Engineering hydrogels that resemble biological tissues of various lengths via conventional fabrication techniques remains challenging.Three-dimensional(3D)bioprinting has emerged as an advanced approach for constructi...Engineering hydrogels that resemble biological tissues of various lengths via conventional fabrication techniques remains challenging.Three-dimensional(3D)bioprinting has emerged as an advanced approach for constructing complex biomimetic 3D architectures,which are currently restricted by the limited number of available bioinks with high printability,biomimicry,biocompatibility,and proper mechanical properties.Inspired by ubiquitous coacervation phenomena in biology,we present a unique mineral-biopolymer coacervation strategy that enables the hierarchical assembly of nanoclay and recombinant human collagen(RHC).This system was observed to undergo a coacervation transition(liquid‒liquid phase separation)spontaneously.The formed dense phase separated from its supernatant is the coacervate of clay-RHC-rich complexes,where polymer chains are sandwiched between silicate layers.Molecular dynamics simulation was first used to verify and explore the coacervation process.Then,the coacervates were demonstrated to be potential bioinks that exhibited excellent self-supporting and shear-thinning viscoelastic properties.Through extrusion-based printing,the versatility of the bioink was demonstrated by reconstructing the key features of several biological tissues,including multilayered lattice,vascular,nose,and ear-like structures,without the need for precrosslinking operations or support baths.Furthermore,the printed scaffolds were cytocompatible,elicited minimal inflammatory responses,and promoted bone regeneration in calvarial defects.展开更多
The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essent...The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essential conditions for bone regeneration.Meanwhile,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis.However,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp.Hence in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were explored.The results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene expression.Further-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions.The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic scaffolds.Besides,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358.In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality.These results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.展开更多
基金the projects of National Natural Science Foundation of China(No.32301209)Key R&D Projects of Henan Province(Nos.231111312400 and 241111220400).
文摘Engineering hydrogels that resemble biological tissues of various lengths via conventional fabrication techniques remains challenging.Three-dimensional(3D)bioprinting has emerged as an advanced approach for constructing complex biomimetic 3D architectures,which are currently restricted by the limited number of available bioinks with high printability,biomimicry,biocompatibility,and proper mechanical properties.Inspired by ubiquitous coacervation phenomena in biology,we present a unique mineral-biopolymer coacervation strategy that enables the hierarchical assembly of nanoclay and recombinant human collagen(RHC).This system was observed to undergo a coacervation transition(liquid‒liquid phase separation)spontaneously.The formed dense phase separated from its supernatant is the coacervate of clay-RHC-rich complexes,where polymer chains are sandwiched between silicate layers.Molecular dynamics simulation was first used to verify and explore the coacervation process.Then,the coacervates were demonstrated to be potential bioinks that exhibited excellent self-supporting and shear-thinning viscoelastic properties.Through extrusion-based printing,the versatility of the bioink was demonstrated by reconstructing the key features of several biological tissues,including multilayered lattice,vascular,nose,and ear-like structures,without the need for precrosslinking operations or support baths.Furthermore,the printed scaffolds were cytocompatible,elicited minimal inflammatory responses,and promoted bone regeneration in calvarial defects.
基金This work was sponsored by the National Science Foundation of China(Nos.32071341,52202358,52003302)The Natural Science Foundation of Guangdong Province(No.2017A030308004)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110824)the Science and Technology Project of Guangdong province(No.2018A050506021).
文摘The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essential conditions for bone regeneration.Meanwhile,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis.However,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp.Hence in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were explored.The results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene expression.Further-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions.The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic scaffolds.Besides,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358.In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality.These results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.
