Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive mol...Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.展开更多
The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical ...The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.展开更多
Background:The healing of bone defects can be challenging for clinicians to manage,especially after exposure to ionizing radiation.In this regard,radiation therapy and accidental exposure to gamma(o inhibit bone forma...Background:The healing of bone defects can be challenging for clinicians to manage,especially after exposure to ionizing radiation.In this regard,radiation therapy and accidental exposure to gamma(o inhibit bone formation and increase the risk of fractures.Cortical bone-derivγ)-ray radiation have been shown ted stem cells(CBSCs)are reportedly essential for osteogenic lineages,bone maintenance and repair.This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect healing.Methods:CBSCs were extracted from C57BL/6 mice and were identified by flow cytometry.Then CBSCs were subjected to 6 Gyγ-ray radiation followed by treatment with various concentrations of melatonin.The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs in vitro were analyzed.The underlying mechanisms involved in genomic stability,apoptosis and oxidative stress-related signaling were further analyzed by Western blotting,flow cytometry and immunofluorescence assays.Moreover,postradiation femoral defect models were established and treated with Matrigel and melatonin.The effects of melatonin on postradiation bone healing in vivo were evaluated by micro-CT and pathological analysis.Results:The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin(P<0.05).Melatonin maintained genomic stability,reduced postradiation CBSC apoptosis and intracellular oxidative stress,and enhanced expression of antioxidant-related enzymes(P<0.05).Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)levels via the extracellular regulated kinase(ERK)/nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling pathway.Melatonin was also found to exhibit antioxidant effects via NRF2 signaling.In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume(BV/TV)and bone mineral density values with lower IL-6 and TNF-αlevels than in the irradiation and the Matrigel groups(P<0.05).Conclusions:This study suggested that melatonin could protect CBSCs against e defects.γ-ray radiation and assist in the healing of postradiation bon.展开更多
基金supported by the National Natural Science Foundation of China(51925304)Natural Science Foundation of Sichuan Province(2024NSFSC1023)Medical Research Program of Sichuan Province(Q23015).
文摘Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.
基金support of the National Natural Science Foundation of China(Grant No.52205593)Shaanxi Natural Science Foundation Project(2024JC-YBMS-711).
文摘The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.
基金funded by the 13th Five-year Plan for Key Discipline Construction Project of PLA(A350109)。
文摘Background:The healing of bone defects can be challenging for clinicians to manage,especially after exposure to ionizing radiation.In this regard,radiation therapy and accidental exposure to gamma(o inhibit bone formation and increase the risk of fractures.Cortical bone-derivγ)-ray radiation have been shown ted stem cells(CBSCs)are reportedly essential for osteogenic lineages,bone maintenance and repair.This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect healing.Methods:CBSCs were extracted from C57BL/6 mice and were identified by flow cytometry.Then CBSCs were subjected to 6 Gyγ-ray radiation followed by treatment with various concentrations of melatonin.The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs in vitro were analyzed.The underlying mechanisms involved in genomic stability,apoptosis and oxidative stress-related signaling were further analyzed by Western blotting,flow cytometry and immunofluorescence assays.Moreover,postradiation femoral defect models were established and treated with Matrigel and melatonin.The effects of melatonin on postradiation bone healing in vivo were evaluated by micro-CT and pathological analysis.Results:The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin(P<0.05).Melatonin maintained genomic stability,reduced postradiation CBSC apoptosis and intracellular oxidative stress,and enhanced expression of antioxidant-related enzymes(P<0.05).Western blotting validated the anti-inflammatory effects of melatonin by downregulating interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)levels via the extracellular regulated kinase(ERK)/nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling pathway.Melatonin was also found to exhibit antioxidant effects via NRF2 signaling.In vivo experiments demonstrated that the newly formed bone in the melatonin plus Matrigel group had higher trabecular bone volume per tissue volume(BV/TV)and bone mineral density values with lower IL-6 and TNF-αlevels than in the irradiation and the Matrigel groups(P<0.05).Conclusions:This study suggested that melatonin could protect CBSCs against e defects.γ-ray radiation and assist in the healing of postradiation bon.
