Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 17 appraisals
Computational biology and chemistry
The intervention of AI and ML generated Xenobots in the perspective of future technology: a review.
The evolution of synthetic mini-robots has contributed much to the field of science and technology. Still, of now, computational technology has shifted to generate AI-based robots from the living matter of Amphibian cells by utilizing evolutionary algorithms. In this aspect, we have discussed the evolution, role, applications, and ethical considerations of the Xenobots (the world's first living, programmable organisms) in this challenging artificial intelligence age. The various techniques involved in programming the xenobots were discussed, such as cell harvesting and culturing, computational design and simulation, assembly and bio-printing, cell differentiation and integration, machine learning and AI integration, etc. Moreover, they find their applications and promise significance in various fields, including medicine and health care. Finally,ethical considerations were discussed to emphasize safety, ensuring responsible development and deployment in various fields.
3 Aug 2026
Read appraisal →Translational stroke research
AI-Guided Patient-Derived Endothelial Modeling Identifies a Reversible Moyamoya-Specific miRNA Deficiency Corrected by Stem Cell-Extracellular Vesicles
Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by abnormal vascular remodeling and impaired angiogenesis. We profiled plasma extracellular vesicle (EV)-derived microRNAs (miRNAs) from MMD patients and healthy controls and generated patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) to investigate disease-associated molecular alterations and therapeutic reversibility. Both plasma EVs and iPSC-ECs from MMD patients showed significant depletion of angiogenesis-related miRNAs. Small RNA sequencing data revealed mesenchymal stem cell-derived EVs (MSC-EVs) contain a miRNA repertoire that substantially overlaps with miRNAs deficient in MMD. Treatment of MMD iPSC-ECs with MSC-EVs restored the majority of the depleted miRNAs to normal levels, normalized predicted target mRNA expression, and rescued angiogenic function in a dose-dependent manner, as demonstrated by tube formation assays. To improve identification of biologically relevant miRNA-mRNA interactions, we developed an artificial intelligence-based framework integrating experimentally validated databases, endothelial-focused literature mining, and large language model (LLM)-assisted mechanistic scoring. Incorporation of LLM-derived contextual features modestly improved prediction performance compared with conventional sequence-based models (baseline AUROC ~ 0.51; LLM-enhanced AUROC ~ 0.72), suggesting that literature-informed biological context provides meaningful signal beyond structural target features alone. Furthermore, our findings demonstrate that MSC-EV therapy can substantially reverse molecular and functional endothelial deficits. Integrated profiling and AI-driven interaction mapping together establish a hypothesis-generating framework ("Exo-Courier") for biologically informed prioritization of EV-based therapeutic targets in vascular disorders.
12 June 2026
Read appraisal →Journal of translational medicine
Mesenchymal stem cell-derived extracellular vesicles for osteochondral defect regeneration: a systematic review and meta-analysis of preclinical studies
BACKGROUND: In recent years, the number of animal studies investigating mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) therapy for osteochondral defects has steadily increased. However, a comprehensive and systematic quantitative analysis is lacking. This meta-analysis aimed to evaluate the efficacy of MSC-EVs in animal models of osteochondral defect through a meta-analysis. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched up to January 31, 2025, to identify and select preclinical studies on MSC-EVs therapy for osteochondral defect models. No restrictions were applied regarding the specific characteristics of MSC-EVs or animal models. A random-effects model was used to perform pooled analyses of osteochondral repair scores, bone structural parameters, and histological scores. Subgroup analyses were conducted to explore potential sources of heterogeneity. Sensitivity analyses, funnel plots, and Egger's test were employed to assess the robustness and stability of the results. RESULTS: A total of 19 studies met the inclusion criteria. MSC-EVs intervention improved International Cartilage Repair Society (ICRS) and Modified O'Driscoll Scale (MODS) scores at both 3 and 6 months, and significantly increased BV/TV, Tb.Th, as well as histological scores of cartilage and subchondral bone. Subgroup analyses indicated that none of the examined subgroups were significant sources of heterogeneity. Sensitivity analyses demonstrated the robustness of the results. CONCLUSIONS: MSC-EVs improved osteochondral repair scores, bone structural parameters, and histological outcomes in preclinical models, indicating their potential for promoting osteochondral regeneration. However, the evidence is primarily derived from small animal models with methodological variability and publication bias. Future studies should focus on large-animal models, standardized EVs preparation and dosing protocols, and long-term safety evaluations to facilitate clinical translation.
31 May 2026
Read appraisal →The New England journal of medicine
Stem-Cell-Derived Biologic Ventricular Assist Tissue in Heart Failure
BACKGROUND: Biologic ventricular assist tissue (BioVAT) is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogeneic induced pluripotent stem cells for cardiac remuscularization in patients with heart failure and a reduced left ventricular ejection fraction. METHODS: We conducted an open-label, phase 1-2 study of tissue-engineered heart repair by means of BioVAT transplantation. Patients with heart failure and a left ventricular ejection fraction of 35% or less and at least one hypokinetic or dyskinetic left ventricular segment were treated with BioVAT allografts, which consisted of 5, 10, or 20 engineered-heart-muscle units. All the patients received immunosuppression. Safety was assessed as adverse events related to the procedure. The primary efficacy end points were the change from baseline in the target heart-wall thickness, the left ventricular ejection fraction, and the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OSS). RESULTS: A total of 20 patients were treated in the study. Three patients died during the study (1 each from vasoplegia, coronavirus disease 2019, and aortic dissection). One patient underwent heart transplantation. Immunosuppression was discontinued in 4 patients because of implantation of a left ventricular assist device (in 2 patients), renal failure (in 1 patient), and urothelial carcinoma (in 1 patient). Of the 16 patients who were treated with the safe maximal dose (20 engineered-heart-muscle units), 12 patients completed the prespecified 3-month interim follow-up. The least-squares mean increase in the target-wall thickness was 4.5 mm (90% confidence interval [CI], 3.7 to 5.4; P<0.001), the increase in the left ventricular ejection fraction was 3.9 percentage points (90% CI, 0.9 to 6.8; P = 0.04), and the increase in the KCCQ-OSS was 6.7 points (90% CI, 1.0 to 12.5; P = 0.06). All the patients had at least one adverse event. CONCLUSIONS: In this interim analysis, cardiac remuscularization with BioVAT was associated with an increase in the target heart-wall thickness, left ventricular ejection fraction, and KCCQ-OSS at 3 months; all the patients had at least one adverse event. Longer-term follow-up and further clinical investigation are warranted. (Funded by the German Center for Cardiovascular Research and Repairon; BioVAT-HF ClinicalTrials.gov number, NCT04396899.).
30 May 2026
Read appraisal →ACS synthetic biology
Prompt-Only Gene-Circuit Modeling with a Large Language Model Simulates the synNotch Spheroids
Morphogenesis emerges from gene regulatory circuits that translate biochemical cues into spatially organized cell fates; yet, constructing quantitative simulations of these processes remains technically demanding. Here, we present a prompt-only pipeline in which a large language model (LLM) automatically generates CompuCell3D (CC3D) simulations directly from natural-language biological specifications. Using the canonical synNotch spheroid assay as a benchmark, we show that the LLM-generated code captures key features of contact-dependent signaling, cadherin-mediated adhesion, and multicellular sorting dynamics without manual programming. Baseline simulations exhibited the expected qualitative ordering of inducer-responder activation but revealed fragmentation into multiple spheroids, implicating premature reciprocal signaling as a kinetic failure mode. Incorporating a cumulative contact-duration threshold for synNotch activation rescued robust single-spheroid formation, suggesting that sustained cell-cell interactions are a critical design principle for this pattern. Our results establish conversational LLM guidance as a powerful accelerator for multiscale modeling, collapsing the steep learning curve of CC3D into a dialog-driven workflow. This framework enables nonspecialists to test gene-circuit hypotheses in silico and provides a generalizable route toward rapid, mechanism-level exploration of developmental design principles.
16 May 2026
Read appraisal →Biofabrication
Resolving the multiscale design trade-off in bone tissue engineering: from generative design to digital twins
The clinical translation of bone tissue engineering is constrained by a severe multiscale design trade-off: the requirement for load-bearing mechanical strength competes directly with the need for vascular-permissive porosity. Conventional approaches address scaffold geometry, material formulation, and fabrication in a sequential, decoupled manner and therefore fail to navigate this multi-objective conflict. To overcome this limitation, we propose an 'AI-Driven Holistic Intelligence' framework. It spans the entire pipeline from generative inverse design to digital twin (DT)-based predictive maturation. The framework integrates gradient scaffold optimization, closed-loop adaptive manufacturing, and virtual clinical trial within a unified workflow. This architecture is designed to co-optimize the boundary conditions of stiffness and perfusion simultaneously, rather than in isolation. Nonetheless, realizing this vision as a clinically viable autonomous regeneration pathway will require bridging persistent translational gaps in data standardization, algorithm interpretability, and regulatory alignment. Importantly, the core innovation of this framework is not merely to navigate the empirical 'trade-off' along a fixed Pareto front, but to resolve it through multiscale co-optimization that expands the accessible design space, enabling simultaneous improvements in mechanical strength and vascular perfusion beyond the limits achievable by conventional single-objective approaches.
13 May 2026
Read appraisal →Neurology
Intrathecal Mesenchymal Stem Cells in Progressive Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial (SMART-MS)
BACKGROUND AND OBJECTIVES: There is an unmet need for neuroregenerative therapies in multiple sclerosis (MS). Mesenchymal stem cells (MSCs) have shown immunomodulatory and regenerative effects in preclinical models and early clinical studies. Intrathecal administration may enhance therapeutic potential by direct delivery to the CNS. However, randomized, placebo-controlled trials are needed to establish safety and efficacy. The objective of this trial was to assess whether a single intrathecal administration of autologous MSCs could provide evidence of a neuroregenerative effect in progressive MS. METHODS: In this randomized, double-blind, placebo-controlled phase I/II trial (NCT04749667), patients with progressive MS enrolled at 4 Norwegian tertiary hospitals received a single intrathecal injection of autologous bone marrow-derived MSCs (1 × 106 cells/kg) in a crossover design. The primary end point was the change in latency of combined evoked potentials at 6 months. Secondary end points included safety, brain MRI measures, functional and ophthalmologic assessments, and serum biomarkers at 6 and 12 months. Exploratory analyses comprised proteomic profiling of CSF. Outcomes were analyzed using baseline-adjusted regression models. RESULTS: A total of 18 patients were included (mean age 46.7 years; 55.6% female). No significant between-group difference was observed for the primary end point (β = -0.31, 95% CI -1.84 to 1.22, p = 0.668). At 6 months, patients in the MSC group showed reduced cerebral atrophy on MRI (β = 9.37, 95% CI 0.29 to 18.45, p = 0.044) and lower serum glial fibrillary acidic protein levels (β = -16.3 pg/mL, 95% CI -33.0 to 0.3, p = 0.054), but neither were sustained at 12 months. Exploratory CSF proteomics revealed reductions in multiple inflammation-related proteins at 6 months. One serious adverse event was deemed probably related to MSC treatment. Common adverse events included fever (n = 9) and low back pain (n = 10) after MSC administration, and spinal MRI abnormalities with fluid loculations and nerve root clumping (n = 7) at 6 months. One patient developed chronic coccygeal pain attributed to arachnoiditis. DISCUSSION: A neuroregenerative effect was not detected, although interpretation may be limited by the small sample size. Adverse events suggest an acute localized inflammatory reaction after MSC administration. Our findings suggest that intrathecal administration of MSCs in progressive MS should be approached with caution in future studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, in patients with progressive multiple sclerosis, treatment with a single intrathecal administration of autologous mesenchymal stem cells does not provide neuroregenerative effect, as assessed by a composite evoked potential score. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04749667); registered February 8, 2021; first patient enrolled August 9, 2021.
10 May 2026
Read appraisal →The Journal of dermatological treatment
Comparative efficacy and safety of platelet-rich plasma (PRP), injectable platelet-rich fibrin (i-PRF) and concentrated growth factors (CGF) for female pattern hair loss (FPHL): a prospective multicenter randomized clinical trial
BACKGROUND: Comparative studies among different autologous platelet concentrate types for FPHL remain lacking. METHODS: Patients with FPHL (Sinclair gradeII-III) were enrolled and randomized to receive 4 sessions of PRP, i-PRF or CGF treatment at 4-week intervals. The primary endpoint was the inter-group comparison of the non-vellus target area hair count (TAHC)-increase (%) at 24 weeks. Secondary endpoints included: within-group changes in TAHC from baseline; within-group changes in hair diameter (HD) from baseline and inter-group comparison of HD-increase (%) at 24 weeks; Growth factor concentrations were quantified to explore correlations with efficacy. RESULTS: Seventy-four patients completed the study. Post-treatment TAHC increased significantly from baseline in all groups (all p < 0.05). The TAHC-increase(%) was significantly greater in the CGF (27.11 ± 14.80%) and i-PRF (26.54 ± 11.46%) groups compared to the PRP group (14.53 ± 8.65%; p < 0.05), with no significant difference between CGF and i-PRF. Regarding HD increase, all three groups showed improvement, with no statistically significant differences observed among groups (p > 0.05). The i-PRF group showed the lowest adverse event rate. Vascular endothelial growth factor (VEGF) concentration demonstrated a significant positive correlation with the percentage increase in TAHC (r = 0.527, R2=0.278, p < 0.05). CONCLUSIONS: CGF and i-PRF demonstrated superior efficacy in increasing TAHC in FPHL patients. The i-PRF group had the lowest adverse event rate. VEGF levels may play a potential role in promoting hair growth.
2 May 2026
Read appraisal →Stem cells (Dayton, Ohio)
Quiescence in the resting zone of the growth plate: a systematic review
Postnatal skeletal growth in childhood and adolescence depends on cartilage organs called (epiphyseal) growth plates. Studies in the last decade have identified populations of skeletal stem cells within mouse growth plates' resting zones. While cellular quiescence is vital for the maintenance of many tissue-resident stem cell populations, the resting zone chondrocytes have been labeled "quiescent" for decades. However, the features of cellular quiescence that have been reported in the postnatal resting zone, how they were defined or experimentally assessed, and knowledge gaps relative to other quiescent cell types, remain to be well described. To address this, we conducted a systematic review, using the PRISMA guidelines, to identify studies of resting zone chondrocytes including the prefix "quiescen*." Definitions, keywords, chronological data and experimental findings were extracted. Our analysis demonstrated that, compared to those in other well-studied tissues, features of cellular quiescence in RZ chondrocytes remain poorly reported and underexplored, with limited molecular and functional characterization. Furthermore, while most identified studies reported changes in cell division parameters, integration between cues controlling resting zone cell quiescence is incomplete and heterogeneity among the various sub-populations of RZ cells/potential quiescent states is yet to be fully determined. This review identifies consensuses and knowledge gaps between studies and between quiescent RZ cells and those in other tissues and can act to enhance consistency and comparability in future studies of "quiescence" in the RZ chondrocytes.
30 Apr 2026
Read appraisal →Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews
Academic Influence and Industry Funding in Platelet-Rich Plasma Injections: Coauthorship Network Analysis
BACKGROUND: Platelet-rich plasma (PRP) injections have gained popularity in the fields of orthopaedics and sports medicine despite inconsistent evidence regarding clinical efficacy. Concerns have placed a role on industry funding in shaping the development of PRP injection literature. Therefore, the aim of this study is to investigate the relationship between industry funding and academic influence in PRP injection research. METHODS: A systematic review was done of PRP injection literature published between 2017 and 2024, all from Q1 (top quartile) peer-reviewed journals based on Scopus journal ranking metrics. Overall, 81 studies were included in final analysis. Authors were linked to the Open Payments Database (OPD) and were identified through their national provider identifier (NPI) number. A coauthorship network analysis was used to map patterns of collaboration among authors in the field. RESULTS: The majority of studies identified were randomized control trials (38.3%). From 2017 to 2024, total industry funding to PRP authors totaled $36.1 million. Markedly more general payments than research payments were there (P < 0.05). Funding did not markedly correlate with publication count (r = 0.368, P = 0.40). No notable association was found between funding type and study outcome for either general (P = 0.482) or research (P = 0.481) payments. A centralized structure of 621 unique authors revealed that the top 10% of contributors accounted for more than 40% of all betweenness activity among these authors. CONCLUSION: The majority of industry funding in PRP injection research is directed as general payments. A small cohort of authors hold disproportionate influence over the community.
26 Apr 2026
Read appraisal →Lab on a chip
Machine learning-driven single-cell phenotyping in size-controlled microenvironments via parallel deterministic droplet microfluidics
Understanding how individual cells respond to distinct physical microenvironments is critical for mechanobiology, cell therapy, and tissue engineering. Current single-cell encapsulation methods are often limited by Poisson loading and fixed droplet sizes, preventing parallel generation of multiple, size-specific microenvironments and constraining high-resolution phenotypic analyses. Here, we present a droplet microfluidic platform that enables deterministic single-cell encapsulation within microgels of multiple sizes from a single precursor stream, achieved through parallelized flow-focusing combined with cell-selective gelation. This system produces distinct microgel size regimes simultaneously, minimizing empty compartments and enabling direct, side-by-side comparisons of cellular behavior under controlled yet variable confinement. Using machine learning to analyze 3D morphological and cytoskeletal features, we reveal heterogeneous, size-dependent phenotypic responses and demonstrate that cellular phenotypes alone can predict microgel confinement across time. Together, these results establish a data-driven framework for mapping single-cell responses across engineered microenvironments and provide a scalable platform for predictive studies of mechanosensitive behavior in heterogeneous niches.
24 Apr 2026
Read appraisal →Stem cell reports
Cellular immunotherapy for COVID-19-induced acute respiratory distress syndrome: Results of the CIRCA-19 phase 1 safety and phase 2 randomized controlled trials
The ability of immunomodulatory mesenchymal stromal cells (MSCs) to improve COVID-19-associated acute respiratory distress syndrome (ARDS) in clinical trials is uncertain. We assessed whether freshly cultured umbilical cord (UC)-derived MSCs improved outcomes in patients with severe COVID-19 ARDS. We enrolled 37 patients with severe COVID-19 ARDS: 15 in the phase 1 dose escalation and open label extension studies (NCT04400032), and 22 patients in the phase 2b randomized clinical trial (NCT04865107). Delivery of up to 270 × 106 MSCs in three divided daily doses was well tolerated and resulted in qualitative improvement in all clinical outcomes. Furthermore, MSCs resulted in resolution of lymphopenia, consistent with an important immunomodulatory effect, with significant improvement in patient reported quality-of-life measures (SF-36) at 6 months pointing to possible durable clinical effects. These findings suggest a potential benefit of freshly cultured, UC-MSCs in severe COVID-19 ARDS, associated with biological evidence of favorable immunomodulatory activity.
17 Apr 2026
Read appraisal →African journal of reproductive health
The therapeutic potential of exosomes derived from mesenchymal stem cells for premature ovarian failure: A systematic review
This review evaluates mesenchymal stem cell-derived exosomes (MSC-Exos) for treating premature ovarian failure (POF). A comprehensive search was conducted across five databases, including PubMed, Embase, and Web of Science (WoS), yielding 17 English-language studies published between 2016 and 2025. Studies primarily using animal and in vitro models assessed the therapeutic effects and mechanisms of MSC-Exos from diverse sources. MSC-Exos significantly elevated estrogen levels, reduced follicle-stimulating hormone (FSH), increased antral follicle counts, and restored estrous cyclicity. Specifically, BMSC-Exos activated the PI3K/AKT pathway via miRNAs to suppress granulosa cell apoptosis; hUCMSC-Exos mitigated cellular senescence and autophagy; ADSC-Exos promoted follicular development through SMAD and SIRT1/FOXO1; PMSC-Exos attenuated ROS damage by improving mitochondrial function; AFSC-Exos together with MenSC-Exos enhanced oocyte maturation via the P53 pathway. Notably, perinatal exosomes showed 18-32% greater efficacy in functional recovery than adult-tissue counterparts with fewer doses. MSC-Exos present a promising therapeutic strategy for POF by targeting apoptosis, autophagy, angiogenesis, and oxidative stress. Perinatal-derived exosomes offer superior potential due to their non-invasive collection and minimal ethical concerns. Nonetheless, challenges pertaining to heterogeneity, long-term safety, and standardized manufacturing necessitate resolution through multicenter clinical trials to advance clinical applicability.. Cette revue évalue l’utilisation d’exosomes dérivés de cellules souches mésenchymateuses (MSC-Exos) pour le traitement de l’insuffisance ovarienne prématurée (IOP). Une recherche exhaustive a été menée dans cinq bases de données, notamment PubMed, Embase et Web of Science (WoS), et a permis d’identifier 17 études publiées en anglais entre 2016 et 2025. Les études, reposant principalement sur des modèles animaux et in vitro, ont examiné les effets thérapeutiques et les mécanismes d’action des MSC-Exos issus de différentes sources. Les MSC-Exos ont significativement augmenté les taux d’œstrogènes, réduit l’hormone folliculostimulante (FSH), accru le nombre de follicules antraux et rétabli la cyclicité œstrale. Plus précisément, les exosomes dérivés de cellules souches mésenchymateuses de la moelle osseuse (BMSC-Exos) ont activé la voie PI3K/AKT via des miARN afin de supprimer l’apoptose des cellules de la granulosa ; les exosomes dérivés de cellules souches mésenchymateuses du cordon ombilical humain (hUCMSC-Exos) ont atténué la sénescence cellulaire et modulé l’autophagie ; les exosomes dérivés de cellules souches mésenchymateuses du tissu adipeux (ADSC-Exos) ont favorisé le développement folliculaire via les voies SMAD et SIRT1/FOXO1 ; les exosomes dérivés de cellules souches mésenchymateuses placentaires (PMSC-Exos) ont réduit les dommages liés aux espèces réactives de l’oxygène (ROS) en améliorant la fonction mitochondriale ; les exosomes dérivés de cellules souches du liquide amniotique (AFSC-Exos), associés aux exosomes dérivés de cellules souches mésenchymateuses menstruelles (MenSC-Exos), ont amélioré la maturation ovocytaire via la voie P53. Il est à noter que les exosomes d’origine périnatale ont montré une efficacité de récupération fonctionnelle supérieure de 18 à 32 % à celle des exosomes issus de tissus adultes, et ce avec un nombre de doses plus faible. Les MSC-Exos constituent une stratégie thérapeutique prometteuse pour l’IOP en ciblant l’apoptose, l’autophagie, l’angiogenèse et le stress oxydatif. Les exosomes d’origine périnatale offrent un potentiel supérieur grâce à un prélèvement non invasif et à des préoccupations éthiques limitées. Néanmoins, des défis liés à l’hétérogénéité, à la sécurité à long terme et à la standardisation de la fabrication doivent être résolus au moyen d’essais cliniques multicentriques afin de favoriser une application clinique. Cette revue évalue l’utilisation d’exosomes dérivés de cellules souches mésenchymateuses (MSC-Exos) pour le traitement de l’insuffisance ovarienne prématurée (IOP). Une recherche exhaustive a été menée dans cinq bases de données, notamment PubMed, Embase et Web of Science (WoS), et a permis d’identifier 17 études publiées en anglais entre 2016 et 2025. Les études, reposant principalement sur des modèles animaux et in vitro, ont examiné les effets thérapeutiques et les mécanismes d’action des MSC-Exos issus de différentes sources. Les MSC-Exos ont significativement augmenté les taux d’œstrogènes, réduit l’hormone folliculostimulante (FSH), accru le nombre de follicules antraux et rétabli la cyclicité œstrale. Plus précisément, les exosomes dérivés de cellules souches mésenchymateuses de la moelle osseuse (BMSC-Exos) ont activé la voie PI3K/AKT via des miARN afin de supprimer l’apoptose des cellules de la granulosa ; les exosomes dérivés de cellules souches mésenchymateuses du cordon ombilical humain (hUCMSC-Exos) ont atténué la sénescence cellulaire et modulé l’autophagie ; les exosomes dérivés de cellules souches mésenchymateuses du tissu adipeux (ADSC-Exos) ont favorisé le développement folliculaire via les voies SMAD et SIRT1/FOXO1 ; les exosomes dérivés de cellules souches mésenchymateuses placentaires (PMSC-Exos) ont réduit les dommages liés aux espèces réactives de l’oxygène (ROS) en améliorant la fonction mitochondriale ; les exosomes dérivés de cellules souches du liquide amniotique (AFSC-Exos), associés aux exosomes dérivés de cellules souches mésenchymateuses menstruelles (MenSC-Exos), ont amélioré la maturation ovocytaire via la voie P53. Il est à noter que les exosomes d’origine périnatale ont montré une efficacité de récupération fonctionnelle supérieure de 18 à 32 % à celle des exosomes issus de tissus adultes, et ce avec un nombre de doses plus faible. Les MSC-Exos constituent une stratégie thérapeutique prometteuse pour l’IOP en ciblant l’apoptose, l’autophagie, l’angiogenèse et le stress oxydatif. Les exosomes d’origine périnatale offrent un potentiel supérieur grâce à un prélèvement non invasif et à des préoccupations éthiques limitées. Néanmoins, des défis liés à l’hétérogénéité, à la sécurité à long terme et à la standardisation de la fabrication doivent être résolus au moyen d’essais cliniques multicentriques afin de favoriser une application clinique.
15 Apr 2026
Read appraisal →PloS one
Advanced microfluidic and 3D cell culture platforms for modeling vascularization in diabetic foot ulcers: A systematic review of translational challenges and perspectives
The healing process of diabetic foot ulcers (DFUs) presents a slow pattern with an increased risk of infections, ischemia, and thrombosis correlated with high levels of reactive oxygen species production. Vascular injury is one of the factors contributing to the difficulty of wound healing in diabetic patients. Although the understanding of the pathophysiology of DFUs has significantly increased in recent years, associated treatments still have a high level of failure, leading to high morbidity rates, mortality, and amputations. Three-dimensional (3D) cell culture platforms offer a new approach to investigating and treating these wounds, as they can reproduce one or more physiological systems in a relevant microenvironment. This systematic review describes the advancements, challenges, and future implications of advanced 3D culture models in vascularization, encompassing pathophysiological understanding, treatment, and prognostic perspectives. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This work was registered under PROSPERO protocol number CRD42022336473. The eligibility criteria addressed studies related to chronic DFUs that analyzed vascularization during the healing process. The selected study designs involved 3D cultures and organ-on-a- chip (OoC) platforms, utilizing either primary or secondary human cell lines. Studies published more than 10 years ago or using only animal cells in 2D culture environments were excluded. The search was conducted in PubMed, LILACS, Embase, MEDLINE, IEEE, the BSV regional portal, ScienceDirect, Scopus, CINAHL, EBSCO, and Web of Science. A total of 2,539 relevant studies were identified as of June 1, 2025. After screening, only seven met the inclusion criteria. These studies reflect a growing interest in using hydrogel scaffolds and microfluidic systems to replicate diabetic skin environments; however, the field remains in an early stage of development. OoC platforms, in particular, stand out for their ability to recreate dynamic, tissue-like conditions and vascular function. While some promising attempts have been made to combine hydrogels with these technologies, the evidence is still limited and inconclusive for chronic wound modeling. This review underscores both the potential and the urgent need for more robust and translational research in this area-especially toward building personalized, clinically relevant models to support future drug testing and therapeutic innovation.
7 Apr 2026
Read appraisal →The International journal of oral & maxillofacial implants
Bone Marrow Aspirate Concentrate and Xenograft Versus Autograft and Xenograft in the 3D Reconstruction of Atrophic Maxillary Ridges: A Split-Mouth Randomized Controlled Trial
PURPOSE: To evaluate bone quality and quantity after 3D augmentation of vertically and horizontally atrophied maxillary ridges and compare the use of bone marrow aspirate concentrate (BMAC) and xenograft versus autograft and xenograft, both using prebent titanium (Ti) mesh over a virtually augmented model. MATERIALS AND METHODS: Ten fully edentulous patients with severe maxillary vertical and horizontal bone loss were recruited. Virtual horizontal and vertical bone augmentation was performed for the deficient ridge to produce virtually augmented models for prebent Ti meshes preoperatively. Each patient was rehabilitated with BMAC and xenograft on one side of their mouth (test side) and with autograft and xenograft on the other (control side). For the test side, the mesh was loaded with a mix of xenograft and BMAC from the anterior iliac crest. For the control side, the mesh was loaded with a 1:1 ratio of xenograft to autograft mix. The meshes on both sides were fixed in place using miniscrews. RESULTS: CBCT scans were performed 6 months postoperatively for all patients. The test side showed a mean vertical bone gain of 3.47 ± 0.87 mm, which was comparable to that of the control side (4.10 ± 0.67 mm). The test side also showed a mean horizontal bone gain of 3.476 ± 0.59 mm, which was higher than that of the control side (2.918 ± 0.80 mm). While the mean resorption rate in the test side (106.2 ± 108.6 mm) was lower than the mean value in the control side (193.3 ± 107.9 mm), the differences in bone gain were not statistically significant. However, a statistically significant higher bone area percentage (47.9%) as well as a higher percentage of mature bone (67.7%) were detected in the test side compared to the control side (28.5% and 26.5%, respectively). CONCLUSIONS: 3D alveolar reconstruction using prebent Ti meshes loaded with xenograft mixed with BMAC could be a reliable and less complicated technique for vertically and horizontally atrophied maxillary ridges.
5 Apr 2026
Read appraisal →Journal of wound care
Micrografts-a novel ally in hard-to-heal wounds: a systematic review.
OBJECTIVE: Wound healing is complex, and hard-to-heal (chronic) wounds pose significant treatment challenges, especially in adults. Micrografts (MGs) are emerging as a promising treatment for wounds refractory to conventional approaches. MG involves transplanting a stem cell suspension to the wound to promote healing. Scientific studies on MG are increasing; however, a systematic review is needed for a comprehensive understanding of its efficacy. METHOD: A systematic review conducted on 30 March 2024 used PubMed, Scopus and Web of Science databases to evaluate skin and dermal MGs in wound healing. PRISMA guidelines were followed and predefined inclusion and exclusion criteria were applied. All authors reviewed the studies and discussed results to ensure consistency in study screening, selection and data extraction. RESULTS: A total of 1251 papers were examined, with 23 eligible for full-text review. After exclusions based on language, reviews, MG size and tissue focus, 15 articles were included in the final review: seven case reports; five case series; two prospective series (one with 70 patients, the other with 30 patients) and a case-control study. CONCLUSION: The results of the reviewed studies suggest that MGs may promote wound healing, with reported reductions in healing time and improvements in clinical symptoms in hard-to-heal wounds. However, standardisation of treatment protocols and application methods is required. The role of MGs in the treatment of acute wounds remains to be clarified.
4 Apr 2026
Read appraisal →Biofabrication
High-fidelity 'top-down' DLP bioprinting of multi-material soft tissue constructs enabled by computer vision-based layer control
Bioprinting continues to redefine the frontiers of regenerative medicine by enabling the fabrication of complex, three-dimensional (3D) tissue constructs that emulate native biological and mechanical functions. However, despite significant progress, critical challenges remain, particularly in achieving precise multi-material integration, high-resolution patterning, and structural fidelity necessary for functional tissue engineering. A major limitation in 'top-down' vat photopolymerization bioprinting, especially digital light processing (DLP)-based approaches, lies in the precise control of layer thickness, a parameter that directly affects mechanical integrity, biological activity, and spatial resolution. This study presents a novel, automated platform designed to overcome one of the most persistent bottlenecks in multi-material top-down DLP bioprinting: the real-time, accurate measurement of the dynamic gap between the cured layer and the bioink surface. Through a comparative assessment of classical computer vision and deep learning (convolutional neural network-based) techniques, we demonstrate a system capable of achieving sub-0.1 mm precision (0.092 mm) with strong correlation to mechanical measurements (R= 0.994). This vision-based system adapts to a wide range of bioinks with varying viscosities, opacities, and photopolymerization kinetics, eliminating the need for manual recalibration during material switching. As a demonstration of its capabilities, we successfully printed a multimaterial vascular-like tissue structure with high spatial fidelity across heterogeneous biomaterials. Further, we bioprinted a multimaterial skin tissue model, featuring compartmentalized dermal/bone analogs, to enablein vitrofunctional evaluation. These case studies highlight the platform's potential to advance biofabrication workflows by improving reproducibility, material adaptability, and structural precision, paving the way toward clinically scalable tissue manufacturing systems.
4 Apr 2026
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