Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complicati...Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complications. To address this problem,researchers have constructed various implantable biomaterials. However, the original pathological microenvironment of bone defects, such as residual tumors, severe infection, or other bone diseases, could further affect bone regeneration. Thus, the rational design of versatile biomaterials with integrated bone therapy and regeneration functions is in great demand. Many strategies have been applied to fabricate smart stimuli-responsive materials for bone therapy and regeneration, with stimuli related to external physical triggers or endogenous disease microenvironments or involving multiple integrated strategies. Typical external physical triggers include light irradiation, electric and magnetic fields, ultrasound, and mechanical stimuli. These stimuli can transform the internal atomic packing arrangements of materials and affect cell fate, thus enhancing bone tissue therapy and regeneration. In addition to the external stimuli-responsive strategy, some specific pathological microenvironments, such as excess reactive oxygen species and mild acidity in tumors, specific p H reduction and enzymes secreted by bacteria in severe infection, and electronegative potential in bone defect sites, could be used as biochemical triggers to activate bone disease therapy and bone regeneration.Herein, we summarize and discuss the rational construction of versatile biomaterials with bone therapeutic and regenerative functions. The specific mechanisms, clinical applications, and existing limitations of the newly designed biomaterials are also clarified.展开更多
Osteoporosis(OP)is an age-related disease of bone metabolism,characterized by bone mass loss and bone mi-croarchitecture deterioration,the poor osteogenesis microenvironment of OP caused hardly repairing of the bone d...Osteoporosis(OP)is an age-related disease of bone metabolism,characterized by bone mass loss and bone mi-croarchitecture deterioration,the poor osteogenesis microenvironment of OP caused hardly repairing of the bone defects.As a dynamic process to fuel cellular renovation,autophagy has been proved to play a vital role in regulating cell differentiation and maintaining bone homeostasis.Traditional bone repairing biomaterials are hardly repairing the bone defects under OP pathological microenvironment.Therefore,it is essential to develop-ment novel biomaterials to improve osteoporotic osteogenesis.Compared to biochemical cues,biophysical cues exhibited more advantages in biocompatible and side effects.Herein,inspired by the importance of enhanced au-tophagic response in osteoporotic environment,we intend to utilize the micro-/nano-structured hydroxyapatite(mnHA)bioceramics as the mimic structure of natural bone tissue to regulate autophagic activity in ovariectomy bone mesenchymal stem cells(OVX-BMSCs),finally promote to bone regeneration in OP condition.The results indicated that mnHA bioceramics promoted cell adhesion and osteogenesis of OVX-BMSCs,and enhanced au-tophagy level in OVX-BMSCs.In the calvarial defects of OVX-rats,the mnHA scaffold acquired excellent bone repair effect.According to the current findings,regulating the level of autophagy could be a promising strategy for improve osteoporotic osteogenesis in the future.展开更多
Tooth defect and loss are common clinical diseases in stomatology.With the extension of life expectancy,there is an increasing demand for tooth tissue and whole tooth regeneration.Compared with traditional oral prosth...Tooth defect and loss are common clinical diseases in stomatology.With the extension of life expectancy,there is an increasing demand for tooth tissue and whole tooth regeneration.Compared with traditional oral prosthetic treatment,tooth regeneration has unique advantages and has become one of the hotspots towards oral biomedical treatment.In this review,we discussed the development and challenges of tooth regeneration based on cells and materials,including tooth enamel,dentin,dental pulp,cementum,dentin-pulp complex,and the whole tooth regeneration,in order to provide a comprehensive,up-to-date,illustrative overview of tooth regeneration issues.The mechanisms of the regeneration were also summarized and discussed.Moreover,this review hints the future perspective and research direction of tooth regeneration in the challenging field of regenerative dentistry.展开更多
基金funded by the National Natural Science Foundation of China(82072396,81871490,81771047,82071096)Double Hundred Plan(20191819),Program of Shanghai Academic/Technology Research Leader(19XD1434500,20XD1433100)+3 种基金Science and Technology Commission of Shanghai Municipality(21490711700)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2021ZD12)Shanghai Collaborative Innovation Center for Translational Medicine(TM202010)Open Project of State Key Laboratory of Oral Diseases(SKLOD2021OF01).
文摘Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complications. To address this problem,researchers have constructed various implantable biomaterials. However, the original pathological microenvironment of bone defects, such as residual tumors, severe infection, or other bone diseases, could further affect bone regeneration. Thus, the rational design of versatile biomaterials with integrated bone therapy and regeneration functions is in great demand. Many strategies have been applied to fabricate smart stimuli-responsive materials for bone therapy and regeneration, with stimuli related to external physical triggers or endogenous disease microenvironments or involving multiple integrated strategies. Typical external physical triggers include light irradiation, electric and magnetic fields, ultrasound, and mechanical stimuli. These stimuli can transform the internal atomic packing arrangements of materials and affect cell fate, thus enhancing bone tissue therapy and regeneration. In addition to the external stimuli-responsive strategy, some specific pathological microenvironments, such as excess reactive oxygen species and mild acidity in tumors, specific p H reduction and enzymes secreted by bacteria in severe infection, and electronegative potential in bone defect sites, could be used as biochemical triggers to activate bone disease therapy and bone regeneration.Herein, we summarize and discuss the rational construction of versatile biomaterials with bone therapeutic and regenerative functions. The specific mechanisms, clinical applications, and existing limitations of the newly designed biomaterials are also clarified.
基金support from the National Natural Science Foundation of China (82072396,32271379)Science and Technology Commission of Shanghai Municipality (21490711700)the Interdisciplinary Program of Shanghai Jiao Tong University (YG2021ZD12).
文摘Osteoporosis(OP)is an age-related disease of bone metabolism,characterized by bone mass loss and bone mi-croarchitecture deterioration,the poor osteogenesis microenvironment of OP caused hardly repairing of the bone defects.As a dynamic process to fuel cellular renovation,autophagy has been proved to play a vital role in regulating cell differentiation and maintaining bone homeostasis.Traditional bone repairing biomaterials are hardly repairing the bone defects under OP pathological microenvironment.Therefore,it is essential to develop-ment novel biomaterials to improve osteoporotic osteogenesis.Compared to biochemical cues,biophysical cues exhibited more advantages in biocompatible and side effects.Herein,inspired by the importance of enhanced au-tophagic response in osteoporotic environment,we intend to utilize the micro-/nano-structured hydroxyapatite(mnHA)bioceramics as the mimic structure of natural bone tissue to regulate autophagic activity in ovariectomy bone mesenchymal stem cells(OVX-BMSCs),finally promote to bone regeneration in OP condition.The results indicated that mnHA bioceramics promoted cell adhesion and osteogenesis of OVX-BMSCs,and enhanced au-tophagy level in OVX-BMSCs.In the calvarial defects of OVX-rats,the mnHA scaffold acquired excellent bone repair effect.According to the current findings,regulating the level of autophagy could be a promising strategy for improve osteoporotic osteogenesis in the future.
基金funded by the National Natural Science Foun-dation of China(82072396,81871490,82071096)Program of Shanghai Academic/Technology Research Leader(19XD1434500,20XD1433100)+4 种基金Science and Technology Commission of Shanghai Municipality(21490711700,21DZ2294600)Double Hundred Plan(20191819)Interdisciplinary Program of Shanghai Jiao Tong Uni-versity(YG2021ZD12)Medical Engineering Cross Project of USST(10-20-310-402)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-037).
文摘Tooth defect and loss are common clinical diseases in stomatology.With the extension of life expectancy,there is an increasing demand for tooth tissue and whole tooth regeneration.Compared with traditional oral prosthetic treatment,tooth regeneration has unique advantages and has become one of the hotspots towards oral biomedical treatment.In this review,we discussed the development and challenges of tooth regeneration based on cells and materials,including tooth enamel,dentin,dental pulp,cementum,dentin-pulp complex,and the whole tooth regeneration,in order to provide a comprehensive,up-to-date,illustrative overview of tooth regeneration issues.The mechanisms of the regeneration were also summarized and discussed.Moreover,this review hints the future perspective and research direction of tooth regeneration in the challenging field of regenerative dentistry.