Antibacterial polyurethane foams with quaternized-chitosan as a chain extender for nasal packing and hemostasis

Annual diagnoses of chronic sinusitis exceed 30 million cases in the world [1]. Functional endoscopic sinus surgery (FESS) is an effective clinical treatment of chronic sinusitis [2,3]. Due to the abundance of blood vessels in nasal cavity, FEES faces many real challenges, such as traumatic adhesions, stenosis, and bleeding, which must be addressed to ensure satisfactory surgery [4]. Consequently, reducing bleeding after surgery is important to wound healing [5]. Given the narrow structure inside the nasal cavity, surgical techniques such as sutures and staples are not applicable to FESS wound hemostasis. In such, nasal packing emerges as the most effective and widely adopted method for preventing bleeding and traumatic adhesion [6]. There has been no golden standard for nasal packing materials so far. Generally, a quality packing material should have the following features [[7], [8], [9], [10]]: (1) applying pressure to aid in hemostasis; (2) filling the nasal cavity to provide support force; (3) maintaining a moisture balance to prevent excessive water vapor evaporation and promote wound healing; (4) establishing a barrier to prevent mucosal adhesion; and (5) being degradable to gradually decrease applied pressure to facilitate easy removal. Commercial hemostatic materials, including Vaseline gauze and PVA medical sponge are utilized to address the hemostasis after FESS. However, these two typical materials are non-dissolvable and often accompanied by nasal mucosa adhesion and scab rupturing upon removal, resulting in secondary injury [11]. To address these problems, the degradable PUF foam with soft tactility and partial degradation capability within 7 days has been developed [12].

Effective antibacterial properties are critical for nasal packing materials in clinical application, to prevent sponge odor and wound infection [[13], [14], [15]]. Nasal packing typically remains in the nasal cavity for five to seven days following FESS, during which microbial colonization is common. After absorbed blood, the packing material serves as a potential medium for bacteria growing and thus may result in the packing material smelling foul and the wound being infected. Incorporating antibacterial agents is a straightforward method to offer polyurethane foam antibacterial capability [[17], [18], [19]]. There are two strategies to add antibacterial agents to the polyurethane foam. The first one involves loading metal ions, such as Zn2+ [[20], [21], [22]] and Ag+ [[23], [24], [25], [26]], or other antibacterial additives into the foam [27,28]. However, there is a concern that the effectiveness is unlikely long enough because of the rapid leaching of bactericidal additives. Another approach is to introduce antimicrobial building blocks into the polyurethane via chemical bonds. Cationic polymers or oligomers are common antibacterial groups or moieties. Cationic oligomers or prepolymers containing polyol groups can serve as chain extenders or crosslinkers in foaming reactions and react with the -NCO groups. Fang et al. [29] synthesized a robust 3D porous sponge with quaternized chitin and partially deacetylated chitin nanofibers. With high-water absorption and positive-charge properties, these 3D porous sponges could induce blood cells and platelets aggregation, meanwhile, demonstrated antibacterial activity. Quaternary ammonium salts with trihydroxyl and tetrahydroxyl groups were synthesized by Udabe et al. [30] and utilized as polyol monomers in preparing polyurethane foams. When the quaternary ammonium component was more than 20 wt%, modified polyurethane foams demonstrated a strong antibacterial activity. However, it also had a negative impact on the material cytotoxicity and foaming reaction.

Over the last decade, chitosan has been widely used as a matrix for clinical applications, due to its good biocompatibility and biodegradability. Especially for chitosan-based sponges, the abundant amino groups contribute to both hemostatic and antibacterial performance [31]. Chemical modification, such as quaternization, enhances these properties further, resulting in quaternized chitosan (QCS) with improved water solubility, hemostatic capacity, and antimicrobial efficacy [32,33]. Quaternary ammonium groups with high hydrophilicity and positive charge, could promote red blood cell coagulation and induce platelet adhesion through electrostatic interactions, meanwhile, break the charge balance of the bacteria due to rupture the negatively charged bacterial cell membranes. Wei et al. [34] prepared composite sponges by a Schiff base reaction to conjugate the QCS with dialdehyde cellulose. The sponges have good physicochemical properties and effective bactericidal rates against both S. aureus and E. coli. In this contribution, a targeted strategy by introducing QCS to prepare polyurethane foam for nasal packing was proposed. At first, QCS was synthesized via a ring-opening addition between the amino groups in CS and 2,3-epoxypropyltrimethyl ammonium chloride. The chemical modification resulted in a significant enhancement of the water solubility and antibacterial performance of QCS in comparison to CS. Then, the QCS was used as a chain extender to prepare polyurethane foam (PUF-QCS) as shown in Scheme 1A. The laboratory tests confirmed that the as-prepared PUF-QCS exhibited satisfactory mechanical properties, liquid absorption capacity, biocompatibility, antibacterial activity, and degradation performance. Furthermore, animal experiments demonstrated that PUF-QCS outperformed the commercial PVA nasal packing materials in terms of hemostatic properties and antibacterial activity in accordance with clinical criteria.

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