Department of Biological Sciences and Bioengineering , Indian Institute of Technology Kanpur , Kanpur 208016 , Uttar Pradesh , India.
ACS Appl Mater Interfaces. 2018 Jun 6;10(22):18458-18469. doi: 10.1021/acsami.8b01736. Epub 2018 May 24.
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.
随着生物材料科学的进步，组织工程支架作为受损组织再生的一种有前途的策略正在发展。然而，只有少数这些支架已被转化为临床应用。现有的支架存在的主要缺点之一是支架内氧气供应不足。已经开发出产氧生物材料作为替代策略，但面临两个主要问题。一个是控制氧气产生的速度，另一个是产生活性氧物种 (ROS)。为了解决这些问题，我们在这里报告了一种用于持续供氧的释氧抗氧化聚合物冷冻凝胶支架 (PUAO-CPO) 的开发。通过将过氧化钙 (CPO) 掺入抗氧化聚氨酯 (PUAO) 支架中，使用冷冻凝胶技术制造 PUAO-CPO 支架。PUAO-CPO 冷冻凝胶减轻了 ROS，并在 10 天的时间内持续释放氧气。对 PUAO-CPO 冷冻凝胶的体外分析表明，它们能够在缺氧条件下维持 H9C2 心肌细胞，细胞活力明显优于普通聚氨酯 (PU) 支架。此外，使用缺血皮瓣模型的体内研究表明，释氧冷冻凝胶支架能够防止组织坏死，最长可达 9 天。组织学检查表明保持组织结构和胶原蛋白含量，而增殖细胞核抗原的免疫染色证实了在提供氧气的情况下缺血组织的活力。我们的研究展示了一种先进的方法，用于开发具有持续供氧能力的释氧生物材料，同时减轻由于缺血或氧气产生而产生的残留 ROS 和自由基的产生。因此，释氧 PUAO-CPO 冷冻凝胶支架可与基于细胞的治疗方法结合使用，用于受损组织的再生，特别是在心肌梗塞和慢性伤口愈合等缺血情况下。
