光聚合聚乳酸—聚乙二醇凝胶薄膜的合成及性能研究
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摘要
近年来,生物可降解高分子材料在材料科学和生物医学领域得到了广泛的应用。聚乳酸(PLA)是一种无毒、可完全降解的聚合物,不仅具有较好的化学惰性、易加工性,而且还具有良好的生物相容性,在生物医学领域受到广泛重视。聚乙二醇(PEG)具有良好的亲水性和生物相容性,能够抗蛋白质吸附,是一种优良的生物医学材料。但二者各有其局限性:聚乳酸是疏水性物质,降低了其生物相容性;而聚乙二醇的降解性较差。人们通过各种手段将PLA与PEG复合,使两者在性能上互补,以获得性能更加优异的生物医学材料。
本文选用L-乳酸、1,6-己二醇、三羟甲基丙烷和季戊四醇为原料,以氯化亚锡为催化剂,通过直接熔融缩聚法,制备了一系列端基结构及分子量各不相同的线形、支链形及星形结构的端羟基聚乳酸(PLLA-OH),进一步与丙烯酰氯反应,得到了相应的聚乳酸丙烯酸酯(PLLA-AC)。在此基础上,将PLLA-AC和聚乙二醇双丙烯酸酯(PEG-DA)按照不同配比,在光引发剂2,2-二甲氧基-2-苯基苯乙酮(DMPA)作用下,经紫外光照射制得PLLA-PEG凝胶薄膜。
利用IR、1H-NMR、GPC和XRD等对PLLA-OH和PLLA-AC的结构和性质进行分析;利用XRD、拉力机和SEM等对PLLA-PEG凝胶薄膜的结晶性能、力学性能和内部形态进行了分析,并对薄膜的溶胀性能、降解性能和药物释放性能进行了详细地研究。
结果表明,通过改变PLLA-AC的结构、分子量以及PLLA-AC与PEG-DA的配比,可以调节PLLA-PEG光聚合水凝胶薄膜的各项性质,并使其成为一种具有优良性能和应用前景的生物材料。
The biodegradable polymer materials have been widely investigated and applied in material science and biomedical field in recent years. Poly(L-lactic acid) has been attached much attention in biomaterial applications owing to its safety, biodegradability, environmental compatibility and so on. However, its clinical applications are sometimes interfered with hydrophobic property, which could decrease the biocompatibility. Poly(ethylene glycol) is also an excellent biomaterial with hydrophilic ability, biocompatibility and resistibility to protein adsorption and cell adhesion. PLLA is usually modified by PEG to get a better material, which could combine the advantages of PLLA and PEG.
In the paper, multi-hydroxyl groups ended poly(L-lactic acid)s (PLLA-OH) were prepared using L-lactic acid and 1, 6-hexanediol / 2-ethyl-2-hydroxymethyl-1, 3-propanediol / pentaerythritol by direct polycondensation. Afterward, acrylated poly (L-lactic acid)s (PLLA-AC) were gained through the reaction of PLLA-OHs and acryloyl chloride. Furthermore, a series of PLLA-PEG hydrogel films were formed by UV photopolymerization using 2, 2-dimethoxy-2-phenylacetophenone (DMPA) as initiator.
The structures and properties of PLLA-OHs and PLLA-ACs were characterized by IR, 1H-NMR, GPC and XRD. The properties of PLLA-PEG hydrogel films were measured by XRD, SEM and so on. Besides, the swelling performance, degradation and drug release behaviors of PLLA-PEG hydrogel films were also studied in detail.
The results show that PLLA-PEG hydrogel films could improve the property and performance by changing PLLA-AC molecular weight, structure and proportion of PEG-DA, which could be widely applied in biomedical field in the future.
本文选用L-乳酸、1,6-己二醇、三羟甲基丙烷和季戊四醇为原料,以氯化亚锡为催化剂,通过直接熔融缩聚法,制备了一系列端基结构及分子量各不相同的线形、支链形及星形结构的端羟基聚乳酸(PLLA-OH),进一步与丙烯酰氯反应,得到了相应的聚乳酸丙烯酸酯(PLLA-AC)。在此基础上,将PLLA-AC和聚乙二醇双丙烯酸酯(PEG-DA)按照不同配比,在光引发剂2,2-二甲氧基-2-苯基苯乙酮(DMPA)作用下,经紫外光照射制得PLLA-PEG凝胶薄膜。
利用IR、1H-NMR、GPC和XRD等对PLLA-OH和PLLA-AC的结构和性质进行分析;利用XRD、拉力机和SEM等对PLLA-PEG凝胶薄膜的结晶性能、力学性能和内部形态进行了分析,并对薄膜的溶胀性能、降解性能和药物释放性能进行了详细地研究。
结果表明,通过改变PLLA-AC的结构、分子量以及PLLA-AC与PEG-DA的配比,可以调节PLLA-PEG光聚合水凝胶薄膜的各项性质,并使其成为一种具有优良性能和应用前景的生物材料。
The biodegradable polymer materials have been widely investigated and applied in material science and biomedical field in recent years. Poly(L-lactic acid) has been attached much attention in biomaterial applications owing to its safety, biodegradability, environmental compatibility and so on. However, its clinical applications are sometimes interfered with hydrophobic property, which could decrease the biocompatibility. Poly(ethylene glycol) is also an excellent biomaterial with hydrophilic ability, biocompatibility and resistibility to protein adsorption and cell adhesion. PLLA is usually modified by PEG to get a better material, which could combine the advantages of PLLA and PEG.
In the paper, multi-hydroxyl groups ended poly(L-lactic acid)s (PLLA-OH) were prepared using L-lactic acid and 1, 6-hexanediol / 2-ethyl-2-hydroxymethyl-1, 3-propanediol / pentaerythritol by direct polycondensation. Afterward, acrylated poly (L-lactic acid)s (PLLA-AC) were gained through the reaction of PLLA-OHs and acryloyl chloride. Furthermore, a series of PLLA-PEG hydrogel films were formed by UV photopolymerization using 2, 2-dimethoxy-2-phenylacetophenone (DMPA) as initiator.
The structures and properties of PLLA-OHs and PLLA-ACs were characterized by IR, 1H-NMR, GPC and XRD. The properties of PLLA-PEG hydrogel films were measured by XRD, SEM and so on. Besides, the swelling performance, degradation and drug release behaviors of PLLA-PEG hydrogel films were also studied in detail.
The results show that PLLA-PEG hydrogel films could improve the property and performance by changing PLLA-AC molecular weight, structure and proportion of PEG-DA, which could be widely applied in biomedical field in the future.
引文
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[2] Cruise G M, Scharp D S, Hubbell J A. Characterization of permeability and network structure of interfacially photopolymerized poly(ethylene glycol) diacrylate hydrogels. BIOMATERIALS, 1998, 19: 287–1294
[3] Sawhney A S, Pathak C P, Hubbell J A. Biomerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(α-hydroxy acid)diacrylate macromers. MACROMOLECULES, 1993, 26: 581-587.
[4] Masters K S, Shah D N, Anseth K S, et al. Designing scaffolds for valvular interstitial cells: Cell adhesion and function on naturally derived materials. J BIOMED MATER RES A, 2004, 71A (1): 172-180.
[5] Masters K S, Shah D N, Anseth K S, et al. Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells. BIOMATERIALS, 2005, 26 (15): 2517-2525.
[6] Ono K, Saito Y, Kurita A, et al. Photocrosslinkable chitosan as a biological adhesive. J BIOMED MATER RES, 2000, 49 (2): 289-295.
[7] Ishihara M, Nakanishi K, Kurita A, et al. Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. BIOMATERIALS, 2002, 23 (3): 833-840.
[8] Burdick J A, Ward M, Langer R, et al. Stimulation of neurite outgrowth by neurotrophins delivered from degradable hydrogels. BIOMATERIALS, 2006, 27 (3): 452-459.
[9] Burdick J A, Mason M N, Anseth K S, et al. Delivery of osteoinductive growth factors from degradable PEG hydrogels influences osteoblast differentiation and mineralization. J CONTROL RELEASE , 2002, 83 (1): 53-63.
[10] Bryant S J, Durand K L, Anseth K S. Manipulations in hydrogel chemistry control photoencapsulated chondrocyte behavior and their extracellular matrix production. J BIOMED MATER RES A, 2003, 67A (4): 1430-1436.
[11] Bryant S J, Anseth K S, Lee D A, et al. Crosslinking density influences the morphology of chondrocytes photoencapsulated in PEG hydrogels during the application of compressive strain. J ORTHOP RES, 2004, 22 (5): 1143-1149.
[12] Bryant S J, Anseth K S. The effects of scaffold thickness on tissue engineered cartilage in photocrosslinked poly(ethylene oxide) hydrogels. BIOMATERIALS, 2001, 22: 619-626
[13] Li Q, Wang J, Elisseeff J H, et al. Biodegradable and photocrosslinkablepolyphosphoester hydrogel. BIOMATERIALS, 2006, 27 (7): 1027-1034.
[14] Hahn M S, Taite L J, West J L, et al. Photolithographic patterning of polyethylene glycol hydrogels. BIOMATERIALS, 2006, 27 (12): 2519-2524.
[15] DeLong S A, Gobin A S, West J L. Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and migration. J CONTROL RELEASE, 2005, 109 (1-3): 139-148.
[16] Cruise G M, Hegre O D, Lamberti F V, et al. In vitro and in vivo performance of porcine islets encapsulated in interfacially photopolymerized poly(ethylene glycol) diacrylate membranes. CELL TRANSPLANT, 1999, 8: 293-306.
[17] Cruise G M, Scharp D S, Hubbell J A. Characterization of permeability and network structure of interfacially photopolymerized poly(ethylene glycol) diacrylate hydrogels. BIOMATERIALS, 1998, 19: 1287-1294.
[18] Elisseeff J, Anseth K, Langer R, et al. Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage. PLAST RECONSTR SURG, 1999, 104 (4): 1014-1022
[19] Patel P N, Gobin A S, West J L, et al. Poly( ethylene glycol) hydrogel system supports preadipocyte viability, adhesion, and proliferation. TISSUE ENG, 2005, 11 (9-10): 1498-1505.
[20] DeLong S A, Moon J J, West J L. Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration. BIOMATERIALS, 2005, 26 (16): 3227-3234.
[21] Gobin A S, West J L. Val-ala-pro-gly, an elastin-derived non-integrin ligand: Smooth muscle cell adhesion and specificity. J BIOMED MATER RES A, 2003, 67A (1): 255-259.
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