A Novel Antibacterial Compound Decreases MRSA Biofilm Formation Without the Use of Antibiotics in A Murine Model

Despite significant advancements in material science, surgical site infection (SSI) rates remain high and prevention is key. This study aimed to demonstrate the in-vivo safety and antibacterial efficacy of titanium implants treated with a novel broad-spectrum biocidal compound (DBG21) against methicillin-resistant Staphylococcus aureus (MRSA). Titanium (Ti) discs were covalently bound with DBG21. Untreated Ti discs were used as controls. All discs were implanted either untreated for 44 control mice or DBG21-treated for 44 treated mice. After implantation, 1x107 colony forming units (CFU) of MRSA were injected into the operating site. Mice were sacrificed at day 7 and 14 to determine the number of adherent bacteria (biofilm) on implants and in the peri-implant surrounding tissues. Systemic and local toxicity were assessed. At both 7 and 14 days, DBG21-treated implants yielded a significant decrease in MRSA biofilm (3.6 median log10 CFU (99.97%) reduction (p<0.001) and 1.9 median log10 CFU (98.7%) reduction (p=0.037), respectively) and peri-implant surrounding tissues (2.7 median log10 CFU/g (99.8%) reduction (p<0.001) and 5.6 median log10 CFU/g (99.9997%) reduction (p<0.001), respectively). There were no significant differences between control and treated mice in terms of systemic and local toxicity. DBG-21 demonstrated a significant decrease in the number of biofilm bacteria without associated toxicity in a small animal implant model of SSI. Preventing biofilm formation has been recognized as a key element of preventing implant-related infections

Polyethylene particules _ induced periprosthetic osteolysis : the inflammation and macrophages perspective

Devant le succès maintenant bien démontré des prothèses totales de hanche, les chirurgiens sont amenés à proposer ce traitement chez des patients dont l’espérance de vie ne cesse d’augmenter. Parallèlement, une population plus jeune et active a aussi recours à ce traitement permettant de reprendre rapidement ses activités professionnelles et de loisirs. Des progrès exceptionnels ont été réalisés par les bio-ingénieurs en collaboration avec les chirurgiens dans la production industrielle d’implants en polyéthylène désormais très performants avec des taux d’usure très faibles. Néanmoins, bien que très diminuée, cette usure aboutit à la production de particules micrométriques libérées autour de la prothèse. Ces particules d’usure interagissent avec les tissus environnants et notamment les macrophages circulants, conduisant à une réaction inflammatoire. Les macrophages, cellules clés de cette cascade inflammatoire, subissent une activation par phagocytose ou par contact membranaire avec les particules puis une polarisation engendrant la libération de molécules à fort pouvoir inflammatoire : cytokines, chemokines, dérivés oxygénés, TNF-α et autres conduisant au maintien d’un niveau inflammatoire élevé autour de la prothèse. A long terme, le risque est l’évolution vers l’ostéolyse péri-prothétique et le descellement aseptique dont le seul traitement est la reprise chirurgicale, intervention difficile chez des patients qui ont vieilli. La compréhension des mécanismes biologiques de cette réaction inflammatoire permet le développement de stratégies modulant ou inversant cette inflammation afin d’augmenter la longévité des prothèses totales de hanche.Total hip replacements are now very succesful and surgeons perform this procedure in patients with an increasing longevity. Young and active patients are also candidates for this surgery allowing them to quickly resume their professional and recreational activities. Exceptional advances have been made by bio-engineers and surgeons in the production of highly efficient polyethylene implants which have very low wear rates. Nevertheless, wear remains and wear particles are still released around the implant. These particles react with the surrounding tissues especially macrophages, leading to an inflammatory reaction. Macrophages are then activated and subsequently polarize releasing inflammatory factors such as cytokines, chemokines, oxide species and TNF-?. This could lead peri-prosthetic osteolysis and aseptic loosening requiring revision surgery, a difficult procedure. Understanding the biological mecanisms of this inflammatory reaction may help creating strategies to mitigate or reverse this inflammation with the goal to increase the longevity of these implants

Inflammation, ageing, and bone regeneration

Bone healing involves complex biological pathways and interactions among various cell types and microenvironments. Among them, the monocyte–macrophage–osteoclast lineage and the mesenchymal stem cell–osteoblast lineage are critical, in addition to an initial inflammatory microenvironment. These cellular interactions induce the necessary inflammatory milieu and provide the cells for bone regeneration and immune modulation. Increasing age is accompanied with a rise in the basal state of inflammation, potentially impairing osteogenesis. The translational potential of this article: Translational research has shown multiple interactions between inflammation, ageing, and bone regeneration. This review presents recent, relevant considerations regarding the effects of inflammation and ageing on bone healing

Arthroscopic Transfer of the Pectoralis Major for Irreparable Tear of the Subscapularis: A Preliminary Report

An irreparable tear of the subscapularis is a surgical challenge. Open approaches have been widely described to restore the anatomy and the function of the shoulder. Pectoralis major transfer is the most common technique used in this difficult clinical situation. Although this procedure has only been performed through an open approach, we describe a new arthroscopic technique for pectoralis major transfer. The critical part in this technique, in general, is the musculocutaneous nerve dissection, which is also possible through the arthroscopic approach. Together with an alternative method of harvesting using chips of bone and a minimal skin incision, this promising, less invasive technique presents all the advantages of the arthroscopic approach and provides a strong fixation to the lesser tuberosity

Mesenchymal stem cells homing to improve bone healing

Cell therapy continues to attract growing interest as a promising approach to treat a variety of diseases. Mesenchymal stem cells (MSCs) have been one of the most intensely studied candidates for cell therapy. Since the homing capacity of MSCs is an important determinant of effective MSC-based therapy, the enhancement of homing efficiency is essential for optimizing the therapeutic outcome. Furthermore, trafficking of endogenous MSCs to damaged tissues, also referred to as endogenic stem cell homing, and the subsequent participation of MSCs in tissue regeneration are considered to be a natural self-healing response. Therefore, strategies to stimulate and reinforce the mobilisation and homing of MSCs have become a key point in regenerative medicine. The current review focuses on advances in the mechanisms and factors governing trafficking of MSCs, and the relationship between MSC mobilisation and skeletal diseases, providing insights into strategies for their potential translational implications

Spontaneous Knee Ankylosis through Heterotopic Ossification after Total Knee Arthroplasty

This paper reports on a case of total ankylosis of the knee after a cruciate-sacrificing cemented total knee arthroplasty (TKA). An 82-year-old female patient previously underwent primary TKA for osteoarthritis twenty years ago in our institution. She had recovered uneventfully and returned to her regular activities. There was no history of postsurgical trauma; however, she progressively lost knee range of motion. Radiographs revealed severe bridging heterotopic ossification

CCL2, CCL5, and IGF-1 participate in the immunomodulation of osteogenesis during M1/M2 transition in vitro

The modulation of macrophage phenotype from pro-inflammatory (M1) to tissue healing (M2) via exogenous addition of interleukin-4 (IL-4) facilitates osteogenesis; however, the molecular mediators underlying this phenomenon remain unknown. This study characterizes the IL-4-dependent paracrine crosstalk between macrophages and osteoprogenitors and its effect on osteogenesis in vitro. Primary murine M1 were co-cultured with MC3T3 cells (M1-MC3T3) in both transwell plates and direct co-cultures. To modulate M1 to M2, M1-MC3T3 were treated with IL-4 (20 ng/mL) at day 3 after seeding (M1+IL-4-MC3T3). Selected molecular targets were assessed at days 3 and 6 after seeding at protein and mRNA levels. Mineralization was assessed at day 21. Transwell M1+IL-4-MC3T3 significantly enhanced the secretion of CCL2/MCP-1, IGF-1 and to a lesser degree, CCL5/RANTES at day 6. At day 3, alkaline phosphatase (Alpl) was upregulated in direct M1-MC3T3. At day 6, Smurf2 and Insulin growth factor-1 (IGF-1) were downregulated and upregulated, respectively, in direct M1+IL-4-MC3T3. Finally, M1+IL-4-MC3T3 increased bone matrix mineralization compared with MC3T3 cells in transwell, but this was significantly less than M1-MC3T3. Taken together, macrophage subtypes enhanced the osteogenesis in transwell setting and the transition from M1 to M2 was associated with an increase in bone anabolic factors CCL2/MCP-1, CCL5/RANTES and IGF-1 in vitro.NIH 2R01AR055650 1R01AR063717 Stanford University's Ellenburg Chair in Surgery University of Chile-Conicyt Becas Chile Award CONICYT PAI/INDUSTRIA 7909001

Different wheat loci are associated to heritable free asparagine content in grain grown under different water and nitrogen availability

International audienceThe amount of free asparagine in grain of a wheat genotype determines its potential to form harmful acrylamide in derivative food products. Here, we explored the variation in the free asparagine, aspartate, glutamine and glutamate contents of 485 accessions refecting wheat worldwide diversity to defne the genetic architecture governing the accumulation of these amino acids in grain. Accessions were grown under high and low nitrogen availability and in water-defcient and well-watered conditions, and plant and grain phenotypes were measured. Free amino acid contents of grain varied from 0.01 to 1.02 mg g−1 among genotypes in a highly heritable way that did not correlate strongly with grain yield, protein content, specifc weight, thousand-kernel weight or heading date. Mean free asparagine content was 4% higher under high nitrogen and 3% higher in water-defcient conditions. After genotyping the accessions, single-locus and multi-locus genome-wide association study models were used to identify several QTLs for free asparagine content located on nine chromosomes. Each QTL was associated with a single amino acid and growing environment, and none of the QTLs colocalised with genes known to be involved in the corresponding amino acid metabolism. This suggests that free asparagine content is controlled by several loci with minor efects interacting with the environment. We conclude that breeding for reduced asparagine content is feasible, but should be frmly based on multi-environment feld trials. Key message: Diferent wheat QTLs were associated to the free asparagine content of grain grown in four diferent conditions. Environmental efects are a key factor when selecting for low acrylamide-forming potentia