined. The bioactivity of bFGF released from fibrin gels was assessed using dermal fibroblast cell culture. To examine the therapeutic potential of the bFGF delivery system, bFGF-loaded fibrin gels were injected into mouse ischemic limbs. The addition of heparin to fibrin gels decreased the bFGF release rate. As the thrombin content in fibrin gels increased, the bFGF release rate significantly decreased. Similarly, increased concentration of fibrinogen in fibrin gels decreased the bFGF release rate. Basic FGF released from fibrin gels exhibited significantly higher extents of fibroblast growth than bFGF added in a free form daily into the culture medium, suggesting that the fibrin gels may stabilize the bFGF bioactivity. Immunohistological analysis of mouse ischemic limbs indicated that the microvessel density was much higher in the ischemic limbs treated with injection of bFGF-loaded fibrin gels than in the ischemic limbs with no treatment. This study showed that the rate of bFGF release from fibrin gels can be controlled and that the bFGF delivery system has therapeutic potentials for angiogenesis.

Angiogenesis Inhibitors↗

PubMedDate not supplied

Poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for cartilage tissue engineering.

Injectable scaffold has raised great interest for tissue regeneration in vivo, because it allows easy filling of irregularly shaped defects and the implantation of cells through minimally invasive surgical procedures. In this study, we evaluated poly(lactic-co-glycolic acid) (PLGA) microsphere as an injectable scaffold for in vivo cartilage tissue engineering. PLGA microspheres (30-80 microm in diameter) were injectable through various gauges of needles, as the microspheres did not obstruct the needles and microsphere size exclusion was not observed at injection. The culture of chondrocytes on PLGA microspheres in vitro showed that the microspheres were permissive for chondrocyte adhesion to the microsphere surface. Rabbit chondrocytes were mixed with PLGA microspheres and injected immediately into athymic mouse subcutaneous sites. Chondrocyte transplantation without PLGA microspheres and PLGA microsphere implantation without chondrocytes served as controls. Four and 9 weeks after implantation, chondrocytes implanted with PLGA microspheres formed solid, white cartilaginous tissues, whereas no gross evidence of cartilage tissue formation was noted in the control groups. Histological analysis of the implants by hematoxylin and eosin staining showed mature and well-formed cartilage. Alcian blue/safranin O staining and Masson's trichrome staining indicated the presence of highly sulfated glycosaminoglycans and collagen, respectively, both of which are the major extracellular matrices of cartilage. Immunohistochemical analysis showed that the collagen was mainly type II, the major collagen type in cartilage. This study demonstrates the feasibility of using PLGA microspheres as an injectable scaffold for in vivo cartilage tissue engineering. This scaffold may be useful to regenerate cartilaginous tissues through minimally invasive surgical procedures in orthopedic, maxillofacial, and urologic applications.

Animals↗