Synthesis and characterization of bioresorbable in situ crosslinkable ultra low molecular weight poly(lactide) macromer

Synthesis and characterization of bioresorbable in situ crosslinkable ultra low molecular weight poly(lactide) macromer
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DOI:
10.1007/s10856-006-0020-2
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发表时间:
2008-01-01
影响因子:
3.7
通讯作者:
He, Xuezhong
He, Xuezhong
中科院分区:
工程技术3区
文献类型:
--
作者:
Jabbari, Esmaiel;He, Xuezhong

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反应性低分子量聚(L-乳酸)(PLA)需要产生具有快速交联速率、高交联密度和足够机械强度的原位硬化支架。本工作的目的是合成不饱和超低分子量聚乳酸(ULMW PLA)作为一种可注射的原位交联大分子单体,用于生物医学应用。以L-丙交酯(LA)为原料,二甘醇(DEG)为引发剂,通过开环聚合合成了低分子量聚乳酸(PLA)。LA与DEG的摩尔比为5至20。使用非溶剂甲醇、乙醚和己烷进行纯化和分馏。在甲醇和乙醚中沉淀的PLA样品具有窄的分布(PDI = 1.2),并且分别产生M-n为4.8的粉末和M-n为3.6kDa的蜡。其中来自醚的上清液在己烷中再沉淀的PLA样品产生粘性ULMW PLA,其M-n和PDI分别为1.2kDa和1.2。将超低分子量聚乳酸(ULMW PLA)与富马酰氯反应,制备了不饱和原位交联聚乳酸富马酸酯(PLAF)大分子单体。在致孔剂的存在下,注射并原位交联PLAF大分子单体与NVP交联剂后制备多孔支架。将其植入裸鼠体内,有新骨形成,证明该支架具有骨传导性。PLAF作为一种反应性大分子单体在制备可生物吸收的可注射原位交联的组织再生支架中具有潜在的用途。
Reactive low molecular weight poly(L-latide) (PLA) is required to produce in situ hardened scaffolds with fast rate of crosslinking, high crosslink density, and adequate mechanical strength. The objective of this work was to synthesize unsaturated ultra low moelcular weight PLA (ULMW PLA) as an injectable in situ crosslinkable macromer for biomedical applications. Low molecular weight PLA was synthesized by ring-opening polymerization of L-lactide (LA) using diethylene glycol (DEG) as the initiator. The molar ratio of the LA to DEG ranged from 5 to 20. Non-solvents methanol, ether, and hexane were used for purification and fractionation. The PLA samples that were precipitated in methanol and ether had narrow distributions (PDI = 1.2) and resulted in a powder with M-n of 4.8 and a wax with M-n of 3.6 kDa, respectively. The PLA sample in which the supernatant from ether was re-precipitated in hexane produced a viscous ULMW PLA with M-n and PDI of 1.2 kDa and 1.2, respectively. The ULMW PLA was reacted with fumaryl chloride to produce unsaturated in situ crosslinkable poly(lactide fumarate) (PLAF) macromer. Porous scaffolds were produced after injection and in situ crosslinking of the PLAF macromer with NVP crosslinker in the presence of a porogen. New bone was formed in the scaffold when it was implanted in nude mice which demonstrated that the scaffold was osteoconductive. PLAF is potentially useful as a reactive macromer in fabrication of bioresorbable injectable in situ crosslinkable scaffolds for tissue regeneration.