Peripheral nerve defects present complex orthopedic challenges with limited efficacy of clinical interventions.The inadequate proliferation and dysfunction of Schwann cells within the nerve scaffold impede the effecti...Peripheral nerve defects present complex orthopedic challenges with limited efficacy of clinical interventions.The inadequate proliferation and dysfunction of Schwann cells within the nerve scaffold impede the effectiveness of nerve repair.Our previ-ous studies suggested the effectiveness of a magnesium-encapsulated bioactive hydrogel in repairing nerve defects.However,its rapid release of magnesium ions limited its efficacy to long-term nerve regeneration,and its molecular mechanism remains unclear.This study utilized electrospinning technology to fabricate a MgO/MgCO_(3)/polycaprolactone(PCL)multi-gradient nanofiber membrane for peripheral nerve regeneration.Our findings indicated that by carefully adjusting the concentration or proportion of rapidly degradable MgO and slowly degradable MgCO_(3),as well as the number of electrospun layers,the multi-gradient scaffold effectively sustained the release of Mg^(2+)over a period of 6 weeks.Additionally,this study provided insight into the mechanism of Mg^(2+)-induced nerve regeneration and confirmed that Mg^(2+)effectively promoted Schwann cell proliferation,migration,and transition to a repair phenotype.By employing transcriptome sequencing technology,the study identified the Wingless/integrase-1(Wnt)signaling pathway as a crucial mechanism influencing Schwann cell function during nerve regeneration.After implantation in 10 mm critically sized nerve defects in rats,the MgO/MgCO_(3)/PCL multi-gradient nanofiber combined with a 3D-engineered PCL nerve conduit showed enhanced axonal regeneration,remyelination,and reinnervation of muscle tissue 12 weeks post-surgery.In conclusion,this study successfully developed an innovative multi-gradient long-acting MgO/MgCO_(3)/PCL nanofiber with a tunable Mg^(2+)release property,which underscored the molecular mechanism of magnesium-encapsulated biomaterials in treating nervous system diseases and established a robust theoretical foundation for future clinical translation.展开更多
Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promi...Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair.Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing practices.Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration.In this study,we propose an endogenous stem cell recruitment strategy for cartilage repair.Based on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.展开更多
The development of an excellent,bioabsorbable hemostatic material for deep wound remains a challenge.In this work,a biodegradable cotton-like biomimetic fibrous mat of poly(L-lactic acid)(PLLA)was made by melt spinnin...The development of an excellent,bioabsorbable hemostatic material for deep wound remains a challenge.In this work,a biodegradable cotton-like biomimetic fibrous mat of poly(L-lactic acid)(PLLA)was made by melt spinning.Subsequently,SD composite was prepared by cross-linking sodium alginate(SA)with dopamine(DA).It was immobilized on the fibre surface,which inspired by mussel byssus.Finally,Fe^(3+)was loaded onto the 0.5SD/PLLA composite by chelation with the carboxyl of alginate and phenolic hydroxy of dopamine.The haemostasis experiment found that the hemostatic time 47 s in vitro.However,the bleeding volume was 0.097 g and hemostatic time was 23 s when 20Fe^(3+)-0.5SD/PLLA was applied in the haemostasis of the rat liver.As a result of its robust hydrophilicity and bouffant cotton-like structure,it could absorb a large water from blood,which could concentrate the component of blood and reduce the clotting time.Furthermore,the addition of Fe^(3+)in the 0.5SD/PLLA had a significant effect on improve hemostatic property.It also displayed excellent antibacterial property for Escherichia coli and Staphylococcus aureus.Notably,it possesses superior hemocompatibility,cytocompatibility and histocompatibility.Hence,20Fe^(3+)-0.5SD/PLLA has high potential application in haemostasis for clinical settings due to its outstanding properties.展开更多
Complete spinal cord injury(SCI)causes permanent locomotor,sensory and neurological dysfunctions.Targeting complex immunopathological microenvironment at SCI sites comprising inflammatory cytokines infiltration,oxidat...Complete spinal cord injury(SCI)causes permanent locomotor,sensory and neurological dysfunctions.Targeting complex immunopathological microenvironment at SCI sites comprising inflammatory cytokines infiltration,oxidative stress and massive neuronal apoptosis,the conductive oriented nanofiber felt with efficient ROS clearance,anti-inflammatory effect and accelerating neural regeneration is constructed by step-growth addition polymerization and electrostatic spinning technique for SCI repair.The formation of innovative Fe3+-PDA-PAT chelate in nanofiber felt enhances hydrophilic,antioxidant,antibacterial,hemostatic and binding factor capacities,thereby regulating immune microenvironment of SCI.With the capabilities of up-regulating COX5A and STAT6 expressions,down-regulating the expressions of IL1β,CD36,p-ERK,NFκB2 and NFκB signaling pathway proteins,the nanofiber felt attenuates oxidative stress injury,promotes M2 macrophage polarization and downregulates inflammatory response.After implantation into complete transection SCI rats,the nanofiber felt is revealed to recruit endogenous NSCs,induce the differentiation of NSCs into neurons while inhibit astrocytes formation and inflammation,reduces glia scar,and promotes angiogenesis,remyelination and neurological functional recovery.Overall,this innovative strategy provides a facile immune regulatory system to inhibit inflammatory response and accelerate nerve regeneration after SCI,and its targeted proteins and mechanisms are first elucidated,which holds great application promise in clinical treatment of complete SCI.展开更多
Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage.Hydrogel is widely used because it could provide rapid defect filling and proper structure supp...Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage.Hydrogel is widely used because it could provide rapid defect filling and proper structure support,and is biocompatible for cell aggregation and matrix deposition.Efforts have been made to seek suitable scaffolds for cartilage tissue engineering.Here Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties.Gelation time,swelling ratio,biodegradability and biocompatibility of the hydrogels were systematically characterized,and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair.Furthermore,the new hydrogel design introduces a pre-gel state before photo-crosslinking,where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition.This granted multiple administration routes to the hydrogels,which brings hydrogels the ability to adapt to complex clinical situations.Pulsed electromagnetic fields(PEMF)have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials.PEMF treatment offers a better clinical outcome with fewer,if any,side effects,and wildly used in musculoskeletal tissue repair.Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering.In this study,the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model,and the potential application of PEMF in cartilage tissue engineering were investigated.PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro,and facilitate chondrogenesis and cartilage repair in vivo.All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment,this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.展开更多
基金supported by the National Key R&D Program of China(2022YFB3808000)the National Natural Science Foundation of China(82402802,82404113,82302713,U23A20490)+6 种基金the China Postdoctoral Science Foundation(2023M742390)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012663,2023A1515220250,2023A1515111068)the Shenzhen Science and Technology Innovation Program(RCBS20231211090537061,JCYJ20230807095203007,JCYJ20230807095121041)the Shenzhen Key Medical Discipline Construction Fund(SZXK023)the Sanming Project of Medicine in Shenzhen(SZSM202211038)the Shenzhen High-level Hospital Construction Fund,and the Scientific Research Foundation of Peking University Shenzhen Hospital(LCYJZD2021005,KYQD2023244,KYQD2023245)The authors also gratefully acknowledged the kindly financial support provided by the Youth Talent Support Program of the China Association for Science and Technology,and the Top Young Talents of Foal Eagle Program of Fujian Province to Jin Zhang.
文摘Peripheral nerve defects present complex orthopedic challenges with limited efficacy of clinical interventions.The inadequate proliferation and dysfunction of Schwann cells within the nerve scaffold impede the effectiveness of nerve repair.Our previ-ous studies suggested the effectiveness of a magnesium-encapsulated bioactive hydrogel in repairing nerve defects.However,its rapid release of magnesium ions limited its efficacy to long-term nerve regeneration,and its molecular mechanism remains unclear.This study utilized electrospinning technology to fabricate a MgO/MgCO_(3)/polycaprolactone(PCL)multi-gradient nanofiber membrane for peripheral nerve regeneration.Our findings indicated that by carefully adjusting the concentration or proportion of rapidly degradable MgO and slowly degradable MgCO_(3),as well as the number of electrospun layers,the multi-gradient scaffold effectively sustained the release of Mg^(2+)over a period of 6 weeks.Additionally,this study provided insight into the mechanism of Mg^(2+)-induced nerve regeneration and confirmed that Mg^(2+)effectively promoted Schwann cell proliferation,migration,and transition to a repair phenotype.By employing transcriptome sequencing technology,the study identified the Wingless/integrase-1(Wnt)signaling pathway as a crucial mechanism influencing Schwann cell function during nerve regeneration.After implantation in 10 mm critically sized nerve defects in rats,the MgO/MgCO_(3)/PCL multi-gradient nanofiber combined with a 3D-engineered PCL nerve conduit showed enhanced axonal regeneration,remyelination,and reinnervation of muscle tissue 12 weeks post-surgery.In conclusion,this study successfully developed an innovative multi-gradient long-acting MgO/MgCO_(3)/PCL nanofiber with a tunable Mg^(2+)release property,which underscored the molecular mechanism of magnesium-encapsulated biomaterials in treating nervous system diseases and established a robust theoretical foundation for future clinical translation.
基金supported by the Shandong Provincial Higher Edu-cation Institutions“Youth Innovation Team Plan”Project(No.2022KJ280)“Stomatology+X”University and Hospital Integration Innovation Project of Binzhou Medical University(No.KQRH2024MS003)Initial Scientific Research Fund of Young Teachers in Binzhou Medical University(No.BY2021KYQD23).
文摘Critical-sized calvarial defects remain a formidable clinical challenge due to dyssynchronous immunomodulation-osteogenesis coupling and unregulated growth factor release.Here,a bioinspired porous core-shell microsphere system(GCI@HPPS)is developed,integrating hydroxyapatite(HA)-loaded shell,surfaceimmobilized SDF-1α,and IGF-1-encapsulated cores to immunomodulate osteoimmune microenvironment and osteogenesis promotion.The hierarchical architecture achieved spatiotemporally programmed release:HA degradation-dependent mineralization,SDF-1α-mediated BMSC chemotaxis,and sustained IGF-1 delivery,mimicking natural bone repair cascades.Dual covalent/vip-host crosslinking(GelMA/Ac-β-CD)enhanced compressive strength,while polydopamine functionalization of microspheres conferred electroactivity,hydro-philicity,ROS/RNS scavenging(97.29%ABTS•+elimination),antibacterial efficacy(>99.8%)and hemostasis.In vitro,GCI@HPPS mitigates oxidative stress,induces M2 macrophage polarization,and suppresses inflamma-tory cascades while concomitantly enhancing endogenous BMSC recruitment,proliferation,and osteogenic differentiation.Proteomics revealed a tetradic anti-inflammatory mechanisms of GCI@HPPS:NF-κB/P-JNK suppression,pro-inflammatory cytokines downregulation,mitochondrial oxidative modulation,and STAT6-driven M2 polarization.In vivo,GCI@HPPS achieved calvarial defect closure at 8 weeks through porous matrix-guided cellular infiltration,and SDF-1α/IGF-1-mediated chemotaxis,Rho/MAPK signaling pathway activation balancing osteoclast-osteoblast dynamics,stage-specific osteogenic induction and AGE-RAGE/VEGFcoupled angiogenesis-osteogenesis.This work pioneers a spatiotemporal delivery paradigm that coordinates inflammation modulation,stem cell recruitment,osteogenic differentiation,and mineralization phases,offering a promising approach for complex cranial reconstruction.
基金supported by grants from the National Natural Science Foundation of China(82172430 and 82272505)University Grants Committee,Research Grants Council of the Hong Kong Special Administrative Region,China(14108720,14121721,14202920,N_CUHK472/22,C7030-18G,T13-402/17-N and AoE/M-402/20)+1 种基金Heath Medical Research Fund(HMRF)Hong Kong(16170951,17180831,08190416 and 09203436)Hong Kong Innovation Technology Commission Funds(PRP/050/19FX).
文摘Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair.Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing practices.Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration.In this study,we propose an endogenous stem cell recruitment strategy for cartilage repair.Based on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.
基金supported by the Jilin Scientific and Technological Development Program(20200404110YY)National Natural Science Foundation of China(51673186).
文摘The development of an excellent,bioabsorbable hemostatic material for deep wound remains a challenge.In this work,a biodegradable cotton-like biomimetic fibrous mat of poly(L-lactic acid)(PLLA)was made by melt spinning.Subsequently,SD composite was prepared by cross-linking sodium alginate(SA)with dopamine(DA).It was immobilized on the fibre surface,which inspired by mussel byssus.Finally,Fe^(3+)was loaded onto the 0.5SD/PLLA composite by chelation with the carboxyl of alginate and phenolic hydroxy of dopamine.The haemostasis experiment found that the hemostatic time 47 s in vitro.However,the bleeding volume was 0.097 g and hemostatic time was 23 s when 20Fe^(3+)-0.5SD/PLLA was applied in the haemostasis of the rat liver.As a result of its robust hydrophilicity and bouffant cotton-like structure,it could absorb a large water from blood,which could concentrate the component of blood and reduce the clotting time.Furthermore,the addition of Fe^(3+)in the 0.5SD/PLLA had a significant effect on improve hemostatic property.It also displayed excellent antibacterial property for Escherichia coli and Staphylococcus aureus.Notably,it possesses superior hemocompatibility,cytocompatibility and histocompatibility.Hence,20Fe^(3+)-0.5SD/PLLA has high potential application in haemostasis for clinical settings due to its outstanding properties.
基金supported by the Youth program of Natural Science Foundation of Shandong Province(No.ZR2021QC057)Shandong Provincial Higher Education Institutions"Youth Innovation Team Plan"Project(No.2022KJ280)+2 种基金Initial Scientific Research Fund of Young Teachers in Binzhou Medical University(No.BY2021KYQD23)"Stomatology+X"College Integration Innovation Project of Binzhou medical university(No.KQRH2024MS003)the Basic research projects of the Yantai Science and Technology Innovation Development Plan(No.2023JCYJ080).
文摘Complete spinal cord injury(SCI)causes permanent locomotor,sensory and neurological dysfunctions.Targeting complex immunopathological microenvironment at SCI sites comprising inflammatory cytokines infiltration,oxidative stress and massive neuronal apoptosis,the conductive oriented nanofiber felt with efficient ROS clearance,anti-inflammatory effect and accelerating neural regeneration is constructed by step-growth addition polymerization and electrostatic spinning technique for SCI repair.The formation of innovative Fe3+-PDA-PAT chelate in nanofiber felt enhances hydrophilic,antioxidant,antibacterial,hemostatic and binding factor capacities,thereby regulating immune microenvironment of SCI.With the capabilities of up-regulating COX5A and STAT6 expressions,down-regulating the expressions of IL1β,CD36,p-ERK,NFκB2 and NFκB signaling pathway proteins,the nanofiber felt attenuates oxidative stress injury,promotes M2 macrophage polarization and downregulates inflammatory response.After implantation into complete transection SCI rats,the nanofiber felt is revealed to recruit endogenous NSCs,induce the differentiation of NSCs into neurons while inhibit astrocytes formation and inflammation,reduces glia scar,and promotes angiogenesis,remyelination and neurological functional recovery.Overall,this innovative strategy provides a facile immune regulatory system to inhibit inflammatory response and accelerate nerve regeneration after SCI,and its targeted proteins and mechanisms are first elucidated,which holds great application promise in clinical treatment of complete SCI.
基金This work was partially supported by grants from University Grants Committee,Research Grants Council of the Hong Kong Special Administrative Region,China(14108720,14121721,14202920,T13-402/17-N and AoE/M-402/20).
文摘Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage.Hydrogel is widely used because it could provide rapid defect filling and proper structure support,and is biocompatible for cell aggregation and matrix deposition.Efforts have been made to seek suitable scaffolds for cartilage tissue engineering.Here Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties.Gelation time,swelling ratio,biodegradability and biocompatibility of the hydrogels were systematically characterized,and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair.Furthermore,the new hydrogel design introduces a pre-gel state before photo-crosslinking,where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition.This granted multiple administration routes to the hydrogels,which brings hydrogels the ability to adapt to complex clinical situations.Pulsed electromagnetic fields(PEMF)have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials.PEMF treatment offers a better clinical outcome with fewer,if any,side effects,and wildly used in musculoskeletal tissue repair.Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering.In this study,the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model,and the potential application of PEMF in cartilage tissue engineering were investigated.PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro,and facilitate chondrogenesis and cartilage repair in vivo.All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment,this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.
