In vitro evaluation of loaded chitosan membranes for pain relief and infection prevention

Abstract

Wounds resulting from surgeries, implantation of medical devices, and musculoskeletal trauma result in pain and can also result in infection of damaged tissue. Up to 80% of these infections are due to biofilm formation either on the surface of implanted devices or on surrounding wounded tissue. Bacteria within a biofilm have intrinsic growth and development characteristics that allow them to withstand up to 1,000 times the minimum inhibitory concentration of antibiotics, demonstrating the need for new therapeutics to prevent and treat these infections. Cis‐2‐decenoic acid (C2DA) is known to disperse preformed biofilms and can prevent biofilm formation entirely for some strains of bacteria. Additionally, local anesthetics like bupivacaine have been shown to have antimicrobial effects against multiple bacterial strains. This study sought to evaluate hexanoic acid‐treated electrospun chitosan membranes (HA‐ESCM) as wound dressings that release C2DA and bupivacaine to simultaneously prevent infection and alleviate pain associated with musculoskeletal trauma. Release profiles of both therapeutics were evaluated, and membranes were tested in vitro against Methicillin‐resistant Staphylococcus aureus (MRSA) to determine efficacy in preventing biofilm infection and bacterial growth. Results indicate that membranes release both therapeutics for 72 hr, and release profile can be tailored by loading concentration. Membranes were effective in preventing biofilm growth but were toxic to fibroblasts when loaded with 2.5 or 5 mg of bupivacaine.

Synthesis and Characterization of 2-Decenoic Acid Modified Chitosan for Infection Prevention and Tissue Engineering

“…Future studies will evaluate the effects of these materials on other cell types, such as immune cells, and will assess biocompatibility in vivo. While this study did not assess as-spun material as controls due to the rapid dissolution and acidity of these materials, the acyl-modified materials performed similarly to previously investigated chitosan-based materials [6,[41][42][43]. There are no signs of acyl-modified materials adversely affecting cells or any signals that healing would be negatively affected [10].…”

“…Nanofibrous chitosan membranes were electrospun using chitosan (86.5% DDA) following previous methods [43]. Briefly, Chitosan was dissolved overnight at 5.5% (w/v) in 70:30% (v/v) TFA and dichloromethane (DCM) purchased from Sigma Fisher (Burlington, MA, USA).…”

Advances in the use of local anesthetic extended-release systems in pain management

“…Harrison et al. prepared chitosan membranes loaded with cis-2-decenoic acid (C2DA) and bupivacaine as biofilms that provided pain relief while preventing infection (Harrison et al., 2021 ). Hanif, S. et al.…”

Chitosan Functionalization: Covalent and Non-Covalent Interactions and Their Characterization

“…The secondary molecules generally do not participate in the physical stability of the matrix. They rather act as active cargos (such as painkillers [ 159 , 160 ], antibacterial agents [ 161 , 162 ], or anti-inflammatory drugs [ 63 ]) meant to be released over time by diffusion. Fluorescent labels have also been successfully incorporated into functionalized CS for localization [ 161 ].…”