Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress SING WAN WONG, 1 YIFEI YAO, 1 YE HONG, 1 ZHIYAO MA, 1 STANTON H. L. KOK, 4 SHAN SUN, 2 MICHAEL CHO, 3 KENNETH K. H. LEE, 4 and ARTHUR F. T. MAK 1 1 Division of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, NT, Hong Kong; 2 Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA; 3 Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA; and 4 School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong (Received 22 April 2016; accepted 10 September 2016) Associate Editor Sean S. Kohles oversaw the review of this article. Abstract—High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypoth- esized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress report- edly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H 2 O 2 ). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive dam- age threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H 2 O 2 . These findings suggest that P188 pre- treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development. Keywords—Poloxamer 188, Skeletal muscle, Oxidative stress, Cell mechanics, Deep tissue injury. INTRODUCTION Deep tissue pressure ulcer is a serious clinical issue affecting millions of people with physical disability. Preventive measures are still limited due to the lack of attention to the many contributing factors. Mechanical deformation due to pressure and shear is a well-rec- ognized predisposing factor in pressure ulcer develop- ment. Ischemic–reperfusion (IR) is believed to be also involved in pressure ulcer development. 23,32 It has been shown that IR can generate high oxidative stress in various tissues, 1,28,38 including skeletal muscle. 3 The effects of oxidative stress in muscle have been widely discussed, such as their contribution to force genera- tion, 25 their involvement in inflammatory responses during muscle repair 13,31 and their role in diseases such as muscle atrophy. 26 Our group has previously de- scribed the effects of oxidative stress on skeletal muscle cell mechanics. We demonstrated that prolong oxida- tive stress would lower muscle cell stiffness, the num- ber of actin filament, pre-tension, 14,34 compressive damage threshold, 36 and membrane repair ability. 7 As muscle tissues become easier to be mechanically dam- aged under prolong oxidative stress due to IR and/or chronic inflammation, oxidative challenge can increase the risk of deep tissue injury (DTI). DTI is hardly detectable clinically at its beginning and can ultimately expand towards the skin surface to become a full- thickness pressure ulcer. Methods that can reduce the combined challenges of oxidative and mechanical stresses may help to lower the risk of deep tissue pressure ulcer. Antioxidant supplements have been proposed to prevent muscle from damage. Researchers have applied vitamin C/vitamin E supplements to patients at risk of pressure ulcer. However, the beneficial effects of antioxidants supplements have yet to be confirmed. A detailed review can be found in McGinley et al. 17 Address correspondence to Arthur F. T. Mak, Division of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, NT, Hong Kong. Electronic mail: arthurmak@cuhk.edu.hk Annals of Biomedical Engineering (Ó 2016) DOI: 10.1007/s10439-016-1733-0 Ó 2016 Biomedical Engineering Society