研究血清胆红素对2型糖尿病患者心脏结构发生改变前心肌功能的影响

目的研究2型糖尿病患者心脏结构发生改变前,血清胆红素对其心肌功能的影响。方法选取符合入选标准的2型糖尿病受试者89例作为糖尿病组,随机选取2020年12月~2022年6月于上海市第一人民医院嘉定分院就诊的无糖尿病和心脑血管疾病史的受试者67例为对照组。分别获取受试者年龄、体质量指数(BMI)、收缩压(SBP)、总胆固醇(TC)、总甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、空腹血糖(FPG)、总胆红素(TBIL)、直接胆红素(DBIL)和间接胆红素(IBIL);左心室舒张末期(LVEDD)和收缩末期内径(LVESD)、室间隔厚度(IVSD)、左心室后壁厚度(LVPWD);E/e'、e'/a'、左心室射血分数(LVEF)、左心室心肌分层环向应变(GCSendo、GCSmid和GCSepi)等。比较两组之间各项指标的差异;采用多因素相关分析胆红素与血生化指标及左心室结构和功能指标的相关性。结果与对照组相比,糖尿病组受试者的年龄、BMI、SBP、TG、FPG和IBIL均较大(P均<0.05)。与对照组相比,糖尿病组受试者左心室舒张功能受损,E/e'较高,而e'/a'较低(P均<0.05),糖尿病组受试者左心室心肌分层环向应变指标GCSendo、GCSmid和GCSepi均较低(P均<0.05)。多因素线性回归分析提示:GCSmid、GCSepi是TBIL、DBIL、IBIL独立影响因素(P均<0.05);HDL和血红蛋白是TBIL的独立影响因素(P均<0.05);LDL是DBIL独立影响因素(P<0.05);血红蛋白是IBIL独立影响因素(P<0.05)。Bland-Altman分析显示心肌分层环向应变测量重复性较好。结论心肌分层环向应变可以早期发现糖尿病患者心肌受损,胆红素对糖尿病早期心肌损害有保护作用。

Micropatterned composite membrane guides oriented cell growth and vascularization for accelerating wound healing

Skin defect is common in daily life,but repairing large skin defects remains a challenge.Using biomaterials to deliver biochemical or physical factors to promote skin tissue regeneration is of great significance for accelerating wound healing.Specific surface micropatterns on biomaterials could affect cell behavior and tissue regeneration.However,few studies have focused on the construction of wound healing biomaterials with surface micropatterns and their role in skin tissue regeneration.In the present study,gelatin-polycaprolactone/silk fibroin composite membranes with different micropatterns were fabricated by photolithography,including line,grid and plane micropatterns.In vitro cell experiments demonstrated that the line micropattern on the composite membrane could guide cell-oriented growth,and more importantly,promote the expression of angiogenesis-related markers andα-smooth muscle actin(α-SMA)at both gene level and protein level.In the rat full-thickness skin defect model,the composite membrane with line micropatterns increasedα-SMA production and neovascularization in wounds,leading to accelerated wound contraction and healing.The current study not only suggests that composite membranes with specific micropatterns can be promising wound repair materials but also provides new insights into the importance of biomaterial surface topology for tissue regeneration.

还原氧化石墨烯介导的磁电效应诱导间质干细胞的神经分化

神经退行性疾病是人类最难治疗的疾病之一.易获取的间充质干细胞(MSCs)可用于自体干细胞移植,间充质干细胞治疗被认为是最有希望的治疗选择之一.然而,传统的生长诱导因子难以实现间充质干细胞的神经分化.电刺激方式可以诱导间充质干细胞的神经分化,但外部电线和复杂的设备给临床治疗带来了很大阻碍.在这项研究中,基于磁电感应效应,我们发现在无需任何生物或化学因子的辅助下,旋转磁场(RMF)驱动下还原氧化石墨烯膜(rGO-M)上产生的无线电信号可以诱导间充质干细胞的神经元样分化.体外实验结果显示,RMF以400 r min^(-1)的速度刺激rGO-M,每天刺激15 min,rGO-M上的MSCs能表达神经元特异性基因和蛋白,连续处理15天后,基因和蛋白的表达量得到明显提升.大鼠体内实验证实,rGO-M上的外源性间充质干细胞可以在旋转磁场的驱动下分化成神经元样细胞.鉴于rGO-M和自体间充质干细胞来源成本较低,rGO-M介导的无线电刺激方法为神经退行性疾病的干细胞治疗提供了一个可行的方案.

Black phosphorus nanosheets-based tumor microenvironment responsive multifunctional nanosystem for highly efficient photo-/sono-synergistic therapy of non-Hodgkin lymphoma

Finding improved therapeutic protocols against non-Hodgkin’s lymphoma(NHL) remains an unmet clinical demand. Phototherapy is a promising alternative treatment for traditional clinical therapeutic methods, but the limited tissue penetration blocks the therapeutics. Inspired by the excellent physical and chemical properties of black phosphorus nanosheets(BPNSs), a fluorescence and thermal imaging guided photo-/sono-synergistic treatment platform BPNSs@PEG-SS-IR780/RGD is developed. This ingenious multifunctional theranostic platform not only exhibits outstanding photothermal conversion efficiency and highly efficient reactive oxygen species generation, but also has good biocompatibility, tumor-targeting and tumor microenvironment responsiveness. In addition, BPNSs@PEG-SS-IR780/RGD could actively target the tumor sites and generate excellent photothermal, photodynamic and sonodynamic therapeutic efficacy. Both in vitro and in vivo experiments indicate that BPNSs@PEG-SS-IR780/RGD can be a promising nanomaterial for NHL imaging and therapy. Taken together, this study not only expands the application field of black phosphorus materials, but also provides a possibility to design a new generation of NHL treatment regimens with clinical application potential.

Injectable bone cement with magnesium-containing microspheres enhances osteogenesis via anti-inflammatory immunoregulation

Injectable bone cement is especially useful in minimally invasive surgeries to repair small and irregular bone defects.Amongst different kinds of injectable bone cements,bioactive calcium phosphate bone cement(CPC)has been widely studied due to its biological activity.However,its dense structure and poor biodegradability prevent the ingrowth of living tissue,which leads to undesirable bone regeneration and clinical translation.To address this issue,we prepared bone cement based on Magnesium-containing microspheres(MMSs)that can not only be cured into a 3D porous scaffold but also have controllable biodegradability that continuously provides space for desired tissue ingrowth.Interestingly,magnesium ions released from MMSs cement(MMSC)trigger positive immunomodulation via upregulation of the anti-inflammatory genes IL-10 and M2 macrophage polarization with increased expression of CD206,which is beneficial to osteogenesis.Moreover,the physicochemical properties of MMSC,including heat release,rheology and setting time,can be tuned to meet the requirements of injectable bone cement for clinical application.Using a rat model,we have demonstrated that MMSC promoted osteogenesis via mediation of tissue ingrowth and anti-inflammatory immunomodulation.The study provides a paradigm for the design and preparation of injectable bone cements with 3D porous structures,biodegradability and anti-inflammatory immunoregulation to efficiently promote osteogenesis.

Zn/Sr dual ions-collagen co-assembly hydroxyapatite enhances bone regeneration through procedural osteo-immunomodulation and osteogenesis

The immune microenvironment induced by biomaterials played vital roles in bone regeneration.Hydroxyapatite(HA)and its ion-substituted derivates represent a large class of core inorganic materials for bone tissue engineering.Although ion substitution was proved to be a potent way to grant HA more biological functions,few studies focused on the immunomodulatory properties of ion-doped HA.Herein,to explore the potential osteoimmunomodulatory effects of ion-doped HA,zinc and strontium co-assembled into HA through a collagen template biomimetic way(ZnSr-Col-HA)was successfully achieved.It was found that ZnSr-Col-HA could induce a favorable osteo-immune microenvironment by stimulating macrophages.Furthermore,ZnSr-Col-HA demonstrated a procedural promoting effect on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.Specifically,the osteo-immune microenvironment acted as a dominant factor in promoting osteogenic gene expressions at the early stage through OSM signal pathway.Whereas the direct stimulating effects on BMSCs by Zn^(2+)/Sr^(2+) were more effectively at the later stage with Nfatc1/Maf and Wnt signals activated.In vivo study confirmed strong promoting effects of ZnSr-Col-HA on critical-sized cranial defect repair.The current study indicated that such a combined biomaterial design philosophy of dual ion-doping and biomimetic molecular co-assembly to endow HA applicable osteoimmunomodulatory characteristics might bring up a new cutting-edge concept for bone regeneration study.

Si-doping bone composite based on protein template- mediated assembly for enhancing bone regeneration

Bio-inspired hybrid materials that contain organic and inorganic networks interpenetration at the molecular level have been a particular focus of interest on designing novel nanoscale composites. Here we firstly synthesized a series of hybrid bone composites, silicon-hydroxyapatites/silk fibroin/collagen, based on a specific molecular assembled strategy. Results of material characterization confirmed that silicate had been successfully doped into nano-hydroxyapatite lattice. In vitro evaluation at the cellular level clearly showed that these Si-doped composites were capable of promoting the adhesion and proliferation of rat mesenchymal stem cells （rMSCs）, extremely enhancing osteoblastic differentiation of rMSCs compared with silicon-free composite. More interestingly, we found there was a critical point of silicon content in the composition on regulating multiple cell behaviors. In vivo animal evaluation further demonstrated that Si-doped composites enabled to significantly improve the repair of cranial bone defect. Consequently, our current work not only suggests fabricating a potential bone repair materials by integrating element-doping and molecular assembled strategy in one system, but also paves a new way for constructing multi-functional composite materials in the future.

Synthesis and thermal stability of selenium-doped hydroxyapatite with different substitutions

Selenium （Se） plays a specific role in human health, especially for its anti- tumor effect. Incorporation of selenium into biocompatible hydroxyapatite （HAP） may endow the materials with novel characteristics. In the current work, a series of seleniumdoped hydroxyapatite （Se-HAP） nanoparticles with different SelP ratios were synthesized by a modified chemical precipitation. It was revealed that the powders with/without heattreatment were nano-sized needle-like HAP while the heat-treated samples have high crystallinity. The addition of selenium decreases the crystallinity of the synthesized apatite, and also takes a negative effect on the thermal stability of the as-prepared powders. The Se-HAP nanoparticles with Se/P molar ratio not more than 5% sintered at 900℃ can achieve good crystallinity and thermal stability.

Albumin-assembled copper-bismuth bimetallic sulfide bioactive nanosphere as an amplifier of oxidative stress for enhanced radio-chemodynamic combination therapy

The tumor microenvironment with overexpressed hydrogen peroxide(H_(2)O_(2))and reinforced antioxidative system(glutathione,GSH)becomes a double-edged sword for the accessibility of nano-therapy.Since reactive oxygen species(ROS)are easily quenched by the developed antioxidative network,ROS-based treatments such as chemodynamic therapy(CDT)and radiotherapy(RT)for killing cancer cells are severely attenuated.To overcome such limitations,a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin(BSA)based bioactive nanospheres that are BSA assembled with in situ generated copper-bismuth sulfide nanodots and diallyl trisulfide(DATS).The copper-bismuth sulfide nanodots react with H_(2)O_(2)to produce·OH and release Cu^(2+).Then,the Cu^(2+)further depletes GSH to generate Cu^(+)for more·OH generation in the way of Fenton-like reaction.Such a cascade reaction can initiate·OH generation and GSH consumption to realize CDT.The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells.With the sensitization of increased oxidative stress and high Z element Bi,an enhanced radio-chemodynamic combination therapy is achieved.The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.

Frontiers in regenerative medical materials

Based on the last 10 successful series of the China–Korea Symposium on Biomaterials and Nano-biotechnology,we initiated a new invitation-based bilateral forum for established leaders and emerging young scientists in the field,the 2014 China–Korea symposium on biomimetic and regenerative medical materials,which was held from November 26 to 28 in Wuhan,China.In the past decade,a lot of breakthrough achievements in biomedical materials and regenerative medicine have been made in our two countries.Currently,biomaterials science and engineering has been evolved into a critical stage of bioactive integration and tissue regeneration from a simple functional replacement and substitution.Biomimetic and regenerative medical materials will become main topics in the field.