Bone defects,characterized by a loss of skeletal structure integrity,represent a prevalent clinical challenge affecting millions of patients.While bone autografts and allografts offer potential solutions,limitations,i...Bone defects,characterized by a loss of skeletal structure integrity,represent a prevalent clinical challenge affecting millions of patients.While bone autografts and allografts offer potential solutions,limitations,including donor scarcity,immune rejection,anatomical constraints,and complications arising from host comorbidities such as diabetes,often lead to unsatisfactory outcomes.This necessitates the need for alternative treatments.Researchers have identified that reactive oxygen species(ROS)play a crucial role in bone regeneration.Although physiological ROS levels are essential for normal healing,excessive ROS accumulation disrupts the balance between bone formation and resorption,hindering regeneration.Antioxidants can mitigate oxidative stress by scavenging ROS or inhibiting their formation,thereby restoring the equilibrium between bone formation and resorption.Advances in nanotechnology have enabled the development of various ROS-scavenging nanomaterials with enhanced therapeutic efficacy.These nanomaterials either function as delivery platforms for conventional antioxidants or as direct ROS-neutralizing agents through intrinsic redox or enzyme-mimicking properties.This review comprehensively summarizes ROS-scavenging nanomaterials for bone tissue regeneration,focusing on their design strategies,underlying mechanisms,applications,and potential for clinical translation.展开更多
Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel wi...Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.展开更多
A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK...A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK-CUR-TPP)to enable synergistic tumor therapy via photodynamic(PDT),chemodynamic(CDT),and mild photothermal therapy(mPTT).In this strategy,AuNPs attached to the surface serve as a“pore locker”,cloaking CeO_(2)and CUR before entering tumor cells.UCNPs convert near-infrared(NIR)light into UV and visible light emission,simultaneously initiating AuNP aggregation via photoclick chemistry,CeO_(2)-mediated reactive oxygen species(ROS)generation,and TPP-CUR-driven PDT.The CeO_(2)amplifies oxidative stress by depleting glutathione(GSH)and catalyzing ROS production(O_(2)^(·-)and·OH),while releasing oxygen to relieve tumor hypoxia.The release of TPP-CUR not merely resumes the negativity of the surface,but also disrupts mitochondrial function and downregulates heat shock proteins(HSPs),further sensitizing tumor cells to mPTT(~45℃)performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion.Importantly,ROS-scavenging ability post-PTT of CeO_(2)has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation.This fully integrated,lightand ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice,reducing tumor volume from 185 to 27 mm^(3)following a single tail-vein injection.展开更多
Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge.Here,a polydopamine-mediated graphene oxide(PGO)and hydroxyapatite nanop...Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge.Here,a polydopamine-mediated graphene oxide(PGO)and hydroxyapatite nanoparticle(PHA)-incorporated conductive alginate/gelatin(AG)scaffold is developed to accelerate periodontal bone regeneration by modulating the diabetic inflammatory microenvironment.PHA confers the scaffold with osteoinductivity and PGO provides a conductive pathway for the scaffold.The conductive scaffold promotes bone regeneration by transferring endogenous electrical signals to cells and activating Ca2+channels.Moreover,the scaffold with polydopamine-mediated nanomaterials has a reactive oxygen species(ROS)-scavenging ability and anti-inflammatory activity.It also exhibits an immunomodulatory ability that suppresses M1 macrophage polarization and activates M2 macrophages to secrete osteogenesis-related cytokines by mediating glycolytic and RhoA/ROCK pathways in macrophages.The scaffold induces excellent bone regeneration in periodontal bone defects of diabetic rats because of the synergistic effects of good conductive,ROS-scavenging,anti-inflammatory,and immunomodulatory abilities.This study provides fundamental insights into the synergistical effects of conductivity,osteoinductivity,and immunomodulatory abilities on bone regeneration and offers a novel strategy to design immunomodulatory biomaterials for treatment of immune-related diseases and tissue regeneration.展开更多
Wound management is an important issue that places enormous pressure on the physical and mental health of patients,especially in cases of infection,where the increased inflammatory response could lead to severe hypert...Wound management is an important issue that places enormous pressure on the physical and mental health of patients,especially in cases of infection,where the increased inflammatory response could lead to severe hypertrophic scars(HSs).In this study,a hydrogel dressing was developed by combining the high strength and toughness,swelling resistance,antibacterial and antioxidant capabilities.The hydrogel matrix was composed of a double network of polyvinyl alcohol(PVA)and agarose with excellent mechanical properties.Hyperbranched polylysine(HBPL),a highly effective antibacterial cationic polymer,and tannic acid(TA),a strong antioxidant molecule,were added to the hydrogel as functional components.Examination of antibacterial and antioxidant properties of the hydrogel confirmed the full play of the efficacy of HBPL and TA.In the in vivo studies of methicillin-resistant Staphylococcus aureus(MRSA)infection,the hydrogel had shown obvious promotion of wound healing,and more profoundly,significant suppression of scar formation.Due to the common raw materials and simple preparation methods,this hydrogel can be mass produced and used for accelerating wound healing while preventing HSs in infected wounds.展开更多
Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ROS)plays a key role in the pathological progression of AKI.Mitochondrial-target...Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ROS)plays a key role in the pathological progression of AKI.Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI.Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases.However,most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules,the main damage site of AKI.Here,an ultra-small Tungsten-based nanodots(TWNDs)with strong ROS scavenging can be very effective for treatment of AKI.TWNDs can reach the tubular site after crossing the glomerular barrier,and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies.To our knowledge,this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI.Through in-depth study of the therapeutic mechanism,such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy.In addition,TWNDs can also reduce the infiltration of inflammatory cells.This work provides a new way to passively target mitochondria for AKI,and give inspiration for the treatment of many major diseases closely related to mitochondria,such as myocardial infarction and cerebral infarction.展开更多
Bone defects are always accompanied by inflammation due to excessive reactive oxygen species(ROS)in injured regions,which greatly impedes the regeneration of bone tissues.Although many conductive polymers have been de...Bone defects are always accompanied by inflammation due to excessive reactive oxygen species(ROS)in injured regions,which greatly impedes the regeneration of bone tissues.Although many conductive polymers have been developed to scavenge ROS,they are typically non-degradable under physiological conditions,making them unsuitable for in vivo applications.Biodegradable polyorganophosphazenes(POPPs)may serve as potent ROS-scavenging biomaterials owing to their versatile chemical structures and ease of functionalization.Herein,a PATGP-type electroactive polyphosphazene with side groups of aniline tetramer and glycine ethyl ester was compared to conventional poly(lactic-co-glycolic acid)(PLGA)in regenerating bone tissues.To conduct in vitro and in vivo evaluations,three kinds of electrospun nanofibrous meshes were prepared:PLGA,PLGA/PATGP blend,and PLGA/PATGP core–shell nanofibers.Among them,PLGA/PATGP core–shell nanofibers outperform the blend and PLGA nanofibers in terms of scavenging ROS,promoting osteogenic differentiation,and accelerating neo-bone formation.The continuous PATGP shell on the PLGA/PATGP core–shell nanofiber surface could apparently provide more significant modulation effects on cellular behaviors than the PLGA/PATGP blend nanofibers with PATGP dispersed in the PLGA matrix.Therefore,the core–shell structured PLGA/PATGP nanofibers were envisioned as a promising candidate scaffold for bone tissue engineering.Additionally,the core–shell design paved the way for biomedical applications of functional POPPs in combination with other polymeric biomaterials,without phase separation or difficulty of increasing the molecular weights of POPPs.展开更多
MG53 is an essential component of the cell membrane repair machinery,participating in the healing of dermal wounds.Here we develop a novel delivery system using recombinant human MG53(rhMG53)protein and a reactive oxy...MG53 is an essential component of the cell membrane repair machinery,participating in the healing of dermal wounds.Here we develop a novel delivery system using recombinant human MG53(rhMG53)protein and a reactive oxygen species(ROS)-scavenging gel to treat diabetic wounds.Mice with ablation of MG53 display defective hair follicle structure,and topical application of rhMG53 can promote hair growth in the mg53/mice.Cell lineage tracing studies reveal a physiological function of MG53 in modulating the proliferation of hair follicle stem cells(HFSCs).We find that rhMG53 protects HFSCs from oxidative stress-induced apoptosis and stimulates differentiation of HSFCs into keratinocytes.The cytoprotective function of MG53 is mediated by STATs and MAPK signaling in HFSCs.The thermosensitive ROS-scavenging gel encapsulated with rhMG53 allows for sustained release of rhMG53 and promotes healing of chronic cutaneous wounds and hair follicle development in the db/db mice.These findings support the potential therapeutic value of using rhMG53 in combination with ROS-scavenging gel to treat diabetic wounds.展开更多
基金supported by the National Natural Science Foundation of China(No.82371102,China)the Key program of Shanghai Science and Technology Commission(No.23JC1402400,China).
文摘Bone defects,characterized by a loss of skeletal structure integrity,represent a prevalent clinical challenge affecting millions of patients.While bone autografts and allografts offer potential solutions,limitations,including donor scarcity,immune rejection,anatomical constraints,and complications arising from host comorbidities such as diabetes,often lead to unsatisfactory outcomes.This necessitates the need for alternative treatments.Researchers have identified that reactive oxygen species(ROS)play a crucial role in bone regeneration.Although physiological ROS levels are essential for normal healing,excessive ROS accumulation disrupts the balance between bone formation and resorption,hindering regeneration.Antioxidants can mitigate oxidative stress by scavenging ROS or inhibiting their formation,thereby restoring the equilibrium between bone formation and resorption.Advances in nanotechnology have enabled the development of various ROS-scavenging nanomaterials with enhanced therapeutic efficacy.These nanomaterials either function as delivery platforms for conventional antioxidants or as direct ROS-neutralizing agents through intrinsic redox or enzyme-mimicking properties.This review comprehensively summarizes ROS-scavenging nanomaterials for bone tissue regeneration,focusing on their design strategies,underlying mechanisms,applications,and potential for clinical translation.
基金This study was partly funded by grants from the National Natural Science Funding of China(82172424,82271629)Outstanding Youth Fund of Zhejiang Province(LR22H060002)+2 种基金Zhejiang Medical and Health Science and Technology Plan Project(2022RC210,2021KY212)Wenzhou Basic Science Research Plan Project(Y20210045)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028).
文摘Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.
基金funded by Hong Kong Research Grant Council(GRF14300822)Faculty of Science of the Chinese University of Hong Kong(CRIMS)+1 种基金the Natural Science Foundation of Shandong Province(ZR2023MC178)Youth Innovation Team Development Project of Shandong Province(Food Nanotechnology innovation team).
文摘A multifunctional nanoplatform(USiCeCurAu)has been developed that integrates upconversion nanoparticles(UCNPs),gold nanoparticles(AuNPs),cerium oxide(CeO_(2)),and a thioketal-curcumin-triphenylphosphonium conjugate(TK-CUR-TPP)to enable synergistic tumor therapy via photodynamic(PDT),chemodynamic(CDT),and mild photothermal therapy(mPTT).In this strategy,AuNPs attached to the surface serve as a“pore locker”,cloaking CeO_(2)and CUR before entering tumor cells.UCNPs convert near-infrared(NIR)light into UV and visible light emission,simultaneously initiating AuNP aggregation via photoclick chemistry,CeO_(2)-mediated reactive oxygen species(ROS)generation,and TPP-CUR-driven PDT.The CeO_(2)amplifies oxidative stress by depleting glutathione(GSH)and catalyzing ROS production(O_(2)^(·-)and·OH),while releasing oxygen to relieve tumor hypoxia.The release of TPP-CUR not merely resumes the negativity of the surface,but also disrupts mitochondrial function and downregulates heat shock proteins(HSPs),further sensitizing tumor cells to mPTT(~45℃)performed by light-induced AuNP aggregation after detachment due to electrostatic repulsion.Importantly,ROS-scavenging ability post-PTT of CeO_(2)has been demonstrated to effectively mitigate excessive inflammation and prevent severe scab formation.This fully integrated,lightand ROS-responsive nanoplatform affords significant therapeutic efficacy in 4T1 tumor-bearing BALB/c mice,reducing tumor volume from 185 to 27 mm^(3)following a single tail-vein injection.
基金grants from Sichuan Key Research and Development Program of China(22ZDYF2034)National Natural Science Foundation of China(grant no.82072071,82072073)+5 种基金Key-Area Research and Development Program of Guang Dong Province(2019B010941002)Shenzhen Funds of the Central Government to Guide Local Scientific and Technological Development(2021SZVUP123)Sichuan Science and Technology Program(2020YFS0170)Fundamental Research Funds for the Central Universities(2682020ZT79)Guangdong Basic and Applied Basic Research Foundation(2021B1515120019)Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202012,RD-03-202101).
文摘Regenerating periodontal bone tissues in the aggravated inflammatory periodontal microenvironment under diabetic conditions is a great challenge.Here,a polydopamine-mediated graphene oxide(PGO)and hydroxyapatite nanoparticle(PHA)-incorporated conductive alginate/gelatin(AG)scaffold is developed to accelerate periodontal bone regeneration by modulating the diabetic inflammatory microenvironment.PHA confers the scaffold with osteoinductivity and PGO provides a conductive pathway for the scaffold.The conductive scaffold promotes bone regeneration by transferring endogenous electrical signals to cells and activating Ca2+channels.Moreover,the scaffold with polydopamine-mediated nanomaterials has a reactive oxygen species(ROS)-scavenging ability and anti-inflammatory activity.It also exhibits an immunomodulatory ability that suppresses M1 macrophage polarization and activates M2 macrophages to secrete osteogenesis-related cytokines by mediating glycolytic and RhoA/ROCK pathways in macrophages.The scaffold induces excellent bone regeneration in periodontal bone defects of diabetic rats because of the synergistic effects of good conductive,ROS-scavenging,anti-inflammatory,and immunomodulatory abilities.This study provides fundamental insights into the synergistical effects of conductivity,osteoinductivity,and immunomodulatory abilities on bone regeneration and offers a novel strategy to design immunomodulatory biomaterials for treatment of immune-related diseases and tissue regeneration.
基金supported by the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(2021SZ-TD004)the Natural Science Foundation of Zhejiang Province(LD21E030001)+1 种基金the Joint Fund of National Natural Science Foundation of China(U22A20155)the Lingyan Program of Zhejiang Province(2022C01106).
文摘Wound management is an important issue that places enormous pressure on the physical and mental health of patients,especially in cases of infection,where the increased inflammatory response could lead to severe hypertrophic scars(HSs).In this study,a hydrogel dressing was developed by combining the high strength and toughness,swelling resistance,antibacterial and antioxidant capabilities.The hydrogel matrix was composed of a double network of polyvinyl alcohol(PVA)and agarose with excellent mechanical properties.Hyperbranched polylysine(HBPL),a highly effective antibacterial cationic polymer,and tannic acid(TA),a strong antioxidant molecule,were added to the hydrogel as functional components.Examination of antibacterial and antioxidant properties of the hydrogel confirmed the full play of the efficacy of HBPL and TA.In the in vivo studies of methicillin-resistant Staphylococcus aureus(MRSA)infection,the hydrogel had shown obvious promotion of wound healing,and more profoundly,significant suppression of scar formation.Due to the common raw materials and simple preparation methods,this hydrogel can be mass produced and used for accelerating wound healing while preventing HSs in infected wounds.
基金National Natural Science Foundation of China(No.81974508,21974134)Hunan Science Fund for Distinguished Young Scholar of China(No.2021JJ10067)+3 种基金Innovation-Driven Project of Central South University(No.202045005)Hunan Provincial Natural Science Foundation of China(No.2021JJ31066)Key Research Project of Ningxia Hui Autonomous Region in 2021 of China(Major Project)(No.2021BEG01001)Key Program of Ningxia Hui Autonomous Region Natural Science Foundation of China(No.2022JJ21059).
文摘Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ROS)plays a key role in the pathological progression of AKI.Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI.Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases.However,most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules,the main damage site of AKI.Here,an ultra-small Tungsten-based nanodots(TWNDs)with strong ROS scavenging can be very effective for treatment of AKI.TWNDs can reach the tubular site after crossing the glomerular barrier,and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies.To our knowledge,this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI.Through in-depth study of the therapeutic mechanism,such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy.In addition,TWNDs can also reduce the infiltration of inflammatory cells.This work provides a new way to passively target mitochondria for AKI,and give inspiration for the treatment of many major diseases closely related to mitochondria,such as myocardial infarction and cerebral infarction.
基金The authors acknowledge financial support from the National Key R&D Program of China(2018YFE0194400)the National Natural Science Foundation of China(51873013)Guangdong Basic and Applied Basic Research Foundation(2020A1515111182).
文摘Bone defects are always accompanied by inflammation due to excessive reactive oxygen species(ROS)in injured regions,which greatly impedes the regeneration of bone tissues.Although many conductive polymers have been developed to scavenge ROS,they are typically non-degradable under physiological conditions,making them unsuitable for in vivo applications.Biodegradable polyorganophosphazenes(POPPs)may serve as potent ROS-scavenging biomaterials owing to their versatile chemical structures and ease of functionalization.Herein,a PATGP-type electroactive polyphosphazene with side groups of aniline tetramer and glycine ethyl ester was compared to conventional poly(lactic-co-glycolic acid)(PLGA)in regenerating bone tissues.To conduct in vitro and in vivo evaluations,three kinds of electrospun nanofibrous meshes were prepared:PLGA,PLGA/PATGP blend,and PLGA/PATGP core–shell nanofibers.Among them,PLGA/PATGP core–shell nanofibers outperform the blend and PLGA nanofibers in terms of scavenging ROS,promoting osteogenic differentiation,and accelerating neo-bone formation.The continuous PATGP shell on the PLGA/PATGP core–shell nanofiber surface could apparently provide more significant modulation effects on cellular behaviors than the PLGA/PATGP blend nanofibers with PATGP dispersed in the PLGA matrix.Therefore,the core–shell structured PLGA/PATGP nanofibers were envisioned as a promising candidate scaffold for bone tissue engineering.Additionally,the core–shell design paved the way for biomedical applications of functional POPPs in combination with other polymeric biomaterials,without phase separation or difficulty of increasing the molecular weights of POPPs.
文摘MG53 is an essential component of the cell membrane repair machinery,participating in the healing of dermal wounds.Here we develop a novel delivery system using recombinant human MG53(rhMG53)protein and a reactive oxygen species(ROS)-scavenging gel to treat diabetic wounds.Mice with ablation of MG53 display defective hair follicle structure,and topical application of rhMG53 can promote hair growth in the mg53/mice.Cell lineage tracing studies reveal a physiological function of MG53 in modulating the proliferation of hair follicle stem cells(HFSCs).We find that rhMG53 protects HFSCs from oxidative stress-induced apoptosis and stimulates differentiation of HSFCs into keratinocytes.The cytoprotective function of MG53 is mediated by STATs and MAPK signaling in HFSCs.The thermosensitive ROS-scavenging gel encapsulated with rhMG53 allows for sustained release of rhMG53 and promotes healing of chronic cutaneous wounds and hair follicle development in the db/db mice.These findings support the potential therapeutic value of using rhMG53 in combination with ROS-scavenging gel to treat diabetic wounds.
