Bulking Agent

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Jin Ho Lee - One of the best experts on this subject based on the ideXlab platform.

  • Regeneration of Paralyzed Vocal Fold by the Injection of Plasmid DNA Complex-Loaded Hydrogel Bulking Agent
    2019
    Co-Authors: In Gul Kim, Mi Ri Park, Young Hwan Choi, Ji Suk Choi, Hee-jin Ahn, Seong Keun Kwon, Jin Ho Lee
    Abstract:

    Various growth factor delivery systems were used in the treatment of glottal insufficiency; however, relatively little attention has been paid to a gene delivery system for aspects of active vocal fold (VF) regeneration. Herein, we present a plasmid DNA (pDNA; bFGF gene encoding) complex-loaded alginate (ALG)/hyaluronic acid (HA) mixture hydrogel dispersed with polycaprolactone (PCL) microspheres that can enhance simultaneous regeneration of VF muscle and lamina propria, as well as have a Bulking effect on atrophied VF. We have demonstrated long-term efficacy of bFGF synthesized from pDNA complex-transfected cells in vitro. PCL microspheres–dispersed ALG/HA hydrogel (with or without pDNA complex loading) are injected into rabbit VFs with recurrent laryngeal nerve denervation. The PCL microspheres dispersed in the hydrogel Bulking Agents remain stable at the applied site, leading to constant medialization of the paralyzed VF without significant initial volume loss even after 24 weeks. A regenerative effect for collagen deposition and HA synthesis around the injected site, which are major components of VF tissue, is well confirmed in the pDNA-complex-loaded hydrogel group. Moreover, the compensation of atrophied VFs also leads to the contact of bilateral VF and the remarkable recovery of voice function in the pDNA-complex-loaded group. Based on the results, pDNA (bFGF encoding) complex-loaded hydrogel dispersed with PCL microspheres may be employed as a bioactive Bulking Agent for the treatment of glottal insufficiency

  • functional recovery of urethra by plasmid dna loaded injectable Agent for the treatment of urinary incontinence
    Biomaterials, 2013
    Co-Authors: Soo Jung Choi, Ji Youl Lee, In Gul Kim, So Young Chun, Jin Ho Lee
    Abstract:

    Stress urinary incontinence (SUI) is an embarrassing problem affecting a large number of women and interfering with their quality of life. The injury or weakness of urethral supporting tissues by childbirth and aging has been considered as key factors in the development of the SUI. In this study, plasmid DNA (pDNA; encoding for bFGF) complex-loaded poly(DL-lactic-co-glycolic acid) (PLGA)/Pluronic F127 mixture dispersed with polycaprolactone (PCL) microspheres was prepared as an injectable bioactive Bulking Agent that may provide Bulking effect (by PCL microspheres) and allow stimulation of the defect tissues around urethra (by synthesis of bFGF from cells or tissues transfected by the pDNA complex) for the effective treatment of SUI. From in vitro experiments, the pDNA complex incorporated in the Bulking Agent was released in a sustained manner over 84 days (≥80% of the initial loading amount). The pDNA complex was effectively transfected into fibroblasts and the cells were continuously producing the target protein, bFGF. From the in vivo study using hairless mice and Sprague-Dawley rats, it was confirmed that the pDNA complex released from the Bulking Agent is transfected into surrounding cells/tissue, and the cells/tissues synthesize sufficient bFGF to regenerate smooth muscle with biological function around the urethra. Basis on these results, the pDNA (encoding for bFGF) complex-loaded PLGA/Pluronic F127 mixture dispersed with PCL microspheres can be a promising bioactive Bulking Agent system for the fundamental cure of SUI.

  • bioactive porous beads as an injectable urethral Bulking Agent in vivo animal study for the treatment of urinary incontinence
    Tissue Engineering Part A, 2011
    Co-Authors: In Gul Kim, Ji Young Lee, Ji Youl Lee, Jin Ho Lee
    Abstract:

    In our previous study, growth factor (basic fibroblast growth factor [bFGF] or vascular endothelial growth factor)-immobilized polycaprolactone (PCL)/Pluronic F127 porous beads were fabricated by an isolated particle-melting/melt-molding particulate-leaching method. The growth factors were easily immobilized onto the pore surfaces of the PCL/F127 beads via heparin binding, and were continuously released for up to 28 days. In this study, the growth factor-immobilized porous beads were investigated for their potential use as an injectable urethral Bulking Agent for the treatment of stress urinary incontinence (SUI). From the in vivo study using Sprague-Dawley rats as an urinary incontinent animal model, it was observed that the growth factor (bFGF or vascular endothelial growth factor)-immobilized porous beads had effective cure behaviors for SUI as follows: the narrowed urethral lumen and the regeneration of smooth muscle around the urethra. In particular, the bFGF-immobilized PCL/F127 porous beads showed ...

  • bioactive porous beads as an injectable urethral Bulking Agent their in vitro evaluation on smooth muscle cell differentiation
    Tissue Engineering Part A, 2011
    Co-Authors: In Gul Kim, Ji Young Lee, Ji Youl Lee, Jin Ho Lee
    Abstract:

    Growth factor (basic fibroblast growth factor or vascular endothelial growth factor)-immobilized polycaprolactone (PCL)/Pluronic F127 porous beads were prepared as an injectable Bulking Agent for effective treatment of urinary incontinence. The growth factor-immobilized porous beads may stimulate smooth muscle cell (SMC) differentiation of muscle-derived stem cells or defect tissues around urethra to improve the sphincter function (bioactive therapy) as well as to provide a Bulking effect (passive therapy). The porous PCL/F127 beads were fabricated by an isolated particle-melting/melt-molding particulate-leaching method. The growth factors were easily immobilized onto the surfaces of the PCL/F127 porous beads via heparin binding and were continuously released for up to 28 days. Both growth factor-immobilized porous beads had a positive effect for the SMC differentiation of muscle-derived stem cells, as were demonstrated by the analyses of quantitative polymerase chain reactions, Western blot using SMC-spe...

  • pcl microparticle dispersed plga solution as a potential injectable urethral Bulking Agent
    Biomaterials, 2006
    Co-Authors: Ji Youl Lee, Sung Ho Ghil, Sang Sup Lee, Soon Hong Yuk, Jin Ho Lee
    Abstract:

    Abstract The PCL microparticle-dispersed PLGA solutions were prepared as a potential injectable urethral Bulking Agent. The mixture solutions were prepared by mixing polycarprolactone (PCL) microparticles (diameter, 100∼200 μm; fabricated by a temperature-induced phase transition method) and poly( dl -lactic- co -glycolic acid) (PLGA) solution (dissolved in tetraglycol to 10 wt%) with different PCL microparticle to PLGA solution ratio. The mixture solution was solidified by the precipitation of PLGA when the solution was contact with water. In contact with water, the PCL microparticles exhibited a well-packed structure entrapped in a solidified porous PLGA matrix, which can effectively prevent the microparticle migration in the body and retain its initial volume even after PLGA matrix degradation. The PCL microparticle-dispersed PLGA solution (particle to solution ratio, 45/55 (w/v)) was easily injected through 18 G needle into back of hairless mouse (subcutaneously) and stably located at the apply site. The surrounding tissue including blood vessel were gradually infiltrated into the implant up to 8 weeks without the initial injected volume change and with little inflammatory response. The PCL microparticle-dispersed PLGA solution may be a good candidate as an injectable Bulking Agent for the treatment of urinary incontinence owing to its good injectability, volume retention potential as well as biocompatibility.

Steven D Glassman - One of the best experts on this subject based on the ideXlab platform.

  • early term and mid term histologic events during single level posterolateral intertransverse process fusion with rhbmp 2 collagen carrier and a ceramic Bulking Agent in a nonhuman primate model implications for bone graft preparation
    Journal of Spinal Disorders & Techniques, 2014
    Co-Authors: Safdar N Khan, Steven D Glassman, Jeffrey M Toth, Kavita Gupta, Munish C Gupta
    Abstract:

    Study design We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. Objective To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic Bulking Agents in 3 different configurations. Summary of background data rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates. Methods Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/β-tricalcium phosphate ceramic Bulking Agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic Bulking Agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. Results Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. Conclusions At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results and previous literature indicate that ceramic Bulking Agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic Bulking Agents may offer long-term scaffolding and a structure to supporting bone formation of the developing fusion mass.

  • early term and mid term histologic events during single level posterolateral intertransverse process fusion with rhbmp 2 collagen carrier and a ceramic Bulking Agent in a nonhuman primate model implications for bone graft preparation
    Journal of Spinal Disorders & Techniques, 2014
    Co-Authors: Safdar N Khan, Steven D Glassman, Jeffrey M Toth, Kavita Gupta, Munish C Gupta
    Abstract:

    STUDY DESIGN: We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. OBJECTIVE: To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic Bulking Agents in 3 different configurations. SUMMARY OF BACKGROUND DATA: rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates. METHODS: Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/β-tricalcium phosphate ceramic Bulking Agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic Bulking Agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. RESULTS: Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. CONCLUSIONS: At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results and previous literature indicate that ceramic Bulking Agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic Bulking Agents may offer long-term scaffolding and a structure to supporting bone formation of the developing fusion mass.

  • recombinant human bone morphogenetic protein 2 on an absorbable collagen sponge with an osteoconductive Bulking Agent in posterolateral arthrodesis with instrumentation a prospective randomized trial
    Journal of Bone and Joint Surgery American Volume, 2009
    Co-Authors: Edgar G Dawson, Hyun W Bae, Kenneth J Burkus, Jeffery L Stambough, Steven D Glassman
    Abstract:

    Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge has been shown to be a safe and effective replacement for iliac crest bone graft when used with a threaded fusion device in anterior lumbar interbody arthrodesis. Use of rhBMP-2 on an absorbable collagen sponge in posterolateral lumbar arthrodesis requires the addition of a Bulking Agent to provide resistance against compression and to serve as an osteoconductive scaffold for new bone formation. Methods: We performed a prospective, randomized, multicenter pilot study to investigate the use of rhBMP-2 on an absorbable collagen sponge combined with a ceramic-granule Bulking Agent as a replacement for autogenous iliac crest bone graft in single-level posterolateral lumbar arthrodesis with instrumentation. The investigational group (twenty-five patients) was treated with a 1.5 mg/mL solution of rhBMP-2 on two strips of absorbable collagen sponge (total dose of rhBMP-2, 12 mg) combined with 10 cm3 of ceramic granules. The control group (twenty-one patients) received iliac crest bone graft. Clinical outcomes were assessed with use of well-established instruments. Radiographs were reviewed to assess consolidation of fusion. Results: Eighty-eight percent (twenty-two) of the twenty-five patients in the investigational group and 86% (eighteen) of the twenty-one patients in the control group were considered to have completed the twenty-four-month follow-up. At all follow-up intervals, there were significant improvements in the clinical outcome measures, including the Oswestry Disability Index (ODI) scores, Short Form-36 scores, and back and leg pain scores, in both groups. At twenty-four months, the improvement in the mean ODI score, as compared with the preoperative score, was 28.2 points in the investigational group and 23.0 points in the control group. By twenty-four months, 95% (eighteen) of nineteen patients in the investigational group compared with 70% (fourteen) of twenty in the control group had a radiographically documented fusion. The overall success rate was 81% (seventeen of twenty-one) in the investigational group and 55% (eleven of twenty) in the control group (p = 0.345). Conclusions: Compared with an iliac crest bone graft, the combination of an absorbable collagen sponge soaked with rhBMP-2 and ceramic granules resulted in trends toward improvements in clinical outcomes and toward a higher rate of radiographic fusion. This combination of an osteoinductive Agent with an osteoconductive matrix may be an effective replacement for autograft in single-level posterolateral lumbar arthrodeses with instrumentation. Level of Evidence: Therapeutic Level II. See Instructions to Authors for a complete description of levels of evidence.

Munish C Gupta - One of the best experts on this subject based on the ideXlab platform.

  • early term and mid term histologic events during single level posterolateral intertransverse process fusion with rhbmp 2 collagen carrier and a ceramic Bulking Agent in a nonhuman primate model implications for bone graft preparation
    Journal of Spinal Disorders & Techniques, 2014
    Co-Authors: Safdar N Khan, Steven D Glassman, Jeffrey M Toth, Kavita Gupta, Munish C Gupta
    Abstract:

    STUDY DESIGN: We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. OBJECTIVE: To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic Bulking Agents in 3 different configurations. SUMMARY OF BACKGROUND DATA: rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates. METHODS: Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/β-tricalcium phosphate ceramic Bulking Agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic Bulking Agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. RESULTS: Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. CONCLUSIONS: At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results and previous literature indicate that ceramic Bulking Agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic Bulking Agents may offer long-term scaffolding and a structure to supporting bone formation of the developing fusion mass.

  • early term and mid term histologic events during single level posterolateral intertransverse process fusion with rhbmp 2 collagen carrier and a ceramic Bulking Agent in a nonhuman primate model implications for bone graft preparation
    Journal of Spinal Disorders & Techniques, 2014
    Co-Authors: Safdar N Khan, Steven D Glassman, Jeffrey M Toth, Kavita Gupta, Munish C Gupta
    Abstract:

    Study design We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. Objective To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic Bulking Agents in 3 different configurations. Summary of background data rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates. Methods Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/β-tricalcium phosphate ceramic Bulking Agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic Bulking Agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. Results Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. Conclusions At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results and previous literature indicate that ceramic Bulking Agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic Bulking Agents may offer long-term scaffolding and a structure to supporting bone formation of the developing fusion mass.

Peter Frey - One of the best experts on this subject based on the ideXlab platform.

  • Microfluidic production of bioactive fibrin micro-beads embedded in crosslinked collagen used as an injectable Bulking Agent for urinary incontinence treatment.
    Acta biomaterialia, 2017
    Co-Authors: Elif Vardar, Hans M. Larsson, Simone Allazetta, E.m. Engelhardt, Kalitha Pinnagoda, Ganesh Vythilingam, Jeffrey A. Hubbell, Matthias P. Lutolf, Peter Frey
    Abstract:

    Abstract Endoscopic injection of Bulking Agents has been widely used to treat urinary incontinence, often due to urethral sphincter complex insufficiency. The aim of the study was to develop a novel injectable bioactive collagen-fibrin Bulking Agent restoring long-term continence by functional muscle tissue regeneration. Fibrin micro-beads were engineered using a droplet microfluidic system. They had an average diameter of 140 μm and recombinant fibrin-binding insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1) was covalently conjugated to the beads. A plasmin fibrin degradation assay showed that 72.5% of the initial amount of α2PI1-8-MMP-IGF-1 loaded into the micro-beads was retained within the fibrin micro-beads. In vitro, the growth factor modified fibrin micro-beads enhanced cell attachment and the migration of human urinary tract smooth muscle cells, however, no change of the cellular metabolic activity was seen. These bioactive micro-beads were mixed with genipin-crosslinked homogenized collagen, acting as a carrier. The collagen concentration, the degree of crosslinking, and the mechanical behavior of this bioactive collagen-fibrin injectable were comparable to reference samples. This novel injectable showed no burst release of the growth factor, had a positive effect on cell behavior and may therefore induce smooth muscle regeneration in vivo, necessary for the functional treatment of stress and other urinary incontinences. Statement of Significance Urinary incontinence is involuntary urine leakage, resulting from a deficient function of the sphincter muscle complex. Yet there is no functional cure for this devastating condition using current treatment options. Applied physical and surgical therapies have limited success. In this study, a novel bioactive injectable Bulking Agent, triggering new muscle regeneration at the injection site, has been evaluated. This injectable consists of cross-linked collagen and fibrin micro-beads, functionalized with bound insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1). These bioactive fibrin micro-beads induced human smooth muscle cell migration in vitro. Thus, this injectable Bulking Agent is apt to be a good candidate for regeneration of urethral sphincter muscle, ensuring a long-lasting treatment for urinary incontinence.

Ji Youl Lee - One of the best experts on this subject based on the ideXlab platform.

  • functional recovery of urethra by plasmid dna loaded injectable Agent for the treatment of urinary incontinence
    Biomaterials, 2013
    Co-Authors: Soo Jung Choi, Ji Youl Lee, In Gul Kim, So Young Chun, Jin Ho Lee
    Abstract:

    Stress urinary incontinence (SUI) is an embarrassing problem affecting a large number of women and interfering with their quality of life. The injury or weakness of urethral supporting tissues by childbirth and aging has been considered as key factors in the development of the SUI. In this study, plasmid DNA (pDNA; encoding for bFGF) complex-loaded poly(DL-lactic-co-glycolic acid) (PLGA)/Pluronic F127 mixture dispersed with polycaprolactone (PCL) microspheres was prepared as an injectable bioactive Bulking Agent that may provide Bulking effect (by PCL microspheres) and allow stimulation of the defect tissues around urethra (by synthesis of bFGF from cells or tissues transfected by the pDNA complex) for the effective treatment of SUI. From in vitro experiments, the pDNA complex incorporated in the Bulking Agent was released in a sustained manner over 84 days (≥80% of the initial loading amount). The pDNA complex was effectively transfected into fibroblasts and the cells were continuously producing the target protein, bFGF. From the in vivo study using hairless mice and Sprague-Dawley rats, it was confirmed that the pDNA complex released from the Bulking Agent is transfected into surrounding cells/tissue, and the cells/tissues synthesize sufficient bFGF to regenerate smooth muscle with biological function around the urethra. Basis on these results, the pDNA (encoding for bFGF) complex-loaded PLGA/Pluronic F127 mixture dispersed with PCL microspheres can be a promising bioactive Bulking Agent system for the fundamental cure of SUI.

  • bioactive porous beads as an injectable urethral Bulking Agent in vivo animal study for the treatment of urinary incontinence
    Tissue Engineering Part A, 2011
    Co-Authors: In Gul Kim, Ji Young Lee, Ji Youl Lee, Jin Ho Lee
    Abstract:

    In our previous study, growth factor (basic fibroblast growth factor [bFGF] or vascular endothelial growth factor)-immobilized polycaprolactone (PCL)/Pluronic F127 porous beads were fabricated by an isolated particle-melting/melt-molding particulate-leaching method. The growth factors were easily immobilized onto the pore surfaces of the PCL/F127 beads via heparin binding, and were continuously released for up to 28 days. In this study, the growth factor-immobilized porous beads were investigated for their potential use as an injectable urethral Bulking Agent for the treatment of stress urinary incontinence (SUI). From the in vivo study using Sprague-Dawley rats as an urinary incontinent animal model, it was observed that the growth factor (bFGF or vascular endothelial growth factor)-immobilized porous beads had effective cure behaviors for SUI as follows: the narrowed urethral lumen and the regeneration of smooth muscle around the urethra. In particular, the bFGF-immobilized PCL/F127 porous beads showed ...

  • bioactive porous beads as an injectable urethral Bulking Agent their in vitro evaluation on smooth muscle cell differentiation
    Tissue Engineering Part A, 2011
    Co-Authors: In Gul Kim, Ji Young Lee, Ji Youl Lee, Jin Ho Lee
    Abstract:

    Growth factor (basic fibroblast growth factor or vascular endothelial growth factor)-immobilized polycaprolactone (PCL)/Pluronic F127 porous beads were prepared as an injectable Bulking Agent for effective treatment of urinary incontinence. The growth factor-immobilized porous beads may stimulate smooth muscle cell (SMC) differentiation of muscle-derived stem cells or defect tissues around urethra to improve the sphincter function (bioactive therapy) as well as to provide a Bulking effect (passive therapy). The porous PCL/F127 beads were fabricated by an isolated particle-melting/melt-molding particulate-leaching method. The growth factors were easily immobilized onto the surfaces of the PCL/F127 porous beads via heparin binding and were continuously released for up to 28 days. Both growth factor-immobilized porous beads had a positive effect for the SMC differentiation of muscle-derived stem cells, as were demonstrated by the analyses of quantitative polymerase chain reactions, Western blot using SMC-spe...

  • pcl microparticle dispersed plga solution as a potential injectable urethral Bulking Agent
    Biomaterials, 2006
    Co-Authors: Ji Youl Lee, Sung Ho Ghil, Sang Sup Lee, Soon Hong Yuk, Jin Ho Lee
    Abstract:

    Abstract The PCL microparticle-dispersed PLGA solutions were prepared as a potential injectable urethral Bulking Agent. The mixture solutions were prepared by mixing polycarprolactone (PCL) microparticles (diameter, 100∼200 μm; fabricated by a temperature-induced phase transition method) and poly( dl -lactic- co -glycolic acid) (PLGA) solution (dissolved in tetraglycol to 10 wt%) with different PCL microparticle to PLGA solution ratio. The mixture solution was solidified by the precipitation of PLGA when the solution was contact with water. In contact with water, the PCL microparticles exhibited a well-packed structure entrapped in a solidified porous PLGA matrix, which can effectively prevent the microparticle migration in the body and retain its initial volume even after PLGA matrix degradation. The PCL microparticle-dispersed PLGA solution (particle to solution ratio, 45/55 (w/v)) was easily injected through 18 G needle into back of hairless mouse (subcutaneously) and stably located at the apply site. The surrounding tissue including blood vessel were gradually infiltrated into the implant up to 8 weeks without the initial injected volume change and with little inflammatory response. The PCL microparticle-dispersed PLGA solution may be a good candidate as an injectable Bulking Agent for the treatment of urinary incontinence owing to its good injectability, volume retention potential as well as biocompatibility.