Prussian Blue Nanozyme Promotes the Survival Rate of Skin Flaps by Maintaining a Normal Microenvironment

Abstract

Ischemia−reperfusion (I/R) injury leads to a low success rate of skin flap transplantation in reconstruction surgery, thus requiring development of new treatments. Necroptosis and apoptosis pathways, along with overexpression of reactive oxygen species and pro-inflammatory factors in skin flap transplantation, are deemed as potential therapeutic targets. This study provides a paradigm for nanozyme-mediated microenvironment maintenance to improve the survival rate of the transplanted skin flap. Prussian blue nanozyme (PBzyme) with multiple intrinsic biological activities was constructed and selected for this proof-of-concept study. The prepared PBzyme shows anti-inflammatory, antiapoptotic, antinecroptotic, and antioxidant activities in both in vitro and in vivo models of I/R injured skin flaps. The multiple inhibitory effects of PBzyme maintained a normal microenvironment and thus significantly promoted the survival rate of the I/R injured skin flap (from 37.21 ± 8.205% to 79.61 ± 7.5%). Of note, PBzyme regulated the expression of the characteristic signal molecules of necroptosis, including Rip 1, Rip 3, and pMLKL, indicating that PBzyme may be a therapeutic agent for necroptosis-related diseases. This study shows great prospects for clinical application of PBzyme in the treatment of skin flaps via local administration.

Engineered Core–Shell Multifunctional Nano‐Tracer in Raman‐Silent Region with Highly Retained Affinity to Enhance Lateral Flow Immunoassays

“…In contrast, APNPs possess a unique Raman spectrum (upside in Figure 4b), which is located in the Raman‐silent region and avoiding the problem of extra interference from endogenous biomolecules and potential spectral overlap. [ 14,17 ] Note that almost all the tested NC members show strong signals in T‐line (calculated from ImageJ software, details described in Supporting Data), it implies that the applicability of the established model (Figure 4d). Given that PALL120 showed a large difference value ( D ‐value) between positive and negative tests (implying that possess better analysis performance), PALL120 was chosen for the evaluation of the analysis performance of APNPs‐LFIA.…”

“…And the existing Fe−CN−Fe in APNPs will demonstrate strong absorbance in the biological window. [ 14 ] The as‐prepared APNPs displayed two strong absorbance at ~546 and ~700 nm (Figure 1g), which was attributed to the AuNPs and PBNPs, respectively. Moreover, the extinction bands of the APNPs demonstrated a broad range of absorption in the biological window (600–900 nm), and it is closed to the 785 nm incident Raman excitation laser, which may induce surface‐enhanced resonance Raman scattering.…”

The role of extracellular traps in ischemia reperfusion injury

“…Cutaneous IRI typically occurs due to pressure ulcers, Raynaud’s phenomenon-induced skin ulcers, and skin flap grafts following reconstructive surgery. It is related to the oxidative damage caused by apoptosis, necroptosis, ROS, and excessive generation of pro-inflammatory factors ( 176 – 178 ). NETs have been reported to delay the healing of skin lesions, and pharmacological targeting of NETs can accelerate wound regeneration ( 179 , 180 ).…”

“…These results show, to some extent, that NETs are associated with the exacerbation of cutaneous IRI. Skin flap tissue IRI caused by skin flap transplantation is one of the primary reasons for the low success rate of the procedure ( 176 ). Hence, there is a need to explore the intrinsic links between NETs and skin flap transplantation-induced IRI along with the related mechanisms.…”

Prussian Blue Nanozyme Normalizes Microenvironment to Delay Osteoporosis

“…[11,12,13] Among existing nanozymes, Prussian blue, an antidote approved by the US Food and Drug Administration, has attracted an increasing attention in biomedicine. [14] In previous studies, we successfully performed preclinical treatment using the Prussian blue nanozyme (PBzyme) leveraging its multiple intrinsic bioactivities for Alzheimer's disease, [15] ischemic stroke, [16,17] inflammatory bowel disease, [18] vascular restenosis, [19] Parkinson's disease, [20] skin flap transplantation, [21] hepatic ischemiareperfusion, [22] and cancer. [23] However, the effect of nanozymes including PBzyme on OP remains unclear.…”