Biological hydroxyapatite(BHA)is widely used in the treatment of clinical bone defects due to its good biocompatibility and osteoconductivity.The clinical application of mateiral size is based on the principle of bone defect area adaptation,which contributes to diversity of BHA sizes.However,different sizes correspond to different hierarchi-cal levels of bone biomimicry.As the size changes,the bone biomimicry hierarchy evolves accordingly and influences the process of bone repair and regeneration through osteo-coagulo-immunomodulation,leading to unstable bone graft outcomes.Therefore,this paper reviews the size effect of clinical BHA,analyzes the multilevel structure of natural bone,proposes the evolution of bone biomimetic hierarchy triggered by the size of BHA,and further analyzes the size-media-ted osteo-coagulo-immunomodulation.Based on the hierarchical levels of bone and its osteo-coagulo-immunomodula-tion effect,we provide a new understanding of the biolog-ical principle of the size effect of biomaterials and a theo-retical basis for the basic research and clinical application of different size BHA materials.

Objective To investigate the effect of Angelica polysaccharides on the balance of Th17/T-regulatory(Treg)cells and the expression of related inflammatory factor proteins in the bone marrow of mice with aplastic anemia.Methods 50 male BALB/c mice were randomly divided into a normal group,model group,cyclosporine A(CsA)group,and angelica polysaccharide low-(APS-L)and high-dose(APS-H)groups.A mouse model of aplastic anemia was prepared by combining irradiation with allogeneic lymphocyte infusion.After modeling,the mice were orally administered with corresponding drugs for 28 days.The general condition,weight changes,and spleen index of the mice were observed.Blood samples were taken to test for changes in basic hematological parameters of peripheral blood,and hematoxylin and eosin staining was used to evaluate the pathological changes in mouse bone marrow tissue.An ELISA method was applied to detect bone marrow TGF-β1.The expression levels of proteins such as IL-10,IL-17A,and IL-6 were analyzed,and flow cytometry was used in detecting the bone marrow Th17/Treg cell ratio.Results Compared with the normal group,the model group mice showed clumsiness during activity;lethargy;pale eyelids,lips,and ears;and reduced food and water intake.Both body weight and spleen index were significantly decreased.Peripheral red blood cell,white blood cell,and platelet counts and hemoglobin concentration were significantly reduced.A disordered bone marrow tissue structure and significantly reduced proliferation of hematopoietic tissue were seen.The expression of IL-17A and IL-6 proteins was significantly upregulated,and the expression of TGF-β1 and IL-10 protein was significantly downregulated.The proportion of Th17 cells in bone marrow significantly increased,the proportion of Treg cells significantly decreased,and the ratio of Th17/Treg cells significantly increased(P＜0.01).Compared with the model group,the general condition of the APS-L and APS-H groups improved,showing an increase in food and water intake;a significant increase in body weight and spleen index;a significant increase in peripheral red blood cells,white blood cells,platelets,and hemoglobin concentration(P＜0.05);an improvement in bone marrow tissue structure;and an increase in hematopoietic tissue proliferation(P＜0.05).The expression of IL-17A and IL-6 proteins was significantly downregulated.The expression of TGF-β1 and IL-10 protein was significantly upregulated(P＜0.05 or P＜0.01).The proportion of Th17 cells in bone marrow significantly decreased,the proportion of Treg cells significantly increased,and the ratio of Th17/Treg cells significantly decreased(P＜0.01).Conclusions Angelica polysaccharides can improve bone marrow hematopoietic function in aplastic anemia mice,and its mechanism of action may include the regulation of Th17/Treg cell balance.

ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.