McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA, 15219, United States; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15260, United States.
McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA, 15219, United States.
Biomaterials. 2019 Nov;222:119376. doi: 10.1016/j.biomaterials.2019.119376. Epub 2019 Jul 25.
Oxidative stress leads to the progression of many diseases including chronic wounds, atherosclerosis, stroke and cancer. The modification of biomolecules with reactive nitrogen or oxygen species has been shown to trigger oxidative stress pathways that are beneficial for healing. Extracellular matrix scaffolds have been used successfully in reconstructive applications due to the beneficial host response they induce. To tailor extracellular matrix scaffolds to enhance antioxidant response, ECM were prepared using reactive nitrogen or oxygen species. These scaffolds were shown to be effectively decellularized and possess oxidative or nitroxidative protein modifications. Macrophage responses in vitro and in an in vivo muscle injury model were shown to have enhanced antioxidant phenotypes without impairment of long-term remodeling. These observations suggest that ECM decellularized with reactive oxygen or nitrogen species could provide better outcomes for the treatment of ischemic diseases.
氧化应激会导致许多疾病的进展，包括慢性伤口、动脉粥样硬化、中风和癌症。已经表明，生物分子与活性氮或氧物种的修饰会引发对愈合有益的氧化应激途径。由于它们诱导的有益宿主反应，细胞外基质支架已成功用于重建应用。为了调整细胞外基质支架以增强抗氧化反应，可以使用活性氮或氧物种来制备 ECM。这些支架已被证明可有效地脱细胞化，并具有氧化或氮氧自由基蛋白修饰。体外和体内肌肉损伤模型中的巨噬细胞反应表明，具有增强的抗氧化表型，而不会损害长期重塑。这些观察结果表明，用活性氧或氮物种脱细胞化的细胞外基质可能为治疗缺血性疾病提供更好的结果。
