本文關(guān)鍵詞： 聚乙二醇 縮聚反應(yīng) 巰-烯點(diǎn)擊反應(yīng) 可注射水凝膠 臨界骨缺損 骨再生修復(fù)　出處：《浙江大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：當(dāng)前人們對骨整形和口腔種植修復(fù)的需求越來越高,如何促進(jìn)或加速骨再生修復(fù),為骨整形或種植體植入創(chuàng)造良好的骨條件一直是眾多學(xué)者研究的熱點(diǎn)。本研究正是鑒于此設(shè)計(jì)并制備出一種新型的可注射原位成型PEG水凝膠,并進(jìn)行了一系列全面的體內(nèi)／外評價(jià),主要研究結(jié)果和結(jié)論如下：1、先將寡聚乙二醇(OEG9)與硫代蘋果酸(MSA)或馬來酸酐(MA)在三氟甲磺酸鈧(Sc(OTf)3)催化的溫和條件下通過“一鍋”法縮聚反應(yīng)大量合成可降解的水溶性PEG衍生物POEGMS和POEGM;反應(yīng)產(chǎn)率高達(dá)81%和87%,且產(chǎn)物中OEG和二酸的摩爾比非常接近初始投料比；核磁共振(1H NMR)譜圖結(jié)果和凝膠滲透色譜(GPC)曲線等結(jié)果表明兩種含有可點(diǎn)擊基團(tuán)(巰基和雙鍵)的凝膠前體(POEGMS和POEGM)被成功合成,且無各自前體的殘留。其次,通過巰-烯“點(diǎn)擊”反應(yīng),所合成的水凝膠前體能在近似人體生理?xiàng)l件下(pH7.4和37℃)約30秒內(nèi)迅速凝膠化形成三維網(wǎng)絡(luò)骨架；其凝膠化時(shí)間可以通過pH值的微調(diào)以適應(yīng)臨床原位成型的實(shí)際操作需要；傅里葉變換紅外譜圖(FTIR)證明水凝膠前體中雙鍵與巰基能全部高效地完成反應(yīng)。2、一系列體外實(shí)驗(yàn)證明了10%固含量的水凝膠不但具有非常好的生物相容性和較好的機(jī)械強(qiáng)度(G’達(dá)69.2kPa),而且具有較低溶脹率(小于50%)和合適的降解速度(2W內(nèi)幾乎很少分解)；成骨前體細(xì)胞(MC3T3-E1)和大鼠骨髓間充質(zhì)干細(xì)胞(rBMSC)能在水凝膠表面較好的粘附、鋪展和增殖,在成骨誘導(dǎo)性培養(yǎng)條件下能成功地發(fā)生成骨向分化；二種細(xì)胞在水凝膠內(nèi)部均能三維生長,其細(xì)胞團(tuán)塊能成功地侵入凝膠內(nèi)部生長；水凝膠荷載rhBMP-2后在近似生理?xiàng)l件下的釋放能維持達(dá)2周之久,并對在凝膠表面黏附生長和凝膠內(nèi)部三維生長的rBMSC的增殖和成骨分化有明顯促進(jìn)作用。3、大鼠顱骨臨界骨缺損(CSD)植入實(shí)驗(yàn)結(jié)果表明：單純的水凝膠植入后,其本身就能促進(jìn)大鼠顱骨CSD缺損骨修復(fù)再生；當(dāng)荷載rBMSC的水凝膠體內(nèi)植入8w后就能達(dá)到缺損的骨性封閉；當(dāng)同時(shí)荷載rhBMP-2和rBMSC時(shí),其骨修復(fù)再生能力有了大幅度提高,在4w時(shí)就幾乎完成CSD缺損部位的大部分的骨質(zhì)修復(fù)再生,無論在新骨體積分?jǐn)?shù)和骨小梁結(jié)構(gòu)形成上都明顯優(yōu)于其他組別。綜上所述,本研究所制備的可注射原位成型PEG水凝膠是一種合成制備方法簡單、使用方便具有很好臨床應(yīng)用前景的新型骨增量材料。
[Abstract]:At present, there is a growing demand for bone orthopedics and dental implants. How to promote or accelerate the repair of bone regeneration. To create a good bone condition for bone plastic or implant implantation has been the focus of many scholars. In this study, we designed and prepared a new injectable in-situ molding PEG hydrogel. A series of in vitro / in vivo evaluations were carried out. The main findings and conclusions are as follows: 1. OTf3) was prepared by using oligosyleneglycol (OEG9) or maleic anhydride (MSA) or maleic anhydride (MAA) in Scandium trifluoromeesulfonate (SC). A large number of degradable water-soluble PEG derivatives POEGMS and POEGM were synthesized by "one-pot" Polycondensation under mild conditions. The yield of the reaction is as high as 81% and 87, and the molar ratio of OEG and diacid in the product is very close to the initial feed ratio. The results of 1H NMR and GPC showed that two kinds of gel precursors containing clickable groups (mercapto and double bonds) were POEGMS and POEGM). Was successfully synthesized. And there was no residue of their precursors. Secondly, through the mercapto "click" reaction. The synthesized hydrogel precursor can rapidly gel to form a three-dimensional network skeleton within about 30 seconds under similar physiological conditions (pH 7.4 and 37 鈩，

本文編號：1492625