Biodegradable polycaprolactone/β-tricalcium phosphate(PT)composites are desirable candidates for bone tissue engineering applications.A higherβ-tricalcium phosphate(TCP)ceramic content improves the mechanical,hydrop...Biodegradable polycaprolactone/β-tricalcium phosphate(PT)composites are desirable candidates for bone tissue engineering applications.A higherβ-tricalcium phosphate(TCP)ceramic content improves the mechanical,hydrophilic and osteogenic properties of PT scaffolds in vitro.Using a dynamic degradation reactor,we estab-lished a steady in vitro degradation model to investigate the changes in the physio-chemical and biological properties of PT scaffolds during degradation.PT46 and PT37 scaffolds underwent degradation more rapidly than PT scaffolds with lower TCP contents.In vivo studies revealed the rapid degradation of PT(PT46 and PT37)scaffolds disturbed macrophage responses and lead to bone healing failure.Macrophage co-culture assays and a subcutaneous implantation model indicated that the scaffold degradation process dynamically affected macro-phage responses,especially polarization.RNA-Seq analysis indicated phagocytosis of the degradation products of PT37 scaffolds induces oxidative stress and inflammatory M1 polarization in macrophages.Overall,this study reveals that the dynamic patterns of biodegradation of degradable bone scaffolds highly orchestrate immune responses and thus determine the success of bone regeneration.Therefore,through evaluation of the biological effects of biomaterials during the entire process of degradation on immune responses and bone regeneration are necessary in order to develop more promising biomaterials for bone regeneration.展开更多
Bioprinting has been a flouring way to fabricate complex tissue and organ mimics via precisely depositing printable cell-laden biomaterials.However,there is a limited number of biomaterials that fulfill the mechanical...Bioprinting has been a flouring way to fabricate complex tissue and organ mimics via precisely depositing printable cell-laden biomaterials.However,there is a limited number of biomaterials that fulfill the mechanical property of printing while meeting the responsive environment desired for the cells.Despite excellent cell compatibility and bioactivity,collagen suffers from difficulties in processing and printability which inhibited its utilization in three-dimensional(3D)bioprinting.Herein,we address this limitation by using ionic liquid as the solvent in the modification process,enabling collagens modified with quantified norbornene for chemical crosslink and extrusion-based 3D printing.With improved solubility and rheological properties,norbornene-functionalized collagen(Col-Nor)exhibited better shape fidelity in extrusion-based 3D printing compared with the one before modification.Photo-crosslinked Col-Nor hydrogel provided structural support and promoted the adhesion,proliferation,and differentiation of various types of cells,which afforded a centimeter-scale liver tissue model.This highly generalizable methodology expands printable,versatile,and tunable hydrogels developed from the natural extracellular matrix,allowing the biofabrication of 3D liver tissue model with branched vascular networks.展开更多
基金National Key Research and Development Program of China(grant number 2017YFC1104900)National Natural Science Foundation of China(No.51871239,51771227,52171244 and 81772328)The authors also appreciate the support from the Incubation Project of the Army’s Medical Technology Youth Cultivation Program of China(17QNP021)。
文摘Biodegradable polycaprolactone/β-tricalcium phosphate(PT)composites are desirable candidates for bone tissue engineering applications.A higherβ-tricalcium phosphate(TCP)ceramic content improves the mechanical,hydrophilic and osteogenic properties of PT scaffolds in vitro.Using a dynamic degradation reactor,we estab-lished a steady in vitro degradation model to investigate the changes in the physio-chemical and biological properties of PT scaffolds during degradation.PT46 and PT37 scaffolds underwent degradation more rapidly than PT scaffolds with lower TCP contents.In vivo studies revealed the rapid degradation of PT(PT46 and PT37)scaffolds disturbed macrophage responses and lead to bone healing failure.Macrophage co-culture assays and a subcutaneous implantation model indicated that the scaffold degradation process dynamically affected macro-phage responses,especially polarization.RNA-Seq analysis indicated phagocytosis of the degradation products of PT37 scaffolds induces oxidative stress and inflammatory M1 polarization in macrophages.Overall,this study reveals that the dynamic patterns of biodegradation of degradable bone scaffolds highly orchestrate immune responses and thus determine the success of bone regeneration.Therefore,through evaluation of the biological effects of biomaterials during the entire process of degradation on immune responses and bone regeneration are necessary in order to develop more promising biomaterials for bone regeneration.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16020804,XDA16020802)the National Natural Science Foundation of China(22021002,22022705)。
文摘Bioprinting has been a flouring way to fabricate complex tissue and organ mimics via precisely depositing printable cell-laden biomaterials.However,there is a limited number of biomaterials that fulfill the mechanical property of printing while meeting the responsive environment desired for the cells.Despite excellent cell compatibility and bioactivity,collagen suffers from difficulties in processing and printability which inhibited its utilization in three-dimensional(3D)bioprinting.Herein,we address this limitation by using ionic liquid as the solvent in the modification process,enabling collagens modified with quantified norbornene for chemical crosslink and extrusion-based 3D printing.With improved solubility and rheological properties,norbornene-functionalized collagen(Col-Nor)exhibited better shape fidelity in extrusion-based 3D printing compared with the one before modification.Photo-crosslinked Col-Nor hydrogel provided structural support and promoted the adhesion,proliferation,and differentiation of various types of cells,which afforded a centimeter-scale liver tissue model.This highly generalizable methodology expands printable,versatile,and tunable hydrogels developed from the natural extracellular matrix,allowing the biofabrication of 3D liver tissue model with branched vascular networks.
