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(A) Schematic diagrams of the ZOL loaded gelatin NPs integrated porous titanium scaffold. (B) Surface characterization of the naked porous titanium scaffold and the ZOL loaded gelatin NPs integrated scaffold using a scanning electron micrograph. The ZOL loaded gelatin NPs are distributed evenly on the surface and inside the pores of the scaffold, and the nanospheres on the scaffold are of appropriate density and amount.
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Osteoporotic bone defect is a major challenge in clinics for bone regeneration. Under the condition of osteoporosis, excessive bone absorption and impaired osteogenesis resulted in unexpected long healing procedure of defects. In order to simultaneously enhance bone formation and reduce bone resorption, a polydopamine-coated porous titanium scaffol...
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Additive manufacturing techniques enable users to produce complex devices that would not be possible by conventional methods, offering unique advantages to the medical industry due to the possibility to customize devices to accurately fit patient geometries. The process as done today needs still to be optimized in many aspects to achieve implants w...
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... Overweight and obesity not only constitute substantial risk factors for high blood pressure and cardiovascular disease, but also exert detrimental impacts on the structure of bones via diverse mechanisms, including interference with bone formation, bone resorption, and the microenvironment of the bone marrow [62]. OP primarily arises from an imbalance between bone formation and resorption, leading to a disturbance in bone metabolism characterized by a reduction in the quantity and functionality of osteoblasts [63]. A dynamic equilibrium exists between the two principal mechanisms of osteoblast bone formation and osteoclast-bone resorption during the process of bone remodeling [63]. ...
... OP primarily arises from an imbalance between bone formation and resorption, leading to a disturbance in bone metabolism characterized by a reduction in the quantity and functionality of osteoblasts [63]. A dynamic equilibrium exists between the two principal mechanisms of osteoblast bone formation and osteoclast-bone resorption during the process of bone remodeling [63]. Moreover, OP is characterized by a significant pathogenic mechanism as an osteoblast cell death that hinders bone formation [64]. ...
Osteoporosis is most prevalent in postmenopausal women and is a widespread condition that impacts millions of individuals worldwide. A decrease in bone mineral density and elevated susceptibility to fractures as a result of bone architecture deterioration are the primary attributes of osteoporosis. Due to the challenging nature of treating osteoporosis as a chronic condition, further research into innovative and efficacious therapeutic and animal models that aim to test these drug approaches is necessary. Numerous preclinical and clinical studies have focused on identifying the most efficacious therapeutic approaches for this condition. Various types of treatment are available for osteoporosis, which vary based on particular characteristics of the patient’s condition. These comprise a combination of recently developed and established medications. This review focuses on novel therapeutic approaches for osteoporosis and their corresponding mechanisms of action, pathophysiology, the animal model, and the parameters that are assessed.
... In addition, there was no significant difference in OC attachment to the scaffold at concentrations of 1-10 µmol/L. The osteogenic effect of ZOL-loaded NPs (ALP activity and expression of genes such as Runx2 and ALP) was highest at 50 µmol/L, and the number of mature OCs (multinucleated cells) decreased at this concentration [149]. ...
Osteoporosis is a pathological condition characterized by an accelerated bone resorption rate, resulting in decreased bone density and increased susceptibility to fractures, particularly among the elderly population. While conventional treatments for osteoporosis have shown efficacy, they are associated with certain limitations, including limited drug bioavailability, non-specific administration, and the occurrence of adverse effects. In recent years, nanoparticle-based drug delivery systems have emerged as a promising approach for managing osteoporosis. Nanoparticles possess unique physicochemical properties, such as a small size, large surface area-to-volume ratio, and tunable surface characteristics, which enable them to overcome the limitations of conventional therapies. These nanoparticles offer several advantages, including enhanced drug stability, controlled release kinetics, targeted bone tissue delivery, and improved drug bioavailability. This comprehensive review aims to provide insights into the recent advancements in nanoparticle-based therapy for osteoporosis. It elucidates the various types of nanoparticles employed in this context, including silica, polymeric, solid lipid, and metallic nanoparticles, along with their specific processing techniques and inherent properties that render them suitable as potential drug carriers for osteoporosis treatment. Furthermore, this review discusses the challenges and future suggestions associated with the development and translation of nanoparticle drug delivery systems for clinical use. These challenges encompass issues such as scalability, safety assessment, and regulatory considerations. However, despite these challenges, the utilization of nanoparticle-based drug delivery systems holds immense promise in revolutionizing the field of osteoporosis management by enabling more effective and targeted therapies, ultimately leading to improved patient outcomes.
... As a widely used antiosteoporotic drug, ZOL has been shown to enhance the osteogenesis of osteoblasts and BMSCs [24]. Additionally, previous experiments have demonstrated that ZOL can effectively promote osseointegration of implants in ovariectomized rats [25], increase numbers of cells committed to the osteoblastic phenotype [26], and promote cell cycle arrest and differentiation in MC3T3-E1 cells [7]. ...
Together with diabetic osteoporosis (DOP), diabetes patients experience poor peri-implant osteogenesis following implantation for dentition defects. Zoledronate (ZOL) is widely used to treat osteoporosis clinically. To evaluate the mechanism of ZOL for the treatment of DOP, experiments with DOP rats and high glucose-grown MC3T3-E1 cells were used. The DOP rats treated with ZOL and/or ZOL implants underwent a 4-week implant-healing interval, and then microcomputed tomography, biomechanical testing, and immunohistochemical staining were performed to elucidate the mechanism. In addition, MC3T3-E1 cells were maintained in an osteogenic medium with or without ZOL to confirm the mechanism. The cell migration, cellular actin content, and osteogenic differentiation were evaluated by a cell activity assay, a cell migration assay, as well as alkaline phosphatase, alizarin red S, and immunofluorescence staining. The mRNA and protein expression of adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK (p-AMPK), osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), bone morphogenetic protein 2 (BMP2), and collagen type I (Col-I) were detected using real-time quantitative PCRs and western blot assays, respectively. In the DOP rats, ZOL markedly improved osteogenesis, enhanced bone strength and increased the expression of AMPK, p-AMPK, and Col-I in peri-implant bones. The in vitro findings showed that ZOL reversed the high glucose-induced inhibition of osteogenesis via the AMPK signaling pathway. In conclusion, the ability of ZOL to promote osteogenesis in DOP by targeting AMPK signaling suggests that therapy with ZOL, particularly simultaneous local and systemic administration, may be a unique approach for future implant repair in diabetes patients.
... Zoledronate enhances osteoblast number and activity thus, improve the osteogenic potential in graft materials. The idea of using zoledronic to take advantage of its osteogenic effects has been proposed in a number of bone regeneration researches [15][16][17]. It was found that local delivery of ZA resulted in the overexpression of bone osteogenic-related markers, enhancing bone volume and mineralization [18,19]. ...
Recent trends in bone tissue engineering have focused on the development of biomimetic constructs with appropriate mechanical and physiochemical properties. Here, we report the fabrication of an innovative biomaterial scaffold based on a new bisphosphonate-containing synthetic polymer combined with gelatin. To this end, zoledronate (ZA)-functionalized polycaprolactone (PCL-ZA) was synthesized by a chemical grafting reaction. After adding gelatin to the PCL-ZA polymer solution, the porous PCL-ZA/gelatin scaffold was fabricated by the freeze-casting method. A scaffold with aligned pores and a porosity of 82.04 % was obtained. During in vitro biodegradability test, 49 % of its initial weight lost after 5 weeks. The elastic modulus of the PCL-ZA/gelatin scaffold was 31.4 MPa, and its tensile strength was 4.2 MPa. Based on the results of MTT assay, the scaffold had good cytocompatibility with human Adipose-Derived Mesenchymal Stem Cells (hADMSCs). Furthermore, cells grown in PCL-ZA/gelatin scaffold showed the highest mineralization and ALP activity compared to other test groups. Results of the RT-PCR test revealed that RUNX2, COL 1A1, and OCN genes were expressed in PCL-ZA/gelatin scaffold at the highest level, suggesting its good osteoinductive capacity. These results revealed that PCL-ZA/gelatin scaffold could be considered a proper biomimetic platform for bone tissue engineering.
... The in vitro results showed enhanced osteoblast differentiation when ZOL concentration was 50 µmol L −1 . The in vivo studies in osteoporotic rabbits showed improved bone growth and osteogenesis [44]. One study reported the use of gold nanoparticles conjugated with gelatin nanoparticles for the purpose of bioimaging as well as a drug delivery system. ...
Biopolymers are polymers obtained from either renewable or non-renewable sources and are the most suitable candidate for tailor-made nanoparticles owing to their biocompatibility, biodegradability, low toxicity and immunogenicity. Biopolymeric nanoparticles (BPn) can be classified as natural (polysaccharide and protein based) and synthetic on the basis of their origin. They have been gaining wide interest in biomedical applications such as tissue engineering, drug delivery, imaging and cancer therapy. BPn can be synthesized by various fabrication strategies such as emulsification, ionic gelation, nanoprecipitation, electrospray drying and so on. The main aim of the review is to understand the use of nanoparticles obtained from biodegradable biopolymers for various biomedical applications. There are very few reviews highlighting biopolymeric nanoparticles employed for medical applications; this review is an attempt to explore the possibilities of using these materials for various biomedical applications. This review highlights protein based (albumin, gelatin, collagen, silk fibroin); polysaccharide based (chitosan, starch, alginate, dextran) and synthetic (Poly lactic acid, Poly vinyl alcohol, Poly caprolactone) BPn that has recently been used in many applications. The fabrication strategies of different BPn are also being highlighted. The future perspective and the challenges faced in employing biopolymeric nanoparticles are also reviewed.
... These agents include vascular endothelial growth factor, PTH and bisphosphonates. Incorporation of these agents compensates for the limited osteogenic potential of a single-phase scaffold material [144,155,159,160]. Nevertheless, problem is encountered when a layer of bone anabolic therapeutic agent (such as bisphosphonate) is applied as a coating on an unmodified implant surface. ...
Osteoporosis is caused by the disruption in homeostasis between bone formation and bone resorption. Conventional management of osteoporosis involves systematic drug administration and hormonal therapy. These treatment strategies have limited curative efficacy and multiple adverse effects. Biomaterials-based therapeutic strategies have recently emerged as promising alternatives for the treatment of osteoporosis. The present review summarizes the current status of biomaterials designed for managing osteoporosis. The advantages of biomaterials-based strategies over conventional systematic drug treatment are presented. Different anti-osteoporotic delivery systems are concisely addressed. These materials include injectable hydrogels and nanoparticles, as well as anti-osteoporotic bone tissue engineering materials. Fabrication techniques such as 3D printing, electrostatic spinning and artificial intelligence are appraised in the context of how the use of these adjunctive techniques may improve treatment efficacy. The limitations of existing biomaterials are critically analyzed, together with deliberation of the future directions in biomaterials-based therapies. The latter include discussion on the use of combination strategies to enhance therapeutic efficacy in the osteoporosis niche.
... Osteoporosis is a systemic skeletal disease characterized by a reduction in bone mineral density and bone strength, which increases the risk of fracture due to increased bone fragility [7]. The pathogenesis of osteoporosis is mainly due to a disruption of the balance between bone resorption and bone formation, resulting in a disorder of bone metabolism, which is associated with a decrease in the number and function of osteoblasts [8,9]. The process of bone reconstruction is based on a dynamic balance between the two main mechanisms of osteoclast-associated bone resorption and osteoblast-associated bone formation [8]. ...
... The pathogenesis of osteoporosis is mainly due to a disruption of the balance between bone resorption and bone formation, resulting in a disorder of bone metabolism, which is associated with a decrease in the number and function of osteoblasts [8,9]. The process of bone reconstruction is based on a dynamic balance between the two main mechanisms of osteoclast-associated bone resorption and osteoblast-associated bone formation [8]. And osteoblast cell death is an important pathogenic mechanism in osteoporosis [9]. ...
Current research suggests that chronic high-fat dietary intake can lead to bone loss in adults; however, the mechanism by which high-fat diets affect the development of osteoporosis in individuals is unclear. As high-fat diets are strongly associated with ferroptosis, whether ferroptosis mediates high-fat diet-induced bone loss was the focus of our current study. By dividing the mice into a high-fat diet group, a high-fat diet + ferroptosis inhibitor group and a normal chow group, mice in the high-fat group were given a high-fat diet for 12 weeks. The mice in the high-fat diet + ferroptosis inhibitor group were given 1 mg/kg Fer-1 per day intraperitoneally at the start of the high-fat diet. Microscopic CT scans, histological tests, and biochemical indicators of ferroptosis were performed on bone tissue from all three groups at the end of the modelling period. Mc3t3-E1 cells were also used in vitro and divided into three groups: high-fat medium group, high-fat medium+ferroptosis inhibitor group, and control group. After 24 hours of incubation in high-fat medium, Mc3t3-E1 cells were assayed for ferroptosis marker proteins and biochemical parameters, and osteogenesis induction was performed simultaneously. Cellular alkaline phosphatase content and expression of osteogenesis-related proteins were measured at day 7 of osteogenesis induction. The results showed that a high-fat diet led to the development of femoral bone loss in mice and that this process could be inhibited by ferroptosis inhibitors. The high-fat diet mainly affected the number of osteoblasts produced in the bone marrow cavity. The high-fat environment in vitro inhibited osteoblast proliferation and osteogenic differentiation, and significant changes in ferroptosis-related biochemical parameters were observed. These findings have implications for the future clinical treatment of bone loss caused by high-fat diets.
... Another study, loading nanotubes with zoledronic acid, described enhanced the implant stability, improved the implant osseointegration, shown with an ovariectomized rat model [38] . Furthermore, a recent study by Yang et al. [39] analyzed the effect of zoledronic acid loaded gelatin nanoparticles incorporated in porous titanium scaffolds in vitro and in vivo. They found indications that this new form of zoledronic acid delivery at the implant site has a superior biocompatibility and bone tissue regeneration capacity and could have great benefits in compromised bone. ...
Since ancient times, reduction and internal fixation has been applied to restore skeletal integrity. Despite advances in the understanding of fracture healing, the risk of complication such as implant loosening or implant-related infection still depicts a challenging complication. Nowadays, a great deal of research is devoted to unreveal the impact of implant surface modifications on osteogenic processes to enhance bone consolidation and osseointegration. This narrative review is aimed to (1) show the evolution and already achieved milestones of implant optimization, and (2) to outline the key factors that contribute to an enhanced osseointegration. Different physical and chemical roughening techniques are currently applied in various studies. Surface patterning on the nanoscale has been found to be an essential factor for the biological response, achievable by e.g. anodisation or laser texturing. Besides surface roughening, also different coating methods are vastly investigated. Next to metal or inorganic compounds as coating material, a variety of biomolecules is currently studied for their osteosupportive capacities. Osseointegration can be improved by surface modification on the micro and nanoscale. Bioactive agents can further improve the osseointegration potential. Used agents at the moment are e.g. inorganic compounds, growth factors (BMPs and non-BMPs) and antiresorptive drugs. The advancement in research on new implant generations therefore aims at actively supporting osseointegration processing.
... The specific mechanism of disuse osteoporosis is still unknown. The process of bone reconstruction is based on the dynamic balance of two main mechanisms: osteoclast-related bone absorption and osteoblast-related bone formation, accompanied by the effects of various stimuli in vivo and in vitro [3]. Mechanical stress stimulation plays an important role in maintaining the stability of bone metabolism and maintaining normal function [4]. ...
Disused osteoporosis is a kind of osteoporosis, a common age-related disease. Neurological disorders are major risk factors for osteoporosis. Though there are many studies on disuse osteoporosis, the genetic mechanisms for the association between glutathione metabolism and ferroptosis in osteoblasts with disuse osteoporosis are still unclear. The purpose of this study is to explore the key genes and other related mechanism of ferroptosis and glutathione metabolism in osteoblast differentiation and disuse osteoporosis. By weighted gene coexpression network analysis (WGCNA), the process of osteoblast differentiation-related genes was studied in GSE30393. And the related functional pathways were found through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. By combining GSE1367 and GSE100933 together, key genes which were separately bound up with glutathione metabolism and ferroptosis were located. The correlation of these key genes was analyzed by the Pearson correlation coefficient. GSTM1 targeted agonist glutathione (GSH) selected by connectivity map (CMap) analysis was used to interfere with the molding disused osteoporosis process in MC3T3-E1 cells. RT-PCR and intracellular reactive oxygen species (ROS) were performed. Two important pathways, glutathione metabolism and ferroptosis pathways, were found. GSTM1 and TFRC were thought as key genes in disuse osteoporosis osteoblasts with the two mechanisms. The two genes have a strong negative correlation. Our experiment results showed that the expression of TFRC was consistent with the negative correlation with the activation process of GSTM1. The strong relationship between the two genes was proved. Glutathione metabolism and ferroptosis are important in the normal differentiation of osteoblasts and the process of disuse osteoporosis. GSTM1 and TFRC were the key genes. The two genes interact with each other, which can be seen as a bridge between the two pathways. The two genes participate in the process of reducing ROS in disuse osteoporosis osteoblasts.
... 59 Following exposure to physiological liquid media, Gel NPs swell and form coral-like multiparous channels that simplify the incorporation of biomolecules and higher loading efficiency. 60 ...
The introduction of nanoparticles into bone tissue engineering strategies is beneficial to govern cell fate into osteogenesis and the regeneration of large bone defects. The present study explored the role of nanoparticles to advance osteogenesis with a focus on the cellular and molecular pathways involved. Pubmed, Pubmed Central, Embase, Scopus, and Science Direct databases were explored for those published articles relevant to the involvement of nanoparticles in osteogenic cellular pathways. As multifunctional compounds, nanoparticles contribute to scaffold-free and scaffold-based tissue engineering strategies to progress osteogenesis and bone regeneration. They regulate inflammatory responses and osteo/angio/osteoclastic signaling pathways to generate an osteogenic niche. Besides, nanoparticles interact with biomolecules, enhance their half-life and bioavailability. Nanoparticles are promising candidates to promote osteogenesis. However, the interaction of nanoparticles with the biological milieu is somewhat complicated, and more considerations are recommended on the employment of nanoparticles in clinical applications because of NP-induced toxicities.
