基于新型PEG衍生物共聚改性聚乳酸的骨再生材料的研究
發(fā)布時(shí)間：2018-07-17 00:44
【摘要】：骨組織工程為廣大骨病患者提供了新的途徑和希望。其中組織再生支架材料的設(shè)計(jì)是骨組織工程成功的關(guān)鍵，通常要求它滿足一定的力學(xué)強(qiáng)度、可控的降解性能和合理的表面誘導(dǎo)細(xì)胞增殖分化及組織再生。然而，目前很少有材料能同時(shí)具備以上性能。本研究的目的是設(shè)計(jì)一種新型的骨組織工程材料，使其集可控降解性能、一定的力學(xué)強(qiáng)度、適當(dāng)?shù)挠H水性能及可功能化的表面等性能于一身。基于PEG衍生物聚（乙二醇-co-均苯四甲酸酐）亞胺（PAPI）與D,L-丙交（D,L-LA）酯共聚，制備了一系性能可調(diào)的PAPI-PDLLA新型共聚物。采用核磁共振（NMR）、傅立葉變換紅外光譜儀（FTIR）、凝膠色譜-十八角激光散射儀（GPC-MALLS）、紫外可見光譜儀（UV）、示差掃描量熱儀（DSC）、X光電子能譜（XPS）、掃描電鏡（SEM）、原子力顯微鏡（AFM）等對(duì)共聚物的化學(xué)物理性能進(jìn)行了表征；詳細(xì)考察了PAPI-PDLLA共聚物的親/疏水性、體外生物降解性能、力學(xué)性能（拉伸性能和壓縮性能），以及降解過(guò)程中的力學(xué)性能變化；對(duì)PAPI-PDLLA共聚物的表面進(jìn)行了氨基和羥基功能化研究；最后，評(píng)價(jià)了PAPI-PDLLA共聚物及表面功能化材料的體外細(xì)胞生物相容性。研究的主要內(nèi)容和結(jié)論如下： 1.較低分子量的氨基封端的PEG（ATPEG，Mr:900）與均苯四甲酸酐（PMDA）通過(guò)高溫縮聚反應(yīng)合成出新型PEG衍生物P(ATPGE-co-PMDA)(PAPI)。在合成條件的優(yōu)化實(shí)驗(yàn)中，考察了單體比例、溫度、反應(yīng)時(shí)間等對(duì)聚合物分子量的影響和反應(yīng)過(guò)程中酰亞胺化的程度等；該衍生物通過(guò)苯酰亞胺環(huán)連接，酰亞胺環(huán)的引入為開環(huán)功能接枝提供了條件，研究了丁二胺、乙醇胺與PAPI中酰亞胺環(huán)反應(yīng)的能力；對(duì)所有合成的材料結(jié)構(gòu)進(jìn)行了表征。 ①FTIR、1H NMR、13C NMR、GPC-MALLA和UV檢測(cè)結(jié)果表明，ATPEG與PMDA成功聚合，ATPEG的微過(guò)量使得合成的PAPI端部具有氨基。當(dāng)二者的摩爾比ATPEG/PMDA=1.05時(shí)，在設(shè)定的梯度高溫溫度下反應(yīng)完成后，酰亞胺化基本完全，所獲得的聚合物分子量較大，聚合物分散系數(shù)較低。熱重分析表明PAPI相對(duì)于PEG的熱穩(wěn)定性增強(qiáng)。 ②FTIR表明，PAPI中酰亞胺環(huán)在室溫?zé)o催化劑下成功與丁二胺和乙醇胺反應(yīng)，可能為接枝功能基團(tuán)提供反應(yīng)位點(diǎn)。 ③在與丁二胺反應(yīng)時(shí)，發(fā)生了交聯(lián)，快速產(chǎn)生了凝膠，該凝膠具有一定的力學(xué)強(qiáng)度和多孔性，有望應(yīng)用于藥物釋放或組織工程領(lǐng)域。 2.PAPI和辛酸亞錫共引發(fā)體系引發(fā)D,L-丙交酯開環(huán)，合成了一系列PAPI-PDLLA共聚物，研究了PAPI/D,L-丙交酯、反應(yīng)溫度、反應(yīng)時(shí)間等對(duì)PAPI-PDLLA共聚物分子量的影響，并表征了其化學(xué)結(jié)構(gòu)和熱性能。 ①FTIR、1H NMR、13C NMR和GPC-MALLS的結(jié)果表明，PAPI的端氨基和辛酸亞錫共引發(fā)體系成功引發(fā)丙交酯開環(huán)，制備了PAPI-PDLLA共聚物，最佳反應(yīng)時(shí)間為36小時(shí)，反應(yīng)溫度為150℃。 ②通過(guò)調(diào)節(jié)PAPI與D,L-丙交酯的物料比，可以制備一系列不同分子量和性能的共聚物，通過(guò)1H NMR計(jì)算了接枝的聚乳酸的量；隨著PAPI/D,L-丙交酯比例的增加，接枝的聚乳酸分子量下降。 ③DSC結(jié)果表明，PAPI-PDLLA共聚物只有一個(gè)玻璃化轉(zhuǎn)變溫度，這表明兩相熱相容性良好，隨著PAPI所占比例的增加，玻璃化溫度下降。熱重分析結(jié)果表明，PAPI-PDLLA出現(xiàn)兩個(gè)明顯分解溫度，首先是PDLLA嵌段分解，然后是PAPI的分解，通過(guò)熱重分析可以得出兩嵌段的質(zhì)量比。 3.研究了PAPI-PDLLA共聚物的親/疏水性能和降解性能。親/疏水性能采用材料表面靜態(tài)水接觸角和整體吸水率兩種方法來(lái)評(píng)價(jià)；通過(guò)失重率、分子量變化、pH值變化和降解后樣品表面形貌的變化等來(lái)評(píng)價(jià)材料的降解性能。 ①親/疏水性能測(cè)試結(jié)果表明，PAPI-PDLLA共聚物的靜態(tài)水接觸角均小于PDLLA，吸水率都大于PDLLA，且隨著共聚物中親水嵌段PAPI比重的增加，親水性能增加。 ②PAPI-PDLLA共聚物的體外降解實(shí)驗(yàn)表明，PAPI-PDLLA系列樣品在降解前五周的失重、分子量下降及pH值變化相對(duì)于PDLLA對(duì)照組都要快些，但在整個(gè)降解過(guò)程中發(fā)現(xiàn)，PDLLA由于降解過(guò)程中酸性積累導(dǎo)致的自催化作用引起了陡降現(xiàn)象，而在PAPI-PDLLA系列材料中，降解速率較為可控，降解的失重率的自然對(duì)數(shù)與時(shí)間經(jīng)擬合，發(fā)現(xiàn)符合假一級(jí)動(dòng)力學(xué)模型Mnmolecular，沒(méi)有陡降現(xiàn)象產(chǎn)生。這是由于親水嵌段PAPI的引入，加速了降解的酸性小分子的擴(kuò)散，沒(méi)有導(dǎo)致材料明顯的自催化降解作用。通過(guò)降解后的掃描電鏡顯示，PDLLA會(huì)產(chǎn)生局部不均勻降解，而PAPI-PDLLA共聚物的降解表面較為均一。因此，相對(duì)于PDLLA，材料的降解可控性能提高。 4.采用拉伸和壓縮測(cè)試考察了材料的力學(xué)性能。結(jié)果表明，共聚物都具有一定的拉伸強(qiáng)度和壓縮強(qiáng)度，并且強(qiáng)度隨著PAPI/D,L-丙交酯的物料比減少而增加，而斷裂伸長(zhǎng)率隨著PAPI/D,L-丙交酯的物料比的增加而顯著增加。合成的共聚物拉伸模量在48-280MPa之間。壓縮模量在108-780MPa之間，與松質(zhì)骨的壓縮模量較為匹配。隨著材料的降解，材料的力學(xué)強(qiáng)度逐漸損失，且隨著PAPI在共聚物中占的比重提高，力學(xué)損失加速，PAPD4/15（即PAPI-PDLLA中PAPI/D,L-LA=4/15)降解四周后，拉伸性能幾乎全部損失，而PAPD4/25僅損失了20%左右。 5.采用濕法化學(xué)法，在PAPI-PDLLA共聚物膜表面引入了氨基和羥基，采用XPS、比色法、AFM等方法定性定量表征了材料表面接枝的氨基和羥基。在無(wú)催化劑、常溫等反應(yīng)條件下，在材料表面易引入氨基和羥基，這為后續(xù)的材料表面活性分子接枝提供了基礎(chǔ)。PAPD4/15-BDA材料表面接枝的氨基密度達(dá)3.41×10~(-6)mol/cm~2。當(dāng)接枝氨基和羥基后，材料表面相對(duì)于反應(yīng)前變得粗糙。 6.采用大鼠乳鼠成骨細(xì)胞為種子細(xì)胞評(píng)價(jià)了PAPI及PAPI-PDLLA的細(xì)胞毒性。從成骨細(xì)胞形態(tài)、粘附、鋪展、增殖、分化和礦化等幾個(gè)方面系統(tǒng)的比較了PAPI-PDLLA及功能化表面與PDLLA的細(xì)胞相容性。 ①采用PAPI浸泡液及PAPI和PAPI-PDLLA降解可能產(chǎn)生的最大量的PMDA的浸泡液用于培養(yǎng)成骨細(xì)胞，發(fā)現(xiàn)成骨細(xì)胞在上述培養(yǎng)液中培養(yǎng)均體現(xiàn)正常形態(tài)，PAPI及含PMA的培養(yǎng)液并不影響細(xì)胞的形態(tài)與增殖，這說(shuō)明了PAPI及PAPI-PDLLA無(wú)明顯細(xì)胞毒性。 ②與PDLLA相比，適當(dāng)?shù)囊隤API促進(jìn)了成骨細(xì)胞的粘附與鋪展，，而過(guò)多的PAPI不利于細(xì)胞的粘附；功能化的PAPI-PDLLA膜表面也有利于細(xì)胞的粘附與鋪展，氨基功能化的表面細(xì)胞粘附最為明顯。 ③相對(duì)于PDLLA，適當(dāng)PAPI含量的PAPI-PDLLA膜有利于細(xì)胞增殖，而氨基和羥基功能化的表面使細(xì)胞增殖更為顯著。 ④成骨細(xì)胞在材料表面的分化和礦化能力采用堿性磷酸酶、無(wú)機(jī)鈣分泌和膠原分泌等指標(biāo)來(lái)衡量。結(jié)果表明，細(xì)胞在氨基功能化的PAPI-PDLLA膜表面的分化礦化能力略優(yōu)于PAPI-PDLLA，而在PAPI-PDLLA膜上的分化礦化能力要優(yōu)于PDLLA。
[Abstract]:Bone tissue engineering provides a new way and hope for the patients with bone disease. The design of tissue regeneration scaffold is the key to the success of bone tissue engineering. It is usually required to meet certain mechanical strength, controllable degradation performance and reasonable surface induction of cell proliferation and differentiation and tissue regeneration. However, few materials can be used at the same time at the same time. The purpose of this study is to design a new type of bone tissue engineering material to make it capable of controlling degradation properties, certain mechanical strength, appropriate hydrophilic properties and functional surfaces. Based on the PEG derivative poly (ethylene glycol -co- benzoate anhydride) imide (PAPI), copolymerization of D, L- C (D, L-LA) ester, and copolymerization of PAPI) A series of new PAPI-PDLLA copolymers with adjustable performance are prepared. Using nuclear magnetic resonance (NMR), Fu Liye transform infrared spectrometer (FTIR), gel chromatography - eighteen angle laser scatterometer (GPC-MALLS), ultraviolet visible spectrometer (UV), differential scanning calorimeter (DSC), X photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), atomic force microscopy (AFM) and other copolymers The properties of chemical and physical properties were characterized. The affinity / hydrophobicity of PAPI-PDLLA copolymer, in vitro biodegradability, mechanical properties (tensile properties and compression properties), and the changes of mechanical properties during the degradation process were investigated. The amino and hydroxyl groups of the PAPI-PDLLA copolymers were studied. Finally, the PAPI-PDLLA was evaluated. Biocompatibility of copolymers and surface functionalized materials in vitro. The main contents and conclusions are as follows:
1. a new PEG derivative P (ATPGE-co-PMDA) (PAPI) was synthesized by the high temperature condensation reaction of PEG (ATPEG, Mr:900) and benzyldianhydride (PMDA) at low molecular weight, and the influence of monomer ratio, temperature and reaction time on the molecular weight of the polymer and the process of imimide during the reaction process were investigated. The derivate was connected by the benzimide ring and the introduction of the imide ring provided the conditions for the opening ring function grafting. The ability of Ding Eran, ethanolamine to react with the imide ring in PAPI was studied, and the structure of all the synthesized materials was characterized.
(1) FTIR, 1H NMR, 13C NMR, GPC-MALLA and UV detection results show that ATPEG and PMDA are successfully polymerized, and the micro excess of ATPEG makes the PAPI end have amino. When the molar ratio of the two is more than ATPEG/PMDA=1.05, after the reaction is completed at a set temperature, the imide base is complete, and the molecular weight of the polymer is larger and the polymer fraction is obtained. Thermogravimetric analysis showed that the thermal stability of PAPI relative to PEG was enhanced.
(2) FTIR showed that the imide ring in PAPI successfully reacted with butyl two amine and ethanolamine at room temperature without catalyst, which might provide a reaction site for graft functional groups.
(3) the gel was produced by crosslinking with butyl two amine, which has a certain mechanical strength and porosity, which is expected to be used in the field of drug release or tissue engineering.
The co initiation system of 2.PAPI and stannous octanate initiated a series of D, L- lactide ring opening and a series of PAPI-PDLLA copolymers. The effects of PAPI/D, L- lactide, reaction temperature and reaction time on the molecular weight of PAPI-PDLLA copolymers were investigated, and the chemical structure and thermal properties of the copolymers were characterized.
(1) the results of FTIR, 1H NMR, 13C NMR and GPC-MALLS showed that the co initiation system of PAPI and stannous octanate initiated the opening ring of lactide, and the PAPI-PDLLA copolymer was prepared. The optimum reaction time was 36 hours and the reaction temperature was 150.
(2) a series of copolymers with different molecular weights and properties can be prepared by adjusting the material ratio of PAPI and D, L- lactide. The amount of polylactic acid graft is calculated by 1H NMR. With the increase of PAPI/D, the proportion of L- lactide is increased, and the molecular weight of the grafted polylactic acid decreases.
(3) DSC results show that the PAPI-PDLLA copolymer has only one glass transition temperature, which indicates that the thermal compatibility of the two phases is good and the glass transition temperature decreases with the increase of the proportion of PAPI. The results of thermogravimetric analysis show that the PAPI-PDLLA has two obvious decomposition temperatures, first of which is PDLLA block decomposition, then the decomposition of PAPI, by thermogravimetric analysis. The mass ratio of the two block is obtained.
3. the Pro / hydrophobicity and degradation properties of PAPI-PDLLA copolymer were studied. The hydrophobicity and hydrophobicity of the copolymer were evaluated by two methods of static water contact angle and total water absorption on the surface of the material, and the degradation properties of the materials were evaluated by the weight loss rate, the change of molecular weight, the change of the pH value and the change of the surface morphology after the degradation.
The results of Pro / hydrophobicity test showed that the static water contact angle of PAPI-PDLLA copolymer was less than PDLLA, and the water absorption rate was greater than that of PDLLA, and the hydrophilic property increased with the increase of the hydrophilic block PAPI in the copolymer.
The in vitro degradation experiment of PAPI-PDLLA copolymer showed that the weight loss of PAPI-PDLLA Series in the five weeks before degradation, the decrease of molecular weight and the change of pH value were faster than that of the PDLLA control group. But in the whole degradation process, it was found that PDLLA caused a steep drop due to the autocatalytic effect of acid accumulation during the degradation process, and in PAPI-PDLLA. In the series of materials, the degradation rate is more controllable and the natural logarithm and time of the degradation weight loss are fitted. It is found that the pseudo first order dynamic model Mnmolecular has no steep drop. This is due to the introduction of the hydrophilic block PAPI, which accelerates the dispersing of the degraded acid small molecules, and does not lead to the apparent autocatalytic degradation of the material. The scanning electron microscopy (SEM) after degradation showed that PDLLA could produce local heterogeneous degradation, while the degradation surface of PAPI-PDLLA copolymer was more uniform. Therefore, the degradation control performance of the material was higher than that of PDLLA.
4. the tensile and compression tests were used to investigate the mechanical properties of the material. The results showed that the copolymer had certain tensile strength and compressive strength, and the strength increased with the reduction of the material ratio of PAPI/D, L- lactide, and the elongation at break increased significantly with the increase of the material ratio of PAPI/D and L- lactide. The compression modulus is between 48-280MPa. The compression modulus is between 108-780MPa and the compression modulus of the cancellous bone. With the degradation of the material, the mechanical strength of the material gradually loses, and with the increase of the proportion of PAPI in the copolymer, the mechanical loss accelerates, and the tensile properties are almost all after the degradation of PAPD4/15 (PAPI-PDLLA PAPI/D, L-LA=4/15) for four weeks. The loss, and PAPD4/25 only lost about 20%.
5. the amino and hydroxyl groups were introduced on the surface of PAPI-PDLLA copolymer membrane by wet chemical method. The amino and hydroxyl groups grafted on the surface of the material were qualitatively and quantitatively characterized by XPS, colorimetric method, AFM and other methods. The amino and hydroxyl groups were easily introduced on the surface of the material without catalyst and at normal temperature. The amino density of the surface grafting of the base.PAPD4/15-BDA material is 3.41 * 10~ (-6) mol/cm~2. when the grafting of the amino group and the hydroxyl group, the surface of the material becomes coarser compared with the reaction before the reaction.
6. the cytotoxicity of PAPI and PAPI-PDLLA was evaluated by rat osteoblasts of rat milk. The cytocompatibility of PAPI-PDLLA and functional surface with PDLLA was systematically compared from the aspects of osteoblast morphology, adhesion, spreading, proliferation, differentiation and mineralization.
(1) the maximum amount of PMDA immersion solution, which could be produced by PAPI immersion and PAPI and PAPI-PDLLA degradation, was used to culture osteoblasts. It was found that osteoblasts were cultured in the above culture medium, and PAPI and PMA culture medium did not affect the morphology and proliferation of the cells, which showed that there was no obvious cytotoxicity of PAPI and PAPI-PDLLA.
Compared with PDLLA, proper introduction of PAPI promotes the adhesion and spreading of osteoblasts, while excessive PAPI is not conducive to cell adhesion, and the functional PAPI-PDLLA membrane surface is also beneficial to cell adhesion and spreading, and the adhesion of amino functional surface cells is most obvious.
(3) relative to PDLLA, the PAPI-PDLLA membrane with proper PAPI content is beneficial to cell proliferation, while the functionalized surface of amino and hydroxyl groups makes cell proliferation more significant.
The differentiation and mineralization of osteoblasts on the surface of the material were measured by alkaline phosphatase, inorganic calcium secretion and collagen secretion. The results showed that the differentiation and mineralization ability of the cells on the surface of the amino functional PAPI-PDLLA membrane was slightly better than that of PAPI-PDLLA, while the mineralization ability on the PAPI-PDLLA membrane was better than that of PDLLA..
【學(xué)位授予單位】：重慶大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.08
本文編號(hào)：2128275
[Abstract]:Bone tissue engineering provides a new way and hope for the patients with bone disease. The design of tissue regeneration scaffold is the key to the success of bone tissue engineering. It is usually required to meet certain mechanical strength, controllable degradation performance and reasonable surface induction of cell proliferation and differentiation and tissue regeneration. However, few materials can be used at the same time at the same time. The purpose of this study is to design a new type of bone tissue engineering material to make it capable of controlling degradation properties, certain mechanical strength, appropriate hydrophilic properties and functional surfaces. Based on the PEG derivative poly (ethylene glycol -co- benzoate anhydride) imide (PAPI), copolymerization of D, L- C (D, L-LA) ester, and copolymerization of PAPI) A series of new PAPI-PDLLA copolymers with adjustable performance are prepared. Using nuclear magnetic resonance (NMR), Fu Liye transform infrared spectrometer (FTIR), gel chromatography - eighteen angle laser scatterometer (GPC-MALLS), ultraviolet visible spectrometer (UV), differential scanning calorimeter (DSC), X photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), atomic force microscopy (AFM) and other copolymers The properties of chemical and physical properties were characterized. The affinity / hydrophobicity of PAPI-PDLLA copolymer, in vitro biodegradability, mechanical properties (tensile properties and compression properties), and the changes of mechanical properties during the degradation process were investigated. The amino and hydroxyl groups of the PAPI-PDLLA copolymers were studied. Finally, the PAPI-PDLLA was evaluated. Biocompatibility of copolymers and surface functionalized materials in vitro. The main contents and conclusions are as follows:
1. a new PEG derivative P (ATPGE-co-PMDA) (PAPI) was synthesized by the high temperature condensation reaction of PEG (ATPEG, Mr:900) and benzyldianhydride (PMDA) at low molecular weight, and the influence of monomer ratio, temperature and reaction time on the molecular weight of the polymer and the process of imimide during the reaction process were investigated. The derivate was connected by the benzimide ring and the introduction of the imide ring provided the conditions for the opening ring function grafting. The ability of Ding Eran, ethanolamine to react with the imide ring in PAPI was studied, and the structure of all the synthesized materials was characterized.
(1) FTIR, 1H NMR, 13C NMR, GPC-MALLA and UV detection results show that ATPEG and PMDA are successfully polymerized, and the micro excess of ATPEG makes the PAPI end have amino. When the molar ratio of the two is more than ATPEG/PMDA=1.05, after the reaction is completed at a set temperature, the imide base is complete, and the molecular weight of the polymer is larger and the polymer fraction is obtained. Thermogravimetric analysis showed that the thermal stability of PAPI relative to PEG was enhanced.
(2) FTIR showed that the imide ring in PAPI successfully reacted with butyl two amine and ethanolamine at room temperature without catalyst, which might provide a reaction site for graft functional groups.
(3) the gel was produced by crosslinking with butyl two amine, which has a certain mechanical strength and porosity, which is expected to be used in the field of drug release or tissue engineering.
The co initiation system of 2.PAPI and stannous octanate initiated a series of D, L- lactide ring opening and a series of PAPI-PDLLA copolymers. The effects of PAPI/D, L- lactide, reaction temperature and reaction time on the molecular weight of PAPI-PDLLA copolymers were investigated, and the chemical structure and thermal properties of the copolymers were characterized.
(1) the results of FTIR, 1H NMR, 13C NMR and GPC-MALLS showed that the co initiation system of PAPI and stannous octanate initiated the opening ring of lactide, and the PAPI-PDLLA copolymer was prepared. The optimum reaction time was 36 hours and the reaction temperature was 150.
(2) a series of copolymers with different molecular weights and properties can be prepared by adjusting the material ratio of PAPI and D, L- lactide. The amount of polylactic acid graft is calculated by 1H NMR. With the increase of PAPI/D, the proportion of L- lactide is increased, and the molecular weight of the grafted polylactic acid decreases.
(3) DSC results show that the PAPI-PDLLA copolymer has only one glass transition temperature, which indicates that the thermal compatibility of the two phases is good and the glass transition temperature decreases with the increase of the proportion of PAPI. The results of thermogravimetric analysis show that the PAPI-PDLLA has two obvious decomposition temperatures, first of which is PDLLA block decomposition, then the decomposition of PAPI, by thermogravimetric analysis. The mass ratio of the two block is obtained.
3. the Pro / hydrophobicity and degradation properties of PAPI-PDLLA copolymer were studied. The hydrophobicity and hydrophobicity of the copolymer were evaluated by two methods of static water contact angle and total water absorption on the surface of the material, and the degradation properties of the materials were evaluated by the weight loss rate, the change of molecular weight, the change of the pH value and the change of the surface morphology after the degradation.
The results of Pro / hydrophobicity test showed that the static water contact angle of PAPI-PDLLA copolymer was less than PDLLA, and the water absorption rate was greater than that of PDLLA, and the hydrophilic property increased with the increase of the hydrophilic block PAPI in the copolymer.
The in vitro degradation experiment of PAPI-PDLLA copolymer showed that the weight loss of PAPI-PDLLA Series in the five weeks before degradation, the decrease of molecular weight and the change of pH value were faster than that of the PDLLA control group. But in the whole degradation process, it was found that PDLLA caused a steep drop due to the autocatalytic effect of acid accumulation during the degradation process, and in PAPI-PDLLA. In the series of materials, the degradation rate is more controllable and the natural logarithm and time of the degradation weight loss are fitted. It is found that the pseudo first order dynamic model Mnmolecular has no steep drop. This is due to the introduction of the hydrophilic block PAPI, which accelerates the dispersing of the degraded acid small molecules, and does not lead to the apparent autocatalytic degradation of the material. The scanning electron microscopy (SEM) after degradation showed that PDLLA could produce local heterogeneous degradation, while the degradation surface of PAPI-PDLLA copolymer was more uniform. Therefore, the degradation control performance of the material was higher than that of PDLLA.
4. the tensile and compression tests were used to investigate the mechanical properties of the material. The results showed that the copolymer had certain tensile strength and compressive strength, and the strength increased with the reduction of the material ratio of PAPI/D, L- lactide, and the elongation at break increased significantly with the increase of the material ratio of PAPI/D and L- lactide. The compression modulus is between 48-280MPa. The compression modulus is between 108-780MPa and the compression modulus of the cancellous bone. With the degradation of the material, the mechanical strength of the material gradually loses, and with the increase of the proportion of PAPI in the copolymer, the mechanical loss accelerates, and the tensile properties are almost all after the degradation of PAPD4/15 (PAPI-PDLLA PAPI/D, L-LA=4/15) for four weeks. The loss, and PAPD4/25 only lost about 20%.
5. the amino and hydroxyl groups were introduced on the surface of PAPI-PDLLA copolymer membrane by wet chemical method. The amino and hydroxyl groups grafted on the surface of the material were qualitatively and quantitatively characterized by XPS, colorimetric method, AFM and other methods. The amino and hydroxyl groups were easily introduced on the surface of the material without catalyst and at normal temperature. The amino density of the surface grafting of the base.PAPD4/15-BDA material is 3.41 * 10~ (-6) mol/cm~2. when the grafting of the amino group and the hydroxyl group, the surface of the material becomes coarser compared with the reaction before the reaction.
6. the cytotoxicity of PAPI and PAPI-PDLLA was evaluated by rat osteoblasts of rat milk. The cytocompatibility of PAPI-PDLLA and functional surface with PDLLA was systematically compared from the aspects of osteoblast morphology, adhesion, spreading, proliferation, differentiation and mineralization.
(1) the maximum amount of PMDA immersion solution, which could be produced by PAPI immersion and PAPI and PAPI-PDLLA degradation, was used to culture osteoblasts. It was found that osteoblasts were cultured in the above culture medium, and PAPI and PMA culture medium did not affect the morphology and proliferation of the cells, which showed that there was no obvious cytotoxicity of PAPI and PAPI-PDLLA.
Compared with PDLLA, proper introduction of PAPI promotes the adhesion and spreading of osteoblasts, while excessive PAPI is not conducive to cell adhesion, and the functional PAPI-PDLLA membrane surface is also beneficial to cell adhesion and spreading, and the adhesion of amino functional surface cells is most obvious.
(3) relative to PDLLA, the PAPI-PDLLA membrane with proper PAPI content is beneficial to cell proliferation, while the functionalized surface of amino and hydroxyl groups makes cell proliferation more significant.
The differentiation and mineralization of osteoblasts on the surface of the material were measured by alkaline phosphatase, inorganic calcium secretion and collagen secretion. The results showed that the differentiation and mineralization ability of the cells on the surface of the amino functional PAPI-PDLLA membrane was slightly better than that of PAPI-PDLLA, while the mineralization ability on the PAPI-PDLLA membrane was better than that of PDLLA..
【學(xué)位授予單位】：重慶大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.08
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 糜麗;潘君;趙明媚;劉穎;王彬;王遠(yuǎn)亮;;一種可促進(jìn)成骨細(xì)胞黏附和生長(zhǎng)的聚乙二醇接枝聚乳酸材料[J];材料導(dǎo)報(bào);2008年08期
2 宋謀道,朱吉亮,張邦華,郝廣杰,周慶業(yè),張瑩,趙芬芝,趙英奇,楊世強(qiáng),范玉玲;聚乙二醇改性聚乳酸的研究[J];高分子學(xué)報(bào);1998年04期
3 張國(guó)棟,馮新德,顧忠偉;端基含葡氨糖衍生物的聚乳酸的合成與表征[J];高分子學(xué)報(bào);1998年04期
4 盧紅斌,何天白;聚酰亞胺反應(yīng)動(dòng)力學(xué)研究進(jìn)展[J];高分子材料科學(xué)與工程;2000年05期
5 趙明媚;潘君;李永剛;劉穎;王遠(yuǎn)亮;牛旭峰;;一種可阻止非特異性蛋白質(zhì)吸附的新型聚乳酸材料——聚乙二醇接枝聚乳酸[J];高分子材料科學(xué)與工程;2007年03期
6 羅彥鳳;王素軍;牛旭鋒;王遠(yuǎn)亮;付春華;黃美娜;;RGDS和膠原改性聚(DL-乳酸)的合成與表征[J];高分子材料科學(xué)與工程;2008年05期
7 蔡開勇,林松柏,姚康德;組織工程相關(guān)生物材料表面工程的研究進(jìn)展[J];化學(xué)進(jìn)展;2001年01期
8 賀亞敏,黃培林,呂曉迎;幾種醫(yī)用材料的細(xì)胞生物相容性評(píng)價(jià)的實(shí)驗(yàn)研究[J];東南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2003年02期
9 路慶華,王宗光,孫立民,劉勇;聚酰亞胺的熱亞胺化動(dòng)力學(xué)研究[J];上海交通大學(xué)學(xué)報(bào);1997年07期
10 楊曉芳,奚廷斐;生物材料生物相容性評(píng)價(jià)研究進(jìn)展[J];生物醫(yī)學(xué)工程學(xué)雜志;2001年01期
相關(guān)博士學(xué)位論文 前4條
1 阮長(zhǎng)順;新型骨修復(fù)材料可降解哌嗪基聚氨酯脲的研究[D];重慶大學(xué);2011年
2 羅彥鳳;聚（DL—乳酸）的改性及體外降解和細(xì)胞相容性研究[D];重慶大學(xué);2003年
3 楊媛;交聯(lián)型生物可控降解骨組織修復(fù)材料的制備及應(yīng)用[D];暨南大學(xué);2007年
4 黃美娜;可預(yù)防骨不連的骨修復(fù)用新型形狀記憶聚氨酯-脲的研究[D];重慶大學(xué);2010年
相關(guān)碩士學(xué)位論文 前1條
1 林福春;力生長(zhǎng)因子E肽（MGF-Ct24E）與應(yīng)力作用對(duì)成骨細(xì)胞基因表達(dá)影響的基因芯片分析[D];重慶大學(xué);2011年
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