Survival and Proliferation under Severely Hypoxic Microenvironments Using Cell-Laden Oxygenating Hydrogels.

Survival and Proliferation under Severely Hypoxic Microenvironments Using Cell-Laden Oxygenating Hydrogels.
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DOI:
10.3390/jfb12020030
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发表时间:
2021-05-02
影响因子:
4.8
通讯作者:
Lobo AO
Lobo AO
中科院分区:
工程技术3区
文献类型:
--
作者:
Hassan S;Cecen B;Peña-Garcia R;Marciano FR;Miri AK;Fattahi A;Karavasili C;Sebastian S;Zaidi H;Lobo AO

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已经采用不同的策略来为工程化活组织提供足够的营养。这些方法主要围绕提供氧气来减轻慢性缺氧或缺氧的影响,慢性缺氧或缺氧导致坏死或弱的新血管形成,导致人工组织植入物失败,因此临床结果不佳。虽然不同的生物材料已被用作体外和体内应用的氧气发生器,但某些问题阻碍了它们的广泛应用。其中包括氧的产生和产生速率以及以活性氧物质(ROS)形式的反应中间体的产生。这两个因素都可能对细胞存活有害,并可能严重影响这些研究的结果。在这里,我们将过氧化钙(CPO)封装在聚己内酯中作为释氧微粒(OMP)。虽然CPO在水解时释放氧,但PCL包封确保水解缓慢发生,从而维持氧的延长释放,而没有本体释放可能赋予包封细胞的应力。我们使用含有这些OMP的明胶甲基丙烯酰(GelMA)水凝胶来刺激包囊的骨骼肌成肌细胞的存活和增殖,并优化OMP浓度以持续超过一周的氧气输送。本研究中描述的氧释放和递送平台为基于细胞的治疗方法开辟了机会,以治疗由缺血性条件引起的疾病,并提高植入物在严重缺氧条件下的存活率,以成功进行临床转化。
Different strategies have been employed to provide adequate nutrients for engineered living tissues. These have mainly revolved around providing oxygen to alleviate the effects of chronic hypoxia or anoxia that result in necrosis or weak neovascularization, leading to failure of artificial tissue implants and hence poor clinical outcome. While different biomaterials have been used as oxygen generators for in vitro as well as in vivo applications, certain problems have hampered their wide application. Among these are the generation and the rate at which oxygen is produced together with the production of the reaction intermediates in the form of reactive oxygen species (ROS). Both these factors can be detrimental for cell survival and can severely affect the outcome of such studies. Here we present calcium peroxide (CPO) encapsulated in polycaprolactone as oxygen releasing microparticles (OMPs). While CPO releases oxygen upon hydrolysis, PCL encapsulation ensures that hydrolysis takes place slowly, thereby sustaining prolonged release of oxygen without the stress the bulk release can endow on the encapsulated cells. We used gelatin methacryloyl (GelMA) hydrogels containing these OMPs to stimulate survival and proliferation of encapsulated skeletal myoblasts and optimized the OMP concentration for sustained oxygen delivery over more than a week. The oxygen releasing and delivery platform described in this study opens up opportunities for cell-based therapeutic approaches to treat diseases resulting from ischemic conditions and enhance survival of implants under severe hypoxic conditions for successful clinical translation.
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