Strontium Functionalized in Biomaterials for Bone Tissue Engineering: A Prominent Role in Osteoimmunomodulation.
Frontiers in bioengineering and biotechnology
With the development of bone tissue engineering bio-scaffold materials by adding metallic ions to improve bone healing have been extensively explored in the past decades. Strontium a non-radioactive element, as an essential osteophilic trace element for the human body, has received widespread attention in the medical field due to its superior biological properties of inhibiting bone resorption and promoting osteogenesis. As the concept of osteoimmunology developed, the design of orthopedic biomaterials has gradually shifted from "immune-friendly" to "immunomodulatory" with the aim of promoting bone healing by modulating the immune microenvironment through implanted biomaterials. The process of bone healing can be regarded as an immune-induced procedure in which immune cells can target the effector cells such as macrophages, neutrophils, osteocytes, and osteoprogenitor cells through paracrine mechanisms, affecting pathological alveolar bone resorption and physiological bone regeneration. As a kind of crucial immune cell, macrophages play a critical role in the early period of wound repair and host defense after biomaterial implantation. Despite Sr-doped biomaterials being increasingly investigated, how extracellular Sr guides the organism toward favorable osteogenesis by modulating macrophages in the bone tissue microenvironment has rarely been studied. This review focuses on recent knowledge that the trace element Sr regulates bone regeneration mechanisms through the regulation of macrophage polarization, which is significant for the future development of Sr-doped bone repair materials. We will also summarize the primary mechanism of Sr in bone, including calcium-sensing receptor (CaSR) and osteogenesis-related signaling pathways.
10.3389/fbioe.2022.928799
Magnesium-based bone implants: immunohistochemical analysis of peri-implant osteogenesis by evaluation of osteopontin and osteocalcin expression.
Bondarenko A,Angrisani N,Meyer-Lindenberg A,Seitz J M,Waizy H,Reifenrath J
Journal of biomedical materials research. Part A
The functions of some bone proteins, as osteopontin (OPN) and osteocalcin (OC), have been discovered by the latest studies. This fact suggests the possibility of their immunodetection to characterize peri-implant osteogenesis and implant impact on it. Cylindrical pins of Mg alloys (MgCa0.8, LAE442, ZEK100, LANd442) and titanium alloy (TiAl6V4) were implanted into the tibial medullae of 46 rabbits. Each group was divided regarding to implant duration (3 and 6 months). Bone samples adjacent to the implants were decalcified and treated with routine histological and immunohistochemical protocols using OC and OPN-antibodies. OC was detected in matrix of compact bone, but very rarely in osteoid and bone cells. OPN was detected intracellularly and in osteoid. After 3 months, the highest level of both markers was found in titanium group, followed by LAE442-group. In contrast to LAE442 and TiAl6V4, the other Mg alloys showed increasing levels of OC after 6 months. Lower levels of OP and OC compared to the control group are related to the continuous implant degradation and instability of bone-implant interface in early post-surgical period. Reduced marker's expression in LAE442 and TiAl6V4 groups after 6 months may indicate stabilization of bone-implant interface and completion of peri-implant neo-osteogenesis. Declining characters of OC and OPN expression over the implantation time, as well as their lowest levels in late post-surgical term, suggest a more appropriate biocompatibility of LAE442, which therefore seems to be the most preferable of the tested materials for the use in orthopaedic applications.
10.1002/jbm.a.34828
Enhanced proliferation and osteogenic differentiation of mesenchymal stem cells on graphene oxide-incorporated electrospun poly(lactic-co-glycolic acid) nanofibrous mats.
Luo Yu,Shen He,Fang Yongxiang,Cao Yuhua,Huang Jie,Zhang Mengxin,Dai Jianwu,Shi Xiangyang,Zhang Zhijun
ACS applied materials & interfaces
Currently, combining biomaterial scaffolds with living stem cells for tissue regeneration is a main approach for tissue engineering. Mesenchymal stem cells (MSCs) are promising candidates for musculoskeletal tissue repair through differentiating into specific tissues, such as bone, muscle, and cartilage. Thus, successfully directing the fate of MSCs through factors and inducers would improve regeneration efficiency. Here, we report the fabrication of graphene oxide (GO)-doped poly(lactic-co-glycolic acid) (PLGA) nanofiber scaffolds via electrospinning technique for the enhancement of osteogenic differentiation of MSCs. GO-PLGA nanofibrous mats with three-dimensional porous structure and smooth surface can be readily produced via an electrospinning technique. GO plays two roles in the nanofibrous mats: first, it enhances the hydrophilic performance, and protein- and inducer-adsorption ability of the nanofibers. Second, the incorporated GO accelerates the human MSCs (hMSCs) adhesion and proliferation versus pure PLGA nanofiber and induces the osteogenic differentiation. The incorporating GO scaffold materials may find applications in tissue engineering and other fields.
10.1021/acsami.5b00862
Comparative study of the osteogenic ability of four different ceramic constructs in an ectopic large animal model.
Viateau Véronique,Manassero Mathieu,Sensébé Luc,Langonné Alain,Marchat David,Logeart-Avramoglou Delphine,Petite Hervé,Bensidhoum Morad
Journal of tissue engineering and regenerative medicine
Tissue-engineered constructs combining bone marrow mesenchymal stem cells with biodegradable osteoconductive scaffolds are very promising for repairing large segmental bone defects. Synchronizing and controlling the balance between scaffold-material resorption and new bone tissue formation are crucial aspects for the success of bone tissue engineering. The purpose of the present study was to determine, and compare, the osteogenic potential of ceramic scaffolds with different resorbability. Four clinically relevant granular biomaterial scaffolds (specifically, Porites coral, Acropora coral, beta-tricalcium phosphate and banked bone) with or without autologous bone marrow stromal cells were implanted in the ectopic, subcutaneous-pouch sheep model. Scaffold material resorption and new bone formation were assessed eight weeks after implantation. New bone formation was only detected when the biomaterial constructs tested contained MSCs. New bone formation was higher in the Porites coral and Acropora coral than in either the beta-tricalcium phosphate or the banked bone constructs; furthermore, there was a direct correlation between scaffold resorption and bone formation. The results of the present study provide evidence that, among the biomaterials tested, coral scaffolds containing MSCs promoted the best new bone formation in the present study.
10.1002/term.1782
Metallic ion doped tri-calcium phosphate ceramics: Effect of dynamic loading on in vivo bone regeneration.
Samanta Sujan Krishna,Devi K Bavya,Das Piyali,Mukherjee Prasenjit,Chanda Abhijit,Roy Mangal,Nandi Samit Kumar
Journal of the mechanical behavior of biomedical materials
The present study was carried out to evaluate the effect of dynamic loading on bone regeneration performance of different doped β-tri-calcium phosphate ceramics. We have developed porous beta tri-calcium phosphate (β-TCP), 5%zinc doped, 5% magnesium doped and 5% titanium doped β-TCP by aqueous solution combustion technique. All the synthesized β-TCP powders showed pore size of 21-146 μm (pure β-TCP), 16-142 μm (Zn-β-TCP), 28-156 μm (Mg- β-TCP) and 14-173 μm (Ti-β-TCP) while their apparent porosity 17.89%, 28.09%, 26.54% and 25.87% respectively. The pure and doped samples were implanted in femoral bone defect model (rabbit) to assess bone regeneration under dynamic loading. Bone regeneration was assessed after 1 and 2 month post-implantation on the basis of clinical radiological, histological, fluorochrome labelling, micro computed tomography (μ-CT) and scanning electron microscopy (SEM). Radiological and fluorochrome labelling study showed reduced size of 5%Ti-β-TCPimplant vis-à-vis more new bone formation as compared to other groups. Micro-CT of the implanted bone sample showed a significant amount of newly formed bony tissue surrounding the Ti-β-TCP implant as compared to other samples. Similar findings of less interfacial gap between the implant and bone were also observed in SEM study. However, all the doped materials are suitable as bone grafting material and have potential for application in bone tissue engineering.
10.1016/j.jmbbm.2019.04.051
Silver ion-doped calcium phosphate-based bone-graft substitute eliminates chronic osteomyelitis: An experimental study in animals.
Köse Nusret,Asfuroğlu Zeynel M,Köse Aydan,Şahintürk Varol,Gürbüz Mevlüt,Doğan Aydın
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Despite the latest technologies and advances in microbiology and orthopedic surgery, chronic osteomyelitis is still a challenging disorder. Antibiotic resistance and bacterially induced bone destruction can have very serious consequences. We hypothesized that calcium phosphate-based bone graft substitution with silver ion doping would simultaneously treat bone infection and the bony defect in the chronic osteomyelitis. An unicortical 10-mm-diameter bone was harvested in the proximal tibial metaphysis of 24 rabbits. After contaminating the wounds with an infective dose of methicillin-resistant Staphylococcus aureus (MRSA), osteomyelitis was proven radiographically and microbiologically in all rabbits. Animals were than divided into three groups. The first group received vancomycin-impregnated bone cement beads (comparative control group), the second/experimental group received silver ion-doped calcium phosphate beads and the third group received pure calcium phosphate beads (negative controls). Radiographs, intraosseous cultures, and histopathological examinations were performed on postoperative Week 10. The cultures showed no evidence of intramedullary infection in the silver ion-doped calcium phosphate beads group, but they were positive for MRSA in four of the six rabbits in the vancomycin- impregnated bone cement beads group and in all of the eight rabbits in the pure calcium phosphate beads group. Quantitative assessment of histopathological examination showed lowest total damage score in silver ion-doped calcium phosphate beads group (p < .001). Percentage of osteoid tissue + bony tissue was also higher in this group compared with other groups. In the final radiological examinations, it was observed that the changes caused by osteomyelitis in the bone tissue in the silver ion-doped calcium phosphate beads group were much improved compared with the vancomycin-impregnated bone cement beads group. Silver ion doped calcium phosphate-based bone-graft substitute offer the ability to stimulate bone growth, combat infection, and, ultimately, treat experimental chronic osteomyelitis in an animal model.
10.1002/jor.24946
Ion incorporation into bone grafting materials.
Periodontology 2000
The use of biomaterials in regenerative medicine has expanded to treat various disorders caused by trauma or disease in orthopedics and dentistry. However, the treatment of large and complex bone defects presents a challenge, leading to a pressing need for optimized biomaterials for bone repair. Recent advances in chemical sciences have enabled the incorporation of therapeutic ions into bone grafts to enhance their performance. These ions, such as strontium (for bone regeneration/osteoporosis), copper (for angiogenesis), boron (for bone growth), iron (for chemotaxis), cobalt (for B12 synthesis), lithium (for osteogenesis/cementogenesis), silver (for antibacterial resistance), and magnesium (for bone and cartilage regeneration), among others (e.g., zinc, sodium, and silica), have been studied extensively. This review aims to provide a comprehensive overview of current knowledge and recent developments in ion incorporation into biomaterials for bone and periodontal tissue repair. It also discusses recently developed biomaterials from a basic design and clinical application perspective. Additionally, the review highlights the importance of precise ion introduction into biomaterials to address existing limitations and challenges in combination therapies. Future prospects and opportunities for the development and optimization of biomaterials for bone tissue engineering are emphasized.
10.1111/prd.12533
Injectable Antiswelling and High-Strength Bioactive Hydrogels with a Wet Adhesion and Rapid Gelling Process to Promote Sutureless Wound Closure and Scar-free Repair of Infectious Wounds.
ACS nano
Developing injectable antiswelling and high-strength bioactive hydrogels with wet tissue adhesiveness and a rapid gelling process to meet the requirements for rapid hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds continues to have ongoing challenges. Herein, injectable, antibacterial, and antioxidant hydrogel adhesives based on poly(citric acid--polyethylene glycol)--dopamine and amino-terminated Pluronic F127 (APF) micelles loaded with astragaloside IV (AS) are prepared. The HO/horseradish peroxidase (HRP) system is used to cause cross-linking of the hydrogel network through oxidative coupling between catechol groups and chemical cross-linking between the catechol group and the amino group. The hydrogels exhibit a rapid gelling process, high mechanical strength, an antiswelling effect, good antioxidant property, HO release behavior, and degradability. In addition, the hydrogels present good wet tissue adhesiveness, high bursting pressure, excellent antibacterial activity, long-term sustained release of AS, and good biocompatibility. The hydrogels perform good hemostasis on mouse liver, rat liver, and rabbit femoral vein bleeding models and achieve much better closure and healing of skin incisions than biomedical glue and surgical sutures. Furthermore, the hydrogel dressing significantly improved the scar-free repair of MRSA-infected full thickness skin defect wounds by modulating inflammation, regulating the ratio of collagen I/III, and improving the vascularization and granulation tissue formation. Thus, AS-loaded hydrogels show huge potential as multifunctional dressings for in vivo hemostasis, sutureless wound closure, and scar-free repair of infected skin wounds.
10.1021/acsnano.3c08625
Metal Ion-Doped Hydroxyapatite-Based Materials for Bone Defect Restoration.
Bioengineering (Basel, Switzerland)
Hydroxyapatite (HA)-based materials are widely used in the bone defect restoration field due to their stable physical properties, good biocompatibility, and bone induction potential. To further improve their performance with extra functions such as antibacterial activity, various kinds of metal ion-doped HA-based materials have been proposed and synthesized. This paper offered a comprehensive review of metal ion-doped HA-based materials for bone defect restoration based on the introduction of the physicochemical characteristics of HA followed by the synthesis methods, properties, and applications of different kinds of metal ion (Ag, Zn, Mg, Sr, Sm, and Ce)-doped HA-based materials. In addition, the underlying challenges for bone defect restoration using these materials and potential solutions were discussed.
10.3390/bioengineering10121367
Ion-Doped Silicate Bioceramic Coating of Ti-Based Implant.
Iranian biomedical journal
Titanium and its alloy are known as important load-bearing biomaterials. The major drawbacks of these metals are fibrous formation and low corrosion rate after implantation. The surface modification of biomedical implants through various methods such as plasma spray improves their osseointegration and clinical lifetime. Different materials have been already used as coatings on biomedical implant, including calcium phosphates and bioglass. However, these materials have been reported to have limited clinical success. The excellent bioactivity of calcium silicate (Ca-Si) has been also regarded as coating material. However, their high degradation rate and low mechanical strength limit their further coating application. Trace element modification of (Ca-Si) bioceramics is a promising method, which improves their mechanical strength and chemical stability. In this review, the potential of trace element-modified silicate coatings on better bone formation of titanium implant is investigated.
10.7508/ibj.2016.04.002
Bioactive glass doped with noble metal nanoparticles for bone regeneration: kinetics and proliferative impact on human bone cell line.
RSC advances
This work investigates the bioactivity of novel silver-doped (BG-Ag) and gold-doped (BG-Au) quaternary 46S6 bioactive glasses synthesized a semi-solid-state technique. A pseudo-second-order kinetic model successfully predicted the uptake kinetic profiles of the initial ion-exchange release of Ca in simulated body fluid, the subsequent Si release, and finally, the adsorption of Ca and P onto the bioactive glasses. Doping with silver nanoparticles enhanced the rate of P uptake by up to approximately 90%; whereas doping with gold nanoparticles improved Ca and P uptake rates by up to about 7 and 2 times, respectively; as well as Ca uptake capacity by up to about 19%. The results revealed that the combined effect of Ca and Si release, and possibly the release of silver and gold ions into solution, influenced apatite formation due to their effect on Ca and P uptake rate and capacity. In general, gold-doped bioactive glasses are favoured for enhancing Ca and P uptake rates in addition to Ca uptake capacity. However, silver-doped bioactive glasses being less expensive can be utilized for applications targeting rapid healing. studies showed that BG, BG-Ag and BG-Au had no cytotoxic effects on osteosarcoma MG-63 cells, while they exhibited a remarkable cell proliferation even at low concentration. The prepared bioactive glass doped with noble metal nanoparticles could be potentially used in bone regeneration applications.
10.1039/d1ra03876a
Magnesium Phosphate Bioceramics for Bone Tissue Engineering.
Chemical record (New York, N.Y.)
Magnesium phosphate (MgP) is a family of newly developed resorbable bioceramics for bone tissue engineering. Although calcium phosphates (CaP) are the most commonly used bioceramics, low solubility, and slow degradation, when implanted in vivo, are their main drawbacks. Magnesium (Mg) is an essential element in the human body as it plays important role in bone metabolism, DNA stabilization, and skeletal development. Recent research on magnesium phosphates has established their higher degradability, in vitro, and in vivo biocompatibility. Compared to CaP, very limited research work has been found in the area of MgP. The prime goal of this review is to bring out the importance of magnesium phosphate ceramics for biomedical applications. In this review, we have discussed the synthesis methods, mechanical properties, in vitro and in vivo biocompatibility of MgP bioceramics. Moreover, we have highlighted the recent developments in metal ion-doped MgPs and MgP scaffolds for bone tissue engineering.
10.1002/tcr.202200136
Copper ion-doped multifunctional hydrogel with mild photothermal enhancement promotes vascularized bone regeneration.
Journal of biomaterials applications
The design and construction of a new and excellent synthetic graft is of great significance in the field of bone defect repair and reconstruction. In this study, a dopamine modified chitosan hydrogel doped with Cu ions with a mild photothermal effect was designed to provide a better microenvironment to advance the bone repair via promote the angiogenesis and osteogenesis. Characterizations showed the successful synthesis of the material while it also presented excellent biocompatibility and mild photothermal effect under the irradiation of near-infrared light. Further, it could enhance the angiogenesis of HUVECs cells through promoting the ability of migration and tube formation and enhance the osteogenic differentiation of MC3T3-E1 cells via increasing the content of vital osteogenic factors including Runx2, Col-1, OPN, OCN, OSX, etc. The in vivo experiment also testified that it could promote the bone defect repair in rat models. These results indicate the multifunctional hydrogel is an ideal material for the treatment of bone defects and has good clinical application potential.
10.1177/08853282241268683