Development of enzyme mimics for the scavenging of excessive mitochondrial superoxide (O2•−) can serve as an effective strategy in the treatment of many diseases. Here, protein reconstruction technology and nanotechnology is taken advantage of to biomimetically create an artificial hybrid nanozyme. These nanozymes consist of ferritin‐heavy‐chain‐based protein as the enzyme scaffold and a metal nanoparticle core as the enzyme active center. This artificial cascade nanozyme possesses superoxide dismutase‐ and catalase‐like activities and also targets mitochondria by overcoming multiple biological barriers. Using cardiac ischemia‐reperfusion animal models, the protective advantages of the hybrid nanozymes are demonstrated in vivo during mitochondrial oxidative injury and in the recovery of heart functionality following infarction via systemic delivery and localized release from adhesive hydrogels (i.e., cardiac patch), respectively. This study illustrates a de novo design strategy in the development of enzyme mimics and provides a promising therapeutic option for alleviating oxidative damage in regenerative medicine.
Developing an anti-infective shape-memory hemostatic sponge able to guide in situ tissue regeneration for noncompressible hemorrhages in civilian and battlefield settings remains a challenge. Here we engineer hemostatic chitosan sponges with highly interconnective microchannels by combining 3D printed microfiber leaching, freeze-drying, and superficial active modification. We demonstrate that the microchannelled alkylated chitosan sponge (MACS) exhibits the capacity for water and blood absorption, as well as rapid shape recovery. We show that compared to clinically used gauze, gelatin sponge, CELOX™, and CELOX™-gauze, the MACS provides higher pro-coagulant and hemostatic capacities in lethally normal and heparinized rat and pig liver perforation wound models. We demonstrate its anti-infective activity against S. aureus and E. coli and its promotion of liver parenchymal cell infiltration, vascularization, and tissue integration in a rat liver defect model. Overall, the MACS demonstrates promising clinical translational potential in treating lethal noncompressible hemorrhage and facilitating wound healing.
Multifunctional
tissue adhesives with excellent adhesion, antibleeding,
anti-infection, and wound healing properties are desperately needed
in clinical surgery. However, the successful development of multifunctional
tissue adhesives that simultaneously possess all these properties
remains a challenge. We have prepared a novel chitosan-based hydrogel
adhesive by integration of hydrocaffeic acid-modified chitosan (CS-HA)
with hydrophobically modified chitosan lactate (hmCS lactate) and
characterized its gelation time, mechanical properties, and microstructure.
Tissue adhesion properties were evaluated using both pigskin and intestine
models. In situ antibleeding efficacy was demonstrated via the rat
hemorrhaging liver and full-thickness wound closure models. Good antibacterial
activity and anti-infection capability toward S. aureus and P. aeruginosa were confirmed
using in vitro contact-killing assays and an infected pigskin model.
The result of coculturing with 3T3 fibroblast cells indicated that
the hydrogels have no significant cytotoxicity. Most importantly,
the biocompatible and biodegradable CS-HA/hmCS lactate hydrogel was
able to close the wound in a sutureless way and promote wound healing.
Our results demonstrate that this hydrogel has great promise for sutureless
closure of surgical incisions.
A multifunctional
hydrogel patch with a combination of high toughness,
superior adhesion, and good antibacterial effect is a highly desired
surgical material. In this study, we developed a novel hydrogel patch
composed of poly(ethylene glycol) diacrylate/quaternized chitosan/tannic
acid (PEGDA/QCS/TA) based on mussel-inspired chemistry. The physical
and biological properties of the hydrogel patch were systematically
evaluated in vitro and in vivo. The results indicated that this hydrogel
patch possessed compact microstructure, low swelling ratio, tough
mechanical properties, good antibacterial activities against S. aureus and E. coli, and excellent dry/wet
adhesive ability to a wide range of substrates. The hydrogel patch
could also be degraded and absorbed in vivo and used as a sutureless
material for wound closure. All these findings demonstrate that the
PEGDA/QCS/TA hydrogel patch with multifunctional properties has great
potential for application in biomedical fields.
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