Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment.However,the therapeutic efficacy of traditional photosensitizers is limited,and they lack the ability to regenerate bone.Here,a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes(denoted as Bi/SrTiO_(3)),which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species.These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels,which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound.In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6%and 67.6%in the respective models.Furthermore,the hydrogel had good filling and retention capabilities in the bone defect region,which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation.This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

A shape-persistent plasticine-like conductive hydrogel with self-healing properties for peripheral nerve regeneration

In recent years,electrically conductive hydrogel-based nerve guidance conduits(NGCs)have yielded promising results for treating peripheral nerve injuries(PNIs).However,developed ones are generally pre-manufactured and exhibit a limited ability to achieve good contact with nerve tissue with irregu-lar surfaces.Herein,we developed a plasticine-like electrically conductive hydrogel consisting of gelatin,conducting polypyrrole,and tannic acid(named GPT)and assessed its ability to promote peripheral nerve regeneration.The shape-persistent GPT hydrogel exhibited good self-healing properties and could easily be molded to form a conduit that could match any injured nerve tissue.Their electrical properties could be tuned by changing the PPy concentration.In vitro,the improved conductivity of the hydrogel pro-moted dorsal root ganglion(DRG)axonal extension.More importantly,we found that the GPT hydrogel enhanced axonal regeneration and remyelination in vivo,preventing denervation atrophy and enhancing functional recovery in a mice model of sciatic nerve injury.These results suggest that our plasticine-like NGC has huge prospects for clinical application in the repair of PNI.