Chitosan is a positively charged natural polymer with several properties conducive to wound-healing applications, such as biodegradability, structural integrity, hydrophilicity, adhesiveness to tissue, and bacteriostatic potential. Along with other mechanical properties, some of the properties discussed in this review are antibacterial properties, mucoadhesive properties, biocompatibility, high fluid absorption capacity, and anti-inflammatory response. Chitosan forms stable complexes with oppositely charged polymers, arising from electrostatic interactions between (+) amino groups of chitosan and (−) groups of other polymers. These polyelectrolyte complexes (PECs) can be manufactured using various materials and methods, which brings a diversity of formulations and properties that can be optimized for specific wound healing as well as other applications. For example, chitosan-based PEC can be made into dressings/films, hydrogels, and membranes. There are various pros and cons associated with manufacturing the dressings; for instance, a layer-by-layer casting technique can optimize the nanoparticle release and affect the mechanical strength due to the formation of a heterostructure. Furthermore, chitosan’s molecular weight and degree of deacetylation, as well as the nature of the negatively charged biomaterial with which it is cross-linked, are major factors that govern the mechanical properties and biodegradation kinetics of the PEC dressing. The use of chitosan in wound care products is forecasted to drive the growth of the global chitosan market, which is expected to increase by approximately 14.3% within the next decade. This growth is driven by products such as chitoderm-containing ointments, which provide scaffolding for skin cell regeneration. Despite significant advancements, there remains a critical gap in translating chitosan-based biomaterials from research to clinical applications.

Cold atmospheric plasmas (CAP) are a versatile tool in medical applications like wound healing. Its therapeutic benefits are partially attributed to the generation of biologically active reactive oxygen and nitrogen species (RONS). Characterization of RONS, however, typically only occurs after treatment. Here we report the first real-time in situ detection of CAP-generated nitric oxide (NO), and the simultaneous detection of cellular calcium ions (Ca²⁺) release using electrochemical sensors during CAP treatment of murine wounds. In vivo, NO rose rapidly within the first minute of CAP treatment but accumulated less overall than in PBS, reflecting reactions with wound-bed targets. In situ measurements revealed nearly double the concentrations of static endpoint assays, underscoring the importance of real-time detection. Ca²⁺ signals displayed transient, burst-like increases, likely due to CAP-induced membrane permeability and as response to oxidative stress. We also investigated the sensitivity, selectivity, and stability of the graphene oxide coated NO sensors and ion-selective Ca²⁺ sensors. Interference studies showed that the NO sensor also responds to H ₂ O ₂ and NO ₂ ⁻ yet remains most sensitive to NO. Raman microscopy revealed progressive degradation of the graphene oxide layer after only one hour of CAP exposure, drastically reducing sensor currents. Improvements in NO sensor design will enable more accurate measurements for feedback control for plasma-based wound therapies. Ca²⁺ sensors are more robust and retained full functionality after three hours and repeated use providing a reliable diagnostic for immediate biological response. The results establish real-time electrochemical sensing as a powerful approach to monitor CAP-tissue interactions.