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임종은,Jeffrey A. Hubbell,이승태,한동근,임정묵 한국고분자학회 2015 Macromolecular Research Vol.23 No.4
The development of an in vitro culture system, comparable to the in vivo environment in terms of effectson oocyte growth and development, could provide a valuable experimental tool for studying the mechanisms governingoocyte development as well as practical clinical, agricultural, zoological, and biotechnological applications. This studyreports on the importance of the microenvironment for the ovarian folliculogenesis process. The complexity of sucha microenvironment was approached with a strategy based on functionalized PEG-hydrogels. The PEG matrix notonly serves as a scaffold, but it is also used a reservoir of immobilized cues. Using tethered integrin-binding peptidesin combination with other signaling factors, we aimed at better understanding the interactions of the oocyte and itssurrounding granulosa that may determine the efficiency of the actual and the future in vitro mature oocyte production. Ina first step, the mechanical properties of PEG-hydrogel were optimized for producing secondary follicles, in whichthe oocyte is surrounded by two layers of granulosa cells. Follicle growth was highly dependent on the mechanicalproperties of the surrounding environment, with the optimal elastic modulus being approx. 1 kPa. The effects of keysoluble factors were also investigated to confirm their compatibility with the established 3-D culture system and tofurther qualitatively and quantitatively improve the produced mature oocytes. Accordingly, various combinations ofthe gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were tested. Interestingly, theeffects of the gonadotropins in the 3-D PEG system were close to their known in vivo effects. In conclusion, this studydemonstrates the efficiency and the flexibility of a novel 3-D culture system, PEG-hydrogel. Circumventing problemsinherent to the “on-plastic” standard culture, such as the loss of the granulosa-oocyte interactions, allowed the emergenceof a culture system tailored for investigating fundamental folliculogenesis-related questions. Furthermore, the reportedculture system may serve as a platform for developing clinical and biotechnology applications.
임종은,Irina Krier,임정묵,심수진,한동근,Jeffrey A. Hubbell 한국고분자학회 2015 Macromolecular Research Vol.23 No.4
Polyethylenimine (PEI) is a promising gene carrier among polymeric vectors because of its high transfectionefficiency, buffering capacity, which is responsible for its escape from endosomes, facility of modification,reasonable price and wide range of molecular weight. However, toxicity of PEI is an important obstacle to overcomefor using it as a gene carrier in gene therapy protocols. In our study, PEI (10 kDa) was modified with urocanic acid,which has an imidazole ring (PEIU). This modification of PEI played an important role by improving transfectionefficiency and reducing toxicity. The PEIU was condensed with DNA in different nitrogen of polycation/phosphateof DNA (N/P) ratios starting from 1.25. The PEIU/DNA complexes formed smaller (60-80 versus 100-400 nm) andless dispersible particles than PEI/DNA complexes. Cell viability test showed that in all the transfection experimentsPEIU was always found less toxic than the PEI on three different cell-lines, Cos-7, HeLa, and 293T. The PEIUdemonstrated improved biocompatibility as compared to the PEI. The in vitro transfection experiments showed thatthe PEIU displayed similar or lower transfection efficiencies than the PEI in the absence of serum. In medium complementedwith serum, the PEIU had higher transfection efficiencies than the PEI. In vivo transfection experimentswere carried out with intravenous and subcutaneous injections into mice. Five different organs were taken and lysedfor quantification of expressed GFP. The quantification of the fluorescence of these organs exhibited that the PEIUhas better transfection efficiency in in vivo experiments compared to the PEI. This study generated a strong evidenceindicating that PEIU can be considered as a promising versatile gene carrier because of its biocompatibility and goodtransfection efficiency.
Lih, Eugene,Park, Wooram,Park, Ki Wan,Chun, So Young,Kim, Hyuncheol,Joung, Yoon Ki,Kwon, Tae Gyun,Hubbell, Jeffrey A.,Han, Dong Keun American Chemical Society 2019 ACS central science Vol.5 No.3
<▼1><P/><P>Kidney diseases are a worldwide public health issue. Renal tissue regeneration using functional scaffolds with biomaterials has attracted a great deal of attention due to limited donor organ availability. Here, we developed a bioinspired scaffold that can efficiently induce renal tissue regeneration. The bioinspired scaffold was designed with poly(lactide-<I>co</I>-glycolide) (PLGA), magnesium hydroxide (Mg(OH)<SUB>2</SUB>), and decellularized renal extracellular matrix (ECM). The Mg(OH)<SUB>2</SUB> inhibited materials-induced inflammatory reactions by neutralizing the acidic microenvironment formed by degradation products of PLGA, and the acellular ECM helped restore the biological function of kidney tissues. When the PLGA/ECM/Mg(OH)<SUB>2</SUB> scaffold was implanted in a partially nephrectomized mouse model, it led to the regeneration of renal glomerular tissue with a low inflammatory response. Finally, the PLGA/ECM/Mg(OH)<SUB>2</SUB> scaffold was able to restore renal function more effectively than the control groups. These results suggest that the bioinspired scaffold can be used as an advanced scaffold platform for renal disease treatment.</P></▼1><▼2><P>PLGA scaffold with Mg(OH)<SUB>2</SUB> and renal ECM facilitates kidney reconstruction (histological structure and biological function) by neutralizing the acidic microenvironment and improving biocompatibility.</P></▼2>
Lih, Eugene,Kum, Chang Hun,Park, Wooram,Chun, So Young,Cho, Youngjin,Joung, Yoon Ki,Park, Kwang-Sook,Hong, Young Joon,Ahn, Dong June,Kim, Byung-Soo,Kwon, Tae Gyun,Jeong, Myung Ho,Hubbell, Jeffrey A.,H American Chemical Society 2018 ACS NANO Vol.12 No.7
<P>Biodegradable polymers have been extensively used in biomedical applications, ranging from regenerative medicine to medical devices. However, the acidic byproducts resulting from degradation can generate vigorous inflammatory reactions, often leading to clinical failure. We present an approach to prevent acid-induced inflammatory responses associated with biodegradable polymers, here poly(lactide-<I>co</I>-glycolide), by using oligo(lactide)-grafted magnesium hydroxide (Mg(OH)<SUB>2</SUB>) nanoparticles, which neutralize the acidic environment. In particular, we demonstrated that incorporating the modified Mg(OH)<SUB>2</SUB> nanoparticles within degradable coatings on drug-eluting arterial stents efficiently attenuates the inflammatory response and in-stent intimal thickening by more than 97 and 60%, respectively, in the porcine coronary artery, compared with that of drug-eluting stent control. We also observed that decreased inflammation allows better reconstruction of mouse renal glomeruli in a kidney tissue regeneration model. Such modified Mg(OH)<SUB>2</SUB> nanoparticles may be useful to extend the applicability and improve clinical success of biodegradable devices used in various biomedical fields.</P> [FIG OMISSION]</BR>