• 한국식품영양학회지
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• 제9권3호
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• pp.242-246
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• 1996

High viscous hyaluronic acid complex from Klebsiella sp. L-10 NTG 50 mutant was purified by two-phase extraction system using PEG-K2HP04 and its physicochemical properties were Investigated. Viscosity of the purified hyaluronic acid complex was decreased as temperature and salts concentration were Increased and also showed low viscosity at below pH 5.0 and above pH 11.0. Hardness, cohesiveness and adhesiveness of the purified hyaluronic acid complex were 1, 20kg, 1.91 and 0.62, respectively. Water holding capacity was 6.9ml per gram of the purified hyaluronic acid complex powder.

• 자연과학논문집
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• 제8권1호
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• pp.33-39
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• 1995

Klebsiella sp. L-10을 N-methyl-N'-nitro-N''-nitrosoguanidine 과 ethylmethane sulfornate 및 자외선 등으로 돌연변이시켜 히아루론산 복합체의 수율이 친주보다 약 2.5배 증대된 NTG 50 변이주를 얻었다. NTG 50변이주를 이용한 히아루론산 복합체의 최적 생산배지 조성은 효모 추출물 0.1%, 트립톤 3%, 포도당 3%, $K_2HPO_4$ 와 $KH_2PO_4$ 각각 30nM 이었고 배양조건은 배지의 초기 pH 6.0-6.5, 배양온도 $37^{\circ}C$, 24시간의 진탕배양이었으며 이때 배양액 리터당 2900mg의 히아루론산 복합체가 생산되었다.

• 자연과학논문집
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• 제7권
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• pp.59-65
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• 1995

토양으로부터 고점성의 히아루론산 복합체를 생산하는 균주를 분리하여 Klebsiella sp.L-10으로 동정하였다. Klebsiella sp. L-10의 히아루론산 복합체 생산 최적 배지 조성은 yeast ext. 0.1%, tryptone 3%, glucose 5%, $K_2HPO_4$와 $KH_2PO_4$ 각각 10mM이었고 배양조건은 배지의 초기 pH6.5, 배양온도 $37^{\circ}C$, 배양시간 18시간 이었으며 이 조건에서 배양액 리터당 약 1,400mg의 점성이 매우 강한 히아루론산 복합체가 생산되었다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제35권3호
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• pp.137-145
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• 2009

As an efficient controlled release system for rhBMP-2, a functional nanoparticle-hydrogel complex, incorporated with matrix metalloproteinase(MMP) sensitive peptide cross-linker, was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase(ALP) activity and mineral contents analysis, based on the rat calvarial critical size defect(8mm in diameter) model. Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded MMP sensitive hyaluronic acid(HA) based hydrogel-Nanoparticles(NP) complex, as compared to only MMP HA, the MMP HA-NP without rhBMP-2, or even with the rhBMP-2. These improvements included the formation pattern of bone and functional marrow, the degree of calcium quantification, and the ALP activity. These results indicate that the MMP sensitive HA with nano-particle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced rhBMP-2 scaffold.

• 방사선산업학회지
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• 제5권2호
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• pp.159-164
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• 2011

A variety of natural polymers have been used as tissue engineering scaffolds, drug delivery system, and cosmetic materials due to their higher biocompatibility and water uptake. As a major component of extracellular matrix, hyaluronic acid consisting of D-glucuronic acid and N-acetylglucosamine has been popularly used as a hydrogel material. Even though it has good properties to be used in the tissue engineering and cosmetic industry, its higher viscosity has limited a potential use in a variety of applications; only low content should be applied in preparing above products. In the present study, we investigated the effect of electron beam irradiation on the properties of hyaluronic acid. Hyaluronic acid paste containing low contents of water changed to solution after electron beam irradiation ranging from 1 to 10 kGy, which didn't exhibit any alteration of surface properties and morphological change after freeze-drying. However, its viscosity was significantly decreased as absorbed dose increased, which was approximately one by hundred in comparison with the viscosity of original hyaluronic acid solution with same concentration. In addition, it can still interact with positive charged chitosan generating polyelectrolyte complex. Therefore, only viscosity was decreased after electron beam irradiation, whereas other properties of hyaluronic acid maintained. Consequently, these hyaluronic acids with lower viscosities can be used in a variety of applications in tissue engineering, drug delivery, and cosmetic industry.

• Biotechnology and Bioprocess Engineering:BBE
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• 제9권3호
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• pp.179-183
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• 2004

A biocompatible polyelectrolyte complex multilayer (PECML) film consisting of poly-L-lysine (PLL) as a polycation and hyaluronic acid (HA) as a polyanion was developed to test its use for surface modification to prevent cell attachment and protein drug delivery. The formation of PECML through the electrostatic interaction of HA and PLL was confirmed by contact angle measurement, ESCA analysis, and HA content analysis. HA content increased rapidly up to 8 cycles for HA/PLL deposition and then slightly increased with an increasing number of deposition cycle. In vitro release of PLL in the PECML continued up to 4 days and ca. 25% of HA remained on the chitosan-coated cover glass after in vitro release test for 7 days. From the results, PECML of HA and PLL appeared to be stable for about 4 days. The surface modification of the chitosan-coated cover glass with PECML resulted in drastically reduced peripheral blood mononuclear cell (PBMC) attachment. Concerned with its use for protein drug delivery, we confirmed that bovine serum albumin (BSA) as a model protein could be incorporated into the PECML and its release might be triggered by the degradation of HA with hyaluronidase.

• Archives of Plastic Surgery
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• 제36권5호
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• pp.548-554
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• 2009

Purpose: To evaluate clinical efficacy and safety of hyaluronic acid based autologous dermal fibroblasts (Hyalograft 3D) in the treatment of diabetic foot ulcers. Methods: A total of 28 patients with diabetic ulcers were randomized to either the control group with nonadherent foam dressings(n=14) or the treatment group with autologous tissue - engineered grafts(n=14). Weekly assessment contained vital sign checks, ulcer size measurements, and wound photos. At 12th week, percentages of complete wound healing and mean healing times were compared. Safety was also monitored by adverse events. Results: Complete wound healing was achieved in 84.6% of the treatment group and 23.1% of the control group (p<0.005). The mean times of closures for the treatment versus control groups were 6.1 weeks and 10.9 weeks, respectively. No adverse events related to the study treatment occurred. Conclusion: The use of hyaluronic acid based autologous fibroblast grafts was found to be a safe and effective treatment for diabetic foot ulcers.

• 대한약리학회지
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• 제28권2호
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• pp.201-212
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• 1992

외인성 taurine이 HOCl, $NH_2Cl$과 그밖의 산화성 물질에 의한 hyaluronic acid의 변성에 미치는 영향을 관찰하였다. HOCl, $NH_2Cl$과 그밖의 산화성 물질에 대한 taurine의 제거 작용을 조사하였다. Taurine의 항 산화 작용을 또한 치올 화합물의 작용과 비교 관찰하였다. Hyaluronic acid의 점성도는 HOCl과 $NH_2Cl$에 의하여 뚜렷하게 용량에 따라 감소하였다. Hyaluronic acid에 대한 HOCl의 변성 효과는 $NH_2Cl$에 의한 것보다 현저하였다. Taurine은 HOCl과 $NH_2Cl$에 의한 hyaluronic acid의 변성을 효과적으로 용량에 따라 억제하였다. HOCl의 변성 효과는 DMSO에 의하여 뚜렷하게 억제되었다. $Fe^{2+}$과 $H_2O_2$에 의한 hyaluronic acid의 변성은 catalase와 DMSO에 의하여 억제되었으나 taurine의 영향은 받지 않았다. Xanthine과 xanthine oxidase의 변성 작용은 SOD와 catalase에 의하여 효과적으로 억제되었으나 taurine의 영향은 받지 않았다. HOCl은 taurine, DMSO, GSH와 MPG에 의하여 유의하게 분해되었다. 파장 250 nm에서의 HOCl의 흡광도와 파장 242 nm에서의 $NH_2Cl$의 흡광도는 taurine의 첨가로 유의하게 증가하였다. $NH_2Cl$과 GSH 또는 MPG의 상호 작용으로 초기에 최대의 흡광도가 관찰되었으나, 이러한 흡광도는 반응 시간에 따라 점차적으로 감소하였다. $Fe^{2+}$와 $H_2O_2$의 존재하에서 OH 의 생성은 catalase와 DMSO에 의하여 억제되었으나 taurine의 영향은 받지 않았다. DABCO와 DABA에 반응하는 자외선 조사에 따른 $^1O_2$의 생성은 taurine의 영향을 받지 않았다. GSH와 MPG는 HOCl의 변성 작용을 뚜렷하게 억제하였다. 이상의 결과로 부터 hyaluronic acid의 변성을 포함한 조직 구성성분의 산화성 손상에 있어서 taurine의 보호 작용은 산소 유리 라디칼에 대한 제거 작용과 관계없으며 HOCl과 $NH_2Cl$에 대한 제거 작용 그리고 taurine과 HOCl 또는 $NH_2Cl$의 복합체 형성에 기인할 것으로 시사된다. Taurine의 치올 기가 HOCl과 $NH_2Cl$에 의한 변성에 부분적으로 보호 작용을 나타 낼 것으로 추정된다.

• Clinical Pain
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• 제19권1호
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• pp.8-15
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• 2020

Objective: To compare the therapeutic efficacy of the bone marrow aspirate concentrate (BMAC)- platelet-rich plasma (PRP) complex with hyaluronic acid in patients with knee osteoarthritis. Method: Thirty-four patients with knee osteoarthritis participated in this study. Seventeen patients in the study group underwent BMAC and PRP extraction followed by intra-articular injection of BMAC-PRP complex within affected knee. Seventeen patients in the control group underwent intra-articular injection of hyaluronic acid. Knee injury, osteoarthritic outcome score (KOOS), and EuroQol-5D (EQ-5D) questionnaire were evaluated before, one month, three months, and six months after the injection. Results: There were statistically significant temporal differences in total KOOS scores in both BMAC-PRP and HA groups. However, there were no significant group difference in the study period. In the Sports and Recreational Function Scale, there was statistically significant improvement in the BMAC-PRP group compared to the HA group at three months (p=0.041). There were no side effects or complications in both groups. Conclusion: Intra-articular injection of BMAC-PRP showed better functional recovery in the OA at three months and this can be an alternative treatment in terms of functional recovery in the OA in addition to the decrease of pain.

• Tissue Engineering and Regenerative Medicine
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• 제15권6호
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• pp.761-769
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• 2018

BACKGROUND: Bioprinting has recently appeared as a powerful tool for building complex tissue and organ structures. However, the application of bioprinting to regenerative medicine has limitations, due to the restricted choices of bio-ink for cytocompatible cell encapsulation and the integrity of the fabricated structures. METHODS: In this study, we developed hybrid bio-inks based on acrylated hyaluronic acid (HA) for immobilizing bio-active peptides and tyramine-conjugated hyaluronic acids for fast gelation. RESULTS: Conventional acrylated HA-based hydrogels have a gelation time of more than 30 min, whereas hybrid bio-ink has been rapidly gelated within 200 s. Fibroblast cells cultured in this hybrid bio-ink up to 7 days showed >90% viability. As a guidance cue for stem cell differentiation, we immobilized four different bio-active peptides: BMP-7-derived peptides (BMP-7D) and osteopontin for osteogenesis, and substance-P (SP) and Ac-SDKP (SDKP) for angiogenesis. Mesenchymal stem cells cultured in these hybrid bio-inks showed the highest angiogenic and osteogenic activity cultured in bio-ink immobilized with a SP or BMP-7D peptide. This bio-ink was loaded in a three-dimensional (3D) bioprinting device showing reproducible printing features. CONCLUSION: We have developed bio-inks that combine biochemical and mechanical cues. Biochemical cues were able to regulate differentiation of cells, and mechanical cues enabled printing structuring. This multi-functional bio-ink can be used for complex tissue engineering and regenerative medicine.