_Applied_  
_sciences_  
_Article_  
**Antibacterial Behavior of Chitosan-Sodium Hyaluronate-PEGDE Crosslinked Films**  
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Footnote 1: Facultad de Odontologia, Universidad Autónoma de Yucatin, Calle 61 A #492 A x 90 y Av. Izies, Centro., Merida C.P. 97000, Mexico; [EMAIL_ADDRESS] (M.G.C.-G.); [EMAIL_ADDRESS] (C.M.C.P); [EMAIL_ADDRESS] (F.J.A.A.)  
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Unidad de Materiales, Centro de Investigacion Cientifica de Yucatin, Calle 43 No. 130 x 32 y 34, Colonia Chuburna de Hidalgo, Mexico; michael.P. 97205, Mexico; michael.P. 98065/xxxx  
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and molecular weights, being more abundant in tissues subjected to mechanical loads, such as cartilage, dermis, and vocal cords [11]. HA plays a key role in cell division and migration, angiogenesis, wound healing, and tissue regeneration. Due to its biocompatibility, biodegradability, and susceptibility to chemically modification, it is of great interest for its potential in the field of bone tissue engineering [11]. A way to modify the properties of a polymer with hyaluronic acid is through polyelectrolyte complexation where HA can be combined with natural polymers such as collagen or chitosan [12; 13].  
In this regard, it has been reported that the introduction of hyaluronic acid on chitosan scaffolds, improves cell proliferation, and extracellular matrix synthesis (ECM) [14]. In addition, chitosan/acid hyaluronic sponges loaded with fibrin nanoparticles and VEGF promoted endothelial cell proliferation as well as capillary tube formation [15]. Chitosan-co-Hylauronic acid cryohydrogels used as a scaffolds showed higher cell proliferation by increasing hyaluronic acid content [16]. Similarly, CHT/HA scaffolds promoted cellular adhesion of chondrocytes [17], pre-osteoblast [18], and have potential uses in cartilage for tissue engineering applications. Finally, Chitosan/HA blends have been suggested as a stable anti-fouling surface [19].  
Chitosan is also identified as a potent antimicrobial and antibofilm polymer [4; 20]. These properties are attributed to the electrostatic interactions between the positively charged group of chitosan and the negatively charged components of the biofilm matrix such as DNA, proteins, and lipids [20]. In addition, the antimicrobial activity of chitosan can be influenced by factors such as molecular weight, degree of deacetylation, pH, temperature, and solvent of the chitosan, among others [3; 21; 22].  
The antimicrobial properties of CHT/HA have been reported as an unfilled matrix or loaded with bactericidal particles (silver, ZnO), antibiotics (gentamicin, penicillin G), and antimicrobial peptides (AMP). For example, interpenetrated hydrogels made of chitosan and hyaluron exhibited activity against _Staphylococcus aureus_[23; 24; 25].  
Therefore, the combination of CHT and HA is expected to render a polymer blend with improved osteomyelitis. However, it is not clear if this association will affect the antibacterial properties of CHT as it is known that CHT kills Gram-negative and Gram-positive bacteria [3] by forming complexes with the anionic phospholipid bacterial membrane [26; 27].