基于介孔硼硅酸盐生物活性玻璃微球的可注射复合骨水泥

以溶胶-凝胶法制备的介孔硼硅酸盐生物活性玻璃微球(MBGS)作为固相, 海藻酸钠(SA)溶液作为液相,开发了一种可注射复合骨水泥。对MBGS中氧化硼/氧化硅的比例对其质构性能及骨水泥的可操作性、抗压强度和生物活性的影响进行表征。实验结果表明, 随着硼含量的增加, MBGS的比表面积从161.71 m²/g增大至214.28 m²/g, 平均孔径以及总孔容也随之增长, 加速了玻璃相中钙离子的释放, 使得玻璃与SA的快速交联, 改善了骨水泥可操作性能和力学性能, 凝固时间由21 min缩短至9 min, 抗压强度由3.4 MPa提升至4.1 MPa, 体外矿化性能也随之提高。综合各方面性能表现, BC-30骨水泥兼具良好的可操作性能、力学性能和体外矿化能力, 是最合适的骨水泥组分。总之, 提高MBGS的质构性能是增强复合骨水泥的可操作性、抗压强度和生物活性的有效方法。     

介孔硼硅酸盐玻璃微球药物载体的制备及其性能表征

介孔二氧化硅微粒具有化学稳定性好、比表面积大和表面易修饰等特点, 作为药物载体具有良好的应用前景, 但其缺乏生物活性且生物降解缓慢等在一定程度上限制了它的应用领域。为克服这些缺陷, 寻找合适的药物载体已成为重要研究方向。与纯二氧化硅相比, 硼硅酸盐玻璃具有良好的生物活性和更高的降解速率。基于此, 本研究尝试合成介孔硼硅酸盐玻璃微球(MBGMs), 并表征了其在负载和释放抗肿瘤药物盐酸阿霉素(DOX)过程中的载体特性和材料降解引发的各种功能性离子的释放行为。结果表明BMGMs具有约25 mg/g的DOX负载量,引入硼不仅可以调控MBGMs的化学活性和降解速率, 而且较高硼含量的MBGMs可促进酸性条件下的药物释放, 具有一定的酸性响应性。此外, MBGMs可在模拟体液中释放SiO₄^4-、BO₃^3-和Ca²⁺等有益骨组织生长的功能性离子, 并诱导生成羟基磷灰石, 具备良好的离子缓释能力和体外矿化活性。因此, MBGMs作为一种新颖的药物载体材料, 既可作为药物和功能离子的双重负载, 又具有良好的生物活性和降解特性, 在病理性骨缺损修复领域具有良好的应用前景。     

硅烷化介孔硼硅酸盐生物玻璃微球对PMMA骨水泥生物活性和力学性能的影响（英文）

聚甲基丙烯酸甲酯(PMMA)骨水泥因具有良好的力学性能、适宜的凝固时间和低毒性等优点而在骨科手术中作为可注射型人工骨修复材料受到广泛的应用。然而，其生物惰性可能导致假体长期植入后产生无菌性松动。本研究采用模板法制备了介孔硼硅酸盐生物玻璃微球(MBGS),并用硅烷偶联剂γ-甲基丙烯酰氧基丙基三甲氧基硅烷(γ-MPS)对其进行改性,制备了MBGSSI。再将硅烷化介孔硼硅酸盐生物玻璃微球(MBGSSI)与聚甲基丙烯酸甲酯(PMMA)骨水泥复合,制备了一种具有良好生物活性和力学性能的复合骨水泥。实验结果表明,由于γ-MPS与MBGS的结合主要发生在介孔微球的近表面,MBGSSI比MBGS具有更大的比表面积和更小的孔容积。与MBGS/PMMA复合骨水泥相比,γ-MPS可以改善复合材料中无机相和有机相之间的结合,因此MBGSSI/PMMA复合骨水泥的力学性能得到了改善,符合ISO 5833:2002对丙烯酸类骨水泥的力学性能要求。此外,在SBF溶液中浸泡42 d后, MBGS/PMMA和MBGSSI/PMMA复合骨水泥的表面均生成了羟基磷灰石(HA),证明复合骨水泥具有良好的生物活性。因此, MB...     

硼硅酸盐生物活性玻璃在直流电场下的体外矿化性能

硼硅酸盐生物活性玻璃具有良好的生物活性和骨传导性, 但大多数生物活性玻璃表现出非线性降解和矿化行为, 矿化性能会随着时间而减缓。电场作为一种外场辅助调节的方法, 能够干预玻璃的离子交换和扩散。本研究利用直流电场干预硼硅酸盐生物活性玻璃的体外矿化, 加快降解较慢阶段中硼硅酸盐生物玻璃的生物活性。将熔融法制备的成分为18SiO₂-6Na₂O-8K₂O-8MgO-22CaO-2P₂O₅-36B₂O₃的硼硅酸盐生物活性玻璃浸泡在SBF生理模拟液中, 施加0~90 mA的电流, 研究直流电场对硼硅酸盐生物玻璃降解及体外矿化性能的影响。研究结果表明, 施加电场不仅可以提高硼硅酸盐生物活性玻璃的降解率和离子释放量, 而且有利于玻璃网络水解和表面羟基化, 加速羟基磷灰石的生成。其中失重率比对照组提高了3%~5%, 硼和钙的离子释放量分别较对照组提高了2.3~2.9倍和1.9~2.3倍。对硼硅酸盐生物活性玻璃表面结构分析得出, 暴露在电场下的样品表面生成了磷灰石层。应用直流电场可以提高生物活性玻璃的降解及体外矿化性能, 为提升骨修复效果提供了一种新思路。     

硼硅酸盐生物活性玻璃在直流电场下的体外矿化性能（英文）

硼硅酸盐生物活性玻璃具有良好的生物活性和骨传导性,但大多数生物活性玻璃表现出非线性降解和矿化行为,矿化性能会随着时间而减缓。电场作为一种外场辅助调节的方法,能够干预玻璃的离子交换和扩散。本研究利用直流电场干预硼硅酸盐生物活性玻璃的体外矿化,加快降解较慢阶段中硼硅酸盐生物玻璃的生物活性。将熔融法制备的成分为18SiO_2-6Na_2O-8K_2O-8MgO-22CaO-2P_2O_5-36B_2O_3的硼硅酸盐生物活性玻璃浸泡在SBF生理模拟液中,施加0～90 m A的电流,研究直流电场对硼硅酸盐生物玻璃降解及体外矿化性能的影响。研究结果表明,施加电场不仅可以提高硼硅酸盐生物活性玻璃的降解率和离子释放量,而且有利于玻璃网络水解和表面羟基化,加速羟基磷灰石的生成。其中失重率比对照组提高了3%～5%,硼和钙的离子释放量分别较对照组提高了2.3～2.9倍和1.9～2.3倍。对硼硅酸盐生物活性玻璃表面结构分析得出,暴露在电场下的样品表面生成了磷灰石层。应用直流电场可以提高生物活性玻璃的降解及体外矿化性能,为提升骨修复效果提供了一种新思路。     

硅酸盐生物活性陶瓷用于骨组织修复及再生的研究

近年来, 硅酸盐生物活性陶瓷越来越受到研究人员的重视, 其主要原因在于硅酸盐生物陶瓷能够通过释放硅(Si)离子等生物活性离子, 显著地促进骨组织细胞的增殖、分化及骨组织修复. 硅酸盐生物活性陶瓷有望作为新的陶瓷体系广泛应用于骨缺损修复和再生。本文将结合本课题组在过去十年的研究, 重点介绍目前硅酸盐生物活性陶瓷用于骨组织修复及再生的研究进展。同时, 通过与传统磷酸钙类生物陶瓷进行比较, 对硅酸盐生物活性陶瓷的优缺点进行分析和归纳, 最后对硅酸盐陶瓷作为新的生物陶瓷体系用于骨组织修复的前景做了展望。     

明胶微球玻璃基骨水泥的制备及性能研究

以生物活性SiO2-CaO-P2O5-CaF2系统玻璃粉末为基体,以磷酸铵溶液为固化液,添加明胶微球,制得了明胶微球多孔玻璃基骨水泥。将骨水泥于置37℃的生理模拟液(SBF)中浸泡后,利用pH计、XRD、SEM和力学试验机等对浸泡液的pH值和钙离子浓度,以及浸泡产物的晶相、显微结构和力学性能等进行了观测和分析。结果表明,明胶微球的加入使玻璃基骨水泥从高pH值降至略大于7.0的弱碱性,并加快了骨水泥对钙离子的吸收和羟基磷灰石(HAP)的生长,使玻璃基骨水泥体现出更好的生物活性。在明胶微球含量为5%(质量分数)时,浸泡后形成的骨水泥的孔隙率接近80%,而其抗压强度仍可达5MPa以上。     

荔枝状CaCO3@HA/Fe3O4磁性介孔多级微球的制备

为了克服常规的生物陶瓷微球缺乏靶向功能的缺点, 本研究制备了内核为CaCO₃, 外壳为磁性可调控羟基磷灰石(HA)的新型荔枝状多孔微球。结果表明: 抗肿瘤药物阿霉素(DOX)能有效地负载于磁性HA微球上, 并具备磁性靶向功能。此外, HA外壳具有良好的生物相容性和pH响应特性, 可在模拟酸性肿瘤细胞环境中控制DOX的释放, 有效杀死肿瘤细胞, 并在模拟正常细胞培养环境中减少对正常细胞的毒副作用。这种新型的微球材料具有超顺磁性能, 且微结构可控, 是一种智能化药物控释微球载体, 可以灵敏地释放DOX, 从而有效地实现抗肿瘤活性。     

光热/pH响应B-CuS-DOX纳米药物用于化疗-光热协同治疗肿瘤

基于纳米材料的化疗-光热协同治疗是一种高效的肿瘤治疗方式, 但如何构建具有高载药量与良好光热转换性能的纳米药物依然面临挑战。本研究通过超声剥离法制备二维硼(boron, B)纳米片, 进一步在其表面原位负载超小粒径硫化铜(CuS)纳米颗粒和化疗药阿霉素(DOX), 形成B-CuS-DOX纳米药物。B-CuS具有高的DOX药物装载能力(864 mg/g)和优异的光热转化性能(在808 nm处的光热转换效率为55.8%), 同时可实现pH及近红外激光双重刺激响应而释放药物。细胞实验表明在808 nm近红外光的照射下, B-CuS-DOX展示了良好的化疗-光热协同治疗效果。本研究构建的纳米药物有望为体内肿瘤治疗提供一种有效的化疗-光热协同治疗策略。     

纳米金刚石/酵母-壳聚糖复合微球的制备及光热控释性能

开发高性能功能性光热凝胶并建立药物控释模型对农药智能输送材料的开发具有重要意义。以酵母-壳聚糖水凝胶(YS-CS)为基体,引入光热材料纳米金刚石(DND),通过碱凝胶法合成了纳米金刚石/酵母-壳聚糖(DND/YS-CS)交联网络结构复合凝胶微球,研究了复合微球的微观结构、力学性能和光热转换性能;以吲哚丁酸(IBA)为模型药物,探讨DND/YS-CS对IBA的负载性能和控释性能,揭示复合微球对IBA的光热控释机制。结果表明：复合微球具有良好的力学性能,在分别超声和离心1 h后,DND含量为2.0 mg/mL复合微球保水能力分别达到70.5%和74%;复合微球具有良好的光热转换能力,一个太阳光强度下,最高温度可达37.6℃;DND含量为1.2 mg/mL复合微球对IBA的吸附量最高,可达到41.73μg/mg;微球在光下药物释放模式符合Korsmeyer-Peppas模型,在光下具有明显的刺激响应行为,药物释放呈现“开-关”模式。通过控制光的照射强度控制药物释放,在农业领域有广阔的应用前景。     

Graphene Quantum Dots‐Capped Magnetic Mesoporous Silica Nanoparticles as a Multifunctional Platform for Controlled Drug Delivery,Magnetic Hyperthermia,and Photothermal Therapy

A multifunctional platform is reported for synergistic therapy with controlled drug release, magnetic hyperthermia, and photothermal therapy, which is composed of graphene quantum dots (GQDs) as caps and local photothermal generators and magnetic mesoporous silica nanoparticles (MMSN) as drug carriers and magnetic thermoseeds. The structure, drug release behavior, magnetic hyperthermia capacity, photothermal effect, and synergistic therapeutic efficiency of the MMSN/GQDs nanoparticles are investigated. The results show that monodisperse MMSN/GQDs nanoparticles with the particle size of 100 nm can load doxorubicin (DOX) and trigger DOX release by low pH environment. Furthermore, the MMSN/GQDs nanoparticles can efficiently generate heat to the hyperthermia temperature under an alternating magnetic field or by near infrared irradiation. More importantly, breast cancer 4T1 cells as a model cellular system, the results indicate that compared with chemotherapy, magnetic hyperthermia or photothermal therapy alone, the combined chemo‐magnetic hyperthermia therapy or chemo‐photothermal therapy with the DOX‐loaded MMSN/GQDs nanosystem exhibits a significant synergistic effect, resulting in a higher efficacy to kill cancer cells. Therefore, the MMSN/GQDs multifunctional platform has great potential in cancer therapy for enhancing the therapeutic efficiency.     

介孔有机硅为载体的纳米递送系统制备及其体外化疗-光热联合治疗性能研究

有机/无机杂化的介孔有机硅纳米颗粒因其高的比表面积、丰富的介孔孔道、功能性的骨架以及高的药物装载量等特点而在生物医学领域受到广泛关注。本研究提出以二硫键桥接的有机/无机杂化介孔有机硅纳米颗粒为载体共装载化疗药物和光热剂, 设计制备以DNA分子作为控释“开关”修饰介孔有机硅纳米颗粒的纳米递送系统(ICG/DOX-MONs @DNA₂₀)。该纳米递送系统结合了光热剂的光热效应以及DNA分子随温度升高而从颗粒表面脱附的特性, 可实现近红外光照射激发药物在肿瘤细胞中的控制释放, 同时获得药物化疗-光热联合治疗肿瘤的效果。实验结果表明, 纳米递送系统在近红外光照下能迅速升温至43 ℃以上的热疗温度, 而且在37 ℃条件下6 h内仅缓慢释放药物12.3%, 而当温度升至43 ℃时则快速释放药物52.4%; 细胞实验显示该纳米递送系统能够被HeLa肿瘤细胞吞噬, 在近红外光照下有明显的药物化疗-光热联合治疗效果。因此, ICG/DOX-MONs@DNA₂₀纳米递送系统在药物化疗-光热联合治疗肿瘤方面具有应用前景。     

FePSe3-Nanosheets-Integrated Cryogenic-3D-Printed Multifunctional Calcium Phosphate Scaffolds for Synergistic Therapy of Osteosarcoma

Clinical treatment of osteosarcoma encounters great challenges of postsurgical tumor recurrence and extensive bone defect. To develop an advanced artificial bone substitute that can achieve synergistic bone regeneration and tumor therapy for osteosarcoma treatment, a multifunctional calcium phosphate composite enabled by incorporation of bioactive FePSe₃-nanosheets within the cryogenic-3D-printed α-tricalcium phosphate scaffold (TCP-FePSe₃) is explored. The TCP-FePSe₃ scaffold exhibits remarkable tumor ablation ability due to the excellent NIR-II (1064 nm) photothermal property of FePSe₃-nanosheets. Moreover, the biodegradable TCP-FePSe₃ scaffold can release selenium element to suppress tumor recurrence by activating of the caspase-dependent apoptosis pathway. In a subcutaneous tumor model, it is demonstrated that tumors can be efficiently eradicated via the combination treatment with local photothermal ablation and the antitumor effect of selenium element. Meanwhile, in a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by TCP-FePSe₃ scaffold have been observed in vivo. The TCP-FePSe₃ scaffold possesses improved capability to promote the repair of bone defects via vascularized bone regeneration, which is induced by the bioactive ions of Fe, Ca, and P released during the biodegradation of the implanted scaffolds. The TCP-FePSe₃ composite scaffolds fabricated by cryogenic-3D-printing illustrate a distinctive strategy to construct multifunctional platform for osteosarcoma treatment.     

Engineering 2D Mesoporous Silica@MXene‐Integrated 3D‐Printing Scaffolds for Combinatory Osteosarcoma Therapy and NO‐Augmented Bone Regeneration

The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb₂C MXene wrapped with S‐nitrosothiol (R? SNO)‐grafted mesoporous silica with 3D‐printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)‐triggered photonic hyperthermia of MXene in the NIR‐II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone‐regeneration bioactivity, augmented by sufficient blood supply triggered by on‐demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.     

A Multilayered Mesoporous Gold Nanoarchitecture for Ultraeffective Near-Infrared Light-Controlled Chemo/Photothermal Therapy for Cancer Guided by SERS Imaging

Surface-enhanced Raman scattering (SERS) imaging has emerged as a promising tool for guided cancer diagnosis and synergistic therapies, such as combined chemotherapy and photothermal therapy (chemo-PTT). Yet, existing therapeutic agents often suffer from low SERS sensitivity, insufficient photothermal conversion, or/and limited drug loading capacity. Herein, a multifunctional theragnostic nanoplatform consisting of mesoporous silica-coated gold nanostar with a cyclic Arg-Gly-Asp (RGD)-coated gold nanocluster shell (named RGD–pAS@AuNC) is reported that exhibits multiple “hot spots” for pronouncedly enhanced SERS signals and improved near-infrared (NIR)-induced photothermal conversion efficiency (85.5%), with a large capacity for high doxorubicin (DOX) loading efficiency (34.1%, named RGD/DOX–pAS@AuNC) and effective NIR-triggered DOX release. This nanoplatform shows excellent performance in xenograft tumor model of HeLa cell targeting, negligible cytotoxicity, and good stability both in vitro and in vivo. By SERS imaging, the optimal temporal distribution of injected RGD/DOX–pAS@AuNCs at the tumor site is identified for NIR-triggered local chemo-PTT toward the tumor, achieving ultraeffective therapy in tumor cells and tumor-bearing mouse model with 5 min of NIR irradiation (0.5 W cm⁻²). This work offers a promising approach to employing SERS imaging for effective noninvasive tumor treatment by on-site triggered chemo-PTT.     

Collaborative Design of MgO/FeOx Nanosheets on Titanium: Combining Therapy with Regeneration

The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeO_x nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeO_x double metal oxide demonstrates good peroxidase activity to catalyze H₂O₂, which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeO_x film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.     

Investigation of emulsified,acid and acid-alkali catalyzed mesoporous bioactive glass microspheres for bone regeneration and drug delivery

Acid-catalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkali co-catalyzed mesoporous bioactive glass microspheres (MBGMs-B) were successfully synthesized via combination of sol-gel and water-in-oil (W/O) micro-emulsion methods. The structural, morphological and textural properties of mesoporous bioactive glass microspheres (MBGMs) were characterized by various techniques. Results show that both MBGMs-A and MBGMs-B exhibit regularly spherical shape but with different internal porous structures, i.e., a dense microstructure for MBGMs-A and internally porous structure for MBGMs-B. ²⁹Si NMR data reveal that MGBMs have low polymerization degree of silica network. The in vitro bioactivity tests indicate that the apatite formation rate of MBGMs-B was faster than that of MBGMs-A after soaking in simulated body fluid (SBF) solution. Furthermore, the two kinds of MBGMs have similar storage capacity of alendronate (AL), and the release behaviors of AL could be controlled due to their unique porous structure. In conclusion, the microspheres are shown to be promising candidates as bone-related drug carriers and filling materials of composite scaffold for bone repair.     

NIR‐Responsive Polycationic Gatekeeper‐Cloaked Hetero‐Nanoparticles for Multimodal Imaging‐Guided Triple‐Combination Therapy of Cancer

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging‐guided therapy of cancer. In this work, a near‐infrared (NIR)‐triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two‐armed ethanolamine‐modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD‐PGEA) has been successfully fabricated for multimodal imaging‐guided triple‐combination treatment of cancer. A hierarchical hetero‐structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X‐ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl‐rich CD‐PGEA/pDNA complexes, realizing the co‐delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR‐triggered release of DOX through the facilitated detachment of CD‐PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging‐guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.