3D-bioprinted, phototunable hydrogel models for studying adventitial fibroblast activation in pulmonary arterial hypertension.
3D-bioprinted, phototunable hydrogel models for studying adventitial fibroblast activation in pulmonary arterial hypertension.
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DOI：
10.1088/1758-5090/aca8cf
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发表时间：
2022-12-19
期刊：
影响因子：
9
通讯作者：
Magin, Chelsea M.
中科院分区：
文献类型：
--
作者：
Davis-Hall, Duncan;Thomas, Emily;Pena, Brisa;Magin, Chelsea M.
关键词：
肺动脉高压（PAH）是一种肺血管系统的进行性疾病，其特征是肺血压升高、肺动脉重塑，并最终导致右心室衰竭。 PAH 的治疗干预措施在一定程度上受到限制，因为缺乏能够准确再现动态动脉壁机械特性的体外筛选平台。在这里，我们提出了肺动脉外膜的 3D 生物打印模型，由基于光可调聚（乙二醇）α 甲基丙烯酸酯 (PEG-αMA) 的水凝胶和原代人肺动脉外膜成纤维细胞 (HPAAF) 组成。这种独特的生物材料通过两步聚合反应在体外模拟 PAH 发病机制。首先，通过将酸性生物墨水溶液 3D 生物打印到碱性明胶支持浴中，引发与合成和可生物降解交联剂的碱催化硫醇-烯反应，将 PEG-αMA 大分子单体进行非化学计量交联。然后，通过未反应的αMA端基的光引发均聚来诱导基质硬化。实验设计方法产生了一个水凝胶平台，该平台的初始弹性模量 (E) 在健康肺动脉组织范围内 (E = 4.7 ± 0.09 kPa)，其硬度达到高血压组织的病理范围 (E = 12.8 ± 0.47 kPa)，并随着时间的推移支持细胞增殖。与软水凝胶中培养的细胞相比，在硬水凝胶中培养的 HPAAF 表达纤维化标记物 α-平滑肌肌动蛋白的百分比更高（88 ± 2% 与 65 ± 4%）。同样，与软模型 (39 ± 6%) 相比，硬模型 (66 ± 6%) 中 HPAAF 的增殖标记物 5-乙炔基-2'-脱氧尿苷 (EdU) 呈阳性的百分比更高。这些结果表明，3D 生物打印、光可调的肺动脉外膜模型是一种能够在体外研究纤维化发病机制的工具。
Pulmonary arterial hypertension (PAH) is a progressive disease of the lung vasculature, characterized by elevated pulmonary blood pressure, remodeling of the pulmonary arteries, and ultimately right ventricular failure. Therapeutic interventions for PAH are limited in part by the lack of in vitro screening platforms that accurately reproduce dynamic arterial wall mechanical properties. Here we present a 3D-bioprinted model of the pulmonary arterial adventitia comprised of a phototunable poly(ethylene glycol) alpha methacrylate (PEG-αMA)-based hydrogel and primary human pulmonary artery adventitia fibroblasts (HPAAFs). This unique biomaterial emulates PAH pathogenesis in vitro through a two-step polymerization reaction. First, PEG-αMA macromer was crosslinked off-stoichiometry by 3D bioprinting an acidic bioink solution into a basic gelatin support bath initiating a base-catalyzed thiol-ene reaction with synthetic and biodegradable crosslinkers. Then, matrix stiffening was induced by photoinitiated homopolymerization of unreacted αMA end groups. A design of experiments approach produced a hydrogel platform that exhibited an initial elastic modulus (E) within the range of healthy pulmonary arterial tissue (E = 4.7 ± 0.09 kPa) that was stiffened to the pathologic range of hypertensive tissue (E = 12.8 ± 0.47 kPa) and supported cellular proliferation over time. A higher percentage of HPAAFs cultured in stiffened hydrogels expressed the fibrotic marker alpha-smooth muscle actin than cells in soft hydrogels (88 ± 2% versus 65 ± 4%). Likewise, a greater percentage of HPAAFs were positive for the proliferation marker 5-ethynyl–2′-deoxyuridine (EdU) in stiffened models (66 ± 6%) compared to soft (39 ± 6%). These results demonstrate that 3D-bioprinted, phototunable models of pulmonary artery adventitia are a tool that enable investigation of fibrotic pathogenesis in vitro.
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影响因子：
13.6
作者：
Hinton TJ;Jallerat Q;Palchesko RN;Park JH;Grodzicki MS;Shue HJ;Ramadan MH;Hudson AR;Feinberg AW
通讯作者：
Feinberg AW
影响因子：
10
作者：
Erdem A;Darabi MA;Nasiri R;Sangabathuni S;Ertas YN;Alem H;Hosseini V;Shamloo A;Nasr AS;Ahadian S;Dokmeci MR;Khademhosseini A;Ashammakhi N
通讯作者：
Ashammakhi N
影响因子：
2.6
作者：
Arvidsson, Mattias;Ahmed, Abdulla;Radegran, Goran
通讯作者：
Radegran, Goran
DOI：
10.1126/science.aav9750
发表时间：
2019-05-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Grigoryan B;Paulsen SJ;Corbett DC;Sazer DW;Fortin CL;Zaita AJ;Greenfield PT;Calafat NJ;Gounley JP;Ta AH;Johansson F;Randles A;Rosenkrantz JE;Louis-Rosenberg JD;Galie PA;Stevens KR;Miller JS
通讯作者：
Miller JS
影响因子：
16.6
作者：
Guvendiren, Murat;Burdick, Jason A.
通讯作者：
Burdick, Jason A.