MXene quantum dots (MQDs) have recently emerged as a distinct zero-dimensional derivative of MXenes, exhibiting unique physicochemical and electronic properties that extend their relevance beyond conventional nanomaterial applications. Owing to their ultrasmall size, rich surface termination chemistry, and transition metal-centered electronic structure, MQDs interact dynamically with biological systems and influence immune behavior in a context-dependent manner. This review provides the first comprehensive and focused overview of MQDs as immunomodulatory nanoplatforms for inflammatory control and regenerative medicine. We systematically analyze the structural evolution of MQDs from two-dimensional MXenes, highlighting how quantum confinement, surface chemistry, and redox-active electronic states define their nano-bio interface. Mechanistic insights into immune regulation are discussed through redox-sensitive signaling pathways, inflammasome dynamics, and immune cell reprogramming. Furthermore, experimental evidence demonstrating MQD-mediated modulation of T-cell activity, endothelial immunogenicity, and spatial immune organization in inflammatory, oncologic, and regenerative models is critically evaluated. By integrating materials chemistry, immunological mechanisms, and translational studies, this review outlines emerging nano-strategies for precision immune regulation. Finally, key challenges related to immunosafety, compositional engineering, and clinical translation are addressed, positioning MQDs as a promising and programmable class of immunoactive nanomaterials for future biomedical applications.
Chronic wounds remain a major global health challenge despite substantial advances in biomaterials, regenerative medicine, and wound-care technologies. Current therapeutic strategies are largely based on the assumption that chronic wounds represent impaired or incomplete healing responses and therefore require augmentation of regenerative processes. This paradigm has driven the development of increasingly sophisticated wound dressings incorporating extracellular matrix analogs, growth factors, stem cells, extracellular vesicles, biosensors, and bioelectronic components. However, the clinical impact of these innovations has often fallen short of expectations. In this review, we propose a conceptual framework intended to generate experimentally testable hypotheses rather than provide a definitive mechanistic model. Persistent alterations in immune, stromal, vascular, extracellular matrix, metabolic, mechanical, and microbial networks create interconnected feedback systems that resist transition toward regeneration. From this perspective, successful therapy requires not only stimulation of repair mechanisms but also disruption of the processes that stabilize chronicity. We discuss how advances in systems biology, immunomodulatory biomaterials, bioelectronics, artificial intelligence, and precision medicine support the emergence of adaptive therapeutic interfaces capable of sensing, interpreting, and reprogramming pathological tissue behavior. Unlike previous reviews that primarily summarize emerging wound dressings or regenerative biomaterials, this Review proposes a systems-level conceptual framework in which chronic wounds are interpreted as stable pathological tissue states maintained by multiscale biological memory. This perspective integrates biomaterials, systems biology, artificial intelligence, and tissue-state dynamics into a unified translational model that has not previously been presented in the wound-healing literature. Previous reviews have predominantly focused on the design, biological activity, or clinical performance of individual biomaterials. In contrast, the present Review proposes a systems-level framework that integrates wound biology, biological memory, tissue-state dynamics, artificial intelligence, and adaptive biomaterials into a unified conceptual model for precision wound medicine. This state-based model reframes advanced wound dressings as tools for biological state engineering and provides a translational framework for the future of chronic wound management.
This study aimed to determine the antibacterial efficacy of sodium dichloro-iso-cyanurate (NaDCC) compared to double antibiotic paste (DAP) and calcium hydroxide (CH) against Enterococcus faecalis (E. faecalis). The study utilized a sample of forty-four human single-rooted teeth, which were decoronated and chemo-mechanically prepared. E. faecalis was then inoculated into the teeth for four weeks. The samples were randomly divided into four groups, each receiving a different intracanal medicament: DAP ([Formula: see text]), NaDCC ([Formula: see text]), CH ([Formula: see text]), and a control group treated with sterile water ([Formula: see text]). After a contact time of 28 days, a sample was taken from each root canal with a paper point. The number of colony-forming units was then calculated, and data analysis was performed using Kruskal Wallis and Mann-Whitney tests. All the medicaments had a significantly higher antibacterial effect than the control group ([Formula: see text]). DAP showed a significantly higher antibacterial effect than NaDCC ([Formula: see text]) and CH ([Formula: see text]). NaDCC showed a significantly higher antibacterial effect than CH ([Formula: see text]). The study's results indicate that DAP is the most effective medicament against E. faecalis. However, the study also revealed that NaDCC, a relatively novel substance in endodontics, demonstrated a higher antibacterial efficacy than CH. This suggests that NaDCC could be a promising addition to the range of medicaments used in regenerative procedures.
Erythropoietin (EPO) is a glycoprotein hormone that exerts pro-angiogenic and anti-inflammatory effects. The present study investigated whether this beneficial profile of action is suitable for improving the in vivo performance of nanofat, an emulsified fat derivative that is clinically used in plastic and reconstructive surgery. Repeated intravital fluorescent microscopic analyses showed that EPO-pretreated nanofat significantly accelerates and enhances the vascularization of the implants, as evidenced by an earlier onset of blood perfusion and an increased functional microvessel density when compared to controls. This was associated with a reduced inflammatory response to the implants, as indicated by lower numbers of adherent leukocytes in venules of the host tissue. Histological and immunohistochemical analyses further revealed an improved implant integration with an increased collagen I deposition and a higher density of nanofat-derived CD31⁺/green fluorescent protein (GFP+) microvessels, along with a reduced macrophage and neutrophil infiltration. Nanofat was mechanically generated from subcutaneous adipose tissue of GFP+ C57BL/6J mice and incubated for 1 h in Hank's Balanced Salt Solution with or without EPO (3 IU/mL). The pretreated nanofat was seeded onto dermal substitutes, which were implanted into dorsal skinfold chambers of GFP⁻ C57BL/6J mice and analyzed over 14 days. These findings identify short-term pretreatment with EPO as an effective strategy to boost the vascularization and regenerative capacity of nanofat.
Stromal vascular fraction (SVF)-based therapies and autologous fat grafting have emerged as promising regenerative strategies due to their pro-angiogenic, immunomodulatory, and trophic properties. However, despite encouraging preclinical and clinical findings, therapeutic outcomes remain highly heterogeneous, with marked variability in graft retention and functional efficacy between patients. Increasing evidence suggests that this variability cannot be explained solely by procedural factors or cellular composition, but may also depend on host-related immune and microenvironmental determinants. This review explores the biological mechanisms governing SVF engraftment and introduces the emerging concept of "SVF therapy resistance," defined as the failure of autologous regenerative therapies resulting from maladaptive interactions between transplanted stromal cells and the host tissue environment. Particular attention is given to sterile inflammation, innate immune activation, and early graft-host interactions. Following transplantation, tissue injury and ischemia induce the release of danger-associated molecular patterns (DAMPs), triggering neutrophil recruitment, macrophage activation, complement signaling, and inflammatory remodeling. While controlled inflammatory responses may support tissue repair and angiogenesis, excessive neutrophil activation, neutrophil extracellular trap (NET) formation, persistent pro-inflammatory macrophage polarization, and impaired vascular adaptation may compromise graft survival and regenerative efficacy. The review further discusses how SVF processing, inflammatory priming, stromal cell heterogeneity, and donor-related factors-including obesity, aging, metabolic dysfunction, and chronic inflammation-may influence therapeutic responsiveness. Emerging evidence from mesenchymal stromal cell biology suggests that stromal cells are highly sensitive to inflammatory licensing and microenvironmental cues. Candidate biomarkers and immune profiling strategies capable of identifying responders and non-responders to SVF-based therapies are also reviewed. Finally, these mechanisms are discussed in spinal cord injury, a condition characterized by chronic inflammation and vascular dysfunction. Overall, this review proposes a translational framework linking innate immunity, sterile inflammation, angiogenesis, and stromal cell heterogeneity to the variability of SVF therapy outcomes, highlighting the need for personalized regenerative medicine approaches.
Bioengineered substitutes and three-dimensional (3D) culture models derived from decellularized plant-based materials have gained increasing attention in tissue engineering (TE). Various plant skeletons exhibit biomimetic architectures resembling human tissues, offering readily available, cost-effective, and sustainable platforms for designing hierarchically organized regenerative scaffolds. Decellularized vegetal tissues, including leaves, stems, fruits, and vegetables, display diverse anatomical, mechanical, and vascular features that can closely emulate the native extracellular matrix (ECM). Given the rapid growth of interest in plant-derived scaffolds, this scoping review provides a comprehensive overview of their current state, applications, and future prospects. To the best of our knowledge, a unified summary of plant-based biomaterials for both regenerative medicine and in vitro meat production has not been previously reported. This review discusses the rationale for using vegetal scaffolds, their preparation and decellularization techniques, chemical and structural modification strategies, and biocompatibility evaluations in both in vitro and in vivo settings. Particular emphasis is placed on their applications in tissue regeneration and cellular agriculture, highlighting how their structural diversity and functional adaptability enable tissue-specific applications. Finally, the review addresses key challenges and future directions required to translate these sustainable, next-generation plant-derived scaffolds for unmet healthcare needs in TE and emerging food technologies.
In embryos, intrinsic and extrinsic signals cooperatively shape cellular decisions to form tissues and organs. Developmental engineering seeks to harness insights into the molecular mechanisms governing embryonic development and leverage pluripotent stem cells to enable the synthetic reconstitution of organ-like multicellular systems in vitro, including organoids. These cellular systems can partially emulate the complexity of in vivo organs in terms of structure and function, facilitating disease modeling and regenerative medicine applications. Nonetheless, the field faces challenges, such as ensuring reproducibility and achieving adult-level maturation. In this Review, we discuss liver development in the human embryo and current models that are routinely used for generating liver organoids in vitro as well as their limitations. Next, we discuss how synthetic biology and computational analyses can be integrated to enhance organoids, particularly liver organoids, by promoting vascularization, establishing zonation, refining fate specification and enabling responsiveness to external cues. Together, these approaches pave the way for next-generation multicellular human stem cell-derived systems.
Despite the therapeutic promise of extracellular vesicles (EVs) in regenerative medicine, immunotherapy, and targeted drug delivery, translation to the clinic remains constrained by persistent manufacturing bottlenecks, including low yields, poor purity-recovery trade-offs, inconsistent cargo composition, variable product quality, and limited scalability. Additive manufacturing (AM) technologies present new strategies to overcome these hurdles by enabling precise control over biomaterial composition, microarchitecture, and spatial organization across three pipeline areas: EV production, isolation and purification, and scaffold-based delivery. This review examines AM applications across those EV production pipeline nodes. We analyze how AM variables - matrix stiffness, scaffold geometry, shear conditions, and crosslinking chemistry - affect EV yield, cargo composition, membrane integrity, and functional potency. By linking engineering approaches with biological considerations, we highlight AM's potential to unify manufacturing efficiency with therapeutic performance, while addressing limitations in throughput, standardization, and translational readiness.
This study explores the influence of melatonin and SRD5A2 on the proliferation and migration of human hair follicle stem cells (hHFSCs), which are vital in the treatment of Androgenic alopecia (AGA), wound healing, and regenerative medicine. Melatonin interacts with various stem cells, including hHFSCs, in multiple ways. In this study, SRD5A2-silenced hHFSCs were established using shRNA and subsequently cultured with melatonin. The effects on cell proliferation and migration were assessed using Cell Counting Kit-8, EdU-555, and the Transwell Migration Assay, while stemness was determined by assessing CD34 expression by immunohistochemistry. In addition, melatonin receptor 1 (MT1) and 5-alpha-reductase (5-αR) were analyzed using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence microscopy. The results demonstrated that SRD5A2 silencing and melatonin treatment significantly enhanced the proliferation and migration of hHFSCs without causing cell differentiation. Furthermore, this combination led to increased MT1 expression and decreased 5-αR levels. These findings suggest that both melatonin and 5-αR are critical in regulating hHFSCs' proliferation and migration, with SRD5A2 potentially playing a role in melatonin metabolism by regulating MT1 expression. However, the precise mechanism by which melatonin downregulates 5-αR remains to be elucidated.
Modeling musculoskeletal diseases such as osteoporosis requires in vitro platforms that accurately reproduce key features of human bone biology. Conventional 3D culture systems provide valuable insight into cell-cell and cell-matrix interactions, but their dependence on costly materials, bioprinters, or specialized infrastructure limits their broader adoption. Here, we describe a robust and cost-effective protocol for generating 3D bone constructs using human-derived osteocytes embedded in GelMA hydrogels, supplemented with decellularized extracellular matrix (dECM) obtained from donated femoral heads. This pipetting-based method enables the fabrication of reproducible, bone-like constructs at physiological temperature (37 °C), using standard laboratory equipment. The resulting constructs maintain high viability and structural integrity, supporting downstream applications such as immunofluorescence imaging and molecular assays. The incorporation of patient-derived dECM enhances translational relevance by better reflecting human bone remodeling and disease progression. This approach provides an accessible, scalable platform for drug testing, regenerative medicine, and mechanistic studies of bone biology. Overall, the protocol offers a practical alternative to high-cost bioprinting techniques and can be readily adapted to other tissue-specific dECM sources.
Engineering skeletal muscle tissues with controllable bioactuation is essential for advances in biohybrid robotics, regenerative medicine, and high-fidelity disease models. Mechanical stimulation has been shown to replicate the effects of physical exercise, while magnetic stimulation allows the manipulation of cells in a non-invasive manner. Here, a platform based on Helmholtz coil pair for magnetic stimulation is developed. To focus the stimulation through mechanotransduction, magnetic microspheres (MMS) were conjugated to myoblast integrins at defined MMS-to-cell ratios, functioning as microscale actuators under alternating magnetic fields. Exposure of non-labeled C2C12 cells to ∼2.9 mT, 50 Hz magnetic fields enhanced myogenic differentiation, with significantly increased fusion indices after 10 and 30 min of daily stimulation. Remarkably, MMS-labeled cells (1:1 ratio) required only 2 min of daily stimulation to achieve comparable enhancement, demonstrating the efficacy of targeted microactuation. Mechanistic analysis revealed elevated nuclear localization of Yes-associated protein (YAP) in stimulated MMS-labeled cells, confirming activation of force-dependent signaling pathways. qRT-PCR analysis further supported these findings, showing stimulation-associated upregulation of myogenic genes, particularly in MMS-labeled cells. The integration of cell labeling with dynamic magnetic fields offers new opportunities for remote stimulation strategies in biofabrication, muscle tissue engineering, and therapeutic approaches for muscle tissue.
Systemic delivery of messenger RNA (mRNA) to target tissues and cells using lipid nanoparticles (LNPs) holds transformative potential for gene therapy. However, most clinically validated LNP exhibit strong liver tropism, and redirecting their organ specificity without redesigning entirely new chemistries remains challenging. Here we present a ligand-mediated lipid reprogramming approach that repurposes chemically defined, liver-tropic, ionizable lipids (lipidoids) for mRNA delivery beyond the liver. From a library of 90 degradable lipidoids, we identified 2-t6b as a potent liver-targeting platform. By site-specific displaying of small molecule ligands onto 2-t6b headgroup, we engineered a series of reconfigured lipidoids that achieve lung-specific targeting while retaining the parent delivery scaffold. Ligand7-2-t6b-lipid-functionalized LNP achieved over 200-fold higher mRNA translation in the lungs compared to the parent liver-tropic LNP. Proteomics and molecular docking analysis revealed enhanced binding of the modified lipid to vitronectin, a serum glycoprotein that improves integrin binding and thus promotes cellular uptake and translation efficiency. Ligand-mediated 2-t6b/ligand7 LNPs achieved outperformed efficacy and therapeutic potential in lung-specific genome editing relative to SORT-constructed 2-t6b LNP system. Our modular reprogramming strategy provides a generalizable framework to upgrade existing liver-biased LNPs into lung-selective mRNA carriers, advancing next-generation tissue-specific mRNA therapies for gene editing, protein replacement therapy, and regenerative medicine.
The rising global prevalence of chronic conditions, notably obesity and type 2 diabetes, demands innovative approaches to mitigate their health and economic impacts. Complications, including neuropathy and chronic limb-threatening ischemia (CLTI), dramatically increase the risk of lower limb amputation, cardiovascular events, and cerebrovascular events, underscoring the urgent need for effective interventions. Emerging neuromodulation and regenerative strategies provide novel approaches to addressing diabetes-related complications. High-frequency (10-kHz) spinal cord stimulation demonstrates marked pain relief and sensory improvement in patients with refractory painful diabetic neuropathy. Peripheral focused ultrasound, including splenic-targeted stimulation, shows promise in reducing systemic inflammation, accelerating wound repair, and enhancing vascular function. Remote ischemic conditioning leverages brief controlled ischemic reperfusion cycles to enhance microcirculation and promote diabetic foot ulcer (DFU) healing. In severe cases, surgical techniques such as tibial transverse transport and lateral tibial periosteum distraction stimulate angiogenesis and enhance distal limb perfusion. Integrated wound care protocols, incorporating these procedures alongside debridement, negative pressure wound therapy, and skin grafting, may further optimize outcomes. Collectively, these therapies address both local and systemic pathophysiology, frequently producing physiologic effects at sites distant from the primary intervention. These seemingly disparate therapies represent a single unifying concept: generating a physiologic effect at locations remote from the primary target. This systematic approach, engaging neural, vascular, and immune pathways, may be key to improving outcomes in DFUs and CLTI. Early clinical data appears promising; however, larger randomized trials are required to validate efficacy, refine patient selection, and determine optimal integration with standard care. If confirmed, these strategies may shift management toward patient-centered, regenerative interventions that preserve limbs, reduce recurrence, and enhance quality of life for the expanding global patient population. Further research is warranted to confirm or refute these early promising physiologic effects.
The development of functional human vasculature is essential for tissue engineering, disease modeling, and regenerative medicine. Conventional differentiation protocols of vascular lineages often exhibit lineage heterogeneity and limited control over cellular ratios. Here, we describe a protocol for generating vascular organoids (VOs) via orthogonal forward programming of hPSCs. By utilizing doxycycline-inducible activation of the transcription factors ETV2 and NKX3.1, hPSCs are rapidly directed toward endothelial and mural cell lineages, respectively. This strategy enables the assembly of VOs with precisely tunable cellular compositions within six days. When combined with fluorescent reporter lines (PECAM1-mRuby3 and ACTA2-EGFP), vascular networks can be visualized in real time without the need for tissue clearing or immunostaining. We detail procedures for stable cell line engineering, 3D organoid assembly, in vitro angiogenesis assays for drug screening, and in vivo transplantation under the mouse kidney capsule to form perfusable human vasculature. This platform provides a flexible, standardized, and scalable tool for investigating vascular biology, modeling inherited vasculopathies, and enhancing the vascularization of co-transplant tissues.
Oral potentially malignant disorders (OPMDs) represent a spectrum of lesions with an increased risk of malignant transformation into oral cancer. Traditional pharmacological interventions such as corticosteroids and immunomodulators have shown variable success. Recently, platelet-rich plasma (PRP), known for its regenerative and anti-inflammatory properties, has emerged as a novel therapeutic option in the management of OPMDs. This review aimed to systematically review and analyse the existing literature on the efficacy of PRP in the management of OPMDs compared to conventional treatment modalities. A comprehensive search was conducted across electronic databases including PubMed, Scopus, Embase, and Google Scholar without year restrictions, limited to English-language studies. Eligible studies included randomised controlled trials (RCTs), evaluating PRP for OPMDs. Inclusion criteria were adults aged 18 years or older diagnosed with OPMDs, treated with PRP, and not undergoing concurrent treatments. Risk of bias was assessed using the Cochrane Risk of Bias RoB 2.0 tool. Data synthesis was done narratively, focussing on lesion response, histological regression, and clinical improvement. Preliminary findings suggest that PRP shows promising efficacy in improving clinical and histological outcomes in patients with OPMDs, particularly oral lichen planus. Compared to conventional treatments such as corticosteroids, PRP demonstrated favourable results in reducing lesion size, improving symptoms, and promoting epithelial healing with minimal adverse effects. PRP appears to be an effective adjunct or alternative to conventional therapy in the management of OPMDs. While early results are encouraging, well-designed large-scale RCTs are needed to establish standardised protocols and validate its long-term efficacy and safety.
Vital pulp therapy (VPT) in mature permanent teeth with irreversible pulpitis represents a paradigm shift toward preserving pulp vitality. Advanced platelet-rich fibrin plus (A-PRF+) is a bioactive scaffold capable of releasing high concentrations of growth factors; however, its concentration-dependent effects on inflamed pulp-derived stem cells remain unclear. This study aimed to evaluate the concentration-dependent effects of A-PRF+ and identify a biologically favorable concentration range for supporting the functional activity of dental pulp stem cells isolated from teeth with irreversible pulpitis. IP-DPSCs were isolated from inflamed pulp tissues and characterized by flow cytometry and trilineage differentiation assays. A-PRF+ was prepared using the low-speed centrifugation concept (LSCC). Cells were exposed to sequential dilutions of A-PRF+ extracts (100%, 50%, and 25%). Cell metabolic activity was assessed using the MTT assay. Cell migration was evaluated using a scratch assay, and wound closure rates were quantified with ImageJ software. Statistical analysis was performed using one-way or two-way ANOVA with appropriate post-hoc tests. Flow-cytometric analysis showed high expression of MSC-associated markers (CD44, CD73, and CD90) and negligible expression of hematopoietic markers, while differentiation along osteogenic, chondrogenic, and adipogenic lineages was observed following induction culture. A-PRF+ exhibited a biphasic concentration-dependent effect. The 25% extract significantly enhanced cell migration, achieving a wound closure rate of 27.09 ± 4.03%, compared with 13.16 ± 4.50% in the 100% extract group (p = 0.013). Undiluted A-PRF+ showed inhibitory effects on both migration and metabolic activity. A-PRF+ exerted concentration-dependent effects on IP-DPSCs, with diluted preparations supporting greater migration and metabolic activity than undiluted extracts. These findings suggest the existence of a biologically favorable concentration range for A-PRF+ and provide a rationale for further investigation of concentration optimization in regenerative endodontic applications.
Conventional chemotherapeutic agents are frequently limited by off-target toxicity and suboptimal therapeutic outcomes. Nanomedicines utilizing cell membrane camouflage provide a promising strategy for precise drug delivery and multimodal combination therapy. Herein, we designed a tumor-microenvironment-responsive cell-membrane-coated nanocomposite (designated as ZnO2@MO-D@Mn-CeO2@CM), which consists of a zinc peroxide (ZnO2) core encapsulated within a drug-loaded mesoporous organosilica (MO-D, where D is doxorubicin for the 4T1 breast cancer model and daunorubicin for the C1498 leukemia model) layer, with the mesopores gated by manganese-doped cerium oxide (Mn-CeO2) nanoparticles, and coated with a homologous cell membrane (CM). This nanocomposite enables the release of therapeutic components under acidic conditions and in the presence of elevated glutathione (GSH). It facilitates a combination therapy by integrating chemotherapy, enhanced chemodynamic therapy (CDT), ferroptosis induction, and immunomodulation. Our results demonstrate that this nanocomposite effectively suppresses the progression in 4T1 solid tumor and C1498 leukemia models, demonstrating its potential as a robust combinatorial strategy.
Ankle sprain is among the most frequent musculoskeletal injuries affecting the anterior talofibular ligament (ATFL). Current management emphasizes symptom relief rather than regeneration, often resulting in prolonged recovery and recurrent instability. Wharton's Jelly-derived mesenchymal stromal cells (WJ-MSCs) have emerged as promising candidates for ligament repair, particularly when primed with growth factors such as insulin-like growth factor-1 (IGF-1) and connective tissue growth factor (CTGF). A two-phase study was conducted. In vitro, WJ-MSCs were stimulated with IGF-1, CTGF, or sequential IGF-1/CTGF, and assessed for MSC marker expression, collagen gene transcription, and protein secretion. In vivo, grade II ATFL sprain was surgically induced in Wistar rats (n = 36), followed by local administration of growth factor-stimulated WJ-MSCs. Functional recovery was evaluated via swelling, locomotor activity, spontaneous rearing, and gait analysis. Histological assessment of ankle joints and major organs was performed on post-operative day (POD) 28. Sequential IGF-1/CTGF stimulation synergistically enhanced Col1a1 expression (~ 8.2-fold vs. control, p < 0.001) and collagen I secretion (~ 19.5 ng/mL, p < 0.01). In vivo, MSCIGF+CTGF treatment accelerated oedema resolution, normalized gait symmetry by POD 6, and restored locomotor to near-baseline by POD 14. Histology revealed near-complete collagen alignment and minimal scarring in treated ankles, with no fibrotic changes in liver or brain and only mild transient pulmonary alterations. Sequential IGF-1/CTGF stimulation significantly augments the regenerative efficacy of WJ-MSCs, promoting structural restoration and multidimensional functional recovery in ligament injury. Local administration of dual-factor-programmed WJ-MSCs represents a safe and translationally relevant strategy for enhancing ATFL healing, with potential applicability to broader orthopaedic rehabilitation.
De Quervain's tenosynovitis (DQT) is a painful wrist condition that impairs daily activities. Corticosteroid (CS) injections are commonly used for symptom relief, but their effects may diminish over time. Platelet-rich plasma (PRP) has emerged as a regenerative alternative that promotes tissue healing rather than merely suppressing inflammation. This systematic review and limited meta-analysis compare the efficacy and safety of PRP versus CS injections in DQT. A limited meta-analysis was chosen due to the high heterogeneity between studies (I2 = 98.7%). A comprehensive literature search identified six studies comparing PRP and CS injections. Pain and functional outcomes were assessed using the Visual Analog Scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, and Mayo Wrist Score (MWS). Statistical significance was analyzed, with follow-up durations ranging from 2 weeks to one year. The risk of bias was evaluated using Cochrane and ROBINS-I tools. Both PRP and CS significantly reduced pain; however, PRP provided superior long-term relief. The VAS scores improved in all studies, with PRP showing significantly greater reduction at 6 months (p < 0.001). A study also found better QuickDASH-9 scores in PRP-treated patients (p < 0.01). The PRP had fewer complications than CS p=0.026, reinforcing its safety advantage. The PRP and CS effectively reduce pain, but preliminary evidence suggests PRP may offer longer-lasting symptom relief than corticosteroids; however, findings are limited by small sample sizes, study heterogeneity, and low certainty of evidence. Further high-quality trials with standardized PRP protocols are warranted.
Type 1 diabetes (T1D) impacts more than 9 million individuals globally. Despite a century since the isolation and clinical introduction of insulin, exogenous insulin injections remain the primary form of treatment for T1D. While continuous glucose monitoring systems and optimized insulin delivery reduce life-threatening hypoglycemic events, they do not provide a permanent cure. Transplantation of pancreatic islets offers a potential long-term solution. Recent advances in stem cell-derived islets (SC-islets) have shown remarkable promise in both clinical and research settings. This article highlights recent clinical reports in the use of SC-islets to restore islet function and their versatility as a platform for disease modeling and drug screening while emphasizing current strategies aimed at overcoming their limitations and enhancing their therapeutic potential. We also discuss exciting emerging approaches that expand investigations beyond pancreatic endocrine cells to encompass nonendocrine cell types in the pancreas, offering a unique bird's-eye view into pancreatic biology and insights into cellular cross talk in health and disease. Our aim is for this article to serve as a resource for up-to-date advances in SC-islet research and to highlight novel platforms for studying diabetes pathogenesis in unprecedented ways, accelerating progress toward a permanent cure. Stem cell-derived islets provide a renewable source of insulin-producing cells for studying diabetes and developing regenerative therapies. Stem cell-derived islets are still functionally immature in comparison with primary human islets, underscoring the need for deeper insights into β-cell biology to improve their fidelity. Nonetheless, they serve as a powerful platform for diabetes disease modeling. Emerging technological advances, including spatial multiomics and multicellular organoid development, are revealing key roles for non-β-cell and nonislet cell types in pancreatic diseases. Integrating these emerging tools is critical for broadening our understanding of diabetes pathophysiology and may enable us to view the disease from previously unexplored perspectives.