Flexible hydrogels containing various osteogenic inorganic constituents,which can accommodate complicated shape variations,are considered as ideal grafts for craniofacial bone defect reconstruction.However,in most hyb...Flexible hydrogels containing various osteogenic inorganic constituents,which can accommodate complicated shape variations,are considered as ideal grafts for craniofacial bone defect reconstruction.However,in most hybrid hydrogels,poor interaction between the polymer network and particles has detrimental effects on hydrogel rheological and structural properties,clinical manipulation and repair efficacy.In this article,we designed and prepared a series of hyaluronic acid composite hydrogel containing Cu-doped bioactive glass(CuBG)and phosphoserine(PS),in which hyaluronic acid was modified by methacrylate groups and phenylboronic acid groups to form a double crosslinked network.PS acted as an interaction bridge of CuBG particles and HAMA-PBA network to improve the mechanical properties of the composite hydrogels.The CuBG/PS hydrogels exhibited suitable rheological properties(injectable,self-healing,shape-adaptable),bone tissue integrating ability and anti-bacterial property.Meanwhile,we found that CuBG and PS have synergistic effect on improving osteogenic efficiency both in vitro and in vivo,particularly when the ratio of CuBG to PS is lower than 3(9CB/3PS).This work provided a versatile and scalable approach to enhanced the interaction within inorganic particles and polymer network in hydrogels without extra modification on components.展开更多
Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer.At present,most of wound repair materials are passive and can’t response to t...Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer.At present,most of wound repair materials are passive and can’t response to the wound microenvironment,resulting in a low utilization of bioactive substances and hence a poor therapeutic effect.Therefore,it’s essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality.In this work,metformin-laden CuPDA NPs composite hydrogel(Met@CuPDA NPs/HG)was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine(Gel-DA),Cu-loaded polydopamine nanoparticles(CuPDA NPs)with hyaluronic acid modified by phenyl boronate acid(HA-PBA),which possessed good injectability,self-healing,adhesive and DPPH scavenging performance.The slow release of metformin was achieved by the interaction with CuPDA NPs,boric groups(B-N coordination)and the constraint of hydrogel network.Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently.Moreover,CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of>95%within 10 min and also the slow release of Cu^(2+)to protect wound from infection for a long time.Met@CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu^(2+).More importantly,Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway.Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria,inhibiting inflammation,improving angiogenesis and accelerating the deposition of ECM and collagen.Therefore,Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.展开更多
Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics.However,most hydrogels offer limited cell growth and tissue formation ability due to the...Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics.However,most hydrogels offer limited cell growth and tissue formation ability due to their submicron-or nano-sized gel networks,which restrict the supply of oxygen,nutrients and inhibit the proliferation and differentiation of encapsulated cells.In recent years,3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds.In this study,we fabricated a macroporous hydrogel scaffold through horseradish peroxidase(HRP)-mediated crosslinking of silk fibroin(SF)and tyramine-substituted gelatin(GT)by extrusion-based low-temperature 3D printing.Through physicochemical characterization,we found that this hydrogel has excellent structural stability,suitable mechanical properties,and an adjustable degradation rate,thus satisfying the requirements for cartilage reconstruction.Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel.Moreover,the chondrogenic differentiation of stem cells was explored.Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used.Finally,the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model.After implantation for 12 and 16 weeks,histological evaluation of the sections was performed.We found that the enzymatic cross-linked and methanol treatment SF5GT15 hydrogel combined with cell aggregates promoted articular cartilage regeneration.In summary,this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.展开更多
基金supported by the Fundamental Research Funds for the Central Universities(grant number 2022ZYGXZR105)the National Natural Science Foundation of China(grant numbers 52272276,52073103,52203164)the Zhongshan Innovation Project of high-end Scientific Research Institutions(grant number 2020AG020)。
文摘Flexible hydrogels containing various osteogenic inorganic constituents,which can accommodate complicated shape variations,are considered as ideal grafts for craniofacial bone defect reconstruction.However,in most hybrid hydrogels,poor interaction between the polymer network and particles has detrimental effects on hydrogel rheological and structural properties,clinical manipulation and repair efficacy.In this article,we designed and prepared a series of hyaluronic acid composite hydrogel containing Cu-doped bioactive glass(CuBG)and phosphoserine(PS),in which hyaluronic acid was modified by methacrylate groups and phenylboronic acid groups to form a double crosslinked network.PS acted as an interaction bridge of CuBG particles and HAMA-PBA network to improve the mechanical properties of the composite hydrogels.The CuBG/PS hydrogels exhibited suitable rheological properties(injectable,self-healing,shape-adaptable),bone tissue integrating ability and anti-bacterial property.Meanwhile,we found that CuBG and PS have synergistic effect on improving osteogenic efficiency both in vitro and in vivo,particularly when the ratio of CuBG to PS is lower than 3(9CB/3PS).This work provided a versatile and scalable approach to enhanced the interaction within inorganic particles and polymer network in hydrogels without extra modification on components.
基金supported by the National Natural Science Foundation of China(Grant No.52272276,52073103,52203164)the Key-Area Research and Development Program of Guangdong Province(Grant No.2020B090924004)+2 种基金the funds for Zhongshan Innovation Project of high-end Scientific Research Institutions(Grant No.2020AG020)the Fundamental Research Funds for the Central Universities(No.2022ZYGXZR105)Guangdong Basic and Applied Basic Research Foundation(Grant No.2021A1515010905).
文摘Bacterial infection,excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer.At present,most of wound repair materials are passive and can’t response to the wound microenvironment,resulting in a low utilization of bioactive substances and hence a poor therapeutic effect.Therefore,it’s essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality.In this work,metformin-laden CuPDA NPs composite hydrogel(Met@CuPDA NPs/HG)was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine(Gel-DA),Cu-loaded polydopamine nanoparticles(CuPDA NPs)with hyaluronic acid modified by phenyl boronate acid(HA-PBA),which possessed good injectability,self-healing,adhesive and DPPH scavenging performance.The slow release of metformin was achieved by the interaction with CuPDA NPs,boric groups(B-N coordination)and the constraint of hydrogel network.Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently.Moreover,CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of>95%within 10 min and also the slow release of Cu^(2+)to protect wound from infection for a long time.Met@CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu^(2+).More importantly,Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway.Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria,inhibiting inflammation,improving angiogenesis and accelerating the deposition of ECM and collagen.Therefore,Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.
基金This work was financially supported by the National Natural Science Foundation of China(Grant nos.52073103,51873069 and 51873071)the National Key R&D Program of China(Grant No.2018YFC1106300)+1 种基金Beijing Municipal Health Commission(Grant nos.BMHC-2019-9,BMHC-2018-4 and PXM2020_026275_000002)the funds for Zhongshan Innovation Project of high-end Scientific Research Institutions(Grant No.2020AG020).
文摘Hydrogel scaffolds are attractive for tissue defect repair and reorganization because of their human tissue-like characteristics.However,most hydrogels offer limited cell growth and tissue formation ability due to their submicron-or nano-sized gel networks,which restrict the supply of oxygen,nutrients and inhibit the proliferation and differentiation of encapsulated cells.In recent years,3D printed hydrogels have shown great potential to overcome this problem by introducing macro-pores within scaffolds.In this study,we fabricated a macroporous hydrogel scaffold through horseradish peroxidase(HRP)-mediated crosslinking of silk fibroin(SF)and tyramine-substituted gelatin(GT)by extrusion-based low-temperature 3D printing.Through physicochemical characterization,we found that this hydrogel has excellent structural stability,suitable mechanical properties,and an adjustable degradation rate,thus satisfying the requirements for cartilage reconstruction.Cell suspension and aggregate seeding methods were developed to assess the inoculation efficiency of the hydrogel.Moreover,the chondrogenic differentiation of stem cells was explored.Stem cells in the hydrogel differentiated into hyaline cartilage when the cell aggregate seeding method was used and into fibrocartilage when the cell suspension was used.Finally,the effect of the hydrogel and stem cells were investigated in a rabbit cartilage defect model.After implantation for 12 and 16 weeks,histological evaluation of the sections was performed.We found that the enzymatic cross-linked and methanol treatment SF5GT15 hydrogel combined with cell aggregates promoted articular cartilage regeneration.In summary,this 3D printed macroporous SF-GT hydrogel combined with stem cell aggregates possesses excellent potential for application in cartilage tissue repair and regeneration.
