本研究論文聚焦用于心臟組織工程的同步類生理電-機(jī)械刺激生物反應(yīng)器。心臟組織工程旨在利用支架、相關(guān)細(xì)胞或其組合高效替代或修復(fù)受損心臟組織。盡管細(xì)胞-支架復(fù)合物具有快速重建心肌的潛力 (可避免緩慢的細(xì)胞募集過(guò)程)，但支架的體外細(xì)胞化仍面臨重大挑戰(zhàn)：其一需為細(xì)胞接種的支架提供充分的營(yíng)養(yǎng)與氧氣擴(kuò)散；其二需構(gòu)建生理樣微環(huán)境以促進(jìn)功能性組織形成。為此，我們開(kāi)發(fā)了一種模塊化生物反應(yīng)器，可在同步機(jī)械與電刺激下對(duì)全厚度心臟支架進(jìn)行動(dòng)態(tài)細(xì)胞化。該生物反應(yīng)器系統(tǒng)通過(guò)模擬左心室容積變化的周期性機(jī)械負(fù)荷實(shí)現(xiàn)穩(wěn)態(tài)刺激，并結(jié)合動(dòng)作電位波形電刺激以復(fù)現(xiàn)心臟微環(huán)境。這些刺激根據(jù)心臟生理節(jié)律同步化，并通過(guò)實(shí)時(shí)反饋調(diào)控。應(yīng)用于接種間充質(zhì)干細(xì)胞 (MSCs) 的厚豬心細(xì)胞外基質(zhì) (pcECM) 支架時(shí)，刺激顯著提升了 MSCs的增殖能力，并誘導(dǎo)其近表面形成致密組織樣結(jié)構(gòu)。最重要的是，經(jīng)35天培養(yǎng)后，實(shí)驗(yàn)組MSCs表達(dá)了早期心臟祖細(xì)胞標(biāo)志物Connexin-43與α-輔肌動(dòng)蛋白 (對(duì)照組未檢出)。本研究為心臟支架在生理樣條件下的細(xì)胞化提供了新型生物反應(yīng)器系統(tǒng)，旨在重建具有興奮-收縮耦聯(lián)功能的動(dòng)態(tài)活性組織。

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Markish MG, Sarig U, Baruch L, et al., 2025. A unique bioreactor that offers synchronized physiological-like electrical and mechanical stimuli for cardiac tissue engineering. Bio-des Manuf 8(4):581–594. https://doi.org/10.1631/bdm.2400370

圖1 機(jī)械刺激系統(tǒng)

圖2 電刺激系統(tǒng)

圖3 機(jī)械與電刺激同步化

圖4 支架細(xì)胞化效果

圖5 支架分子結(jié)構(gòu)分析

上下滑動(dòng)以閱覽

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