Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
Arranging multiple identical sub-arrays in a special way can enhance degrees of freedom(DOFs)and obtain a hole-free difference co-array(DCA).In this paper,by adjusting the interval of adjacent sub-arrays,a kind of gen...Arranging multiple identical sub-arrays in a special way can enhance degrees of freedom(DOFs)and obtain a hole-free difference co-array(DCA).In this paper,by adjusting the interval of adjacent sub-arrays,a kind of generalized array architecture with larger aperture is proposed.Although some holes may exist in the DCA of the proposed array,they are distributed uniformly.Utilizing the partial continuity of the DCA,an extended covariance matrix can be constructed.Singular value decomposition(SVD)is used to obtain an extended signal sub-space,by which the direction-of-arrival(DOA)estimation algorithm for quasi-stationary signals is given.In order to eliminating angle ambiguity caused by the holes of DCA,the estimation of signal parameters via rotational invariance techniques(ESPRIT)is used to construct a matrix that includes all angle information.Utilizing this matrix,a secondary extended signal sub-space can be obtained.This signal sub-space is corresponding to a hole-free DCA.Then,dealing with the further extended signal sub-space by multiple signal classification(MUSIC)algorithm,the unambiguous DOAs of all incident signals can be estimated.Some simulation results are shown to prove the improved performance of proposed generalized array architecture in DOA estimation and the effectiveness of corresponding hole-repair algorithm in eliminating angle ambiguity.展开更多
In this paper, a two-dimensional(2D) DOA estimation algorithm of coherent signals with a separated linear acoustic vector-sensor(AVS) array consisting of two sparse AVS arrays is proposed. Firstly,the partitioned spat...In this paper, a two-dimensional(2D) DOA estimation algorithm of coherent signals with a separated linear acoustic vector-sensor(AVS) array consisting of two sparse AVS arrays is proposed. Firstly,the partitioned spatial smoothing(PSS) technique is used to construct a block covariance matrix, so as to decorrelate the coherency of signals. Then a signal subspace can be obtained by singular value decomposition(SVD) of the covariance matrix. Using the signal subspace, two extended signal subspaces are constructed to compensate aperture loss caused by PSS.The elevation angles can be estimated by estimation of signal parameter via rotational invariance techniques(ESPRIT) algorithm. At last, the estimated elevation angles can be used to estimate automatically paired azimuth angles. Compared with some other ESPRIT algorithms, the proposed algorithm shows higher estimation accuracy, which can be proved through the simulation results.展开更多
The treatment of intervertebral disc (IVD) degeneration remains a significant challenge due to the uniqueischemic structure of the IVD, which comprises the scavengingof inflammatory cytokines, alleviation of cellular ...The treatment of intervertebral disc (IVD) degeneration remains a significant challenge due to the uniqueischemic structure of the IVD, which comprises the scavengingof inflammatory cytokines, alleviation of cellular oxidativestress responses, restoration of nuclei pulposus (NP) cell viability,and recovery of IVD biomechanical function. Herein,we developed an injectable microsphere (CS-MnO_(2)@PC) byincorporating chitosan microspheres (CS) with manganesedioxide (MnO_(2)) nanozymes and celecoxib encapsulated inPluronic F-127 (PC) nanosized micelles, via in situ redox orSchiff base reaction. The hybrid carrier demonstrates robustcapabilities in scavenging free radicals, alleviating extracellularoxidative stress, and reducing inflammatory cytokinesin NP cells, as evidenced by RT-qPCR and immunofluorescence staining assays. In vivo evaluations further indicatethat this hybrid carrier helps preserve NP hydration andthe lamellar structure of the annulus fibrosus (AF), as confirmed by radiological analysis and histological staining evaluations.These injectable chitosan microspheres, combiningnanozymes and nanosized drug micelles, represent a promising therapeutic strategy for degenerative IVD.展开更多
Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell ...Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements.In the present study,we prepared a semi-interpenetrating network composite gel(CG)by incorporating short chain chitosan(CS)into a covalent tetra-armed poly(ethylene glycol)network.In addition to satisfying physicochemical,mechanics,biocompatibility,and cell affinity requirements,this CG easily encapsulated acetylsalicylic acid(ASA)via electrostatic interactions and chain entanglement,achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell(PDLSC)proliferation and osteogenic differentiation.In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model.This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1,which upregulated M2 macrophage recruitment and polarization in situ,indicating its appealing potential in bone tissue engineering.展开更多
In spite of biological tissue-like peculiarity,multifarious functionalities and great application prospect,the low mechanics and soften behavior of hydrogels still retain a problem to be addressed for repetitive weigh...In spite of biological tissue-like peculiarity,multifarious functionalities and great application prospect,the low mechanics and soften behavior of hydrogels still retain a problem to be addressed for repetitive weight-bearing fields of flexible electronics,actuators,substitutions of soft tissues,wound dressing,wearable or implantable devices.Due to the distinct combination of diversity,reversibility and impressive disruption-reconstruction capacity,the chitosan physical cross-links can server as recoverable“sacrificial bonds”to construct multifarious energy-dissipative and anti-soften hydrogels and further broaden their diversified applications.In this review,we summarized the gelation mechanisms of chitosan physical networks and highlighted the chitosan physical network based hydrogels in rational design,construction principle,and structure and performance regulation.The recent progress in functional hydrogels for flexible electronics and biomaterials was systematically discussed.Overall,the review will provide comprehensive guidelines on the design principle,performance modulation and functionality construction of energy-dissipative and soften resistant hydrogels.展开更多
It is of great sighificance to develop rapid crosslinking strategies to enrich the functions of hydrogels and simplify the preparation process of hydrogels.Herein,we applied the ternary condensation reaction of o-phth...It is of great sighificance to develop rapid crosslinking strategies to enrich the functions of hydrogels and simplify the preparation process of hydrogels.Herein,we applied the ternary condensation reaction of o-phthalaldehyde(OPA)with thiol and amino moieties to con struct hydrogel n etworks with fast gelati on rate,excellent mecha nical stre ngth,and favorable stability.展开更多
Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment,which remains an unmet clinical challenge.Herein,an injectable Tetra-PEG hydrogel tha...Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment,which remains an unmet clinical challenge.Herein,an injectable Tetra-PEG hydrogel that possesses rapid gelation,firm tissue adhesion,high mechanical strength,suitable degradability,and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets.Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing.In vivo experiments using an anticoagulated rat tooth extraction model show that the hydrogel significantly outperformed clinically used cotton and gelatin sponge in hemostatic efficacy,wound closure,alveolar ridge preservation,and in situ alveolar bone regeneration.Histomorphological evaluations reveal the mechanisms for accelerated bone repair through suppressed long-term inflammation,elevated collagen deposition,higher osteoblast activity,and enhanced angiogenesis.Together,our study highlights the clinical potential of the developed injectable Tetra-PEG hydrogel for treating anticoagulant-related post-extraction hemorrhage and improving socket healing.展开更多
Hydrogel bioadhesives represent promising and efficient alternatives to sutures or staples for gastrointestinal(GI)perforation management.However,several concerns remain for the existing bioadhesives including slow an...Hydrogel bioadhesives represent promising and efficient alternatives to sutures or staples for gastrointestinal(GI)perforation management.However,several concerns remain for the existing bioadhesives including slow and/or weak adhesive,poor mechanical strength,low biocompatibility,and poor biodegradability,which largely limit their clinical application in GI perforation repair.In this work,we introduce an in situ injectable Tetra-PEG hydrogel bioadhesive(SS)composed of tetra-armed poly(ethylene glycol)amine(Tetra-PEG-NH2)and tetra-armed poly(ethylene glycol)succinimidyl succinate(Tetra-PEG-SS)for the sutureless repair of GI defects.The SS hydrogel exhibits rapid gelation behavior and high burst pressure and is capable of providing instant robust adhesion and fluid-tight sealing in the ex vivo porcine intestinal and gastric models.Importantly,the succinyl ester linkers in the SS hydrogel endow the bioadhesive with suitable in vivo degradability to match the new GI tissue formation.The in vivo evaluation in the rat GI injured model further demonstrates the successful sutureless sealing and repair of the intestine and stomach by the SS hydrogel with the advantages of neglectable postsurgical adhesion,suppressed inflammation,and enhanced angiogenesis.Together,our results support potential clinical applications of the SS bioadhesive for the high-efficient repair of GI perforation.展开更多
Development of versatile theranostic agents that simultaneously integrate therapeutic and diagnostic features remains a clinical urgent.Herein,we aimed to prepare uniform PEGylated(lactic-co-glycolic acid)(PLGA)microc...Development of versatile theranostic agents that simultaneously integrate therapeutic and diagnostic features remains a clinical urgent.Herein,we aimed to prepare uniform PEGylated(lactic-co-glycolic acid)(PLGA)microcapsules(PB@(Fe_(3)O_(4)@PEG-PLGA)MCs)with superparamagnetic Fe3O4 nanoparticles embedded in the shell and Prussian blue(PB)NPs inbuilt in the cavity via a premix membrane emulsification(PME)method.On account of the eligible geometry and multiple load capacity,these MCs could be used as efficient multi-modality contrast agents to simultaneously enhance the contrasts of US,MR and PAT imaging.In-built PB NPs furnished the MCs with excellent photothermal conversion property and embedded Fe_(3)O_(4)NPs endowed the magnetic location for fabrication of targeted drug delivery system.Notably,after further in-situ encapsulation of antitumor drug of DOX,(PB+DOX)@(Fe_(3)O_(4)@PEG-PLGA)MCs possessed more unique advantages on achieving near infrared(NIR)-responsive drug delivery and magnetic-guided chemo-photothermal synergistic osteosarcoma therapy.In vitro and in vivo studies revealed these biocompatible(PB+DOX)@(Fe_(3)O_(4)@PEG-PLGA)MCs could effectively target to the tumor tissue with superior therapeutic effect against the invasion of osteosarcoma and alleviation of osteolytic lesions,which will be developed as a smart platform integrating multi-modality imaging capabilities and synergistic effect with high therapy efficacy.展开更多
Oxidative stress and aging lead to progressive senescence of nucleus pulposus(NP)cells,resulting in intervertebral disc(IVD)degeneration(IVDD).In some cases,degenerative IVD can further cause low back pain(LBP).Severa...Oxidative stress and aging lead to progressive senescence of nucleus pulposus(NP)cells,resulting in intervertebral disc(IVD)degeneration(IVDD).In some cases,degenerative IVD can further cause low back pain(LBP).Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD.However,the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs.Here,we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl(GP)with quercetin to alleviate IVDD by removing senescent NP cells.The hydrogel exhibited injectability,biodegradability,prominent biocompatibility and responsive release of quercetin under pathological conditions.In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells.In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models,indicating a potential therapeutic approach for ameliorating IVDD and LBP.This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD,providing a new strategy for IVDD treatment.展开更多
The research on the supramolecular hyperbranched polymers(SHPs) that combines the advantages of supramolecular polymer and hyperbranched architecture has attracted considerable interests in many applications. Here we ...The research on the supramolecular hyperbranched polymers(SHPs) that combines the advantages of supramolecular polymer and hyperbranched architecture has attracted considerable interests in many applications. Here we demonstrate a simple approach to prepare POSS-embedded supramolecular hyperbranched polymers(POSS-SHPs) with varied morphology and size by controlling monomer concentration and mixed solvents. The SHPs formations can further transfer into the core-shell structured micelles by addition of competitive vips based on the double supramolecular driving forces.展开更多
Owing to the tremendous advantages and unique well-defined nanoscale structure,polyhedral oligomeric silsesquioxanes(POSS)have received considerable interest in the design of novel organic-inorganic hybrid nanomateria...Owing to the tremendous advantages and unique well-defined nanoscale structure,polyhedral oligomeric silsesquioxanes(POSS)have received considerable interest in the design of novel organic-inorganic hybrid nanomaterials with all manner of prominent capabilities,which is rec-ognized as a new generation of promising materials for advanced applications of material sci-ence,engineering science and biomedical fields.Benefitting from the recent progress in combi-nation of controlled/living polymerization and emerging click chemistry,POSS-based hybrid ma-terials with ingenious design,versatile topological structure and sophisticated multifunctionality have been successfully fabricated and developed into abundant well-defined hybrid nanostruc-tures with desired physicochemical properties.Tailor-made amphiphilic molecular design and nanosized hybrid architecture provide opportunities for the self-assembly of POSS-based hybrid materials with unique hierarchical morphologies in selective solvents.Through the in-depth understanding of structure-properties relationship,POSS-based hybrid materials can achieve the modulation of precise control of self-assembling process and multi-purpose applications with improved material performances.In this review,we summarize the recent advances of POSS-based hybrid materials in molecular design,self-assembly behavior in solutions and poten-tial biomedical applications with main concerns on drug delivery,gene therapy,bioimaging and tissue engineering field.Finally,future directions and remaining challenges for further advance-ment of POSS-based hybrid materials are proposed and discussed.展开更多
Simple, efficient and accurate controllable systems for materials are becoming more essential, in response to the explosively growing demands in the fields of chemistry and material science. Herein, tailored hydrogels...Simple, efficient and accurate controllable systems for materials are becoming more essential, in response to the explosively growing demands in the fields of chemistry and material science. Herein, tailored hydrogels are explored depending on synergistic regulation of p H-responsive chemical networks with an "on/off" function and physical networks with dynamic selfoptimized arrangement. Thiol-disulfide exchange reaction endows hydrogels with controlled architectures while hydrogen bondstrengthened 2-ureido-4[1H]-pyrimidinone(UPy) moieties contributes a significant increase in mechanical strengths. The integration of that dual cross-linking(DC) network ensures the hydrogels with customized structure and enhanced mechanical property. Such controllably strategy is universally applicable and will open a new avenue to flexibly fabricate desired hybrid hydrogels with distinctive features and functions for their potential applications.展开更多
Annulus fibrosus(AF)plays a crucial role in the biomechanical loading of intervertebral disc(IVD).AF is difficult to self-heal when the annulus tears develop,because AF has a unique intricate structure and biologic mi...Annulus fibrosus(AF)plays a crucial role in the biomechanical loading of intervertebral disc(IVD).AF is difficult to self-heal when the annulus tears develop,because AF has a unique intricate structure and biologic milieu in vivo.Tissue engineering is promising for repairing AF rupture,but construction of suitable mechanical matching devices or scaffolds is still a grand challenge.To deeply know the varied forces involved in the movement of the native annulus is highly beneficial for designing biomimetic scaffolds to recreate the AF function.In this review,we overview six freedom degrees of forces and adhesion strength on AF tissue.Then,we summarize the mechanical modalities to simulate related forces on AF and to assess the characteristics of biomaterials.We finally outline some current advanced techniques to develop mechanically adaptable biomaterials for AF rupture repair.展开更多
Multicomponent polymerizations have become powerful tools for the construction of sequence-defined polymers. Although the Passerini multicomponent reaction has been widely used in the synthesis of sequence-defined pol...Multicomponent polymerizations have become powerful tools for the construction of sequence-defined polymers. Although the Passerini multicomponent reaction has been widely used in the synthesis of sequence-defined polymers, the tandem usage of the Passerini multicomponent reaction and other multicomponent reactions in one-pot for the synthesis of sequence-defined polymers has not been developed until now. In this contribution, we report the tandem usage of the Passerini three-component reaction and the three-component amine-thiol-ene conjugation reaction in one pot for the synthesis of sequence-defined polymers. The Passerini reaction between methacrylic acid, adipaldehyde, and 2-isocyanobutanoate was carried out, affording a new molecule containing two alkene units. Subsequently, an amine and a thiolactone were added to the reaction system, whereupon the three-component amine-thiol-ene conjugating reaction occurred to yield a sequence-defined polymer. This method offers more rapid access to sequence-defined polymers with high molecular diversity and complexity.展开更多
Advances in nanotechnology depend upon expanding the ability to create biologically inspired complex materials with well-defined multidimensional structures.Fabrication of hybrid hierarchical structures by combining c...Advances in nanotechnology depend upon expanding the ability to create biologically inspired complex materials with well-defined multidimensional structures.Fabrication of hybrid hierarchical structures by combining colloidal organic and inorganic building blocks remains a challenge due to the difficulty in preparing a diverse spectrum of rigid-flexible coupling units of precise shape and size.Herewe reportageneral strategy for crafting amyriad of uniform aggregates via manipulating self-assembly of distinct dendimers with precisely controlled polyhed raloligomeric silse squioxane(POSS)-embedded cores integrating stiffness and ductility.The rigidity of POSS units exerts steric effects onself-amplification of hydrophobic do mains while the flexibility from internally ductile linkages provides ideal scenarios in establishing self-adaptive structural optimization,which subsequently drive the assemblies to proceed into hierarchical self-assembly via multiple coordination effects,generating highly complex multi compartment micelles(MCMs)without any preprocessing.Our facile approach enables a robust modular nanofabrication of well-organized dendrimers toward artificial functional systems with defined geometric architectures and intriguing functions for advanced biological applications.展开更多
We present a highly adaptable design platform for multi-responsive,multilayered composite nanoparticles(MC-NPs)with fine-tunable functional layers.A flexible disulfide-linked nanogel template is obtained by a controll...We present a highly adaptable design platform for multi-responsive,multilayered composite nanoparticles(MC-NPs)with fine-tunable functional layers.A flexible disulfide-linked nanogel template is obtained by a controlled in-situ gelation method,enabling a high degree of control over each successive layer.From this template,we optimize“smart”biomaterials with biofunctional surfaces,tunable drug release kinetics,and magnetic or pH-responsive functionality,fabricated into MC-NPs for targeted drug release and periosteum-mimetic structures for controlled rhBMP-2 release towards bone tissue formation in-vivo.Such a versatile platform for the design of MC-NPs is a powerful tool that shows considerable therapeutic potential in clinical fields such as oncology and orthopedics.展开更多
Hydrogels have emerged as three-dimensional biomaterials with potential biomedical applications in numerous fields including drug delivery and tissue engineering.They have particularly garnered great interest from res...Hydrogels have emerged as three-dimensional biomaterials with potential biomedical applications in numerous fields including drug delivery and tissue engineering.They have particularly garnered great interest from researchers due to their excellent biocompatibility,ability to encapsulate,protect,and deliver bioactive therapeutics,capacity for sustained release,and their ability to act as implantable scaffolds and support tissue regeneration.This special issue,consisting of eight papers,addresses some of the greatest challenges in hydrogel technology and showcases its capabilities,focusing on the applications of hydrogels in bone regeneration[1][2],stem cell therapy[3],hemostasis[4],stroke[5],cancer treatments[6][7],and biological activities in general[8].展开更多
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
基金This work was supported by supported by the National Natural Science Foundation of China(51877015,U1831117)the Cooperation Agreement Project by the Department of Science and Technology of Guizhou Province of China(LH[2017]7320,LH[2017]7321)+2 种基金the Foundation of Top-notch Talents by Education Department of Guizhou Province of China(KY[2018]075)the nature and science fund from the Education Department of Guizhou province the Innovation Group Major Research Program Funded by Guizhou Provincial Education Department(KY[2016]051)PhD Research Startup Foundation of Tongren University(trxyDH1710).
文摘Arranging multiple identical sub-arrays in a special way can enhance degrees of freedom(DOFs)and obtain a hole-free difference co-array(DCA).In this paper,by adjusting the interval of adjacent sub-arrays,a kind of generalized array architecture with larger aperture is proposed.Although some holes may exist in the DCA of the proposed array,they are distributed uniformly.Utilizing the partial continuity of the DCA,an extended covariance matrix can be constructed.Singular value decomposition(SVD)is used to obtain an extended signal sub-space,by which the direction-of-arrival(DOA)estimation algorithm for quasi-stationary signals is given.In order to eliminating angle ambiguity caused by the holes of DCA,the estimation of signal parameters via rotational invariance techniques(ESPRIT)is used to construct a matrix that includes all angle information.Utilizing this matrix,a secondary extended signal sub-space can be obtained.This signal sub-space is corresponding to a hole-free DCA.Then,dealing with the further extended signal sub-space by multiple signal classification(MUSIC)algorithm,the unambiguous DOAs of all incident signals can be estimated.Some simulation results are shown to prove the improved performance of proposed generalized array architecture in DOA estimation and the effectiveness of corresponding hole-repair algorithm in eliminating angle ambiguity.
基金supported by the National Natural Science Foundation of China (62261047,62066040)the Foundation of Top-notch Talents by Education Department of Guizhou Province of China (KY[2018]075)+3 种基金the Science and Technology Foundation of Guizhou Province of China (ZK[2022]557,[2020]1Y004)the Science and Technology Research Program of the Chongqing Municipal Education Commission (KJQN202200637)PhD Research Start-up Foundation of Tongren University (trxyDH1710)Tongren Science and Technology Planning Project ((2018)22)。
文摘In this paper, a two-dimensional(2D) DOA estimation algorithm of coherent signals with a separated linear acoustic vector-sensor(AVS) array consisting of two sparse AVS arrays is proposed. Firstly,the partitioned spatial smoothing(PSS) technique is used to construct a block covariance matrix, so as to decorrelate the coherency of signals. Then a signal subspace can be obtained by singular value decomposition(SVD) of the covariance matrix. Using the signal subspace, two extended signal subspaces are constructed to compensate aperture loss caused by PSS.The elevation angles can be estimated by estimation of signal parameter via rotational invariance techniques(ESPRIT) algorithm. At last, the estimated elevation angles can be used to estimate automatically paired azimuth angles. Compared with some other ESPRIT algorithms, the proposed algorithm shows higher estimation accuracy, which can be proved through the simulation results.
基金supported by the Ministry of Science and Technology of China (2020YFA0908900)National Natural Science Foundation of China (21935011)+1 种基金Shenzhen Science and Technology Innovation Commission (KQTD20200820113012029, JCYJ20220530114409020, and 20231115134555001)Guangdong Provincial Key Laboratory of Advanced Biomaterials (2022B1212010003)。
文摘The treatment of intervertebral disc (IVD) degeneration remains a significant challenge due to the uniqueischemic structure of the IVD, which comprises the scavengingof inflammatory cytokines, alleviation of cellular oxidativestress responses, restoration of nuclei pulposus (NP) cell viability,and recovery of IVD biomechanical function. Herein,we developed an injectable microsphere (CS-MnO_(2)@PC) byincorporating chitosan microspheres (CS) with manganesedioxide (MnO_(2)) nanozymes and celecoxib encapsulated inPluronic F-127 (PC) nanosized micelles, via in situ redox orSchiff base reaction. The hybrid carrier demonstrates robustcapabilities in scavenging free radicals, alleviating extracellularoxidative stress, and reducing inflammatory cytokinesin NP cells, as evidenced by RT-qPCR and immunofluorescence staining assays. In vivo evaluations further indicatethat this hybrid carrier helps preserve NP hydration andthe lamellar structure of the annulus fibrosus (AF), as confirmed by radiological analysis and histological staining evaluations.These injectable chitosan microspheres, combiningnanozymes and nanosized drug micelles, represent a promising therapeutic strategy for degenerative IVD.
基金supported by the National Key R&D Program of China(2020YFA0710401)National Natural Science Foundation of China(51972005,51903003,51973226,81871782 and 51672009)the Youth Innovation Promotion Association CAS(No.2019031)for financial support.
文摘Hydrogels are extracellular-matrix-like biomimetic materials that have wide biomedical applications in tissue engineering and drug delivery.However,most hydrogels cannot simultaneously fulfill the mechanical and cell compatibility requirements.In the present study,we prepared a semi-interpenetrating network composite gel(CG)by incorporating short chain chitosan(CS)into a covalent tetra-armed poly(ethylene glycol)network.In addition to satisfying physicochemical,mechanics,biocompatibility,and cell affinity requirements,this CG easily encapsulated acetylsalicylic acid(ASA)via electrostatic interactions and chain entanglement,achieving sustained release for over 14 days and thus promoting periodontal ligament stem cell(PDLSC)proliferation and osteogenic differentiation.In vivo studies corroborated the capacity of PDLSCs and ASA-laden CG to enhance new bone regeneration in situ using a mouse calvarial bone defect model.This might be attributed to PDLSCs and host mesenchymal stem cells expressing monocyte chemoattractant protein-1,which upregulated M2 macrophage recruitment and polarization in situ,indicating its appealing potential in bone tissue engineering.
基金supported by the National Natural Science Foundation of China(Nos.52173144,51803188 and 21725403)the Excellent Youth Fund Project of Henan Natural Science Foundation(No.222300420079)+1 种基金the Shenzhen Science and Technology Innovation Commission(No.KQTD20200820113012029)the Key Research and Development and Promotion Projectsof Henan Province(No.212102210635).
文摘In spite of biological tissue-like peculiarity,multifarious functionalities and great application prospect,the low mechanics and soften behavior of hydrogels still retain a problem to be addressed for repetitive weight-bearing fields of flexible electronics,actuators,substitutions of soft tissues,wound dressing,wearable or implantable devices.Due to the distinct combination of diversity,reversibility and impressive disruption-reconstruction capacity,the chitosan physical cross-links can server as recoverable“sacrificial bonds”to construct multifarious energy-dissipative and anti-soften hydrogels and further broaden their diversified applications.In this review,we summarized the gelation mechanisms of chitosan physical networks and highlighted the chitosan physical network based hydrogels in rational design,construction principle,and structure and performance regulation.The recent progress in functional hydrogels for flexible electronics and biomaterials was systematically discussed.Overall,the review will provide comprehensive guidelines on the design principle,performance modulation and functionality construction of energy-dissipative and soften resistant hydrogels.
基金This work was supported by the Ministry of Science and Technology of China(No.2020YFA0908900)the National Natural Science Foundation of China(Nos.21935011,21725403,and 51973226)the Youth Innovation Promotion Association CAS(No.2019031).
文摘It is of great sighificance to develop rapid crosslinking strategies to enrich the functions of hydrogels and simplify the preparation process of hydrogels.Herein,we applied the ternary condensation reaction of o-phthalaldehyde(OPA)with thiol and amino moieties to con struct hydrogel n etworks with fast gelati on rate,excellent mecha nical stre ngth,and favorable stability.
基金support for the work from the Ministry of Science and Technology of China (2020YFA0908900)National Natural Science Foundation of China (21935011 and 21725403)+2 种基金Shenzhen Science and Technology Innovation Commission (KQTD20200820113012029,JCYJ20190814114605162,and JCYJ20220818100601003)Guangdong Basic and Applied Basic Research Foundation (2022A1515110321)Guangdong Provincial Key Laboratory of Advanced Biomaterials (2022B1212010003).
文摘Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment,which remains an unmet clinical challenge.Herein,an injectable Tetra-PEG hydrogel that possesses rapid gelation,firm tissue adhesion,high mechanical strength,suitable degradability,and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets.Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing.In vivo experiments using an anticoagulated rat tooth extraction model show that the hydrogel significantly outperformed clinically used cotton and gelatin sponge in hemostatic efficacy,wound closure,alveolar ridge preservation,and in situ alveolar bone regeneration.Histomorphological evaluations reveal the mechanisms for accelerated bone repair through suppressed long-term inflammation,elevated collagen deposition,higher osteoblast activity,and enhanced angiogenesis.Together,our study highlights the clinical potential of the developed injectable Tetra-PEG hydrogel for treating anticoagulant-related post-extraction hemorrhage and improving socket healing.
基金gratefully acknowledge the support for the work from Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 21725403)+2 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and JCYJ20220818100601003)Guangdong Basic and Applied Basic Research Foundation(2022A1515110321,2019A1515110511)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Hydrogel bioadhesives represent promising and efficient alternatives to sutures or staples for gastrointestinal(GI)perforation management.However,several concerns remain for the existing bioadhesives including slow and/or weak adhesive,poor mechanical strength,low biocompatibility,and poor biodegradability,which largely limit their clinical application in GI perforation repair.In this work,we introduce an in situ injectable Tetra-PEG hydrogel bioadhesive(SS)composed of tetra-armed poly(ethylene glycol)amine(Tetra-PEG-NH2)and tetra-armed poly(ethylene glycol)succinimidyl succinate(Tetra-PEG-SS)for the sutureless repair of GI defects.The SS hydrogel exhibits rapid gelation behavior and high burst pressure and is capable of providing instant robust adhesion and fluid-tight sealing in the ex vivo porcine intestinal and gastric models.Importantly,the succinyl ester linkers in the SS hydrogel endow the bioadhesive with suitable in vivo degradability to match the new GI tissue formation.The in vivo evaluation in the rat GI injured model further demonstrates the successful sutureless sealing and repair of the intestine and stomach by the SS hydrogel with the advantages of neglectable postsurgical adhesion,suppressed inflammation,and enhanced angiogenesis.Together,our results support potential clinical applications of the SS bioadhesive for the high-efficient repair of GI perforation.
基金This work is supported by the National Natural Science Foundation of China(51973226,51773004,51920105006 and 81630056)National Key Basic Research Program of China(2014CB542202)the Youth Innovation Promotion Association CAS(No.2019031)for financial support.
文摘Development of versatile theranostic agents that simultaneously integrate therapeutic and diagnostic features remains a clinical urgent.Herein,we aimed to prepare uniform PEGylated(lactic-co-glycolic acid)(PLGA)microcapsules(PB@(Fe_(3)O_(4)@PEG-PLGA)MCs)with superparamagnetic Fe3O4 nanoparticles embedded in the shell and Prussian blue(PB)NPs inbuilt in the cavity via a premix membrane emulsification(PME)method.On account of the eligible geometry and multiple load capacity,these MCs could be used as efficient multi-modality contrast agents to simultaneously enhance the contrasts of US,MR and PAT imaging.In-built PB NPs furnished the MCs with excellent photothermal conversion property and embedded Fe_(3)O_(4)NPs endowed the magnetic location for fabrication of targeted drug delivery system.Notably,after further in-situ encapsulation of antitumor drug of DOX,(PB+DOX)@(Fe_(3)O_(4)@PEG-PLGA)MCs possessed more unique advantages on achieving near infrared(NIR)-responsive drug delivery and magnetic-guided chemo-photothermal synergistic osteosarcoma therapy.In vitro and in vivo studies revealed these biocompatible(PB+DOX)@(Fe_(3)O_(4)@PEG-PLGA)MCs could effectively target to the tumor tissue with superior therapeutic effect against the invasion of osteosarcoma and alleviation of osteolytic lesions,which will be developed as a smart platform integrating multi-modality imaging capabilities and synergistic effect with high therapy efficacy.
基金National Natural Science Foundation of China(82072490 and 21935011)Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Oxidative stress and aging lead to progressive senescence of nucleus pulposus(NP)cells,resulting in intervertebral disc(IVD)degeneration(IVDD).In some cases,degenerative IVD can further cause low back pain(LBP).Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD.However,the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs.Here,we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl(GP)with quercetin to alleviate IVDD by removing senescent NP cells.The hydrogel exhibited injectability,biodegradability,prominent biocompatibility and responsive release of quercetin under pathological conditions.In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells.In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models,indicating a potential therapeutic approach for ameliorating IVDD and LBP.This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD,providing a new strategy for IVDD treatment.
基金supported by the National Natural Science Foundation of China(21504096,21674120,21474115)Ministry of Science and Technology of China(2014CB932200)“Young Thousand Talents”Program
文摘The research on the supramolecular hyperbranched polymers(SHPs) that combines the advantages of supramolecular polymer and hyperbranched architecture has attracted considerable interests in many applications. Here we demonstrate a simple approach to prepare POSS-embedded supramolecular hyperbranched polymers(POSS-SHPs) with varied morphology and size by controlling monomer concentration and mixed solvents. The SHPs formations can further transfer into the core-shell structured micelles by addition of competitive vips based on the double supramolecular driving forces.
基金This research was supported by NSFC(51973226,21725403 and 21504096)the Youth Innovation Promotion Association CAS(No.2019031).
文摘Owing to the tremendous advantages and unique well-defined nanoscale structure,polyhedral oligomeric silsesquioxanes(POSS)have received considerable interest in the design of novel organic-inorganic hybrid nanomaterials with all manner of prominent capabilities,which is rec-ognized as a new generation of promising materials for advanced applications of material sci-ence,engineering science and biomedical fields.Benefitting from the recent progress in combi-nation of controlled/living polymerization and emerging click chemistry,POSS-based hybrid ma-terials with ingenious design,versatile topological structure and sophisticated multifunctionality have been successfully fabricated and developed into abundant well-defined hybrid nanostruc-tures with desired physicochemical properties.Tailor-made amphiphilic molecular design and nanosized hybrid architecture provide opportunities for the self-assembly of POSS-based hybrid materials with unique hierarchical morphologies in selective solvents.Through the in-depth understanding of structure-properties relationship,POSS-based hybrid materials can achieve the modulation of precise control of self-assembling process and multi-purpose applications with improved material performances.In this review,we summarize the recent advances of POSS-based hybrid materials in molecular design,self-assembly behavior in solutions and poten-tial biomedical applications with main concerns on drug delivery,gene therapy,bioimaging and tissue engineering field.Finally,future directions and remaining challenges for further advance-ment of POSS-based hybrid materials are proposed and discussed.
基金This work was supported by the National Natural Science Foundation of China(21674120,51973226,21725403).
文摘Simple, efficient and accurate controllable systems for materials are becoming more essential, in response to the explosively growing demands in the fields of chemistry and material science. Herein, tailored hydrogels are explored depending on synergistic regulation of p H-responsive chemical networks with an "on/off" function and physical networks with dynamic selfoptimized arrangement. Thiol-disulfide exchange reaction endows hydrogels with controlled architectures while hydrogen bondstrengthened 2-ureido-4[1H]-pyrimidinone(UPy) moieties contributes a significant increase in mechanical strengths. The integration of that dual cross-linking(DC) network ensures the hydrogels with customized structure and enhanced mechanical property. Such controllably strategy is universally applicable and will open a new avenue to flexibly fabricate desired hybrid hydrogels with distinctive features and functions for their potential applications.
基金support for the work from the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 21725403)+2 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and JCYJ20220818100601003)Guangdong Basic and Applied Basic Research Foundation(2022A1515110321)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Annulus fibrosus(AF)plays a crucial role in the biomechanical loading of intervertebral disc(IVD).AF is difficult to self-heal when the annulus tears develop,because AF has a unique intricate structure and biologic milieu in vivo.Tissue engineering is promising for repairing AF rupture,but construction of suitable mechanical matching devices or scaffolds is still a grand challenge.To deeply know the varied forces involved in the movement of the native annulus is highly beneficial for designing biomimetic scaffolds to recreate the AF function.In this review,we overview six freedom degrees of forces and adhesion strength on AF tissue.Then,we summarize the mechanical modalities to simulate related forces on AF and to assess the characteristics of biomaterials.We finally outline some current advanced techniques to develop mechanically adaptable biomaterials for AF rupture repair.
基金supported by the National Natural Science Foundation of China(51273187,21374107)the Fundamental Research Funds for the Central Universities(WK2060200012)the Program for New Century Excellent Talents in Universities(NCET-11-0882)
文摘Multicomponent polymerizations have become powerful tools for the construction of sequence-defined polymers. Although the Passerini multicomponent reaction has been widely used in the synthesis of sequence-defined polymers, the tandem usage of the Passerini multicomponent reaction and other multicomponent reactions in one-pot for the synthesis of sequence-defined polymers has not been developed until now. In this contribution, we report the tandem usage of the Passerini three-component reaction and the three-component amine-thiol-ene conjugation reaction in one pot for the synthesis of sequence-defined polymers. The Passerini reaction between methacrylic acid, adipaldehyde, and 2-isocyanobutanoate was carried out, affording a new molecule containing two alkene units. Subsequently, an amine and a thiolactone were added to the reaction system, whereupon the three-component amine-thiol-ene conjugating reaction occurred to yield a sequence-defined polymer. This method offers more rapid access to sequence-defined polymers with high molecular diversity and complexity.
基金This work was supported by NSFC(nos.51973226,21725403,51803188,and 21504096),the Ministry of Science and Technology of China(no.2014CB932200),and the China Postdoctoral Science Foundation(nos.2018M642783 and 2019T120636).
文摘Advances in nanotechnology depend upon expanding the ability to create biologically inspired complex materials with well-defined multidimensional structures.Fabrication of hybrid hierarchical structures by combining colloidal organic and inorganic building blocks remains a challenge due to the difficulty in preparing a diverse spectrum of rigid-flexible coupling units of precise shape and size.Herewe reportageneral strategy for crafting amyriad of uniform aggregates via manipulating self-assembly of distinct dendimers with precisely controlled polyhed raloligomeric silse squioxane(POSS)-embedded cores integrating stiffness and ductility.The rigidity of POSS units exerts steric effects onself-amplification of hydrophobic do mains while the flexibility from internally ductile linkages provides ideal scenarios in establishing self-adaptive structural optimization,which subsequently drive the assemblies to proceed into hierarchical self-assembly via multiple coordination effects,generating highly complex multi compartment micelles(MCMs)without any preprocessing.Our facile approach enables a robust modular nanofabrication of well-organized dendrimers toward artificial functional systems with defined geometric architectures and intriguing functions for advanced biological applications.
文摘We present a highly adaptable design platform for multi-responsive,multilayered composite nanoparticles(MC-NPs)with fine-tunable functional layers.A flexible disulfide-linked nanogel template is obtained by a controlled in-situ gelation method,enabling a high degree of control over each successive layer.From this template,we optimize“smart”biomaterials with biofunctional surfaces,tunable drug release kinetics,and magnetic or pH-responsive functionality,fabricated into MC-NPs for targeted drug release and periosteum-mimetic structures for controlled rhBMP-2 release towards bone tissue formation in-vivo.Such a versatile platform for the design of MC-NPs is a powerful tool that shows considerable therapeutic potential in clinical fields such as oncology and orthopedics.
文摘Hydrogels have emerged as three-dimensional biomaterials with potential biomedical applications in numerous fields including drug delivery and tissue engineering.They have particularly garnered great interest from researchers due to their excellent biocompatibility,ability to encapsulate,protect,and deliver bioactive therapeutics,capacity for sustained release,and their ability to act as implantable scaffolds and support tissue regeneration.This special issue,consisting of eight papers,addresses some of the greatest challenges in hydrogel technology and showcases its capabilities,focusing on the applications of hydrogels in bone regeneration[1][2],stem cell therapy[3],hemostasis[4],stroke[5],cancer treatments[6][7],and biological activities in general[8].
