Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold...Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC_(50))of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal“dead ends”and“safe bets”for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogeneoxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.展开更多
Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation...Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.展开更多
Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomime...Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing.This highly in-tegrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen(rhCOLIII-MA),gelatin methacrylate(GelMA),and liposomes encapsulating SB431542 to target TGF-β1(Lip@SB).The rhCOLIII-MA/GelMA(CG)scaffold retained inherent biomaterial characteristics,exhibited tailored physicochemical properties,and demonstrated favorable biocompatibility.Moreover,the Lip@SB-loaded CG scaffold(CGL)effectively promoted in vitro wound healing,while enabling controlled release of SB431542 to inhibit pathological collagen deposition.In a full-thickness skin defect rat model,the CGL dermal scaffold combined with split-thickness skin graft(STSG)minimized scar contraction,stimulated functional neovascularization,and enhanced graft aesthetics comparable to normal skin.Remarkably,the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives.This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged,painful postoperative rehabilitation.展开更多
The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.T...The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.展开更多
Current modifications of Ti-based materials with porous scaffolds for achieving biological fixation often decrease corrosion fatigue strength(σ_(cf))of the resultant implants,thereby shortening their service lifes-pa...Current modifications of Ti-based materials with porous scaffolds for achieving biological fixation often decrease corrosion fatigue strength(σ_(cf))of the resultant implants,thereby shortening their service lifes-pan.To resolve this issue,in the present,a step-wise graded porous Ti-6Al-7Nb scaffold was additively manufactured on optimally surface mechanical attrition treated(SMATed)Ti-6Al-7Nb(specifically de-noted as S-Ti6Al7Nb)using laser powder bed fusion(PBF)technology.The microstructure,bond strength,residual stress distribution,and corrosion fatigue behavior of porous scaffolds modified S-Ti6Al7Nb were investigated and compared with those of mechanically polished Ti-6Al-7Nb(P-Ti6Al7Nb),S-Ti6Al7Nb,and porous scaffolds modified P-Ti6Al7Nb.Results showed that corrosion fatigue of porous scaffolds modi-fied Ti-6Al-7Nb was propagation controlled.Moreover,the crack propagation behavior in the PBF scaf-fold’s fusion zone(FZ)and heat-affected zone(HAZ),exhibiting insensitivity to the microstructural con-figurations characterized by columnar prior-βgrain(PBG)boundaries and acicularα''martensites,cou-pled with the PBF-induced residual tensile stresses in these regions,resulted in a considerable decrease inσ_(cf) for porous scaffolds modified P-Ti6Al7Nb compared to P-Ti6Al7Nb.In contrast,step-wise graded porous scaffold-modified S-Ti6Al7Nb demonstrated an improvedσ_(cf) which was even higher than that of P-Ti6Al7Nb.Such an advancement in corrosion fatigue strength is primarily attributed to the presence of residual compressive stresses within the underlying S-Ti6Al7Nb substrate,extending beyond FZ and HAZ.These stresses increased the crack propagation threshold,leading to crack deflection/branching and increased crack-path tortuosity,thereby synergistically markedly enhancing the crack propagation resis-tance of porous scaffolds modified S-Ti6Al7Nb.展开更多
Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and hi...Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.展开更多
Introduction It is necessary for an ideal bioceramic scaffold to have a suitable structure.The structure can affect the mechanical properties of the scaffold(i.e.,elastic modulus and compressive strength)and the biolo...Introduction It is necessary for an ideal bioceramic scaffold to have a suitable structure.The structure can affect the mechanical properties of the scaffold(i.e.,elastic modulus and compressive strength)and the biological properties of the scaffold(i.e.,degradability and cell growth rate).Lattice structure is a kind of periodic porous structure,which has some advantages of light weight and high strength,and is widely used in the preparation of bioceramic scaffolders.For the structure of the scaffold,high porosity and large pore size are important for bone growth,bone integration and promoting good mechanical interlocking between neighboring bones and the scaffold.However,scaffolds with a high porosity often lack mechanical strength.In addition,different parts of the bone have different structural requirements.In this paper,scaffolds with a non-uniform structure or a hierarchical structure were designed,with loose and porous exterior to facilitate cell adhesion,osteogenic differentiation and vascularization as well as relatively dense interior to provide sufficient mechanical support for bone repair.Methods In this work,composite ceramics scaffolds with 10%akermanite content were prepared by DLP technology.The scaffold had a high porosity outside to promote the growth of bone tissue,and a low porosity inside to withstand external forces.The compressive strength,fracture form,in-vitro degradation performance and bioactivity of graded bioceramic scaffolds were investigated.The models of scaffolds were imported into the DLP printer with a 405 nm light.The samples were printed with the intensity of 8 mJ/cm^(2)and a layer thickness of 50μm.Finally,the ceramic samples were sintered at 1100℃.The degradability of the hierarchical gyroid bioceramic scaffolds was evaluated through immersion in Tris-HCl solution and SBF solution at a ratio of 200 mL/g.The bioactivity of bioceramic was obtained via immersing them in SBF solution for two weeks.The concentrations of calcium,phosphate,silicon,and magnesium ions in the soaking solution were determined by an inductively coupled plasma optical emission spectrometer.Results and discussion In this work,a hierarchical Gyroid structure HA-AK10 scaffold(sintered at 1100℃)with a radial internal porosity of 50%and an external porosity of 70%is prepared,and the influence of structural form on the compressive strength and degradation performance of the scaffold is investigated.The biological activity of the bioceramics in vitro is also verified.The mechanical simulation results show that the stress distribution corresponds to the porosity distribution of the structure,and the low porosity is larger and the overall stress concentration phenomenon does not appear.After soaking in SBF solution,Si—OH is firstly formed on the surface of bioceramics,and then silicon gel layer is produced due to the presence of calcium and silicon ions.The silicon gel layer is dissociated into negatively charged groups under alkaline environment secondary adsorption of calcium ions and phosphate ions,forming amorphous calcium phosphate,and finally amorphous calcium phosphate crystals and adsorption of carbonate ions,forming carbonate hydroxyapatite.This indicates that the composite bioceramics have a good biological activity in-vitro and can provide a good environment for the growth of bone cells.A hierarchical Gyroid ceramic scaffold with a bone geometry is prepared via applying the hierarchical structure to the bone contour scaffold.The maximum load capacity of the hierarchical Gyroid ceramic scaffold is 8 times that of the uniform structure.Conclusions The hierarchical structure scaffold designed had good overall compressive performance,good degradation performance,and still maintained a good mechanical stability during degradation.In addition,in-vitro biological experimental results showed that the surface graded composite scaffold could have a good in-vitro biological activity and provide a good environment for bone cells.Compared to the heterosexual structure,the graded scaffold had greater mechanical properties.展开更多
Pyridazine has garnered increasing attention as a privileged scaffold and bioisosterism in drug discovery due to its unique structural characteristics.It can serve as a hydrogen bond acceptor when interacting with rec...Pyridazine has garnered increasing attention as a privileged scaffold and bioisosterism in drug discovery due to its unique structural characteristics.It can serve as a hydrogen bond acceptor when interacting with receptors due to its two adjacent nitrogen atoms.Upon conversion to pyridazinone,it exhibits the ability to act as both a hydrogen bond acceptor and donor,showcasing its versatility.This inherent flexibility has prompted extensive research exploring its bioactivity in pesticides and pharmaceuticals.In order to promote the development of pyridazine-based pesticides,this review provides a comprehensive summary of advancements for pyridazine-based pesticides on herbicidal(36.9%),insecticidal(26.2%),antifungal and antibacterial(24.6%),plant growth regulatory(10.8%),and antiviral activities(1.5%)from2000 to 2024.It serves as an invaluable reference and source of inspiration for agricultural scientists conducting future research.展开更多
The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel...The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel that leveraged the spatiotemporal immunomodulatory effects of a naturally degradable protein-based nanocomposite hydrogel.The hydrogel acted as a scaffold that created a favorable microenvironment for cartilage regeneration.The hydrogel recruited macrophages and human mesenchymal stem cells(hMSCs),which supported the growth and adhesion of osteoblasts,and degraded to provide nutrition.Silk protein nanoparticles were chemically cross-linked with kartogenin,and humanlike collagen was physically cross-linked with dexamethasone through hydrogen bonding.In the early stages of cartilage repair,a large quantity of dexamethasone was released.The dexamethasone acted as an anti-inflammatory agent and a spatiotemporal modulator of the polarization of M1 macrophages into M2 macrophages.In the middle and late stages of cartilage repair,kartogenin underwent sustained release from the hydrogel,inducing the differentiation of hMSCs into chondrocytes and maintaining chondrocyte stability.Therefore,kartogenin and dexamethasone acted synergistically to induce cartilage repair.In conclusion,we developed an integrated therapeutic system by constructing a cartilage regeneration microenvironment and inducing synergistic drug-based cartilage regeneration.The therapeutic system demonstrated satisfactory efficacy for repairing cartilage damage in rabbits.展开更多
Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffol...Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.展开更多
Metallic scaffolds with lightweight,low elastic modulus,and high energy-absorbing capacity are widely utilized in industrial applications but usually require post-heat treatment to enhance their comprehen-sive mechani...Metallic scaffolds with lightweight,low elastic modulus,and high energy-absorbing capacity are widely utilized in industrial applications but usually require post-heat treatment to enhance their comprehen-sive mechanical properties.However,it is unclear how to utilize the impact ofβ-Nb on the surrounding matrix for NiTiNb ternary alloys to achieve strength-ductility-superelasticity enhancement.Here,we pre-pared rhomboidal dodecahedral NiTiNb porous scaffolds with a porosity of 85.9%by additive manufac-turing.Subsequently,annealing treatment was employed to drastically reduce the phase transformation temperatures and expand the thermal hysteresis.Interestingly,the 850℃ annealed scaffold exhibited exceeding double compressive strength of the as-built sample,with a remarkable improvement in ductil-ity and superelasticity.From the microstructure perspective,high-temperature annealing caused a further eutectic reaction of the unmelted Nb particles with the NiTi matrix and the transformation of mesh-likeβ-Nb into dispersedly distributed sphericalβ-Nb particles.The microstructure evolution after defor-mation indicated that stress-induced martensitic transformation occurred in the matrix away from the NiTi-Nb eutectic region whereas almost no martensite formed nearbyβ-Nb particles.Atom probe tomog-raphy characterization revealed an element diffusion zone in several nanometers surrounding theβ-Nb particle,where the substitution of Nb with Ti led to a higher Ni:Ti atomic ratio,lowering transforma-tion temperatures.Molecular dynamics simulations illustrated thatβ-Nb particles can not only entangle dislocations internally,acting as reinforcements but also hinder the twin growth,contributing to strain hardening.This work elucidates the influence ofβ-Nb particles on the deformation mechanism of the NiTi-Nb eutectic region through in-depth atomic-scale investigation,which can provide inspiration for the improvement of comprehensive mechanical properties of NiTiNb alloys.展开更多
The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infan...The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.展开更多
Multienzyme cascades enable the sequential synthesis of complex chemicals by combining multiple catalytic processes in one pot,offering considerable time and cost savings compared to a series of separate batch reactio...Multienzyme cascades enable the sequential synthesis of complex chemicals by combining multiple catalytic processes in one pot,offering considerable time and cost savings compared to a series of separate batch reactions.However,challenges related to coordination and regulatory interplay among multiple enzymes reduce the catalytic efficiency of such cascades.Herein,we genetically programmed a scaffold framework that selectively and orthogonally recruits enzymes as designed.The system was then used to generate multienzyme complexes of D-allulose 3-epimerase(DAE),ribitol dehydrogenase(RDH),and formate dehydrogenase(FDH)for rare sugar production.This scaffolded multienzymatic assembly achieves a 10.4-fold enhancement in the catalytic performance compared to its unassembled counterparts,obtaining allitol yield of more than 95%.Molecular dynamics simulations revealed that shorter distances between neighboring enzymes in scaffold-mounted complexes facilitated the transfer of reaction intermediates.A dual-module catalytic system incorporating(1)scaffold-bound complexes of DAE,RDH,and FDH and(2)scaffold-bound complexes of alcohol dehydrogenase and NADH oxidase expressed intracellularly in E.coli was used to synthesize D-allulose from D-fructose.This system synthesized 90.6%D-allulose from 300 g L^(−1)D-fructose,with a space-time yield of 13.6 g L^(−1)h^(−1).Our work demonstrates the programmability and versatility of scaffold-based strategies for the advancement of multienzyme cascades.展开更多
In clinical practice,the irregular shapes of traumas pose a significant challenge in rapidly manufacturing personalized scaffolds.To address these challenges,inspired by LEGO■ bricks,this study proposed a novel conce...In clinical practice,the irregular shapes of traumas pose a significant challenge in rapidly manufacturing personalized scaffolds.To address these challenges,inspired by LEGO■ bricks,this study proposed a novel concept of modular scaffolds and developed an innovative system based on machine vision for their rapid and intelligent assembly tailored to defect shapes.Trapezoidal interfaces effectively connect standardized bone units based on magnesium-doped silicate calcium,ensuring high stability of the modular scaffolds,with compressive strength up to 135 MPa and bending strength up to 17 MPa.Through self-developed defect recognition and reconstruction algorithms,defect recognition and personalized assembly schemes for bone scaffolds can be achieved autonomously.Modular scaffolds seamlessly integrate with surrounding bone tissue,promoting new bone growth,with no apparent differences compared to fully 3D printed integral scaffolds in the skull and femur repair experiments.In summary,the adoption of modular scaffolds not only integrates personalization and standardization but also satisfies the optimal treatment window.展开更多
Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO...Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.展开更多
Regulating lithium(Li)plating/stripping behavior in three-dimensional(3D)conductive scaffolds is critical to stabilizing Li metal batteries(LMBs).Surface protrusions and roughness in these scaffolds can induce uneven ...Regulating lithium(Li)plating/stripping behavior in three-dimensional(3D)conductive scaffolds is critical to stabilizing Li metal batteries(LMBs).Surface protrusions and roughness in these scaffolds can induce uneven distributions of the electric fields and ionic concentrations,forming“hot spots.”Hot spots may cause uncontrollable Li dendrites growth,presenting significant challenges to the cycle stability and safety of LMBs.To address these issues,we construct a Li ionic conductive-dielectric gradient bifunctional interlayer(ICDL)onto a 3D Li-injected graphene/carbon nanotube scaffold(LGCF)via in situ reaction of exfoliated hexagonal boron nitride(fhBN)and molten Li.Microscopic and spectroscopic analyses reveal that ICDL consists of fhBN-rich outer layer and inner layer enriched with Li_(3)N and Li-boron composites(Li-B).The outer layer utilizes dielectric properties to effectively homogenize the electric field,while the inner layer ensures high Li ion conductivity.Moreover,DFT calculations indicate that ICDL can effectively adsorb Li and decrease the Li diffusion barrier,promoting enhanced Li ion transport.The modulation of Li kinetics by ICDL increases the critical length of the Li nucleus,enabling suppression of Li dendrite growth.Attributing to these advantages,the ICDL-coated LGCF(ICDL@LGCF)demonstrates impressive long-term cycle performances in both symmetric cells and full cells.展开更多
Porous metals fabricated via three-dimensional(3D)printing have attracted extensive attention in many fields owing to their open pores and customization potential.However,dense internal structures produced by the powd...Porous metals fabricated via three-dimensional(3D)printing have attracted extensive attention in many fields owing to their open pores and customization potential.However,dense internal structures produced by the powder bed fusion technique fails to meet the feature of porous materials in scenarios that demand large specific surface areas.Herein,we propose a strategy for 3D printing of titanium scaffolds featuring multiscale porous internal structures via powder modification and digital light processing(DLP).After modification,the titanium powders were composited with acrylic resin and maintained spherical shapes.Compared with the raw powder slurries,the modified powder slurries exhibited higher stability and preferable curing characteristics,and the depth sensitivity of the modified powder slurries with 45 vol%solid loading increased by approximately 72%.Green scaffolds were subsequently printed from the slurries with a solid loading reaching 45 vol%via DLP 3D printing.The scaffolds had macropores(pore diameters of approximately 1 mm)and internal open micropores(pore diameters of approximately 5.7-13.0μm)after sintering.Additionally,these small-featured(approximately 320μm)scaffolds retained sufficient compressive strength((70.01±3.53)MPa)even with high porosity(approximately 73.95%).This work can facilitate the fabrication of multiscale porous metal scaffolds with high solid loading slurries,offering potential for applications requiring high specific surface area ratios.展开更多
BACKGROUND Bioresorbable scaffolds(BRS)are a promising alternative to traditional drugeluting stents(DES)for the treatment of acute coronary syndrome(ACS).They offer the potential for complete resorption,which may red...BACKGROUND Bioresorbable scaffolds(BRS)are a promising alternative to traditional drugeluting stents(DES)for the treatment of acute coronary syndrome(ACS).They offer the potential for complete resorption,which may reduce long-term complications such as stent thrombosis and late restenosis.However,the safety,compatibility,and long-term outcomes of BRS in patients with intermediate to low-risk ACS have yet to be thoroughly investigated.AIM To investigate the safety,compatibility,and long-term outcomes of BRS in patients with intermediate to low-risk ACS.METHODS Patients with intermediate to low-risk ACS who underwent percutaneous coronary intervention with either DES or BRS,and were continuously recruited from January 2019 to June 2022 at a single center,were analyzed.Baseline data and clinical follow-up were collected for patients who underwent DES implantation(control group)and BRS implantation(observation group),and the survival outcomes and complications during a maximum follow-up period of 3 years were compared.The primary clinical endpoint was device-oriented composite endpoint(DoCE),representing the occurrence of one of the following events:Cardiac death,stent thrombosis,target vessel myocardial infarction,and clinically driven target lesion revascularization.Secondary endpoints included coronary artery bypass grafting,target vessel revascularization,and non-cardiac death.RESULTS A total of 128 patients were included in this study,with an average age of 63 years.Among them,95 were male(74%).The study involved treatment of 201 blood vessels:87(43%)received BRS,and 114(57%)received DES.A total of 97 patients completed the full 3-year follow-up.During this period,5 patients(17%)in the observation group and 7 patients(16%)in the control group experienced a major cardiovascular event(DoCE).At the 1-year follow-up,7 patients(15%)in the observation group and 6 patients(10%)in the control group experienced DoCE,and this difference was statistically significant(P<0.05).At the 2-year follow-up,there was also a significant difference between the two groups in the number of patients who needed repeat treatment of the target blood vessel(P<0.05).In the observation group,18 patients(33%)underwent follow-up coronary angiography.During the follow-up period,one patient in the observation group was found to have re-narrowing in the proximal and middle segments of the left anterior descending artery,possibly due to BRS collapse.Another patient in the observation group developed chronic total occlusion in multiple vessels at the 3-year follow-up and underwent coronary artery bypass grafting.CONCLUSION In low-to intermediate-risk ACS patients,those who got BRS had their first major heart event sooner than those who got DES.BRS is more tissue-friendly,yet over three years both groups had about the same amount of problems-only a few BRS patients still saw the scaffold collapse or the vessel slowly block.展开更多
Achieving exact printing fidelity in polymer-based bone regeneration scaffolds through additive manufacturing,particularly those of dispensing-type,remains a significant challenge.During fabrication,scaffolds often de...Achieving exact printing fidelity in polymer-based bone regeneration scaffolds through additive manufacturing,particularly those of dispensing-type,remains a significant challenge.During fabrication,scaffolds often deviate from the intended design geometry,which can negatively affect their performance.Additionally,achieving mechanical properties similar to natural bone in scaffolds remains challenging.Therefore,this study introduces the Hybrid Modified Cubic-Honeycomb Plate(hybrid MCHP)structure to improve printing fidelity and mechanical properties over previous bone regeneration scaffolds through innovative geometry design.This hybrid MCHP scaffold was inspired by cubic honeycomb and plate-lattice structures due to their excellent mechanical performance and well-optimized geometry,which ensure optimal printability.The effective elastic stiffness of the proposed structure and control group was predicted using a numerical Asymptotic Expansion Homogenization(AEH)model.Bone regeneration scaffolds were fabricated using Polycaprolactone(PCL)and a 3D printer with a Precision Extrusion Deposition(PED)system.Printing fidelity in manufactured scaffolds was then evaluated,resulting in a printing fidelity of 97.93±1.1%for the hybrid MCHP-structure scaffold(compared to 82.31±3.6%and 92.00±2.5%in the case of Kagome-structure and modified honeycomb(MHC)-structure scaffolds,which are the control groups).Mechanical testing of the hybrid MCHP-structure scaffold using a Universal Testing Machine(UTM)depicted similarity with 91.1%of the numerical estimated effective elastic stiffness(compared to 82.8%and 79.0%in the case of Kagome-structure and MHC-structure scaffolds,which serve as the control groups).The biological potential of the scaffolds was evaluated through in vitro studies using MC3T3-E1 pre-osteoblasts.The CCK-8 assay showed significantly enhanced cell viability and proliferation on the hybrid MCHP scaffold at all time points(days 1,7,and 14),consistently outperforming the Kagome and MHC scaffolds.Additionally,immunofluorescence staining analysis revealed abundant focal adhesions and uniform nuclear distribution,highlighting the superior cytocompatibility and effective support for cellular activity of the hybrid MCHP scaffold.展开更多
This article takes the theory of power space as an starting point for an in-depth comparison of the clan hall in White Deer Plains and the scaffold in The Scarlet Letter.In White Deer Plains,The clan hall,as the core ...This article takes the theory of power space as an starting point for an in-depth comparison of the clan hall in White Deer Plains and the scaffold in The Scarlet Letter.In White Deer Plains,The clan hall,as the core place of family activities,has a spatial layout that implies a hierarchy of power,and the taboos it represents relate to various aspects such as marriage and bloodline,and maintains the order of the clan through a variety of disciplinary mechanisms.The scaffold in The Scarlet Letter is located in the town’s central square and is a symbol of Puritan social power and moral discipline,behind which Puritan taboos influence people’s behaviors and public punishments are used to achieve the discipline of the people.The research reveals the similarities and differences between the two in terms of sources of power,modes of operation and influence,and opens up new horizons for cross-cultural literary studies.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82173699 and 32200531)Shanghai Jiao Tong University Trans-Med Awards Research,China(STAR Project No.:20230101)Shanghai Science and Technol-ogy Commission,China(Grant No.:23DZ2290600).
文摘Numerous c-mesenchymal-epithelial transition(c-MET)inhibitors have been reported as potential anticancer agents.However,most fail to enter clinical trials owing to poor efficacy or drug resistance.To date,the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed.In this study,we constructed the largest c-MET dataset,which included 2,278 molecules with different struc-tures,by inhibiting the half maximal inhibitory concentration(IC_(50))of kinase activity.No significant differences in drug-like properties were observed between active molecules(1,228)and inactive mol-ecules(1,050),including chemical space coverage,physicochemical properties,and absorption,distri-bution,metabolism,excretion,and toxicity(ADMET)profiles.The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding(t-SNE)high-dimensional data.Further clustering and chemical space networks(CSNs)analyses revealed commonly used scaffolds for c-MET inhibitors,such as M5,M7,and M8.Activity cliffs and structural alerts were used to reveal“dead ends”and“safe bets”for c-MET,as well as dominant structural fragments consisting of pyr-idazinones,triazoles,and pyrazines.Finally,the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules,including at least three aromatic het-erocycles,five aromatic nitrogen atoms,and eight nitrogeneoxygen atoms.Overall,our analyses revealed potential structure-activity relationship(SAR)patterns for c-MET inhibitors,which can inform the screening of new compounds and guide future optimization efforts.
基金supported by the National Natural Science Foundation of China(Nos.51975400 and 62031022)the Shanxi Provincial Key Medical Scientific Research Project(No.2020XM06)+2 种基金the Shanxi Provincial Basic Research Project(Nos.202103021221006,20210302123040,and 202103021223069)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2021L044)the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2022SX-TD026).
文摘Dermal substitutes have provided a template for the regeneration and reconstruction of the dermis.However,the healed skin tissue often exhibits abnormal morphology and functionality,including scarring and inflammation.In this study,a composite bioink composed of methacrylated gelatin(GelMA)and chitosan oligosaccharide(COS)was proposed for printing a dermal scaffold using digital light processing(DLP)technology.The GelMA/COS bioink exhibited suitable porosity,swelling,degradation rate,and mechanical properties.The inclusion of COS demonstrated antibacterial effects against both Gram positive and Gram-negative bacteria,while simultaneously fostering the proliferation of human dermal fibroblasts(HDFs).Additionally,the application of COS could effectively reduce the expression levels of fibrosis-related genes,such as collagen I,collagen III,and fibronectin I.The three-dimensionally printed cell-laden dermal scaffold exhibited excellent shape fidelity and high cellular viability,facilitating the extension of HDFs along the scaffold and the simultaneous secretion of extracellular matrix proteins.Furthermore,the HDF-laden dermal scaffold transplanted into full-thickness skin defect sites in nude mice was shown to accelerate wound closure,reduce inflammation,and improve wound healing.Overall,the DLP-printed dermal scaffold provides an appealing approach for effectively treating full-thickness skin defects in clinical settings.
基金supported by the National Natural Science Foundation of China(No.82272297).
文摘Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing.This highly in-tegrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen(rhCOLIII-MA),gelatin methacrylate(GelMA),and liposomes encapsulating SB431542 to target TGF-β1(Lip@SB).The rhCOLIII-MA/GelMA(CG)scaffold retained inherent biomaterial characteristics,exhibited tailored physicochemical properties,and demonstrated favorable biocompatibility.Moreover,the Lip@SB-loaded CG scaffold(CGL)effectively promoted in vitro wound healing,while enabling controlled release of SB431542 to inhibit pathological collagen deposition.In a full-thickness skin defect rat model,the CGL dermal scaffold combined with split-thickness skin graft(STSG)minimized scar contraction,stimulated functional neovascularization,and enhanced graft aesthetics comparable to normal skin.Remarkably,the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives.This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged,painful postoperative rehabilitation.
基金supported by the National Natural Science Foundation of China(Grant No.52473121,52403370 and 52221006)Fundamental Research Funds for the Central Universities(buctrc202020,buctrc202312).
文摘The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.
基金the National Key Research and Development Program of China(Grant No.2023YFC2412600)the National Natural Science Foundation of China(Grant No.51971171)for financially supporting this work.
文摘Current modifications of Ti-based materials with porous scaffolds for achieving biological fixation often decrease corrosion fatigue strength(σ_(cf))of the resultant implants,thereby shortening their service lifes-pan.To resolve this issue,in the present,a step-wise graded porous Ti-6Al-7Nb scaffold was additively manufactured on optimally surface mechanical attrition treated(SMATed)Ti-6Al-7Nb(specifically de-noted as S-Ti6Al7Nb)using laser powder bed fusion(PBF)technology.The microstructure,bond strength,residual stress distribution,and corrosion fatigue behavior of porous scaffolds modified S-Ti6Al7Nb were investigated and compared with those of mechanically polished Ti-6Al-7Nb(P-Ti6Al7Nb),S-Ti6Al7Nb,and porous scaffolds modified P-Ti6Al7Nb.Results showed that corrosion fatigue of porous scaffolds modi-fied Ti-6Al-7Nb was propagation controlled.Moreover,the crack propagation behavior in the PBF scaf-fold’s fusion zone(FZ)and heat-affected zone(HAZ),exhibiting insensitivity to the microstructural con-figurations characterized by columnar prior-βgrain(PBG)boundaries and acicularα''martensites,cou-pled with the PBF-induced residual tensile stresses in these regions,resulted in a considerable decrease inσ_(cf) for porous scaffolds modified P-Ti6Al7Nb compared to P-Ti6Al7Nb.In contrast,step-wise graded porous scaffold-modified S-Ti6Al7Nb demonstrated an improvedσ_(cf) which was even higher than that of P-Ti6Al7Nb.Such an advancement in corrosion fatigue strength is primarily attributed to the presence of residual compressive stresses within the underlying S-Ti6Al7Nb substrate,extending beyond FZ and HAZ.These stresses increased the crack propagation threshold,leading to crack deflection/branching and increased crack-path tortuosity,thereby synergistically markedly enhancing the crack propagation resis-tance of porous scaffolds modified S-Ti6Al7Nb.
基金supported by the Innovative Research Group Project of the National Natural Science Foundation of China(T2121004)Key Programme(52235007)National Outstanding Youth Foundation of China(52325504).
文摘Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.
文摘Introduction It is necessary for an ideal bioceramic scaffold to have a suitable structure.The structure can affect the mechanical properties of the scaffold(i.e.,elastic modulus and compressive strength)and the biological properties of the scaffold(i.e.,degradability and cell growth rate).Lattice structure is a kind of periodic porous structure,which has some advantages of light weight and high strength,and is widely used in the preparation of bioceramic scaffolders.For the structure of the scaffold,high porosity and large pore size are important for bone growth,bone integration and promoting good mechanical interlocking between neighboring bones and the scaffold.However,scaffolds with a high porosity often lack mechanical strength.In addition,different parts of the bone have different structural requirements.In this paper,scaffolds with a non-uniform structure or a hierarchical structure were designed,with loose and porous exterior to facilitate cell adhesion,osteogenic differentiation and vascularization as well as relatively dense interior to provide sufficient mechanical support for bone repair.Methods In this work,composite ceramics scaffolds with 10%akermanite content were prepared by DLP technology.The scaffold had a high porosity outside to promote the growth of bone tissue,and a low porosity inside to withstand external forces.The compressive strength,fracture form,in-vitro degradation performance and bioactivity of graded bioceramic scaffolds were investigated.The models of scaffolds were imported into the DLP printer with a 405 nm light.The samples were printed with the intensity of 8 mJ/cm^(2)and a layer thickness of 50μm.Finally,the ceramic samples were sintered at 1100℃.The degradability of the hierarchical gyroid bioceramic scaffolds was evaluated through immersion in Tris-HCl solution and SBF solution at a ratio of 200 mL/g.The bioactivity of bioceramic was obtained via immersing them in SBF solution for two weeks.The concentrations of calcium,phosphate,silicon,and magnesium ions in the soaking solution were determined by an inductively coupled plasma optical emission spectrometer.Results and discussion In this work,a hierarchical Gyroid structure HA-AK10 scaffold(sintered at 1100℃)with a radial internal porosity of 50%and an external porosity of 70%is prepared,and the influence of structural form on the compressive strength and degradation performance of the scaffold is investigated.The biological activity of the bioceramics in vitro is also verified.The mechanical simulation results show that the stress distribution corresponds to the porosity distribution of the structure,and the low porosity is larger and the overall stress concentration phenomenon does not appear.After soaking in SBF solution,Si—OH is firstly formed on the surface of bioceramics,and then silicon gel layer is produced due to the presence of calcium and silicon ions.The silicon gel layer is dissociated into negatively charged groups under alkaline environment secondary adsorption of calcium ions and phosphate ions,forming amorphous calcium phosphate,and finally amorphous calcium phosphate crystals and adsorption of carbonate ions,forming carbonate hydroxyapatite.This indicates that the composite bioceramics have a good biological activity in-vitro and can provide a good environment for the growth of bone cells.A hierarchical Gyroid ceramic scaffold with a bone geometry is prepared via applying the hierarchical structure to the bone contour scaffold.The maximum load capacity of the hierarchical Gyroid ceramic scaffold is 8 times that of the uniform structure.Conclusions The hierarchical structure scaffold designed had good overall compressive performance,good degradation performance,and still maintained a good mechanical stability during degradation.In addition,in-vitro biological experimental results showed that the surface graded composite scaffold could have a good in-vitro biological activity and provide a good environment for bone cells.Compared to the heterosexual structure,the graded scaffold had greater mechanical properties.
基金the financial support from the National Key Research and Development Program of China(No.2021YFD1700102)the National Natural Science Foundation of China(No.32472608)+3 种基金the Guizhou Provincial Fundation for Excellent Scholars Program(No.GCC[2023]069)the Central Government Guides Local Science and Technology Development Fund Projects(No.Qiankehezhongyindi[2024]007)the Guizhou Province Program of Major Scientific and Technological(No.Qiankehechengguo[2024]zhongda007)the Central Government Guides Local Science and Technology Development Fund Projects(No.Qiankehezhongyindi(2023)001)。
文摘Pyridazine has garnered increasing attention as a privileged scaffold and bioisosterism in drug discovery due to its unique structural characteristics.It can serve as a hydrogen bond acceptor when interacting with receptors due to its two adjacent nitrogen atoms.Upon conversion to pyridazinone,it exhibits the ability to act as both a hydrogen bond acceptor and donor,showcasing its versatility.This inherent flexibility has prompted extensive research exploring its bioactivity in pesticides and pharmaceuticals.In order to promote the development of pyridazine-based pesticides,this review provides a comprehensive summary of advancements for pyridazine-based pesticides on herbicidal(36.9%),insecticidal(26.2%),antifungal and antibacterial(24.6%),plant growth regulatory(10.8%),and antiviral activities(1.5%)from2000 to 2024.It serves as an invaluable reference and source of inspiration for agricultural scientists conducting future research.
基金supported by the National Key Research and Development Program of China(2019YFA0905200).
文摘The treatment of prolonged inflammation and cartilage damage due to osteoarthritis(OA)is a major clinical challenge.We developed a comprehensive cartilage repair therapy using a dual drug-loaded nanocomposite hydrogel that leveraged the spatiotemporal immunomodulatory effects of a naturally degradable protein-based nanocomposite hydrogel.The hydrogel acted as a scaffold that created a favorable microenvironment for cartilage regeneration.The hydrogel recruited macrophages and human mesenchymal stem cells(hMSCs),which supported the growth and adhesion of osteoblasts,and degraded to provide nutrition.Silk protein nanoparticles were chemically cross-linked with kartogenin,and humanlike collagen was physically cross-linked with dexamethasone through hydrogen bonding.In the early stages of cartilage repair,a large quantity of dexamethasone was released.The dexamethasone acted as an anti-inflammatory agent and a spatiotemporal modulator of the polarization of M1 macrophages into M2 macrophages.In the middle and late stages of cartilage repair,kartogenin underwent sustained release from the hydrogel,inducing the differentiation of hMSCs into chondrocytes and maintaining chondrocyte stability.Therefore,kartogenin and dexamethasone acted synergistically to induce cartilage repair.In conclusion,we developed an integrated therapeutic system by constructing a cartilage regeneration microenvironment and inducing synergistic drug-based cartilage regeneration.The therapeutic system demonstrated satisfactory efficacy for repairing cartilage damage in rabbits.
基金supported by grants from the China Postdoctoral Science Foundation(Nos.2022TQ0397,2022MD723744,2022M710564,2022M720603)Natural Science Foundation of China(Nos.82272553,82102571,81974346,8210257,82472404)+8 种基金Chongqing Municipal Medical Youth Talent Support Program,Chongqing,China(No.YXQN202408)Natural Science Foundation of Chongqing,China(Nos.CSTB2022NSCQ-MSX0089,CSTB2022NSCQ-MSX0104,CSTB2024NSCQMSX0532)Joint Medical Research Project of Health Commission&Science and Technology Bureau of Chongqing,China(No.2024QNXM032)Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province(No.2023ZYD0071)National Natural Science Foundation of Sichuan(No.24NSFSC1274)Project of Innovative Science Research for Postgraduate of Chongqing Municipal Education Committee,Chongqing,China(Nos.CYS22389,CYB240224)National Natural Science Foundation of Sichuan(No.2024NSFSC0678)Research Project of the Affiliated Hospital of North Sichuan Medical College(Nos.2023ZD002,2023-2ZD001,2024JB001)Disciplines Construction Program of The Third Affiliated Hospital of Chongqing Medical University(Nos.KY23035,KY23041).
文摘Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.
基金financial supports of National Natural Science Foundation of China under Grant Nos.52274387 and 52311530772.
文摘Metallic scaffolds with lightweight,low elastic modulus,and high energy-absorbing capacity are widely utilized in industrial applications but usually require post-heat treatment to enhance their comprehen-sive mechanical properties.However,it is unclear how to utilize the impact ofβ-Nb on the surrounding matrix for NiTiNb ternary alloys to achieve strength-ductility-superelasticity enhancement.Here,we pre-pared rhomboidal dodecahedral NiTiNb porous scaffolds with a porosity of 85.9%by additive manufac-turing.Subsequently,annealing treatment was employed to drastically reduce the phase transformation temperatures and expand the thermal hysteresis.Interestingly,the 850℃ annealed scaffold exhibited exceeding double compressive strength of the as-built sample,with a remarkable improvement in ductil-ity and superelasticity.From the microstructure perspective,high-temperature annealing caused a further eutectic reaction of the unmelted Nb particles with the NiTi matrix and the transformation of mesh-likeβ-Nb into dispersedly distributed sphericalβ-Nb particles.The microstructure evolution after defor-mation indicated that stress-induced martensitic transformation occurred in the matrix away from the NiTi-Nb eutectic region whereas almost no martensite formed nearbyβ-Nb particles.Atom probe tomog-raphy characterization revealed an element diffusion zone in several nanometers surrounding theβ-Nb particle,where the substitution of Nb with Ti led to a higher Ni:Ti atomic ratio,lowering transforma-tion temperatures.Molecular dynamics simulations illustrated thatβ-Nb particles can not only entangle dislocations internally,acting as reinforcements but also hinder the twin growth,contributing to strain hardening.This work elucidates the influence ofβ-Nb particles on the deformation mechanism of the NiTi-Nb eutectic region through in-depth atomic-scale investigation,which can provide inspiration for the improvement of comprehensive mechanical properties of NiTiNb alloys.
文摘The ability to replicate the microenvironment of the human body through the fabrication of scaffolds is a significant achievement in the biomedical field.However,the search for the ideal scaffold is still in its infancy and there are significant challenges to overcome.In the modern era,the scientific community is increasingly turned to natural substances due to their superior biological ability,lower cost,biodegradability,and lower toxicity than synthetic lab-made products.Chitosan is a well-known polysaccharide that has recently garnered a high amount of attention for its biological activities,especially in 3D bone tissue engineering.Chitosan closely matches the native tissues and thus stands out as a popular candidate for bioprinting.This review focuses on the potential of chitosan-based scaffolds for advancements and the drawbacks in bone treatment.Chitosan-based nanocomposites have exhibited strong mechanical strength,water-trapping ability,cellular interaction,and biodegradability.Chitosan derivatives have also encouraged and provided different routes for treatment and enhanced biological activities.3D tailored bioprinting has opened new doors for designing and manufacturing scaffolds with biological,mechanical,and topographical properties.
文摘Multienzyme cascades enable the sequential synthesis of complex chemicals by combining multiple catalytic processes in one pot,offering considerable time and cost savings compared to a series of separate batch reactions.However,challenges related to coordination and regulatory interplay among multiple enzymes reduce the catalytic efficiency of such cascades.Herein,we genetically programmed a scaffold framework that selectively and orthogonally recruits enzymes as designed.The system was then used to generate multienzyme complexes of D-allulose 3-epimerase(DAE),ribitol dehydrogenase(RDH),and formate dehydrogenase(FDH)for rare sugar production.This scaffolded multienzymatic assembly achieves a 10.4-fold enhancement in the catalytic performance compared to its unassembled counterparts,obtaining allitol yield of more than 95%.Molecular dynamics simulations revealed that shorter distances between neighboring enzymes in scaffold-mounted complexes facilitated the transfer of reaction intermediates.A dual-module catalytic system incorporating(1)scaffold-bound complexes of DAE,RDH,and FDH and(2)scaffold-bound complexes of alcohol dehydrogenase and NADH oxidase expressed intracellularly in E.coli was used to synthesize D-allulose from D-fructose.This system synthesized 90.6%D-allulose from 300 g L^(−1)D-fructose,with a space-time yield of 13.6 g L^(−1)h^(−1).Our work demonstrates the programmability and versatility of scaffold-based strategies for the advancement of multienzyme cascades.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LY22E050011)National Natural Science Foundation of China(T2121004,51805475)。
文摘In clinical practice,the irregular shapes of traumas pose a significant challenge in rapidly manufacturing personalized scaffolds.To address these challenges,inspired by LEGO■ bricks,this study proposed a novel concept of modular scaffolds and developed an innovative system based on machine vision for their rapid and intelligent assembly tailored to defect shapes.Trapezoidal interfaces effectively connect standardized bone units based on magnesium-doped silicate calcium,ensuring high stability of the modular scaffolds,with compressive strength up to 135 MPa and bending strength up to 17 MPa.Through self-developed defect recognition and reconstruction algorithms,defect recognition and personalized assembly schemes for bone scaffolds can be achieved autonomously.Modular scaffolds seamlessly integrate with surrounding bone tissue,promoting new bone growth,with no apparent differences compared to fully 3D printed integral scaffolds in the skull and femur repair experiments.In summary,the adoption of modular scaffolds not only integrates personalization and standardization but also satisfies the optimal treatment window.
基金supported by the following funds:The National Natural Science Foundation of China(Nos.52275393,51935014,and 82072084)Jiangxi Provincial Natural Science Foundation of China(No.20224ACB204013)+2 种基金The Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performancethe National Key Research and Development Program of China(No.2023YFB4605800)the Independent Exploration and Innovation Project of Central South University(No.1053320221707).
文摘Fast electron-hole recombination issues during titanium dioxide(TiO_(2))photocatalysis limit its application in preventing bacterial infection during bone defect repair.In this study,TiO_(2)@reduced graphene oxide(rGO)composites were synthesized using a hydrothermal method in which rGO,which possesses very high electrical conductivity,promotes the separation of photoelectron-hole pairs of TiO_(2),thus improving the efficiency of photocatalytic production of reactive oxygen species(ROS).Subsequently,TiO_(2)@rGO composites were introduced into poly-L-lactic acid(PLLA)to prepare bone scaffolds with photocatalytic antibacterial function via selective laser sintering.The results showed that TiO_(2)grew on the surface of rGO and formed a covalent bond connection(Ti-O-C)with rGO.A decreased electrochemical impedance of TiO_(2)@rGO composites was observed,and the transient photocurrent intensity increased from 0.05 to 0.5μA/cm^(2).Analysis of electron spin resonance found that the photocatalytic products of TiO_(2)were·OH and·O^(2-),two kinds of ROS capable of killing bacteria via disrupting the structure of the bacterial membrane in vitro.Antibacterial experiments showed that the PLLA/TiO_(2)@rGO scaffolds had good antibacterial properties against Escherichia coli and Staphylococcus aureus.Finally,we report that these scaffolds exhibited both enhanced mechanical properties due to the addition of TiO_(2)@rGO as a reinforcement material and good biocompatibility during cell proliferation.
基金the financial support from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2023R1A2C2007699 and 2022R1A6A1A0306303912)the Nano Material Technology Development Program through the NRF funded by the Ministry of Science and ICT (NRF-2015M3A7B6027970)the Technology Innovation Program by the Ministry of Trade, Industry & Energy (RS-202300236794)
文摘Regulating lithium(Li)plating/stripping behavior in three-dimensional(3D)conductive scaffolds is critical to stabilizing Li metal batteries(LMBs).Surface protrusions and roughness in these scaffolds can induce uneven distributions of the electric fields and ionic concentrations,forming“hot spots.”Hot spots may cause uncontrollable Li dendrites growth,presenting significant challenges to the cycle stability and safety of LMBs.To address these issues,we construct a Li ionic conductive-dielectric gradient bifunctional interlayer(ICDL)onto a 3D Li-injected graphene/carbon nanotube scaffold(LGCF)via in situ reaction of exfoliated hexagonal boron nitride(fhBN)and molten Li.Microscopic and spectroscopic analyses reveal that ICDL consists of fhBN-rich outer layer and inner layer enriched with Li_(3)N and Li-boron composites(Li-B).The outer layer utilizes dielectric properties to effectively homogenize the electric field,while the inner layer ensures high Li ion conductivity.Moreover,DFT calculations indicate that ICDL can effectively adsorb Li and decrease the Li diffusion barrier,promoting enhanced Li ion transport.The modulation of Li kinetics by ICDL increases the critical length of the Li nucleus,enabling suppression of Li dendrite growth.Attributing to these advantages,the ICDL-coated LGCF(ICDL@LGCF)demonstrates impressive long-term cycle performances in both symmetric cells and full cells.
基金supported by the National Natural Science Foundation of China(Nos.52405326,52105588 and 52075421)the Key Research and Development Program of Shaanxi(Nos.2024GX-YBXM-222 and 2023-YBSF-276)。
文摘Porous metals fabricated via three-dimensional(3D)printing have attracted extensive attention in many fields owing to their open pores and customization potential.However,dense internal structures produced by the powder bed fusion technique fails to meet the feature of porous materials in scenarios that demand large specific surface areas.Herein,we propose a strategy for 3D printing of titanium scaffolds featuring multiscale porous internal structures via powder modification and digital light processing(DLP).After modification,the titanium powders were composited with acrylic resin and maintained spherical shapes.Compared with the raw powder slurries,the modified powder slurries exhibited higher stability and preferable curing characteristics,and the depth sensitivity of the modified powder slurries with 45 vol%solid loading increased by approximately 72%.Green scaffolds were subsequently printed from the slurries with a solid loading reaching 45 vol%via DLP 3D printing.The scaffolds had macropores(pore diameters of approximately 1 mm)and internal open micropores(pore diameters of approximately 5.7-13.0μm)after sintering.Additionally,these small-featured(approximately 320μm)scaffolds retained sufficient compressive strength((70.01±3.53)MPa)even with high porosity(approximately 73.95%).This work can facilitate the fabrication of multiscale porous metal scaffolds with high solid loading slurries,offering potential for applications requiring high specific surface area ratios.
文摘BACKGROUND Bioresorbable scaffolds(BRS)are a promising alternative to traditional drugeluting stents(DES)for the treatment of acute coronary syndrome(ACS).They offer the potential for complete resorption,which may reduce long-term complications such as stent thrombosis and late restenosis.However,the safety,compatibility,and long-term outcomes of BRS in patients with intermediate to low-risk ACS have yet to be thoroughly investigated.AIM To investigate the safety,compatibility,and long-term outcomes of BRS in patients with intermediate to low-risk ACS.METHODS Patients with intermediate to low-risk ACS who underwent percutaneous coronary intervention with either DES or BRS,and were continuously recruited from January 2019 to June 2022 at a single center,were analyzed.Baseline data and clinical follow-up were collected for patients who underwent DES implantation(control group)and BRS implantation(observation group),and the survival outcomes and complications during a maximum follow-up period of 3 years were compared.The primary clinical endpoint was device-oriented composite endpoint(DoCE),representing the occurrence of one of the following events:Cardiac death,stent thrombosis,target vessel myocardial infarction,and clinically driven target lesion revascularization.Secondary endpoints included coronary artery bypass grafting,target vessel revascularization,and non-cardiac death.RESULTS A total of 128 patients were included in this study,with an average age of 63 years.Among them,95 were male(74%).The study involved treatment of 201 blood vessels:87(43%)received BRS,and 114(57%)received DES.A total of 97 patients completed the full 3-year follow-up.During this period,5 patients(17%)in the observation group and 7 patients(16%)in the control group experienced a major cardiovascular event(DoCE).At the 1-year follow-up,7 patients(15%)in the observation group and 6 patients(10%)in the control group experienced DoCE,and this difference was statistically significant(P<0.05).At the 2-year follow-up,there was also a significant difference between the two groups in the number of patients who needed repeat treatment of the target blood vessel(P<0.05).In the observation group,18 patients(33%)underwent follow-up coronary angiography.During the follow-up period,one patient in the observation group was found to have re-narrowing in the proximal and middle segments of the left anterior descending artery,possibly due to BRS collapse.Another patient in the observation group developed chronic total occlusion in multiple vessels at the 3-year follow-up and underwent coronary artery bypass grafting.CONCLUSION In low-to intermediate-risk ACS patients,those who got BRS had their first major heart event sooner than those who got DES.BRS is more tissue-friendly,yet over three years both groups had about the same amount of problems-only a few BRS patients still saw the scaffold collapse or the vessel slowly block.
基金supported by a National Research Foundation of Korea(NRF)grant funded by Korean government(Nos.NRF-2022R1A4A1028747 and RS-2024-00344151).
文摘Achieving exact printing fidelity in polymer-based bone regeneration scaffolds through additive manufacturing,particularly those of dispensing-type,remains a significant challenge.During fabrication,scaffolds often deviate from the intended design geometry,which can negatively affect their performance.Additionally,achieving mechanical properties similar to natural bone in scaffolds remains challenging.Therefore,this study introduces the Hybrid Modified Cubic-Honeycomb Plate(hybrid MCHP)structure to improve printing fidelity and mechanical properties over previous bone regeneration scaffolds through innovative geometry design.This hybrid MCHP scaffold was inspired by cubic honeycomb and plate-lattice structures due to their excellent mechanical performance and well-optimized geometry,which ensure optimal printability.The effective elastic stiffness of the proposed structure and control group was predicted using a numerical Asymptotic Expansion Homogenization(AEH)model.Bone regeneration scaffolds were fabricated using Polycaprolactone(PCL)and a 3D printer with a Precision Extrusion Deposition(PED)system.Printing fidelity in manufactured scaffolds was then evaluated,resulting in a printing fidelity of 97.93±1.1%for the hybrid MCHP-structure scaffold(compared to 82.31±3.6%and 92.00±2.5%in the case of Kagome-structure and modified honeycomb(MHC)-structure scaffolds,which are the control groups).Mechanical testing of the hybrid MCHP-structure scaffold using a Universal Testing Machine(UTM)depicted similarity with 91.1%of the numerical estimated effective elastic stiffness(compared to 82.8%and 79.0%in the case of Kagome-structure and MHC-structure scaffolds,which serve as the control groups).The biological potential of the scaffolds was evaluated through in vitro studies using MC3T3-E1 pre-osteoblasts.The CCK-8 assay showed significantly enhanced cell viability and proliferation on the hybrid MCHP scaffold at all time points(days 1,7,and 14),consistently outperforming the Kagome and MHC scaffolds.Additionally,immunofluorescence staining analysis revealed abundant focal adhesions and uniform nuclear distribution,highlighting the superior cytocompatibility and effective support for cellular activity of the hybrid MCHP scaffold.
文摘This article takes the theory of power space as an starting point for an in-depth comparison of the clan hall in White Deer Plains and the scaffold in The Scarlet Letter.In White Deer Plains,The clan hall,as the core place of family activities,has a spatial layout that implies a hierarchy of power,and the taboos it represents relate to various aspects such as marriage and bloodline,and maintains the order of the clan through a variety of disciplinary mechanisms.The scaffold in The Scarlet Letter is located in the town’s central square and is a symbol of Puritan social power and moral discipline,behind which Puritan taboos influence people’s behaviors and public punishments are used to achieve the discipline of the people.The research reveals the similarities and differences between the two in terms of sources of power,modes of operation and influence,and opens up new horizons for cross-cultural literary studies.
