Nitric Oxide Nanomotor Driving Exosomes-Loaded Microneedles for Achilles Tendinopathy Healing

Abstract

The microneedle (MN) provides a promising strategy for transdermal delivery of exosomes (EXO), in which the therapeutic effects and clinical applications are greatly reduced by the fact that EXO can only partially reach the injury site by passive diffusion. Here, we designed a detachable MN array to deliver EXO modified by a nitric oxide nanomotor (EXO/MBA) for Achilles tendinopathy (AT) healing. With the releasing of EXO/MBA, L-arginine was converted to nitric oxide by NOS or ROS as the driving force. Benefiting from the motion ability and the property of MPC tending to lower pH, EXO could accumulate at the injury site more efficiently. This work demonstrated that EXO/MBA-loaded MN notably suppressed the inflammation of AT, facilitated the proliferation of tendon cells, increased the expression of Col1a, and prevented extracellular matrix degradation, indicating its potential value in enthesiopathy healing and other related biomedical fields.

A Practical Guide to Analyzing and Reporting the Movement of Nanoscale Swimmers

“…These concerns are not hypothetical but are already widespread in the nanoswimmer literature. By surveying 40+ recent literature reports of nanoswimmers, − we see reoccurring inconsistencies that include blurry, drifting trajectories captured by optical microscopes, ,,,,,,,, inappropriate speed calculations and fitting of mean squared displacement, ,,,− ,,,,, and lack of proper and complete control experiments. ,,, These inconsistencies are often accompanied by other issues, such as an incomplete reporting of experimental details, a casual discussion of the propulsion mechanism of a nanoswimmer, and sometimes even a lack of supporting videos to confirm self-propulsion. , Moreover, since many of these studies aspire to apply nanoswimmers in a biomedical or environmental setting, mistakes in fabricating, measuring, and analyzing the movement of nanoswimmers continue to propagate and to undermine their utility in these applications.…”

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

“…Additionally, several studies have indicated that exosomes inhibit the expression of various pro-inflammatory mediators and cytokines, including NF-kB, IL-1β, IL-6, IL-8, IL-18, COX-2, MMP1, MMP3 MMP9, iNOS, CXCL, IFNγ, and TNFα, leading to attenuated inflammation, which is ideal for tendon regeneration [ 56 , 57 , 59 , 61 , 63 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. Zhang et al observed dramatically suppressed COX-2 factor in the TSC-Exos treatment group [ 63 ].…”

“…Specifically, Liu et al reported their experience in treating Achilles tendinopathy with nitric oxide nanomotor-driving exosome-loaded microneedles (EXO/MBA-loaded MN) to improve the efficiency of exosome delivery and permeation. The EXO/MBA-loaded MN patch group demonstrated notably more efficient tendon healing than the single exosome injection group [ 71 ]. Further studies on evaluating the physiological and mechanical properties of different delivery systems exosomes in the long-term are necessary.…”

Recent advances on transdermal delivery systems for the treatment of arthritic injuries: From classical treatment to nanomedicines

“…A chemical nanomotor that responded to nitric oxide species (NOS) or ROS was also utilized to drive the penetration of exosomes to injured tendons. A series of results demonstrated the system could promote tendon cell proliferation, reduce ECM degradation, and alleviate inflammation (A. Liu, Wang, et al, 2021; Figure 5). This study inspires that chemically generated gas can further push nanomedicines to reach the deeper skin tissue.…”