Search Results (278)

The amniotic membrane is widely recognized in regenerative medicine due to its rich content of extracellular matrix proteins and growth factors that confer anti-inflammatory and pro-regenerative properties. However, its rapid degradation restricts its standalone clinical use. To overcome these limitations, we developed biofilms by incorporating decellularized human amniotic membrane matrix (dHAM) into polycaprolactone (PCL) and polyvinylpyrrolidone (PVP) matrices using spin-coating. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were used to evaluate film biocompatibility through cell viability, proliferation, and wound healing migration assays. Surface characterization was performed using contact angle measurements, Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy, and scanning electron microscopy. Soluble dHAM extracts (4–6 mg/mL) significantly enhanced BM-MSC proliferation at 48 h compared to controls (p ≤ 0.01 and p ≤ 0.0001). Both PCL-dHAM and PVP-dHAM biofilms exhibited high cell viability (>90%) and improved initial adhesion. Notably, dHAM incorporation significantly increased wound closure rates at 24 h, reaching 98.47% for PCL-dHAM and 93.13% for PVP-dHAM, compared to 76.56% and 64.20% for pure polymers (p = 0.0001). All scaffolds maintained hydrophilic surfaces (<90°), favorable for cell interaction. The integration of dHAM into PCL and PVP by spin-coating produces biofilms biocompatible with enhanced regenerative potential, representing promising candidates for wound healing applications. In conclusion, these coatings support BM-MSC adhesion, proliferation, and migration, while significantly accelerating wound closure, underscoring their value as advanced bioactive coatings for regenerative medicine. Full article

Background/Objectives: Chorioamnionitis (CA), an inflammation, with or without infection, involving the amniotic fluid, placenta, fetal membranes or decidua, can significantly impact fetal and neonatal development. This study aimed to determine the prevalence of chorioamnionitis and confirm its correlation with neonatal morbidity and mortality, in a single tertiary center. Methods: This observational, retrospective study was conducted over three years (2019–2021) in a tertiary neonatal intensive care unit, examining 80 preterm infants born at 23–28 weeks of gestation. Spearman rank correlation, χ² tests, and multivariate logistic regression were used to assess associations between chorioamnionitis exposure and neonatal outcomes. Results: Among the 80 newborns analysed, clinical chorioamnionitis was identified in 12 preterm infants, while 65 (81.3%) presented histological chorioamnionitis. No significant association was found between histological chorioamnionitis stage and gestational age at birth (Spearman ρ = −0.15, p = 0.195). Premature rupture of membranes was significantly more frequent in the CA-exposed group (46.2% vs. 13.3%, p = 0.019). In unadjusted analyses, histological chorioamnionitis exposure was associated with higher rates of adverse neonatal outcomes, including early-onset sepsis (46.2% vs. 26.7%), intraventricular haemorrhage (73.8% vs. 60.0%), bronchopulmonary dysplasia (15.9% vs. 6.7%), and retinopathy of prematurity (11.3% vs. 0.0%); however, most of these differences did not reach statistical significance. After multivariate adjustment, histological chorioamnionitis remained independently associated with severe respiratory distress syndrome (adjusted OR 25.84, 95% CI 2.49–268.44, p = 0.006). Mortality was numerically lower in the CA-exposed group (27.7% vs. 46.7%); however, this difference did not reach statistical significance (p = 0.216). Conclusions: Histological chorioamnionitis was independently associated with severe respiratory distress syndrome. Associations with early onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity were observed in unadjusted analyses but were not independently significant after adjustment for perinatal confounders. No significant association was found between chorioamnionitis and neonatal mortality. While clinical diagnostic criteria for chorioamnionitis demonstrated good specificity, their poor sensitivity underscores the urgent need for improved diagnostic tools, including routine histological examination of the placenta. Full article

Background/Objectives: Acute myocardial infarction (AMI) remains a major cause of global morbidity and mortality and is a leading factor in the development of heart failure. This study investigated the regenerative potential of decellularized human amniotic membrane (HAM) and Wharton’s jelly (WJ) in a rat model of left ventricular dysfunction induced by acute myocardial infarction (AMI). Methods: Twenty-three rats underwent left anterior descending coronary artery ligation and were randomized into three groups: control (saline), WJ (decellularized WJ), and HAM (decellularized HAM). Results: After 30 days, echocardiographic, histopathological, and immunohistochemical assessments were performed. No significant differences in ventricular function were observed among groups. However, the HAM-treated group showed a significant reduction in myocardial fibrosis compared with the control (p = 0.009), suggesting attenuation of post-infarction remodeling. Despite the absence of measurable functional recovery, HAM demonstrated potential to promote more favorable tissue organization. Study limitations include the lack of a sham-operated group, short follow-up period, and absence of quantitative decellularization validation. Conclusions: Overall, the results indicate that decellularized HAM may act as a structural modulator of myocardial remodeling, warranting further studies with longer follow-up and combination approaches, such as cell-based or growth factor-enhanced therapies. Full article

Preterm birth is a major cause of neonatal morbidity and mortality, and many spontaneous cases remain idiopathic. Increasing evidence suggests that intrauterine inflammation may occur in the absence of detectable infection, leading to the recognition of sterile intrauterine inflammation as an important mechanism contributing to threatened preterm labor and spontaneous preterm birth. This review summarizes current knowledge regarding the role of damage-associated molecular patterns (DAMPs), alarmins, pattern recognition receptors, inflammasome activation, cellular senescence, and pyroptosis in the initiation of sterile inflammatory pathways associated with labor. Key mediators including HMGB1, IL-1α, fetal cell-free DNA, platelet-activating factor, and S100 proteins appear to promote inflammatory activation within fetal membranes and the amniotic cavity. The review also discusses the emerging contribution of fetal immune activation, maternal–fetal immune dysregulation, maternal microchimerism, and epigenetic mechanisms to idiopathic preterm birth. Current diagnostic and therapeutic options remain limited, and no targeted treatment for sterile intrauterine inflammation has yet been established. Future approaches may include precision biomarkers, multiomics-based risk stratification, targeted immunomodulatory therapies, and modulation of maternal–fetal immune interactions. Improved understanding of sterile inflammatory mechanisms may ultimately support development of personalized strategies to prevent preterm birth and improve perinatal outcomes. Full article

Chronic wound management remains a significant clinical challenge, requiring adaptive therapeutic approaches to achieve wound closure that nonetheless frequently prove fruitless. Balancing the initial pro-inflammatory response with debris removal and tissue rebuilding remains elusive in most cases, leading to pain, drastic quality-of-life deterioration, and, eventually, amputation. Meanwhile, patient adherence is an overarching theme. Furthermore, non-surgical alternatives that effectively promote tissue rebuilding are essential for patients seeking to avoid further invasive procedures. We report a patient with a recalcitrant ulcer managed using human amniotic membrane dressing (hAM-pe) and a bovine collagen matrix (BCM) in spatially distinct areas as an intra-patient control. Methodology included clinical monitoring and ad hoc molecular and histological analyses to assess inflammatory markers and tissue architecture. Following 59 days of observation, the superior evolution of the hAM-pe-treated zone led to the clinical decision to extend hAM-pe treatment over the adjacent BCM area, resulting in total wound closure. The hAM-pe-treated site demonstrated accelerated closure and clinical resolution of inflammation without the presence of a granulomatous response. Molecular analysis revealed downregulated pro-inflammatory mediators (IL-1β, TNF-α, CXCL-10) and upregulated markers associated with angiogenesis (VEGF, CD34) and tissue repair (Arginase-1). In this case, the non-surgical hAM-pe treatment was associated with a favorable healing trajectory, characterized by superior inflammation resolution and enhanced tissue organization (collagen type I/III maturation). While these descriptive findings suggest the potential advantages of amniotic membrane dressings in promoting advanced tissue repair, they remain limited to this individual observation. Further research in larger cohorts is required to validate these mechanisms. Full article

Purpose: To evaluate the clinical efficacy and safety of eye drops containing lyophilized amniotic membrane (AM) in the treatment of dry eye disease (DED), with a focus on tear film stabilization and epithelial–immune balance. Methods: In this prospective cohort study, 40 patients (80 eyes) with DED were followed over six visits. The primary outcome was tear break-up time (TBUT). Secondary outcomes included corneal and conjunctival staining graded by the Oxford scale, meibomian gland parameters, corneal sensitivity (Cochet–Bonnet esthesiometry), best-corrected visual acuity, intraocular pressure (IOP), and Schirmer I test. Continuous variables were analyzed using repeated-measures ANOVA with Greenhouse–Geisser correction and Bonferroni post hoc testing; ordinal outcomes were analyzed using the Friedman test with Dunn–Bonferroni correction. Results: TBUT increased significantly in both eyes (OD: +5.3 s; OS: +4.9 s; both p < 0.001; ηp² ≈ 0.33). Corneal and conjunctival staining scores decreased (p < 0.001), meibomian gland quality and expressibility improved (p < 0.001), and corneal sensitivity increased (p < 0.001), while visual acuity and IOP remained stable. Schirmer I values showed no significant change. The combined pattern of changes (TBUT ↑, staining ↓, meibum/expressibility ↑, sensitivity ↑) indicates tear film stabilization and ocular surface improvement with a preserved safety profile. Conclusions: Lyophilized AM eye drops significantly prolong TBUT and improve clinical signs of DED, presumably by restoring the extracellular matrix (ECM) niche and the heavy-chain hyaluronan/pentraxin 3 (HC-HA/PTX3) complex, reducing proteolytic burden, and promoting a pro-resolving immune balance, with potential neurotrophic effects. These findings support the adjunctive use of AM-derived eye drops within contemporary TFOS DEWS II-based management algorithms for dry eye disease. Full article

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited disorder characterized by extreme epithelial fragility and progressive cicatrization, frequently leading to severe ocular surface disease and early visual impairment. Surgical interventions such as ocular surface reconstruction (OSR) in childhood are often delayed because of anesthetic risks and concerns regarding recurrence. Consequently, the effectiveness of OSR, including amniotic membrane transplantation (AMT), and its impact on visual development remain poorly documented. Methods: We report a case series of two pediatric patients (three eyes) with genetically confirmed RDEB who underwent single-step OSR using AMT. Clinical outcomes, long-term visual acuity, perioperative management, and histopathological findings were evaluated. Results: Ocular manifestations included corneal epithelial damage, symblepharon, and pseudopterygium extending over the cornea. One patient underwent symblepharon lysis, superficial keratectomy, and AMT onto the bare sclera in the right eye at age 4 and in the left eye at age 8, both under intubated general anesthesia. The other patient underwent the same procedure in the right eye at age 6. Best spectacle-corrected visual acuity improved from ≤20/300 to 20/30 in all eyes, and pupillary zone clarity was maintained during the follow-up period (up to 6 years). Histopathology confirmed pseudopterygium with squamous metaplasia, goblet cell loss, and fibrovascular stroma. Safe general anesthesia was achieved through meticulous multidisciplinary perioperative planning involving anesthesiologists, dermatologists, and pediatricians. No systemic complications related to anesthesia or perioperative management were observed. Conclusions: Single-step OSR with on-lay AMT can restore and preserve visual function in pediatric RDEB. Early surgical intervention may prevent profound amblyopia and provide durable ocular surface stability. A multidisciplinary approach enables safe general anesthesia and perioperative management. Full article

Eyelid anomalies represent a relevant cause of corneal injury, including epithelial instability and recurrent erosions up to progressive stromal thinning, corneal melt, and, in severe cases, perforation leading to permanent visual impairment. Correction of eyelid dysfunction is the first step in managing these lesions. However, corneal damage may persist or progress despite adequate eyelid treatment. Therefore, a corneal surgical approach is necessary to preserve ocular surface integrity and visual function. This review synthesizes literature published between 2008 and 2025 on corneal complications secondary to eyelid anomalies and postoperative eyelid procedures. We analyzed the mechanisms of eyelid-induced corneal injury, indications for surgical treatment, and corneal surgical strategies, from surface-stabilizing techniques to tectonic interventions. Entropion and ectropion are the most common eyelid abnormalities associated with mechanical trauma and exposure-related corneal disease. Although definitive eyelid correction is necessary for corneal recovery, persistent epithelial defects, stromal thinning, corneal melt, and perforation frequently require corneal surgical management. Surface-stabilizing procedures, such as amniotic membrane transplantation, are effective in early disease stages, whereas progressive stromal defects necessitate tectonic approaches such as lamellar patch grafting or therapeutic keratoplasty. Interventions aimed at visual rehabilitation should be postponed until sustained ocular surface stability has been achieved. Effective management of eyelid-related corneal damage requires both eyelid surgical correction and corneal management. Close collaboration between corneal and oculoplastic surgeons helps achieving good anatomical outcomes and long-term ocular surface stability. Full article

Acute myocardial infarction (AMI) results from a lack of oxygen supply to the myocardium, leading to the loss of cardiomyocytes and their replacement with fibrotic scar tissue. This process is closely associated with the development of heart failure. Regenerative medicine has emerged as a promising strategy to enhance treatment outcomes in severe cases of heart failure. This study aimed to evaluate myocardial regeneration after AMI using a biomaterial composed of mononuclear stem cells and human amniotic membrane. A total of 120 Wistar rats were subjected to experimentally induced AMI. On the 7th day post-infarction, rats with an ejection fraction of <50% on echocardiography were randomized into four groups: (1) control; (2) stem cells; (3) amniotic membrane; and (4) amniotic membrane combined with stem cells. On the 30th day, the surviving animals underwent a second echocardiographic evaluation and were subsequently euthanized. The group treated with the combination of amniotic membrane and stem cells showed reduced systolic and diastolic ventricular volumes. Histological analysis revealed that these animals exhibited less fibrosis and a lower percentage of type I collagen. Based on the results of the study, it was concluded that the combination of human amniotic membrane and mononuclear stem cells decreased ventricular volumes and myocardial fibrosis, suggesting more favorable ventricular remodeling in this experimental model. Full article

DRG adhesion is a key pathological feature of failed back surgery syndrome and a major cause of neuropathic pain. DRG, or epidural adhesion, commonly results from spinal surgery, leakage of disk material into the epidural space, or inflammation. To better mimic this clinical condition, we developed a novel and reliable animal model of DRG adhesion-induced neuropathic pain. Using this model, we investigated the therapeutic potential and underlying mechanisms of CLARIX FLO, a sterile, particulate human amniotic membrane and umbilical cord tissue product. Our results demonstrate that CLARIX FLO exerts significant analgesic and anti-inflammatory effects in the DRG adhesion model. The application of CLARIX FLO to the injured DRG markedly attenuated mechanical allodynia. CLARIX FLO treatment also reduced outer sheath thickening, suppressed the inflammatory microenvironment, and decreased hypersensitivity of isolectin B4-positive neurons. Mechanistically, CD44 was identified as a potential downstream mediator of CLARIX FLO. Furthermore, a high dose of HC-HA/PTX3, the key bioactive component of CLARIX FLO, effectively reversed mechanical allodynia and inflammation. Notably, CLARIX FLO inhibited the overexpression of TNF-α and TRPV1 adhering to the DRG. In this study, we demonstrated that CLARIX FLO effectively alleviates DRG adhesion-induced neuropathic pain through a CD44–TRPV1-dependent mechanism. Full article

The regeneration and repair of scarless skin tissue remain a significant challenge for full-thickness wounds. Traditional wound management approaches, particularly passive healing through scabbing and conventional mechanical debridement, are frequently associated with significant pain, high infection risks, and abnormal scar formation, often failing to support the regeneration of skin appendages like hair follicles. In recent years, collagen-based scaffolds have been widely adopted in tissue-engineered skin substitutes owing to their favorable biocompatibility. However, their simplistic, single-component architecture inherently lacks the dynamic, cell-instructive microenvironment found in native skin, which not only compromises the long-term survival and functional integration of seeded cells but also directly leads to insufficient reconstruction of the dermo-epidermal junction, thereby impairing skin barrier function and ultimately limiting overall regenerative efficacy. In this study, we propose a biomimetic multilayer composite scaffold system in which decellularized amniotic membrane matrix (AM) is combined with fibroblast-laden collagen gel (FCG) and seeded with epidermal stem cells (EpiSCs). This bionic skin (denoted as AM-FCG-EpiSCs) is designed to achieve hierarchical regeneration of full-thickness skin defects. Compared with injured skin treated with Moropicin ointment, the injured skin treated with AM-FCG-EpiSCs healed more quickly and regenerated appendages like hair follicles without scarring. The results show that the biomimetic structure of AM-FCG-EpiSCs can mediate dynamic cell–cell interactions and regulate the microenvironment. This breakthrough overcomes the dual challenges of scar suppression and functional restoration in full-thickness skin regeneration, offering an innovative solution for translational medicine. Full article

Cartilage is an important yet vulnerable tissue with limited self-healing capacity, where damage often progresses to joint degeneration, which eventually leads to severe osteoarthritis (OA). Current tissue engineering strategies focus on biocompatible scaffolds for cartilage regeneration, particularly amnion (or amniotic membrane), emerging as a promising biomaterial due to its wide availability, low immunogenicity, and naturally derived microenvironment that is advantageous for cartilage regeneration. This systematic review aims to evaluate the existing evidence on the efficacy of amnion as a tissue scaffolding material for cartilage regeneration in both preclinical and clinical studies. Using terms such as “cartilage damage”, “cartilage injuries”, “amnion” and “amniotic membrane”, 19 relevant studies were identified across three major databases (PubMed, Scopus and Web of Science) until 25 December 2025. All preclinical and clinical studies that utilized amnion for cartilage repair or as cartilage tissue engineering scaffolding materials were included. Evidence quality was assessed using the OHAT and MINORS risk of bias tool. This study is prospectively registered in the PROSPERO database under the ID 1178444. The findings consistently indicate that amniotic scaffolds, regardless of processing methods or cell seeding, yield favorable outcomes without adverse effects across different species. In vitro analysis revealed that treatment groups with amnion show better cell attachment, viability, and proliferation, and higher content of cartilage-related markers expressed by the seeded cells, either chondrocyte, bone marrow-derived mesenchymal stem cells (MSCs), adipose tissue-derived MSCs, placenta-derived MSCs, umbilical cord-derived MSCs, amniotic MSCs or amniotic epithelial cells. In in vivo and ex vivo studies, amnion-treated groups demonstrated improved quality of the treated cartilage, with better integration, as indicated by higher histological scores and the presence of type II collagen (COL-II). There was an inconsistency in the reporting of cartilage defect dimensions in the in vivo models across the different studies. Nevertheless, the outcome measurements were consistently reported with histological analysis, with or without International Cartilage Repair Society (ICRS) scoring and immunohistochemistry (IHC) analysis, across the studies. Clinically, most subjects show improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Sports and Recreation score and KOOS Quality of Life score, as well as reduced Visual Analogue Scale (VAS) average and maximum pain scores. In conclusion, preclinical and clinical studies support amnion as an ideal scaffold material for cartilage tissue engineering and regeneration. Future research should focus on optimizing and standardizing amnion scaffold preparation at a production scale to facilitate the translation of these positive outcomes into clinical applications. This study is funded by the Ministry of Higher Education Malaysia via Prototype Research Grant Scheme (PRGS/1/2021/SKK01/UM/02/1) and UM International Collaboration Grant—2023 SATU Joint Research Scheme Program: ST007-2024. Full article

Autoimmune ocular surface diseases represent a complex group of disorders in which systemic immune dysregulation triggers chronic inflammation, epithelial dysfunction, and progressive tissue fibrosis. Systemic lupus erythematosus, primary Sjögren’s syndrome, and ocular cicatricial pemphigoid are the principal entities linking systemic autoimmunity to ocular surface pathology. These conditions share convergent mechanisms—including dysregulated cytokine signaling (IFN-I, IL-6, and IL-17), complement activation, and epithelial–mesenchymal transition—culminating in tear film instability and visual impairment. Recent advances in molecular immunology and omics profiling have elucidated disease-specific pathways and identified actionable therapeutic targets. Conventional immunosuppressants such as corticosteroids and cyclosporine remain fundamental, yet emerging biologics targeting BAFF, IFNAR, and JAK/STAT signaling—alongside regenerative strategies employing mesenchymal and induced pluripotent stem cells—are transforming disease management. Parallel innovations in amniotic membrane transplantation, keratoprosthesis, and bioengineered corneal scaffolds integrate structural reconstruction with immune modulation. Furthermore, the convergence of multi-omics analytics, artificial intelligence-assisted diagnostics, and microbiome-based immunomodulation heralds a new era of precision ophthalmology. This review synthesizes current molecular insights, clinical observations, and translational advances that collectively redefine autoimmune ocular surface diseases—from chronic inflammatory disorders into a targetable, regenerative, and potentially reversible spectrum of conditions. Full article

Background/Objectives: Refractory macular holes (MHs) that persist after conventional internal limiting membrane (ILM) peeling pose a significant surgical challenge. In this study, we analyzed the anatomical and functional outcomes of epiretinal human amniotic membrane (hAM) transplantation in patients with MHs. Methods: This retrospective study included 10 eyes of 10 patients with refractory MHs. All patients underwent 25-gauge pars plana vitrectomy, epiretinal cryopreserved hAM transplantation, and C3F8 gas tamponade. The large hAM graft was placed over the macula with the stromal side facing the retina. Preoperative and postoperative best-corrected visual acuity (BCVA), optical coherence tomography (OCT) findings, and MH dimensions were recorded. Results: The mean follow-up period was 7 months (range: 3–14 months). The mean preoperative minimum linear diameter and base diameter of the MHs were 715 ± 212 μm and 1114 ± 258 μm, respectively. Anatomical closure was achieved in all patients (100%). Postoperative OCT revealed rearrangement of the inner and other retinal layers in 7 out of 10 patients (70%), with partial restoration of the outer retinal layers. The mean logMAR BCVA improved significantly from 1.60 ± 0.37 preoperatively to 1.00 ± 0.45 postoperatively (p < 0.001). No graft dislocation, rejection, or other significant complications were observed. Conclusions: Our preliminary results suggest that epiretinal human amniotic membrane transplantation is a feasible and promising surgical technique for achieving anatomical closure and functional improvement in refractory macular holes in which conventional ILM peeling has failed. Full article

Background: Cultivated oral mucosal epithelial transplantation (COMET/CAOMECS) is an autologous, immunosuppression-sparing option for ocular surface reconstruction in limbal stem cell deficiency (LSCD). After two decades, indications, platforms and outcome definitions vary, and COMET’s position relative to limbal-derived epithelium remains uncertain. Methods: We conducted a PRISMA-ScR scoping review of human clinical studies (PubMed, 2000–30 December 2025) with hand-searching and regulatory sources. Eligible reports included COMET/CAOMECS series and comparative cohorts (CLET/ACLET, SLET, KLAL/CLAL). The primary outcome was anatomical success (stable epithelialised cornea without recurrent persistent epithelial defect, progressive conjunctivalisation or uncontrolled neovascularisation at last assessment). Given heterogeneity in definitions and analytic frames (fixed-time vs. Kaplan–Meier [KM]), results were synthesised narratively by indication and platform. Results: Twenty-five reports (893 eyes; 821 patients) were included. Aetiologies were predominantly burns and SJS/TEN. Across amniotic membrane-based mixed-aetiology series, 12-month anatomical success clustered around 55–70%. Aggregated descriptively across COMET eyes, 211/467 (45%) had a stable surface at last follow-up. Epithelialisation was generally rapid in quiet AM-based reconstructions and slower with severe adnexal disease or carrier-free platforms. Mean BCVA improved from 1.8 ± 0.7 to 1.4 ± 0.7 logMAR (471 eyes); ≥2-line gains occurred in 308/471 (65.4%). A matched comparison suggested better 12-month survival, less neovascularisation and better BCVA with substrate-free versus AM-carried COMET; a biomaterial-/feeder-free platform reconstructed most eyes but failed more often with four-quadrant symblepharon. Observational comparative cohorts suggested higher surface survival and average visual gain with limbal-derived epithelium, at the cost of systemic immunosuppression. Conclusions: In appropriately selected bilateral LSCD, COMET offers immunosuppression-sparing reconstruction with moderate, durable surface stability and clinically meaningful visual gains when performed on a quiet, optimised surface. Platform refinements—particularly substrate-free constructs—and prospective, indication-defined comparative studies with harmonised outcomes are needed to define COMET’s role relative to limbal-derived epithelium. Full article