A self-monitoring microneedle patch for light-controlled synergistic treatment of melanoma

Melanoma is the most aggressive and malignant form of skin cancer.Current melanoma treatment methods generally suffer from frequent drug administration as well as difficulty in direct monitoring of drug release.Here,a self-monitoring microneedle(MN)-based drug delivery system,which integrates a dissolving MN patch with aggregation-induced emission(AIE)-active PATC microparticles,is designed to achieve light-controlled pulsatile chemo-photothermal synergistic therapy of melanoma.The PATC polymeric particles,termed D/I@PATC,encapsulate both of chemotherapeutic drug doxorubicin(DOX)and the photothermal agent indocyanine green(ICG).Upon light illumination,PATC gradually dissociates into smaller particles,causing the release of encapsulated DOX and subsequent fluorescence intensity change of PATC particles,thereby not only enabling direct observation of the drug release process under light stimuli,but also facilitating verification of drug release by fluorescence recovery after light trigger.Moreover,encapsulation of ICG in PATC particles displays significant improvement of its photothermal stability both in vitro and in vivo.In a tumor-bearing mouse,the application of one D/I@PATC MN patch combining with two cycles of light irradiation showed excellent controllable chemo-photothermal efficacy and exhibited~97%melanoma inhibition rate without inducing any evident systemic toxicity,suggesting a great potential for skin cancer treatment in clinics.

Heparinized PGA host-guest hydrogel loaded with paracrine products from electrically stimulated adipose-derived mesenchymal stem cells for enhanced wound repair

The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-guest hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-guest hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.

Engineering topography: Effects on corneal cell behavior and integration into corneal tissue engineering

Cell-material interactions are important to tissue engineering.Inspired by the natural topographic structures on the extracellular matrix,a growing number of studies have integrated engineering topography into investigations of cell behavior on biomaterials.Engineering topography has a significant influence on cell behaviors.These cell-topography interactions play an important role in regenerative medicine and tissue engineering.Similarly,cell-topography interactions are important to corneal reconstruction and regeneration.In this review,we primarily summarized the effects of topographic cues on the behaviors of corneal cells,including cell morphology,adhesion,migration,and proliferation.Furthermore,the integration of engineering surface topography into corneal tissue engineering was also discussed.

Visualizing phase transition of upper critical solution temperature (UCST) polymers with AIE

The stimuli-responsive polymers with upper critical solution temperatures(UCST) are highly attractive for drug delivery applications. However, the phase transition process of UCST polymer is usually characterized by turbidity measurement and electron microscopy, which are significantly restricted by low sensitivity and static observation. In contrary, the fluorescence technique has significant advantages in terms of high sensitivity, easy operation, and dynamic observation. However, the conventional fluorophores suffer from the drawbacks of aggregation-caused quenching(ACQ) after being encapsulated by UCST polymers, which are not suitable for direct visualization of the phase transition process. To tackle this challenge, we herein developed a series of UCST polymers based on polyacrylamides decorated with bile acid and aggregation-induced emission(AIE)-active tetraphenylethene(TPE) groups, which can be used for direct fluorescence monitoring of the phase transition process. Moreover, the AIE-active UCST polymers can serve as drug carriers, which can not only monitor the drug release process under thermal stimuli, but also verify the drug release by fluorescence recovery after thermal stimuli. It is expected that the AIE-active UCST polymers with self-monitoring ability are promising for biomedical applications.