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of its thermal and mechanical properties, permeability, and susceptibility to hydrolytic chain scission in vitro and in vivo In addition to the initiator, reaction time, temperature and monomer/initiator(M/D)ratio were varied Reactivities of six-membered cyclic carbonates were studied and a carbonate-modified acrylic olymer was synthesized, which was expected to show good water resistance The effect of polymer chemistry on adhesion, proliferation, and morphology of human articular cartilage(HAC)was evaluated In order to study the degradation mechanism of these polycarbonates in more detail, a series of small model compounds were designed that mimic the repeat unit of the polymer. Tyrosine -PEG derived poly(ether carbonate)s were prepared by condensation copolymerization with phosgene.. Chemical structure and purity were confirmed by NMR and FTIR spectral The mechanism of decarboxylation was discussed from the viewpoint of Based on the symmetrical structure of these products, a mechanism for chain initiation and.was 根据具体内容,有时要用一般现在时或其它 The novel convergent growth approach to topological macromolecules based on dendritic fragment is described In present paper plasma methods are discussed with respect to other techniques which also nduce micropatterned cell growth 也有少部分用主动态 Our study focused on the role of poly(ethylene glycol)(PEG)in actively regulating the biological responsiveness of protein-adsorbed biomaterials. To this end, we designed PEG-variant biomaterials from a family of tyrosine/PEG-derived polycarbonate to present surfaces ranging from low to intermediate levels of PEG concentration,. We analyzed the effect of PEG concentration on the amount, conformation and bioactivity We have investigated the ability of these dendrimers to function as an effective delivery system This paper describes the synthesis and evaluation of biodegradable derivatives of poly-L-glutamic acid as suitable vectors for gene therapy 三.阐明得到了哪些主要结论

2 of its thermal and mechanical properties, permeability, and susceptibility to hydrolytic chain scission in vitro and in vivo. …In addition to the initiator, reaction time, temperature, and monomer/initiator (M/I) ratio were varied. Reactivities of six-membered cyclic carbonates were studied and a carbonate-modified acrylic polymer was synthesized, which was expected to show good water resistance. The effect of polymer chemistry on adhesion, proliferation, and morphology of human articular cartilage (HAC) was evaluated. In order to study the degradation mechanism of these polycarbonates in more detail, a series of small model compounds were designed that mimic the repeat unit of the polymer. Tyrosine-PEG derived poly(ether carbonate)s were prepared by condensation copolymerization with phosgene. …Chemical structure and purity were confirmed by NMR and FTIR spectral analysis. The mechanism of decarboxylation was discussed from the viewpoint of … Based on the symmetrical structure of these products, a mechanism for chain initiation and …was proposed. 根据具体内容有时要用一般现在时或其它 The novel convergent growth approach to topological macromolecules based on dendritic fragment is described. In present paper plasma methods are discussed with respect to other techniques which also induce micropatterned cell growth. 也有少部分用主动态 Our study focused on the role of poly(ethylene glycol) (PEG) in actively regulating the biological responsiveness of protein-adsorbed biomaterials. To this end, we designed PEG-variant biomaterials from a family of tyrosine/PEG-derived polycarbonate to present surfaces ranging from low to intermediate levels of PEG concentration, … We analyzed the effect of PEG concentration on the amount, conformation and bioactivity… We have investigated the ability of these dendrimers to function as an effective delivery system… This paper describes the synthesis and evaluation of biodegradable derivatives of poly-L-glutamic acid as suitable vectors for gene therapy. 三阐明得到了哪些主要结论

● Introduction 时态根据具体内容而定 ntroduction通常由以下几方面组成: 介绍研究背景、研究意义 Spiro orthocarbonates(SOCs) undergo double ring-opening polymerization with an expansion in volume[1-4. This unique property attracted the interest of polymer chemists [5, 6 Since the early 1960s, several synthetic, degradable polymer systems have been used as medical implant materials. Some widely investigated examples include poly (lactic acid)[1, 21, and polyorthoesters[6,71 Wichterle and Lim developed the first synthetic polymeric hydrogels based on hydroxyethyl methacrylate, for use as biomaterials [2]. Since then, there has been continuing interest in the development of novel types of hydrogel materials for biomedical application elopment of biodegra ing extensively promoted as one of the solutions to plastic waste disposal. Aliphatic polyesters are currently considered the most promising materials for the production of biodegradable plastics In recent years more and more technical fields have begun to use low-temperature plasm Important new applications have been found in biomedical techniques.. Good examples for novel techniques very near application and already applied are plasmas sterilization..This is important not only for polymeric biomaterials, but also for other materials. A lot of publications already exist in this field. It is well known that poly(N-isopropylacrylamide)(PNIPA) gel is thermally sensitive in its response to external temperature changes... PNIPA gel has attracted great interest and been extensively studied in the recent 20 years due to its applications in many fields, such as artificial muscle [2], on-off switches [3], and immobilization of enzymes[4], etc Very recently, Kricheldorf et al. have reported the synthesis of high molecular weight polycarbonate., although the detailed mechanism is not clear The anionic living polymerization technique yielding polymers with narrow molecular weight distributions has been widely adopted as a method to prepare homo and especially block copolymers Gene therapy is a relatively new technic the field of biotechnology and medicine that is attracting a lot of attention

4 z Introduction 时态根据具体内容而定 Introduction 通常由以下几方面组成一介绍研究背景﹑ 研究意义 Spiro orthocarbonates (SOCs) undergo double ring-opening polymerization with an expansion in volume [1-4]. This unique property attracted the interest of polymer chemists [5,6]. Since the early 1960s, several synthetic, degradable polymer systems have been used as medical implant materials. Some widely investigated examples include poly(lactic acid) [1,2], …, …, and polyorthoesters [6,7]. Wichterle and Lim developed the first synthetic polymeric hydrogels based on hydroxyethyl methacrylate, for use as biomaterials [2]. Since then, there has been continuing interest in the development of novel types of hydrogel materials for biomedical application. Development of biodegradable plastics is being extensively promoted as one of the solutions to plastic waste disposal. Aliphatic polyesters are currently considered the most promising materials for the production of biodegradable plastics. In recent years more and more technical fields have begun to use low-temperature plasmas. Important new applications have been found in biomedical techniques….Good examples for novel techniques very near application and already applied are plasmas sterilization….This is important not only for polymeric biomaterials, but also for other materials. A lot of publications already exist in this field. It is well known that poly(N-isopropylacrylamide) (PNIPA) gel is thermally sensitive in its response to external temperature changes. … PNIPA gel has attracted great interest and been extensively studied in the recent 20 years due to its applications in many fields, such as artificial muscle [2], on-off switches [3], and immobilization of enzymes [4], etc. Very recently, Kricheldorf et al. have reported the synthesis of high molecular weight polycarbonate…, although the detailed mechanism is not clear. 5 The anionic living polymerization technique yielding polymers with narrow molecular weight distributions has been widely adopted as a method to prepare homo- and especially block copolymers1). Gene therapy is a relatively new technique in the field of biotechnology and medicine that is attracting a lot of attention

The free radical polymerizations of cyclic ketene acetals have recently evoked a lot of interest The use of enzyme catalysis in organic media for polymer-forming reactions is gaining increasing attention. The hallmark of enzymes is their ability to achieve high enantio- and regioselectivity for various chemical transformations. Furthermore, enzymes represent a family of environmentally friendly"catalysts. Advantages of using enzymes in organic as opposed to aqueous media are as follows:(i) increased enzyme thermal stability, (ii) solubility of a wide range of substrate types in the reaction media, (iii) no requirement for pH adjustment as the reaction proceeds, and(iv) readily recyclable. 2,3 Whereas aromatic polycarbonates have achieved wide application and great importance as polymer materials since 1954, aliphatic polycarbonates have been less interesting due to their poor thermal stability and easy hydrolysis. During the past decade, increasing attention has been paid to aliphatic polycarbonates for their potential in the medical field and in the environmental control of plastics Stimulated by the need for bioresorbable medical materials with a wide range of physical properties and degradation rates, there has been considerable interest in exploring aliphatic polycarbonate prepared by ring-opening polymerization of cyclic carbonate monomers. Efforts have thus far focused on polymerizations of five- and Six-membered ring aliphatic cyclic 阐述目前该领域的研究现状、存在问题、待解决的问题 Ring-opening polymerization of six-membered cyclic carbonates have been studied in detail by Kricheldorf et al. [4, 5] and Sarell et al. [6-8 after the first work on their reactivity by Searles [9] In recent years there has been renewal of interest in polymerization of six-membered cyclic carbonate since Endo et al. demonstrated that TMC showed volume expansion during olymerization[10] only a low molecular weight(MW) polymer was obtained and the MW cannot be controlle vely, Although the cationic ring-opening polymerization of soCs has been investigated extensi Although the utility of these materials as sutures and in a number of drug delivery applications is well established, some material,'s needs cannot be satisfied by their use. For example, all polyesters release acidic degradation products [6-8), limiting their utility to applications where acidity at the implant site is not a concern. The above polyesters also tend to be relatively rigid inflexible materials [9], This can be a definite disadvantage when mechanical compliance with soft tissue or blood vessels is required. Finally, none of the above polyesters provides a chemically reactive pendent chain for the easy attachment of drugs, crosslinkers and biologically active moieties The investigation of poly(ether carbonate)s started in the 1960s.. However, copolymers of

5 The free radical polymerizations of cyclic ketene acetals have recently evoked a lot of interest. The use of enzyme catalysis in organic media for polymer-forming reactions is gaining increasing attention. The hallmark of enzymes is their ability to achieve high enantio- and regioselectivity for various chemical transformations.1 Furthermore, enzymes represent a family of “environmentally friendly” catalysts. Advantages of using enzymes in organic as opposed to aqueous media are as follows: (i) increased enzyme thermal stability, (ii) solubility of a wide range of substrate types in the reaction media, (iii) no requirement for pH adjustment as the reaction proceeds, and (iv) readily recyclable. 2,3 Whereas aromatic polycarbonates have achieved wide application and great importance as polymer materials since 1954,1 aliphatic polycarbonates have been less interesting due to their poor thermal stability and easy hydrolysis. During the past decade, increasing attention has been paid to aliphatic polycarbonates for their potential in the medical field and in the environmental control of plastics.2-8 Stimulated by the need for bioresorbable medical materials with a wide range of physical properties and degradation rates, there has been considerable interest in exploring aliphatic polycarbonate prepared by ring-opening polymerization of cyclic carbonate monomers.1-7 Efforts have thus far focused on polymerizations of five- and six-membered ring aliphatic cyclic carbonates. 二阐述目前该领域的研究现状﹑存在问题﹑待解决的问题 Ring-opening polymerization of six-membered cyclic carbonates have been studied in detail by Kricheldorf et al. [4,5] and Sarell et al. [6-8] after the first work on their reactivity by Searles [9]. In recent years there has been renewal of interest in polymerization of six-membered cyclic carbonate since Endo et al. demonstrated that TMC showed volume expansion during polymerization [10]. Although the cationic ring-opening polymerization of SOCs has been investigated extensively, only a low molecular weight (MW) polymer was obtained and the MW cannot be controlled. Although the utility of these materials as sutures and in a number of drug delivery applications is well established, some material’s needs cannot be satisfied by their use. For example, all polyesters release acidic degradation products [6-8], limiting their utility to applications where acidity at the implant site is not a concern. The above polyesters also tend to be relatively rigid, inflexible materials [9], This can be a definite disadvantage when mechanical compliance with soft tissue or blood vessels is required. Finally, none of the above polyesters provides a chemically reactive pendent chain for the easy attachment of drugs, crosslinkers and biologically active moieties. The investigation of poly(ether carbonate)s started in the 1960s. …However, copolymers of

diphenols and PEG have so far not been studied as medical implant materials A number of studies have illustrated the strong effects of PEg on the activity and conformation of proteins in solution[15-17. However, the role of lower-range PEG interactions that may allow protein adsorption and cell adhesion on biomaterial has been largely overlooked. Thus, the biological "regulatory"behavior of PEG-bearing surfaces is not clearly understood, especially at low and intermediate levels of Peg surface concentration Thus, there is a need to design biomaterial surfaces that are systematically responsive to protein adsorption in a precise, tissue-specific manner Unfortunately, the current treatment options for articular cartilage repair suffer from certain limitations [1, 2]. The clinical need for improved methods for articular repair have motivated many researchers to explore tissue engineering approaches Practical application to environmental-friendly materials has been restricted by the low melting point, and more efforts have been, therefore, directed to overcome the thermal unstability Although many reports have been published on the polymer blends of PCL [3-9 there are only a few on the study of biodegradation In view of the widespread use of silicones(polysiloxanes), it is rather surprising that the literature documents have seldom reported systematic approaches to the synthesis of structurally defined oligosiloxanes Although synthetic poly( id)have been widely investigated, very few practical applications have been identified for these polymers 三,指出本文的研究内容、目的及其独到之处 The objective of the present study was to synthesize well -defined ABa copolymers. and to investigate feasibility of preparing phase-separated structures in blends. In this work we attempt to minimize transesterification reactions Our model PEG-variant surface were based on a family of tyrosine-derived biomaterials, which have been well characterized both in vitro and in vivo, and have shown great promise for use ineering appl This study reports for the first time that PEG, when present on a biomaterial surface in small, controlled amount, can modify, in a systematic manner, the attachment of proteins and in turn, the adhesion and migration of cells

6 diphenols and PEG have so far not been studied as medical implant materials. A number of studies have illustrated the strong effects of PEG on the activity and conformation of proteins in solution [15-17]. However, the role of lower-range PEG interactions that may allow protein adsorption and cell adhesion on biomaterial has been largely overlooked. Thus, the biological “regulatory” behavior of PEG-bearing surfaces is not clearly understood, especially at low and intermediate levels of PEG surface concentration. Thus, there is a need to design biomaterial surfaces that are systematically responsive to protein adsorption in a precise, tissue-specific manner. Unfortunately, the current treatment options for articular cartilage repair suffer from certain limitations [1,2]. The clinical need for improved methods for articular repair have motivated many researchers to explore tissue engineering approaches… Practical application to environmental-friendly materials has been restricted by the low melting point, and more efforts have been, therefore, directed to overcome the thermal unstability. Although many reports have been published on the polymer blends of PCL [3-9], there are only a few on the study of biodegradation. In view of the widespread use of silicones (polysiloxanes),1 it is rather surprising that the literature documents have seldom reported systematic approaches to the synthesis of structurally defined oligosiloxanes. Although synthetic poly(amino acid) have been widely investigated, very few practical applications have been identified for these polymers. 三指出本文的研究内容﹑目的及其独到之处 The objective of the present study was to synthesize well –defined ABA copolymers…and to investigate feasibility of preparing phase-separated structures in blends…In this work we attempt to minimize transesterification reactions. Our model PEG-variant surface were based on a family of tyrosine-derived biomaterials, which have been well characterized both in vitro and in vivo, and have shown great promise for use in tissue engineering applications. This study reports for the first time that PEG, when present on a biomaterial surface in small, controlled amount, can modify, in a systematic manner, the attachment of proteins and in turn, the adhesion and migration of cells

All solvents were freshly distilled before use 合成的产物要说明具体合成方法 y-Benzylglutamate was prepared by the method of Gutmann and Boissinnas (101 was synthesized according to Ref. [4] were synthesized according to published procedures [1 Trimethylene carbonate was synthesized following a procedure described elsewhere. The product was recrystallized twice from diethyl ether. White crystal was obtained in 55% yield: mp 45C). The H-NMR spectrum(4H, 4.50 ppm; 2H, 2.21 ppm) was consistent with that reported previously. 25 Novozym-435(2.0 g)was suspended in 25 mL of nanopure water in a 100 mL round-bottomed flask fitted with a water cooled condenser. The lipase suspension was refluxed for 14 h. The suspension was then allowed to cool to room temperature, and water was removed by freeze drying.. The reaction vials were capped tightly and shaken vigorously for a few minutes. The reaction vials were then placed in a constant-temperature water bath maintained at 37C for 3 h with magnetic stirrin Pentaerythritol (50.0 g, 0.36 mol) and p-toluene-sulfonic acid monohydrate(0.61 g)were dissolved in 500 mL of N, N-dimethylformamide at about 80C, and then the mixture was allowed to cool undisturbed. When the solution cooled to about 40oC. stirring was starte and 55.4 mL of 2, 2-dimethoxypropane(0. 36 mol) was added. After stirring for 24 h at room temperature, the solution was stirred at room temperature with 9.0 g of based-treated DOWEX lXZ-100 ion exchange resin for I h and filtered, and then the solvent was evaporated under reduced pressure below 85C... After the treatment with this resin, the dry product was ground and extracted, first with light petroleum ether(bp 40-60C) for 6 h and then with diethyl ether for 12 h, collected and dried. Yield: 40.0 g, white crystals(61.9 of theory); mp 124.5-125.5°C.H-NMR(300MHz, DMSO-d6):1.28ppm(s,6H), Synthesis of Cyclic Carbonate Monomer Triethylamine (84.0 g, 0.825 mol) was added dropwise to a solution of 1,3-propanediol (29.9 g, 0.393 mol) and ethyl chloroformate (85.4 g, 0.786 mol) in 2L of THF at0C over a period 30 min. The reaction mixture was stirred for 2h at room temperature. Precipitated triethylamine hydrochloride salt was filtered off, and the filtrate was concentrated under vacuum. The residue was recrystallized three times from THF-ether 1000 g of glycolic acid was placed in a three necked flask fitted with a stirrer, distillation head and condenser, a thermalmeter for monitoring the temperature of the melt, and a nitrogen bleed. I g of Sb2O3 was added and the vessel was heated to 120C. Polycondensation began and as the rate of water elimination fell, the temperature was increased to 180C and

8 All solvents were freshly distilled before use. 合成的产物要说明具体合成方法 -Benzylglutamate was prepared by the method of Gutmann and Boissinnas [10]. …was synthesized according to Ref. [4]. …were synthesized according to published procedures [1]. Trimethylene carbonate was synthesized following a procedure described elsewhere.25 The product was recrystallized twice from diethyl ether. White crystal was obtained in 55% yield: mp 45°C). The 1 H-NMR spectrum (4H, 4.50 ppm; 2H, 2.21 ppm) was consistent with that reported previously. 25 Novozym-435 (2.0 g) was suspended in 25 mL of nanopure water in a 100 mL round-bottomed flask fitted with a water cooled condenser. The lipase suspension was refluxed for 14 h. The suspension was then allowed to cool to room temperature, and water was removed by freeze drying…. The reaction vials were capped tightly and shaken vigorously for a few minutes. The reaction vials were then placed in a constant-temperature water bath maintained at 37 °C for 3 h with magnetic stirring…. Pentaerythritol (50.0 g, 0.36 mol) and p-toluene-sulfonic acid monohydrate (0.61 g) were dissolved in 500 mL of N, N-dimethylformamide at about 80 °C, and then the mixture was allowed to cool undisturbed. When the solution cooled to about 40 °C, stirring was started and 55.4 mL of 2,2-dimethoxypropane (0.36 mol) was added. After stirring for 24 h at room temperature, the solution was stirred at room temperature with 9.0 g of based-treated DOWEX 1XZ-100 ion exchange resin for 1 h and filtered, and then the solvent was evaporated under reduced pressure below 85 °C. …After the treatment with this resin, the dry product was ground and extracted, first with light petroleum ether (bp 40-60 °C) for 6 h and then with diethyl ether for 12 h, collected and dried. Yield: 40.0 g, white crystals (61.9 % of theory); mp 124.5-125.5 °C. 1 H-NMR (300 MHz, DMSO-d6): 1.28 ppm (s, 6H), … Synthesis of Cyclic Carbonate Monomer Triethylamine (84.0 g, 0.825 mol) was added dropwise to a solution of 1,3-propanediol (29.9 g, 0.393 mol) and ethyl chloroformate (85.4 g, 0.786 mol) in 2L of THF at 0 °C over a period 30 min. The reaction mixture was stirred for 2h at room temperature. Precipitated triethylamine hydrochloride salt was filtered off, and the filtrate was concentrated under vacuum. The residue was recrystallized three times from THF-ether. 1000 g of glycolic acid was placed in a three necked flask fitted with a stirrer, distillation head and condenser, a thermalmeter for monitoring the temperature of the melt, and a nitrogen bleed. 1 g of Sb2O3 was added and the vessel was heated to 120 °C. Polycondensation began and as the rate of water elimination fell, the temperature was increased to 180 °C and

pressure reduced gradually from 760-5 mmHg over a period of 4-6 hours The structure of htC was confirmed by Ftir and H-NMR ,仪器表征 Nuclear Magnetic Resonance(NMR) Spectroscopy H-NMR spectra were recorded on a Bruker ARX-250 spectrometer at 250 MHz Fourier Transform-Infrared Spectroscopy(FTIR) A P-E 1720 FTIR spectrometer was used to obtain the spectra(16 scans, resolution 2 cm )of he monomer and polymers over the range from 4000 to 400 cm Differential Scanning Calorimetry(DSC) Differential Scanning Calorimetry(DSC) was carried out with a Perkin-Elmer DSC 7 thermal analyzer. All the samples were heated at 20C/min heating rate from 25C to 200C for th first scan, then cooled at 50-100C/min to 25C, and immediately heated a second time Peak melting temperatures(Tm)and melting enthalpy(AHm)were measured on the first scan, and glass transition temperatures (Tg) were measured on the second scan DSC was measured using a Perkin-Elmer DSC 7 calorimeter with heating and cooling rates of 0°C/ min from-20°Cto200°C Scanning Electron Microscopy(SEM) Fiber samples were fractured in liquid nitrogen to obtain tidy cross-section, and then sputter-coated with gold and visualized by SEM(PHILIPS XL 30) Samples were then covered by an ultrathin layer of gold and observed and micrographed with a scanning electron microscope(JSM 6400) X-ray Analysis Wide-angle X-ray scattering of a solution cast film aged for 2 weeks at 40C was performed using a Philips Vertical Diffractometer with Bragg-Brentano geometry and a graphite diffracted beam monochrometer at 40 k v/20 mA and Cu Ka radiation(1.5405 A). A scanning speed of 2/min with a sample interval of 0.05 was used Gel Permeation Chromatography(GPC) GPC analyses were carried out using a Waters HPLC pump with an ERMA 75 15A refractive index detector and a Carlo Erba UVis 20 ultraviolet detector Molecular weight data was obtained by gel permeation chromatography(GPC), using two PL el columns connected to a Water 410 RI detector(Waters Corp, MA)

9 pressure reduced gradually from 760-5 mmHg over a period of 4-6 hours…. The structure of C HTC was confirmed by FTIR and 1 H-NMR. 二仪器表征 Nuclear Magnetic Resonance (NMR) Spectroscopy 1 H-NMR spectra were recorded on a Bruker ARX-250 spectrometer at 250 MHz. Fourier Transform-Infrared Spectroscopy (FTIR) A P-E 1720 FTIR spectrometer was used to obtain the spectra (16 scans, resolution 2 cm-1) of the monomer and polymers over the range from 4000 to 400 cm-1. Differential Scanning Calorimetry (DSC) Differential Scanning Calorimetry (DSC) was carried out with a Perkin-Elmer DSC 7 thermal analyzer. All the samples were heated at 20 °C/min heating rate from 25 °C to 200 °C for the first scan, then cooled at 50-100 °C/min to 25 °C, and immediately heated a second time. Peak melting temperatures (Tm) and melting enthalpy ( Hm) were measured on the first scan, and glass transition temperatures (Tg) were measured on the second scan. DSC was measured using a Perkin-Elmer DSC 7 calorimeter with heating and cooling rates of 10 °C/min from -20 °C to 200 °C. Scanning Electron Microscopy (SEM) Fiber samples were fractured in liquid nitrogen to obtain tidy cross-section, and then sputter-coated with gold and visualized by SEM (PHILIPS XL 30). Samples were then covered by an ultrathin layer of gold and observed and micrographed with a scanning electron microscope (JSM 6400). X-ray Analysis Wide-angle X-ray scattering of a solution cast film aged for 2 weeks at 40 °C was performed using a Philips Vertical Diffractometer with Bragg-Brentano geometry and a graphite diffracted beam monochrometer at 40 kV/20 mA and Cu Ka radiation (1.5405 Å). A scanning speed of 2°/min with a sample interval of 0.05° was used. Gel Permeation Chromatography (GPC) GPC analyses were carried out using a Waters HPLC pump with an ERMA 7515A refractive index detector and a Carlo Erba UVIS 20 ultraviolet detector. Molecular weight data was obtained by gel permeation chromatography (GPC), using two PL gel columns connected to a Water 410 RI detector (Waters Corp, MA)