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(A) Effects of eTi, cTi, and cTi/VEGF on HUVECs invasion (B) HUVECs stained with crystal violet were quantitatively analyzed (n = 3) (C) The effects of eTi, cTi, and cTi/VEGF on wound healing, as observed under a phase contrast microscope (D) Assessment of wound healing rates (n = 3).
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Tumor resection and treatment of trauma-related regional large bone defects have major challenges in the field of orthopedics. Scaffolds that treat bone defects are the focus of bone tissue engineering. 3D printing porous titanium alloy scaffolds, prepared via electron beam melting technology, possess customized structure and strength. The addition...
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... Inspired by the adhesion of mussels, Ma et al utilized the adhesive properties of dopamine to immobilize Mg ions and functionalize 3D-printed porous tantalum scaffolds. Subsequently, they conducted a series of in vitro and in vivo experiments to verify that the treated porous tantalum scaffolds had enhanced surface biological activity and improved angiogenesis and osteogenic effects [168] figure 4. In addition, in previous studies, VEGF has been proven to modify bone-implanted scaffolds to achieve superior angiogenic effects [169]. ...
Tantalum and porous tantalum are ideal materials for making orthopedic implants due to their stable chemical properties and excellent biocompatibility. However, their utilization is still affected by loosening, infection, and peripheral inflammatory reactions, which sometimes ultimately lead to implant removal. An ideal bone implant should have exceptional biological activity, which can improve the surrounding biological microenvironment to enhance bone repair. Recent advances in surface functionalization have produced various strategies for developing compatibility between either of the two materials and their respective microenvironments. This review provides a systematic overview of state-of-the-art strategies for conferring biological functions to tantalum and porous tantalum implants. Furthermore, the review describes methods for preparing active surfaces and different bioactive substances that are used, summarizing their functions. Finally, this review discusses current challenges in the development of optimal bone implant materials.
... These results suggest that Ti2448-GelMA scaffolds can facilitate osteogenic differentiation of MC3T3-E1 cells, thereby promoting further biomineralization. GelMA recently attracts more attention, which can be used to mimic the natural bone extracellular matrix and is beneficial to vascular growth and bone regeneration (Dong et al., 2019;Heltmann-Meyer et al., 2021;Li Y et al., 2021). For example, the GelMA scaffolds were prepared by the thermally induced phase separation technique, and the ALP activity of the adipose derived stem cells cultured on the GelMA group was approximate 2 times of the untreated group after 14 and 21 days (Fang et al., 2016). ...
Repair of large bone defects remains challenge for orthopedic clinical treatment. Porous titanium alloys have been widely fabricated by the additive manufacturing, which possess the elastic modulus close to that of human cortical bone, good osteoconductivity and osteointegration. However, insufficient bone regeneration and vascularization inside the porous titanium scaffolds severely limit their capability for repair of large-size bone defects. Therefore, it is crucially important to improve the osteogenic function and vascularization of the titanium scaffolds. Herein, methacrylated gelatin (GelMA) were incorporated with the porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds prepared by the electron beam melting (EBM) method (Ti2448-GelMA). Besides, the deferoxamine (DFO) as an angiogenic agent was doped into the Ti2448-GelMA scaffold (Ti2448-GelMA/DFO), in order to promote vascularization. The results indicate that GelMA can fully infiltrate into the pores of Ti2448 scaffolds with porous cross-linked network (average pore size: 120.2 ± 25.1 μm). Ti2448-GelMA scaffolds facilitated the differentiation of MC3T3-E1 cells by promoting the ALP expression and mineralization, with the amount of calcium contents ∼2.5 times at day 14, compared with the Ti2448 scaffolds. Impressively, the number of vascular meshes for the Ti2448-GelMA/DFO group (∼7.2/mm²) was significantly higher than the control group (∼5.3/mm²) after cultivation for 9 h, demonstrating the excellent angiogenesis ability. The Ti2448-GelMA/DFO scaffolds also exhibited sustained release of DFO, with a cumulative release of 82.3% after 28 days. Therefore, Ti2448-GelMA/DFO scaffolds likely provide a new strategy to improve the osteogenesis and angiogenesis for repair of large bone defects.
... However, the porosity of the scaffold is negatively correlated with its mechanical strength, and excessive porosity is not conducive to early mechanical support during implantation [18]. Based on previous research, we believe that titanium alloy scaffolds with a porosity of 70% can not only ensure inward growth of bone tissue, but also provide sufficient mechanical property [54,55]. We will verify the combination of titanium alloy scaffolds with different pore sizes and porosity with In the past decades, research on collagen materials have received widespread attention. ...
Mineralized collagen (MC) is the fundamental unit of natural bone tissue and can induce bone regeneration. Unmodified MC has poor mechanical properties and a single component, making it unable to cope with complex physiological environment. In this study, we introduced sodium alginate (SA) and vascular endothelial growth factor (VEGF) into the MC material to construct functionalized mineralized collagen (FMC) with good mechanical strength and the ability to continuously release growth factors. The FMC is filled into the pores of 3D printed titanium alloy scaffold to form a new organic-inorganic bioactive interface. With the continuous degradation of FMC, bone marrow mesenchymal stem cells (BMSCs) and vascular endothelial cells (VECs) in the surrounding environment are recruited to the surface of the scaffold to promote bone and vascular regeneration. After implanting the scaffold into the distal femoral defect of rabbits, Micro CT, histological, push-out, as well as immunohistochemical analysis showed that the composite interface can significantly promote osseointegration. These findings provide a new strategy for the development and application of mineralized collagen materials.
... Besides osteogenesis, collagen coating can support the timely conversion of macrophages from the pro-inflammatory M1 to the pro-healing M2 phenotype, inhibiting inflammatory reaction and generating a beneficial osteoimmune microenvironment [42,43] (Figure 2). Simultaneously, collagen coating prominently facilitates angiogenesis of endothelial cells [42] and strengthens local blood supply restoration through sustained release of vascular endothelial growth factor (VEGF) [44]. ...
... The combination of simvastatin-loaded hydrogel coating with porous titanium alloy significantly improved the formation of new blood vessels around rabbit tibial implants, providing an effective strategy for bone integration and bone growth [140]. The heat-sensitive collagen hydrogel/porous titanium alloy scaffold system equipped with VEGF, increased vascular permeability, promoted proliferation and induction of HUVECs, and aided in angiogenic-mediated bone regeneration [44] ( Figure 9). The composite scaffold loaded with VEGF and BMP continuously provided angiogenic and osteogenic growth factors at the site of osseous defect, thus exhibiting higher bone integration capacity and new bone amount [46,141]. ...
... Sustained release of VEGF promotes COL I (A) and CD 31 (B) expression in bone-surrounding scaffolds 6 and 12 weeks after implantation (n = 3)[44]. ...
Although titanium and titanium alloys have become the preferred materials for various medical implants, surface modification technology still needs to be strengthened in order to adapt to the complex physiological environment of the human body. Compared with physical or chemical modification methods, biochemical modification, such as the introduction of functional hydrogel coating on implants, can fix biomolecules such as proteins, peptides, growth factors, polysaccharides, or nucleotides on the surface of the implants, so that they can directly participate in biological processes; regulate cell adhesion, proliferation, migration, and differentiation; and improve the biological activity on the surface of the implants. This review begins with a look at common substrate materials for hydrogel coatings on implant surfaces, including natural polymers such as collagen, gelatin, chitosan, and alginate, and synthetic materials such as polyvinyl alcohol, polyacrylamide, polyethylene glycol, and polyacrylic acid. Then, the common construction methods of hydrogel coating (electrochemical method, sol–gel method and layer-by-layer self-assembly method) are introduced. Finally, five aspects of the enhancement effect of hydrogel coating on the surface bioactivity of titanium and titanium alloy implants are described: osseointegration, angiogenesis, macrophage polarization, antibacterial effects, and drug delivery. In this paper, we also summarize the latest research progress and point out the future research direction. After searching, no previous relevant literature reporting this information was found.
... Engineered scaffolds that are substitutes for native tissues/ organs have failed repeatedly due to a lack of functional vasculature. So far, the gold standard for inducing angiogenesis in scaffolds relies on incorporating essential bioactive molecules within the scaffolds and providing their temporal release (Turner et al., 2017;Kuttappan et al., 2018;Ruskowitz and DeForest, 2018;Wang D. et al., 2019;Stejskalova et al., 2019;Mastrullo et al., 2020;Li et al., 2021;Shokrani et al., 2022). Pathophysiological stimuli can hinder scaffold performance in many cases as opposed to simple diffusion and degradation-based release, which occur typically. ...
... Ti and its alloys have good corrosion resistance, mechanical strength, and biocompatibility, making them ideal materials for dental implants [23][24][25][26][27][28][29][30][31][32][33]. However, the lack of biological activity on the surface of natural Ti implants makes them highly prone to bacterial infections [32,34,35] and often causes insufficient bone tissue integration [14]. ...
Breakthroughs in the field of nanotechnology, especially in nanochemistry and nanofabrication technologies, have been attracting much attention, and various nanomaterials have recently been developed for biomedical applications. Among these nanomaterials, nanoscale titanium dioxide (nano-TiO2) has been widely valued in stomatology due to the fact of its excellent biocompatibility, antibacterial activity, and photocatalytic activity as well as its potential use for applications such as dental implant surface modification, tissue engineering and regenerative medicine, drug delivery carrier, dental material additives, and oral tumor diagnosis and treatment. However, the biosafety of nano-TiO2 is controversial and has become a key constraint in the development of nano-TiO2 applications in stomatology. Therefore, in this review, we summarize recent research regarding the applications of nano-TiO2 in stomatology, with an emphasis on its performance characteristics in different fields, and evaluations of the biological security of nano-TiO2 applications. In addition, we discuss the challenges, prospects, and future research directions regarding applications of nano-TiO2 in stomatology that are significant and worthy of further exploration.
... The dual release of growth factors can promote the process of bone regeneration more effectively than either factor alone. Studies have shown that topical application of VEGF can promote bone repair in nonunion models, especially in the early stage of fracture healing (Percival and Richtsmeier, 2013;Li et al., 2021a;Li A. et al., 2021). Therefore, in order to promote bone regeneration more effectively, rapid early release of VEGF and sustained slow release of BMP-2 should be achieved, which is consistent with the law of bone growth and angiogenesis may be critical for bone tissue regeneration. ...
... Therefore, a stable coating can greatly increase the success rate of implantation and osseointegration (Kayabasi et al., 2013;Shen et al., 2016;Wu S. et al., 2018;Zhu et al., 2021). At present, coating technology is developing rapidly, such as dip coating, bionic coating, sol-gel, electrophoretic deposition, vapour deposition, laser processing, ion spraying and 3D printing (Teng et al., 2019;Li et al., 2021a;Koons et al., 2021). Incorporation of BMPs into a bionic coating allows high pharmacodynamic activity at a low pharmacological level and maintenance of this activity for a long period of time. ...
... Among implant metal materials, titanium alloys are the most widely used orthopaedic implant materials due to their outstanding characteristics, such as high strength, high corrosion resistance, and biological inertness. However, due to the naturally inert nature of titanium alloys, they do not have sufficient biological activity and cannot be well combined with bone tissue; thus, there may be a gap between the bone and the implant, leading to unstable healing and resulting in failure of bone healing (Sul et al., 2002;Geetha et al., 2009;Li et al., 2021a). The porous structure of titanium alloy is constructed by 3D printing and other technologies, and surface modification of titanium alloy is carried out using various methods, such as electrodeposition, so that biologically active molecules (such as BMP) can be loaded on the surface coating of titanium alloy to achieve slow and continuous release. ...
At present, bone nonunion and delayed union are still difficult problems in orthopaedics. Since the discovery of bone morphogenetic protein (BMP), it has been widely used in various studies due to its powerful role in promoting osteogenesis and chondrogenesis. Current results show that BMPs can promote healing of bone defects and reduce the occurrence of complications. However, the mechanism of BMP in vivo still needs to be explored, and application of BMP alone to a bone defect site cannot achieve good therapeutic effects. It is particularly important to modify implants to carry BMP to achieve slow and sustained release effects by taking advantage of the nature of the implant. This review aims to explain the mechanism of BMP action in vivo, its biological function, and how BMP can be applied to orthopaedic implants to effectively stimulate bone healing in the long term. Notably, implantation of a system that allows sustained release of BMP can provide an effective method to treat bone nonunion and delayed bone healing in the clinic.
Large bone defects are the leading contributor to disability worldwide, affecting approximately 1.71 billion people. Conventional bone graft treatments show several disadvantages that negatively impact their therapeutic outcomes and limit their clinical practice. Therefore, much effort has been made to devise new and more effective approaches. In this context, bone tissue engineering (BTE), involving the use of biomaterials which are able to mimic the natural architecture of bone, has emerged as a key strategy for the regeneration of large defects. However, although different types of biomaterials for bone regeneration have been developed and investigated, to date, none of them has been able to completely fulfill the requirements of an ideal implantable material. In this context, in recent years, the field of nanotechnology and the application of nanomaterials to regenerative medicine have gained significant attention from researchers. Nanotechnology has revolutionized the BTE field due to the possibility of generating nanoengineered particles that are able to overcome the current limitations in regenerative strategies, including reduced cell proliferation and differentiation, the inadequate mechanical strength of biomaterials, and poor production of extrinsic factors which are necessary for efficient osteogenesis. In this review, we report on the latest in vitro and in vivo studies on the impact of nanotechnology in the field of BTE, focusing on the effects of nanoparticles on the properties of cells and the use of biomaterials for bone regeneration.
