Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies

Croes, Michiel; Wal, Bart C. H. van der; Charles, Hubert

doi:10.1002/jor.24422

Cited by 66 publications

(48 citation statements)

References 120 publications

(435 reference statements)

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“…Известно, что при диабетической остеоартропатии преобладают процессы распада костной ткани, при недостатке инсулина снижается функция остеобластов, а метаболический ацидоз стимулирует активность остеокластов [23]. Остеомиелит еще больше усугубляет потерю костной ткани, поскольку известно, что остеомиелит характеризуется неконтролируемым ремоделированием кости и потерей костной массы [24].…”

Section: Discussionunclassified

Microscopic Examination of Foot Joints Components in Charcot Arthropathy Complicated by Osteomyelitis

Ступина

Migalkin

Щудло

et al. 2020

Traumatology and Orthopedics of Russia

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Background. Charcot arthropathy is a serious medical and social problem. Histological studies of foot joints components in Charcot arthropathy complicated by osteomyelitis are few. The purpose of this study was to assess structural changes in the articular cartilage and subchondral bone of the foot joints in Charcot arthropathy complicated by osteomyelitis. Materials and Methods. The bone-cartilage fragments of the ankle, subtalar and metatarsophalangeal joints with the surrounding soft tissues of 20 patients with Charcot arthropathy complicated by chronic osteomyelitis were examined. Part of the material was fixed in neutral formalin. All samples were subjected to standard histological processing. Paraffin sections were stained by Masson’s tricolor method, hematoxylin and eosin. Part of the material was embedded in epoxy resins. Then semi-thin sections were stained with methylene blue and basic fuchsin. Histological preparations were studied by digitizing images under the AxioScope A1 microscope (Carl Zeiss MicroImaging GmbH, Germany).The phase of chronic osteomyelitis inflammation was assessed semi-quantitatively using the histopathological scale by A. Tiemann et al. (2014). Results. In 80% of the patients, the inflammatory phase of chronic osteomyelitis was characterized as active and subacute. In all cases, the areas with full-layer of articular cartilage unweaving, up to the subchondral zone, with cartilaginous tissue fragments rejection into the joint cavity were revealed. Cytoarchitectonics was disrupted. The main part of chondrocytes was in a state of destruction. The articular surface was covered with pannus. There were no basophilic line and the zone of calcified cartilage. The hyaline cartilage was replaced by granulation and/or fibrous tissue. An inflammatory infiltrates was noted in the superficial and deep areas of the cartilage. The impairment of the structure and/or complete absence of the subchondral bone due to the high activity of osteoclasts in the subchondral zone were revealed. An excessive amount of osteoclasts at the border with the articular cartilage was noted, while the signs of reparative bone formation were poorly expressed. Edema and thickening of the vascular walls of the microvasculature were recorded. Conclusion. The microscopic examination of the foot joints in Charcot arthropathy complicated by osteomyelitis revealed structural impairment and/or complete absence of the subchondral bone due to the high activity of osteoclasts in the subchondral zone. Structural changes in the subchondral bone and synovial pannus led to irreversible destruction of articular cartilage and the penetration of infection. These should be taken into account in surgical planning.

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Section: Discussionunclassified

Microscopic Examination of Foot Joints Components in Charcot Arthropathy Complicated by Osteomyelitis

Ступина

Migalkin

Щудло

et al. 2020

Traumatology and Orthopedics of Russia

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“…Several innate immune cells already attach to biomaterials within a timeframe of hours, while lymphocytes are not initially observed. [29,41] Moreover, neutrophils and macrophages are the main innate immune effectors against planktonic Staphylococci species. [50] Their ability to directly kill bacteria is a prerequisite for successful infection clearance.…”

Section: Host Immune Response To Biomaterials Infectionmentioning

confidence: 99%

“…[87] From a bone healing perspective, persisting neutrophils and the accompanying inflammation will dysregulate the bone matrix production by delaying the recruitment of proangiogenic and pro-osteogenic macrophages, [33] or directly interfering with the differentiation of bone progenitor cells. [42,87,88] Excessive inflammation mediated by neutrophils can for instance be seen in chronic bone infections, major trauma or in the case of a non-immunocompatible biomaterial, [28,29,87] and are associated with a suppressed antibacterial function. [28] This local imbalance in host response is not easily reversed, as a defect in the first wave of neutrophils at the biomaterial will also lead to defective host defense mechanisms in subsequent waves of neutrophils.…”

Section: Neutrophils-first Responders Around the Biomaterialsmentioning

confidence: 99%

“…A possible role of MSDC in the tissue healing response also has not been described, but it cannot be excluded considering the various roles of mature myeloid cells in bone regeneration. [29,122] The role of MDSCs in chronic implant infections seems analogous to those seen during the progression of tumors, wherein the accumulation of MDSCs leads to a tumor tolerant environment by suppression of proinflammatory responses in macrophages and T cells. [119] Several inhibitors of MSDC activity have been developed as an anticancer therapy.…”

Section: Host Immune Modulation By Myeloid-derived Suppressor Cells (mentioning

confidence: 99%

“…[27,28] In general, persisting inflammation impedes tissue repair and favors bacterial overgrowth. [28][29][30][31][32] A balanced inflammatory environment around the biomaterial is critical, since both downregulated and excessive inflammatory responses lead to suboptimal bone regeneration clinically. [32,33] Moreover, a balanced inflammation seems to be an optimal state at which the host innate immune system operates to eradicate infections.…”

Section: Introductionmentioning

confidence: 99%

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Combating Implant Infections: Shifting Focus from Bacteria to Host

et al. 2020

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commensal skin bacteria, Staphylococci, and in particular Staphylococcus aureus, have a strong tendency to colonize foreign bodies and cause IAI. [3,4] Important for the underlying pathophysiology, Staphylococci are highly competent at producing biofilms on implant surfaces, which encapsulate the bacterial niche from the outside environment, [5,6] thereby protecting the bacteria from host defense systems and antibiotics. [7] Antibiotics are administered as a routine procedure. [8] However, as a consequence of widespread antibiotics usage, bacteria are exposed to subinhibitory concentrations of antibiotics at a larger scale, driving their development toward antibiotic resistance, [9] as illustrated by the emergence of methicillin-resistant S. aureus (MRSA). [10,11] As an improvement over current clinically applied local antibiotics delivery systems, [12] the recent developments in implant surface engineering approaches allow better antimicrobial functionalities to be incorporated to allow for more tunable and controlled drug release. [13-15] The "race to the surface" model is popular among biomaterials researchers to predict the biomaterials fate, resulting from the competition between eukaryotic cells and bacteria at the material surface. [16] Using this template, implant antibacterial properties are being stemmed from direct contact killing mechanisms due to implant surface modifications [17,18] or firm immobilization of drugs, [19,20] as they both "shield" the implant from bacterial adhesion. The current anti-infective biomaterials strategies being explored can be categorized as: 1) implant functionalization with antibiotics or antibacterial drugs such as host defense peptides (HDPs), inorganic materials (e.g., chitosan and derivatives), and inorganics (e.g., silver, copper, and zinc metal nanoparticles (NPs)), 2) anti-biofilm surface modification (e.g., coating with antifouling polymers or quorum sensor inhibitors), or 3) physical surface changes for direct contact-killing properties (e.g., nanotubes, nanopillars, and metal implantation). [15,21] Emerging as a serious alternative or adjuvant therapy to antibiotics, bacteriophage (phage) therapy uses viruses responsible for the lysis of specific bacterial strains. [22,23] As a natural predator of bacteria, phages employ different killing mechanisms, making multidrug resistant bacteria susceptible for phages. [24] Moreover, phages are highly specific for pathogenic cells, which can eliminate disastrous off-target effects in the host. [25] As a limitation, the use of phage cocktails is needed for therapeutic efficacy, [26] while there is currently is no conclusive data on possible long-term side effects of phage therapy in The widespread use of biomaterials to support or replace body parts is increasingly threatened by the risk of implant-associated infections. In the quest for finding novel anti-infective biomaterials, there generally has been a one-sided focus on biomaterials with direct antibacterial properties, which leads to excessive use of antibacterial ag...

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A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles

Sadowska,

Power,

Genoud

et al. 2023

Advanced Materials

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Treating bone infections and ensuring bone repair is one of the greatest global challenges of modern orthopedics, made complex by antimicrobial resistance (AMR) risks due to long‐term antibiotic treatment and debilitating large bone defects following infected tissue removal. An ideal multi‐faceted solution would will eradicate bacterial infection without long‐term antibiotic use, simultaneously stimulating osteogenesis and angiogenesis. Here, a multifunctional collagen‐based scaffold that addresses these needs by leveraging the potential of antibiotic‐free antimicrobial nanoparticles (copper‐doped bioactive glass, CuBG) to combat infection without contributing to AMR in conjunction with microRNA‐based gene therapy (utilizing an inhibitor of microRNA‐138) to stimulate both osteogenesis and angiogenesis, is developed. CuBG scaffolds reduce the attachment of gram‐positive bacteria by over 80%, showcasing antimicrobial functionality. The antagomiR‐138 nanoparticles induce osteogenesis of human mesenchymal stem cells in vitro and heal a large load‐bearing defect in a rat femur when delivered on the scaffold. Combining both promising technologies results in a multifunctional antagomiR‐138‐activated CuBG scaffold inducing hMSC‐mediated osteogenesis and stimulating vasculogenesis in an in vivo chick chorioallantoic membrane model. Overall, this multifunctional scaffold catalyzes killing mechanisms in bacteria while inducing bone repair through osteogenic and angiogenic coupling, making this platform a promising multi‐functional strategy for treating and repairing complex bone infections.

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Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies

Cited by 66 publications

References 120 publications

Microscopic Examination of Foot Joints Components in Charcot Arthropathy Complicated by Osteomyelitis

Microscopic Examination of Foot Joints Components in Charcot Arthropathy Complicated by Osteomyelitis

Combating Implant Infections: Shifting Focus from Bacteria to Host

A Multifunctional Scaffold for Bone Infection Treatment by Delivery of microRNA Therapeutics Combined With Antimicrobial Nanoparticles

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