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Pharmaceutics Jul 2023Ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, have had a profound impact on millions of patients. In the past couple of decades, these... (Review)
Review
Ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, have had a profound impact on millions of patients. In the past couple of decades, these diseases have been treated using conventional techniques but have also presented certain challenges and limitations that affect patient experience and outcomes. To address this, biomaterials have been used for ocular drug delivery, and a wide range of systems have been developed. This review will discuss some of the major classes and examples of biomaterials used for the treatment of prominent ocular diseases, including ocular implants (biodegradable and non-biodegradable), nanocarriers (hydrogels, liposomes, nanomicelles, DNA-inspired nanoparticles, and dendrimers), microneedles, and drug-loaded contact lenses. We will also discuss the advantages of these biomaterials over conventional approaches with support from the results of clinical trials that demonstrate their efficacy.
PubMed: 37514145
DOI: 10.3390/pharmaceutics15071959 -
Advanced Healthcare Materials Nov 2023Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local...
Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local sustained release. A novel PTHrP (PTHrP-2) that can be used locally to promote osseointegration of macroporous titanium alloy scaffold (mTAS) and counteract implant slippage in osteoporosis patients is designed. In vitro, PTHrP-2 enhances the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) within the mTAS. Further, it promotes proliferation, migration, angiogenesis-related protein expression, and angiogenesis in human umbilical vein endothelial cells (HUVECs). Compared to PTH(1-34), PTHrP-2 can partially weaken the osteoclast differentiation of RAW 264.7 cells. Even in an oxidative stress microenvironment, PTHrP-2 safeguards the proliferation and migration of BMSCs and HUVECs, reduces reactive oxygen species generation and mitochondrial damage, and partially preserves the angiogenesis of HUVECs. In the Sprague-Dawley (SD) rat osteoporosis model, the therapeutic benefits of PTHrP-2-releasing mTAS (mTAS ) and ordinary mTAS implanted for 12 weeks via micro-CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTAS exhibits high bone growth rate, without osteophyte formation. Consequently, PTHrP-2 exhibits unique local synthesis properties and holds the potential for assisting the osseointegration of alloy implants in osteoporosis patients.
Topics: Rats; Animals; Humans; Osseointegration; Parathyroid Hormone-Related Protein; Titanium; Rats, Sprague-Dawley; Osteogenesis; Alloys; Endothelial Cells; Osteoporosis; Printing, Three-Dimensional
PubMed: 37584445
DOI: 10.1002/adhm.202301604 -
Biomaterials Oct 2023Although biodegradable polymer coatings can impede corrosion of magnesium (Mg)-based orthopedic implants, they are prone to excessive degradation and accidental...
Although biodegradable polymer coatings can impede corrosion of magnesium (Mg)-based orthopedic implants, they are prone to excessive degradation and accidental scratching in practice. Bone implant-related infection and limited osteointegration are other factors that adversely impact clinical application of Mg-based biomedical implants. Herein, a self-healing polymeric coating is constructed on the Mg alloy together with incorporation of a stimuli-responsive drug delivery nanoplatform by a spin-spray layer-by-layer (SSLbL) assembly technique. The nanocontainers are based on simvastatin (SIM)-encapsulated hollow mesoporous silica nanoparticles (S@HMSs) modified with polydopamine (PDA) and polycaprolactone diacrylate (PCL-DA) bilayer. Owing to the dynamic reversible reactions, the hybrid coating shows a fast, stable, and cyclical water-enabled self-healing capacity. The antibacterial assay indicates good bacteria-killing properties under near infrared (NIR) irradiation due to synergistic effects of hyperthermia, reactive oxygens species (ROS), and SIM leaching. In vitro results demonstrate that NIR laser irradiation promotes the cytocompatibility, osteogenesis, and angiogenesis. The coating facilitates alkaline phosphatase activity and expedites extracellular matrix mineralization as well as expression of osteogenesis-related genes. This study reveals a useful strategy to develop multifunctional coatings on bioabsorbable Mg alloys for orthopedic implants.
Topics: Osteogenesis; Alloys; Magnesium; Coated Materials, Biocompatible; Bacteria; Hydrogen-Ion Concentration; Corrosion
PubMed: 37467596
DOI: 10.1016/j.biomaterials.2023.122237 -
The Journal of Laryngology and Otology Nov 2023A retrospective cross-sectional analysis was conducted of the US Food and Drug Administration's MAUDE (Manufacturer and User Facility Device Experience) database, to... (Review)
Review
OBJECTIVE
A retrospective cross-sectional analysis was conducted of the US Food and Drug Administration's MAUDE (Manufacturer and User Facility Device Experience) database, to evaluate the complication profile of cochlear implantation according to manufacturer.
METHODS
A review of the MAUDE database was conducted from 1 January 2010 to 31 December 2020. Complications, including infection, extrusion, facial nerve stimulation, meningitis and cerebrospinal fluid leak, were identified using key word searches. The categorised data were analysed using a chi-square test to determine a difference in global complication incidence between three major cochlear implant manufacturers: manufacturer A (Cochlear Limited), manufacturer B (Med-El) and manufacturer C (Advanced Bionics).
RESULTS
A total of 31 857 adverse events were analysed. Implants of manufacturer C were associated with a statistically higher rate of infection (0.97 per cent), cerebrospinal fluid leak (0.07 per cent), extrusion (0.44 per cent) and facial nerve stimulation (0.11 per cent). Implants of manufacturer B were associated with a statistically higher rate of meningitis (0.07 per cent).
CONCLUSION
Consideration of patient risk factors along with cochlear implant manufacturers can heighten awareness of cochlear implant complications pre-operatively, intra-operatively and post-operatively.
Topics: Humans; Cochlear Implants; Cochlear Implantation; Retrospective Studies; Cross-Sectional Studies; Databases, Factual; Meningitis; Cerebrospinal Fluid Leak
PubMed: 37278214
DOI: 10.1017/S0022215123000828 -
The International Journal of Oral &... Oct 2023To examine whether patient-level disease diagnoses, drug treatments, and dental clinical factors are correlates of early implant failure.
PURPOSE
To examine whether patient-level disease diagnoses, drug treatments, and dental clinical factors are correlates of early implant failure.
MATERIALS AND METHODS
This historical, nested case-control study used electronic medical records to retrieve patient-level data on individuals with implant failure occurring up to 6 months after implantation, including demographics, clinical information (number, location, and complicated status of implants), underlying diseases (osteoporosis, diabetes, hypertension, inflammatory bowel disease [IBD], myocardial infarction [MI]), and drug purchases (chemotherapy, bisphosphonates, selective serotonin inhibitors, antihypertensive medications, proton pump inhibitors [PPIs], disease-modifying antirheumatic drugs, corticosteroids, and nonsteroidal anti-inflammatory drugs) among adult members of a large, state-mandated health provider in Israel between 2015 and 2020. Individuals with implant extraction occurring up to 6 months after implantation were matched 1:1 to controls. Univariate and adjusted multivariate conditional logistic regression models were used to examine the odds ratios (ORs) of all dental implant risk factors among the patients.
RESULTS
A total of 585 individuals with implant failure (mean age, 53 years [42,62], 51.3% females and 49.7% males) were identified among 29,378 eligible patients. Compared to controls, patients who experienced implant failure (ie, cases) were more likely to have smoked in their lifetime (18% vs 11.5%, P = .009), experienced IBD (1.5% vs 0.02%, P = .059), and consumed PPIs within 6 months of the implant surgery (40.0% vs 32.5%, P = .028). Clinical factors, including the number of implants per person (individuals with two implants, OR = 1.53; individuals with at least four implants, OR = 3.33; P < .01), location of implant (maxilla; OR = 1.59; 95% CI: 1.2-2.04), and smoking (OR = 1.57; 95% CI: 1.09-2.26) were significant correlates of early implant failure among the included cases. Crohn's disease, MI, and osteoporosis were found to be borderline significant correlates of early dental implant failure.
CONCLUSIONS
Among the factors examined, the number of implants, the location of implants, and smoking history were significant correlates of early implant failure, while Crohn's disease, MI, and osteoporosis were found to not be significant. Larger patient-level studies are needed to examine the individual and combined effects of diseases, medications, and clinical factors on early implant failure.
Topics: Male; Adult; Female; Humans; Middle Aged; Dental Implants; Dental Implantation, Endosseous; Retrospective Studies; Case-Control Studies; Crohn Disease; Osteoporosis; Dental Restoration Failure
PubMed: 37847831
DOI: 10.11607/jomi.10199 -
Zeitschrift Fur Rheumatologie Dec 2023Endoprosthesis infections represent a major challenge for doctors and patients. Due to the increase in endoprosthesis implantation because of the increasing life... (Review)
Review
BACKGROUND
Endoprosthesis infections represent a major challenge for doctors and patients. Due to the increase in endoprosthesis implantation because of the increasing life expectancy, an increase in endoprosthesis infections is to be expected. In addition to infection prophylaxis, methods of infection control become highly relevant, especially in the group of geriatric and multimorbid patients. The aim is to reduce the high 1‑year mortality from prosthesis infections through a structured algorithm.
ALGORITHM FOR PROSTHESIS INFECTIONS
Prosthesis infections can basically be divided into early and late infections. According to the criteria of the International Consensus Meeting, a late infection is defined as the occurrence more than 30 days after implantation. With respect to the planned approach, the (p)TNM classification offers an orientation. In the early postoperative interval the clinical appearance is crucial as in this phase neither laboratory parameters nor an analysis of synovial fluid show a high sensitivity. It is fundamental that, apart from patients with sepsis, environment diagnostics should be initiated. If a late infection is suspected, in addition to radiological diagnostics (X-ray, skeletal scintigraphy and if necessary, computed tomography, CT), laboratory (C-reactive protein, CRP, leukocytes, blood sedimentation, and if necessary, interleukin‑6, procalcitonin) and microbiological diagnostics (arthrocentesis with synovial analysis and microbiology) are indicated; however, in addition to the arthrocentesis result, the clinical appearance is crucial in cases where an exclusion cannot be confirmed by laboratory parameters. If an infection is confirmed, the treatment depends on the spectrum of pathogens, the soft tissue situation and the comorbidities, including a multistage procedure with temporary explantation and, if necessary, implantation of an antibiotic-containing spacer is necessary. A prosthesis preservation using the debridement, antibiotics and implant retention (DAIR) regimen is only appropriate in an acute infection situation. Basically, radical surgical debridement should be carried out to reduce the pathogen load and treatment of a possible biofilm formation for both early and late infections. The subsequent antibiotic treatment (short or long interval) should be coordinated with the infectious disease specialists.
CONCLUSION
A structured approach for prosthesis infections oriented to an evidence-based algorithm provides a sufficient possibility of healing. An interdisciplinary approach involving cooperation between orthopedic and infectious disease specialists has proven to be beneficial. Surgical treatment with the aim of reducing the bacterial load by removing the biofilm with subsequent antibiotic treatment is of intrinsic importance.
Topics: Humans; Aged; Prosthesis-Related Infections; Arthroplasty, Replacement, Hip; Prostheses and Implants; Anti-Bacterial Agents; Communicable Diseases; Retrospective Studies; Treatment Outcome
PubMed: 37851164
DOI: 10.1007/s00393-023-01421-7 -
Frontiers in Surgery 2023Many complications related to silicone implants have been reported recently, from clinical symptoms manifestations to association with some specific types of cancer.... (Review)
Review
Many complications related to silicone implants have been reported recently, from clinical symptoms manifestations to association with some specific types of cancer. During the early 2010s, it was believed that implants were biocompatible and inert to the human body and that gel bleeding/leakage events were rare and without repercussions for the human body. However, at the end of 2010s, several studies pointed out that gel bleeding was more frequent than previously believed, and the pathogenic potential of free silicone should not be ignored. The Food and Drug Administration recommends performing magnetic resonance imaging in asymptomatic patients 5-6 years after implant placement. The descriptors in the Breast Imaging and Reporting Data System lexicon seem outdated for classifying the new generations of implants with cohesive gel, which hinders the diagnosis of device complications. In this review, supported by our research data publications related to silicone implants for 6 years on a prospective study protocol, most of them being original articles, we summarized the main complications observed in clinical practice and discuss the impact of these changes on patients' outcomes focusing on the pericapsular space.
PubMed: 37780912
DOI: 10.3389/fsurg.2023.1249078 -
Injury Aug 2023This narrative review aims to investigate the effects of drugs on implant osseointegration, analyzing their potential positive or negative impact on the direct... (Review)
Review
OBJECTIVE
This narrative review aims to investigate the effects of drugs on implant osseointegration, analyzing their potential positive or negative impact on the direct structural and functional connection between bone and load-carrying implants.
BACKGROUND
The review seeks to provide a comprehensive understanding of osseointegration, which refers to the successful integration of an implant with living bone, resulting in no progressive relative movement between them. Exploring the effects of drugs on implant osseointegration is crucial for optimizing outcomes and enhancing patient care in orthopedic implant procedures.
METHODS
Relevant studies on the effects of drugs on implant osseointegration were identified through a literature search. Electronic databases, including PubMed, Embase, and Google Scholar, were utilized, employing appropriate keywords and MeSH terms related to osseointegration, implants, and drug interventions. The search was limited to English studies.
DISCUSSION
This overview presents a detailed analysis of the effects of drugs on implant osseointegration. It explores drugs such as bisphosphonates, teriparatide, statins, angiotensin-converting enzyme inhibitors, beta-blockers, nitrites, and thiazide diuretics as promoters of osseointegration. Conversely, loop diuretics, non-steroidal anti-inflammatory drugs, corticosteroids, cyclosporine A, cisplatin, methotrexate, antibiotics, proton pump inhibitors (PPIs), antiepileptics, selective serotonin reuptake inhibitors (SSRIs), and anticoagulants are discussed as inhibitors of the process. The role of vitamin D3 remains uncertain. The complex relationship between drugs and the biology of implant osseointegration is emphasized, underscoring the need for further in vitro and in vivo studies to validate their effects CONCLUSION: This narrative review contributes to the literature by providing an overview of the effects of drugs on implant osseointegration. It highlights the complexity of the subject and emphasizes the necessity for more extensive and sophisticated studies in the future. Based on the synthesis of the reviewed literature, certain drugs, such as bisphosphonates and teriparatide, show potential for promoting implant osseointegration, while others, including loop diuretics and certain antibiotics, may impede the process. However, additional research is required to solidify these conclusions and effectively inform clinical practice.
Topics: Humans; Osseointegration; Teriparatide; Sodium Potassium Chloride Symporter Inhibitors; Prostheses and Implants; Diphosphonates
PubMed: 37390787
DOI: 10.1016/j.injury.2023.110888 -
Advanced Science (Weinheim,... Oct 2023Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone... (Review)
Review
Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone fractures. However, the intrinsic bioinertness of Ti and its alloys often impedes the effective osseointegration of the implants, leading to severe adverse complications including implant loosening, detachment, and secondary bone damage. Consequently, new Ti implant engineering strategies are urgently needed to improve their osseointegration after implantation. Remarkably, metalorganic frameworks (MOFs) are a class of novel synthetic material consisting of coordinated metal species and organic ligands, which have demonstrated a plethora of favorable properties for modulating the interfacial properties of Ti implants. This review comprehensively summarizes the recent progress in the development of MOF-coated Ti implants and highlights their potential utility for modulating the bio-implant interface to improve implant osseointegration, of which the discussions are outlined according to their physical traits, chemical composition, and drug delivery capacity. A perspective is also provided in this review regarding the current limitations and future opportunities of MOF-coated Ti implants for orthopedic applications. The insights in this review may facilitate the rational design of more advanced Ti implants with enhanced therapeutic performance and safety.
Topics: Osseointegration; Metal-Organic Frameworks; Titanium; Prostheses and Implants; Bone and Bones
PubMed: 37705110
DOI: 10.1002/advs.202303958 -
Journal of Materials Chemistry. B Jul 2023Drug delivery in the brain is challenging due to the existence of the blood brain barrier, which prevents most drugs from entering the target site in the brain. Compared... (Review)
Review
Drug delivery in the brain is challenging due to the existence of the blood brain barrier, which prevents most drugs from entering the target site in the brain. Compared to systematic drug administration, localized and site-specific drug delivery in a minimally invasive manner is effective for the treatment of brain disease. However, its implementation relies on advanced technologies and miniaturized implants/devices for controllable drug delivery. Recent research endeavors have provided a broad range of creative neural implants and platforms for this purpose. In this review, we provide an overview of recent advances in miniaturized neural implants for precise, controllable and minimally invasive drug delivery in the brain. This review will focus on neural implants with proven functionalities by discussing the technologies and materials used to fabricate these miniaturized multi-functional drug delivery implants with either externally connected pumps or integrated microfluidic pumps. The vibrancy of engineering technologies and emerging materials associated with these implants and their significance to targeted and minimally invasive drug delivery for brain disease treatment will motivate continued advance and growth of this area of research.
Topics: Humans; Drug Delivery Systems; Brain; Blood-Brain Barrier; Brain Diseases
PubMed: 37310392
DOI: 10.1039/d3tb00728f