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Human Reproduction Update May 2024The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and...
BACKGROUND
The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes.
OBJECTIVE AND RATIONALE
This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches.
OUTCOMES
From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested.
WIDER IMPLICATIONS
Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis.
REGISTRATION NUMBER
https://osf.io/th8yf/.
PubMed: 38796750
DOI: 10.1093/humupd/dmae013 -
Frontiers in Chemistry 2024Lung cancer is the leading cause of cancer death in both men and women. It represents a public health problem that must be addressed through the early detection of... (Review)
Review
Lung cancer is the leading cause of cancer death in both men and women. It represents a public health problem that must be addressed through the early detection of specific biomarkers and effective treatment. To address this critical issue, it is imperative to implement effective methodologies for specific biomarker detection of lung cancer in real clinical samples. Electrochemical methods, including microfluidic devices and biosensors, can obtain robust results that reduce time, cost, and assay complexity. This comprehensive review will explore specific studies, methodologies, and detection limits and contribute to the depth of the discussion, making it a valuable resource for researchers and clinicians interested in lung cancer diagnosis.
PubMed: 38764920
DOI: 10.3389/fchem.2024.1390050 -
Journal of Pharmaceutical Sciences Jul 2024The production of paediatric pharmaceutical forms represents a unique challenge within the pharmaceutical industry. The primary goal of these formulations is to ensure... (Review)
Review
The production of paediatric pharmaceutical forms represents a unique challenge within the pharmaceutical industry. The primary goal of these formulations is to ensure therapeutic efficacy, safety, and tolerability in paediatric patients, who have specific physiological needs and characteristics. In recent years, there has been a significant increase in attention towards this area, driven by the need to improve drug administration to children and ensure optimal and specific treatments. Technological innovation has played a crucial role in meeting these requirements, opening new frontiers in the design and production of paediatric pharmaceutical forms. In particular, three emerging technologies have garnered considerable interest and attention within the scientific and industrial community: 3D printing, prilling/vibration, and microfluidics. These technologies offer advanced approaches for the design, production, and customization of paediatric pharmaceutical forms, allowing for more precise dosage modulation, improved solubility, and greater drug acceptability. In this review, we delve into these cutting-edge technologies and their impact on the production of paediatric pharmaceutical forms. We analyse their potential, associated challenges, and recent developments, providing a comprehensive overview of the opportunities that these innovative methodologies offer to the pharmaceutical sector. We examine different pharmaceutical forms generated using these techniques, evaluating their advantages and disadvantages.
Topics: Printing, Three-Dimensional; Humans; Child; Microfluidics; Dosage Forms; Technology, Pharmaceutical; Pediatrics; Pharmaceutical Preparations; Drug Compounding; Chemistry, Pharmaceutical; Solubility
PubMed: 38582283
DOI: 10.1016/j.xphs.2024.04.001 -
Journal of Oral Pathology & Medicine :... Apr 2024The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development.... (Review)
Review
BACKGROUND
The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient-derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine.
METHODS
We conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient-derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions.
RESULTS
In tumor development, the interaction between cellular and non-cellular components in the tumor microenvironment (TME) has a crucial role. Co-culture, Air-liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis.
CONCLUSION
An accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer.
Topics: Humans; Tumor Microenvironment; Head and Neck Neoplasms; Organoids; Databases, Factual; Extracellular Matrix
PubMed: 38561906
DOI: 10.1111/jop.13532 -
Bioengineering & Translational Medicine Mar 2024The aim of assisted reproductive technology (ART) is to select the high-quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However,... (Review)
Review
The aim of assisted reproductive technology (ART) is to select the high-quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However, functional evaluation is hindered by intra- and inter-operator variability. Microfluidic chips emerge as the one of the most powerful tools to analyze biological samples for reduced size, precise control, and flexible extension. Herein, a systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and IEEE Xplore databases until March 2023. We displayed and prospected all detection strategies based on microfluidics in the ART field. After full-text screening, 71 studies were identified as eligible for inclusion. The percentages of human and mouse studies equaled with 31.5%. The prominent country in terms of publication number was the USA ( = 13). Polydimethylsiloxane ( = 49) and soft lithography ( = 28) were the most commonly used material and fabrication method, respectively. All articles were classified into three types: sperm ( = 38), oocytes ( = 20), and embryos ( = 13). The assessment contents included motility, counting, mechanics, permeability, impedance, secretion, oxygen consumption, and metabolism. Collectively, the microfluidic chip technology facilitates more efficient, accurate, and objective evaluation in ART. It can even be combined with artificial intelligence to assist the daily activities of embryologists. More well-designed clinical studies and affordable integrated microfluidic chips are needed to validate the safety, efficacy, and reproducibility. Trial registration: The protocol was registered in the Open Science Frame REGISTRIES (identification: osf.io/6rv4a).
PubMed: 38435817
DOI: 10.1002/btm2.10625 -
Gels (Basel, Switzerland) Jan 2024Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This... (Review)
Review
Organs-on-a-chip (OoCs) are microfluidic devices constituted by PDMS or hydrogel in which different layers of cells are separated by a semipermeable membrane. This technology can set many parameters, like fluid shear stress, chemical concentration gradient, tissue-organ interface, and cell interaction. The use of these devices in medical research permits the investigation of cell patterning, tissue-material interface, and organ-organ interaction, mimicking the complex structures and microenvironment of human and animal bodies. This technology allows us to reconstitute in vitro complex conditions that recapitulate in vivo environments. One of the main advantages of these systems is that they represent a very realistic model that, in many cases, can replace animal experimentation, eliminating costs and related ethical issues. Organ-on-a-chip can also contain bacteria or cancer cells. This technology could be beneficial in dentistry for testing novel antibacterial substances and biomaterials, performing studies on inflammatory disease, or planning preclinical studies. A significant number of publications and reviews have been published on this topic. Still, to our knowledge, they mainly focus on the materials used for fabrication and the different patterns of the chip applied to the experimentations. This review presents the most recent applications of organ-on-a-chip models in dentistry, starting from the reconstituted dental tissues to their clinical applications and future perspectives.
PubMed: 38391432
DOI: 10.3390/gels10020102 -
Dentistry Journal Dec 2023This systematic review evaluated the potential clinical use of microfluidic lab-on-a-chip (LOC) technology in the identification and antibiotic susceptibility testing of... (Review)
Review
The Potential Clinical Applications of a Microfluidic Lab-on-a-Chip for the Identification and Antibiotic Susceptibility Testing of -Associated Endodontic Infections: A Systematic Review.
This systematic review evaluated the potential clinical use of microfluidic lab-on-a-chip (LOC) technology in the identification and antibiotic susceptibility testing of in endodontic infections. The search methodology employed in this review adhered to the PRISMA guidelines. Multiple scientific databases, including PubMed/MEDLINE, SCOPUS, and SCIELO, were utilized, along with exploration of grey literature sources. Up to September 2023, these resources were searched using specific keywords and MeSH terms. An initial comprehensive search yielded 202 articles. Ultimately, this systematic review incorporated 12 studies. Out of these, seven aimed to identify , while the remaining five evaluated its susceptibility to different antibiotics. All studies observed that the newly developed microfluidic chip significantly reduces detection time compared to traditional methods. This enhanced speed is accompanied by a high degree of accuracy, efficiency, and sensitivity. Most research findings indicated that the entire process took anywhere from less than an hour to five hours. It is important to note that this approach bypasses the need for minimum inhibitory concentration measurements, as it does not rely on traditional methodologies. Microfluidic devices enable the rapid identification and accurate antimicrobial susceptibility testing of , which are crucial for timely diagnosis and treatment in endodontic infections.
PubMed: 38248213
DOI: 10.3390/dj12010005 -
Arthroscopy : the Journal of... Jun 2024To assess the efficacy of intra-articular viscosupplementation as a therapeutic intervention for hip osteoarthritis (OA), as well as to assess the duration of efficacy,... (Review)
Review
PURPOSE
To assess the efficacy of intra-articular viscosupplementation as a therapeutic intervention for hip osteoarthritis (OA), as well as to assess the duration of efficacy, effect of dose, composition and number of injections of the viscosupplement, and the incidence of adverse effects.
METHODS
We performed a systematic review using the literature search from the following databases: Embase, Medline, PubMed, Web of Science, and Scopus. Quality assessment of the included studies was performed using the Modified Newcastle-Ottawa Quality Assessment Scale. Random-effects meta-analysis and mixed-effects subgroup analysis were carried out, but due to the high heterogeneity, low level of evidence, and high risk of bias of the included studies after analyzing the data, weighted means and pooled estimates have not been provided. Instead, we have provided a subjective synthesis of the results.
RESULTS
Forty studies were included in the analysis from an initial search of 3,265 studies, with data from a total of 3,350 patients. The level of available evidence was low with an overall high risk of bias. Nearly all studies showed a reduction in mean pain at 1 month, 3 months, and 6 months of follow-up, as well as at the end point, and an improvement in mean patient-reported function was also seen at these time points. However, heterogeneity was extremely high at all time points and remained despite attempts at removing outliers. Subgroup analyses looking at the effects of dose, volume, composition of viscosupplement, and number of injections were carried out, but substantial heterogeneity still remained. There were no lasting adverse effects.
CONCLUSIONS
Weak evidence suggests that viscosupplementation improves patient-reported pain and function at end point compared to baseline, regardless of dose, volume, composition, and number of injections. However, due to the high heterogeneity, low level of evidence, and high risk of bias in the current available literature, the strength of our conclusions is limited.
LEVEL OF EVIDENCE
Level IV, systematic review of level I to IV studies.
Topics: Humans; Viscosupplementation; Osteoarthritis, Hip; Injections, Intra-Articular; Viscosupplements; Hyaluronic Acid; Treatment Outcome
PubMed: 38000487
DOI: 10.1016/j.arthro.2023.11.010 -
Dentistry Journal Oct 2023, , and , collectively recognized as periodontopathogens within the red complex, have been extensively studied in clinical samples collected from individuals with... (Review)
Review
, , and , collectively recognized as periodontopathogens within the red complex, have been extensively studied in clinical samples collected from individuals with periodontitis. A lab-on-a-chip (LOC) is a miniature mechanism that integrates various laboratory operations onto a single microchip or a small-scale platform. This systematic review evaluates the application of LOC technology in identifying microorganisms from the red complex. This study adhered to PRISMA recommendations, and the review process encompassed several databases. In the electronic search, a total of 58 reports were found, and ultimately, 10 studies were considered relevant for inclusion. All these studies described effective, rapid, and reliable LOC systems for detecting and amplifying , , and . Compared to traditional methods, the LOC approach demonstrated minimal reagent requirements. Additionally, the results indicated that the amplification process took approximately 2 to 8 min, while detection could be completed in as little as 2 min and 40 s, resulting in a total experimental duration of around 11 min. Integrating miniaturization, speed, accuracy, and automation within microchip platforms makes them promising tools for detecting and amplifying microorganisms associated with the red complex in periodontal diseases.
PubMed: 37999009
DOI: 10.3390/dj11110245 -
PloS One 2023The microfluidic sperm selection (MFSS) device has emerged as a promising adjunct in assisted reproduction treatments (ART). It employs mechanisms of biomimicry based on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The microfluidic sperm selection (MFSS) device has emerged as a promising adjunct in assisted reproduction treatments (ART). It employs mechanisms of biomimicry based on the microanatomy of the female reproductive tract through strategies like chemotaxis and rheotaxis. Numerous studies assert improvements in ART outcomes with the use of MFSS, often attributed to the theoretical reduction in sperm DNA damage compared to other techniques. However, these attributed benefits lack validation through large-scale clinical trials, and there is no significant evidence of enhanced assisted reproductive treatments (ART) outcomes.
OBJECTIVE
To evaluate whether the utilization of MFSS enhances clinical pregnancy results and abortion outcomes in couples undergoing ART compared to standard sperm selection techniques for Intracytoplasmic Sperm Injection (ICSI). We also assessed laboratory outcomes as a supplementary analysis.
SEARCH METHODS
We conducted searches across databases including PubMed, NIH, LILACS, CENTRAL, Crossref, Scopus, and OpenAlex. A total of 1,255 records were identified. From these, 284 duplicate records were eliminated, and an additional 895 records were excluded due to their association with patent applications, diagnostic tests, forensic analyses, or irrelevance to the research focus. Among the initially eligible 76 studies, 63 were excluded, encompassing abstracts, studies lacking adequate control groups, and ongoing clinical trials. Ultimately, 13 studies were selected for inclusion in the ensuing meta-analysis.
RESULTS
Regarding clinical pregnancy, we assessed a total of 868 instances of clinical pregnancies out of 1,646 embryo transfers. Regarding miscarriage, we examined 95 cases of pregnancy loss among the 598 confirmed clinical pregnancies in these studies.
CONCLUSION
The utilization of MFSS demonstrates marginal positive outcomes compared to standard sperm selection techniques, without statistical significance in any of the analyses.
BROADER IMPLICATIONS
This study conducted the first meta-analysis to evaluate clinical pregnancy rates, miscarriage rates, and laboratory results associated with the use of MFSS compared to standard sperm selection techniques. We have also listed potentially eligible studies for future inclusion. It's important to emphasize the need for multicenter studies with standardized parameters to attain a more robust clarification of this issue.
Topics: Pregnancy; Male; Female; Humans; Abortion, Spontaneous; Microfluidics; Semen; Sperm Injections, Intracytoplasmic; Pregnancy Rate; Spermatozoa; Live Birth
PubMed: 37983267
DOI: 10.1371/journal.pone.0292891