Silk fibroin(SF)is considered biocompatible and biodegradable for osteochondral repair.However,it lacks a bioactive domain for cell adhesion,proliferation and differentiation,limiting its therapeutic efficacy.To revam...Silk fibroin(SF)is considered biocompatible and biodegradable for osteochondral repair.However,it lacks a bioactive domain for cell adhesion,proliferation and differentiation,limiting its therapeutic efficacy.To revamp SF as a biomimicking and bioactive microenvironment to regulate cell behaviours,we engineered an elastin-like polypeptide(ELP,Val-Pro-Gly-Xaa-Gly)to modify SF fibers via simple and green dehydrothermal(DHT)treatment.Our results demonstrated that the ELP successfully bound to SF,and the scaffold was reinforced by the fusion of the silk fiber intersections with ELP(S-ELP-DHT)via the DHT treatment.Both bone mesenchymal stem cells(BMSCs)and chondrocytes exhibited improved spreading and proliferation on the S-ELP-DHT scaffolds.The ex vivo and in vivo experiments further demonstrated enhanced mature bone and cartilage tissue formation using the S-ELP-DHT scaffolds compared to the naked SF scaffolds.These results indicated that a recombinant ELPmodified silk scaffold can mimic three-dimensional(3D)cell microenvironment,and improve bone and cartilage regeneration.We envision that our scaffolds have huge clinical potential for osteochondral repair.展开更多
Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathifnding; however, the interplay between these two factors is less studied. While previous work has shown that the bioch...Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathifnding; however, the interplay between these two factors is less studied. While previous work has shown that the biochemical identity of the matrix can alter the outgrowth of neurites in response to neurotrophins, the importance of the concentration of cell-adhesive ligands is unknown. Using engineered elastin-like protein matrices, we recently demonstrated a synergistic effect between matrix-bound cell-adhesive ligand density and soluble nerve growth factor treat-ment on neurite outgrowth from dorsal root ganglia. This synergism was mediated by Schwann cell-neurite contact through L1CAM. Cell-adhesive ligand density was also shown to alter the pathifnding behavior of dorsal root ganglion neurites in response to a gradient of nerve growth factor. While more cell-adhesive matrices promoted neurite outgrowth, less cell-adhesive ma-trices promoted more faithful neurite pathifnding. These studies emphasize the importance of considering both matrix biochemistry and neurotrophic factors when designing biomaterials for peripheral nerve regeneration.展开更多
Therapeutic proteins and peptides are characteristic by their high biological activity and specificity,but their clinical uses are bottlenecked by their poor stability,short in vivo half-life and immunogenicity[1].One...Therapeutic proteins and peptides are characteristic by their high biological activity and specificity,but their clinical uses are bottlenecked by their poor stability,short in vivo half-life and immunogenicity[1].One typical example is recombinant human interferon alpha(IFN-α),FDA-approved and widely used in treatments of viral diseases and cancer,yet its short plasma half-life(t1/2=2-4 h)necessi-展开更多
Biopolymers, including DNA and peptides have been used as excellent self-assembling building blocks for programmable single-component or hybrid materials, due to their controlled molecular interactions.However, combin...Biopolymers, including DNA and peptides have been used as excellent self-assembling building blocks for programmable single-component or hybrid materials, due to their controlled molecular interactions.However, combining two assembling principles of DNA-based programmability and peptide-based specific molecular interactions for hybrid structures to microscale has not yet been achieved. In this study,we describe a hybrid microsystem that emerges from the co-assembly of DNA origami structure and short elastin-like polypeptide conjugated oligonucleotides, and initiates liquid-liquid phase separation to generate microdroplets upon heating above the transition temperature. Moreover, the hybrid microdroplets are capable for guest molecule trapping and perform bi-/tri-enzymatic cascades with rate enhancements as open “microreactors”. Our programmed assembled DNA-peptide microsystem represents a new combination of DNA nanotechnology and peptide science and opens potential application routes toward lifeinspired biomaterials.展开更多
Alzheimer’s disease(AD)is a neurodegenerative disorder,and the etiology of AD has not been completely elucidated.It remains unknown how the components from the brain’s extracellular matrix(ECM),particularly fibrous ...Alzheimer’s disease(AD)is a neurodegenerative disorder,and the etiology of AD has not been completely elucidated.It remains unknown how the components from the brain’s extracellular matrix(ECM),particularly fibrous entities,may influence the pathogenesis of AD.Herein,we report that treatment with elastin-like polypeptides(ELPs),a component of the brain ECM,significantly increases the extracellular levels of AD-related amyloid-beta(Aβ)peptides and decreases intracellular Aβlevels in human microglial cell model HMC3 cells(HMC3).展开更多
The integration of implants or medical devices into the body tissues requires of good cell–material interactions.However,most polymeric materials used for these applications lack on biological cues,which enhanced mid...The integration of implants or medical devices into the body tissues requires of good cell–material interactions.However,most polymeric materials used for these applications lack on biological cues,which enhanced mid-and long-term implant failure due to weak integration with the surrounding tissue.Commonly used strategies for tissue–material integration focus on functionalization of the material surface by means of natural proteins or short peptides.However,the use of these biomolecules involves major drawbacks such as immunogenic problems and oversimplification of the constructs.Here,designed elastin-like recombinamers(ELRs)are used to enhance poly(methyl methacrylate)surface properties and compared against the use of short peptides.In this study,cell response has been analysed for different functionalization conditions in the presence and absence of a competing protein,which interferes on surface–cell interaction by unspecific adsorption on the interface.The study has shown that ELRs can induce higher rates of cell attachment and stronger cell anchorages than short peptides,being a better choice for surface functionalization.展开更多
基金supported by the Departmental General Research Fund of the Hong Kong Polytechnic University(UAH2)the National Natural Science Foundation of P.R.China(No.31670975,21706212)Special Support Plan for High-level Talents,and Innovation Team Program in Shaanxi Province.
文摘Silk fibroin(SF)is considered biocompatible and biodegradable for osteochondral repair.However,it lacks a bioactive domain for cell adhesion,proliferation and differentiation,limiting its therapeutic efficacy.To revamp SF as a biomimicking and bioactive microenvironment to regulate cell behaviours,we engineered an elastin-like polypeptide(ELP,Val-Pro-Gly-Xaa-Gly)to modify SF fibers via simple and green dehydrothermal(DHT)treatment.Our results demonstrated that the ELP successfully bound to SF,and the scaffold was reinforced by the fusion of the silk fiber intersections with ELP(S-ELP-DHT)via the DHT treatment.Both bone mesenchymal stem cells(BMSCs)and chondrocytes exhibited improved spreading and proliferation on the S-ELP-DHT scaffolds.The ex vivo and in vivo experiments further demonstrated enhanced mature bone and cartilage tissue formation using the S-ELP-DHT scaffolds compared to the naked SF scaffolds.These results indicated that a recombinant ELPmodified silk scaffold can mimic three-dimensional(3D)cell microenvironment,and improve bone and cartilage regeneration.We envision that our scaffolds have huge clinical potential for osteochondral repair.
基金supported by the National Institutes of Health(1DP2-OD006477,R01-DK085720,R21-AR062359-01)the National Science Foundation(DMR-0846363)
文摘Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathifnding; however, the interplay between these two factors is less studied. While previous work has shown that the biochemical identity of the matrix can alter the outgrowth of neurites in response to neurotrophins, the importance of the concentration of cell-adhesive ligands is unknown. Using engineered elastin-like protein matrices, we recently demonstrated a synergistic effect between matrix-bound cell-adhesive ligand density and soluble nerve growth factor treat-ment on neurite outgrowth from dorsal root ganglia. This synergism was mediated by Schwann cell-neurite contact through L1CAM. Cell-adhesive ligand density was also shown to alter the pathifnding behavior of dorsal root ganglion neurites in response to a gradient of nerve growth factor. While more cell-adhesive matrices promoted neurite outgrowth, less cell-adhesive ma-trices promoted more faithful neurite pathifnding. These studies emphasize the importance of considering both matrix biochemistry and neurotrophic factors when designing biomaterials for peripheral nerve regeneration.
文摘Therapeutic proteins and peptides are characteristic by their high biological activity and specificity,but their clinical uses are bottlenecked by their poor stability,short in vivo half-life and immunogenicity[1].One typical example is recombinant human interferon alpha(IFN-α),FDA-approved and widely used in treatments of viral diseases and cancer,yet its short plasma half-life(t1/2=2-4 h)necessi-
基金supported by the National Natural Science Foundation of China (No. 31600802)。
文摘Biopolymers, including DNA and peptides have been used as excellent self-assembling building blocks for programmable single-component or hybrid materials, due to their controlled molecular interactions.However, combining two assembling principles of DNA-based programmability and peptide-based specific molecular interactions for hybrid structures to microscale has not yet been achieved. In this study,we describe a hybrid microsystem that emerges from the co-assembly of DNA origami structure and short elastin-like polypeptide conjugated oligonucleotides, and initiates liquid-liquid phase separation to generate microdroplets upon heating above the transition temperature. Moreover, the hybrid microdroplets are capable for guest molecule trapping and perform bi-/tri-enzymatic cascades with rate enhancements as open “microreactors”. Our programmed assembled DNA-peptide microsystem represents a new combination of DNA nanotechnology and peptide science and opens potential application routes toward lifeinspired biomaterials.
基金from National Key R&D Program of China(grant no.2018YFA0902600)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(grant no.ZDKYYQ20180001)+1 种基金the Jilin Province Science Fund for Excellent Young Scholars(20190103072JH),K.C.Wong Education Foundation(grant no.GJTD-2018-09)and the National Natural Science Foundation of China(grant nos.21704099,21877104,and 21834007)and the Cure Alzheimer’s Fund.
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder,and the etiology of AD has not been completely elucidated.It remains unknown how the components from the brain’s extracellular matrix(ECM),particularly fibrous entities,may influence the pathogenesis of AD.Herein,we report that treatment with elastin-like polypeptides(ELPs),a component of the brain ECM,significantly increases the extracellular levels of AD-related amyloid-beta(Aβ)peptides and decreases intracellular Aβlevels in human microglial cell model HMC3 cells(HMC3).
基金This work was supported by the Spain’s Ministerio de Economı´a y Competitividad[projects MAT2008-06887-C03-01,MAT2010-15310,MAT2013-41723-R,MAT2013-42473-R,VA313U14 and VA244U13].X.P.acknowledges grant BES-2009-027524 from the Spain’s Ministerio de Economı´a y Competitividad.
文摘The integration of implants or medical devices into the body tissues requires of good cell–material interactions.However,most polymeric materials used for these applications lack on biological cues,which enhanced mid-and long-term implant failure due to weak integration with the surrounding tissue.Commonly used strategies for tissue–material integration focus on functionalization of the material surface by means of natural proteins or short peptides.However,the use of these biomolecules involves major drawbacks such as immunogenic problems and oversimplification of the constructs.Here,designed elastin-like recombinamers(ELRs)are used to enhance poly(methyl methacrylate)surface properties and compared against the use of short peptides.In this study,cell response has been analysed for different functionalization conditions in the presence and absence of a competing protein,which interferes on surface–cell interaction by unspecific adsorption on the interface.The study has shown that ELRs can induce higher rates of cell attachment and stronger cell anchorages than short peptides,being a better choice for surface functionalization.
