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Military Medical Research May 2023Treatment of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of...
Elimination of methicillin-resistant Staphylococcus aureus biofilms on titanium implants via photothermally-triggered nitric oxide and immunotherapy for enhanced osseointegration.
BACKGROUND
Treatment of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium (Ti) implants. There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.
METHODS
Herein, an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles (PDA), nitric oxide (NO) release donor sodium nitroprusside (SNP) and osteogenic growth peptide (OGP) onto Ti implants, denoted as Ti-PDA@SNP-OGP. The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy, X-ray photoelectron spectroscope, water contact angle, photothermal property and NO release behavior. The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2',7'-dichlorofluorescein diacetate probe, 1-N-phenylnaphthylamine assay, adenosine triphosphate intensity, o-nitrophenyl-β-D-galactopyranoside hydrolysis activity, bicinchoninic acid leakage. Fluorescence staining, assays for alkaline phosphatase activity, collagen secretion and extracellular matrix mineralization, quantitative real‑time reverse transcription‑polymerase chain reaction, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells (MSCs), RAW264.7 cells and their co-culture system. Giemsa staining, ELISA, micro-CT, hematoxylin and eosin, Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms, inhibition of inflammatory response, and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.
RESULTS
Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light irradiation, and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species (ROS)-mediated oxidative stress, destroying bacterial membrane integrity and causing leakage of intracellular components (P < 0.01). In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs, but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype (P < 0.05 or P < 0.01). The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways (P < 0.01). In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model (P < 0.01).
CONCLUSIONS
These findings suggest that Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.
Topics: Rats; Animals; Methicillin-Resistant Staphylococcus aureus; Osseointegration; Titanium; Nitric Oxide; Rats, Sprague-Dawley; Osteogenesis; Anti-Bacterial Agents; Immunotherapy; Biofilms
PubMed: 37143145
DOI: 10.1186/s40779-023-00454-y -
Nature Communications Jun 2021Peri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial...
Peri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial efficacy, which is difficult to promisingly prevent peri-implant infection. Herein, we report an N-halamine polymeric coating on titanium surface that simultaneously has long-lasting renewable antibacterial efficacy with good stability and biocompatibility. Our coating is powerfully biocidal against both main pathogenic bacteria of peri-implant infection and complex bacteria from peri-implantitis patients. More importantly, its antibacterial efficacy can persist for a long term (e.g., 12~16 weeks) in vitro, in animal model, and even in human oral cavity, which generally covers the whole formation process of osseointegrated interface. Furthermore, after consumption, it can regain its antibacterial ability by facile rechlorination, highlighting a valuable concept of renewable antibacterial coating in dental implant. These findings indicate an appealing application prospect for prevention and treatment of peri-implant infection.
Topics: Amines; Animals; Anti-Bacterial Agents; Biofilms; Coated Materials, Biocompatible; Dental Implants; Drug Stability; Humans; In Vitro Techniques; Male; Materials Testing; Osseointegration; Peri-Implantitis; Porosity; Rabbits; Surface Properties; Titanium
PubMed: 34083518
DOI: 10.1038/s41467-021-23069-0 -
Journal of Orthopaedic Research :... Jul 2020Osseointegration (OI) is the direct anchorage of a metal implant into bone, allowing for the connection of an external prosthesis to the skeleton. Osseointegration was... (Review)
Review
Osseointegration (OI) is the direct anchorage of a metal implant into bone, allowing for the connection of an external prosthesis to the skeleton. Osseointegration was first discovered in the 1960s based on the microscopic analysis of titanium implant placed into host bone. New bone was observed to attach directly to the metal surface. Following clinical investigations into dentistry applications, OI was adapted to treat extremity amputations. These bone anchored implants, which penetrate the skin and soft tissues, eliminate many of the challenges of conventional prosthetic sockets, such as poor fit and suspension, skin breakdown, and pain. Osseointegrated implants show promise to improve prosthesis use, pain, and function for amputees. The successful process of transcutaneous metal integration into host bone requires three synergistic systems: the host bone, the metal implant, and the skin-implant interface. All three systems must be optimized for successful incorporation and longevity of the implant. Osseointegration begins during surgical implantation of the metal components through a complex interplay of cellular mechanisms. While implants can vary in design-including the original screw, press fit implants, and compressive osseointegration-they face common challenges to successful integration and maintenance of fixation within the host bone. Overcoming these challenges requires the understanding of the complex interactions between each element of OI. This review outlines (a) the basic components of OI, (b) the science behind both the bone-implant and the skin-implant interfaces, (c) the current challenges of OI, and (d) future opportunities within the field.
Topics: Artificial Limbs; Bone-Implant Interface; Humans; Osseointegration
PubMed: 31876306
DOI: 10.1002/jor.24576 -
Ugeskrift For Laeger Jul 2023Osseointegrated implants is a surgical treatment permitting a direct skeletal attachment of an external prosthesis. It is a treatment for healthy transfemoral amputated... (Review)
Review
Osseointegrated implants is a surgical treatment permitting a direct skeletal attachment of an external prosthesis. It is a treatment for healthy transfemoral amputated patients who cannot tolerate or use a socket prosthesis, thereby alleviating related issues with poor fit, skin problems or discomfort. This review provides a summary of the indications and contraindications for surgery, the most common implants and reported outcomes.
Topics: Humans; Amputees; Prosthesis Design; Artificial Limbs; Prosthesis Implantation; Osseointegration; Femur; Treatment Outcome
PubMed: 37539803
DOI: No ID Found -
Experimental Physiology Mar 2023What is the topic of this review? In this review, we consider the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive... (Review)
Review
NEW FINDINGS
What is the topic of this review? In this review, we consider the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and bone resorption during osseointegration. What advances does it highlight? Mitochondria contribute to the behaviours of peri-implant cell lines based on metabolic and reactive oxygen species signalling modulations, which will contribute to the research field and the development of new treatment strategies for improving implant success.
ABSTRACT
Osseointegration is a dynamic biological process in the local microenvironment adjacent to a bone implant, which is crucial for implant performance and success of the implant surgery. Recently, the role of mitochondria in the peri-implant microenvironment during osseointegration has gained much attention. Mitochondrial regulation has been verified to be essential for cellular events in osseointegration and as a therapeutic target for peri-implant diseases in the peri-implant microenvironment. In this review, we summarize our current knowledge of the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and resorption during osseointegration, which will contribute to the research field and the development of new treatment strategies to improve implant success. In addition, we indicate limitations in our current understanding of the regulation of mitochondria in osseointegration and suggest topics for further study.
Topics: Humans; Reactive Oxygen Species; Bone and Bones; Osteogenesis; Bone Resorption; Osseointegration; Mitochondria
PubMed: 36648334
DOI: 10.1113/EP090988 -
Connective Tissue Research May 2022A healthy musculoskeletal system requires complex functional integration of bone, muscle, cartilage, and connective tissues responsible for bodily support, motion, and... (Review)
Review
PURPOSE
A healthy musculoskeletal system requires complex functional integration of bone, muscle, cartilage, and connective tissues responsible for bodily support, motion, and the protection of vital organs. Conditions or injuries to musculoskeeltal tissues can devastate an individual's quality of life. Some conditions that are particularly disabling include severe bone and muscle injuries to the extremities and amputations resulting from unmanageable musculoskeletal conditions or injuries. Monitoring and managing musculoskeletal health is intricate because of the complex mechanobiology of these interconnected tissues.
METHODS
For this article, we reviewed literature on implantable biosensors related to clinical data of the musculoskeletal system, therapeutics for complex bone injuries, and osseointegrated prosthetics as example applications.
RESULTS
As a result, a brief summary of biosensors technologies is provided along with review of noteworthy biosensors and future developments needed to fully realize the translational benefit of biosensors for musculoskeletal health.
CONCLUSIONS
Novel implantable biosensors capable of tracking biophysical parameters in vivo are highly relevant to musculoskeletal health because of their ability to collect clinical data relevant to medical decisions, complex trauma treatment, and the performance of osseointegrated prostheses.
Topics: Biosensing Techniques; Bone and Bones; Osseointegration; Prostheses and Implants; Quality of Life
PubMed: 35172654
DOI: 10.1080/03008207.2022.2041002 -
Periodontology 2000 Feb 2024Implant dentistry has evolved to the point that standard implant osseointegration is predictable. This is attributed in part to the advancements in material sciences... (Review)
Review
Implant dentistry has evolved to the point that standard implant osseointegration is predictable. This is attributed in part to the advancements in material sciences that have led toward improvements in implant surface technology and characteristics. Nonetheless, there remain several cases where implant therapy fails (specifically at early time points), most commonly attributed to factors affecting bone metabolism. Among these patients, smokers are known to have impaired bone metabolism and thus be subject to higher risks of early implant failure and/or late complications related to the stability of the peri-implant bone and mucosal tissues. Notably, however, emerging data have unveiled other critical factors affecting osseointegration, namely, those related to the metabolism of bone tissues. The aim of this review is to shed light on the effects of implant-related factors, like implant surface or titanium particle release; surgical-related factors, like osseodensification or implanted biomaterials; various drugs, like selective serotonin reuptake inhibitors, proton pump inhibitors, anti-hypertensives, nonsteroidal anti-inflammatory medication, and statins, and host-related factors, like smoking, diet, and metabolic syndrome on bone metabolism, and aseptic peri-implant bone loss. Despite the infectious nature of peri-implant biological complications, these factors must be surveyed for the effective prevention and management of peri-implantitis.
Topics: Humans; Dental Implants; Osseointegration; Alveolar Bone Loss; Peri-Implantitis; Dental Implantation, Endosseous; Titanium; Surface Properties; Smoking
PubMed: 37904311
DOI: 10.1111/prd.12532 -
Periodontology 2000 Feb 2024The recognition and importance of immune cells during bone regeneration, including around bone biomaterials, has led to the development of an entire field termed... (Review)
Review
The recognition and importance of immune cells during bone regeneration, including around bone biomaterials, has led to the development of an entire field termed "osteoimmunology," which focuses on the connection and interplay between the skeletal system and immune cells. Most studies have focused on the "osteogenic" capacity of various types of bone biomaterials, and much less focus has been placed on immune cells despite being the first cell type in contact with implantable devices. Thus, the amount of literature generated to date on this topic makes it challenging to extract needed information. This review article serves as a guide highlighting advancements made in the field of osteoimmunology emphasizing the role of the osteoimmunomodulatory properties of biomaterials and their impact on osteoinduction. First, the various immune cell types involved in bone biomaterial integration are discussed, including the prominent role of osteal macrophages (OsteoMacs) during bone regeneration. Thereafter, key biomaterial properties, including topography, wettability, surface charge, and adsorption of cytokines, growth factors, ions, and other bioactive molecules, are discussed in terms of their impact on immune responses. These findings highlight and recognize the importance of the immune system and osteoimmunology, leading to a shift in the traditional models used to understand and evaluate biomaterials for bone regeneration.
Topics: Humans; Biocompatible Materials; Bone Regeneration; Osteogenesis; Macrophages; Bone and Bones; Cytokines; Osseointegration; Bone Substitutes; Animals
PubMed: 37658591
DOI: 10.1111/prd.12519 -
Mesenchymal stem cells and dental implant osseointegration during aging: from mechanisms to therapy.Stem Cell Research & Therapy Dec 2023Dental implants are widely used to replace missing teeth, providing patients with unparalleled levels of effectiveness, convenience, and affordability. The biological... (Review)
Review
Dental implants are widely used to replace missing teeth, providing patients with unparalleled levels of effectiveness, convenience, and affordability. The biological basis for the clinical success of dental implants is osseointegration. Bone aging is a high-risk factor for the reduced osseointegration and survival rates of dental implants. In aged individuals, mesenchymal stem cells (MSCs) in the bone marrow show imbalanced differentiation with a reduction in osteogenesis and an increase in adipogenesis. This leads to impaired osseointegration and implant failure. This review focuses on the molecular mechanisms underlying the dysfunctional differentiation of aged MSCs, which primarily include autophagy, transcription factors, extracellular vesicle secretion, signaling pathways, epigenetic modifications, microRNAs, and oxidative stress. Furthermore, this review addresses the pathological changes in MSCs that affect osseointegration and discusses potential therapeutic interventions to enhance osseointegration by manipulating the mechanisms underlying MSC aging.
Topics: Humans; Aged; Osseointegration; Dental Implants; Osteogenesis; Aging; Mesenchymal Stem Cells; Surface Properties
PubMed: 38124153
DOI: 10.1186/s13287-023-03611-1 -
Periodontology 2000 Feb 2022Implant therapy aims at providing the patient with a functional and esthetically pleasing rehabilitation in a long-term perspective. The loss of an implant constitutes a... (Review)
Review
Implant therapy aims at providing the patient with a functional and esthetically pleasing rehabilitation in a long-term perspective. The loss of an implant constitutes a major complication, which may have an impact on the treatment plan and/or jeopardize the longevity of the restoration. Implant loss may occur during the phase of osseointegration (early) or at a later time when the previously achieved osseointegration is lost (late). The present work evaluates the evidence on the occurrence of both events and discusses etiology, risk factors, and consequences.
Topics: Alveolar Bone Loss; Dental Implantation, Endosseous; Dental Implants; Dental Prosthesis, Implant-Supported; Humans; Osseointegration
PubMed: 35103324
DOI: 10.1111/prd.12408