Ultraporous Polyquaternium-Carboxylated Chitosan Composite Hydrogel Spheres with Anticoagulant, Antibacterial, and Rapid Endotoxin Removal Profiles for Sepsis Treatment

Abstract

Hemoperfusion is an important method to remove endotoxins and save the lives of patients with sepsis. However, the current adsorbents for hemoperfusion have disadvantages of insufficient endotoxin adsorption capacity, poor blood compatibility, and so on. Herein, we proposed a novel emulsion templating (ET) method to prepare ultraporous and double-network carboxylated chitosan (CCS)-poly(diallyl dimethylammonium chloride) (PDDA) hydrogel spheres (ET-CCSPD), bearing both negative and positive charges. CCS was introduced to balance the strong positive charges of PDDA to improve hemocompatibility, and emulsion templates endowed the adsorbent with an ultraporous structure for enhanced adsorption efficacy. The ET-CCSPDs neither damaged blood cells nor activated complement responses. In addition, the activated partial thromboplastin time (APTT) was prolonged to 8.5 times, which was beneficial for reducing the injection of anticoagulant in patients. The ET-CCSPDs had excellent scavenging performance against bacteria and endotoxin, with removal ratios of 96.7% for E. coli and 99.8% for S. aureus, respectively, and the static removal ratio of endotoxin in plasma was as high as 99.1% (C 0 = 5.50 EU/mL, critical illness level). An adsorption cartridge filled with the ET-CCSPDs could remove 84.7% of endotoxin within 1 h (C 0 = 100 EU/mL in PBS). Interestingly, the ET-CCSPDs had a good inhibitory effect on the cytokines produced by endotoxin-mediated septic blood. By developing the ET method to prepare ultraporous and double-network adsorbents, the problems of low adsorption efficiency and poor blood compatibility of traditional endotoxin adsorbents have been solved, thus opening a new route to fabricate absorbents for blood purification.

Broad-Spectrum Clearance of Lipopolysaccharides from Blood Based on a Hemocompatible Dihistidine Polymer

“…Apart from natural ligands, several synthetic materials have also been developed. Poly­(1-vinylimidazole), allantoin crystals, chitosan, − poly-ε-caprolactone, imidazolium-type polyurethane, and amino acids − have been reported for LPS clearance. Unfortunately, although these synthetic materials exhibited LPS clearance capability to a certain extent, they generally suffer from poor selectivity toward LPSs when it comes to complicated biosamples, severely limiting their further applications in blood purification.…”

Protein/Polysaccharide Composite toward Multi‐in‐One Toxin Removal in Blood with Self‐Anticoagulation and Biocompatibility

“…Besides biocompatibility, another fundamental property of the adsorbent is its resistance to bacterial adhesion, which can effectively avoid the risk of infection to the patient during hemoperfusion therapy. [26] Moreover, the reduction of cells and platelets in the blood due to non-specific adsorption on adsorbents is often an unavoidable risk during the use of traditional adsorbents. [6,27] In this regard, the anti-biological fouling ability of the adsorbent is important for determining its applicability (Figure 2c).…”

Recent advances in double network hydrogels based on naturally-derived polymers: synthesis, properties, and biological applications

“…Following a reverse synthetic approach, Liu et al prepared DN hydrogel spheres for sepsis treatment using carboxylated chitosan (CCS) and diallyl dimethylammonium chloride (DDA). 99 In this case, the network of ionically crosslinked CCS was first formed through Zr 4+ coordination as shown in Fig. 15a.…”