A barrier against reactive oxygen species: chitosan/acellular dermal matrix scaffold enhances stem cell retention and im

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A barrier against reactive oxygen species: chitosan/acellular dermal matrix scaffold enhances stem cell retention and improves cutaneous wound healing Wei Lin1,2, Xiaoyang Qi3, Wenjing Guo4, Danyang Liang1,2, Heting Chen1,2, Baoping Lin1,2 and Xiaoyuan Deng1,2*

Abstract Background: Stem cell therapies have gained great attention for providing novel solutions for treatment of various injuries and diseases due to stem cells’ self-renewal, ability to differentiate into various cell types, and favorite paracrine function. Nevertheless, the low retention of transplanted stem cell still limits their clinical applications such as in wound healing in view of an induced harsh microenvironment rich in reactive oxygen species (ROS) during inflammatory reactions. Methods: Herein, a novel chitosan/acellular dermal matrix (CHS/ADM) stem cell delivery system is developed, which is of great ROS scavenging activity and significantly attenuates inflammatory response. Result: Under ROS microenvironment, this stem cell delivery system acts as a barrier, effectively scavenging an amount of ROS and protecting mesenchymal stem cells (MSCs) from the oxidative stress. It notably regulates intracellular ROS level in MSCs and reduces ROS-induced cellular death. Most importantly, such MSCs delivery system significantly enhances in vivo transplanted stem cell retention, promotes the vessel growth, and accelerates wound healing. Conclusions: This novel delivery system, which overcomes the limitations of conventional plain collagen-based delivery system in lacking of ROS-environmental responsive mechanisms, demonstrates a great potential use in stem cell therapies in wound healing. Keywords: Chitosan/Acellular dermal matrix scaffold, ROS barrier in inflammatory response, Stem cell retention, Wound healing

Background There is a great potential for stem cell-based therapies to treat a myriad of diseases and injuries by means of stem cells’ ability to modulate immune or inflammatory responses through releasing trophic factors [1–3]. However, * Correspondence: [email protected] 1 MOE Key Laboratory of Laser Life Science, College of Biophotonics & Institute of Laser Life Science, South China Normal University, Guangzhou 510631, China 2 Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China Full list of author information is available at the end of the article

the low engraftment rates and low retention of transplanted stem cells, caused by lacking of an appropriate 3D supporting matrix for efficient stem cells delivery as well as survival microenvironment providing for stem cells, are still the critical factors that limit their clinical applications in wound healing [4]. To address this issue, scaffolds have been proposed as an effective strategy to deliver stem cells to the desired site of repair, which offer stem cells a structural support and a bio-functionally living microenvironment for cell adhesion, migration and proliferation [