Metallic bone screws are clinically used to fix the fractured bone fragments in bone defect treatment;yet they present compromised therapeutic efficacy due to poor osseointegration and tissue support.Here,we develop a...Metallic bone screws are clinically used to fix the fractured bone fragments in bone defect treatment;yet they present compromised therapeutic efficacy due to poor osseointegration and tissue support.Here,we develop a novel thermoresponsive shape memory(SMP)bone screw with osteogenesis-angiogenesis coupling for enhanced bone regeneration.The SMP bone screws are prepared by die casting of shape memory polyurethane/hydroxyapatite(PU/HA)composite,coated with L-arginine(Arg)and calcium ions(Ca^(2+)).The SMP bone screw could shrink and be easily reshaped at room temperature(25◦C)and then rapidly recover to its original state(37℃),granting it robust internal fixation capacity(2-fold increase in pull-out force)and beneficial compressive force to nearby tissues.Additionally,the long-term release of L-arginine and calcium ions synergistically activate the nitric oxide-cyclic guanosine monophosphate(NO-cGMP)signaling pathway of native cells.Synergized with its shape memory function,the SMP bone screw activated calcium signaling pathway under the stimulation of mechanical stress,promote the activation of various osteogenic pathways(e.g.PI3K-Akt signaling pathway),and upregulate the NO-cGMP pathway by regulating the influx of calcium ions and arginine to synchronously coordinate osteogenesis and angiogenesis to accelerate bone repair.We envision that our slot-in,snap-back and homeothermal shape memory bone screw,with its easily reshaped and fast stress release properties and osteogenesis-angiogenesis coupling efficacy,can shed new light on the development of clinical bone screws.展开更多
Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Althoug...Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Although microneedles are initially designed to penetrate stratum corneum of skin for transdermal drug delivery, they, recently, have been used to promote wound healing and regeneration of diverse tissues and organs and the results are promising. Despite there are reviews about microneedles, few of them focus on wound healing and tissue regeneration. Here, we review the recent advances of microneedles in this field. We first give an overview of microneedle system in terms of its potential cargos (e.g., small molecules, macromolecules, nucleic acids, nanoparticles, extracellular vesicle, cells), structural designs (e.g., multidrug structures, adhesive structures), material selection, and drug release mechanisms. Then we briefly summarize different microneedle fabrication methods, including their advantages and limitations. We finally summarize the recent progress of microneedle-assisted wound healing and tissue regeneration (e.g., skin, cardiac, bone, tendon, ocular, vascular, oral, hair, spinal cord, and uterine tissues). We expect that our article would serve as a guideline for readers to design their microneedle systems according to different applications, including material selection, drug selection, and structure design, for achieving better healing and regeneration efficacy.展开更多
Preservation of growth factor sensitivity and bioactivity(e.g.,bone morphogenetic protein-2(BMP-2))post-immobilization to tissue engineering scaffolds remains a great challenge.Here,we develop a stable and soft surfac...Preservation of growth factor sensitivity and bioactivity(e.g.,bone morphogenetic protein-2(BMP-2))post-immobilization to tissue engineering scaffolds remains a great challenge.Here,we develop a stable and soft surface modification strategy to address this issue.BMP-2(a model growth factor)is covalently immobilized onto homogeneous poly(glycidyl methacrylate)(PGMA)polymer brushes which are grafted onto substrate surfaces(Au,quartz glass,silica wafer,or common biomaterials)via surface-initiated atom transfer radical polymerization.This surface modification method multiplies the functionalized interfacial area;it is simple,fast,gentle,and has little effect on the loaded protein owing to the cilia motility.The immobilized BMP-2(i-BMP-2)on the surface of homogeneous PGMA polymer brushes exhibits excellent bioactivity(-87%bioactivity of free BMP-2 in vitro and 20%-50%higher than scaffolds with free BMP-2 in vivo),with conformation and secondary structure well-preserved after covalent immobilization and ethanol sterilization.Moreover,the osteogenic activity of i-BMP-2 on the nanoline pattern(PGMA-poly(N-isopropylacrylamide))shows-110%bioactivity of free BMP-2.This is superior compared to conventional protein covalent immobilization strategies in terms of both bioactivity preservation and therapeutic efficacy.PGMA polymer brushes can be used to modify surfaces of different tissue-engineered scaffolds,which facilitates in situ immobilization of growth factors,and accelerates repair of a wide range of tissue types.展开更多
Gelatin methacryloyl(GelMA)has attracted the widespread interest of researchers because of its excellent biocompatibility,biodegradability,and moldability.Various structures have been constructed from GelMA hydrogel,i...Gelatin methacryloyl(GelMA)has attracted the widespread interest of researchers because of its excellent biocompatibility,biodegradability,and moldability.Various structures have been constructed from GelMA hydrogel,including 3D scaffold,injectable gel,bio-printed scaffold,and electrospun fibrous membrane via precise fabrication methods such as light-induced crosslinking,extrusion 3D printing,electrospinning,or microfluidics.Due to its unique characteristics and simple preparation,GelMA hydrogel demonstrates superior performance and promising potential in a broad range of biomedical applications involving wound healing,drug delivery,biosensing,and tissue regeneration.This review integrates sufficient research works on GelMA hydrogels in the regeneration of tissues such as skin,tendon,bone,cartilage,blood vessel,and cardiovascular system,in addition to applications in drug delivery,organ-on-a-chip,and biosensing,providing a critical review of present work and offering future implications.展开更多
基金supported by the Guangdong-Foshan Joint Fund from Guangdong Basic and Applied Basic Research Foundation(2020B15153000)the Excellent Young Scholars Projects from the National Natural Science Foundation of China(NSFC,82122002)+4 种基金General Program of NSFC(52335004,52275199)the Collaborative Research Fund(C5044-21G)NSFC/RGC Joint Research Scheme(N_PolyU526/22)from the Research Grants Council of Hong Kong,the Innovation and Technology Fund from the Innovation and Technology Commission(ITS/085/21)Beijing Natural Science Foundation(J230001,L248029)Young Scholars Program of Shandong University.
文摘Metallic bone screws are clinically used to fix the fractured bone fragments in bone defect treatment;yet they present compromised therapeutic efficacy due to poor osseointegration and tissue support.Here,we develop a novel thermoresponsive shape memory(SMP)bone screw with osteogenesis-angiogenesis coupling for enhanced bone regeneration.The SMP bone screws are prepared by die casting of shape memory polyurethane/hydroxyapatite(PU/HA)composite,coated with L-arginine(Arg)and calcium ions(Ca^(2+)).The SMP bone screw could shrink and be easily reshaped at room temperature(25◦C)and then rapidly recover to its original state(37℃),granting it robust internal fixation capacity(2-fold increase in pull-out force)and beneficial compressive force to nearby tissues.Additionally,the long-term release of L-arginine and calcium ions synergistically activate the nitric oxide-cyclic guanosine monophosphate(NO-cGMP)signaling pathway of native cells.Synergized with its shape memory function,the SMP bone screw activated calcium signaling pathway under the stimulation of mechanical stress,promote the activation of various osteogenic pathways(e.g.PI3K-Akt signaling pathway),and upregulate the NO-cGMP pathway by regulating the influx of calcium ions and arginine to synchronously coordinate osteogenesis and angiogenesis to accelerate bone repair.We envision that our slot-in,snap-back and homeothermal shape memory bone screw,with its easily reshaped and fast stress release properties and osteogenesis-angiogenesis coupling efficacy,can shed new light on the development of clinical bone screws.
基金supported by the grant from the Guangdong Basic and Applied Basic Research Foundation(2020B1515130002)Collaborative Research with World-leading Research Groups from The Hong Kong Polytechnic University(P0039523)+2 种基金National Excellent Young Scientists Fund(Hong Kong and Macao),National Natural Science Foundation of China(No.82122002)National Natural Science Foundation of China(No.U1909218)the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.T2121004).
文摘Microneedle, as a novel drug delivery system, has attracted widespread attention due to its non-invasiveness, painless and simple administration, controllable drug delivery, and diverse cargo loading capacity. Although microneedles are initially designed to penetrate stratum corneum of skin for transdermal drug delivery, they, recently, have been used to promote wound healing and regeneration of diverse tissues and organs and the results are promising. Despite there are reviews about microneedles, few of them focus on wound healing and tissue regeneration. Here, we review the recent advances of microneedles in this field. We first give an overview of microneedle system in terms of its potential cargos (e.g., small molecules, macromolecules, nucleic acids, nanoparticles, extracellular vesicle, cells), structural designs (e.g., multidrug structures, adhesive structures), material selection, and drug release mechanisms. Then we briefly summarize different microneedle fabrication methods, including their advantages and limitations. We finally summarize the recent progress of microneedle-assisted wound healing and tissue regeneration (e.g., skin, cardiac, bone, tendon, ocular, vascular, oral, hair, spinal cord, and uterine tissues). We expect that our article would serve as a guideline for readers to design their microneedle systems according to different applications, including material selection, drug selection, and structure design, for achieving better healing and regeneration efficacy.
基金financial support from RGC Senior Research Fellow Scheme(SRFS2122-5S04),Research Grants Council of Hong KongCollaborative Research Fund(C5044-21GF)from the Research Grants Council of Hong Kong and National Excellent Young Scientists Fund(Hong Kong and Macao,82122002),National Natural Science Foundation of China+1 种基金support from National Natural Science Foundation of China(No.32071337)Shanghai Pujiang Program(20PJ1402600).
文摘Preservation of growth factor sensitivity and bioactivity(e.g.,bone morphogenetic protein-2(BMP-2))post-immobilization to tissue engineering scaffolds remains a great challenge.Here,we develop a stable and soft surface modification strategy to address this issue.BMP-2(a model growth factor)is covalently immobilized onto homogeneous poly(glycidyl methacrylate)(PGMA)polymer brushes which are grafted onto substrate surfaces(Au,quartz glass,silica wafer,or common biomaterials)via surface-initiated atom transfer radical polymerization.This surface modification method multiplies the functionalized interfacial area;it is simple,fast,gentle,and has little effect on the loaded protein owing to the cilia motility.The immobilized BMP-2(i-BMP-2)on the surface of homogeneous PGMA polymer brushes exhibits excellent bioactivity(-87%bioactivity of free BMP-2 in vitro and 20%-50%higher than scaffolds with free BMP-2 in vivo),with conformation and secondary structure well-preserved after covalent immobilization and ethanol sterilization.Moreover,the osteogenic activity of i-BMP-2 on the nanoline pattern(PGMA-poly(N-isopropylacrylamide))shows-110%bioactivity of free BMP-2.This is superior compared to conventional protein covalent immobilization strategies in terms of both bioactivity preservation and therapeutic efficacy.PGMA polymer brushes can be used to modify surfaces of different tissue-engineered scaffolds,which facilitates in situ immobilization of growth factors,and accelerates repair of a wide range of tissue types.
基金supported by Health and Medical Research Fund(06173186)from Food and Health Bureau of Hong Kong.
文摘Gelatin methacryloyl(GelMA)has attracted the widespread interest of researchers because of its excellent biocompatibility,biodegradability,and moldability.Various structures have been constructed from GelMA hydrogel,including 3D scaffold,injectable gel,bio-printed scaffold,and electrospun fibrous membrane via precise fabrication methods such as light-induced crosslinking,extrusion 3D printing,electrospinning,or microfluidics.Due to its unique characteristics and simple preparation,GelMA hydrogel demonstrates superior performance and promising potential in a broad range of biomedical applications involving wound healing,drug delivery,biosensing,and tissue regeneration.This review integrates sufficient research works on GelMA hydrogels in the regeneration of tissues such as skin,tendon,bone,cartilage,blood vessel,and cardiovascular system,in addition to applications in drug delivery,organ-on-a-chip,and biosensing,providing a critical review of present work and offering future implications.
