Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes

Beck, Frances W.J.; Hartmann, Eliza S.; Koehler, M; Redeker, Julia I.; Schluessel, Sabine; Schmitt, Bärbel; Fottner, Andreas; Unger, Marina; Griensven, Martijn van; Michael, Jan; Summer, Burkhard; Kunzelmann, Karl‐Heinz; Beutner, René; Scharnweber, Dieter; Kostenuik, Paul J.; Mayer-Wagner, Susanne

doi:10.3390/ijms20051002

Cited by 7 publications

(5 citation statements)

References 33 publications

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“…[46][47][48][49][50][51][52] Since bone remodeling and osteoconductive properties are essential for osteointegration into the pores of a biomaterial, surface derivatization using various biological agents and inorganic elements can additionally enhance the process by creating an osteoconductive milieu. These include anti-osteoporosis drugs such as Strontium ranelate and simvastatin, [53][54][55][56][57] bioactive molecules such as bone morphogenetic protein (BMP) and vascular endothelial growth factor (VEGF), 48,[58][59][60] and bioactive inorganic elements such as calcium (Ca), strontium (Sr), magnesium (Mg), zinc (Zn), and silicon (Si). [61][62][63] Mechano-transduction is a critical determinant of new bone formation, repair and regeneration, and adaptation of bone to its external environment.…”

Section: Discussionmentioning

confidence: 99%

A porous swelling copolymeric material for improved implant fixation to bone

et al. 2023

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Most metallic commercial bone anchors, such as screws and suture anchors achieve their fixation to bone through shear of the bone located between the threads. They have several deficiencies, potentially leading to failure, which are particularly evident in low‐density bone. These include stress‐shielding resulting from mechanical properties mismatch; lack of mechanically induced remodeling and osteointegration; and when the pullout force on the anchor, during functional activities, exceeds their pullout strength, catastrophic failure occurs leaving behind large bone defects that may be hard to repair. To overcome these deficiencies, we introduced in this study a porous swelling co‐polymeric material and studied its swelling and compressive mechanical characteristics as bone anchor under different configurations. Porosity was achieved by adding a non‐dissolvable agent (NaCl) during the process of polymerization, which was later dissolved in water, leaving behind a porous structure with adequate porosity for osteointegration. Three different groups of cylindrical samples of the swelling co‐polymer were investigated. Solid, fully porous, and partially porous with a solid core and a porous outer layer. The results of the swelling and simple compression study show that the partially porous swelling co‐polymer maintains excellent mechanical properties matching those of cancellous bone, quick swelling response, and an adequate porous outer layer for mechanically induced osteointegration. These suggest that this material may present an effective alternative to conventional bone anchors particularly in low‐density bone.

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Section: Discussionmentioning

confidence: 99%

A porous swelling copolymeric material for improved implant fixation to bone

et al. 2023

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“…Buffy coats (n = 4, male donors, blood group A (2 times), B and 0 respectively, all rhesus positive) were received from the German Red Cross Blood Donor Service at the university of Ulm, Germany. Buffy coats were processed on the same day following the established protocol (33).…”

Section: Isolation Of Pbmcsmentioning

confidence: 99%

Dental and Orthopaedic Implant Loosening: Overlap in Gene Expression Regulation

et al. 2022

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ObjectivesEndoprosthetic loosening still plays a major role in orthopaedic and dental surgery and includes various cellular immune processes within peri-implant tissues. Although the dental and orthopaedic processes vary in certain parts, the clinical question arises whether there are common immune regulators of implant loosening. Analyzing the key gene expressions common to both processes reveals the mechanisms of osteoclastogenesis within periprosthetic tissues of orthopaedic and dental origin.MethodsDonor peripheral blood mononuclear cells (PBMCs) and intraoperatively obtained periprosthetic fibroblast-like cells (PPFs) were (co-)cultured with [± macrophage-colony stimulating factor (MCSF) and Receptor Activator of NF-κB ligand (RANKL)] in transwell and monolayer culture systems and examined for osteoclastogenic regulations [MCSF, RANKL, osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα)] as well as the ability of bone resorption. Sequencing analysis compared dental and orthopaedic (co-)cultures.ResultsMonolayer co-cultures of both origins expressed high levels of OPG, resulting in inhibition of osteolysis shown by resorption assay on dentin. The high OPG-expression, low RANKL/OPG ratios and a resulting inhibition of osteolysis were displayed by dental and orthopaedic PPFs in monolayer even in the presence of MCSF and RANKL, acting as osteoprotective and immunoregulatory cells. The osteoprotective function was only observed in monolayer cultures of dental and orthopaedic periprosthetic cells and downregulated in the transwell system. In transwell co-cultures of PBMCs/PPFs profound changes of gene expression, with a significant decrease of OPG (20-fold dental versus 100 fold orthopaedic), were identified. Within transwell cultures, which offer more in vivo like conditions, RANKL/OPG ratios displayed similar high levels to the original periprosthetic tissue. For dental and orthopaedic implant loosening, overlapping findings in principal component and heatmap analysis were identified.ConclusionsThus, periprosthetic osteoclastogenesis may be a correlating immune process in orthopaedic and dental implant failure leading to comparable reactions with regard to osteoclast formation. The transwell cultures system may provide an in vivo like model for the exploration of orthopaedic and dental implant loosening.

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“…Bisphosphonates reduce osteoclast activity by inhibiting farnesyl pyrophosphate synthase and protein prenylation in the mevalonate pathway, and SERMs have an agonist effect on the estrogen receptor in osteoclasts, thereby inducing apoptosis ( Apostu et al, 2017 ). Beck et al (2019) immobilized the RANKL antibody denosumab on the implant surface to inhibit osteoclast differentiation, which could competitively block the interaction between receptor activator of nuclear factor kB and RANKL.…”

Section: Loading Bioactive Agents To Promote Osseointegrationmentioning

confidence: 99%

Dental Implants Loaded With Bioactive Agents Promote Osseointegration in Osteoporosis: A Review

Zhang

Geng

et al. 2021

Front. Bioeng. Biotechnol.

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Implant-supported dentures are widely used in patients with defect or loss of dentition because these have higher chewing efficiency and do not damage the adjacent teeth compared with fixed or removable denture. An implant-supported denture carries the risk of failure in some systemic diseases, including osteoporosis, because of a non-ideal local microenvironment. Clinically common physical and chemical modifications are used to change the roughness of the implant surface to promote osseointegration, but they have limitations in promoting osteoinduction and inhibiting bone resorption. Recently, many researchers have focused on the study of bioactive modification of implants and have achieved promising results. Herein we have summarized the progress in bioactive modification strategy to promote osseointegration by regulating the local osteoporotic microenvironment.

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Immobilization of Denosumab on Titanium Affects Osteoclastogenesis of Human Peripheral Blood Monocytes

Cited by 7 publications

References 33 publications

A porous swelling copolymeric material for improved implant fixation to bone

A porous swelling copolymeric material for improved implant fixation to bone

Dental and Orthopaedic Implant Loosening: Overlap in Gene Expression Regulation

Dental Implants Loaded With Bioactive Agents Promote Osseointegration in Osteoporosis: A Review

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