Oxygen-Releasing Antioxidant Cryogel Scaffolds with Sustained Oxygen Delivery for Tissue Engineering Applications
Oxygen-Releasing Antioxidant Cryogel Scaffolds with Sustained Oxygen Delivery for Tissue Engineering Applications
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DOI：
10.1021/acsami.8b01736
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发表时间：
2018-06-06
影响因子：
9.5
通讯作者：
Kumar, Ashok
中科院分区：
文献类型：
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作者：
Shiekh, Parvaiz A.;Singh, Anamika;Kumar, Ashok
随着生物材料科学的发展，组织工程支架作为修复组织缺损的一种有效手段，正日益受到人们的重视。然而，这些支架中只有少数已经转化为临床应用。现有支架的主要缺点之一是支架内缺乏足够的氧气供应。产氧生物材料已被开发作为一种替代策略，但面临着两个主要问题。一个是氧气产生速率的控制，另一个是活性氧（ROS）的产生。为了解决这些问题，在这里，我们报告的氧气释放抗氧化剂聚合物冻凝胶支架（PUAO-CPO）持续供氧的发展。通过在抗氧化聚氨酯（PUAO）支架中引入过氧化钙（CPO），采用冷冻干燥技术制备PUAO-CPO支架。PUAO-CPO冻凝胶减弱了ROS，并在10天内持续释放氧气。PUAO-CPO冷冻凝胶的体外分析显示，它们在缺氧条件下维持H9 C2成心肌细胞的能力，细胞活力明显优于正常聚氨酯（PU）支架。此外，使用缺血皮瓣模型的体内研究显示了释氧冷冻凝胶支架防止组织坏死长达9天的能力。组织学检查表明，组织结构和胶原蛋白含量的维护，而增殖细胞核抗原的免疫染色证实了与氧输送的缺血组织的活力。我们的研究证明了一种先进的方法，用于开发释放氧气的生物材料，该材料具有持续的氧气输送以及由于缺血或氧气产生而产生的残余ROS和自由基的衰减。因此，释放氧的PUAO-CPO冻凝胶支架可以与基于细胞的治疗方法一起用于受损组织的再生，特别是缺血性病症如心肌梗死和慢性伤口愈合。
With the advancement in biomaterial sciences, tissue-engineered scaffolds are developing as a promising strategy for the regeneration of damaged tissues. However, only a few of these scaffolds have been translated into clinical applications. One of the primary drawbacks of the existing scaffolds is the lack of adequate oxygen supply within the scaffolds. Oxygen-producing biomaterials have been developed as an alternate strategy but are faced with two major concerns. One is the control of the rate of oxygen generation, and the other is the production of reactive oxygen species (ROS). To address these concerns, here, we report the development of an oxygen-releasing antioxidant polymeric cryogel scaffold (PUAO-CPO) for sustained oxygen delivery. PUAO-CPO scaffold was fabricated using the cryogelation technique by the incorporation of calcium peroxide (CPO) in the antioxidant polyurethane (PUAO) scaffolds. The PUAO-CPO cryogels attenuated the ROS and showed a sustained release of oxygen over a period of 10 days. An in vitro analysis of the PUAO-CPO cryogels showed their ability to sustain H9C2 cardiomyoblast cells under hypoxic conditions, with cell viability being significantly better than the normal polyurethane (PU) scaffolds. Furthermore, in vivo studies using an ischemic flap model showed the ability of the oxygen-releasing cryogel scaffolds to prevent tissue necrosis upto 9 days. Histological examination indicated the maintenance of tissue architecture and collagen content, whereas immunostaining for proliferating cell nuclear antigen confirmed the viability of the ischemic tissue with oxygen delivery. Our study demonstrated an advanced approach for the development of oxygen-releasing biomaterials with sustained oxygen delivery as well as attenuated production of residual ROS and free radicals because of ischemia or oxygen generation. Hence, the oxygen-releasing PUAO-CPO cryogel scaffolds may be used with cell-based therapeutic approaches for the regeneration of damaged tissue, particularly with ischemic conditions such as myocardial infarction and chronic wound healing.