Phosphorylcholine-Based Zwitterionic Biocompatible Thermogel

Zwitterionic polymers have been investigated as surface-coating materials due to their low protein adsorption properties, which reduce immunogenicity, biofouling, and bacterial adsorption of coated materials. Most zwitterionic polymers, reported so far, are based on (meth)acrylate polymers which can induce toxicity by residual monomers or amines produced by degradation. Here, we report a new zwitterionic polymer consisting of phosphorylcholine (PC) and biocompatible poly-(propylene glycol) (PPG) as a new thermogelling material. The PC-PPG-PC polymer aqueous solution undergoes unique multiple sol-gel transitions as the temperature increases. A heat-induced unirner-to-micelle transition, changes in ionic interactions, and dehydration of PPG are involved in the sol-gel transitions. Based on the broad gel window and low protein adsorption properties, the PC-PPG-PC thermogel is proved for sustained delivery of protein drugs and stem cells over 1 week

Thermal gelation or gel melting: (Ethylene glycol)113-(l -Alanine)12 and (ethylene glycol)113-(l -lactic acid) 12

block copolymers; micelles; self-assembly; sol-gel transition; stimuli-sensitive polymer

Molecular captain: A light-sensitive linker molecule in poly(ethylene glycol)-poly(L -alanine)-poly(ethylene glycol) triblock copolymer directs molecular nano-assembly, conformation, and sol-gel transition

We report a poly(ethylene glycol)-poly(L-alanine)-azobenzene-poly(L- alanine)-poly(ethylene glycol) (PEG-PA-Z-PA-PEG) as a temperature and light sensitive polymer. The poly(ethylene glycol)-poly(L-alanine) diblock copolymers with a flexible-rigid block structure were coupled by an azobenzene group that undergoes a reversible configurational change between "trans" and "cis" upon exposure to UV and vis light. The single azobenzene molecule embedded in the middle of a block copolymer with a flexible (shell)-rigid (core) structure significantly affected molecular assembly, micelle size, polypeptide secondary structure, and sol-to-gel transition temperature of the polymer aqueous solution, depending on its exposure to UV or vis light. © 2012 Wiley Periodicals, Inc

Microsphere-Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells

Neuronal differentiation of tonsil-derived mesenchymal stem cells (TMSCs) is investigated in a 3D hybrid system. The hybrid system is prepared by increasing the temperature of poly(ethylene glycol)-poly(l-alanine) aqueous solution to 37 °C through the heat-induced sol-to-gel transition, in which TMSCs and growth factor releasing microspheres are suspended. The in situ formed gel exhibits a modulus of 800 Pa at 37 °C, similar to that of brain tissue, and it is robust enough to hold the microspheres and cells during the 3D culture of TMSCs. The neuronal growth factors are released over 12-18 d, and the TMSCs in a spherical shape initially undergo multipolar elongation during the 3D culture. Significantly higher expressions of the neuronal biomarkers such as nuclear receptor related protein (Nurr-1), neuron specific enolase, microtubule associated protein-2, neurofilament-M, and glial fibrillary acidic protein are observed in both mRNA level and protein level in the hybrid systems than in the control experiments. This study proves the significance of a controlled drug delivery concept in tissue engineering or regenerative medicine, and a 3D hybrid system with controlled release of growth factors from microspheres in a thermogel can be a very promising tool. A microsphere-incorporated hybrid hydrogel is prepared by thermogellation of a microsphere- and stem cell-suspended poly(ethylene glycol)-b-poly(l-alanine) aqueous solution. The controlled supply of neuronal growth factors from the microspheres to the coencapsulated tonsil derived mesenchymal stem cells provides an effective tool in controlling neuronal differentiation of the stem cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

생활기본시설 설치비 부담에 관한 연구

학위논문 (석사)-- 서울대학교 행정대학원 : 공기업정책학과, 2015. 8. 홍준형.공익사업 시행으로 인한 손실보상의 일환으로 이루어지는 생활대책과 관련하여 당사자간 이해관계가 첨예하게 대립되고, 많은 분쟁이 발생하는 지점이 바로 생활대책 중에서도 이주자에 대한 택지 및 주택의 특별공급에 관한 것이라 할 수 있다. 종래 이주자대책의 중심은 댐건설 등으로 생활의 근거를 상실하는 이주자들에게 사업지구 밖에 별도의 이주정착지를 조성하여 종래의 생활 상태를 회복시켜 주는 방법이 주를 이루었다면, 공익사업의 규모가 커지고 대규모 신도시 개발 등 사업시행으로 인해 생활의 근거를 상실하는 이주자의 규모 또한 커짐에 따라 최근의 이주자대책의 중심은 택지개발사업지구 등 당해 사업지구 내에 조성된 택지나 주택을 이주자에게 우선하여 공급하는 이른바 특별공급이 주를 이루고 있다고 할 수 있다. 과거 부동산 가격이 꾸준히 상승하던 시기에는 사업시행지구 인근의 이주정착지로 이전하는 것보다는 사업지구 내에 조성된 주택이나 택지를 공급 받는 것이 전매를 통한 양도차익 등 경제적 이익을 도모할 수 있는 여지가 많다는 점에서 이주대상자들은 이러한 특별공급을 선호하였으나, 최근에 부동산 가액이 하락하면서 이주대상자들이 취할 수 있는 경제적 이익이 작아지고 극단적인 경우에는 손실을 보는 사례도 나타남에 따라, 사업시행자를 상대로 이주자택지나 특별공급주택의 분양가격에 이주대상자에게 부담시킬 수 없는 생활기본시설 설치비가 포함되어 있음을 주장하여 많은 소송이 제기되고 있는 실정이다. 본 연구에서는 이러한 배경을 바탕으로 2007년 선고된 대법원 2007다63089 전원합의체 판결에 대한 분석을 논의의 중심으로 삼아 생활보상의 일종인 이주대책의 일환으로 이루어지는 택지 및 주택의 특별공급을 둘러싼 제도의 문제점 및 이주정착지 제공과 특별공급의 차이점을 분석하고 이주자택지나 주택을 공급하는 경우에도 이주정착지의 경우와 같이 생활기본시설 설치비를 사업시행자가 부담하여야 하는지에 대하여 비판적으로 검토하였다.목 차 제 1 장 서론 1 제 1 절 연구의 배경 및 목적 1 제 2 절 연구의 범위와 방법 6 제 2 장 이론적 배경 및 선행연구 8 제 1 절 선행연구 8 제 2 절 생활보상의 일반론 9 제 3 절 이주대책의 의의와 실정법적 근거 28 제 4 절 택지조성원가와 공동주택 분양가격 40 제 3 장 생활기본시설설치비 관련 판례 고찰 46 제 1 절 2007다63089 전원합의체 판결 분석 46 제 2 절 판례에 표출된 관련 규정의 해석론 53 제 3 절 전원합의체 판결이후 하급심 판례 동향 70 제 4 장 실제 운용상 문제점 및 정책적 제언 84 제 1 절 각 사업시행자의 관련 내부규정 비교 84 제 2 절 실제 운용상의 문제점 91 제 3 절 정책적 제언 99 제 5 장 결론 105 참고문헌 108 Abstract 110Maste

Synthesis and characterization of novel thermo-responsive F68 block copolymers with cell-adhesive RGD peptide

Thermosensitive poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer, Pluronic F68, containing a hydrophobic unit, oligo-(lactic acid)(oligo-LA) or oligo-caprolactone (oligo-CL), 2-META and RGD as side groups was successfully synthesized and characterized by 1H NMR, FTIR, and elemental analysis. Their aqueous solution displayed special gel-sol-gel phase transition behavior with increasing temperature from 10 to 70°C, when the polymer concentration was above critical micelle concentration (CMC). The gel-sol phase diagram was investigated using tube inversion method, rheological measurement, and dynamic light scattering. Based on these results, the gelation properties of modified F68 were affected by several factors such as the composition of the substituents, chain length of oligo l-LA or oligo -CL, and the concentration of the polymer solutions. The unique phase transition behavior with temperature was observed by modified F68 triblock copolymer, composed of the PPO blocks core and the PEO blocks shell in aqueous solution. This phenomenon was elucidated using 1H NMR data; the alteration of hydrophobic interaction and chain mobility led to the formation of transparent gel, coexistence of gel-sol, and opaque gel. These hydrogels may be useful in drug delivery and tissue engineering. © 2011 Elsevier Inc

Biodegradable thermogels

All living creatures respond to external stimuli. Similarly, some polymers undergo conformational changes in response to changes in temperature, pH, magnetic field, electrical field, or the wavelength of light. In one type of stimuli-responsive polymer, thermogel polymers, the polymer aqueous solution undergoes sol-to-gel transition as the temperature increases. Drugs or cells can be mixed into the polymer aqueous solution when it is in its lower viscosity solution state. After injection of the solution into a target site, heating prompts the formation of a hydrogel depot in situ, which can then act as a drug releasing system or a cell growing matrix.In this Account, we describe key materials developed in our laboratory for the construction of biodegradable thermogels. We particularly emphasize recently developed polypeptide-based materials where the secondary structure and nanoassembly play an important role in the determining the material properties. This Account will provide insights for controlling parameters, such as the sol-gel transition temperature, gel modulus, critical gel concentration, and degradability of the polymer, when designing a new thermogel system for a specific biomedical application.By varying the stereochemistry of amino acids in polypeptides, the molecular weight of hydrophobic/hydrophilic blocks, the composition of the polypeptides, the hydrophobic end-capping of the polypeptides, and the microsequences of a block copolymer, we have controlled the thermosensitivity and nanoassembly patterns of the polymers. We have investigated a series of thermogel biodegradable polymers. Polymers such as poly(lactic acid-co-glycolic acid), polycaprolactone, poly(trimethylene carbonate), polycyanoacrylate, sebacic ester, polypeptide were used as hydrophobic blocks, and poly(ethylene glycol) and poly(vinyl pyrrolidone) were used as hydrophilic blocks. To prepare a polymer sensitive to pH and temperature, carboxylic acid or amine groups were introduced along the polymer backbone. The sol-gel transition mechanism involves changes in the secondary structures of the hydrophobic polypeptide and in the conformation of the hydrophilic block. The polypeptide copolymers were stable in the phosphate buffered saline, but the presence of proteolytic enzymes such as elastase, cathepsin B, cathepsin C, and matrix metallopreoteinase accelerated their degradation.We also describe several biomedical applications of biogradable thermogel polymers. One subcutaneous injection of the insulin formulation of thermogel polypeptide copolymers in diabetic rats provided hypoglycemic efficacy for more than 16 days. The thermogels also provided a compatible microenvironment for chondrocytes, and these cells produced biomarkers for articular cartilage such as sulfated glucoaminoglycan (sGAG) and type II collagen. The thermogels were also used as a fixing agent for in situ cell imaging, and cellular activities such as endocytosis were observed by live cell microscopy. © 2011 American Chemical Society

Reverse thermogelling biodegradable polymer aqueous solutions

A reverse thermogelling polymer aqueous solution is a free-flowing sol at a low temperature and becomes a semisolid gel as the temperature increases. It is expected to be a very promising biomaterial as a minimally invasive injectable system for drug delivery and tissue engineering applications. The principles of materials design are (1) balancing the hydrophobicity and hydrophilicty of a polymer, (2) controlling the topology of a polymer, (3) matching the degradation kinetics of a polymer with a specific biomedical application, and (4) controlling the biocompatibility of the material with a drug as well as a host. This article covers recent progress of reverse theromogelling biodegradable polymers based on aliphatic polyesters, polyphosphazenes, poloxamer derivatives, polysaccharides, polypeptides, poly(propylene phosphate)s, polyorthoesters, polycarbonates, polycyanoacrylates, and poly(N-(2-hydroxyethyl) methacrylamide-lactate)s. The material characteristics, driving forces or mechanism for sol-gel transition, and their biomedical applications are summarized. In addition, the authors' perspectives on future reverse theromogelling materials design are suggested. © The Royal Society of Chemistry 2009

Alpha-beta transition induced by C18-conjugation of polyalanine and its implication in aqueous solution behavior of poly(ethylene glycol)-polyalanine block copolymers

Background: The aqueous solution behavior of thermosensitive PEG-PA block copolymers as well as secondary structure of PA is expected to significantly change through modification of the hydrophobic PA by long chain alkyl (C18) groups with different configurations. Method: Oleoyl and stearoyl (C18) groups were conjugated to poly(ethylene glycol)-poly(L-alanine) (PEG-PA; EG45A16) diblock copolymers to compare their conjugation effect on nano-assemblies and corresponding aqueous solution behavior of the polymers. Results: Due to the nature of a hydrophilic PEG block and a hydrophobic PA or C18-modified PA, PEG-PA, oleoyl group-conjugated PEG-PA (PEG-PAO), and stearoyl group-conjugated PEG-PA (PEG-PAS) block copolymers form micelles in water. Compared with PEG-PA, the micelle size of PEG-PAO and PEG-PAS increased. Circular dichroism and FTIR spectra of aqueous polymer solutions showed that β sheet content increased, whereas α helix content decreased by C18 modification of PEG-PA. PEG-PAS showed better performance in ice crystallization inhibition than PEG-PAO. The sol-to-gel transition temperatures of aqueous PEG-PAO solutions were 25–37 °C higher than those of aqueous PEG-PA solutions, whereas aqueous PEG-PAS solutions remained as gels in the temperature range of 0–80 °C. 1H-NMR spectra indicated that the oleoyl groups increased core mobility, whereas stearoyl groups decreased the core mobility of the micelles in water. The difference in micromobility between PAO and PAS interfered or promoted gelation of the aqueous polymer solutions, respectively. Conclusions: This study suggests that a hydrophobic C18-modification of polypeptide induces α helix-to-β sheet transition of the polypeptide; however, aqueous solution behaviors including ice recrystallization inhibition and gelation are significantly affected by the nature of the hydrophobic molecule. Graphical abstract: [Figure not available: see fulltext.] © 2020, The Author(s)

Vesicle-to-spherical micelle-to-tubular nanostructure transition of monomethoxy-poly(ethylene glycol)-poly(trimethylene carbonate) diblock copolymer

Recently, we reported a temperature-sensitive biodegradable diblock copolymer of monomethoxy-poly(ethylene glycol)-b-poly(trimethylene carbonate) (mPEG-PTMC; Macromolecules 2007, 40, 5519-5525). In this paper, we report the detailed morphological transition of the polymer in water as a function of polymer concentration and temperature, using cryo-transmission electron microscopy (cryo-TEM). At a low polymer concentration (0.05 wt %), the mPEG-PTMC diblock copolymers formed vesicles in water. On the other hand, vesicle-tomicelle transition was observed as the polymer concentration increased. The polymer predominantly formed micelles above 2.0 wt %. In the 2.0 wt % polymer solution, the mPEG-PTMC underwent spherical micelle-to-tubular nanostructure transition as the temperature increased from 10 to 40°C, and the transition accompanied an increase in turbidity of the polymer aqueous solution due to the increase in the apparent size of the polymer aggregates. Here, we report that the morphology of vesicles, spherical micelles, and tubular nanostructures is reversibly controlled by a thermosensitive polymer of mPEG-PTMC and the variation of the morphology can be carefully traced by using cryo-TEM. This paper will not only provide an important method for morphological control of an amphiphilic polymer but also improve our understanding of a temperature-sensitive transition mechanism of the polymer. © 2008 American Chemical Society