Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved n...Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.展开更多
Macrophages play a key role in wound healing.Dysfunction of their MO polarization to M2 leads to disorders of the wound immune microenvironment and chronic inflammation,which affects wound healing.Regulating the polar...Macrophages play a key role in wound healing.Dysfunction of their MO polarization to M2 leads to disorders of the wound immune microenvironment and chronic inflammation,which affects wound healing.Regulating the polarization of Mo macrophages to M2 macro-phages is an effective strategy for treating wound healing.Mesenchymal stem cells(MsCs)deliver endogenous regulatory factors via paracrine extracellular vesicles,which may play a key role in wound healing,and previous studies have shown that apoptotic bodies(ABs)are closely associated with inflammation regression and macrophage polarization.However,the specific regulatory mechanisms involved in ABs remain unknown.In the present study,we de-signed an MSC-AB(MSC-derived AB)-loaded polycaprolactone(PCL)scaffold,evaluated the macrophage phenotype and skin wound inflammation in vivo and in vitro,and explored the ability of MSC-AB-loaded PCL scaffolds to promote wound healing.Our data suggest that the PCL scaffold regulates the expression of the CCL-1 gene by targeting the delivery of mmu-miR-21a-5p by local sustained-release MSC-ABs,and drives MO macrophages to program M2 macrophages to regulate inflammation and angiogenesis,thereby synergistically promoting wound healing.This study provides a promising therapeutic strategy and experimental basis for treating various diseases associated with imbalances in proinflammatory and anti-inflammatory immuneresponses.展开更多
文摘Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue.Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment.Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants(SCVs).Moreover,microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process,leading to impaired bone defect repair.Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade,challenges remain in clinical management.The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections,but a comprehensive review of their research progress is lacking.This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration,and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections.It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.
基金supported by the National Natural Science Foundation of China (No.82072443,82372425)the Chongqing Outstanding Project of Overseas Chinese Entrepreneurship and Innovation Support Program (China) (No.CX2022032)+6 种基金the Articular Cartilage Tissue Engineering and Regenerative Medicine Team,Chongqing Medical University (No.W0080)the General Project of Natural Science Foundation of Chongqing,China (No.CSTB2023NSCQMSX0166)the"Tomorrow Cup"Teacher-Student Cocreation Teaching and Research Innovation Project of International Medical College of Chongqing Medical University (No.KY20220204)the Chengdu Medical Research Project (Sichuan,China) (No.2023191)the China Postdoctoral Science Foundation (No.2022M710557)the Natural Science Foundation of Chongqing,China (No.CSTB2023NSCQBHx0011)the Young Excellent Science and Technology Talent Project of the First Affiliated Hospital of Chongqing Medical University (No.ZYRC2022-05).
文摘Macrophages play a key role in wound healing.Dysfunction of their MO polarization to M2 leads to disorders of the wound immune microenvironment and chronic inflammation,which affects wound healing.Regulating the polarization of Mo macrophages to M2 macro-phages is an effective strategy for treating wound healing.Mesenchymal stem cells(MsCs)deliver endogenous regulatory factors via paracrine extracellular vesicles,which may play a key role in wound healing,and previous studies have shown that apoptotic bodies(ABs)are closely associated with inflammation regression and macrophage polarization.However,the specific regulatory mechanisms involved in ABs remain unknown.In the present study,we de-signed an MSC-AB(MSC-derived AB)-loaded polycaprolactone(PCL)scaffold,evaluated the macrophage phenotype and skin wound inflammation in vivo and in vitro,and explored the ability of MSC-AB-loaded PCL scaffolds to promote wound healing.Our data suggest that the PCL scaffold regulates the expression of the CCL-1 gene by targeting the delivery of mmu-miR-21a-5p by local sustained-release MSC-ABs,and drives MO macrophages to program M2 macrophages to regulate inflammation and angiogenesis,thereby synergistically promoting wound healing.This study provides a promising therapeutic strategy and experimental basis for treating various diseases associated with imbalances in proinflammatory and anti-inflammatory immuneresponses.
