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

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

Injury causes a systemic inflammatory response syndrome (SIRS) clinically much like sepsis 1. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors 2. Similarly, cellular injury can release endogenous damage-associated molecular patterns (DAMPs) that activate innate immunity 3. Mitochondria are evolutionary endosymbionts that were derived from bacteria 4 and so might bear bacterial molecular motifs. We show here that injury releases mitochondrial DAMPs (MTD) into the circulation with functionally important immune consequences. MTD include formyl peptides and mitochondrial DNA. These activate human neutrophils (PMN) through formyl peptide receptor-1 and TLR9 respectively. MTD promote PMN Ca2+ flux and phosphorylation of MAP kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTD can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These can then signal through identical innate immune pathways to create a sepsis-like state. The release of such mitochondrial ‘enemies within’ by cellular injury is a key link between trauma, inflammation and SIRS.

Designing wound dressing materials with outstanding therapeutic effects, self-healing, adhesiveness and suitable mechanical property has great practical significance in healthcare, especially for joints skin wound healing. Here, we designed a kind of self-healing injectable micelle/hydrogel composites with multi-functions as wound dressing for joint skin damage. By combining the dynamic Schiff base and copolymer micelle cross-linking in one system, a series of hydrogels were prepared by mixing quaternized chitosan (QCS) and benzaldehyde-terminated Pluronic®F127 (PF127-CHO) under physiological conditions. The inherent antibacterial property, pH-dependent biodegradation and release behavior were investigated to confirm multi-functions of wound dressing. The hydrogel dressings showed suitable stretchable and compressive property, comparable modulus with human skin, good adhesiveness and fast self-healing ability to bear deformation. The hydrogels exhibited efficient hemostatic performance and biocompatibility. Moreover, the curcumin loaded hydrogel showed good antioxidant ability and pH responsive release profiles. In vivo experiments indicated that curcumin loaded hydrogels significantly accelerated wound healing rate with higher granulation tissue thickness and collagen disposition and upregulated vascular endothelial growth factor (VEGF) in a full-thickness skin defect model. Taken together, the antibacterial adhesive hydrogels with self-healing and good mechanical property offer significant promise as dressing materials for joints skin wound healing.