經(jīng)過近10年的研究和探索，在中國工程院院士王正國的帶領(lǐng)下,，第三軍大學(xué)大坪醫(yī)院,、野戰(zhàn)外科研究所副研究員張波等人研制出了具有組織相容性、無免疫源性和可降解,，具備增強(qiáng)血液灌注和促血管化的骨組織工程支架材料——肝素/殼聚糖/脫細(xì)胞骨基質(zhì)仿生支架材料,，攻克了異種脫骨基質(zhì)跨種屬應(yīng)用的大動(dòng)物實(shí)驗(yàn)。該項(xiàng)研究成果的論文發(fā)表在美國《組織工程》雜志上,，預(yù)計(jì)不久將有望應(yīng)用于臨床對人體骨缺損修復(fù),。
據(jù)了解，骨缺損修復(fù)一直是骨科醫(yī)學(xué)的難題,，而自然災(zāi)害,、突發(fā)事故及戰(zhàn)爭等導(dǎo)致需植骨修復(fù)的人數(shù)呈上升趨勢。應(yīng)用組織工程技術(shù)構(gòu)建的組織工程骨作為骨缺損修復(fù)的發(fā)展方向,，雖臨床初步應(yīng)用效果確切,，但因組織工程骨的血管化等問題成為世界關(guān)注的瓶頸，制約了臨床大規(guī)模應(yīng)用,。研制新一代有特定結(jié)構(gòu)和功能的仿生“智能”基質(zhì)材料,，成為當(dāng)今組織工程學(xué)和生物材料學(xué)研究領(lǐng)域的前沿課題。
2002年,，課題組開始異種骨基質(zhì)的研究,。他們采用牛骨經(jīng)生化,、理化處理去抗原、去細(xì)胞,，經(jīng)生物安全性檢測達(dá)標(biāo)后,，將該骨基質(zhì)材料應(yīng)用于豬尺骨缺損修復(fù)，實(shí)驗(yàn)表明,，3個(gè)月內(nèi)骨基質(zhì)全部降解,，缺損修復(fù)效果良好。
2009年,，團(tuán)隊(duì)受到水蛭抗血凝及負(fù)壓吸血的啟發(fā),，模擬其原理解決組織工程骨植入?yún)^(qū)血液循環(huán)障礙等難題。
實(shí)驗(yàn)結(jié)果顯示,，構(gòu)建的肝素/殼聚糖/脫細(xì)胞骨基質(zhì)仿生支架材料在超微結(jié)構(gòu)上骨小梁結(jié)構(gòu)無變化,，而材料表面變平滑更利于種子細(xì)胞黏附；材料表面的分子結(jié)構(gòu)檢測證實(shí)肝素成功復(fù)合到材料表面,，且體外肝素緩釋檢測表明一周內(nèi)肝素可以有效釋放,，抗凝效果明顯延長。動(dòng)物實(shí)驗(yàn)結(jié)果證實(shí)肝素/殼聚糖/脫細(xì)胞骨基質(zhì)仿生支架材料可以有效促進(jìn)血液灌注,。
課題組通過肝素/殼聚糖自組裝表面改性后脫細(xì)胞骨基質(zhì)材料,，解決了植入材料被血凝塊包圍，以及移植物的氧和營養(yǎng)物質(zhì)灌注障礙等瓶頸問題,，為臨床大塊骨缺損修復(fù)提供了技術(shù)支持,；同時(shí)也為進(jìn)一步采用仿生學(xué)方法模擬水蛭療法在斷指再植、皮瓣移植及肢體循環(huán)障礙等領(lǐng)域促進(jìn)微循環(huán)血液流動(dòng),，改善組織血液循環(huán)提供了理論依據(jù),，經(jīng)過臨床試驗(yàn)后便可普遍推廣應(yīng)用。(生物谷 Bioon.com)
doi:10.1089/ten.tea.2011.0027
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Heparin-Chitosan-Coated Acellular Bone Matrix Enhances Perfusion of Blood and Vascularization in Bone Tissue Engineering Scaffolds
Xin-jun Sun,Wei Peng,Zai-liang Yang,Ming-liang Ren,Shi-chang Zhang,Wei-guo Zhang,Lian-yang Zhang,Kai Xiao,Zheng-guo Wang,Bo Zhang,andJin Wang
Currently, the main hurdle in the tissue engineering field is how to provide sufficient blood supply to grafted tissue substitutes in the early post-transplanted period. For three-dimensional, cell-dense, thick tissues to survive after transplantation, treatments are required for hypoxia, nutrient insufficiency, and the accumulation of waste products. In this study, a biomacromolecular layer-by-layer coating process of chitosan/heparin onto a decellularized extracellular bone matrix was designed to accelerate the blood perfusion and re-endothelialization process. The results of in vitro measurements of the activated partial thromboplastin time supported the theory that the combination of chitosan and heparin could bring both anticoagulation and hemocompatibility to the scaffold. A rabbit bone defect model was established for further evaluation of the application of this kind of surface-modified scaffold in vivo. The final results of computed tomography (CT) perfusion imaging and histological examination proved that this facile coating approach could significantly promote blood perfusion and re-endothelialization in the early post-transplanted period compared with an acellular bone matrix due to its much-improved anticoagulation property.
