Bone mesenchymal stem cell-derived exosomes involved co-delivery and synergism effect with icariin via mussel-inspired multifunctional hydrogel for cartilage protection

Mesenchymal stem cells(MSC)are particularly effective in promoting cartilage regeneration due to their immunomodulatory,anti-inflammatory and regenerative repair functions of tissues and organs.Meanwhile,the intra-articular delivery and synergy with other therapeutic drugs have been the key issues driving their further application.We report a mussel-inspired multifunctional hydrogel system,which could achieve co-delivery and synergism effect of MSC-derived exosomes(Exos)with icariin(ICA).The ICA and Exos co-delivered articular cavity injection system are expected to retain in the joint cavity and promote cartilage regeneration,due to the thermosensitive,self-healing and adhesion properties of the mussel-inspired multifunctional hydrogel.The experimental results proved that Exos enhanced the cellular uptake of ICA by more than 2-fold evenly,and the synergism of Exos and ICA efficiently improve the cell proliferation and migration.After synergic treatment,the content of matrix metalloproteinase 13 in the supernatant and intracellular decreased by 47%and 59%,respectively.In vivo study,ICA-loaded Exos exhibited prolonged retention behavior bymultifunctional hydrogel delivery,thus displayed an increased cartilage protection.In the model of osteoarthritis,co-delivery hydrogel system relieved the cartilage recession,ensuring appropriate cartilage thickness.

Polymer Hydrogel Electrolytes for Flexible and Multifunctional Zinc-Ion Batteries and Capacitors

Flexibility and multifunctionality are now becoming inevitable worldwide tendencies for electronic devices to meet modern life's convenience,efficiency,and quality demand.To that end,developing flexible and wearable energy storage devices is a must.Recently,aqueous zinc-ion batteries(ZIBs)and zinc-ion capacitors(ZICs)stand out as two of the most potent candidates for wearable electronics due to their excellent electrochemical performance,intrinsic safety,low cost,and functional controllability.Simultaneously,polymer electrolytes'introduction and rational design,especially various hydrogels,have endowed conventional ZIBs and ZICs with colorful functions,which has been regarded as a perfect answer for energy suppliers integrated into those advanced wearable electronic devices.This review focuses on the functional hydrogel electrolytes(HEs)and their application for ZIBs and ZICs.Previously reported HEs for ZIBs and ZICs were classified and analyzed,from the flexibility to mechanical endurance,temperature adaptability,electrochemical stability,and finally cell-level ZIBs and ZICs based on multifunctional HEs.Besides introducing the diverse and exciting functions of HEs,working principles were also analyzed.Ultimately,all the details of these examples were summarized,and the related challenges,constructive solutions,and futural prospects of functional ZIBs and ZICs were also dedicatedly evaluated.

Construction of multifunctional hydrogel based on the tannic acid-metal coating decorated MoS2 dual nanozyme for bacteria-infected wound healing

Bacterial infection,tissue hypoxia and inflammatory response can hinder the infected wound repair process.To mitigate the above issues,tannic acid-chelated Fe-decorated molybdenum disulfide nanosheets(MoS2@TA/Fe NSs)with dual enzyme activities were developed and anchored to a multifunctional hydrogel.The hydrogel exhibited excellent antibacterial ability owing to the combined effects of photothermal therapy(PTT),glutathione(GSH)loss,and the peroxidase(POD)-like activity(catalyse H2O_(2)into⋅OH under acid condition)of MoS2@TA/Fe NSs.Benefitting from the catalase(CAT)-like activity,the hydrogel could decompose H2O_(2)into O_(2)at neutral pH to relieve hypoxia and supply adequate O_(2).POD-like activity was mainly attributed to MoS2 NSs,while CAT-like activity was primarily due to TA/Fe complex.Moreover,MoS2@TA/Fe NSs endowed the hydrogel with outstanding anti-oxidant ability to scavenge redundant reactive oxygen species(ROS)and reactive nitrogen species(RNS)under neutral environment to maintain the balance of antioxidant systems and prevent inflammation.In addition,the hydrogel could inhibit the release of inflammatory factors for the anti-inflammatory property of TA.TA retained partial phenolic hydroxyl groups,which cross-linked the nanosheets to the network structure of the hydrogel and promoted the adhesion of hydrogels.Due to the dynamic boron ester bonds between polyvinyl alcohol(PVA),dextran(Dex),MoS2@TA/Fe,and borax,the hydrogel demonstrated fast self-healing and rapid shape adaptability.This shape-adaptable adhesive hydrogel could fill the whole wound and closely contact the wound,ensuring that it achieved its functions with maximum efficiency.The MoS2@TA/Fe nanozyme-anchored multifunctional hydrogel showed high potential for bacteria-infected wound healing.

Ultrasound-triggered piezocatalytic composite hydrogels for promoting bacterial-infected wound healing

Wound healing has become one of the basic issues faced by the medical community because of the susceptibility of skin wounds to bacterial infection.As such,it is highly desired to design a nanocomposite hydrogel with excellent antibacterial activity to achieve high wound closure effectiveness.Here,based on ultrasound-triggered piezocatalytic therapy,a multifunctional hydrogel is designed to promote bacteria-infected wound healing.Under ultrasonic vibration,the surface of barium titanate(BaTiO_(3),BT)nanoparticles embedded in the hydrogel rapidly generate reactive oxygen species(ROS)owing to the established strong built-in electric field,endowing the hydrogel with superior antibacterial efficacy.This modality shows intriguing advantages over conventional photodynamic therapy,such as prominent soft tissue penetration ability and the avoidance of serious skin phototoxicity after systemic administration of photosensitizers.Moreover,the hydrogel based on N-[tris(hydroxymethyl)methyl]acrylamide(THM),N-(3-aminopropyl)methacrylamide hydrochloride(APMH)and oxidized hyaluronic acid(OHA)exhibits outstanding self-healing and bioadhesive properties able to accelerate full-thickness skin wound healing.Notably,compared with the widely reported mussel-inspired adhesive hydrogels,OHA/THM-APMH hydrogel due to the multiple hydrogen bonds from unique tri-hydroxyl structure overcomes the shortage that catechol groups are easily oxidized,giving it long-term and repeatable adhesion performance.Importantly,this hybrid hydrogel confines BT nanoparticles to wound area and locally induced piezoelectric catalysis under ultrasound to eradicate bacteria,markedly improving the therapeutic biosafety and exhibits great potential for harmless treatment of bacteria-infected tissues.

A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury

The repair and motor functional recovery after spinal cord injury(SCI)remains a worldwide challenge.The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI.Using mesenchymal stem cells(MSCs)derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation.However,the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied.Herein,we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel(FE)with sustainable and long term extracellular vesicle release(FE@EVs)for improving motor functional recovery after SCI.The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord,thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation,reducing inflammatory reaction,promoting remyelination and axonal regeneration.This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.

A Mg^(2+)/polydopamine composite hydrogel for the acceleration of infected wound healing

Bacterial infection is a vital factor to delay the wound healing process.The antibiotics abuse leads to drug resistance of some pathogenic bacteria.Non-antibiotic-dependent multifunctional biomaterials with accelerated wound healing performance are urgently desired.Herein,we reported a composite antibacterial hydrogel PDA-PAM/Mg^(2+)that shows excellent self-healing and tissue adhesive property,and photothermal antibacterial functions for accelerating wound healing.The gel was composed of polyacrylamide(PAM),polydopamine(PDA),and magnesium(Mg^(2+))and prepared via a two-step procedure:an alkali-induced dopamine pre-polymerization and followed radical polymerization process.The composite gel shows excellent tissue adhesiveness and Mg^(2+)-synergized photothermal antibacterial activity,inducing a survival rate of 5.29% for S.aureus and 7.06%for E.coli after near infrared light irradiation.The composite hydrogel further demonstrated efficient bacteria inhibition,enhanced wound healing and collagen deposition in a full-thickness skin defect rat model.Together,the PDA-PAM/Mg^(2+) hydrogel presents an excellent wound dressing with excellent tissue adhesion,wound healing,and antibacterial functions.

A multifunctional nanocomposite hydrogel with controllable release behavior enhances bone regeneration

Autologous and allogeneic bone grafts remain the gold standard for repairing bone defects.However,donor shortages and postoperative infections contribute to unsatisfactory treatment outcomes.Tissue engineering technology that utilizes biologically active composites to accelerate the healing and reconstruction of segmental bone defects has led to new ideas for in situ bone repair.Multifunctional nanocomposite hydrogels were constructed by covalently binding silver(Ag^(+))core-embedded mesoporous silica nanoparticles(Ag@MSN)to bone morphogenetic protein-2(BMP-2),which was encapsulated into silk fibroin methacryloyl(SilMA)and photo-crosslinked to form an Ag@MSN-BMP-2/SilMA hydrogel to preserve the biological activity of BMP-2 and slow its release.More importantly,multifunctional Ag+-containing nanocomposite hydrogels showed antibacterial properties.These hydrogels possessed synergistic osteogenic and antibacterial effects to promote bone defect repair.Ag@MSN-BMP-2/SilMA exhibited good biocompatibility in vitro and in vivo owing to its interconnected porosity and improved hydrophilicity.Furthermore,the multifunctional nanocomposite hydrogel showed controllable sustained-release activity that promoted bone regeneration in repairing rat skull defects by inducing osteogenic differentiation and neovascularization.Overall,Ag@MSN-BMP-2/SilMA hydrogels enrich bone regeneration strategies and show great potential for bone regeneration.