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Biomedical subjects

Soo Hyun Kim

Publications and source records attributed to Soo Hyun Kim.

At least 19 recordsLinked to original sources

A Decade of Achievements and Future Directions in Global Antimicrobial Resistance Surveillance System in Korea (Kor-GLASS).

OBJECTIVES: To comprehensively evaluate the 10-year operational outcomes (2016-2025) Global Antimicrobial Resistance Surveillance System in Korea (Kor-GLASS), assess its public health significance for national stewardship and global surveillance, and propose strategies for future development. METHODS: The study described the operational framework of Kor-GLASS, including its strain collection, analysis, and quality control systems, based on surveillance data. It analyzed resistance trends among key bloodstream pathogen isolates collected from 2016 to 2024 and evaluated major achievements, including alignment with the World Health Organization (WHO)'s Global Antimicrobial Resistance Surveillance System (GLASS), integration with the Emerging Antimicrobial Resistance Reporting (EAR) system, and activities as a WHO Collaborating Centre. RESULTS: Kor-GLASS operates on a foundation of standardized, isolate-based surveillance supported by an independent quality management system that complies with WHO GLASS standards. In alignment with the strategic direction of WHO GLASS, the surveillance scope has progressively expanded in terms of catchment areas, target pathogens, specimen types, and antimicrobial panels. From 2016 to 2024, a total of 116,955 clinical isolates were collected and analyzed through the network of collection and analysis centers. This has enabled the continuous generation of nationally representative antimicrobial resistance (AMR) data from general hospitals. The accumulated surveillance data provide fundamental evidence for tracking long-term resistance trends and elucidating the molecular epidemiological characteristics of key pathogens. These outcomes are disseminated through the publication of the "National Antimicrobial Resistance Surveillance Annual Report" and data submissions to WHO GLASS and GLASS-EAR, thereby supporting both national and global AMR surveillance efforts. Furthermore, Kor-GLASS has strengthened international surveillance and One Health collaboration capacities through its designation and redesignation as a WHO Collaborating Centre for AMR Surveillance. CONCLUSIONS: Over the past decade, Kor-GLASS has served as the cornerstone of national antimicrobial resistance surveillance, providing evidence to inform policy and supporting global surveillance systems. Moving forward, Kor-GLASS is expected to evolve into a pivotal national AMR surveillance system through the introduction of whole-genome sequencing and stronger integration with national antimicrobial consumption surveillance.

Anti-bacterial agents↗

Trophoblast Enrichment by Maternal Immune-Cell Depletion Using CD45 and CD56 Surface Markers in Trophoblast Retrieval and Isolation from the Cervix (TRIC).

Background: Trophoblast retrieval and isolation from the cervix (TRIC) has emerged as a promising alternative to invasive prenatal diagnostic procedures. However, contamination by maternal immune cells remains a major challenge that may compromise trophoblast purity and the reliability of downstream fetal genetic analyses. Methods: Maternal immune cells were selectively depleted by immunomagnetic sorting using antibodies targeting CD45 or CD56. The remaining cells were subsequently enriched for HLA-G-positive trophoblasts and characterized by immunofluorescence and gene-expression analyses using CD45, CD56, HLA-G, cytokeratin 7 (CK7), and β-human chorionic gonadotropin (β-hCG). Results: Compared with CD45-mediated depletion, CD56-mediated depletion demonstrated more efficient removal of maternal immune cells, as indicated by significantly reduced CD56 expression. CK7 expression showed an increasing trend following CD56 depletion, whereas β-hCG expression remained largely unchanged. Immunofluorescence analysis further demonstrated a significant increase in the proportion of CK7+/β-hCG+ trophoblast cells after CD56 depletion. Conclusions: Among the evaluated depletion strategies, CD56-mediated depletion demonstrated a more favorable profile for trophoblast-associated characteristics than CD45-mediated depletion, suggesting its potential contribution to further methodological optimization of trophoblast isolation in TRIC-based noninvasive prenatal genetic testing.

maternal immune cell↗

GWAS Meta-analysis Identifies Novel Associated Loci and Points to Causal Tissues in Central Serous Chorioretinopathy.

OBJECTIVE: To define CSC genetic architecture and identify implicated ocular tissues, cell types, genes, and circulating proteins. DATA SOURCES: Genome-wide data were assembled from FinnGen, All of Us, Mass General Brigham Biobank, Million Veteran Program, and a Dutch chronic CSC cohort. Serum protein quantitative trait loci, human single-cell ocular atlases, and UK Biobank macular optical coherence tomography (OCT) imaging were used for downstream analyses. STUDY SELECTION: Five European-ancestry cohorts with genome-wide data and cohort-specific CSC case-control definitions were included, comprising 2,584 cases and 1,044,455 controls. Variants present in at least 2 cohorts were meta-analyzed. DATA EXTRACTION AND SYNTHESIS: Cohort-level GWASs were adjusted for age, age squared, sex, genotyping array or batch, and 10 genetic principal components, then combined using fixed-effects inverse-variance meta-analysis. Post-GWAS analyses included gene prioritization, colocalization, Mendelian randomization, single-cell disease-relevance scoring, and testing of a CSC genetic risk score in UK Biobank OCT images. MAIN OUTCOMES AND MEASURES: Genome-wide significant CSC loci, effector genes and proteins, tissue and cell-type enrichment, and CSC-relevant OCT abnormalities. RESULTS: Across 11,068,938 variants, 10 loci reached genome-wide significance (P < 5 &#xd7; 10-8), including 3 novel loci near TGFB1, LINC00551, and LOC105375630 and 7 replicated loci near CFH, CD46, NOTCH4, PREX1, PTPRB, GATA5, and TNFRSF10A. Integrative analyses prioritized 10 candidate effector genes. Colocalization and Mendelian randomization implicated circulating TNFRSF10A, TGFB1, and CASP10 levels. Single-cell analyses localized genetic risk to sclera (P = 2.0 &#xd7; 10-4) and vascular endothelial cells (P = 4.0 &#xd7; 10-4), with fibroblast enrichment. In UK Biobank, OCT abnormalities were more frequent in the top vs bottom 1% of CSC genetic risk (18 of 109 [16.5%] vs 8 of 134 [6.0%]; odds ratio, 4.05; 95% CI, 1.65-10.87; P = .002). CONCLUSIONS AND RELEVANCE: In this GWAS meta-analysis, CSC susceptibility localized predominantly to scleral and vascular biology rather than primary retinal pigment epithelial dysfunction. These findings support CSC as a sclerovascular disorder and nominate complement regulation, endothelial signaling, and extracellular matrix pathways for future study.

Journal Article↗

Symptom experience, psychological distress, and quality of life in Korean patients with liver cirrhosis: a cross-sectional survey.

BACKGROUND: In patients with cirrhosis, quality of life (QOL) is seriously impaired and associated with particular symptoms such as fatigue, muscle cramps or pruritus. However, there is lack of evidence about the overall symptom experience in patients with cirrhosis, in addition, most studies on QOL have focused only on identifying the relationship between disease-related variables such as disease severity, etiology or serological markers and QOL. OBJECTIVES: This study aimed to describe symptom experience, psychological distress, and QOL in Korean patients with liver cirrhosis, and to identify the factors that predict their quality of life. DESIGN: This study is a cross-sectional, descriptive design. SETTINGS: The participants were recruited over a 2-month period, September 27 to November 25, 2003 from the outpatient or inpatient departments of gastroenterology at two large university hospitals in Seoul, Korea. PARTICIPANTS: There were 129 patients, mean age was 53.6 years, who met eligibility criteria and agreed to participate in the study. METHODS: Symptom experience was measured with a scale developed by the researchers through a literature review on liver cirrhosis. Psychological distress was measured with the anxiety/depression category from the modified Korean version of the profile of mood states (POMS) [Shin, 1996. A study on verification of the profile of mood states (POMS) for Korean elders. Journal of Korean Academic Nursing 26, 743-758], and QOL was measured with quality of life index (QLI) developed by Ferrans and Powers [1985, Quality of life index: development and psychometric properties. Advances in Nursing Science 8, 15-24. ]. RESULTS: The results indicated that (1) overall symptom experience score was relatively low, major symptoms needing a management were fatigue, ascites and/or edema, and muscle cramps; (2) the mean score of psychological distress revealed mild to moderate levels of anxiety and depression; (3) quality of life was found to be seriously impaired; (4) psychological distress, employment status, and symptom experience were significant predictors of QOL, and explained 29.8% of the total variance. CONCLUSION: These results indicate that symptom management, which includes attention to associated psychological intervention, is imperative for improvement in the QOL in Korean patients with liver cirrhosis.

Adaptation, Psychological↗

Peripheral blood neutrophil activation patterns are associated with pulmonary inflammatory responses to lipopolysaccharide in humans.

Increased nuclear accumulation of NF-kappaB in LPS-stimulated peripheral blood neutrophils has been shown to be associated with more severe clinical course in patients with infection associated acute lung injury. Such observations suggest that differences in neutrophil response may contribute to the pulmonary inflammation induced by bacterial infection. To examine this question, we sequentially measured LPS-induced DNA binding of NF-kappaB in neutrophils collected from healthy humans on at least three occasions, each separated by at least 2 wk, and then determined pulmonary inflammatory responses after instillation of LPS into the lungs. Consistent patterns of peripheral blood neutrophil responses, as determined by LPS-induced NF-kappaB DNA binding, were present in volunteers, with a >80-fold difference between individuals in the mean area under the curve for NF-kappaB activation. The number of neutrophils recovered from bronchoalveolar lavage after exposure to pulmonary LPS was significantly correlated with NF-kappaB activation in peripheral blood neutrophils obtained over the pre-LPS exposure period (r = 0.65, p = 0.009). DNA binding of NF-kappaB in pulmonary neutrophils also was associated with the mean NF-kappaB area under the curve for LPS-stimulated peripheral blood neutrophils (r = 0.63, p = 0.01). Bronchoalveolar lavage levels of IL-6 and TNFRII were significantly correlated with peripheral blood neutrophil activation patterns (r = 0.75, p = 0.001 for IL-6; and r = 0.48, p = 0.049 for TNFRII. These results demonstrate that stable patterns in the response of peripheral blood neutrophils to LPS exist in the human population and correlate with inflammatory response following direct exposure to LPS in the lung.

Active Transport, Cell Nucleus↗

Renal angiomyolipoma with minimal fat: differentiation from other neoplasms at double-echo chemical shift FLASH MR imaging.

PURPOSE: To prospectively evaluate the diagnostic performance of double-echo gradient-echo (GRE) chemical shift magnetic resonance (MR) imaging in the differentiation of angiomyolipoma (AML) with minimal fat from other renal neoplasms, with pathologic examination or follow-up data serving as the reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Double-echo GRE chemical shift MR imaging was performed in 55 patients (29 men and 26 women; mean age, 49 years +/- 14 [standard deviation]) with 55 renal tumors, including 37 (67%) pathologically proved tumors (23 renal cell carcinomas, nine AMLs, two oncocytomas, two lymphomas, and one reninoma) and 18 (33%) clinically diagnosed tumors (17 AMLs and one indeterminate malignancy). All tumors showed no intratumoral fat and had homogeneous enhancement and a prolonged or gradual enhancement pattern on biphasic helical computed tomographic scans. Signal intensity was measured in the renal tumor and spleen on in-phase and opposed-phase images. The signal intensity index and tumor-to-spleen ratio in AMLs and non-AMLs were calculated and compared with the Student t test. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of the signal intensity index and tumor-to-spleen ratio and to extract the optimal cut-off values in the differentiation of AMLs and non-AMLs. RESULTS: The signal intensity index and tumor-to-spleen ratio were different between AMLs (42% +/- 11 and -43% +/- 17, respectively) and non-AMLs (5% +/- 14 and -4% +/- 16, respectively) (P < .001). The area under the ROC curve was 0.975 for the signal intensity index and 0.952 for the tumor-to-spleen ratio. For differentiation of AMLs from non-AMLs, sensitivity and specificity were (a) 96% and 93%, respectively, with a signal intensity index of 25% and (b) 88% and 97%, respectively, with a tumor-to-spleen ratio of -32%. CONCLUSION: Double-echo GRE chemical shift MR imaging can be used to differentiate AML with minimal fat from other renal neoplasms.

Adult↗

New technique of seeding chondrocytes into microporous poly(L-lactide-co-epsilon-caprolactone) sponge by cyclic compression force-induced suction.

The initial requirement for a functional engineered cartilage tissue is the effective and reproducible seeding of chondrocytes into the interior of microporous scaffolds. High seeding efficiency, high cell viability, uniform cell distribution, and short operation time are also essential. We devised a new technique of seeding rabbit chondrocytes into microporous poly(L-lactide-co-epsilon-caprolactone) (PLCL) (porosity, 71- 80%; wall thickness, 2 and 6 mm) sponges under compression force-induced suction using a custom designed loading apparatus. Cell distribution and cell viability were determined using confocal laser scanning microscopy with fluorescent dye-staining techniques. Factors that affect the quality of a cell seeded construct were studied, namely, the porosity and thickness of sponges and suction cycles. Under 1 cycle of suction, an increase in porosity promoted cell seeding efficiency (CSE; defined as the percentage of the number of cells in the sponges relative to the initial number of cells seeded), cell viability (at 1 day post seeding), and a relatively uniform cell distribution, whereas thick sponges exhibited an inhomogeneous cell distribution irrespective of incubation time. Multiple cycles of suction of 5 and 10 at 0.1 Hz significantly improved the CSE, whereas high cell viability was maintained and even spatial cell distribution was achieved in 1 week. This study revealed that our newly developed cell seeding technique with multiple cycles of suction is a promising approach to inoculating cells into microporous sponges with high CSE, high cell viability, and homogeneous cell distribution.

Animals↗

Mechano-active scaffold design based on microporous poly(L-lactide-co-epsilon-caprolactone) for articular cartilage tissue engineering: dependence of porosity on compression force-applied mechanical behaviors.

An essential component of functional articular cartilage tissue engineering is a mechano-active scaffold, which responds to applied compression stress and causes little permanent deformation. As the first paper of a series on mechano-active scaffold-based cartilage tissue engineering, this study focused on mechanical responses to various modes of loading of compression forces and subsequent selection of mechano-active scaffolds from the biomechanical viewpoint. Scaffolds made of elastomeric microporous poly(L-lactide-co-epsilon-caprolactone) (PLCL) with open-cell structured pores (300 approximately 500 microm) and with different porosities ranging from 71 to 86% were used. The PLCL sponges and rabbit articular cartilage tissue were subjected to compression/unloading tests (0.1 and 0.005 Hz) at 5 kPa, and stress relaxation tests at 10, 30, and 50% strain. The measurements of the maximum strain under loading and residual strain under unloading for compression tests and the maximum stress and equilibrium stress in the stress relaxation test showed that the lower the porosity, the closer the mechanical properties are to those of native cartilage tissue. Among the PLCL sponges, the sponge with 71% porosity appears to be a suitable cartilage scaffold.

Animals↗

Mechano-active tissue engineering of vascular smooth muscle using pulsatile perfusion bioreactors and elastic PLCL scaffolds.

Blood vessels are subjected in vivo to mechanical forces in a form of radial distention, encompassing cyclic mechanical strain due to the pulsatile nature of blood flow. Vascular smooth muscle (VSM) tissues engineered in vitro with a conventional tissue engineering technique may not be functional, because vascular smooth muscle cells (VSMCs) cultured in vitro typically revert from a contractile phenotype to a synthetic phenotype. In this study, we hypothesized that pulsatile strain and shear stress stimulate VSM tissue development and induce VSMCs to retain the differentiated phenotype in VSM engineering in vitro. To test the hypothesis, rabbit aortic smooth muscle cells (SMCs) were seeded onto rubber-like elastic, three-dimensional PLCL [poly(lactide-co-caprolactone), 50:50] scaffolds and subjected to pulsatile strain and shear stress by culturing them in pulsatile perfusion bioreactors for up to 8 weeks. As control experiments, VSMCs were cultured on PLCL scaffolds statically. The pulsatile strain and shear stress enhanced the VSMCs proliferation and collagen production. In addition, a significant cell alignment in a direction radial to the distending direction was observed in VSM tissues exposed to radial distention, which is similar to that of native VSM tissues in vivo, whereas VSMs in VSM tissues engineered in the static condition randomly aligned. Importantly, the expression of SM alpha-actin, a differentiated phenotype of SMCs, was upregulated by 2.5-fold in VSM tissues engineered under the mechano-active condition, compared to VSM tissues engineered in the static condition. This study demonstrates that tissue engineering of VSM tissues in vitro by using pulsatile perfusion bioreactors and elastic PLCL scaffolds leads to the enhancement of tissue development and the retention of differentiated cell phenotype.

Animals↗

Vascular patches tissue-engineered with autologous bone marrow-derived cells and decellularized tissue matrices.

Synthetic polymer vascular patches used in cardiovascular surgery have shortcomings such as thrombosis, intimal hyperplasia, calcification, infection, and no growth potential. Tissue-engineered vascular patches using autologous vascular cells may solve these problems. In this study, we developed a tissue-engineered vascular patch using autologous bone marrow-derived cells (BMCs) and decellularized tissue matrices. Vascular smooth muscle cells and endothelial cells were differentiated from bone marrow mononuclear cells in vitro. Tissue-engineered vascular patches were fabricated by seeding these cells onto decellularized canine inferior vena cava matrices and implanted into the inferior vena cava of dogs. Three weeks after implantation, the tissue-engineered vascular patches were patent with no sign of thrombus formation. Histological, immunohistochemical, and electron microscopic analyses of the vascular patches retrieved 3 weeks after implantation revealed regeneration of endothelium and smooth muscle and the presence of collagen and elastin. BMCs labeled with a fluorescent dye prior to implantation were detected in the retrieved vascular patches, indicating that the BMCs survived after implantation and contributed to the vascular tissue regeneration. This study demonstrates that vascular patches can be tissue-engineered with autologous BMCs and decellularized tissue matrices.

Animals↗

A poly(lactic acid)/calcium metaphosphate composite for bone tissue engineering.

A new method to prepare PLA/CMP (poly-L-lactide/calcium metaphosphate) composite scaffolds was developed for effective bone tissue engineering. This novel sintering method is composed of pressing the mixture of PLA, CMP, and salt particles at 150 MPa for 3 min followed by heat treatment at 210 degrees C for 30 min. The scaffolds had a homogeneously interconnected porous structure without a skin layer, and they exhibited a narrower pore size distribution and higher mechanical strength in comparison with scaffolds made by a solvent casting method. The scaffolds were seeded by osteoblasts and cultured in vitro or implanted into nude mice subcutaneously for up to 5 weeks. The number of cells attached to and proliferated on the scaffolds at both in vitro and in vivo was in the order of; PLA by novel sintering < PLA/CMP by solvent casting < PLA/CMP by novel sintering. In addition, the alkaline phosphatase activity of and calcium deposition in the scaffolds explanted from mice were enhanced significantly for the scaffolds by novel sintering compared to them by solvent casting. The in vitro results agreed well with the in vivo data. Such a superior characteristic of the novel sintering method should have resulted from the fact that the CMP particles could contact directly with cells/tissues to stimulate the cell proliferation and osteogenic differentiation, while the CMP particles would be coated by polymers and hindered to interact with cells/tissues in the case of a solvent casting method. As the novel sintering method does not use any solvents it offers another advantage to avoid problems associated with solvent residue.

Animals↗

Comparison of virtual cystoscopy, multiplanar reformation, and source CT images with contrast material-filled bladder for detecting lesions.

OBJECTIVE: The objective of our study was to compare the diagnostic accuracy of virtual cystoscopy, multiplanar reformation, and source CT images for lesion detection in the contrast material-filled bladder. SUBJECTS AND METHODS: Two observers independently evaluated 47 patients (28 men and 19 women; mean age +/- SD, 59 +/- 16 years) with virtual cystoscopy, multiplanar reconstruction, and source CT images acquired with contrast material-filled bladder using an MDCT scanner (detector array, 4 x 1.25 mm; beam pitch, 0.75). Agreement between the two observers was evaluated for the three reconstruction methods using kappa statistics. Using the conventional cystoscopic findings as a reference, we compared the results of the three reconstruction techniques both by bladder site and by patient using the McNemar test. RESULTS: The interobserver agreement for the number of positive sites was excellent for virtual cystoscopy (kappa = 0.816), fair for multiplanar reconstruction (kappa = 0.461), and good for source CT images kappa = 0.676). For both observers, the sensitivity for lesion detection by bladder site was significantly greater with virtual cystoscopy (observer 1, 95%; observer 2, 90%) than with multiplanar reconstruction (78% and 60%) and source CT (68% and 65%) images (p < 0.05), whereas the specificity by bladder site and the sensitivity and specificity by patient did not differ with the three methods (p > 0.05). For determining the presence or absence of lesion at each site, virtual cystoscopy was more accurate than multiplanar reconstruction and source CT images for both observers (p < 0.05). CONCLUSION: Virtual cystoscopy is more accurate than multiplanar reconstruction and source CT images for the detection of lesions in the bladder.

Adult↗

Renal cell carcinoma: analysis of postoperative recurrence patterns.

PURPOSE: To retrospectively analyze the recurrence patterns of renal cell carcinoma (RCC) and the factors affecting tumor recurrence. MATERIALS AND METHODS: The institutional review board approved this study; patient informed consent was not required. There were 162 men (mean age, 54 years +/- 13 [standard deviation]) and 32 women (mean age, 56 years +/- 11) who had undergone complete surgical resection of RCC. Mean follow-up period was 45 months (range, 7-92 months). In consensus, two radiologists determined the presence or absence of tumor recurrence and recorded the time and sites of tumor recurrence. The relationships between tumor recurrence and tumor factors, including greatest diameter (> or =5 cm or <5 cm), T stage, N stage, stage group, histologic subtype, and nuclear grade, were evaluated by using Kaplan-Meier statistics. RESULTS: Tumor recurred in 41 (21%) patients. The mean time of tumor recurrence was 17 months (range, 3-50 months). Tumor recurred within 2 years after surgery in 34 (83%) patients. Tumor recurrence sites included lung (n = 29), bone (n = 13), the nephrectomy site (n = 7), brain (n = 6), liver (n = 5), mediastinal lymph nodes (n = 5), the contralateral kidney (n = 4), and the neck muscles (n = 2). The recurrence rate was greater for tumors 5 cm or larger than for those smaller than 5 cm, greater for T3a or T3b tumors than for T1 tumors, greater for stage III tumors than for stage I tumors, and greater for tumors with a nuclear grade of 3 or 4 than for those with a nuclear grade of 1 or 2 (P < .05 for all). CONCLUSION: RCC usually recurs within 2 years after surgery, with the lung being the most vulnerable site; greatest tumor diameter, T stage, stage group, and nuclear grade are important factors for recurrence.

Adolescent↗

Thermally produced biodegradable scaffolds for cartilage tissue engineering.

A novel process was developed to fabricate biodegradable polymer scaffolds for tissue engineering applications, without using organic solvents. Solvent residues in scaffolds fabricated by processes involving organic solvents may damage cells transplanted onto the scaffolds or tissue near the transplantation site. Poly(L-lactic acid) (PLLA) powder and NaCl particles in a mold were compressed and subsequently heated at 180 degrees C (near the PLLA melting temperature) for 3 min. The heat treatment caused the polymer particles to fuse and form a continuous matrix containing entrapped NaCl particles. After dissolving the NaCl salts, which served as a porogen, porous biodegradable PLLA scaffolds were formed. The scaffold porosity and pore size were controlled by adjusting the NaCl/PLLA weight ratio and the NaCl particle size. The characteristics of the scaffolds were compared to those of scaffolds fabricated using a conventional solvent casting/particulate leaching (SC/PL) process, in terms of pore structure, pore-size distribution, and mechanical properties. A scanning electron microscopic examination showed highly interconnected and open pore structures in the scaffolds fabricated using the thermal process, whereas the SC/PL process yielded scaffolds with less interconnected and closed pore structures. Mercury intrusion porosimetry revealed that the thermally produced scaffolds had a much more uniform distribution of pore sizes than the SC/PL process. The utility of the thermally produced scaffolds was demonstrated by engineering cartilaginous tissues in vivo. In summary, the thermal process developed in this study yields tissue-engineering scaffolds with more favorable characteristics, with respect to, freedom from organic solvents, pore structure, and size distribution than the SC/PL process. Moreover, the thermal process could also be used to fabricate scaffolds from polymers that are insoluble in organic solvents, such as poly(glycolic acid). Cartilage tissue regenerated from thermally produced PLLA scaffold.

Animals↗

Ring-opening polymerization of L-lactide and preparation of its microsphere in supercritical fluids.

The ring-opening polymerization of L-lactide initiated by stannous octoate was carried out in supercritical chlorodifluoromethane (scR22) at various reaction conditions (time and temperature) and reactant concentrations (initiator, monomer, and solvent). The monomer conversion increased to ca. 70% on increasing the reaction time to 1 h. The molecular weight of the poly(L-lactide) (PLLA) product also increased to ca. 160,000 g x mol(-1) over the same period. Increasing reaction temperature from 90 to 130 degrees C resulted in increased monomer conversion and PLLA molecular weight. A series of polymerizations conducted at various 1-dodecanol and stannous octoate concentrations suggested that stannous octoate does not act as an initiator by itself, and that the tin-alkoxide formed from 1-dodecanol and stannous octoate serves as the initiating species in scR22. While enhancements of the monomer conversion and PLLA molecular weight were observed with increasing monomer concentration, the chlorodifluoromethane concentration had the opposite on both. After the polymerization, PLLA microspheres were prepared in situ by using a continuous supercritical antisolvent process without residual organic solvent and monomer to yield highly purified microspheres for environmental and biomedical applications.

Chromatography, Supercritical Fluid↗

Smooth muscle-like tissues engineered with bone marrow stromal cells.

Bone marrow-derived cells have demonstrated the ability to differentiate into multiple mesenchymal cell lineages. Here we tested whether smooth muscle (SM)-like tissues can be created in vivo with bone marrow stromal cells (BMSCs). Cultured canine BMSCs, which expressed SM cell-specific markers including SM alpha-actin and SM myosin heavy chain, were seeded on three-dimensional, biodegradable polymer scaffolds and implanted into peritoneal cavity of athymic mice. The cell-scaffold constructs retrieved 4 weeks after implantation formed three-dimensional tissues. Immunohistochemical analyses showed that the tissue reconstructs expressed SM alpha-actin and SM myosin heavy chain. Masson's trichrome staining showed the presence of significant amounts of collagen in the tissue reconstructs. Cells labeled with a fluorescent tracer prior to implantation were still present in the tissue reconstructs 4 weeks after implantation. Non-seeded scaffolds (control groups) retrieved 4 weeks after implantation did not exhibit extensive tissue formation. This study demonstrates the potential of BMSCs as an alternative cell source for tissue engineering of SM.

Absorbable Implants↗

In vivo biocompatibilty and degradation behavior of elastic poly(L-lactide-co-epsilon-caprolactone) scaffolds.

Tubular scaffolds were fabricated from very elastic poly(L-lactide-co-epsilon-caprolactone) (PLCL, 50:50). The scaffolds were seeded with smooth muscle cells (SMCs) and implanted in nude mice to investigate the tissue compatibility and in vivo degradation behavior. Histological examination of all the implants with haematoxylin and eosin staining, masson trichrome staining, SM alpha-actin antibody, and CM-DiI labeling confirmed that the regular morphology and biofunction of the SMCs seeded and the expression of the vascular smooth muscle matrices in PLCL scaffolds. The implanted PLCL scaffolds displayed a slow degradation on time, where caprolactone units were faster degraded than lactide did. This could be explained by the fact that amorphous regions composed of mainly CL moieties degraded earlier than hard domains where most of the LA units were located. From these results, the scaffolds applied in this study were found to exhibit excellent tissue compatibility to SMCs and might be very useful for vascular tissue engineering.

Animals↗

Manufacture of elastic biodegradable PLCL scaffolds for mechano-active vascular tissue engineering.

A soft and very elastic poly(lactide-co-epsilon-caprolactone) (PLCL)(50:50, Mn 185 x 10(3)) was synthesized. Tubular scaffolds were prepared by an extrusion-particulate leaching method for mechano-active vascular tissue engineering. The copolymer was very flexible but completely rubber-like elastic. Even the high porous PLCL scaffolds (90% salt wt) exhibited 200% elongation, but recovery over 85% in a tensile test. Moreover, the PLCL scaffolds maintained their high elasticity also in culture media under cyclic mechanical strain conditions. The highly porous scaffold (90% salt wt) withstood for an initial 1 week without any deformation and sustained for 2 weeks in culture media under cyclic stress of 10% amplitude and at 1 Hz frequency which are similar to the natural vascular conditions. Vascular smooth muscle cells (VSMCs) were seeded on to the PLCL scaffolds. The cell adhesion and proliferation on the scaffolds of various pore-size were increased with increasing pore size. For the pore sizes of 50-100 microm, 100-150 microm, 150-200 microm and 200-250 microm, the ratios of cell numbers were about 1:1.2:1.9:2.2, respectively, at both 12 h and 5 days. Similarly, the higher porous scaffolds exhibited more cell adhesion and proliferation compared to lower porous one, where the effect was more pronounced in the longer proliferation period. SMC-seeded scaffolds were implanted subcutaneously in athymic nude mice to confirm the biocompatibility. Such a high elastic property and proper biocompatibility to SMCs of PLCL scaffolds prepared in this study will be very useful to engineer SM-containing tissues such as blood vessels under mechanically dynamic environments (mechano-active tissue engineering).

Animals↗