animal-model-of-implant-associated-infections-in-mice

Animal Model of Implant-Associated Infections in Mice

Implant-associated infections represent a significant clinical challenge, as they arise when pathogenic microorganisms infiltrate the site of medical ...

University of Science and Technology of China

Fibroblast-like synoviocytes (FLS) are essential cellular components in inflammatory joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Despite the growing use of FLS isolated from OA and RA patients, a detailed functional and parallel comparison of FLS from these two types of arthritis has not been performed.

Parallel comparison of fibroblast-like synoviocytes from the surgically removed hyperplastic synovial tissues of rheumatoid arthritis and osteoarthritis patients.

Alginate hydrogels have been widely used as excellent scaffold materials for implantation in biological systems because of their good biocompatibility. However, it is difficult to repair bone defects with these materials because of their poor mechanical properties. The aim of the present study was to fabricate a novel degradable alginate/palygorskite (PAL) composite hydrogel with good mechanical properties and investigate its potential for application in bone defect repair. The modified alginate-based hydrogel with increasing PAL content exhibited better mechanical properties than the original alginate hydrogel. In addition, the resulting composite hydrogel was thoroughly characterized by scanning electron microscopy (SEM). With increasing PAL content, the swelling ratio of the hydrogel increased in PBS (pH = 7.4).  cytocompatibility was evaluated using bone marrow-derived mesenchymal stem cells (BMSCs) to confirm that the developed composite hydrogel was cytocompatible after 1, 3, and 7 days. All these results suggest that the developed composite hydrogel has great potential for bone tissue engineering applications. JWH133 is a selective agonist of cannabinoid receptor type 2 (CB2), which exerts dual anti-inflammatory and anti-osteoclastogenic effects. We co-cultured BMSCs with composite hydrogels loaded with JWH133, and analysis of proliferation and osteogenic differentiation indicated that the composite hydrogel loaded with JWH133 may enhance the osteogenic differentiation of rat BMSCs. Furthermore, we found that the composite hydrogel loaded with JWH133 inhibited osteoclast formation and the mRNA expression of osteoclast-specific markers. In summary, the developed composite hydrogel has a high drug-loading capacity, good biocompatibility, and strong potential as a drug carrier for treating osteoporosis by promoting osteoblast and inhibiting osteoclast formation and function.

Modified Alginate-Based Hydrogel as a Carrier of the CB2 Agonist JWH133 for Bone Engineering.

An isolated bone fragment from the posterolateral tibial plateau retrieved from the patellofemoral compartment is a rarely seen Schatzker type II tibial plateau fracture and is prone to misdiagnosis. To the best of our knowledge, this injury mechanism has not been previously described.

Diagnosis and Treatment of Schatzker Type II Tibial Plateau Fracture with An Isolated Bone Fragment: A Case Report and Literature Review.

Biofilms are colonies of bacteria embedded inside a complicated self-generating intercellular. The formation and scatter of a biofilm is an extremely complex and progressive process in constant cycles. Once formed, it can protect the inside bacteria to exist and reproduce under hostile conditions by establishing tolerance and resistance to antibiotics as well as immunological responses. In this article, we reviewed a series of innovative studies focused on inhibiting the development of biofilm and summarized a range of corresponding therapeutic methods for biological evolving stages of biofilm. Traditionally, there are four stages in the biofilm formation, while we systematize the therapeutic strategies into three main periods precisely:(i) period of preventing biofilm formation: interfering the colony effect, mass transport, chemical bonds and signaling pathway of plankton in the initial adhesion stage; (ii) period of curbing biofilm formation:targeting several pivotal molecules, for instance, polysaccharides, proteins, and extracellular DNA (eDNA)  polysaccharide hydrolases, proteases, and DNases respectively in the second stage before developing into irreversible biofilm; (iii) period of eliminating biofilm formation: applying novel multifunctional composite drugs or nanoparticle materials cooperated with ultrasonic (US), photodynamic, photothermal and even immune therapy, such as adaptive immune activated by stimulated dendritic cells (DCs), neutrophils and even immunological memory aroused by plasmocytes. The multitargeted or combinational therapies aim to prevent it from developing to the stage of maturation and dispersion and eliminate biofilms and planktonic bacteria simultaneously.

Strategies to prevent, curb and eliminate biofilm formation based on the characteristics of various periods in one biofilm life cycle.

Poor wound healing after diabetes mellitus remains a challenging problem, and its pathophysiological mechanisms have not yet been fully elucidated. Persistent bleeding, disturbed regulation of inflammation, blocked cell proliferation, susceptible infection and impaired tissue remodeling are the main features of diabetic wound healing. Conventional wound dressings, including gauze, films and bandages, have a limited function. They generally act as physical barriers and absorbers of exudates, which fail to meet the requirements of the whol diabetic wound healing process. Wounds in diabetic patients typically heal slowly and are susceptible to infection due to hyperglycemia within the wound bed. Once bacterial cells develop into biofilms, diabetic wounds will exhibit robust drug resistance. Recently, the application of stimuli-responsive hydrogels, also known as "smart hydrogels", for diabetic wound healing has attracted particular attention. The basic feature of this system is its capacities to change mechanical properties, swelling ability, hydrophilicity, permeability of biologically active molecules, etc., in response to various stimuli, including temperature, potential of hydrogen (pH), protease and other biological factors. Smart hydrogels can improve therapeutic efficacy and limit total toxicity according to the characteristics of diabetic wounds. In this review, we summarized the mechanism and application of stimuli-responsive hydrogels for diabetic wound healing. It is hoped that this work will provide some inspiration and suggestions for research in this field.

Recent advances in responsive hydrogels for diabetic wound healing.

Over the past decade, a proliferation of research has used nanoparticles to deliver gaseous signaling molecules for medical purposes. The discovery and revelation of the role of gaseous signaling molecules have been accompanied by nanoparticle therapies for their local delivery. While most of them have been applied in oncology, recent advances have demonstrated their considerable potential in diagnosing and treating orthopedic diseases. Three of the currently recognized gaseous signaling molecules, nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (HS), are highlighted in this review along with their distinctive biological functions and roles in orthopedic diseases. Moreover, this review summarizes the progress in therapeutic development over the past ten years with a deeper discussion of unresolved issues and potential clinical applications.

Local delivery of gaseous signaling molecules for orthopedic disease therapy.

The recurrence of biofilm-associated infections (BAIs) remains high after implant-associated surgery. Biofilms on the implant surface reportedly shelter bacteria from antibiotics and evade innate immune defenses. Moreover, little is currently known about eliminating residual bacteria that can induce biofilm reinfection. Herein, novel "interference-regulation strategy" based on bovine serum albumin-iridium oxide nanoparticles (BIONPs) as biofilm homeostasis interrupter and immunomodulator via singlet oxygen ( O )-sensitized mild hyperthermia for combating BAIs is reported. The catalase-like BIONPs convert abundant H O inside the biofilm-microenvironment (BME) to sufficient oxygen gas (O ), which can efficiently enhance the generation of  O under near-infrared irradiation. The  O -induced biofilm homeostasis disturbance (e.g., sigB, groEL, agr-A, icaD, eDNA) can disrupt the sophisticated defense system of biofilm, further enhancing the sensitivity of biofilms to mild hyperthermia. Moreover, the mild hyperthermia-induced bacterial membrane disintegration results in protein leakage and  O penetration to kill bacteria inside the biofilm. Subsequently, BIONPs-induced immunosuppressive microenvironment re-rousing successfully re-polarizes macrophages to pro-inflammatory M1 phenotype in vivo to devour residual biofilm and prevent biofilm reconstruction. Collectively, this  O -sensitized mild hyperthermia can yield great refractory BAIs treatment via biofilm homeostasis interference, mild-hyperthermia, and immunotherapy, providing a novel and effective anti-biofilm strategy.

Biofilm Homeostasis Interference Therapy via  O -Sensitized Hyperthermia and Immune Microenvironment Re-Rousing for Biofilm-Associated Infections Elimination.

Modular reconstruction systems based on porous tantalum (PT) prosthetic components have been increasingly used for the treatment of complex acetabular bone defects in revision total hip arthroplasty. We report a novel technique that applies a revision cup as a "super-augment" to form a "double-cup" construct for Paprosky type III defects.

Outcomes of a Double-Cup Construct to Treat Paprosky 3A and 3B Acetabular Defects at a Mean of 39 Months.

The effectiveness of robot-assisted surgery remains contentious due to the lack of high-quality randomized controlled trials (RCTs) to elevate the level of evidence. We aimed to evaluate the postoperative radiographic outcomes of robot-assisted (RAS-THA) versus manual (M-THA) total hip arthroplasty.

Radiographic evaluation of robot-assisted versus manual total hip arthroplasty: a multicenter randomized controlled trial.

Pathogen-host competition for manganese and intricate immunostimulatory pathways severely attenuates the efficacy of antibacterial immunotherapy against biofilm infections associated with orthopaedic implants. Herein, we introduce a spatiotemporal sono-metalloimmunotherapy (SMIT) strategy aimed at efficient biofilm ablation by custom design of ingenious biomimetic metal-organic framework (PCN-224)-coated MnO-hydrangea nanoparticles (MnPM) as a metalloantibiotic. Upon reaching the acidic HO-enriched biofilm microenvironment, MnPM can convert abundant HO into oxygen, which is conducive to significantly enhancing the efficacy of ultrasound (US)-triggered sonodynamic therapy (SDT), thereby exposing bacteria-associated antigens (BAAs). Moreover, MnPM disrupts bacterial homeostasis, further killing more bacteria. Then, the Mn ions released from the degraded MnO can recharge immune cells to enhance the cGAS-STING signaling pathway sensing of BAAs, further boosting the immune response and suppressing biofilm growth via biofilm-specific T cell responses. Following US withdrawal, the sustained oxygenation promotes the survival and migration of fibroblasts, stimulates the expression of angiogenic growth factors and angiogenesis, and neutralizes excessive inflammation. Our findings highlight that MnPM may act as an immune costimulatory metalloantibiotic to regulate the cGAS-STING signaling pathway, presenting a promising alternative to antibiotics for orthopaedic biofilm infection treatment and pro-tissue repair.

Biodegradable oxygen-evolving metalloantibiotics for spatiotemporal sono-metalloimmunotherapy against orthopaedic biofilm infections.

Excessive inflammation caused by bacterial infection is the primary cause of implant failure. Antibiotic treatment often fails to prevent peri-implant infection and may induce unexpected drug resistance. Herein, a non-antibiotic strategy based on the synergy of silver ion release and macrophage reprogramming is proposed for preventing infection and bacteria-induced inflammation suppression by the organic-inorganic hybridization of silver nanoparticle (AgNP) and quercetin (Que) into a polydopamine (PDA)-based coating on the 3D framework of porous titanium (SQPdFT). Once the planktonic bacteria (, ) reach the surface of SQPdFT, released Que disrupts the bacterial membrane. Then, AgNP can penetrate the invading bacterium and kill them, which further inhibits the biofilm formation. Simultaneously, released Que can regulate macrophage polarization homeostasis via the peroxisome proliferators-activated receptors gamma (PPARγ)-mediated nuclear factor kappa-B (NF-κB) pathway, thereby terminating excessive inflammatory responses. These advantages facilitate the adhesion and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), concomitantly suppressing osteoclast maturation, and eventually conferring superior mechanical stability to SQPdFT within the medullary cavity. In summary, owing to its excellent antibacterial effect, immune remodeling function, and pro-osteointegration ability, SQPdFT is a promising protective coating for titanium-based implants used in orthopedic replacement surgery.

Silver-quercetin-loaded honeycomb-like Ti-based interface combats infection-triggered excessive inflammation via specific bactericidal and macrophage reprogramming.

Article	Year
Parallel comparison of fibroblast-like synoviocytes from the surgically removed hyperplastic synovial tissues of rheumatoid arthritis and osteoarthritis patients. BMC musculoskeletal disorders\| PubMed ID: 31812161	2019
Modified Alginate-Based Hydrogel as a Carrier of the CB2 Agonist JWH133 for Bone Engineering. ACS omega\| PubMed ID: 33748600	2021
Diagnosis and Treatment of Schatzker Type II Tibial Plateau Fracture with An Isolated Bone Fragment: A Case Report and Literature Review. Orthopaedic surgery\| PubMed ID: 35343059	2022
Strategies to prevent, curb and eliminate biofilm formation based on the characteristics of various periods in one biofilm life cycle. Frontiers in cellular and infection microbiology\| PubMed ID: 36211965	2022
Recent advances in responsive hydrogels for diabetic wound healing. Materials today. Bio\| PubMed ID: 36504542	2023
Local delivery of gaseous signaling molecules for orthopedic disease therapy. Journal of nanobiotechnology\| PubMed ID: 36810201	2023
Biofilm Homeostasis Interference Therapy via O -Sensitized Hyperthermia and Immune Microenvironment Re-Rousing for Biofilm-Associated Infections Elimination. Small (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 36850031	2023
Outcomes of a Double-Cup Construct to Treat Paprosky 3A and 3B Acetabular Defects at a Mean of 39 Months. The Journal of arthroplasty\| PubMed ID: 38823520	2024
Radiographic evaluation of robot-assisted versus manual total hip arthroplasty: a multicenter randomized controlled trial. Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology\| PubMed ID: 38926175	2024
Biodegradable oxygen-evolving metalloantibiotics for spatiotemporal sono-metalloimmunotherapy against orthopaedic biofilm infections. Nature communications\| PubMed ID: 39277594	2024
Silver-quercetin-loaded honeycomb-like Ti-based interface combats infection-triggered excessive inflammation via specific bactericidal and macrophage reprogramming. Bioactive materials\| PubMed ID: 39318638	2025

Ruixiang Ma

Biography

JoVE Journal Publications

Other Publications