The influence of yttrium and manganese additions on the degradation and biocompatibility of magnesium-zinc-based alloys:In vitro and in vivo studies

The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone.The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration.In this study,we prepared and modified Mg-3Zn,Mg-3Zn-1Y,and Mg-2Zn-1Mn by hot extrusion,and used Mg-2.5Y-2.5Nd was as a control.We then investigated the effect of additions of Y and Mn on alloys'properties.Our results show that Mn and Y can improve not only compression strength but also corrosion resistance.The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro,and for this reason we selected it for implantation in vivo.The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction,and the degradation products left no signs of damage to the heart,liver,kidney,or brain.Furthermore,we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.

Tb/Mg掺杂对羟基磷灰石纳米颗粒基因载体理化特性的影响（英文）

羟基磷灰石纳米颗粒(HAnps)基因载体的转染效率与粒径、形貌、表面电荷、表面改性等有关。本研究通过水热合成法制备掺杂Tb/Mg的HAnps,观察Tb/Mg掺杂量对HAnps形貌、粒径、表面电荷、成分和细胞胞吞作用的影响。结果表明,掺Mg组的分散性优于掺Tb组的分散性。增加掺杂量使Tb-HAnps的粒径增大,而Mg-HAnps的粒径减小。掺Mg组的粒径及zeta电位均低于掺Tb组的。掺Mg量为7.5%的HAnps平均粒径约30 nm,呈相对均匀的细长杆状,而掺Mg量为10%的HAnps易于团聚。被胞吞入MG63细胞的Mg-HAnps-GFP呈点状分布于核周区域并形成荧光圈,而Tb-HAnps易于团聚。因此,作为基因载体,Mg-HAnps明显优于Tb-HAnps。

表面改性多孔钛植入体孔径和孔隙率对骨长入的影响（英文）

研究表面改性多孔钛种植体孔隙率和孔径对骨整合的影响。用粉末注射成形技术制备3种多孔钛植入体(A30,A40和A50,造孔剂NaCl的体积分数分别为30%,40%和50%)。将改性后的多孔植入体分别植入狗的背部肌肉和股骨内28、56和84 d后,检测多孔钛植入体与宿主骨之间界面成骨活性和骨组织长入孔隙内的情况。结果表明,喂料中造孔剂NaCl的添加量从30%增至50%(体积分数),多孔钛的总孔隙率从42.4%增至62.0%,大孔径(>50μm)多孔钛的质量分数从8.3%增至69.3%。组织学和荧光标记结果显示,A50植入体在28 d时骨界面的成骨活性明显高于其他组,在84d时A30植入体骨长入的量低于其他组。因此,A50植入体的孔结构适合新骨组织长入多孔植入体。

ATP50 Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress

Objective.Chronic stress(CS)-induced abnormal metabolism and other subsequent aspects of abnormality are threatening human health.Little is known regarding whether and how protein post-translational-modifications(PTMs)correlate with abnormal metabolism under CS.The aim of this study was to address this issue and also identify novel key protein PTM.Methods.First,we screened which pan-PTM had significant change between control and CS female mice and whether clinical CS females had similar pan-PTM change.Second,we performed quantitative PTM-omics and metabolomics to verify the correlation between abnormal protein PTMs and atypical metabolism.Third,we performed quantitative phospho-omics to identify the key PTM-regulating enzyme and investigate the interaction between PTM protein and PTM-regulating enzyme.Fourth,we attempted to rectify the abnormal metabolism by correcting the activity of the PTM-regulating enzyme.Finally,we examined whether the selected key protein was also correlated with stress scores and atypical metabolism in clinical women.Results.We initially found that multiple tissues of CS female mice have downregulated pan-crotonylation,and verified that the plasma of clinical CS females also had downregulated pan-crotonylation.Then we determined that ATP5O-K51 crotonylation decreased the most and also caused gross ATP5O decrement,whereas the plasma of CS mice had downregulated phospholipids.Next,downregulating ATP5O crotonylation partially recapitulated the downregulated phospholipid metabolism in CS mice.Next,we verified that HDAC2-S424 phosphorylation determined its decrotonylation activity on ATP5O-K51.Furthermore,correcting HDAC2 hyper-phosphorylation recovered the gross ATP5O level and partially rescued the downregulated phospholipid metabolism in CS mice.Finally,the ATP5O level was also significantly iower and correlated with high stress scores and downregulated phospholipid metabolism in clinical female plasma.Conclusion.This study discovered a novel PTM mechanism involving two distinct types of PTM in CS and provided a novel reference for the clinical precautions and treatments of CS.

Degradation and biological performance of porous osteomimetic biphasic calcium phosphate in vitro and in vivo

The combination between biphasic calcium phosphate(BCP)and the osteomimetic porous microstructure obtained via freeze casting is hoped to achieve excellent bone regeneration,while the effects of HA and b-TCP ratio changes on the degradation and biological performance of the BCP scaffolds with this unique microstructure need to be determined.Here,we prepared the osteomimetic BCP scaffolds with different HA/b-TCP ratios(HA30/b-TCP70,HA50/b-TCP50,HA70/b-TCP30)and the effects of different HA/b-TCPHA/b-TCP ratios on the degradation and biological performance were studied in vitro and vivo.These BCP scaffolds with different HA/b-TCP ratios exhibited similar microstructure,mechanical performance,and protein absorption capability,while HA70/b-TCP30 BCP scaffolds showed an advisable degradation rate.Study in vitro confirmed the bio-compatibility and promotion on the proliferation,differentiation of MG63 cells in the porous osteomimetic BCP scaffolds with a HA/b-TCP ratio at 30:70.Implantation experiments also showed that the porous osteomimetic BCP scaffolds with a HA/b-TCP ratio at 30:70 had excellent bone regeneration capacity and proper degradation rate compatible with bone growth.These results reveal that the porous osteomimetic BCP scaffold with a HA/b-TCP ratio at 30:70 is a potential candidate of biodegradable bone substitutes used for bone repair.

Polarized hydroxyapatite/BaTiO_(3) scaffolds with bio-inspired porous structure for enhanced bone penetration

The porous HA/BaTiO_(3)ceramics have the potential to exhibit superior capabilities to promote bone in-growth.However,there are few reports on in vivo studies.Here,we fabricated bio-inspired porous HA/BaTiO_(3)composites for bone repair via freeze-casting.These composites had a unique microstructure composed of the central canal and radically distributed lamellae,similar to the structure of nature cortical bone unite,the Haversian system.Polarized and non-polarized bio-inspired porous HA/BaTiO_(3)samples were implanted into the femoral condyle of the New Zealand rabbits.It was demonstrated that the polarization of the porous HA/BaTiO_(3)played a favorable part in bone regeneration.Moreover,the combination between the osteoconductivity of the microstructure and augmented osteogenic cell behavior induced by charges on surfaces of polarized porous HA/BaTiO_(3)facilitated bone penetration through the implants.The bio-inspired porous HA/BaTiO_(3)composites are demonstrated to be promising scaffolds for bone repair.