Biological receptor-ligand adhesion governed by mammalian cells involves a series of mechanochemical pro-cesses that can realize reversible,loading rate-dependent specific interfacial bonding,and even exhibit a counte...Biological receptor-ligand adhesion governed by mammalian cells involves a series of mechanochemical pro-cesses that can realize reversible,loading rate-dependent specific interfacial bonding,and even exhibit a counterintuitive behavior called catch bonds that tend to have much longer lifetimes when larger pulling forces are applied.Inspired by these catch bonds,we designed a hydrogen bonding-meditated hydrogel made from acrylic acid-N-acryloyl glycinamide(AA-NAGA)copolymers and tannic acids(TA),which formed repeatable specific adhesion to polar surfaces in an ultra-fast and robust way,but hardly adhered to nonpolar materials.It demonstrated up to five-fold increase in shear adhesive strength and interfacial adhesive toughness with external loading rates varying from 5 to 500 mm min^(-1).With a mechanochemical coupling model based on Monte Carlo simulations,we quantitatively revealed the nonlinear dependence of rate-sensitive interfacial adhesion on external loading,which was in good agreement with the experimental data.Likewise,the developed hydrogels were biocompatible,possessed antioxidant and antibacterial properties and promoted wound healing.This work not only reports a stimuli-responsive hydrogel adhesive suitable for multiple biomedical applications,but also offers an innovative strategy for bionic designs of smart hydrogels with loading rate-sensitive specific adhesion for various emerging areas including flexible electronics and soft robotics.展开更多
Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes a...Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes and ineffective delivery method,are still persisted.Here,we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth(SHEDs)via comprehensive proteomics analysis,and the corresponding hypoxic exosomes(H-Exo)exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion,VEGF signaling pathway,and thyroid hormone synthesis.Then,we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection.This platform is based on a simple adsorbing technique,where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide)(PLGA)microspheres with bioinspired polydopamine(PDA)coating(PMS-PDA microspheres).The PMS-PDA microspheres could effectively adsorb exosomes,show sustained release of H-Exo for 21 days with high bioactivity,and induce vascularized bone regeneration in 5-mm rat calvarial defect.These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration,hence facilitating the clinical translation of exosome-based therapy.展开更多
基金National Natural Science Foundation of China(Grant nos.11972001,11972002,12072001 and 91848201)Beijing Natural Science Foundation(Grant no.Z200017)National Key Research and Development Program of China(Grant no.2021YFA1000201).
文摘Biological receptor-ligand adhesion governed by mammalian cells involves a series of mechanochemical pro-cesses that can realize reversible,loading rate-dependent specific interfacial bonding,and even exhibit a counterintuitive behavior called catch bonds that tend to have much longer lifetimes when larger pulling forces are applied.Inspired by these catch bonds,we designed a hydrogen bonding-meditated hydrogel made from acrylic acid-N-acryloyl glycinamide(AA-NAGA)copolymers and tannic acids(TA),which formed repeatable specific adhesion to polar surfaces in an ultra-fast and robust way,but hardly adhered to nonpolar materials.It demonstrated up to five-fold increase in shear adhesive strength and interfacial adhesive toughness with external loading rates varying from 5 to 500 mm min^(-1).With a mechanochemical coupling model based on Monte Carlo simulations,we quantitatively revealed the nonlinear dependence of rate-sensitive interfacial adhesion on external loading,which was in good agreement with the experimental data.Likewise,the developed hydrogels were biocompatible,possessed antioxidant and antibacterial properties and promoted wound healing.This work not only reports a stimuli-responsive hydrogel adhesive suitable for multiple biomedical applications,but also offers an innovative strategy for bionic designs of smart hydrogels with loading rate-sensitive specific adhesion for various emerging areas including flexible electronics and soft robotics.
基金the financial support from Beijing Natural Science Foundation(7212135)National Natural Science Foundation of China(NSFC)(11972001,11972002 and 12072001).
文摘Exosomes derived from mesenchymal stem cells(MSCs)have demonstrated regenerative potential for cell-free bone tissue engineering,nevertheless,certain challenges,including the confined therapeutic potency of exosomes and ineffective delivery method,are still persisted.Here,we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth(SHEDs)via comprehensive proteomics analysis,and the corresponding hypoxic exosomes(H-Exo)exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion,VEGF signaling pathway,and thyroid hormone synthesis.Then,we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection.This platform is based on a simple adsorbing technique,where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide)(PLGA)microspheres with bioinspired polydopamine(PDA)coating(PMS-PDA microspheres).The PMS-PDA microspheres could effectively adsorb exosomes,show sustained release of H-Exo for 21 days with high bioactivity,and induce vascularized bone regeneration in 5-mm rat calvarial defect.These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration,hence facilitating the clinical translation of exosome-based therapy.
