• Journal of Veterinary Clinics
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• v.41 no.5
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• pp.270-276
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• 2024

This study was conducted to evaluate the anti-adhesion effect by applying monophasic cross-linked hyaluronic acid after induction of intraperitoneal adhesions in rats. A total of 18 rats were divided into the control group, the hyaluronic acid (HA) group treated intraperitoneally with HA gel, and the monophasic crosslinked hyaluronic acid (MCHA) group treated with a MCHA gel intraperitoneally. To evaluate the degree of intra-abdominal adhesion, the thickness of the adhesion site, the degree of inflammatory cell infiltration, the degree of collagen fiber formation, and the adhesion formation score were evaluated. The thickness of adhesion site between the abdominal wall and intestinal mucosa was 1,591.25 ± 263.10 ㎛ in the control group, 989.12 ± 163.46 ㎛ in the HA group, and 716.83 ± 94.01 ㎛ in the MCHA group. The number of inflammatory cells was 341.67 ± 115.69 cells/mm², 175.00 ± 29.14 cells/mm² and 99.67 ± 17.22 cells/mm² in the control, HA, and MCHA group, respectively. The degree of collagen fiber formation at the adhesion site was 71.77 ± 10.26%/mm², 50.12 ± 5.41%/mm² and 42.83 ± 7.30 %/mm² in the control, HA, and MCHA group, respectively. The histopathological grades of adhesion sites were 2.90 ± 0.32, 2.30 ± 0.48, and 1.00 ± 0.47 in the control, HA, and MCHA group, respectively. The results showed the anti-adhesive effect through the anti-inflammatory and anti-fibrotic activity according to the intraperitoneal treatment of monophasic cross-linked hyaluronic acid gel. Therefore, intraperitoneal treatment of monophasic cross-linked hyaluronic acid gel can be used as an effective anti-adhesion agent in abdominal surgery.

• Archives of Plastic Surgery
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• v.51 no.1
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• pp.20-26
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• 2024

The etiology and pathophysiology of delayed inflammatory reactions caused by hyaluronic acid fillers have not yet been elucidated. Previous studies have suggested that the etiology can be attributed to the hyaluronic acid filler itself, patient's immunological status, infection, and injection technique. Hyaluronic acid fillers are composed of high-molecular weight hyaluronic acids that are chemically cross-linked using substances such as 1,4-butanediol diglycidyl ether (BDDE). The mechanism by which BDDE cross-links the two hyaluronic acid disaccharides is still unclear and it may exist as a fully reacted cross-linker, pendant cross-linker, deactivated cross-linker, and residual cross-linker. The hyaluronic acid filler also contains impurities such as silicone oil and aluminum during the manufacturing process. Impurities can induce a foreign body reaction when the hyaluronic acid filler is injected into the body. Aseptic hyaluronic acid filler injections should be performed while considering the possibility of biofilm formation or delayed inflammatory reaction. Delayed inflammatory reactions tend to occur when patients experience flu-like illnesses; thus, the patient's immunological status plays an important role in delayed inflammatory reactions. Large-bolus hyaluronic acid filler injections can induce foreign body reactions and carry a relatively high risk of granuloma formation.

• Proceedings of the Membrane Society of Korea Conference
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• 2005.11a
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• pp.165-165
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• 2005

• Journal of Biomedical Engineering Research
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• v.38 no.1
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• pp.1-8
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• 2017

The successful synthesis of hyaluronic acid micro-threads is very promising approach for the broad application in tissue engineering such as dermal fillers. Because hyaluronic acid has the excellent biocompatibility and ability to maintain the moisture of up to several hundred times its own weight. In order to generate the hyaluronic acid micro-threads in microfluidic system, we employed two-phase flow microfluidic chip to make a rapid synthesis of the hyaluronic acid hydrogel. Hyaluronic acid was mixed with 0.02N NaOH solution and 1, 4-Butanediol diglycidyl ether (BDDE) solution and then injected into core channel. The ethanol was used for the 3-dimensional micro-thread formation in sheath channel. We manipulated the diameter of HA micro-threads using controlling of flow rates in microfluidic chip, and showed the feasibility of immobilization in HA micro-threads with florescent substances. Also, the generated HA micro-threads were evaluated and showed the suitable properties with tensile strength, bending property, and swelling profiles for dermal fillers. As a result, we suggested an innovative method for microfluidic chip-based HA micro-threads which could safely be applied as dermal filler in tissue engineering.

• Membrane Journal
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• v.18 no.2
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• pp.124-131
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• 2008

The biodegradable hyaluronic acid membranes cross-linked with lactide using the crosslinking agent, 1,3-butadiene diepoxide (BD), were prepared as a potential biocompatible material for tissue engineering. The degree of lactide and BD reaction of the crosslinked membrane was determined by the analysis of nuclear magnetic resonance spectroscopy 6% of growth inhibition was observed in case of high BD concentration but the value is low enough not to affect cell growth. As the crosslinking reaction temperature increased, elongation increased and swelling ratio decreased. The rate of degradation was found to increase with the crosslinking temperature. The drug release experiment showed that the transport of drug through the membrane decreased with the crosslinking temperature.

• Journal of Biomedical Engineering Research
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• v.40 no.4
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• pp.137-142
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• 2019

Numerous efforts are being made to develop an ideal dermal filler that should be bio-compatibility, non-immunogenicity, long-lasting and biodegradable without a toxic secretion. Biomaterials of dermal fillers are hyaluronic acid filler, calcium filler, PMMA filler and collagen filler depending on the ingredient. Although hyaluronic acid (HA) is most widely used, it has shortages such as short shelf life and low mechanical strength compare to extracellular matrix (ECM). The cartilage ECM composed of collagen type II, proteoglycans, glycosaminoglycans (GAGs) and in a minor part with glycoproteins. In this study, we developed a cartilage ECM injectable filler capable of improving biocompatibility and longevity compared with hyaluronic acid (HA) fillers. The ECM hydrogel was cross-linked by the reaction of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) for mechanical enhancement. Prepared ECM filler was compared with cross-linked HA by butanediol diglycidyle ether (BDDE), which is the most widely used natural polymers for dermal filler. In the results, the articular cartilage ECM hydrogel has great potential as a dermal filler to improve the biophysical and biological performance.

• Membrane Journal
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• v.19 no.4
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• pp.310-316
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• 2009

The degradation characteristics of cross-linked lactide/hyaluronic acid (LA/HA) membranes were investigated for purpose of applying to tissue engineering. The lactide/hyaluronic acid cross-linked with 1,3-butadiene diepoxide (BD) and 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) was degradated in deionized water in water bath at $37^{\circ}C$. As the LA/HA mole ratio or crosslinking agent concentration decreased, the degradation rate of the crosslinked membranes increased. In order to investigate the structure change of the membrane in the degradation process, the control sample and 3, 6, 9 days-degradated samples were analysed by the nuclear magnetic resonance spectroscopy. In case of the membranes crosslinked with EDC, the HA-EDC bonding structure was degradated slowly whereas the HA-LA bonding structure was degradated quickly and dissappeared completely after 6 days. In case of the membranes crosslinked with BD, all the crosslinked bonding structure degradated slowly. The HA-BD bonding structure maintained its original state about 89, 83% in case of 3, 6 days-degardated samples respectively whereas the HA-LA bonding structure maintained its original state about 83, 65%. The scanning electron microscopy of the degradated membranes showed that the pore density in the surface, and the structure in the surface and cross section, of the before and after-degradation membranes did not change greatly, so the membranes was shown to be applied to materials for tissue engineering.

• YAKHAK HOEJI
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• v.55 no.1
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• pp.69-74
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• 2011

Hyaluronic acid (HA) is a natural polymer consisting of disaccharide units of D-glucuronic acid and N-acetyl-D-glucosamine. It has a great potential and success in cosmetic and biomedical applications. However, native HA is highly soluble and easily metabolized by enzymes such as hyaluronidase. Thus, various studies have been reported on modifying the physicochemical properties of HA, while maintaining its biocompatibility. For controlled drug delivery, many trials for fabricating HA microspheres were achieved under chemical reaction. The HA microspheres fabricated to improve the physical stability of HA using adipic acid dihydrazide (ADH) by cross-linking reaction has been reported earlier, however it lacks the desired physical stability and rapidly decomposes by swelling or enzymes. Therefore, we prepared double cross-linked HA microspheres (DC-HA microspheres) and alginate containing HA microspheres (AC-HA microspheres) to enhance its physicochemical properties. DC-HA microspheres were prepared using trisodium trimetaphosphate (STMP) under crosslinking reaction after ADH cross-linking reaction. AC-HA microspheres were prepared by adding alginate as a networking polymer. These microspheres were characterized by morphology, particle size, zeta potential, stability against hyaluronidase. Results showed that the DC-HA and AC-HA microspheres are more stable than that of HA microspheres.

• The Korean Journal of Vision Science
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• v.20 no.4
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• pp.513-521
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• 2018

Purpose : : In this study, we made dopamine-functionalized hydrogels containing a cross-linked hyaluronic acid (HA) network and investigated their antioxidant activities. Methods : In the first step, we made poly hydroxyethyl methacrylate(p(HEMA))-based hydrogels post-modified with an interpenetrating polymer network(IPN) structure composed of HA polymers and a p(HEMA) network. The subsequent functionalization with dopamine via an amide coupling reaction resulted in the antioxidant hydrogels. Their antioxidant activities were evaluated using 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays. Results : The dopamine-modified hydrogels exhibited significant antioxidant activities, when compared to unmodified control. The presence of the HA-IPN structure improved the surface wettability of the hydrogel while dopamine-conjugated IPN hydrogel did not demonstrate the significant difference compared to hydrogel control. Dopamine-modified hydrogels exhibited high transmittance (>88%). Conclusion : The results demonstrate that the development of antioxidant hydrogels based on dopamine-conjugated HA-IPN structures may help develop ophthalmic and biomedical materials.

• Polymer(Korea)
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• v.32 no.4
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• pp.390-396
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• 2008

The hyaluronic acid (HA) polymers cross-linked with lactide (LA) using the crosslinking agent, 1,3-butadiene diepoxide (BD), were prepared in order to develop a biomedical material for tissue engineering. The degree of lactide and BD reaction of the crosslinked polymer was determined by the analysis of nuclear magnetic resonance spectroscopy. Both degree of reaction and swelling ratio increased with BD concentration or LA/HA mole ratio. Tensile modulus decreased with increasing BD concentration or decreasing LA/HA mole ratio. Degradation was shown to be progressed at two different stages and became slow with increasing BD concentration. It was shown that the first stage degradation was mainly due to the decomposition of ester linkage in the crosslinked structure. The cell growth inhibition increased with BD concentration. Although cytotoxicity was slightly observed in the high BD concentration, the value was very low (below 6%) enough not to affect the cell growth.