Delivery of Nitric Oxide by Chondroitin Sulfate C Increases the Rate of Wound Healing through Immune Modulation

Chronic wounds impact 2.5% of the United States population and will continue to be a major clinical challenge due to increases in population age, chronic disease diagnoses, and antibiotic-resistant infection. Nitric oxide (NO) is an endogenous signaling molecule that represents an attractive, simple therapeutic for chronic wound treatment due to its innate antibacterial and immunomodulatory function. Unfortunately, modulating inflammation for extended periods by low levels of NO is not possible with NO gas. Herein, we report the utility of a NO-releasing glycosaminoglycan biopolymer (GAG) for promoting wound healing. GAGs are naturally occurring biopolymers that are immunomodulatory and known to be involved in the native wound healing process. Thus, the combination of NO and GAG biopolymers represents an attractive wound therapeutic due to these known independent roles. The influence and contribution of chondroitin sulfate C (CSC) modified to facilitate controlled and targeted delivery of NO (CSC-HEDA/NO) was evaluated using in vitro cell proliferation and migration assays and an in vivo wound model.