• Macromolecular Research
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• v.16 no.8
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• pp.704-710
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• 2008

Injectable hydrogels are quite promising materials due to their potential to minimize invasive implantation and this provides versatile fitness irrespective of the damaged regions and facilitates the incorporation of bioactive agents or cells. In situ gel formation through stereocomplex formation is a promising candidate for injectable hydrogels. In this paper, a new series of enantiomeric, four-arm, PEG-PLA block copolymers and their stereocomplexed hydrogels were prepared by bulk ring-opening polymerization of D-lactide and L-lactide, respectively, with stannous octoate as a catalyst. The prepared polymers were characterized by $^1H$ nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FT IR) spectroscopy, gel permeation chromatography (GPC) and thermal gravitational analysis (TGA), confirming the tailored structure and chain lengths. The swelling and degradation behavior of the hydrogels formed from a selected copolymer series were observed in different concentrations. The degradation rate decreased with increasing polymer content in the solution. The rheological behavior indicated that the prepared hydrogel underwent in situ gelation and had favorable mechanical strength. In addition, its feasibility as an injectable scaffold was evaluated using a media dependence test for cell culture. A Tris solution was more favorable for in situ gel formation than PBS and DMEM solutions were. These results demonstrated the in situ formation of hydrogel through the construction of a stereocomplex with enantiomeric, 4-arm, PEG-PLA copolymers. Overall, enantiomeric, 4-arm, PEG-PLA copolymers are a new species of stereocomplexed hydrogels that are suitable for further research into injectable hydrogels.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.6
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• pp.374-378
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• 2003

Aim : Several injectable materials have been used in the application of osteogenic bone substitute; however, nothing has won universal acceptance. This study was performed to investigate whether chitosan-alginate gel/MSCs/BMP-2 composites are potentially injectable materials for new bone formation. Material and Methods : The composites were injected into the subcutaneous space on the dorsum of the nude mouse to investigate whether new bone would be tissue engineered in the mouse. The composites were examined histologically over a 12-week period. Results : The composites implanted in the mouse were able to tissue engineer new bone, and the newly formed bone consisted of trabecular bone and calcified bone matrix. Conclusions : The present study shows that chitosan-alginate gel/MSCs/BMP-2 composites have the potential to become real injectable materials for new bone formation.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.165-172
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• 2002

Injectable gel composed of egg phosphatidylcholine (egg PC), hyaluronate (HA) and water was formulated for local drug delivery. The lamellar liquid crystalline structure of the egg PC/water system did not change by adding HA in the formulation. However, egg PC/HA/water gel was more resistant to erosion than the egg PC/water gel. The egg PC/HA/water and egg PC/water gels containing model drugs, tetracycline and sudan IV were prepared to perform in vitro and in vivo drug release experiments. In vitro release of tetracycline was sustained in the gel type formulations. The release rate of hydrophobic sudan IV was extremely slow. More than 99% of sudan IV remained inside the gel after 5 days. In vivo release of drugs from the air pouch model in Balb/c mice shows that lipophilic sudan IV remained for more than 10 days whereas tetracycline remained for 1 day in the pouch. The compatibility of the gels was also examined by histopathology. The gels did not cause any adverse inflammatory effect in the air pouch.

• Journal of Periodontal and Implant Science
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• v.46 no.4
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• pp.277-287
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• 2016

Purpose: The purpose of this study was to evaluate the clinical efficacy of enhancing deficient interdental papilla with hyaluronic acid gel injection by assessing the radiographic anatomical factors affecting the reconstruction of the interdental papilla. Methods: Fifty-seven treated sites from 13 patients (6 males and 7 females) were included. Patients had papillary deficiency in the upper anterior area. Prior to treatment, photographic and periapical radiographic standardization devices were designed for each patient. A 30-gauge needle was used with an injection-assistance device to inject a hyaluronic acid gel to the involved papilla. This treatment was repeated up to 5 times every 3 weeks. Patients were followed up for 6 months after the initial gel application. Clinical photographic measurements of the black triangle area (BTA), height (BTH), and width (BTW) and periapical radiographic measurements of the contact point and the bone crest (CP-BC) and the interproximal distance between roots (IDR) were undertaken using computer software. The interdental papilla reconstruction rate (IPRR) was calculated to determine the percentage change of BTA between the initial and final examination and the association between radiographic factors and the reconstruction of the interdental papilla by means of injectable hyaluronic acid gel were evaluated. Results: All sites showed improvement between treatment examinations. Thirty-six sites had complete interdental papilla reconstruction and 21 sites showed improvement ranging from 19% to 96%. The CP-BC correlated with the IPRR. More specifically, when the CP-BC reached 6 mm, virtually complete interdental papilla reconstruction via injectable hyaluronic acid gel was achieved. Conclusions: These results suggest that the CP-BC is closely related to the efficacy of hyaluronic acid gel injection for interdental papilla reconstruction.

• Polymer(Korea)
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• v.28 no.4
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• pp.344-351
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• 2004

Poly(ethylene glycol)-based diblock and triblock polyester copolymers stimulating to temperature were studied as injectable biomaterials in drug delivery system because of their nontoxicity, biocompatibility and biodegradability. We synthesized the diblock copolymers consisting of methoxy poly(ethylene glycol) (MPEG) (M$_{n}$=750 g/mole) and poly($\varepsilon$-caprolactone) (PCL) by ring opening polymerization of $\varepsilon$-CL with MPEG as an initiator in the presence of HCl . Et$_2$O. The aqueous solution of synthesized diblock copolymers represented sol phase at room temperature and a sol to gel phase transition as the temperature increased from room temperature to body temperature. To confirm the in vivo gel formation, we observed the formation of gel in the mice body after injection of 20 wt% aqueous solution of each block copolymer. After 2 months, we observed the maintenance of gel without dispersion in mice. In this study, we synthesized diblock copolymers exhibiting sol-gel phase transition and confirmed the feasibility as biomaterials of injectable implantation.n.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.644-647
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• 2003

Materials currently used as an injectable bulking agent in the dermatologic and urologic fields revealed several drawbacks such as particles migration, inflammatory reaction, allergic reaction, rapid volume shrinkage, and necessity of a donor site. In this study, we have developed injectable biomaterial comprising poly (DL- lactide-co-glycolide)(PLGA) and hyaluronic acid gel to overcome these problems. PLGA is a biocompatible synthetic material and hyaluronic acid is a common substance found in living organisms. We examined the feasibility of injection through needle and tested biocompatibility in animal model. After transplantation, injected sites and distant organs were examined histologically to verify a new tissue formation, inflammation, and particles migrations. Injected volume was maintained approximately 80 percent for 2 months. Results demonstrated that the developed material was injectable through various gauges of needles and induced a new bulking tissue formation without serious inflammatory reaction.

• Biomaterials Research
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• v.22 no.4
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• pp.235-248
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• 2018

Background: Injectable hydrogels have been extensively researched for the use as scaffolds or as carriers of therapeutic agents such as drugs, cells, proteins, and bioactive molecules in the treatment of diseases and cancers and the repair and regeneration of tissues. It is because they have the injectability with minimal invasiveness and usability for irregularly shaped sites, in addition to typical advantages of conventional hydrogels such as biocompatibility, permeability to oxygen and nutrient, properties similar to the characteristics of the native extracellular matrix, and porous structure allowing therapeutic agents to be loaded. Main body: In this article, recent studies of injectable hydrogel systems applicable for therapeutic agent delivery, disease/cancer therapy, and tissue engineering have reviewed in terms of the various factors physically and chemically contributing to sol-gel transition via which gels have been formed. The various factors are as follows: several different non-covalent interactions resulting in physical crosslinking (the electrostatic interactions (e.g., the ionic and hydrogen bonds), hydrophobic interactions, ${\pi}$-interactions, and van der Waals forces), in-situ chemical reactions inducing chemical crosslinking (the Diels Alder click reactions, Michael reactions, Schiff base reactions, or enzyme-or photo-mediated reactions), and external stimuli (temperatures, pHs, lights, electric/magnetic fields, ultrasounds, or biomolecular species (e.g., enzyme)). Finally, their applications with accompanying therapeutic agents and notable properties used were reviewed as well. Conclusion: Injectable hydrogels, of which network morphology and properties could be tuned, have shown to control the load and release of therapeutic agents, consequently producing significant therapeutic efficacy. Accordingly, they are believed to be successful and promising biomaterials as scaffolds and carriers of therapeutic agents for disease and cancer therapy and tissue engineering.

• Proceedings of the Korean Society of Soil and Groundwater Environment Conference
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• 2002.04a
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• pp.98-101
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• 2002

Numerical experiments were performed to investigate horizontal barrier formation in unsaturated soils by permeation grouting through multiple vertical injection pipes. The results were compared with the horizontal barrier formation achieved by using multiple horizontal injection pipes. It was observed that tile point injection of the vertical pipe system generates a gel barrier that has a less lateral area than the injection through the horizontal pipe.

• Macromolecular Research
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• v.14 no.1
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• pp.87-93
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• 2006

Copolymers composed of hyaluronic acid (HA) and poly(N-isopropylacrylamide) (PNIPAAm) were prepared to create temperature-sensitive injectable gels for use in controlled drug delivery applications. Semi-telechelic PNIPAAm, with amino groups at the end of each main chain, was synthesized by radical polymerization using 2-aminoethanethiol hydrochloride (AESH) as the chain transfer agent, and was then grafted onto the carboxyl groups of HA using carbodiimide chemistry. The result of the thermo-optical analysis revealed that the phase transition of the PNIPAAm-grafted HA solution occurred at around 30$\∼$33$^{circ}C$. As the graft yield of PNIPAAm onto the HA backbone increased, the HA-g-PNIPAAm copolymer solution exhibited sharper phase transition. The short chain PNIPAAm-grafted HA ($M_{w}$=6,100) showed a narrower temperature range for optical turbidity changes than the long chain PNIPAAm-grafted HA ($M_{w}$=13,100). PNIPAAm-grafted HA exhibited an increase in viscosity above 35$^{circ}C$, thus allowing the gels to maintain their shape for 24 h after in vivo administration. From the in vitro riboflavin release study, the HA-g-PNIPAAm gel showed a more sustained release behavior when the grafting yield of PNIPAAm onto the HA backbone was increased. In addition, BSA released from the PNIPAAm-g-HA gels showed a maximum concentration in the blood 12 h after being injected into the dorsal surface of a rabbit, followed by a sustained release profile after 60 h.

• Macromolecular Research
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• v.12 no.5
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• pp.507-511
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• 2004

We have developed an injectable thermosensitive hydrogel for local drug delivery to treat cancers clinically. We selected chitosan as a polymer matrix because of its biocompatibility and biodegradability. Glycerol 2-phosphate disodium salt hydrate (${\beta}$-GP) was used to neutralize the chitosan solution to physiological pH. The chitosan solution displayed a sol-gel phase transition in a pH-and temperature-dependent manner and formed an endothermic hydrogel after subcutaneous injection into mouse in the presence of ${\beta}$-GP. Additionally, we evaluated the biodegradation of chitosan hydrogel in mice by measuring the volume of injected chitosan hydrogel after subcutaneous injection. The injected chitosan hydrogel in mice was sected and stained with hematoxylin-eosin reagent for histological observation to confirm biodegradation of the hydrogel by the infiltrated cells. Chitosan hydrogel systems that possess biocompatibility and biodegradability could be promising thermosensitive injectable materials useful as depot systems for local anti-cancer drug delivery.