Proximal Femur Bionic Nail (PFBN): A Panacea for Unstable Intertrochanteric Femur Fracture

With the aging population,intertrochanteric femur fracture in the elderly has become one of the most serious public health issues and a hot topic of research in trauma orthopedics.Due to the limitations of internal fixation techniques and the insufficient mechanical design of nails,the occurrence of complications delays patient recovery after surgical treatment.Design of a proximal femur bionic nail(PFBN)based on Zhang’s N triangle theory provides triangular supporting fixation,which dramatically decreases the occurrence of complications and has been widely used for clinical treatment of unstable intertrochanteric femur fracture worldwide.In this work,we developed an equivalent biomechanical model to analyze improvement in bone remodeling of unstable intertrochanteric femur fracture through PFBN use.The results show that compared with proximal femoral nail antirotation(PFNA)and InterTan,PFBN can dramatically decrease the maximum strain in the proximal femur.Based on Frost’s mechanostat theory,the local mechanical environment in the proximal femur can be regulated into the medium overload region by using a PFBN,which may render the proximal femur in a state of physiological overload,favoring post-operative recovery of intertrochanteric femur fracture in the elderly.This work shows that PFBN may constitute a panacea for unstable intertrochanteric femur fracture and provides insights into improving methods of internal fixation.

Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma

The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-cell RNA sequencing(sc RNA-seq)data,which characterize the transcription state at single-cell resolution,we produced an atlas of the immune microenvironment in OS.The results suggested that a cluster of regulatory dendritic cells(DCs)might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells.We also found that major histocompatibility complex class I(MHC-I)molecules were downregulated in cancer cells.The findings indicated a reduction in tumor immunogenicity in OS,which can be a potential mechanism of tumor immune escape.Of note,CD24 was identified as a novel“don’t eat me”signal that contributed to the immune evasion of OS cells.Altogether,our findings provide insights into the immune landscape of OS,suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.

Research advances of nanomaterials for the acceleration of fracture healing

The bone fracture cases have been increasing yearly,accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture.Although clinical materials facilitate fracture healing(e.g.,metallic and composite materials),they cannot fulfill the requirements due to the slow degradation rate,limited osteogenic activity,inadequate osseointegration ability,and suboptimal mechanical properties.Since early 2000,nanomaterials successfully mimic the nanoscale features of bones and offer unique properties,receiving extensive attention.This paper reviews the achievements of nanomaterials in treating bone fracture(e.g.,the intrinsic properties of nanomaterials,nanomaterials for bone defect filling,and nanoscale drug delivery systems in treating fracture delayed union).Furthermore,we discuss the perspectives on the challenges and future directions of developing nanomaterials to accelerate fracture healing.

ROS-responsive and triple-synergistic mitochondria-targeted polymer micelles for efficient induction of ICD in tumor therapeutics

Immunogenic cell death(ICD)represents a modality of apoptosis distinguished by the emanation of an array of damage-related molecular signals.This mechanism introduces a novel concept in the field of contemporary tumor immunotherapy.The inception of reactive oxygen species(ROS)within tumor cells stands as the essential prerequisite and foundation for ICD induction.The formulation of highly efficacious photodynamic therapy(PDT)nanomedicines for the successful induction of ICD is an area of significant scientific inquiry.In this work,we devised a ROS-responsive and triple-synergistic mitochondria-targeted polymer micelle(CAT/CPT-TPP/PEG-Ce6,CTC)that operates with multistage amplification of ROS to achieve the potent induction of ICD.Utilizing an“all-in-one”strategy,we direct both the PDT and chemotherapeutic units to the mitochondria.Concurrently,a multistage cyclical amplification that caused by triple synergy strategy stimulates continuous,stable,and adequate ROS generation(domino effect)within the mitochondria of cells.Conclusively,influenced by ROS,tumor cell-induced ICD is effectively activated,remodeling immunogenicity,and enhancing the therapeutic impact of PDT when synergized with chemotherapy.Empirical evidence from in vitro study substantiates that CTC micelles can efficiently provoke ICD,catalyzing CRT translocation,the liberation of HMGB1 and ATP.Furthermore,animal trials corroborate that polymer micelles,following tail vein injection,can induce ICD,accumulate effectively within tumor tissues,and markedly inhibit tumor growth subsequent to laser irradiation.Finally,transcriptome analysis was carried out to evaluate the changes in tumor genome induced by CTC micelles.This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology.

Advances in osseointegration of biomimetic mineralized collagen and inorganic metal elements of natural bone for bone repair

At this stage,bone defects caused by trauma,infection,tumor,or congenital diseases are generally filled with autologous bone or allogeneic bone transplantation,but this treatment method has limited sources,potential disease transmission and other problems.Ideal bone-graft materials remain continuously explored,and bone defect reconstruction remains a significant challenge.Mineralized collagen prepared by bionic mineralization combining organic polymer collagen with inorganic mineral calcium phosphate can effectively imitate the composition and hierarchical structure of natural bone and has good application value in bone repair materials.Magnesium,strontium,zinc and other inorganic components not only can activate relevant signaling pathways to induce differentiation of osteogenic precursor cells but also stimulate other core biological processes of bone tissue growth and play an important role in natural bone growth,and bone repair and reconstruction.This study reviewed the advances in hydroxyapatite/collagen composite scaffolds and osseointegration with natural bone inorganic components,such as magnesium,strontium and zinc.

“Genetic scissors”CRISPR/Cas9 genome editing cutting-edge biocarrier technology for bone and cartilage repair

CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in biological research.As a disruptive technique,CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as well.This review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair,illustrates its mechanism for promoting osteogenesis and chondrogenesis,and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.