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Journal of Advanced Research Dec 2023Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the...
INTRODUCTION
Treating orthopedic implant-associated infections, especially those caused by Staphylococcus aureus (S. aureus), remains a significant challenge. S. aureus has the ability to invade host cells, enabling it to evade both antibiotics and immune responses during infection, which may result in clinical treatment failures. Therefore, it is critical to identify the host cell type of implant-associated intracellular S. aureus infections and to develop a strategy for highly targeted delivery of antibiotics to the host cells.
OBJECTIVES
Introduced an antibody-antibiotic conjugate (AAC) for the targeted elimination of intracellular S. aureus.
METHODS
The AAC comprises of a human monoclonal antibody (M0662) directly recognizes the surface antigen of S. aureus, Staphylococcus protein A, which is conjugated with vancomycin through cathepsin-sensitive linkers that are cleavable in the proteolytic environment of the intracellular phagolysosome. AAC, vancomycin and vancomycin combined with AAC were used in vitro intracellular infection and mice implant infection models. We then tested the effect of AAC in vivo and in vivo by fluorescence imaging, in vivo imaging, bacterial quantitative analysis and bacterial biofilm imaging.
RESULTS
In vitro, it was observed that AAC captured extracellular S. aureus and co-entered the cells, and subsequently released vancomycin to induce rapid elimination of intracellular S. aureus. In the implant infection model, AAC significantly improved the bactericidal effect of vancomycin. Scanning electron microscopy showed that the application of AAC effectively blocked the formation of bacterial biofilm. Further histochemical and micro-CT analysis showed AAC significantly reduced the level of bone marrow density (BMD) and bone volume fraction (BV/TV) reduction caused by bacterial infection in the distal femur of mice compared to vancomycin treatment alone.
CONCLUSIONS
The application of AAC in an implant infection model showed that it significantly improved the bactericidal effects of vancomycin and effectively blocked the formation of bacterial biofilms, without apparent toxicity to the host.
PubMed: 38048846
DOI: 10.1016/j.jare.2023.12.001 -
Frontiers in Neurology 2023For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option....
INTRODUCTION
For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy.
METHODS
This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed.
RESULTS
Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale.
DISCUSSION
Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.
PubMed: 37745648
DOI: 10.3389/fneur.2023.1202631 -
Cureus Aug 2023After a loss of a tooth, alveolar bone resorption is immutable, leaving the area devoid of sufficient bone quality and mass for a successful and satisfactory implant or... (Review)
Review
After a loss of a tooth, alveolar bone resorption is immutable, leaving the area devoid of sufficient bone quality and mass for a successful and satisfactory implant or any other dental treatment. To treat this problem of irreversible bone loss, bone grafting is the primary solution and a well-accepted technique. The use of bone grafting procedures has increased in recent years. This review is about the various bone grafting techniques and best-situated material available currently along with their trump cards and limitations. In the thorough discussion regarding bone grafting materials and their substitutes, one alloplastic material has shown unbeaten and the most satisfactory properties than any other material, "bicalcium phosphate" (BCP). BCP is a mixture of hydroxyapatite (HA) and beta-tricalcium phosphate (B-TCP) usually obtained through sintering calcium-deficient apatite (CDA) at or above 700°C or by other methods such as hydrolysis or precipitation. The review also shows comparative studies done to understand the effect, most adequate balance, and impact of ratios of HA/B-TCP on the properties, structure, and success rate of this material. The objective of the review is to enlighten the principal characteristic of the most likely used bone graft material presently, i.e., BCP. The most impeccable characteristic of BCP is its capability to osteointegrate, which results in a superior interface. This interface depicts a dynamic process that includes physicochemical reactions, crystal-protein interactions, cell and tissue colonization, and bone remodeling. BCP has certain essential properties that could be put forth as its advantage over any other substitute. These properties include bioactivity, osteointegration, osteoinduction, osteogenesis, and biodegradation, which are mostly governed by modifying the HA/B-TCP ratio. Other applications of BCP are feasible, such as in drug administration and scaffolds for tissue engineering.
PubMed: 37750142
DOI: 10.7759/cureus.44079 -
Molecules (Basel, Switzerland) Feb 2024During the past two decades, tremendous progress has been made in the development of biodegradable polymeric materials for various industrial applications, including... (Review)
Review
During the past two decades, tremendous progress has been made in the development of biodegradable polymeric materials for various industrial applications, including human and veterinary medicine. They are promising alternatives to commonly used non-degradable polymers to combat the global plastic waste crisis. Among biodegradable polymers used, or potentially applicable to, veterinary medicine are natural polysaccharides, such as chitin, chitosan, and cellulose as well as various polyesters, including poly(ε-caprolactone), polylactic acid, poly(lactic-co-glycolic acid), and polyhydroxyalkanoates produced by bacteria. They can be used as implants, drug carriers, or biomaterials in tissue engineering and wound management. Their use in veterinary practice depends on their biocompatibility, inertness to living tissue, mechanical resistance, and sorption characteristics. They must be designed specifically to fit their purpose, whether it be: (1) facilitating new tissue growth and allowing for controlled interactions with living cells or cell-growth factors, (2) having mechanical properties that address functionality when applied as implants, or (3) having controlled degradability to deliver drugs to their targeted location when applied as drug-delivery vehicles. This paper aims to present recent developments in the research on biodegradable polymers in veterinary medicine and highlight the challenges and future perspectives in this area.
Topics: Humans; Polyesters; Biocompatible Materials; Tissue Engineering; Polyhydroxyalkanoates; Drug Delivery Systems; Chitosan
PubMed: 38398635
DOI: 10.3390/molecules29040883 -
Journal of Functional Biomaterials Dec 2023Biomimetic dental implants are regarded as one of the recent clinical advancements in implant surface modification. Coatings with varying thicknesses and roughness may... (Review)
Review
Biomimetic dental implants are regarded as one of the recent clinical advancements in implant surface modification. Coatings with varying thicknesses and roughness may affect the dental implant surface's chemical inertness, cell adhesion, and antibacterial characteristics. Different surface coatings and mechanical surface changes have been studied to improve osseointegration and decrease peri-implantitis. The surface medication increases surface energy, leading to enhanced cell proliferation and growth factors, and, consequently, to a rise in the osseointegration process. This review provides a comprehensive update on the numerous biomimetic coatings used to improve the surface characteristics of dental implants and their applications in two main categories: coating to improve osseointegration, including the hydroxyapatite layer and nanocomposites, growth factors (BMPs, PDGF, FGF), and extracellular matrix (collagen, elastin, fibronectin, chondroitin sulfate, hyaluronan, and other proteoglycans), and coatings for anti-bacterial performance, covering drug-coated dental implants (antibiotic, statin, and bisphosphonate), antimicrobial peptide coating (GL13K and human beta defensins), polysaccharide antibacterial coatings (natural chitosan and its coupling agents) and metal elements (silver, zinc, and copper).
PubMed: 38248682
DOI: 10.3390/jfb15010015 -
Advanced Science (Weinheim,... Feb 2024The complex anatomy and physiological barriers of the eye make delivering ocular therapeutics challenging. Generally, effective drug delivery to the eye is hindered by... (Review)
Review
The complex anatomy and physiological barriers of the eye make delivering ocular therapeutics challenging. Generally, effective drug delivery to the eye is hindered by rapid clearance and limited drug bioavailability. Biomaterial-based approaches have emerged to enhance drug delivery to ocular tissues and overcome existing limitations. In this review, some of the most promising long-acting injectables (LAIs) in ocular drug delivery are explored, focusing on novel design strategies to improve therapeutic outcomes. LAIs are designed to enable sustained therapeutic effects, thereby extending local drug residence time and facilitating controlled and targeted drug delivery. Moreover, LAIs can be engineered to enhance drug targeting and penetration across ocular physiological barriers.
Topics: Eye; Drug Delivery Systems; Injections; Ocular Physiological Phenomena; Biological Availability
PubMed: 38018313
DOI: 10.1002/advs.202306463 -
Advanced Science (Weinheim,... Aug 2023The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune...
The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic-tolerant persister cells. This need is addressed herein through an engineering of antibody-drug conjugates (ADCs) that contain an anti-neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non-specific counterpart, in suspension and within biofilms, in vitro, and in an implant-associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.
Topics: Mice; Animals; Immunoconjugates; Drug Liberation; Bacteria; Anti-Infective Agents; Biofilms
PubMed: 37290045
DOI: 10.1002/advs.202301340 -
Advanced Drug Delivery Reviews Sep 2023Adherence to daily oral antiretroviral therapy (ART) is a barrier to both treatment and prevention of human immunodeficiency virus (HIV) infection. To overcome... (Review)
Review
Adherence to daily oral antiretroviral therapy (ART) is a barrier to both treatment and prevention of human immunodeficiency virus (HIV) infection. To overcome limitations of life-long daily regimen adherence, long-acting (LA) injectable antiretroviral (ARV) drugs, nanoformulations, implants, vaginal rings, microarray patches, and ultra-long-acting (ULA) prodrugs are now available or in development. These medicines enable persons who are or at risk for HIV infection to be treated with simplified ART regimens. First-generation LA cabotegravir, rilpivirine, and lenacapavir injectables and a dapivirine vaginal ring are now in use. However, each remains limited by existing dosing intervals, ease of administration, or difficulties in finding drug partners. ULA ART regimens provide an answer, but to date, such next-generation formulations remain in development. Establishing the niche will require affirmation of extended dosing, improved access, reduced injection volumes, improved pharmacokinetic profiles, selections of combination treatments, and synchronization of healthcare support. Based on such needs, this review highlights recent pharmacological advances and a future treatment perspective. While first-generation LA ARTs are available for HIV care, they remain far from ideal in meeting patient needs. ULA medicines, now in advanced preclinical development, may close gaps toward broader usage and treatment options.
Topics: Female; Humans; HIV Infections; Rilpivirine; Anti-HIV Agents; Injections; HIV-1
PubMed: 37451501
DOI: 10.1016/j.addr.2023.115009 -
Periodontology 2000 Oct 2023Bone regeneration is often required concomitant with implant placement to treat a bone fenestration, a dehiscence, and for contouring. This systematic review assessed... (Meta-Analysis)
Meta-Analysis Review
Bone regeneration is often required concomitant with implant placement to treat a bone fenestration, a dehiscence, and for contouring. This systematic review assessed the impact of different biomaterials employed for guided bone regeneration (GBR) simultaneous to implant placement on the stability of radiographic peri-implant bone levels at ≥12 months of follow-up (focused question 1), as well as on bone defect dimension (width/height) changes at re-assessment after ≥4 months (focused question 2). Only randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared different biomaterials for GBR were considered. A Bayesian network meta-analysis (NMA) was performed using a random-effects model. A ranking probability between treatments was obtained, as well as an estimation of the surface under the cumulative ranking value (SUCRA). Overall, whenever the biological principle of GBR was followed, regeneration occurred in a predictable way, irrespective of the type of biomaterial used. A lower efficacy of GBR treatments was suggested for initially large defects, despite the trend did not reach statistical significance. Regardless of the biomaterial employed, a certain resorption of the augmented bone was observed overtime. While GBR was shown to be a safe and predictable treatment, several complications (including exposure, infection, and soft tissue dehiscence) were reported, which tend to be higher when using cross-linked collagen membranes.
Topics: Humans; Alveolar Ridge Augmentation; Biocompatible Materials; Bone Regeneration; Dental Implantation, Endosseous; Dental Implants; Guided Tissue Regeneration, Periodontal; Network Meta-Analysis
PubMed: 37752820
DOI: 10.1111/prd.12531 -
Molecules (Basel, Switzerland) Aug 2023Dental caries is the most prevalent chronic disease globally, significantly impacting individuals' quality of life. A key reason behind the failure of implanted... (Review)
Review
Dental caries is the most prevalent chronic disease globally, significantly impacting individuals' quality of life. A key reason behind the failure of implanted restorations is their biological inactivity, meaning they are unable to form crosslinks with the surrounding tooth structures, thus making patients susceptible to implant loss and recurrent tooth decay. For the treatment of caries, antibacterial medicine and remineralization are effective means of treating the recurrence of caries. Owing to the rapid progression in the biomaterials field, several biomaterials have been reported to display antimicrobial properties and aid in dentin remineralization. Bioactive materials hold considerable potential in diminishing biofilm accumulation, inhibiting the process of demineralization, enabling dentin remineralization, and combating bacteria related to caries. Bioactive materials, such as fluoride, amorphous calcium phosphate, bioactive glass, collagen, and resin-based materials, have demonstrated their effectiveness in promoting dentin remineralization and exerting antibacterial effects on dental caries. However, the concentration of fluoride needs to be strictly controlled. Although amorphous calcium phosphate can provide the necessary calcium and phosphorus ions for remineralization, it falls short in delivering the mechanical strength required for oral mastication. Resin-based materials also offer different advantages due to the complexity of their design. In this review, we delve into the application of advanced bioactive materials for enhancing dentin remineralization and antibacterial properties. We eagerly anticipate future developments in bioactive materials for the treatment of dental caries.
Topics: Humans; Fluorides; Dental Caries; Quality of Life; Anti-Bacterial Agents; Biocompatible Materials
PubMed: 37687202
DOI: 10.3390/molecules28176373