An Injectable Antibiotic Hydrogel that Scavenges Proinflammatory Factors for the Treatment of Severe Abdominal Trauma

Abstract

Bacterial infection and excessive inflammation following abdominal injury can cause life-threatening complications that lead to multiple organ failure and death. Removing bacteria and proinflammatory factors-which are predominantly negatively charged-from the wound site with a cationic, antibiotic-containing hydrogel wound dressing is therefore a promising treatment approach for severe abdominal trauma. Here an injectable, self-healing hydrogel composed of the gel-forming glycosaminoglycan oxidized chondroitin sulfate (OCS), cationic polyethylenimine (PEI), and the antibiotic tobramycin (Tob) via a Schiff's base reaction is developed. Compared with hydrogels lacking either PEI or Tob, only the Tob/PEI/OCS hydrogels exhibit a large binding capacity for negatively-charged proinflammatory factors including cell-free DNA, lipopolysaccharides, TNF-α, and high mobility group box 1 protein, and a large reduction in bacterial populations in vitro. In a murine model of severe abdominal trauma, the Tob/PEI/OCS hydrogel exhibits good biodegradability and biosafety, reduced local and systemic inflammation and infection, and prevents multiple organ failure, resulting in 100% survival. This hydrogel dressing is thus a promising biomaterial for preventing complications and improving outcomes following severe abdominal trauma.

Chemical signal regulated injectable coacervate hydrogels

“…Since the gels were self-healable and responded quickly to the strain changes, we investigated whether our coacervate gels were also injectable. 5,[38][39][40] As shown in Fig. 4D, a rhodamine B dyed gel was prepared and put into a syringe, then we extruded it from needles with various diameters (20G -0.9 mm, 21G -0.8 mm and 26G -0.45 mm).…”

“…Conventional coacervate hydrogels are rendered degradable because of their salt, pH or temperature responsiveness, however the degradation time can be exceedingly long under physiological conditions. 9,11,12,39,41 Previous work in our group on related pyridine-based polymeric systems has shown that (in addition to secondary amines) primary amines and thiols can be used to trigger deionization. 35,36 Treating our coacervate gels with two representative chemical signalsglycine (Gly, a primary amine) and sodium-3-mercaptopropane-sulfonate (SH-Na, a thiol), we indeed observed gel-sol transitions at a similar rate to that achieved with P (within 5 min).…”

Injectable In Situ Photocrosslinked Hydrogel Dressing for Infected Wound Healing

“…In addition, due to the positive charge of PVA-SBQ, it has a certain promoting effect on cell adhesion and migration. 44,45 For wound healing, the hydrogel is a temporary scaffold for epidermal cell migration. Through vitro cell adhesion, we demonstrated that the PS 12 -OSA 1 -P 0.03 hydrogel could attract and attach a large number of living cells (Figure 3c).…”

Functionalized Core–Shell Nanogel Scavenger for Immune Modulation Therapy in Sepsis

“…[10] Yang et al developed an injectable cationic hydrogel which exhibited a high binding capacity for proinflammatory molecules and thus reduced both local and systemic inflammation. [11] In our previous study, we have developed a size exclusive hydrogel resin functionalized with telodendrimer nanotrap (TD NT), which exhibits high binding affinity to LPS and pro-inflammatory cytokines with both charge and size selectivity. TD NT hydrogel resin has demonstrated 100% survival when combined with antibiotics in a severe sepsis mouse model.…”