• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.33-43
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• 2010

Hyaluronic acid (HA) is a biodegradable, biocompatible, non-toxic, non-immunogenic and non-inflammatory linear polysaccharide, which has been used for various medical applications including arthritis treatment, wound healing, ocular surgery, and tissue augmentation. Because of its mucoadhesive property and safety, HA has received much attention as a tool for drug delivery system development. It has been used as a drug delivery carrier in both nonparenteral and parenteral routes. The nonparenteral application includes the ocular and nasal delivery systems. On the other hand, its use in parenteral systems has been considered important as in the case of sustained release formulation of protein drugs through subcutaneous injection. Particles and hydrogels by various methods using HA and HA derivatives as well as by conjugation with other polymer have been the focus of many studies. Furthermore, the affinity of HA to the CD44 receptor which is overexpressed in various tumor cells makes HA an important means of cancer targeted drug delivery. Current trends and development of HA as a tool for drug delivery will be outlined in this review.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제28권3호
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• pp.205-215
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• 2002

The purpose of this study was to evaluate the tissue response in various bone grafting materials, especially xenogenous bone materials in vivo, compare of bone formation capacity of various bone grafting materials on rat skull defects and evaluate the effect of Hyaluronic acid on healing of human Demineralized Freezed Dried Bone allogenous graft (DFDBA) materials in rat calvarial defects. 30 Sprague-Dawly rats were divided into 4 groups. $7{\times}7mm$ size bony defect were artificially prepared in the calvaria (both parietal bone) of all 30 rats and follwed group grafting of autogenous bone graft on right side and allogenic DFDBA on left side bone graft (rat DFDB) in 15 control group, but in 15 experimental group, xenograft (human DFDB) on left side, hyaluronic acid treated with xenograft on right side. Sequential sacrifices was performed at 1, 2, 4, 6, 8 weeks of experiment. These specimens were stained with H&E and MT stain, and then histologic analysis under light microscope was carried out. There were inflammatory reaction in all graft material during early stage. Autogenous and Allogenous DFDBA graft group observed inflammatory reaction at 1 week. Xenograft group persistant inflammatory reaction until 4 weeks, but in HA treated xenograft group inflammatory reaction was decreased at 2 weeks. Osteoblastic activity in control group was begun at 2 week, xenograft group was delayed at 6 weeks, however HA treated xenograft group was begun at 4 weeks. At 2 week, mild osteoclastic activity were observed in all xenograft group not in concerned to HA, but there was no difference each group after 4 weeks. There are most activated angiogenesis around graft mateirals in xenograft group at 2 weeks, but in HA treated xenograft group, decreased angiogenesis was observed at same time. Bone formation and bone maturation of xenograft group, there was no difference in HA treatment, was less than control group. Fibrosis around xenograft materials were observed until 6 weeks, there was no difference between xenograft and HA treated groups.

• 대한수의학회지
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• 제44권4호
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• pp.663-668
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• 2004

This study was conducted to investigate the effect of hyaluronic acid (HA) on prevention of abdominal adhesions depending on various concentrations thereof by inducing an abrasion experimentally in the cecum of rats. Each group was consisted of 10 rats, and 40 rats were divided into 4 groups comprising the saline treatment group, HA 0.4% treated group, 0.6% treated group, and 0.8% treated group. And abrasion was caused in the cecum by using dry gauze and thereby, adhesion was induced. On 7 days after the operation, adhesions of each region were evaluated into the range of 0-4. Significant difference was found in the adhesion score between the control group and each experimental group (P<0.05). Also, HA 0.4% treatment group showed the lowest adhesion score (P<0.05). In the light of the above results, HA 0.4% solution was more effective on prevention of adhesion than HA 0.6% and 0.8% solution.

• Journal of Microbiology and Biotechnology
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• 제15권3호
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• pp.510-518
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• 2005

In this study, we investigated whether PLGA microspheres in combination with hyaluronic acid (HA) gel have appropriate properties as a bulking agent for urologic injection therapies and whether the implantation of PLGA microspheres and HA gel induces angiogenesis in the newly formed tissues. In order to investigate whether this bulking agent is injectable, this material was injected through 24-gauge needles into the subcutaneous dorsum of the mouse. The bulking agent was easily injected without needle obstruction. Histological analyses of the hybrid tissues at 2 weeks showed that host cells at the surrounding tissues migrated into the spaces between the implanted PLGA microspheres and formed tissue-like structures. An inflammatory response to the implants was mild at 2 weeks and diminished at 8 weeks. Importantly, extensive ingrowth of blood vessels was observed in the hybrid tissues formed by the injection of PLGA microspheres and HA, whereas blood vessels rarely formed in the hybrid tissues formed by the injection of PLGA microspheres only. The implant volume was conserved for almost the entire implantation period. Histological analyses of the distant organs of the bulking agent-implanted animals, such as the lungs, liver, heart, brain, kidney, and spleen, showed no evidence of the injected microsphere migration. These results show that PLGA microspheres in combination with HA possess the appropriate characteristics for a bulking agent for urologic injection therapies and induce extensive blood vessel formation in the hybrid tissues.

• 멤브레인
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• 제19권4호
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• pp.310-316
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• 2009

조직 공학용 지지체로 사용할 목적으로 제조된 가교된 lactide/hyaluronic acid (LA/HA) 막의 분해 특성을 살펴보았다. 가교제 1,3-butadiene diepoxide (BD), 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)를 사용하여 얻어진 고분자 막을 $37^{\circ}C$로 조절된 항온조에서 증류수에 침전시켜 분해시켰다. 가교반응시 LA/HA 몰비가 작을수록, 가교제의 농도가 작을수록 생성된 고분자 막의 분해속도가 증가하였다. 분해될 때 막의 구조 변화를 살펴보기 위해 분해 전, 3일, 6일, 9일 후의 시료를 채취하여 핵자기 공명 분광법으로 분자 구조를 살펴보았다. EDC로 가교시킨 막의 경우 시간이 지남에 따라 HA-EDC 결합구조는 서서히 분해되는데 HA-LA 결합구조는 급격히 분해되어 6일 후에는 완전히 소멸되었다. BD로 가교시킨 막의 경우 가교된 결합 구조 모두 서서히 분해되었으며 3일, 6일이 지나면서 HA-BD 결합 구조는 원래의 89, 83%가 유지되었으나 HA-LA 결합 구조는 원래의 83, 65%로 유지되었다. 분해된 막을 전자 현미경으로 측정한 결과 분해 전후 표면에서 기공의 밀도는 크게 차이나지 않았으며, 표면과 측면의 구조도 크게 차이가 나지 않아 조직공학용 재료로써 사용할 때 아무런 문제가 없는 것으로 관찰되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.189-195
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• 2017

This study aimed to compare the cellular toxicities of three clinically used dry eye treatments; 3% diquafosol tetrasodium and hyaluronic acid at 0.3 and 0.18%. A methyl thiazolyltetrazoiun (MTT)-based calorimetric assay was used to assess cellular proliferation and a lactate dehydrogenase (LDH) leakage assay to assess cytotoxicity, using Human corneal epithelial cells (HCECs) exposed to 3% diquafosol tetrasodium, 0.3% hyaluronic acid (HA), or 0.18% HA or 1, 6 or 24 h. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy, and wound widths were measured 24 h after confluent HCECs were scratched. Diquafosol had a significant, time-dependent, inhibitory effect on HCEC proliferation and cytotoxicity. HCECs treated with diquafosol detached more from the bottoms of dishes and damaged cells showed degenerative changes, such as, reduced numbers of microvilli, vacuole formation, and chromatin of the nuclear remnant condensed along the nuclear periphery. All significantly stimulated reepithelialization of HCECs scratched, which were less observed in diquafosol. Therefore, epithelial toxicity should be considered after long-term usage of diquafosol and in overdose cases, especially in dry eye patients with pre-existing punctated epithelial erosion.

• 센서학회지
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• 제21권4호
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• pp.256-262
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• 2012

Hyaluronic acid(HA) hydrogels were synthesized by immersing HA microbeads in phosphate buffered saline solutions having different pH levels to assess the effect of pH on the swelling ratio of HA hydrogels for smart drug delivery systems. No beads were formed when the HA solution(below pH 9) was crosslinked with divinyl sulfone(DVS) because DVS is a basic solution. The variation regarding the size of the microbead was not significant, suggesting that the bead size is not a function of pH(10 ~ 14). However, the pore size of the microbeads decreased with increasing pH from 10 to 14, leading to the surface smoothness and dense network as a result of higher crosslinking. The swelling ratio of hydrogels increased when the pH rose from 2(acidic) to 6(neutral). Afterwards, it decreased with further increasing pH(basic). The lower swelling ratio may be due to the lack of ionization of the carboxyl groups. On the other hand, a higher swelling ratio is likely due to the increased electrostatic repulsions between negatively charged carboxyl groups on different chains. Experimental results suggested that pH-responsive HA hydrogels can be applicable to the controlled drug delivery systems.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권3호
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• pp.218-224
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• 2005

Surface modification of glutaraldehyde fixed bovine pericardium (GFBP) was success­fully carried out with hyaluronic acid (HA) derivatives. At first, HA was chemically modified with adipic dihydrazide (ADH) to introduce hydrazide functional group into the carboxyl group of HA backbone. Then, GFBP was surface modified by grafting HA-ADH to the free aldehyde groups on the tissue and the subsequent HA-ADH hydrogel coating. HA-ADH hydrogels could be prepared through selective crosslinking at low pH between hydrazide groups of HA-ADH and crosslinkers containing succinimmidyl moieties with minimized protein denaturation. When HA­ADH hydrogels were prepared at low pH of 4.8 in the presence of erythropoietin (EPO) as a model protein, EPO release was continued up to $85\%$ of total amount of loaded EPO for 4 days. To the contrary, only $30\%$ of EPO was released from HA-ADH hydrogels prepared at pH=7.4, which might be due to the denaturation of EPO during the crosslinking reaction. Because the carboxyl groups on the glucuronic acid residues are recognition sites for HA degradation by hyaluronidase, the HA-ADH hydrogels degraded more slowly than HA hydrogels prepared by the crosslinking reaction of divinyl sulfone with hydroxyl groups of HA. Following a two-week subcutaneous implantation in osteopontin-null mice, clinically significant levels of calcification were observed for the positive controls without any surface modification. However, the calcification of surface modified GFBP with HA-ADH and HA-ADH hydrogels was drastically reduced by more than $85\%$ of the positive controls. The anti-calcification effect of HA surface modification was also confirmed by microscopic analysis of explanted tissue after staining with Alizarin Red S for calcium, which followed the trend as observed with calcium quantification.

• Annals of dermatology
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• 제30권6호
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• pp.704-707
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• 2018

Parry Romberg Syndrome (PRS), also known as idiopathic progressive hemifacial atrophy, is a rare neurocutaneous disorder characterized by loss of skin and subcutaneous fat of face, muscles, and bones causing unilateral atrophy. Most patients require only soft tissue augmentation although syndrome has varying grades of severity. In the majority of reported cases, it has been treated with surgical flap or autologous fat transplantation. However, these treatments need complicated surgical skills which take a lot of time and cost. Herein we report the first case of PRS augmented by hyaluronic acid (HA) filler in a 42-year-old female patient to suggest that HA filler could be a safe, simple, and even rational economic alternative to surgical treatment.

• 폴리머
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• 제32권5호
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• pp.415-420
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• 2008

면역 거부반응이 없는 돼지 소장점막하조직(small intestinal submucosa, SIS)과 천연보습제인 히알루론산(hyaluronic acid, HA)은 생체재료로 널리 사용되고 있다. 본 연구에서는 이를 이용하여 스폰지를 제조하고 이들의 특성을 분석하였다. SIS-HA 스폰지는 완성된 SIS 스폰지에 1w%의 HA겔을 첨가하여 동결건조법으로 제조하고 100mM의 가교제를 통해 가교하여 이를 전자주사현미경, 적외선분광기, 물흡수성 실험을 하였다. 초기 세포부착률을 확인하고자 NIH/3T3를 분주하여 MTT 분석법을 수행하였다. FT-IR 분석을 통해 C-O관능기가 관찰되어 SIS-HA 스폰지 내부의 HA가 빠져나가지 않고 고르게 분포되어 있음을 확인하였고, MTT분석을 통하여 제조된 스폰지에서의 높은 세포생존율을 확인하였다. 즉, 본 연구에서 제조한 SIS-HA 스폰지는 SIS와 HA 각각의 특성을 모두 내재하고 있어 조직공학적 담체로 적합할 것이다.