Zhi Cui, Baofeng Yang, Ren-Ke Li,*
aInstitute of Medical Science & Department of Surgery, Division of Cardiovascular Surgery, University of Toronto, Toronto, ON M5G 2M9, CanadabDepartment of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150001, China
cDivision of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada
生物材料在心臟修復和再生中的應用
Zhi Cuia,c, Baofeng Yangb, Ren-Ke Lia,c,*
aInstitute of Medical Science & Department of Surgery, Division of Cardiovascular Surgery, University of Toronto, Toronto, ON M5G 2M9, CanadabDepartment of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150001, China
cDivision of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, ON M5G 1L7, Canada
a r t i c l e i n f o
Article history:
Received 24 November 2015
Revised 7 March 2016
Accepted 9 March 2016
Available online 31 March 2016
心肌梗死
心臟再生
生物材料
組織工程
干細胞
心血管疾病是全世界主要致死原因之一。人們對新的干預性治療手段的需求與日俱增。雖然藥物和手術治療極大地改善了心血管疾病患者的生活質量,但人們還是需要價格更便宜、副作用更小的治療手段。天然和合成生物材料無論是作為給藥載體,還是替代支架的細胞外基質,在心臟修復和再生中都展現(xiàn)出巨大的潛力。本文探討了目前治療心血管疾病的幾種方式和應用于上述疾病干預性治療的生物材料;著重研究了導電聚合物在糾正局部缺血性心臟病引發(fā)的傳導異常及其在心臟起搏器中應用的可能性,以改善心肌梗死狀態(tài)下的傳導路徑。
? 2016 THE AUTHORS.Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
根據(jù)加 拿大公共衛(wèi)生局發(fā)布的報告《加拿大疾病經濟負擔》表明,2008年加拿大與心血管疾病相關的治療、醫(yī)院護理和藥物成本為117億加元,成為醫(yī)療系統(tǒng)最大的經濟負擔[1]。同樣,心血管疾病在世界范圍內也是主要的致死原因,嚴重影響了人們的生活質量[2]。因為心臟自身修復能力非常有限,所以一些常見的心血管疾病目前仍然無法得到完全治愈,如心肌梗死和心律失常。藥物干預、冠狀動脈旁路移植術和心室輔助裝置等治療方法可以顯著改善患者的生活質量,延長他們的壽命[3-5]。然而,未來仍然需要新的、低成本且高效的治療干預手段。
過去幾十年里,再生醫(yī)學治療心血管疾病的研究逐漸興起。此外,近幾年基因和分子醫(yī)學的發(fā)展為治療心血管疾病確立了個性化治療的概念[6]。人體誘導性多能干細胞(iPSC)的出現(xiàn)為再生醫(yī)學的發(fā)展開啟了新的篇章,因其可能成為心臟修復中心肌細胞的潛在來源[7]。事實上,人體iPSC源性心肌細胞已通過組織工程方法培養(yǎng)成功,并在植入患有心肌梗死的大鼠心臟組織后顯著提升了心臟功能[8]。iPSC源性心肌細胞已被用于研究心臟離子通道病變和心律失常的體內發(fā)病機制[9]。然而,移植干細胞存活能力較差仍然是心臟再生的主要障礙。
生物材料能夠被獨立傳輸,也可作為支架、細胞或生長因子的載體[10-12],因此可以改善上述問題。天然和合成生物材料的治療潛力均已在心肌梗死的動物模型和外周動脈疾病(PAD)的治療中得到證實[13]。特別是可注射生物材料的應用,使左心室壁擴張減少、新生血管增多, 通過內源性干細胞募集增強組織修復,并達到保護心臟功能的效果[12,14]。
本文關注的是引發(fā)傳導異常的心血管疾病及其目前的干預治療手段,心血管研究中所應用的生物材料的類型,以及這些生物材料用于干預性治療的潛力。目前的研究主要集中在如何提高心臟功能和心臟組織再生,而在評估導電聚合物用于糾正心臟活動相關的心律失常以及體內傳導阻滯的潛力方面的研究相對較少。本文著重探討將導電聚合物用于糾正心律失常和提高梗死心肌的傳導能力,同時分析未來將導電聚合物從基礎研究應用到臨床治療中所面臨的挑戰(zhàn)。
2.1.細胞療法治療缺血性心臟病
冠狀動脈粥樣硬化性心臟病(CAD)是最常見的心臟病之一,也是世界上主要的致死原因之一[2]。冠狀動脈為心臟組織提供含氧血和營養(yǎng)。CAD的發(fā)生是由于在動脈內壁上含膽固醇的斑塊沉積,導致血管壁增厚、血管腔變窄,進而導致血流量減少,造成心肌細胞缺血性損傷。心肌供血量減少的患 者會感到胸痛(心絞痛)、氣短且活動能力受限。而血管完全阻塞會導致心肌梗死,造成心肌細胞壞死和大量損失[15]。目前針對局部缺血性心臟病的標準干預療法主要是改變生活方式、藥物干預和手術治療[16]。所有可用治療方案都無效的患者會逐步發(fā)展至心臟衰竭,這種情況需要進行心臟移植。
細胞療法(向動物或患者體內注射細胞)成為治療心肌梗死的一種潛在策略。研究者提出并研究了多種備選細胞類型,如骨髓單核細胞[17,18]、胚胎干細胞[19,20]、成肌細胞[21,22]、內皮祖細胞[23]和心臟干細胞[24,25]。雖然在動物和人類研究中都觀察到細胞療法有助于改善心臟功能[26-28],但仍然存在一些問題,如較低的細胞保留/移植率、細胞傳輸效率問題、機電一體化問題和長期安全問題[29-33]。改進這些問題對未來細胞治療研究至關重要。生物材料也許是解決問題的答案,因為生物材料可作為細胞的載體,直接運送細胞至受損位置,或者在以生物材料為基礎的支架上 培育細胞,用于移植[34,35]。
2.2.生物材料在心臟修復和再生中的應用
生物材料用于心臟修復的必備條件是生物相容性和生物降解性。它能降低局部微環(huán)境的排斥性,可長時間促進移植細胞融入自然組織,并作為生物活性分子緩慢釋放的容器[36-38]。天然生物材料(明膠[39]、膠原[40]、藻酸鹽[41,42]、殼聚糖[43]和纖維蛋白膠[44])和合成生物材料(聚乳酸-羥基乙酸共聚物(PLGA) [45]、碳納米管[46]和聚氨酯[47])都是用于心臟再生的備選材料[37]。
2.3.天然生物材料
天然生物材料可通過注射水凝膠或補片的方式引入心臟[48]。膠原是細胞外基質(ECM)的一種主要成分,也是一種用于心臟修復的很受歡迎的天然材料。Miyagi等[10]研究發(fā)現(xiàn)在右心室缺陷大鼠模型中,膠原補片作為血管內皮生長因子(VEGF)-165的載體能夠達到緩慢釋放并促進血管形成的效果。在體外實驗中,他們發(fā)現(xiàn)含固定化VEGF的膠原補片能夠促進內皮和骨髓細胞的生長。VEGF-膠原補片植入缺損的右心室游離壁后與僅植入單獨的膠原補片的對照組相比,促進了血管生成和心室壁增厚。這些發(fā)現(xiàn)說明固定化生長因子的膠原補片可通過促進細胞募集和增殖進而促進心臟修 復[10]。而單獨的膠原補片可以保護梗死的心臟的收縮性,減少不利重構,提高心臟功能,因為膠原補片可以降低梗死區(qū)的纖維化,促進梗死區(qū)和補片之間供應血管的生成,吸引各種內源性細胞(如平滑肌細胞、心外膜細胞和未成熟的心肌細胞)填充到補片上[49]。膠原也可作為細胞的載體,在心肌梗死后將各種類型的細胞運輸?shù)焦K绤^(qū)。Frederick等[50]已經證實種植了內皮祖細胞的玻連蛋白/膠原支架可以募集血管生成素,并保護心肌梗死大鼠的心室功能。
殼聚糖是自然界第二豐富的多糖,被廣泛用于農業(yè)、食品、營養(yǎng)、環(huán)境保護和材料科學等領域[51]。殼聚糖凝膠具有多孔的海綿狀結構[52],可作為細胞支架[53]或載體,用于受控和局部給藥[54]。Liu等[43]已經證實殼聚糖凝膠可以通過清除活性氧和募集趨化因子,提高缺血心肌的氧化應激,進而促進干細胞移植和存活。脫乙酰殼聚糖凝膠也被用來傳輸一種血管生成素-1類似物,增強內皮細胞功能和存活率。事實上 ,結合了血管生成素-1類似物的水凝膠減緩了內皮細胞的凋亡并刺激了細胞管狀結構的形成[55]。同時,在患有心肌梗死的大鼠左心室中植入的殼聚糖透明質酸/絲纖蛋白補片可以減輕左心室擴張,增加室壁厚度,提高心臟功能[56]。
除了膠原和殼聚糖,其他天然生物材料也被用作心臟再生治療的備選研究材料。藻酸鹽是一種提取自海藻的多聚糖[57],已被廣泛用于傷口愈合、給藥和組織工程研究[58]。研究證實,藻酸鹽凝膠注射進心肌后可完全被吸收,并在六周內被結締組織取代。在心肌梗死模型中,注射藻酸鹽7天和60天后,對疤痕厚度的增加、不利心室擴張的減緩和心臟功能的提升都是有效的[41]。這些結果對設定注射時間均有參考意義。在嚴重心肌梗死老鼠模型中,在梗死灶周圍區(qū)域注射藻酸鹽-殼聚糖凝膠后可以有效阻止左心室重構。其機制是通過減少細胞凋亡和增加新生血管促進組織修復[59]。纖維蛋白膠主要由纖維蛋白原和凝血酶構成,可用來形成纖維蛋白凝塊。它經常用于嚴重心肌梗死繼發(fā)破裂后的左心室壁修復。這種膠可以立刻封住破裂的心肌,并被自然吸收[60-62]。Christman等[44]研究了心肌梗死后種植纖維蛋白膠支架對心臟功能的保護作用。在缺血再灌注損傷的老鼠模型體內種植支架五周后,發(fā)現(xiàn)其能維持梗死室壁厚度和心臟功能[44]。
2.4.合成生物材料
合成生物材料通常由合成聚合物、金屬或兩者的組合構成。合成生物材料擁有很高的強度和耐久性,但毒性也較強,并且存在生物相容性等問題[48]。同天然生物材料一樣,合成生物材料也是作為緩釋和受控給藥的容器以及支持細胞移植和融合的載體。
聚乳酸(PLA)、聚乙交酯(PLG)及其共聚物PLGA是常用的合成材料。Mukherjee等[63]采用了一種納米結構的基質來模仿心肌的原生微環(huán)境,該基質由聚(L-乳酸)、聚(ε-己內酯)和膠原組成。在這項研究中,納米級PLA-聚(ε-己內酯)共聚物/膠原生物復合材料支架被用來培養(yǎng)和支撐依附于支架上的單個兔心肌細胞。結果顯示依附在支架上的成年兔心肌細胞的生長與原生心肌相當[63]。類胰島素生長因子(IGF)-1結合在PLGA納米粒子上,在心肌梗死后立即被傳輸至梗死周圍區(qū)域。結果顯示IGF-1合成PLGA納米粒子延長了IGF-1在組織內的保留時間,減少了心肌細胞的凋亡,并提高了左心室功能[45]。
碳納米纖維主要應用于心臟組織工程。Martins等[64]將傳導性碳納米管和殼聚糖混合,得到一種殼聚糖/碳支架,和原生心肌有相似的彈性。這種傳導性支架不僅提高了新生老鼠心肌細胞在體外的存活率,而且增加了肌球蛋白重鏈、肌鈣蛋白-T和連接蛋白-43的表達,這些蛋白的表達與肌肉收縮和電耦合相關,且對細胞電信號傳輸非常重要[64]。Zhou等[65]也研發(fā)出一種碳納米纖維/動物凝膠支架用來支持新生老鼠心臟細胞的體外培育,且再植入心肌梗死的模型鼠心臟后可融入宿主心肌層。注入這種明膠后,心臟功能和射血分數(shù)均得到提高,同時抑制了病理惡化(如心室擴張) [65]。
人們也對合成多肽生物材料進行了研究。合成多肽可以自組裝形成三維(3D)凝膠,具有調節(jié)纖維空間的性質和縮放比例的作用[66]。它們可直接注射進心肌,改善細胞募集和存活的微環(huán)境[67],也可以作為藥物或細胞運輸?shù)妮d體[68]。Tokunaga等[69]利用自組裝多肽凝膠肽在心肌梗死后將心臟祖細胞運輸至心肌邊界區(qū),確保了有效的細胞傳輸并提高了細胞的存活率。除此之外,多肽納米纖維也以一種可持續(xù)的方式被用于運輸血小板源生長因子(PDGF),以防止心肌細胞死亡,在心肌梗死后保護心臟功能[70]。
聚氨酯是一種具有持久性和彈性的合成聚 合物,被稱為彈性體薄膜,可以適應原生心臟組織的物理和機械性能,也被研究用作組織工程的支架。種植于聚氨酯薄膜上的心肌細胞可以隨著薄膜的生長而生長,形成多層的收縮組織結構[71]。
盡管檢驗生物材料應用于心臟病治療的臨床試驗還很 少,但最近的一項臨床研究記錄了隨訪6個月的治療結果[72]。隨訪的結果證明,在標準藥物治療(SMT)中加入藻酸鹽凝膠與單獨使用SMT相比,可以更有效地提高老年慢性心力衰竭(HF)患者的運動能力。延長跟蹤一年后的結果[73]顯示,對于老年慢性HF患者,SMT加藻酸鹽凝膠的療法與單 獨使用SMT相比,在改善患者運動能力、癥狀和臨床狀態(tài)方面更有效,且這種效果持續(xù)了一年。這些數(shù)據(jù)表明對這種 新穎療法可以做進一步更廣泛的評估。
3.1.室性心律失常
心律失常發(fā)病率升高通常與心肌梗死有關,特別是室性心律失常[74,75]。由于心臟的再生能力有限,心肌梗死后大量的心肌細胞死亡導致形成瘢痕組織,這種瘢痕組織主要由成纖維細胞和膠原蛋白組成。瘢痕組織的收縮性和電信號傳導能力明顯減弱,導致形成異常的傳導通道或發(fā)展成傳導阻滯。室性心律失常、室性心動過速(VT)或心室顫動(VF)在心肌梗死患者中很常見,也是心源性猝死(SCD)的主要原因[76]。對于嚴重的心肌梗死,梗死區(qū)周圍的缺血性心肌細胞的電生理學性質已經被改變,有形成凹角回路(一種圓形電路)的潛在風險,該回路是導致持續(xù)室性心律失常的一種機制。隨著心肌梗死度過急性 期,瘢痕開始穩(wěn)定,瘢痕組織實際上成為一種結構塊,促進了凹角回路的形成,觸發(fā)SCD [76]。雖然醫(yī)療干預極大地降低了發(fā)病率和死亡率,但SCD仍然占據(jù)醫(yī)院門診CAD患者死亡人數(shù)的70 %,和所有患者死亡人數(shù)的50 % [77,78]。收縮不同步(心臟的心室收縮存在時間差或同步性差)導致患者從VF發(fā)展到血液動力降低、循環(huán)衰竭和腦功能損失。
心律失常觸發(fā)機制主要包括電解質紊亂[79]、結構變化、局部缺血[74]、組織缺氧[80]和身體及精神波動[81]?,F(xiàn)有療法的主要目標是恢復正常心律。VF或無脈動持續(xù)性VT患者需要立即去心臟纖顫或恢復心律。早期使用β受體阻滯劑(一種藥物,可穩(wěn)定細胞膜并使心臟的整體代謝需求最小化)可以降低VF發(fā)病率[82,83]。另外一種臨床干預是使用埋入式復律除顫器(ICD),這是一種電氣裝置,可停止纖維性顫動,恢復正常心律,通常用于心肌病患者和心臟驟停(SCA)患者 [78,84]。即使在臨床上應用ICD來消除患者的心律失常,VT或VF仍然會發(fā)生,且會提高死亡率和HF風險[85]。
3.2.房室(AV)阻滯
心率和心臟收縮受右心房壁上竇房結的控制。竇房結是一種天然起搏器,可通過心房產生并發(fā)送電脈沖。在到達心室完成心房收縮前,這種信號會被位于心房間隔下部靠后區(qū)域的房室 (AV)結減慢。脈沖信號隨后通過房室束到達心室,房室束分為左束支和右束支,且終止于浦肯野纖維系統(tǒng),促進心室同步收縮[86]。此過程的任何一部分發(fā)生異常都會導致傳導紊亂,影響心臟的泵血功能[87]。
房室傳導阻滯是一種傳導疾病,其發(fā)生機制是由于從心房發(fā)出的電信號被房室結部分或完全阻滯,進而導致室性心律減慢。肌肉神經紊亂(如肌肉萎縮癥)[88,89]、系統(tǒng)性疾病(如心臟結節(jié)病[90]和淀粉樣變性[91])、心肌缺血/梗死[92,93]、腫瘤疾病(如原發(fā)性心臟淋巴瘤[94])和導管消融[95,96]等疾病都可能導致AV傳導異常[86]。電信號傳導中斷可能發(fā)生在AV結、AV結下部或AV結上部結構以及房室束和左、右束支的分叉點上[97-100]。結果導致心房電脈沖延遲或只是部分傳導至心室,如果不進行治療就有可能導致HF和SCD [101]。
目前無癥狀的AV阻滯不需要干預治療,而有癥狀的AV阻滯(先天或運動中激發(fā)的)通過起搏器安置術治療[100,101]。事實上,對于患有AV阻滯的患者,推薦采用永久性心臟起搏器安置術治療,除非有原因導致AV阻滯可逆,或存在起搏器植入術禁忌[101]。
改善心臟功能和控制心律失常同等重要。但是目前治療效果會因患者不同病癥表現(xiàn)而有所限制[102]。因此需要 新的療法來終止異常傳導通路并提高患者存活率。AV阻滯和室性心律失常等傳導紊亂患者可使用傳導性生物材料——聚合物。這種材料有較高的導電性。初步研究證實傳導性生物材料對改善缺血性心臟病和傳導阻滯誘發(fā)的傳導異常有巨大的潛力。
3.3.導電生物材料
1977年,Alan J.Heeger、Alan G.MacDiarmid和Hideki Shirakawa發(fā)現(xiàn)了一種有機導電高分子——聚乙炔,并在2000年獲得諾貝爾獎[103]。人們對導電高分子感興趣不僅是因為它們的導電性能,還因為它們很容易合成,且具有生物相容性和生物降解性[104]。導電高分子已成功被用作生物傳感器、神經植入物、給藥裝置和組織工程支架的材料[105]。這一類高分子具有傳導性是因為其獨特的結構:一系列交替排列的單雙鍵形成了一條共軛的主鏈。這些交替排列的鍵可以使電子在鏈之間和鏈內自由移動[106]。人們也對導電高分子促進生成電活性組織(如神經組織和心臟組織)的效果進行了研究[107,108]。
導電高分子有很多種,如聚吡咯(PPy)、聚苯胺(PANI)、聚(3,4-乙烯二氧噻吩) (PEDT, PEDOT)、聚薁(PAz)和聚噻吩衍生物[105]。其中PPy是一種性能較好的高分子,已在神經系統(tǒng)科學和心臟研究中得到廣泛應用。George等[109]研究出一種含PPy的導電植入物,可引導神經干細胞(NSC)分化和神經突伸長,用于神經修復。他們發(fā)現(xiàn)含PPy的導電植入物植入大鼠的大腦皮層后,促進了植入物周圍神經元和神經膠質細胞的生長[109]。一種導電性層粘連蛋白/PPy可以將人類胚胎干細胞引導至神經系統(tǒng)內,用于神經再生和修復[110]。另外,研究發(fā)現(xiàn)混合了十二烷基苯磺酸(DBS)的反荷離子可以支持NSC的存活,并誘導NSC向神經系統(tǒng)分化[111]。
人們也研究了PPy在心臟領域的應用。Kai等[112]制成了一種納米纖維膜,由PPy、聚(ε-己內酯)和凝膠構成,用來模擬ECM來開展心臟組織工程。他們證明這種薄膜能夠提高人體心肌細胞的附著性、擴散性、相互作用和心臟蛋白質的表達[112]。研究人員已制成一種3D PPy包覆的PLGA高分子支架,用于心肌梗死后進行干細胞移植。這種導電聚合物支架具有生物相容性,可支持心臟祖細胞和iPSC的生長與擴散。另外PPy包覆的PLGA支架在受到電刺激后可以調節(jié)細胞行為[113]。PPy也被證明在心肌梗死后可以刺激血管生成。Mihardja等[114]制成了一種藻酸鹽-PPy聚合物,并將其注射進梗死區(qū),和注射了生理鹽水的動物進行對照,注射五周后,觀察到前者血管生成增多。此外,梗死區(qū)的肌成纖維細胞滲透液也增多了[114]。
總而言之,PPy導電性聚合物不僅為心臟細胞提供了可持續(xù)的ECM,也影響了細胞的生物行為。在結合了細胞療法的組織工程中,將導電性聚合物的心臟組織結構移植入心肌梗死后的心臟可以促進點信號傳導,使植入細胞與宿主細胞融合。
導電聚合物的另外一項潛在應用是作為生物起搏器?;加袀鲗ё铚騂F的患者采用植入電子起搏器治療可以控制心律和心臟收縮,進而維持心臟的泵血功能[115]。雖然這種裝置被證明有降低死亡率和患者住院治療率的潛力,但因為非傳導性組織或異常傳導通道仍存在于心臟中,所以傳導阻滯這一根本性問題仍然未解決。與生物起搏器開發(fā)相關的研究早在十年前就開始了,但主要是針對電子起搏器面臨的限制,包括電池更換、慢性感染、高昂的手術成本和小兒患者的設備適應性(如胸腔和血管大小、兒童成長和先天性心臟缺陷) [116-118]。在正常心臟中,竇房結是一個觸發(fā)器,發(fā)送電信號至基質——感受并接受該信號的細胞。觸發(fā)器-基質的連接對組織的起搏和傳導非常重要。生物起搏器能夠與心臟結合,對內源性刺激沖動做出反應,增加或降低心臟活動性[1 19]。另外,植入生物起搏器會使侵入性最小化,很適合對電子起搏器有禁忌證的患者[116]。生物材料在 生物起搏器研究中發(fā)揮了重要作用,它能結合植入細胞,標記和追蹤體內移植細胞,建立植入起搏細胞和其基質細胞之間的聯(lián)系[120-122]。導電性聚合物在作為ECM支持細胞存活的同時能夠建立細胞間的導電連接,是一種優(yōu)秀的備選生物材料(圖1)。同樣地,導電性聚合物-起搏細胞結合的發(fā)展很可能成為未來制成用于治療的生物起搏器的第一步。
圖1.重連梗死心臟內中斷的電信號。(a) 心肌梗死引發(fā)心肌細胞大量損失,導致瘢痕組織形成。瘢痕組織中斷了電信號傳輸,增加了患者心律失常的風險。(b) 導電聚合物的引入可利用現(xiàn)有的健康心肌重新連接受損區(qū)域,修復中斷的電傳導。
生物材料在心臟修復和再生方面有著巨大的潛力。大部分可用生物材料的生物相容性和生物降解性已被不同的團隊通過不同的方式驗證。生物材料和組織工程的研究方向正在轉向尋找理想的生物材料-細胞類型組合。由于心臟是一種精確平衡的環(huán)境,由心肌細胞、成纖維細胞、內皮細胞和平滑肌細胞構成,目前仍然有很多問題沒有得到解決。生物材料應用于心臟病的主要問題是創(chuàng)造一種用于心律失常的基質的可能性。盡管鮮有研究專門解決這一問題,但最近的一項研究證明,電生理變化的程度取決于生物材料的傳播性能[123]。該研究發(fā)現(xiàn),注入了高傳導性生物材料的心臟不存在傳導異常。然而,顯示出最低間隙擴散的生物材料可在注入后短時間內通過引起左心室激活延遲和降低注射位置的間隙連接密度為心律失常構造基質。這項工作證明傳輸位置和間隙擴散特性是生物材料應用于心律失常的重要原因。另外,制備彈性和強度性能與原生心肌細胞相似的生物材料也非常重要[124]。將免疫反應最小化,防止生物材料或組織結構的包囊形成是另外一個問題,因為形成包囊會阻止移植細胞適時地融入原生環(huán)境[125]。由于心臟是身體最大的生物電來源[126],合成導電聚合物(可促進心肌細胞的同步跳動)將增強移植組織結構與原生心肌之間的信號傳遞。這一點非常重要,因為電場刺激會增加蛋白質組織,促進細胞極化,并增強電信號傳播[107]。但是,引入生物材料或組織結構的最佳時間仍不清楚,該時間對在限制瘢痕組織形成的同時將炎癥反應最小化是非常重要的。
盡管存在很多挑戰(zhàn),生物材料和組織工程研究仍然具有廣闊前景,且在過去二十年間已取得了很大進展。這項研究最終目標是利用生物材料支架結合適當?shù)募毎愋停糜诓糠只蛉科鞴俚纳苫蛟偕?。這將最終降低器官移植的需求,提高生活質量。
筆者在此對Leigh Botly博士在原稿撰寫和編輯方面提供的幫助表示感謝。圖1中的說明由Ren-Ke Li教授設計,圖形由大學健康網的研究通信員Benjamin Pakuts制作。本項工作由安大略心臟與卒中基金會向Ren-Ke Li提供的資金(G140005765)支持。Ren-Ke Li是心臟再生領域加拿大首席科學家。本項工作也由Eileen Mercier的慷慨捐款支持。
Zhi Cui, Baofeng Yang, and Ren-Ke Li declare that they have no conflict of interest or financial conflicts to disclose.
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* Corresponding author.
E-mail address: renkeli@uhnres.utoronto.ca
2095-8099/? 2016 THE AUTHORS.Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
英文原文: Engineering 2016, 2(1): 141—148
Zhi Cui, Baofeng Yang, Ren-Ke Li.Application of Biomaterials in Cardiac Repair and Regeneration.Engineering,
http://dx.doi.org/10.1016/J.ENG.2016.01.028