The treatment of large-area bone defects still faces many difficulties and challenges.Here,we developed a blood clot delivery platform loaded with BMP-2 protein(BMP-2@BC)for enhanced bone regeneration.Blood clot gel p...The treatment of large-area bone defects still faces many difficulties and challenges.Here,we developed a blood clot delivery platform loaded with BMP-2 protein(BMP-2@BC)for enhanced bone regeneration.Blood clot gel platform as natural biomaterials can be engineered from autologous blood.Once implanted into the large bone defect site,it can be used for BMP-2 local delivery,as well as modulating osteoimmunology by recruiting a great number of macrophages and regulating their polarization at different stages.Moreover,due to the deep-red color of blood clot gel,mild localized hyperthermia under laser irradiation further accelerated bone repair and regeneration.We find that the immune niche within the bone defect microenvironment can be modulated in a controllable manner by the blood clots implantation and laser treatment.We further demonstrate that the newly formed bone covered almost 95%of the skull defect area by our strategy in both mice and rat disease models.Due to the great biocompatibility,photothermal potential,and osteoimmunomodulation capacity,such technology shows great promise to be used in further clinical translation.展开更多
Implanted biomaterials have transformed healthcare and the treatment of injury and disease,but their infuence on the local immune landscape remains unclear.Here we discovered that degradation-resistant titanium-based ...Implanted biomaterials have transformed healthcare and the treatment of injury and disease,but their infuence on the local immune landscape remains unclear.Here we discovered that degradation-resistant titanium-based implants establish an immunosuppressive microenvironment by recruiting myeloid cells,including monocytes,macrophages,neutrophils,and myeloid-lineage dendritic cells.Unlike normal tissues,the tissues nearby implants exhibit an chronic inflamed and immunosuppressive status characterised by myeloid-rich,T cell-exhaustion gene signature by single-cell RNA sequencing.Vitamin C treatment provides an effective strategy to rescue the immunosuppressive microenvironment,which can be used as a regular supplement to reduce the risk of malignant cell survival around the implants.展开更多
基金the Program for Jiangsu Specially-Appointed Professors to C.W.This work was also supported by National Natural Science Foundation of China(No.32022043,81873995)the Preponderant Discipline Supporting Program of Discipline Construction Supporting Project of the Second Affiliated Hospital of Soochow University(XKTJ-XK202003)+5 种基金Suzhou Special Foundation of Clinical Key Diseases Diagnosis and Therapy(LCZX201904,LCZX201708)the Social Development Program for Clinical Advanced Technology in Jiangsu Province(BE2019662,BE2018656)the Key Laboratory for Peripheral Nerve Injury Repair Research of Suzhou(SZS201720)The Advanced Ph.D.research project of the Second Affiliated Hospital of Soochow University(SDFEYBS2011)The Open Project of Jiangsu Key Laboratory for Carbon-Based Functional Materials&Devices(KJS1905)This work is partly supported by Collaborative Innovation Center of Suzhou Nano Science and Technology,the Priority Academic Program Development of Jiangsu Higher Education Institutions,the 111 Project.
文摘The treatment of large-area bone defects still faces many difficulties and challenges.Here,we developed a blood clot delivery platform loaded with BMP-2 protein(BMP-2@BC)for enhanced bone regeneration.Blood clot gel platform as natural biomaterials can be engineered from autologous blood.Once implanted into the large bone defect site,it can be used for BMP-2 local delivery,as well as modulating osteoimmunology by recruiting a great number of macrophages and regulating their polarization at different stages.Moreover,due to the deep-red color of blood clot gel,mild localized hyperthermia under laser irradiation further accelerated bone repair and regeneration.We find that the immune niche within the bone defect microenvironment can be modulated in a controllable manner by the blood clots implantation and laser treatment.We further demonstrate that the newly formed bone covered almost 95%of the skull defect area by our strategy in both mice and rat disease models.Due to the great biocompatibility,photothermal potential,and osteoimmunomodulation capacity,such technology shows great promise to be used in further clinical translation.
基金supported by the National Natural Science Foundation of China(Grants No.32022043,81873995,82102611)the Natural Science Foundation of Jiangsu Province(Grant No.SBK2019040088)+2 种基金the Jiangsu Province Six Talent Peaks Project(Grant No.SWYY-110)and the Social Development Key Programs of Jiangsu Province-Advanced Clinical Technology(Grant No.BE2019662)supported by the Program for Jiangsu Specially-Appointed Professors to C.W,and by the Collaborative Innovation Center of Suzhou Nano Science&Technology,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),and the 111 Project.
文摘Implanted biomaterials have transformed healthcare and the treatment of injury and disease,but their infuence on the local immune landscape remains unclear.Here we discovered that degradation-resistant titanium-based implants establish an immunosuppressive microenvironment by recruiting myeloid cells,including monocytes,macrophages,neutrophils,and myeloid-lineage dendritic cells.Unlike normal tissues,the tissues nearby implants exhibit an chronic inflamed and immunosuppressive status characterised by myeloid-rich,T cell-exhaustion gene signature by single-cell RNA sequencing.Vitamin C treatment provides an effective strategy to rescue the immunosuppressive microenvironment,which can be used as a regular supplement to reduce the risk of malignant cell survival around the implants.
