A lithium-doped surface inspires immunomodulatory functions for enhanced osteointegration through PI3K/AKT signaling axis regulation

Peng, Feng; Qiu, Longhai; Yao, Mengyu; Liu, Lidan; Zheng, Yufeng; Wu, Shuilin; Ruan, Qingdong; Liu, Xuanyong; Li, Mei; Chu, Paul K.

doi:10.1039/d1bm01075a

Cited by 23 publications

(30 citation statements)

References 45 publications

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“…In accordance with the histomorphometric analysis, the ZDI‐Li implants revealed significantly higher BV/TV, Tb.Th, and BIC values at 4 weeks postimplantation, indicating the favorable new bone formation around the implants with ECD‐Li coatings. A recent study has also proved our findings that favorable immune‐modulated osteogenesis and osseointegration of bone implants could be realized by the incorporation of Li 73 . Meanwhile, as illustrated in the hard tissue sections, more mature bone trabeculae and lamellar bone were common in ZDI‐Li group at 4 weeks, while ZDI group showed sparse trabeculae distribution.…”

Section: Discussionsupporting

confidence: 71%

“…A recent study has also proved our findings that favorable immune-modulated osteogenesis and osseointegration of bone implants could be realized by the incorporation of Li. 73 Meanwhile, as illustrated in the hard tissue sections, more mature bone trabeculae and lamellar bone were common in ZDI-Li group at 4 weeks, while ZDI group showed sparse trabeculae distribution. As the crucial indexes of osseointegration assessment, higher BIC values were also detected in ZDI-Li group at 4 weeks.…”

Section: Discussionmentioning

confidence: 81%

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Electrochemical deposition of lithium coating on titanium implant with enhanced early stage osseointegration

Huang

Zhang

et al. 2022

J Biomed Mater Res

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Recently, a large number of studies have reported that lithium (Li) displayed a positive effect on osteogenesis. However, only a few studies have investigated the Liincorporated surfaces through electrochemical deposition. In this study, electrochemical deposition was conducted on a CHI600E electrochemical workstation. The characterization of electrochemical deposition (ECD) and ECD-Li surfaces were detected by field-emission scanning electron microscopy with energy-dispersive spectrometer.rBMSCs were cultured on two surfaces for subsequent adhesion, proliferation and live/dead assay. To evaluate the effects of Li-incorporated implants by electrochemical deposition on osseointegration in vivo, teeth extraction of two premolars and one first molar in bilateral mandible were performed on six male beagle dogs. After 3 months, ZDI and ZDI-Li implants were inserted into the bilateral mandible of each beagle dog.Micro Computed Tomography (Micro-CT) and hard tissue sectioning analysis were carried out to evaluate the osseointegration at 4-and 8-weeks post-implantation. Resultsshowed that ECD-Li surface promoted adhesion and proliferation of BMSCs in the early stage. More importantly, through micro-CT analysis, the values of bone volume/ total volume (BV/TV) (0.374 ± 0.015), bone-implant contact (BIC) (0.831 ± 0.025), and Tb.Th (0.412 ± 0.007) in ZDI-Li group was significantly higher than those of ZDI group (0.302 ± 0.009, 0.700 ± 0.023, 0.353 ± 0.001, p < .01) at 4 weeks. Similarly, ZDI-Li group manifested more bone contact with the implant surfaces at 4 weeks based on hard tissue sectioning analysis, whereas no significant difference was detected between two groups at 8 weeks. Therefore, incorporating Li into implant surface through ECD could enhance early osseointegration in vivo.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 81%

Electrochemical deposition of lithium coating on titanium implant with enhanced early stage osseointegration

Huang

Zhang

et al. 2022

J Biomed Mater Res

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“…Huang et al [ 14 ] applied LiCl in osteoporotic model, demonstrating that LiCl was beneficial to the proliferation of bone marrow‐derived mesenchymal stem cells (BMSCs) and promoted osteogenesis by regulating autophagy. Peng et al [ 15 ] found that the appropriate addition of lithium could enhance cell attachment and stimulate osteogenesis. Interestingly, our previous study has proved that LiCl may promote interface osteointegration by suppressing osteoclast differentiation and enhancing osteogenesis.…”

Section: Introductionmentioning

confidence: 99%

Regulating Macrophage Polarization in High Glucose Microenvironment Using Lithium‐Modified Bioglass‐Hydrogel for Diabetic Bone Regeneration

Bai

et al. 2022

Adv Healthcare Materials

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Diabetes mellitus is a chronic metabolic disease with a proinflammatory microenvironment, causing poor vascularization and bone regeneration. Due to the lack of effective therapy and one-sided focus on the direct angiogenic properties of biomaterials and osteogenesis stimulation, the treatment of diabetic bone defect remains challenging and complex. In this study, using gelatin methacryloyl (GelMA) as a template, a lithium (Li) -modified bioglass-hydrogel for diabetic bone regeneration is developed. It exhibits a sustained ion release for better bone regeneration under diabetic microenvironment. The hydrogel is shown to be mechanically adaptable to the complex shape of the defect. In vitro, Li-modified bioglass-hydrogel promoted cell proliferation, direct osteogenesis, and regulated macrophages in high glucose (HG) microenvironment, with the secretion of bone morphogenetic protein-2 and vascular endothelial growth factor to stimulate osteogenesis and neovascularization indirectly. In vivo, composite hydrogels containing GelMA and Li-MBG (GM/M-Li) release Li ions to relieve inflammation, providing an anti-inflammatory microenvironment for osteogenesis and angiogenesis. Applying Li-modified bioglass-hydrogel, significantly enhances bone regeneration in a diabetic rat bone defect. Together, both remarkable in vitro and in vivo outcomes in this study present an opportunity for diabetic bone regeneration on the basis of HG microenvironment.

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“…The critical factor for successful implantation in vivo depends on excellent integration between the implant and bone. Previous studies showed that osseointegration was affected by different factors, such as bacterial infection, inflammation, etc., during the bone healing phase after implantation [ 25 , 187 , 188 , 189 ]. These factors may result in Ti-based implants failing to stimulate the biological activity of surrounding osteocytes, triggering infection and activating abnormal phagocytosis of macrophages.…”

Section: Discussionmentioning

confidence: 99%

Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration

et al. 2022

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Titanium and its alloys are the most widely applied orthopedic and dental implant materials due to their high biocompatibility, superior corrosion resistance, and outstanding mechanical properties. However, the lack of superior osseointegration remains the main obstacle to successful implantation. Previous traditional surface modification methods of titanium-based implants cannot fully meet the clinical needs of osseointegration. The construction of local drug delivery systems (e.g., antimicrobial drug delivery systems, anti-bone resorption drug delivery systems, etc.) on titanium-based implants has been proved to be an effective strategy to improve osseointegration. Meanwhile, these drug delivery systems can also be combined with traditional surface modification methods, such as anodic oxidation, acid etching, surface coating technology, etc., to achieve desirable and enhanced osseointegration. In this paper, we review the research progress of different local drug delivery systems using titanium-based implants and provide a theoretical basis for further research on drug delivery systems to promote bone–implant integration in the future.

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A lithium-doped surface inspires immunomodulatory functions for enhanced osteointegration through PI3K/AKT signaling axis regulation

Abstract: The response of immune systems is crucial to the success of biomedical implants in vivo and in particular, orthopedic implants must possess proper immunomodulatory functions to allow sufficient osteointegration. In...

Cited by 23 publications

References 45 publications

Electrochemical deposition of lithium coating on titanium implant with enhanced early stage osseointegration

Electrochemical deposition of lithium coating on titanium implant with enhanced early stage osseointegration

Regulating Macrophage Polarization in High Glucose Microenvironment Using Lithium‐Modified Bioglass‐Hydrogel for Diabetic Bone Regeneration

Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration

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