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

China has the largest population of patients with epilepsy worldwide, which imposes a heavy burden on the public and health care systems. Several epidemiological surveys on epilepsy have been performed in China. Although these surveys grossly describe the prevalence and gap in treatment of epilepsy, the status of epilepsy centers is unclear. The number of epilepsy centers has increased substantially in recent decades. Therefore, a nationwide investigation of the scale and distribution, personnel, equipment, and epilepsy care capacity of each epilepsy center is of great value.

Epilepsy centers in China: Current status and ways forward.

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.

Implant-associated infection (IAI) is increasingly emerging as a serious threat with the massive application of biomaterials. Bacteria attached to the surface of implants are often difficult to remove and exhibit high resistance to bactericides. In the quest for novel antimicrobial strategies, conventional antimicrobial materials often fail to exert their function because they tend to focus on direct bactericidal activity while neglecting the modulation of immune systems. The inflammatory response induced by host immune cells was thought to be a detrimental force impeding wound healing. However, the immune system has recently received increasing attention as a vital player in the host's defense against infection. Anti-infective strategies based on the modulation of host immune defenses are emerging as a field of interest. This review explains the importance of the immune system in combating infections and describes current advanced immune-enhanced anti-infection strategies. First, the characteristics of traditional/conventional implant biomaterials and the reasons for the difficulty of bacterial clearance in IAI were reviewed. Second, the importance of immune cells in the battle against bacteria is elucidated. Then, we discuss how to design biomaterials that activate the defense function of immune cells to enhance the antimicrobial potential. Based on the key premise of restoring proper host-protective immunity, varying advanced immune-enhanced antimicrobial strategies were discussed. Finally, current issues and perspectives in this field were offered. This review will provide scientific guidance to enhance the development of advanced anti-infective biomaterials.

Immunomodulatory biomaterials for implant-associated infections: from conventional to advanced therapeutic strategies.

The attention on orthopedic biomaterials has shifted from their direct osteogenic properties to their osteoimmunomodulation, especially the modulation of macrophage polarization. Presently, advanced technologies endow polyetheretherketone (PEEK) with good osteoimmunomodulation by modifying PEEK surface characteristics or incorporating bioactive substances with regulating macrophage polarization. Recent studies have demonstrated that the fabrication of a hydrophilic surface and the incorporation of bioactive substances into PEEK (e.g., zinc, calcium, and phosphate) are good strategies to promote osteogenesis by enhancing the polarization of M2 macrophages. Furthermore, the modification by other osteoimmunomodulatory composites (e.g., lncRNA-MM2P, IL-4, IL-10, and chitosan) and their controlled and desired release may make PEEK an optimal bio-activated implant for regulating and balancing the osteogenic system and immune system. The purpose of this review is to comprehensively evaluate the potential of bio-activated PEEK in polarizing macrophages into M2 phenotype to improve osteogenesis. For this objective, we retrieved and discussed different kinds of bio-activated PEEK regarding improving osteogenesis through modulating macrophage polarization. Meanwhile, the relevant challenges and outlook were presented. We hope that this review can shed light on the development of bio-activated PEEK with more favorable osteoimmunomodulation.

Bio-Activated PEEK: Promising Platforms for Improving Osteogenesis through Modulating Macrophage Polarization.

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 leading cause of steroid-induced femoral head osteonecrosis (ONFH) is the imbalance of bone homeostasis. Bone marrow-derived mesenchymal stem cell (BMSC) differentiation and fate are closely associated with bone homeostasis imbalance. Blocking monoacylglycerol lipase (MAGL) could effectively ameliorate ONFH by mitigating oxidative stress and apoptosis in BMSCs induced by glucocorticoids (GC). Nevertheless, whether MAGL inhibition can modulate the balance during BMSC differentiation, and therefore improve ONFH, remains elusive. Our study indicates that MAGL inhibition can effectively rescue the enhanced BMSC adipogenic differentiation caused by GC and promote their differentiation toward osteogenic lineages. Cannabinoid receptor 2 (CB2) is the direct downstream target of MAGL in BMSCs, rather than cannabinoid receptor 1(CB1). Using RNA sequencing analyses and a series of in vitro experiments, we confirm that the MAGL blockade-induced enhancement of BMSC osteogenic differentiation is primarily mediated by the phosphoinositide 3-kinases (PI3K)/ the serine/threonine kinase (AKT)/ (glycogen synthase kinase-3 beta) GSK3β pathway. Additionally, MAGL blockade can also reduce GC-induced bone resorption by directly suppressing osteoclastogenesis and indirectly reducing the expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) in BMSCs. Thus, our study proposes that the therapeutic effect of MAGL blockade on ONFH is partly mediated by restoring the balance of bone homeostasis and MAGL may be an effective therapeutic target for ONFH.

Article	Year
Epilepsy centers in China: Current status and ways forward. Epilepsia\| PubMed ID: 34510417	2021
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
Immunomodulatory biomaterials for implant-associated infections: from conventional to advanced therapeutic strategies. Biomaterials research\| PubMed ID: 36471454	2022
Bio-Activated PEEK: Promising Platforms for Improving Osteogenesis through Modulating Macrophage Polarization. Bioengineering (Basel, Switzerland)\| PubMed ID: 36550953	2022
Local delivery of gaseous signaling molecules for orthopedic disease therapy. Journal of nanobiotechnology\| PubMed ID: 36810201	2023
MAGL blockade alleviates steroid-induced femoral head osteonecrosis by reprogramming BMSC fate in rat. Cellular and molecular life sciences : CMLS\| PubMed ID: 39368012	2024

Wenzhi Wang

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