Surface wettability is important to design biointerfaces and fimctional biomaterials in various biological applications. However, to date, it remains some confusions about how cells would response to the surfaces with...Surface wettability is important to design biointerfaces and fimctional biomaterials in various biological applications. However, to date, it remains some confusions about how cells would response to the surfaces with different wettabilities. Herein, we systematically explore the adhesive spectra of cells to the surface with wettability gradient from superhydrophilicity to superhydrophobicity, clarifying the effect of wettability on cell adhesion. We envision that this study may provide valuable information for the design of biomedical implants with controllable cell adhesion, such as neural interface devices and flexible implant.展开更多
Nanotopographical cues endow biomaterials the ability to guide cell adhesion, proliferation, and differentiation. Cellular mechanical memory can maintain the cell status by retaining cellular information obtained from...Nanotopographical cues endow biomaterials the ability to guide cell adhesion, proliferation, and differentiation. Cellular mechanical memory can maintain the cell status by retaining cellular information obtained from past mechanical microenvironments. Here, we propose a new concept “morphology memory of small extracellular vesicles (sEV)” for bone regeneration. We performed nanotopography on titanium plates through alkali and heat (Ti8) treatment to promote human mesenchymal stem cell (hMSC) differentiation. Next, we extracted the sEVs from the hMSC, which were cultured on the nanotopographical Ti plates for 21 days (Ti8-21-sEV). We demonstrated that Ti8-21-sEV had superior pro-osteogenesis ability in vitro and in vivo. RNA sequencing further confirmed that Ti8-21-sEV promote bone regeneration through osteogenic-related pathways, including the PI3K-AKT signaling pathway, MAPK signaling pathway, focal adhesion, and extracellular matrix-receptor interaction. Finally, we decorated the Ti8-21-sEV on a 3D printed porous polyetheretherketone scaffold. The femoral condyle defect model of rabbits was used to demonstrate that Ti8-21-sEV had the best bone ingrowth. In summary, our study demonstrated that the Ti8-21-sEV have memory function by copying the pro-osteogenesis information from the nanotopography. We expect that our study will encourage the discovery of other sEV with morphology memory for tissue regeneration.展开更多
Finely tuning mechanosensitive membrane proteins holds great potential in precisely controlling inflammatory responses.In addition to macroscopic force,mechanosensitive membrane proteins are reported to be sensitive t...Finely tuning mechanosensitive membrane proteins holds great potential in precisely controlling inflammatory responses.In addition to macroscopic force,mechanosensitive membrane proteins are reported to be sensitive to micro-nano forces.Integrinβ_(2),for example,might undergo a piconewton scale stretching force in the activation state.High-aspect-ratio nanotopographic structures were found to generate nN-scale biomechanical force.Together with the advantages of uniform and precisely tunable structural parameters,it is fascinating to develop low-aspect-ratio nanotopographic structures to generate micro-nano forces for finely modulating their conformations and the subsequent mechanoimmiune responses.In this study,low-aspect-ratio nanotopographic structures were developed to finely manipulate the conformation of integrinβ_(2).The direct interaction of forces and the model molecule integrinαXβ_(2)was first performed.It was demonstrated that pressing force could successfully induce conformational compression and deactivation of integrinαXβ_(2),and approximately 270 to 720 pN may be required to inhibit its conformational extension and activation.Three low-aspect-ratio nanotopographic surfaces(nanohemispheres,nanorods,and nanoholes)with various structural parameters were specially designed to generate the micro-nano forces.It was found that the nanorods and nanohemispheres surfaces induce greater contact pressure at the contact interface between macrophages and nanotopographic structures,particularly after cell adhesion.These higher contact pressures successfully inhibited the conformational extension and activation of integrinβ_(2),suppressing focal adhesion activity and the downstream PI3K-Akt signaling pathway,reducing NF-κB signaling and macrophage inflammatory responses.Our findings suggest that nanotopographic structures can be used to finely tune mechanosensitive membrane protein conformation changes,providing an effective strategy for precisely modulating inflammatory responses.展开更多
Stem cells have been one of the ideal sources for tissue regeneration owing to their capability of self-renewal and differentiation.In vivo,the extracellular microenvironment plays a vital role in modulating stem cell...Stem cells have been one of the ideal sources for tissue regeneration owing to their capability of self-renewal and differentiation.In vivo,the extracellular microenvironment plays a vital role in modulating stem cell fate.When developing biomaterials for regenerative medicine,incorporating biochemical and biophysical cues to mimic extracellular matrix can enhance stem cell lineage differentiation.More specifically,modulating the stem cell fate can be achieved by controlling the nanotopographic features on synthetic surfaces.Optimization of nanotopographical features leads to desirable stem cell functions,which can maximize the effectiveness of regenerative treatment.In this review,nanotopographical surfaces,including static patterned surface,dynamic patterned surface,and roughness are summarized,and their fabrication,as well as the impact on stem cell behaviour,are discussed.Later,the recent progress of applying nanotopographical featured biomaterials for altering different types of stem cells is presented,which directs the design and fabrication of functional biomaterial.Last,the perspective in fundamental research and for clinical application in this field is discussed.展开更多
There is a compelling need for delicate nanomaterial design with various intricate functions and applications.Electrohydrodynamics applies electrostatic force to overcome the surface tension of a liquid jet,shrinking ...There is a compelling need for delicate nanomaterial design with various intricate functions and applications.Electrohydrodynamics applies electrostatic force to overcome the surface tension of a liquid jet,shrinking the jet through intrinsic jetting instabiity into submicron fibers or spheres,with versatilty from a huge selection of materials,feasibllity of extracellular matrix structure mimicry and multicompartmentalization for tissue engineering and drug delivery.The process typically involves the collection and drying of fibers at a solid substrate,but the introduction of a liquid phase collection by replacing the solid collector with a coagulation bath can introduce a variety of new opportunities for both chemical and physical functionalizations in one single step.The so-called wet electrohydrodynamics is an emerging technique that enables a facile,homogeneous functionalization of the intrinsic large surface area of the submicron fibers/spheres.With a thorough literature sweep,we herein highlight the three main engineering features integrated through the single step wet electrospinning process in terms of creating functional biomaterials:(i)The fabrication of 3D macrostructures,(ii)in situ chemical functionalization,and(iii)tunable nano-topography.Through an emerging technique,wet electrohydrodynamics has demonstrated a great potential in interdisciplinary research for the development of functional 3D interfaces and materials with pertinent applications in all fields where secondary structured,functional surface is desired.Among these,engineered biomaterials bridging materials science with biology have already shown particular potential..展开更多
基金supported by the National Natural Science Foundation of China(21425314,21501184,21434009,21421061,21504098)the Key Research Program of the Chinese Academy of Sciences(KJZD-EW-M01)+2 种基金Ministry of Science and Technology(2013YQ190467)the Top-Notch Young Talents Program of ChinaBeijing Municipal Science&Technology Commission(Z161100000116037)
文摘Surface wettability is important to design biointerfaces and fimctional biomaterials in various biological applications. However, to date, it remains some confusions about how cells would response to the surfaces with different wettabilities. Herein, we systematically explore the adhesive spectra of cells to the surface with wettability gradient from superhydrophilicity to superhydrophobicity, clarifying the effect of wettability on cell adhesion. We envision that this study may provide valuable information for the design of biomedical implants with controllable cell adhesion, such as neural interface devices and flexible implant.
基金This study was supported by the National Key R&D Program of China(2018YFB1105700)the National Natural Science Foundation of China(81902261,81772401)+2 种基金the Fundamental Research Funds for the Cen-tral Universities(2019kfyXMBZ063)the Application Foundation and Advanced Program of Wuhan Science and Technology Bureau(2019020701011457)We also thank the Medical Subcenter of HUST Analytical&Testing Center in data acquisition.
文摘Nanotopographical cues endow biomaterials the ability to guide cell adhesion, proliferation, and differentiation. Cellular mechanical memory can maintain the cell status by retaining cellular information obtained from past mechanical microenvironments. Here, we propose a new concept “morphology memory of small extracellular vesicles (sEV)” for bone regeneration. We performed nanotopography on titanium plates through alkali and heat (Ti8) treatment to promote human mesenchymal stem cell (hMSC) differentiation. Next, we extracted the sEVs from the hMSC, which were cultured on the nanotopographical Ti plates for 21 days (Ti8-21-sEV). We demonstrated that Ti8-21-sEV had superior pro-osteogenesis ability in vitro and in vivo. RNA sequencing further confirmed that Ti8-21-sEV promote bone regeneration through osteogenic-related pathways, including the PI3K-AKT signaling pathway, MAPK signaling pathway, focal adhesion, and extracellular matrix-receptor interaction. Finally, we decorated the Ti8-21-sEV on a 3D printed porous polyetheretherketone scaffold. The femoral condyle defect model of rabbits was used to demonstrate that Ti8-21-sEV had the best bone ingrowth. In summary, our study demonstrated that the Ti8-21-sEV have memory function by copying the pro-osteogenesis information from the nanotopography. We expect that our study will encourage the discovery of other sEV with morphology memory for tissue regeneration.
基金This work was financially supported by the National Natural Science Foundation of China(No.82061167)the National Key Research and Development Program of China(No.2022YFA1104400)+3 种基金the International Team for Implantology(ITI)Research Grant(No.1536_2020)Fundamental Research Funds of Sun Yat-sen University(No.22ykqb06)Science and Technology Program of Guangzhou(No.SL2022B03J00507)Guangdong Financial Fund for High-Caliber Hospital Construction,and National Undergraduate Training Program for Innovation and Entrepreneurship(No.202210772).
文摘Finely tuning mechanosensitive membrane proteins holds great potential in precisely controlling inflammatory responses.In addition to macroscopic force,mechanosensitive membrane proteins are reported to be sensitive to micro-nano forces.Integrinβ_(2),for example,might undergo a piconewton scale stretching force in the activation state.High-aspect-ratio nanotopographic structures were found to generate nN-scale biomechanical force.Together with the advantages of uniform and precisely tunable structural parameters,it is fascinating to develop low-aspect-ratio nanotopographic structures to generate micro-nano forces for finely modulating their conformations and the subsequent mechanoimmiune responses.In this study,low-aspect-ratio nanotopographic structures were developed to finely manipulate the conformation of integrinβ_(2).The direct interaction of forces and the model molecule integrinαXβ_(2)was first performed.It was demonstrated that pressing force could successfully induce conformational compression and deactivation of integrinαXβ_(2),and approximately 270 to 720 pN may be required to inhibit its conformational extension and activation.Three low-aspect-ratio nanotopographic surfaces(nanohemispheres,nanorods,and nanoholes)with various structural parameters were specially designed to generate the micro-nano forces.It was found that the nanorods and nanohemispheres surfaces induce greater contact pressure at the contact interface between macrophages and nanotopographic structures,particularly after cell adhesion.These higher contact pressures successfully inhibited the conformational extension and activation of integrinβ_(2),suppressing focal adhesion activity and the downstream PI3K-Akt signaling pathway,reducing NF-κB signaling and macrophage inflammatory responses.Our findings suggest that nanotopographic structures can be used to finely tune mechanosensitive membrane protein conformation changes,providing an effective strategy for precisely modulating inflammatory responses.
基金This work was supported by Research Funding from West China School/Hospital of Stomatology,Sichuan University(Nos.RD-03-202010,RCDWJS2021-15,RD-02-202004)the China Postdoctoral Science Foundation(No.2020TQ0211).
文摘Stem cells have been one of the ideal sources for tissue regeneration owing to their capability of self-renewal and differentiation.In vivo,the extracellular microenvironment plays a vital role in modulating stem cell fate.When developing biomaterials for regenerative medicine,incorporating biochemical and biophysical cues to mimic extracellular matrix can enhance stem cell lineage differentiation.More specifically,modulating the stem cell fate can be achieved by controlling the nanotopographic features on synthetic surfaces.Optimization of nanotopographical features leads to desirable stem cell functions,which can maximize the effectiveness of regenerative treatment.In this review,nanotopographical surfaces,including static patterned surface,dynamic patterned surface,and roughness are summarized,and their fabrication,as well as the impact on stem cell behaviour,are discussed.Later,the recent progress of applying nanotopographical featured biomaterials for altering different types of stem cells is presented,which directs the design and fabrication of functional biomaterial.Last,the perspective in fundamental research and for clinical application in this field is discussed.
基金We gratefully acknowledge the funding from Aarhus University Research Foundation(AUFF-E-2015-FLS-7-27).
文摘There is a compelling need for delicate nanomaterial design with various intricate functions and applications.Electrohydrodynamics applies electrostatic force to overcome the surface tension of a liquid jet,shrinking the jet through intrinsic jetting instabiity into submicron fibers or spheres,with versatilty from a huge selection of materials,feasibllity of extracellular matrix structure mimicry and multicompartmentalization for tissue engineering and drug delivery.The process typically involves the collection and drying of fibers at a solid substrate,but the introduction of a liquid phase collection by replacing the solid collector with a coagulation bath can introduce a variety of new opportunities for both chemical and physical functionalizations in one single step.The so-called wet electrohydrodynamics is an emerging technique that enables a facile,homogeneous functionalization of the intrinsic large surface area of the submicron fibers/spheres.With a thorough literature sweep,we herein highlight the three main engineering features integrated through the single step wet electrospinning process in terms of creating functional biomaterials:(i)The fabrication of 3D macrostructures,(ii)in situ chemical functionalization,and(iii)tunable nano-topography.Through an emerging technique,wet electrohydrodynamics has demonstrated a great potential in interdisciplinary research for the development of functional 3D interfaces and materials with pertinent applications in all fields where secondary structured,functional surface is desired.Among these,engineered biomaterials bridging materials science with biology have already shown particular potential..
