含镁介孔生物活性玻璃/锌黄长石复合支架的成骨活性

骨修复支架的成骨活性和力学性能对其使用效果至关重要。以具有良好力学性能的锌黄长石（Ca₂ZnSi₂O₇,HT）为基体,以 Mg 掺杂的生物可降解介孔生物活性玻璃（MBG）为涂层,制备 Mg-M/HT 多孔复合支架。研究 Mg 掺杂对复合支架微观结构和成骨活性的影响。利用 X 射线衍射仪、透射电子显微镜和 Fourier 变换红外吸收光谱仪等手段对复合支架的物化性能进行表征。利用人骨髓间充质干细胞（h BMSCs）考察 Mg 掺杂对支架成骨活性的影响。结果表明：Mg 掺杂虽然一定程度上降低了 MBG 的介孔有序度,但 Mg-M/HT 复合支架仍具有均匀有序的孔道结构。与 MBG 改性的 HT 生物支架（M/HT）相比,Mg-M/HT 支架具有更高的细胞内黏着斑蛋白和整合素以及碱性磷酸酶、钙结节和骨钙素的表达量,表明 Mg 掺杂可促进 M/HT支架的成骨细胞活性,在骨组织修复领域具有较好的应用潜力。     

四氧化三铁/介孔生物玻璃复合骨水泥的制备及其理化性能研究

通过将介孔生物玻璃(MBG)和四氧化三铁(Fe_3O_4)纳米颗粒复合制备出Fe_3O_4/MBG复合骨水泥,并详细研究了Fe_3O_4纳米颗粒的添加对骨水泥凝结时间、抗压强度、生物活性、降解性能以及磁热性能的影响。研究结果表明,Fe_3O_4/MBG骨水泥具有较好的抗压强度,随着Fe_3O_4纳米颗粒量的增加,Fe_3O_4/MBG骨水泥的凝结时间延长、磁热性能提高,但几乎没有对骨水泥的生物活性和降解性能产生影响。     

可注射nHA/PU复合多孔骨修复支架制备及表征

兼具良好孔隙率和原位任意塑形固化的可注射复合多孔骨修复材料在临床不规则骨缺损的治疗方面显示出巨大的优势。本研究通过优化双组分设计,以水为发泡剂制备可注射纳米羟基磷灰石/聚氨酯（nHA/PU）复合多孔支架。利用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）、力学测试及Gillmore针测试等手段对制备的支架进行结构形貌、化学组成、力学性能和固化时间表征。结果表明,本研究制备的可注射nHA/PU复合多孔支架孔隙率高、孔隙贯通性好,孔径分布在100~700μm,适宜细胞和组织向孔内生长;添加20% nHA显著提高了PU支架的力学强度,但降低了支架的孔隙率;可注射支架在8h固化,适宜临床操作。本研究制备的可注射nHA/PU复合多孔支架在不规则骨缺损修复领域具有较大的应用潜力。     

三维打印珍珠粉-硫酸钙/聚己内酯复合支架及性能研究

具有生物相容性的支架可以作为可控的细胞外环境,供细胞附着、增殖、分化以及组织生成,在组织工程中有着重要的作用。本研究运用三维打印技术制备了珍珠粉-硫酸钙/聚己内酯(Pearl-CaSO_4/PCL)复合支架,详细研究了珍珠粉含量对复合支架的理化性能和生物学性能的影响。结果表明,复合支架具有350mm左右的三维连通大孔,其孔隙率约60%,支架强度可达8 MPa。珍珠粉的复合能够有效调节复合支架的降解速率并稳定支架周围的体液环境。细胞实验结果表明,Pearl-CaSO_4/PCL复合支架能够促进骨髓间充质干细胞的增殖与分化,且与珍珠粉的含量呈正相关。因此,Pearl-CaSO_4/PCL复合支架在骨缺损修复领域具有应用前景。     

细菌纤维素/羟基磷灰石@聚醚砜骨膜支架的制备及其性能研究

骨膜作为骨缺损修复过程中营养物质的来源及膜内成骨过程中的核心位点,其结构和功能的重建对大尺度骨缺损的修复起到极其重要的作用。基于此,为了模拟天然骨膜的结构和功能,将聚醚砜（PES）和羟基磷灰石（HAp）混合,通过静电纺丝制备HAp@PES静电纺纤维膜（HPES）,然后通过膜液界面培养法与细菌纤维素（BC）复合,获得了具有微米―纳米结构的BC/HAp@PES(BC/HPES)支架。扫描电镜结果表明,该支架微米―纳米纤维交错分布,且HAp成功复合在微米纤维上。所制备的支架具有良好的力学性能。进一步研究表明,成骨细胞在支架表面表现出良好的增殖和铺展能力,不仅如此,该支架还具有良好的成骨分化诱导能力。因此,这种具有仿生微纳纤维结构且负载HAp的骨膜支架有望用于大尺度骨缺损修复领域。     

模板法合成介孔无机生物材料的研究进展

简述了介孔无机生物材料的分类、制备方法及应用前景。重点介绍了通过模板法合成介孔磷酸钙陶瓷、介孔羟基磷灰石以及介孔生物玻璃的研究进展,并对其在器官修复、骨组织诊疗等领域的应用进行了展望,为获得更好的生物组织替换材料提供了基础条件。     

模板法合成介孔无机生物材料的研究进展

简述了介孔无机生物材料的分类、制备方法及应用前景。重点介绍了通过模板法合成介孔磷酸钙陶瓷、介孔羟基磷灰石以及介孔生物玻璃的研究进展,并对其在器官修复、骨组织诊疗等领域的应用进行了展望,为获得更好的生物组织替换材料提供了基础条件。     

生物质基含硅骨修复复合支架材料的制备、特性及评价

模仿天然骨的精密结构制备有机-无机复合骨修复支架材料已成为骨组织工程发展的重要方向。生物质材料如胶原、明胶、壳聚糖、丝素蛋白等由于具有优良的生物学性能而得到广泛关注。含硅生物活性材料由于具有良好的骨传导性和骨诱导性,成为骨修复支架材料中重要的无机组分。本文主要介绍了粉体复合和原位复合两种骨支架材料组分的复合技术,阐述了冷冻干燥、静电纺丝、仿生矿化以及3D打印等骨支架材料结构的构建策略,着重总结了生物质基含硅骨修复支架材料研究进展,阐明当前骨支架材料制备的难点在于支架材料的力学性能和多孔性结构以及生物降解性能与新骨生成速率之间的匹配性问题,并对骨支架材料的发展进行了展望。     

多孔型羟基磷灰石/骨诱导蛋白复合人工骨的研究与临床应用

本实验制备出多孔结构的羟基磷灰石与骨诱导蛋白复合（简称ＨＡＰ－ＢＩＰ）人工骨。经物理性能测试，电镜观察、动物实验及临床应用研究，认为该材料用于缺血性股骨坏死的修复，具有临床要求的力学性能和生物性能。植入人体后，既为成骨提供支架，又为新骨形成提供诱骨物质，具有较好的临床效果。     

多孔型羟基磷灰石／骨计导蛋白复合人工骨的研究与临床应用

本实验制备出多孔结构的羟基磷灰石与骨诱导蛋白复合（简称ＨＡＰ－ＢＩＰ）人工骨。经物理性能测试，电镜观察、动物实验及临床应用研究，认为该材料用于缺血性肌骨坏死的修复，具有临床要求的力学性能和生物性能。植入人体后，既为成骨提供支架，又为新骨形成提供诱骨物质，具有较好的临床效果。     

Highly interconnected macroporous MBG/PLGA scaffolds with enhanced mechanical and biological properties via green foaming strategy

In this study, mesoporous bioactive glass particles (MBGs) are incorporated into poly(lactic-co-glycolic acid) (PLGA) to fabricate highly interconnected macroporous composite scaffolds with enhanced mechanical and biological properties via a developed supercritical carbon dioxide (scCO₂) foaming method. Scaffolds show favorable highly interconnected and macroporous structure through a high foaming pressure and long venting time foaming strategy. Specifically, scaffolds with porosity from 73% to 85%, pore size from 120 μm to 320 μm and interconnectivity of over 95% are controllably fabricated at MBG content from 0 wt% to 20 wt%. In comparison with neat PLGA scaffolds, composite scaffolds perform improved strength (up to 1.5 folds) and Young's modulus (up to 3 folds). The interconnected macroporous structure is beneficial to the ingrowth of cells. More importantly, composite scaffolds also provide a more promising microenvironment for cellular proliferation and adhesion with the release of bioactive ions. Hopefully, MBG/PLGA scaffolds developed by the green foaming strategy in this work show promising morphological, mechanical and biological features for tissue regeneration.     

Effect of Morphological Characteristics and Biomineralization of 3D-Printed Gelatin/Hyaluronic Acid/Hydroxyapatite Composite Scaffolds on Bone Tissue Regeneration

The use of porous three-dimensional (3D) composite scaffolds has attracted great attention in bone tissue engineering applications because they closely simulate the major features of the natural extracellular matrix (ECM) of bone. This study aimed to prepare biomimetic composite scaffolds via a simple 3D printing of gelatin/hyaluronic acid (HA)/hydroxyapatite (HAp) and subsequent biomineralization for improved bone tissue regeneration. The resulting scaffolds exhibited uniform structure and homogeneous pore distribution. In addition, the microstructures of the composite scaffolds showed an ECM-mimetic structure with a wrinkled internal surface and a porous hierarchical architecture. The results of bioactivity assays proved that the morphological characteristics and biomineralization of the composite scaffolds influenced cell proliferation and osteogenic differentiation. In particular, the biomineralized gelatin/HA/HAp composite scaffolds with double-layer staggered orthogonal (GEHA20-ZZS) and double-layer alternative structure (GEHA20-45S) showed higher bioactivity than other scaffolds. According to these results, biomineralization has a great influence on the biological activity of cells. Hence, the biomineralized composite scaffolds can be used as new bone scaffolds in bone regeneration.     

Effects of the methyl methacrylate addition,polymerization temperature and time on the MBG@PMMA core-shell structure and its application as addition in electrospun composite fiber bioscaffold

Mesoporous bioactive glass (MBG) possesses a high specific surface area and excellent biocompatibility making it a promising biomaterial. In the present study, poly(methyl methacrylate) (PMMA) was coated on MBG to obtain a MBG@PMMA core-shell structure to further expand the potential applications of MBG. Changes in the MMA to MBG ratio, polymerization temperature and time were investigated to determine their effects on the core-shell structure. The as-prepared core-shell powders were evaluated using scanning electron microscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy to determine the optimal core-shell structure for electrospinning application. Electrospun composite fiber scaffolds prepared by adding MBG with or without an optimized PMMA shell were examined through microstructural observation, mechanical testing, Raman spectroscopy, and in vitro bioactivity evaluation. Experimental results showed that optimized MBG@PMMA core-shell powder was prepared using MMA: MBG = 3: 1, with polymerization at 70 °C for 4 h. The spherical core-shell powder exhibited a relatively smooth surface and the flake- or cotton-like shell structure was beneficial to electrospinning. Electrospun composite fiber scaffold prepared using MBG@PMMA powder exhibited superior mechanical performance and excellent biocompatibility compared to its shell-less MBG counterpart.     

3D-printed barium strontium titanate-based piezoelectric scaffolds for bone tissue engineering

In order to promote bone healing, new generations of biomaterials are under development. These biomaterials should demonstrate proper biological and mechanical properties preferably similar to the natural bone tissue. In this research, 3D-printed barium strontium titanate (BST)/β-tricalcium phosphate (β-TCP) composite scaffolds have been synthesized as an alternative strategy for bone regeneration to not only induce appropriate bioactive characteristics but also piezoelectric behavior. The physical, chemical and biological performance of the scaffolds have been examined in terms of mechanical, dielectric properties, apatite-forming ability, Alizarin Red Staining (ARS), Alkaline Phosphatase activity (ALP), and cytotoxicity. The samples composed of 60% BST and 40% β-TCP showed the highest compressive strength, bending module, elastic modulus and the Young's modulus. The dielectric constant increased with further addition of the BST phase in the constructs. Scanning Electron Microscope (SEM) and energy dispersive X-ray (EDX) analyses showed that 60% BST/40% β-TCP sample had the highest amount of bone-like apatite formation after 28 days in simulated body fluid (SBF). Moreover, the results of ARS proved that 60% BST/40% β-TCP composite could present higher quantities of mineral deposition. The ALP activity of osteosarcoma cells on 60% BST/40% β-TCP sample showed higher activities compare with the other composites. None of the samples demonstrated any sign of toxicity using MTT test. It can be suggested that BST/β-TCP composite scaffolds can be potentially used as the next generation of bone tissue engineering scaffold materials.     

In vitro bone engineering based on polycaprolactone and polycaprolactone–tricalcium phosphate composites

The filling of bone defects in load‐bearing areas requires scaffolds possessing physical properties that are in the range of those of the host bone. In this report, composite scaffolds comprising medical‐grade polycaprolactone and tricalcium phosphate (mPCL‐TCP) (80:20), which have been designed for load‐bearing applications, are characterized and compared with mPCL scaffolds, using in vitro studies. The composite scaffolds exhibited improved hydrophilicity, compressive modulus and strength. Human alveolar osteoblasts (AOs) grown on the composite achieved higher seeding efficiencies and more uniform distribution when compared with mPCL preparations alone. AOs demonstrated better proliferation, denser multilayered cell‐sheets and showed earlier expression of bone matrix‐related proteins on the composite than on mPCL during 28 days in vitro culture. The calcium content in the media decreased in both scaffold/cell constructs. Alkaline phosphatase activity increased significantly in mPCL matrices after osteogenic induction but no distinct change was observed in the composite. Osteocalcin expression was down‐regulated by induction in the composite but was up‐regulated in mPCL at both RNA and protein level. Immuno‐reactive signals for osteopontin and collagen type I, in combination with mineral nodules were found to be stronger in mPCL‐TCP scaffolds. We conclude that the composite scaffolds were more hydrophilic and had improved mechanical properties over mPCL scaffolds. Moreover, the primary AOs achieved better cell proliferation, and showed earlier and different matrix protein expression patterns on the composite scaffolds than on the mPCL scaffolds. Copyright © 2006 Society of Chemical Industry     

3D porous HA/TCP composite scaffolds for bone tissue engineering

Calcium phosphates (apatites) are considered as a research frontier for bone regeneration applications by virtue of similarity to the mineral constituent of bone, suitable biocompatibility and remarkable osteogenesis ability. In this regard, the biodegradability and mechanical properties of monophasic apatites, typically hydroxyapatite (HA) and tricalcium phosphate (TCP), are imperfect and do not fulfill some requirements. To overcome these drawbacks, 3D porous HA/TCP composite scaffolds prepared by conventional and more recently, 3D printing techniques have shown to be promising since their bioperformance is adjustable by the HA/TCP ratio and pores. Despite the publication of several reviews on either 3D porous scaffolds or biphasic calcium phosphates (BCPs), no review paper has to our knowledge focused on 3D porous BCP scaffolds. This paper comprehensively reviews the production methods, properties, applications and modification approaches of 3D porous HA/TCP composite scaffolds for the first time. In addition, new insights are introduced towards developing HA/TCP scaffolds with more impressive bioperformance for further tissue engineering applications, including those with different interior and exterior frameworks, patient-specific specifications and drugs (or other biological factors) loading.     

Physico-chemical and biological studies on three-dimensional porous silk/spray-dried mesoporous bioactive glass scaffolds

The incorporation of a bioactive inorganic phase in polymeric scaffolds is a good strategy for the improvement of the bioactivity and the mechanical properties, which represent crucial features in the field of bone tissue engineering. In this study, spray-dried mesoporous bioactive glass particles (SD-MBG), belonging to the binary system of SiO₂-CaO (80:20 mol%), were used to prepare composite scaffolds by freeze-drying technique, using a silk fibroin matrix. The physico-chemical and biological properties of the scaffolds were extensively studied. The scaffolds showed a highly interconnected porosity with a mean pore size in the range of 150 µm for both pure silk and silk/SD-MBG scaffolds. The elastic moduli of the silk and silk/SD-MBG scaffolds were 1.1±0.2 MPa and 6.9±1.0 MPa and compressive strength were 0.5±0.05 MPa and 0.9±0.2 MPa, respectively, showing a noticeable increase of the mechanical properties of the composite scaffolds compared to the silk ones. The contact angle value decreased from 105.3° to 71.2° with the incorporation of SD-MBG particles. Moreover, the SD-MBG incorporation countered the lack of bioactivity of the silk scaffolds inducing the precipitation of hydroxyapatite layer on their surface already after 1 day of incubation in simulated body fluid. The composite scaffolds showed good biocompatibility and a good alkaline phosphatase activity toward human mesenchymal stromal cells, showing the ability for their use as three-dimensional constructs for bone tissue engineering.     

β-Tricalcium phosphate/ԑ-polycaprolactone composite scaffolds with a controllable gradient: Fabrication and characterization

β-tricalcium phosphate (β-TCP)/ԑ-polycaprolactone (PCL) composite scaffolds with a controllable gradient were developed with a two-step process: fabrication of the β-TCP scaffolds using digital light processing (DLP) 3D printing and then immersion of the β-TCP scaffolds into a PCL melt for different times. The gradient structure was controlled by the immersion time of the β-TCP scaffolds in the molten PCL. The composite scaffolds with a gradient exhibited a substantially higher compressive strength and toughness than the bare β-TCP scaffolds. Moreover, the increase in infiltration time also enhanced the compressive strength and toughness of the composite scaffolds because the infiltration thickness increased with infiltration time. The gradient structure resulted in a gradient degradation and may provide a better response to time-varying mechanical properties than pure β-TCP scaffolds during its absorption process. Therefore, composite scaffolds with a gradient are promising candidates for load-bearing bones or large segmental bone repair.     

Development and Characterization of Novel Biomimetic Composite Scaffolds Based on Bioglass‐Collagen‐Hyaluronic Acid‐Phosphatidylserine for Tissue Engineering Applications

Summary: Biomimetic scaffolds are appealing products for the repair of bone defects using tissue engineering strategies. The present study prepared novel biomimetic composite scaffolds with similar composite to natural bone using bioactive glass, collagen, hyaluronic acid, and phosphatidylserine. The microstructure, swelling ratio, biodegradability, and biomineralization characteristic of the composite scaffolds with and without hyaluronic acid and phosphatidylserine were compared and analyzed by SEM/EDAX, XRD, and FTIR techniques and in vitro test, and the properties can be influenced by 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC)/N‐hydroxysuccinimide (NHS) crosslinking. The optimized properties of the crosslinked composite scaffolds observed in this study show the possibility of their use of bioactive and bioresorbable scaffolds in bone tissue engineering.

SEM micrographs of BG‐COL‐HYA‐PS composite scaffolds after immersion in SBF for 1 d.