Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manu...Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.展开更多
Over the past few decades,biomaterials have made rapid advances in tissue engineering.In particular,there have been several studies on vascularization during skin flap regeneration for plastic surgery.From the perspec...Over the past few decades,biomaterials have made rapid advances in tissue engineering.In particular,there have been several studies on vascularization during skin flap regeneration for plastic surgery.From the perspective of function,the biomaterials used to improve the vascularization of skin flaps are primarily classified into two types:(1)electrospun nanofibrous membranes as porous scaffolds,and(2)hydrogels as cell or cytokine carriers.Based on their source,various natural,synthetic,and semi-synthetic biomaterials have been developed with respective characteristics.For the ischemic environment of the flap tissue,the therapeutic effect of the combination of biomaterials was better than that of drugs,cytokines,and cells alone.Biomaterials could improve cell migration,prolong the efficacy of cytokines,and provide an advantageous survival environment to transplanted cells.展开更多
The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary...The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary functions.Inspired by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response activation.With the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early angiogenesis.The silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being provided.At room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)inside.Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier.The vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.When embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the scaffold.Furthermore,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone.This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.展开更多
Bioelectrical stimulation is a powerful technique used to promote tissue regeneration,but it can be hindered by an“electrical overload”phenomenon in the core region of stimulation.We develop a threaded microneedle e...Bioelectrical stimulation is a powerful technique used to promote tissue regeneration,but it can be hindered by an“electrical overload”phenomenon in the core region of stimulation.We develop a threaded microneedle electrode system that protects against“electrical overload”by delivering medicinal hydrogel microspheres into the core regions.The threaded needle body is coated with polydopamine and chitosan to enhance the adhesion of microspheres,which are loaded into the threaded grooves,allowing for their stereoscopic release in the core regions.After the electrode is inserted,the microspheres can be delivered three-dimensionally through physical swelling and the shear-thinning effect of chitosan,mitigating the electrical damage.Microspheres are designed to release alkylated vitamin B12 and vitamin E,providing antioxidant and cell protection effects upon in-situ activation,reducing reactive oxygen species(ROS)by 72.8%and cell death by 59.5%.In the model of peripheral nerve injury,the electrode system improves the overall antioxidant capacity by 78.5%and protects the surrounding cells.Additionally,it leads to an improved nerve conduction velocity ratio of 41.9%and sciatic nerve function index of 12.1%,indicating enhanced neuroregeneration.The threaded microneedle electrode system offers a promising approach for nerve repair by inhibiting“electrical overload”,potentially improving outcomes for tissue regeneration.展开更多
In the intricate labyrinth of modern medical advancements,the quest for non-invasive and precise diagnostic tools is a journey of continual discovery and innovation.One of the most compelling frontiers in this realm i...In the intricate labyrinth of modern medical advancements,the quest for non-invasive and precise diagnostic tools is a journey of continual discovery and innovation.One of the most compelling frontiers in this realm is the monitoring of cerebral blood flow,a critical parameter that holds the key to understanding a myriad of neurological conditions[1,2].Traditional Transcranial Doppler(TCD)sonography,despite its widespread application,has been hindered by a number of limitations[3].展开更多
Given the high malignancy of liver cancer and the liver's unique role in immune and metabolic regulation,current treatments have limited efficacy,resulting in a poor prognosis.Hydrogels,soft 3-dimensional network ...Given the high malignancy of liver cancer and the liver's unique role in immune and metabolic regulation,current treatments have limited efficacy,resulting in a poor prognosis.Hydrogels,soft 3-dimensional network materials comprising numerous hydrophilic monomers,have considerable potential as intelligent drug delivery systems for liver cancer treatment.The advantages of hydrogels include their versatile delivery modalities,precision targeting,intelligent stimulus response,controlled drug release,high drug loading capacity,excellent slow-release capabilities,and substantial potential as carriers of bioactive molecules.This review presents an in-depth examination of hydrogel-assisted advanced therapies for hepatocellular carcinoma,encompassing small-molecule drug therapy,immunotherapy,gene therapy,and the utilization of other biologics.Furthermore,it examines the integration of hydrogels with conventional liver cancer therapies,including radiation,interventional therapy,and ultrasound.This review provides a comprehensive overview of the numerous advantages of hydrogels and their potential to enhance therapeutic efficacy,targeting,and drug delivery safety.In conclusion,this review addresses the clinical implementation of hydrogels in liver cancer therapy and future challenges and design principles for hydrogel-based systems,and proposes novel research directions and strategies.展开更多
The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system(CNS)injury.Maintaining brain immune homeostasis is crucial for restoring neuro...The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system(CNS)injury.Maintaining brain immune homeostasis is crucial for restoring neurovascular function.In this study,an interactive bridge was developed via an immunomodulatory hydrogel microsphere to link the interaction network between microglia and the neurovascular unit,thereby precisely regulating immune-neurovascular crosstalk and achieving neural function recovery.This immunomodulatory crosstalk microsphere(MP/RIL4)was composed of microglia-targeted RAP12 peptide-modified interleukin-4(IL-4)nanoparticles and boronic ester-functionalized hydrogel using biotin-avidin reaction and air-microfluidic techniques.We confirmed that the immunomodulatory microspheres reduced the expression of pro-inflammatory factors including IL-1β,iNOS,and CD86,while upregulating levels of anti-inflammatory factors such as IL-10,Arg-1,and CD206 in microglia.In addition,injection of the MP/RIL4 significantly mitigated brain atrophy volume in a mouse model of ischemic stroke,promoted neurobehavioral recovery,and enhanced the crosstalk between immune cells and the neurovascular unit,thus increasing angiogenesis and neurogenesis of stroke mice.In summary,the immunomodulatory microspheres,capable of orchestrating the interaction between immune cells and neurovascular unit,hold considerable therapeutic potential for ischemic stroke and other CNS diseases.展开更多
A traumatic tissue adhesive technology is highly sought after in ophthalmic surgery;however,many polymeric adhesives face significant limitations in clinical ophthalmology, particularly incorneal transplantation. A ma...A traumatic tissue adhesive technology is highly sought after in ophthalmic surgery;however,many polymeric adhesives face significant limitations in clinical ophthalmology, particularly incorneal transplantation. A major challenge is achieving rapid adhesion without introducingpolymer barriers or chemical toxicity from cross-linking. To address this, we developed a novelcornea-specific nanoadhesive constructed through protein-DNA co-assembly and applied it tocorneal transplantation. In this system, a rigid tetrahedral DNA framework was employed toguide the spatial distribution of polycationic recombinant proteins (K72) and serve as the coreof the nanoadhesive, facilitating energy conversion during tissue connection. The adhesivedemonstrated a strength of 2.3 kPa between corneal lenticules. After modification with RGDpeptides, the adhesive system significantly enhanced corneal epithelialization, reducedinflammation and neovascularization, and ultimately promoted corneal repair. This studyrepresents the first application of a nanoadhesive in ophthalmic surgery, providing a novelsolution for developing ophthalmic-specific adhesives for clinical use.展开更多
Recognizing cell surface proteins through protein–protein interactions or broader receptor-ligand interactions is a central strategy for regulating intracellular signal transduction,as well as for the diagnosis and t...Recognizing cell surface proteins through protein–protein interactions or broader receptor-ligand interactions is a central strategy for regulating intracellular signal transduction,as well as for the diagnosis and treatment of diseases,particularly autoimmune disorders[1].The most widely used approach involves functionalizing nanoparticles through post-grafting methods such as chemical bonding,physical adsorption,and electrostatic interactions to modulate signal transduction mediated by membrane receptor proteins.These synthetic particles—comprising polymers,dendrimers,inorganic particles,nanofibers,and others—possess nanoscale features that translate the subtle differences in ligand nanostructures into diverse cellular responses through ligand-receptor interactions[2].Notably,protein receptors on the cell surface typically exhibit a heterogeneous or discontinuous dynamic distribution,complicating the precise recognition and targeted isolation of these membrane receptors.Furthermore,certain membrane protein receptors tend to aggregate into specific structural domains,or even form higher-order clusters,coexisting with adjacent proteins to regulate their functions[3].Traditional particle surface technologies have typically relied on simple anchored ligand approaches.These methods often fail to effectively control the density,spacing,and spatial arrangement of ligands,posing challenges in precisely regulating cellular signal transduction.By contrast,DNA origami technology capitalizes on the self-assembly capabilities of DNA molecules to create precise nanoscale structures.It is notable for its programmability,high precision,and excellent biocompatibility.By designing specific DNA strands,various shapes and patterns can be folded,achieving the meticulous spatial design of molecular arrangements.DNA origami enables the construction of arbitrary 2D nanostructures and provides templates for arranging nanomaterials and 3D structures,making a significant advancement in DNA nanotechnology[4].In summary,DNA origami technology offers a method for precisely constructing and displaying biomolecules at the nanoscale.By patterning modified ligands to match the spatial arrangement of cell surface receptor clusters accurately,this technology activates downstream signal transduction.This approach offers new strategies for modulating cellular signal transduction and treating autoimmune diseases through receptor-ligand interactions.展开更多
Regulating macrophage activation precisely is crucial in treating chronic inflammation in osteoarthritis(OA).However,the stable pro-inflammatory state and deep distribution of macrophages in vivo pose a great challeng...Regulating macrophage activation precisely is crucial in treating chronic inflammation in osteoarthritis(OA).However,the stable pro-inflammatory state and deep distribution of macrophages in vivo pose a great challenge to treatment.In this study,inspired by the innate immune,immune cell mobilized hydrogel microspheres were constructed by microfluidic methods and load chemokines,macrophage antibodies and engineered cell membrane vesicles(sEVs)via covalent and non-covalent junctions.The immune cell mobilized hydrogel microspheres,based on a mixture of streptavidin grafted hyaluronic acid methacrylate(HAMA-SA)and Chondroitin sulfate methacrylate(ChSMA)microspheres(HCM),can recruit,capture and reprogram proinflammatory macrophages in the joint cavity to improve the joint inflammatory microenvironment.In vitro experiments demonstrated that immune cell mobilized hydrogel microspheres had excellent macrophage recruitment,capture,and reprogramming abilities.Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5%.Animal experiments also revealed significant reduction in synovial inflammation and cartilage matrix degradation of OA.Therefore,the immune cell mobilized hydrogel microspheres may be an effective treatment of OA inflammation for the future.展开更多
Intervertebral disc degeneration(IVDD)is rising worldwide and leading to significant health issues and financial strain for patients.Traditional treatments for IVDD can alleviate pain but do not reverse disease progre...Intervertebral disc degeneration(IVDD)is rising worldwide and leading to significant health issues and financial strain for patients.Traditional treatments for IVDD can alleviate pain but do not reverse disease progression,and surgical removal of the damaged disc may be required for advanced disease.The inflammatory microenvironment is a key driver in the development of disc degeneration.Suitable anti-inflammatory substances are critical for controlling inflammation in IVDD.Several treatment options,including glucocorticoids,non-steroidal anti-inflammatory drugs,and biotherapy,are being studied for their potential to reduce inflammation.However,anti-inflammatories often have a short half-life when applied directly and are quickly excreted,thus limiting their therapeutic effects.Biomaterial-based platforms are being explored as anti-inflammation therapeutic strategies for IVDD treatment.This review introduces the pathophysiology of IVDD and discusses anti-inflammatory therapeutics and the components of these unique biomaterial platforms as comprehensive treatment systems.We discuss the strengths,shortcomings,and development prospects for various biomaterials platforms used to modulate the inflammatory microenvironment,thus providing guidance for future breakthroughs in IVDD treatment.展开更多
Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective...Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energy to prevent degeneration, thereby treating osteoarthritis. Herein, to achieve an ideal subcellular therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded with mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria. As a result, this system demonstrated an advantage in mitochondria function restoration, reactive oxygen species scavenging, cell survival rescue, and chondrocyte homeostasis maintenance through increasing mitophagy. In a rat post-traumatic osteoarthritis model, the intra-articular injection of HM@WY-Lip/UA ameliorated cartilage matrix degradation, osteophyte formation, and subchondral bone sclerosis at 8 weeks. Overall, this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner, and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis.展开更多
There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel m...There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel microsphere,characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis,is employed for in situ sustained macrophage targeting and regulation,and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers.The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle,thus keeping it in joints,while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages,and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages.展开更多
Human-machine interaction(HMI)has always been at the frontier of technological innovation,making our interactions with technology more intuitive and effi-cient,as well as driving much of the research interest in this ...Human-machine interaction(HMI)has always been at the frontier of technological innovation,making our interactions with technology more intuitive and effi-cient,as well as driving much of the research interest in this field.Wearable electronic systems can seamlessly and accurately receive,store,process,and output information.This endows them with tremendous potential applications ranging from daily life interactions to monitoring physiological signals and clinical medical treatments.Building upon this foundation,researchers have embarked on a series of innovations concerning textile fibers’materials,manufacturing techniques,and further functional payloads.展开更多
Irregular bone defects,characterized by unpredictable size,shape,and depth,pose a major challenge to clinical treatment.Although various bone grafts are available,none can fully meet the repair needs of the defective ...Irregular bone defects,characterized by unpredictable size,shape,and depth,pose a major challenge to clinical treatment.Although various bone grafts are available,none can fully meet the repair needs of the defective area.Here,this study fabricates a dough-type hydrogel(DR-Net),in which the first dynamic network is generated by coordination between thiol groups and silver ions,thereby possessing kneadability to adapt to various irregular bone defects.The second rigid covalent network is formed through photocrosslinking,maintaining the osteogenic space under external forces and achieving a better match with the bone regeneration process.In vitro,an irregular alveolar bone defect is established in the fresh porcine mandible,and the dough-type hydrogel exhibits outstanding shape adaptability,perfectly matching the morphology of the bone defect.After photocuring,the storage modulus of the hydrogel increases 8.6 times,from 3.7 kPa(before irradiation)to 32 kPa(after irradiation).Furthermore,this hydrogel enables effective loading of P24 peptide,which potently accelerates bone repair in Sprague–Dawley(SD)rats with critical calvarial defects.Overall,the dough-type hydrogel with kneadability,space-maintaining capability,and osteogenic activity exhibits exceptional potential for clinical translation in treating irregular bone defects.展开更多
Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life.Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of ...Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life.Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of tendinopathy.Herein,injectable methacrylate gelatin(GelMA)microspheres(GM)were fabricated and loaded with heparin-dopamine conjugate(HDC)and hepatocyte growth factor(HGF).GM@HDC@HGF were designed to balance the inflammatory microenvironment by inhibiting oxidative stress and inflammation,thereby regulating extracellular matrix(ECM)metabolism and halting tendon degeneration.Combining growth factors with heparin was expected to improve the encaption,the catechol groups on dopamine have adhesion and antioxidant properties,allowing potential attachment at the injured site,and better function synergized with HGF.GM@HDC@HGF injected in situ in rat Achilles tendinopathy(AT)models significantly downregulated oxidative stress and inflammation,and ameliorated ECM degradation.In conclusion,the multifunctional platform developed presents a promising alternative for the treatment of tendinopathy.展开更多
Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases.However,unidirectional targeting gene therapy is a...Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases.However,unidirectional targeting gene therapy is always desired at the tissue interface.In this study,inspired by the principle that like charges repulse each other,a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers,thus realizing unidirectional gene therapy at the tendon-paratenon interface.Under the charge repulsion of positively charged layer,more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue,which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation,but also avoided adverse effects on the fragile endogenous healing of tendon itself.In summary,this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.展开更多
Surgical sutures serve as foundational elements in surgical procedures,facilitating wound closure,exudation minimization,infection prevention,structural support maintenance,and healing promotion.The classification of ...Surgical sutures serve as foundational elements in surgical procedures,facilitating wound closure,exudation minimization,infection prevention,structural support maintenance,and healing promotion.The classification of traditional surgical suturing methods is intricate,and contingent upon variables such as tissue type,wound morphology,and desired healing outcomes.展开更多
Bionic lubricant materials are a class of materials inspired by natural organisms and offer excellent lubrication properties and biocompatibility.In the field of sports medicine,their application opens up new possibil...Bionic lubricant materials are a class of materials inspired by natural organisms and offer excellent lubrication properties and biocompatibility.In the field of sports medicine,their application opens up new possibilities for the prevention and treatment of sports-related diseases.The authors will introduce the existing theoretical models of friction in the locomotor system,the characteristics and advantages of biomimetic lubrication materials and discuss in depth their applications in the field of sports medicine.The development of bionic lubrication materials opens up unprecedented opportunities for sports medicine to provide more effective and long-lasting treatment options for patients.展开更多
Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Her...Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.展开更多
基金supported by grants from the National Key Research and Development Program of China (2020YFA0908200)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20171906)+2 种基金Shanghai Municipal Health and Family Planning Commission (2022XD055)Natural Science Foundation of Shandong Province (Shandong) (ZR2020QH121)GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine
文摘Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.
基金Yunkun Pei and Liucheng Zhang contributed equally to this work.This work was supported,in part,by the National Natural Science Foundation of China(81772099,81701907,81801928,and 81772087)Shanghai Sailing Program(18YF1412400)+3 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906)Shanghai talent development fund(2018099)Shanghai Municipal Health and Family Planning Commission(201840027)and Shanghai Jiao Tong University“Medical and Research”Program(ZH2018ZDA04)。
文摘Over the past few decades,biomaterials have made rapid advances in tissue engineering.In particular,there have been several studies on vascularization during skin flap regeneration for plastic surgery.From the perspective of function,the biomaterials used to improve the vascularization of skin flaps are primarily classified into two types:(1)electrospun nanofibrous membranes as porous scaffolds,and(2)hydrogels as cell or cytokine carriers.Based on their source,various natural,synthetic,and semi-synthetic biomaterials have been developed with respective characteristics.For the ischemic environment of the flap tissue,the therapeutic effect of the combination of biomaterials was better than that of drugs,cytokines,and cells alone.Biomaterials could improve cell migration,prolong the efficacy of cytokines,and provide an advantageous survival environment to transplanted cells.
基金supported by the National Key Research and Development Program of China(2019YFA0112000 and 2018YFB1105600)the National Natural Science Foundation of China(81930051)+2 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906)Shanghai Jiao Tong University “Medical and Research”Program(ZH2018ZDA04)Foundation of National Facility for Translational Medicine(Shanghai)(TMSK-2020-117)。
文摘The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary functions.Inspired by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response activation.With the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early angiogenesis.The silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being provided.At room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)inside.Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier.The vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.When embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the scaffold.Furthermore,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone.This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.
基金supported by various grants,including the National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China General Program(81930051,82205244)China Postdoctoral Science Foundation(2022M712135).
文摘Bioelectrical stimulation is a powerful technique used to promote tissue regeneration,but it can be hindered by an“electrical overload”phenomenon in the core region of stimulation.We develop a threaded microneedle electrode system that protects against“electrical overload”by delivering medicinal hydrogel microspheres into the core regions.The threaded needle body is coated with polydopamine and chitosan to enhance the adhesion of microspheres,which are loaded into the threaded grooves,allowing for their stereoscopic release in the core regions.After the electrode is inserted,the microspheres can be delivered three-dimensionally through physical swelling and the shear-thinning effect of chitosan,mitigating the electrical damage.Microspheres are designed to release alkylated vitamin B12 and vitamin E,providing antioxidant and cell protection effects upon in-situ activation,reducing reactive oxygen species(ROS)by 72.8%and cell death by 59.5%.In the model of peripheral nerve injury,the electrode system improves the overall antioxidant capacity by 78.5%and protects the surrounding cells.Additionally,it leads to an improved nerve conduction velocity ratio of 41.9%and sciatic nerve function index of 12.1%,indicating enhanced neuroregeneration.The threaded microneedle electrode system offers a promising approach for nerve repair by inhibiting“electrical overload”,potentially improving outcomes for tissue regeneration.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0500700)Program of Shanghai Academic/Technology Research Leader(22XD1422600)。
文摘In the intricate labyrinth of modern medical advancements,the quest for non-invasive and precise diagnostic tools is a journey of continual discovery and innovation.One of the most compelling frontiers in this realm is the monitoring of cerebral blood flow,a critical parameter that holds the key to understanding a myriad of neurological conditions[1,2].Traditional Transcranial Doppler(TCD)sonography,despite its widespread application,has been hindered by a number of limitations[3].
基金supported by National Natural Science Foundation of China(grant numbers 52273133 and 32101104)The Shanghai Municipal Health and Family Planning Commission(grant number 2022XD055)+3 种基金National Science Fund for Distinguished Young Scholars(grant number 82003147)China Postdoctoral Science Foundation(grant number 2023MD734156)Nanchong Science and Technology Bureau Basic Research Platform Project(grant number 23JCYJPT0043)Affiliated Hospital of North SiChuan Medical College unveils marshal program(grant number 2022JB003).
文摘Given the high malignancy of liver cancer and the liver's unique role in immune and metabolic regulation,current treatments have limited efficacy,resulting in a poor prognosis.Hydrogels,soft 3-dimensional network materials comprising numerous hydrophilic monomers,have considerable potential as intelligent drug delivery systems for liver cancer treatment.The advantages of hydrogels include their versatile delivery modalities,precision targeting,intelligent stimulus response,controlled drug release,high drug loading capacity,excellent slow-release capabilities,and substantial potential as carriers of bioactive molecules.This review presents an in-depth examination of hydrogel-assisted advanced therapies for hepatocellular carcinoma,encompassing small-molecule drug therapy,immunotherapy,gene therapy,and the utilization of other biologics.Furthermore,it examines the integration of hydrogels with conventional liver cancer therapies,including radiation,interventional therapy,and ultrasound.This review provides a comprehensive overview of the numerous advantages of hydrogels and their potential to enhance therapeutic efficacy,targeting,and drug delivery safety.In conclusion,this review addresses the clinical implementation of hydrogels in liver cancer therapy and future challenges and design principles for hydrogel-based systems,and proposes novel research directions and strategies.
基金supported by National Natural Science Foundation of China 81930051(WC)“Chenguang Program”(22CGA16)supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission,the National Key R&D Program of China#2019YFA0112000(YT)+4 种基金National Natural Science Foundation of China 82071284(YT),82371307(YT),82372120(HR)Shanghai Rising-Star Program(21QA1405200,YT)Young Leading Scientists Cultivation Plan supported by Shanghai Municipal Education Commission(ZXWH1082101,YT)“Two Hundred Talent”Program supported by Shanghai Jiao Tong University School of Medicine(20240701,HR)the Fundamental Research Funds for the Central Universities(YG2023ZD02,YT).
文摘The crosstalk between immune cells and the neurovascular unit plays a pivotal role in neural regeneration following central nervous system(CNS)injury.Maintaining brain immune homeostasis is crucial for restoring neurovascular function.In this study,an interactive bridge was developed via an immunomodulatory hydrogel microsphere to link the interaction network between microglia and the neurovascular unit,thereby precisely regulating immune-neurovascular crosstalk and achieving neural function recovery.This immunomodulatory crosstalk microsphere(MP/RIL4)was composed of microglia-targeted RAP12 peptide-modified interleukin-4(IL-4)nanoparticles and boronic ester-functionalized hydrogel using biotin-avidin reaction and air-microfluidic techniques.We confirmed that the immunomodulatory microspheres reduced the expression of pro-inflammatory factors including IL-1β,iNOS,and CD86,while upregulating levels of anti-inflammatory factors such as IL-10,Arg-1,and CD206 in microglia.In addition,injection of the MP/RIL4 significantly mitigated brain atrophy volume in a mouse model of ischemic stroke,promoted neurobehavioral recovery,and enhanced the crosstalk between immune cells and the neurovascular unit,thus increasing angiogenesis and neurogenesis of stroke mice.In summary,the immunomodulatory microspheres,capable of orchestrating the interaction between immune cells and neurovascular unit,hold considerable therapeutic potential for ischemic stroke and other CNS diseases.
基金supported by National Natural Science Foundation of China(Grant Nos.82471116,82271119,82371096,82401300,and 22277018)Shanghai RisingStar Program(23QA1401000)+3 种基金Healthy Young Talents Project of Shanghai Municipal Health Commission(2022YQ015)National Funded Postdoctoral Program of China(GZB20230158)China Postdoctoral Science Foundation(2024M750550)Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR23B030001)。
文摘A traumatic tissue adhesive technology is highly sought after in ophthalmic surgery;however,many polymeric adhesives face significant limitations in clinical ophthalmology, particularly incorneal transplantation. A major challenge is achieving rapid adhesion without introducingpolymer barriers or chemical toxicity from cross-linking. To address this, we developed a novelcornea-specific nanoadhesive constructed through protein-DNA co-assembly and applied it tocorneal transplantation. In this system, a rigid tetrahedral DNA framework was employed toguide the spatial distribution of polycationic recombinant proteins (K72) and serve as the coreof the nanoadhesive, facilitating energy conversion during tissue connection. The adhesivedemonstrated a strength of 2.3 kPa between corneal lenticules. After modification with RGDpeptides, the adhesive system significantly enhanced corneal epithelialization, reducedinflammation and neovascularization, and ultimately promoted corneal repair. This studyrepresents the first application of a nanoadhesive in ophthalmic surgery, providing a novelsolution for developing ophthalmic-specific adhesives for clinical use.
基金China Postdoctoral Science Foundation(2023M742361,GZB20230443,and 2022M712135)National Natural Science Foundation of China(82205244)Program of Shanghai Academic/Technology Research Leader(22XD1422600).
文摘Recognizing cell surface proteins through protein–protein interactions or broader receptor-ligand interactions is a central strategy for regulating intracellular signal transduction,as well as for the diagnosis and treatment of diseases,particularly autoimmune disorders[1].The most widely used approach involves functionalizing nanoparticles through post-grafting methods such as chemical bonding,physical adsorption,and electrostatic interactions to modulate signal transduction mediated by membrane receptor proteins.These synthetic particles—comprising polymers,dendrimers,inorganic particles,nanofibers,and others—possess nanoscale features that translate the subtle differences in ligand nanostructures into diverse cellular responses through ligand-receptor interactions[2].Notably,protein receptors on the cell surface typically exhibit a heterogeneous or discontinuous dynamic distribution,complicating the precise recognition and targeted isolation of these membrane receptors.Furthermore,certain membrane protein receptors tend to aggregate into specific structural domains,or even form higher-order clusters,coexisting with adjacent proteins to regulate their functions[3].Traditional particle surface technologies have typically relied on simple anchored ligand approaches.These methods often fail to effectively control the density,spacing,and spatial arrangement of ligands,posing challenges in precisely regulating cellular signal transduction.By contrast,DNA origami technology capitalizes on the self-assembly capabilities of DNA molecules to create precise nanoscale structures.It is notable for its programmability,high precision,and excellent biocompatibility.By designing specific DNA strands,various shapes and patterns can be folded,achieving the meticulous spatial design of molecular arrangements.DNA origami enables the construction of arbitrary 2D nanostructures and provides templates for arranging nanomaterials and 3D structures,making a significant advancement in DNA nanotechnology[4].In summary,DNA origami technology offers a method for precisely constructing and displaying biomolecules at the nanoscale.By patterning modified ligands to match the spatial arrangement of cell surface receptor clusters accurately,this technology activates downstream signal transduction.This approach offers new strategies for modulating cellular signal transduction and treating autoimmune diseases through receptor-ligand interactions.
基金supported by the National Natural Science Foundation of China-Joint Fund Project(U22A20284)the National Natural Science Foundation of China(81972069,82202724)+1 种基金Doctoral Cultivating Project of the First Affiliated Hospital of Chongqing Medical University(CYYY-BSYJSCXXM-202227202204).
文摘Regulating macrophage activation precisely is crucial in treating chronic inflammation in osteoarthritis(OA).However,the stable pro-inflammatory state and deep distribution of macrophages in vivo pose a great challenge to treatment.In this study,inspired by the innate immune,immune cell mobilized hydrogel microspheres were constructed by microfluidic methods and load chemokines,macrophage antibodies and engineered cell membrane vesicles(sEVs)via covalent and non-covalent junctions.The immune cell mobilized hydrogel microspheres,based on a mixture of streptavidin grafted hyaluronic acid methacrylate(HAMA-SA)and Chondroitin sulfate methacrylate(ChSMA)microspheres(HCM),can recruit,capture and reprogram proinflammatory macrophages in the joint cavity to improve the joint inflammatory microenvironment.In vitro experiments demonstrated that immune cell mobilized hydrogel microspheres had excellent macrophage recruitment,capture,and reprogramming abilities.Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5%.Animal experiments also revealed significant reduction in synovial inflammation and cartilage matrix degradation of OA.Therefore,the immune cell mobilized hydrogel microspheres may be an effective treatment of OA inflammation for the future.
基金supported by the National Natural Science Foundation of China(82102578,82102571)Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province(23ZYZYTS0235)+4 种基金China Postdoctoral Science Foundation(2022M720603,2022M710564)Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX0104,CSTB2022NSCQ-MSX0089)Research Project of Health Commission of Sichuan Province(2023-1601)Research Project of Nanchong Science and Technology Bureau(22SXJCQN0004)Research Project of the Affiliated Hospital of North Sichuan Medical College(2022JB008,2023ZD002).
文摘Intervertebral disc degeneration(IVDD)is rising worldwide and leading to significant health issues and financial strain for patients.Traditional treatments for IVDD can alleviate pain but do not reverse disease progression,and surgical removal of the damaged disc may be required for advanced disease.The inflammatory microenvironment is a key driver in the development of disc degeneration.Suitable anti-inflammatory substances are critical for controlling inflammation in IVDD.Several treatment options,including glucocorticoids,non-steroidal anti-inflammatory drugs,and biotherapy,are being studied for their potential to reduce inflammation.However,anti-inflammatories often have a short half-life when applied directly and are quickly excreted,thus limiting their therapeutic effects.Biomaterial-based platforms are being explored as anti-inflammation therapeutic strategies for IVDD treatment.This review introduces the pathophysiology of IVDD and discusses anti-inflammatory therapeutics and the components of these unique biomaterial platforms as comprehensive treatment systems.We discuss the strengths,shortcomings,and development prospects for various biomaterials platforms used to modulate the inflammatory microenvironment,thus providing guidance for future breakthroughs in IVDD treatment.
基金the National Natural Science Foundation of China(82072443 and 82372425)the China Postdoctoral Science Foundation(Grant No.2022M710557)+1 种基金the Natural Science Foundation of Chongqing,China(Grant No.CSTB2023NSCQ-BHX0011)the Young Excellent Science and Technology Talent Project of the First Affiliated Hospital of Chongqing Medical University(Grant No.ZYRC2022-05).
文摘Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energy to prevent degeneration, thereby treating osteoarthritis. Herein, to achieve an ideal subcellular therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded with mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria. As a result, this system demonstrated an advantage in mitochondria function restoration, reactive oxygen species scavenging, cell survival rescue, and chondrocyte homeostasis maintenance through increasing mitophagy. In a rat post-traumatic osteoarthritis model, the intra-articular injection of HM@WY-Lip/UA ameliorated cartilage matrix degradation, osteophyte formation, and subchondral bone sclerosis at 8 weeks. Overall, this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner, and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis.
基金funded by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52103174,52273133,and 82202686)+4 种基金the Shanghai Pujiang Program(2021PJD044)the Shanghai Municipal Heaith and Family Planning Commission(2022XD055)the China Postdoctoral Science Foundation(2022T150420 and 2022M712100)the Shanghai Jiading District Health Committee(2022-QN-05)the GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine.
文摘There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel microsphere,characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis,is employed for in situ sustained macrophage targeting and regulation,and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers.The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle,thus keeping it in joints,while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages,and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages.
基金supported by the National Natural Science Foundation of China(81930051)the Program of Shanghai Academic/Technology Research Leader(22XD1422600).
文摘Human-machine interaction(HMI)has always been at the frontier of technological innovation,making our interactions with technology more intuitive and effi-cient,as well as driving much of the research interest in this field.Wearable electronic systems can seamlessly and accurately receive,store,process,and output information.This endows them with tremendous potential applications ranging from daily life interactions to monitoring physiological signals and clinical medical treatments.Building upon this foundation,researchers have embarked on a series of innovations concerning textile fibers’materials,manufacturing techniques,and further functional payloads.
基金supported by the National Natural Science Foundation of China(82071104/32101104/82202663)Science and Technology Commission of Shanghai Municipality(23XD1434200/22Y21901000)+2 种基金Program of Shanghai Academic/Technology Research Leader(22XD1422600)Shanghai Municipal Health Planning Commission(202140127)Shanghai Hospital Development Center(SHDC12022120).
文摘Irregular bone defects,characterized by unpredictable size,shape,and depth,pose a major challenge to clinical treatment.Although various bone grafts are available,none can fully meet the repair needs of the defective area.Here,this study fabricates a dough-type hydrogel(DR-Net),in which the first dynamic network is generated by coordination between thiol groups and silver ions,thereby possessing kneadability to adapt to various irregular bone defects.The second rigid covalent network is formed through photocrosslinking,maintaining the osteogenic space under external forces and achieving a better match with the bone regeneration process.In vitro,an irregular alveolar bone defect is established in the fresh porcine mandible,and the dough-type hydrogel exhibits outstanding shape adaptability,perfectly matching the morphology of the bone defect.After photocuring,the storage modulus of the hydrogel increases 8.6 times,from 3.7 kPa(before irradiation)to 32 kPa(after irradiation).Furthermore,this hydrogel enables effective loading of P24 peptide,which potently accelerates bone repair in Sprague–Dawley(SD)rats with critical calvarial defects.Overall,the dough-type hydrogel with kneadability,space-maintaining capability,and osteogenic activity exhibits exceptional potential for clinical translation in treating irregular bone defects.
基金the Program of Jiangsu science and technology Department(BK20211083,BE2022737)Jiangsu Graduate Student Cultivation Innovative Engineering Graduate Research and Practice Innovation Program(KYCX21_1578)the Program of Suzhou Health Commission(GSWS2020078,SZXK202111).
文摘Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life.Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of tendinopathy.Herein,injectable methacrylate gelatin(GelMA)microspheres(GM)were fabricated and loaded with heparin-dopamine conjugate(HDC)and hepatocyte growth factor(HGF).GM@HDC@HGF were designed to balance the inflammatory microenvironment by inhibiting oxidative stress and inflammation,thereby regulating extracellular matrix(ECM)metabolism and halting tendon degeneration.Combining growth factors with heparin was expected to improve the encaption,the catechol groups on dopamine have adhesion and antioxidant properties,allowing potential attachment at the injured site,and better function synergized with HGF.GM@HDC@HGF injected in situ in rat Achilles tendinopathy(AT)models significantly downregulated oxidative stress and inflammation,and ameliorated ECM degradation.In conclusion,the multifunctional platform developed presents a promising alternative for the treatment of tendinopathy.
基金supported by the National Natural Science Foundation of China (No.82172408 and 81902234)Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program (No.20191829)+1 种基金Program of Shanghai Academic/Technology Research Leader (22XD1422600)Shanghai Municipal Health Commission (Grant No.2022YQ073).
文摘Gene therapy is capable of efficiently regulating the expression of abnormal genes in diseased tissues and expected to be a therapeutic option for refractory diseases.However,unidirectional targeting gene therapy is always desired at the tissue interface.In this study,inspired by the principle that like charges repulse each other,a positively charged micro-nano electrospun fibrous membrane with dual-layer structure was developed by electrospinning technology to achieve unidirectional delivery of siRNA-loaded cationic nanocarriers,thus realizing unidirectional gene therapy at the tendon-paratenon interface.Under the charge repulsion of positively charged layer,more cationic COX-2 siRNA nanocarriers were enriched in peritendinous tissue,which not only improved the bioavailability of the gene drug to prevent the peritendinous adhesion formation,but also avoided adverse effects on the fragile endogenous healing of tendon itself.In summary,this study provides an innovative strategy for unidirectional targeting gene therapy of tissue interface diseases by utilizing charge repulsion to facilitate unidirectional delivery of gene drugs.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China(51873107)+3 种基金Program of Shanghai Academic/Technology Research Leader(22XD1422600)Shanghai Jiao Tong University“Medical and Research”Program(YG2021ZD06)Clinical Trial Project of Shanghai Municipal Health Commission(20204Y0355)Guang Ci Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine。
文摘Surgical sutures serve as foundational elements in surgical procedures,facilitating wound closure,exudation minimization,infection prevention,structural support maintenance,and healing promotion.The classification of traditional surgical suturing methods is intricate,and contingent upon variables such as tissue type,wound morphology,and desired healing outcomes.
基金Shanghai Municipal Health and Family Planning Commission,Grant/Award Number:2022XD055National Nature Science Foundation of China,Grant/Award Number:52273133。
文摘Bionic lubricant materials are a class of materials inspired by natural organisms and offer excellent lubrication properties and biocompatibility.In the field of sports medicine,their application opens up new possibilities for the prevention and treatment of sports-related diseases.The authors will introduce the existing theoretical models of friction in the locomotor system,the characteristics and advantages of biomimetic lubrication materials and discuss in depth their applications in the field of sports medicine.The development of bionic lubrication materials opens up unprecedented opportunities for sports medicine to provide more effective and long-lasting treatment options for patients.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(82272176 and 82003658)+2 种基金the Shanghai Science and Technology Commission(19411963100)the Shanghai Municipal Health and Family Planning Commission(2022XD055)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906).
文摘Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.
