Role of dendritic cells in MYD88-mediated immune recognition and osteoinduction initiated by the implantation of biomaterials

Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects.Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials.Previous studies have mainly focused on innate immune cells such as macrophages.In our previous work,we found that T lymphocytes,as adaptive immune cells,are also essential in the osteoinduction procedure.As the most important antigen-presenting cell,whether dendritic cells(DCs)can recognize non-antigen biomaterials and participate in osteoinduction was still unclear.In this study,we found that surgical trauma associated with materials implantation induces necrocytosis,and this causes the release of high mobility group protein-1(HMGB1),which is adsorbed on the surface of bone substitute materials.Subsequently,HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells,and the inflammatory response was activated.Finally,activated DCs release regeneration-related chemokines,recruit mesenchymal stem cells,and initiate the osteoinduction process.This study sheds light on the immune-regeneration process after bone substitute materials implantation,points out a potential direction for the development of bone substitute materials,and provides guidance for the development of clinical surgical methods.

Analytical solutions for inflation of pre-stretched elastomeric circular membranes under uniform pressure

Elastomeric membranes are frequently used in several emerging fields such as soft robotics and flexible electronics.For convenience of the structural design,it is very attractive to find simple analytical solutions to well describe their elastic deformations in response to external loadings.However,both the material/geometrical nonlinearity and the deformation inhomogeneity due to boundary constraints make it much challenging to get an exact analytical solution.In this paper,we focus on the inflation of a prestretched elastomeric circular membrane under uniform pressure,and derive an approximate analytical solution of the pressure-volume curve based upon a reasonable assumption on the shape of the inflated membrane.Such an explicit expression enables us to quantitatively design the material and geometrical parameters of the pre-stretched membrane to generate a target pressure-volume curve with prescribed peak point and initial slope.This work would be of help in the simplified mechanical design of structures involving elastomeric membranes.

The authors acknowledge the financial support from the National Natural Science Foundation of China(project No.31971247).

Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration.At present,autograft harvest procedures may cause secondary trauma to patients,while bone scaffold materials lack osteogenic activity,resulting in a limited application.Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft,but the explosive release of growth factor may also cause side effects.In this study,we innovatively used platelet-rich fibrin(PRF)-modified bone scaffolds(Bio-Oss®)to replace autograft,and used cytokine(BMP-2)to enhance osteogenesis.Encouragingly,this mixture,which we named“Autograft Mimic(AGM)”,has multiple functions and advantages.(1)The fiber network provided by PRF binds the entire bone scaffold together,thereby shaping the bone grafts and maintaining the space of the defect area.(2)The sustained release of BMP-2 from bone graft promoted bone regeneration continuously.(3)AGM recruited bone marrow mesenchymal stem cells(BMSCs)and promote their proliferation,migration,and osteogenic differentiation.Thus,AGM developed in this study can improve osteogenesis,and provide new guidance for the development of clinical bone grafts.

Role of neuroinflammation in neurodegeneration development

Studies in neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease and Amyotrophic lateral sclerosis,Huntington’s disease,and so on,have suggested that inflammation is not only a result of neurodegeneration but also a crucial player in this process.Protein aggregates which are very common pathological phenomenon in neurodegeneration can induce neuroinflammation which further aggravates protein aggregation and neurodegeneration.Actually,inflammation even happens earlier than protein aggregation.Neuroinflammation induced by genetic variations in CNS cells or by peripheral immune cells may induce protein deposition in some susceptible population.Numerous signaling pathways and a range of CNS cells have been suggested to be involved in the pathogenesis of neurodegeneration,although they are still far from being completely understood.Due to the limited success of traditional treatment methods,blocking or enhancing inflammatory signaling pathways involved in neurodegeneration are considered to be promising strategies for the therapy of neurodegenerative diseases,and many of them have got exciting results in animal models or clinical trials.Some of them,although very few,have been approved by FDA for clinical usage.Here we comprehensively review the factors affecting neuroinflammation and the major inflammatory signaling pathways involved in the pathogenicity of neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,and Amyotrophic lateral sclerosis.We also summarize the current strategies,both in animal models and in the clinic,for the treatment of neurodegenerative diseases.