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International Journal of Biological... Jun 2024The multifaceted role of hyaluronic acid (HA) across diverse biomedical disciplines underscores its versatility in tissue regeneration and repair. HA hydrogels employ... (Review)
Review
The multifaceted role of hyaluronic acid (HA) across diverse biomedical disciplines underscores its versatility in tissue regeneration and repair. HA hydrogels employ different crosslinking including chemical (chitosan, collagen), photo- initiation (riboflavin, LAP), enzymatic (HRP/H2O2), and physical interactions (hydrogen bonds, metal coordination). In biophysics and biochemistry, HA's signaling pathways, primarily through CD44 and RHAMM receptors, modulate cell behavior (cell migration; internalization of HA), inflammation, and wound healing. Particularly, smaller HA fragments stimulate inflammatory responses through toll-like receptors, impacting macrophages and cytokine expression. HA's implications in oncology highlight its involvement in tumor progression, metastasis, and treatment. Elevated HA in tumor stroma impacts apoptosis resistance and promotes tumor growth, presenting potential therapeutic targets to halt tumor progression. In orthopedics, HA's presence in synovial fluid aids in osteoarthritis management, as its supplementation alleviates pain, enhances synovial fluid's viscoelastic properties, and promotes cartilage integrity. In ophthalmology, HA's application in dry eye syndrome addresses symptoms by moisturizing the eyes, replenishing tear film deficiencies, and facilitating wound healing. Intravitreal injections and hydrogel-based systems offer versatile approaches for drug delivery and vitreous humor replacement. For skin regeneration and wound healing, HA hydrogel dressings exhibit exceptional properties by promoting moist wound healing and facilitating tissue repair. Integration of advanced regenerative tools like stem cells and solubilized amnion membranes into HA-based systems accelerates wound closure and tissue recovery. Overall, HA's unique properties and interactions render it a promising candidate across diverse biomedical domains, showcasing immense potentials in tissue regeneration and therapeutic interventions. Nevertheless, many detailed cellular and molecular mechanisms of HA and its applications remain unexplored and warrant further investigation.
Topics: Hyaluronic Acid; Humans; Wound Healing; Animals; Regeneration; Hydrogels; Bioengineering; Tissue Engineering
PubMed: 38763255
DOI: 10.1016/j.ijbiomac.2024.132454 -
Talanta Aug 2024Human amniotic mesenchymal stromal cells (hAMSCs) have unique immunomodulatory properties making them attractive candidates for regenerative applications in inflammatory...
Human amniotic mesenchymal stromal cells (hAMSCs) have unique immunomodulatory properties making them attractive candidates for regenerative applications in inflammatory diseases. Most of their beneficial properties are mediated through their secretome. The bioactive factors concurring to its therapeutic activity are still unknown. Evidence suggests synergy between the two main components of the secretome, soluble factors and vesicular fractions, pivotal in shifting inflammation and promoting self-healing. Biological variability and the absence of quality control (QC) protocols hinder secretome-based therapy translation to clinical applications. Moreover, vesicular secretome contains a multitude of particles with varying size, cargos and functions whose complexity hinders full characterization and comprehension. This study achieved a significant advancement in secretome characterization by utilizing native, FFF-based separation and characterizing extracellular vesicles derived from hAMSCs. This was accomplished by obtaining dimensionally homogeneous fractions then characterized based on their protein content, potentially enabling the identification of subpopulations with diverse functionalities. This method proved to be successful as an independent technique for secretome profiling, with the potential to contribute to the standardization of a qualitative method. Additionally, it served as a preparative separation tool, streamlining populations before ELISA and LC-MS characterization. This approach facilitated the categorization of distinctive and recurring proteins, along with the identification of clusters associated with vesicle activity and functions. However, the presence of proteins unique to each fraction obtained through the FFF separation tool presents a challenge for further analysis of the protein content within these cargoes.
Topics: Humans; Mesenchymal Stem Cells; Secretome; Amnion; Extracellular Vesicles; Quality Control; Cells, Cultured
PubMed: 38761653
DOI: 10.1016/j.talanta.2024.126216 -
Tissue Engineering. Part C, Methods 2024Human amniotic epithelial cells (hAECs) are novel and promising therapeutic agents for patients suffering from degenerative diseases. Studies have demonstrated that the...
Human amniotic epithelial cells (hAECs) are novel and promising therapeutic agents for patients suffering from degenerative diseases. Studies have demonstrated that the therapeutic effects of hAECs mainly depend on their paracrine components. Currently, appropriate pretreatment is a widely confirmed strategy for enhancing the repair potential of stem cells; however, the effect of proinflammatory factor pretreatment on hAECs and their secretome is still unclear. In this study, we used the well-characterized proinflammatory factors tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) to stimulate hAECs and analyzed the effect of TNF-α and IFN-γ on hAECs, including gene expression profile, paracrine proteins, and microRNAs (miRNAs) in exosomes. Results showed that TNF-α and IFN-γ pretreatment improved the viability of hAECs but inhibited the proliferation of hAECs. TNF-α and IFN-γ pretreatment altered the gene expression profile of hAECs, and upregulated differentially expressed genes were predominantly enriched in biological adhesion, antioxidant activity, and response to IFN-beta. In addition, TNF-α and IFN-γ pretreatment enhanced the paracrine secretion of cytokines by hAECs. The upregulated differentially expressed proteins were mainly enriched in tissue remodeling proteins and cytokine-cytokine receptor. Notably, the expression of miRNAs in exosomes from hAECs was also changed by TNF-α and IFN-γ pretreatment. The target genes of upregulated exosomal miRNAs substantially contributed to the response to stimulus, metabolic pathways, and PI3K-Akt signaling pathway. Our findings improve our understanding of the biological characteristics of hAECs after proinflammatory factor pretreatment and provide novel insights to strengthen and optimize the therapeutic potential of hAECs and their secretome in regenerative medicine.
Topics: Humans; Amnion; Epithelial Cells; Secretome; Exosomes; Interferon-gamma; Tumor Necrosis Factor-alpha; Cell Proliferation; MicroRNAs; Cell Survival; Female; Cytokines; Cells, Cultured; Inflammation Mediators
PubMed: 38756098
DOI: 10.1089/ten.TEC.2024.0065 -
ACS Biomaterials Science & Engineering Jun 2024There is an arising need for effective wound dressings that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with...
There is an arising need for effective wound dressings that retain the bioactivity of a cellular treatment, but without the high costs and complexities associated with manufacturing, storing, and applying cell-based products. As skin wound recovery is a dynamic and complicated process, a significant obstacle to the healing of skin wounds is the lack of an appropriate wound dressing that can imitate the microenvironment of healthy skin and prevent bacterial infection. It requires the well-orchestrated integration of biological and molecular events. In this study, we have fabricated full-thickness skin graft biocomposite membranes to target full-thickness skin excision wounds. We reinforced human amniotic membrane (hAM) with electrospun polycaprolactone (PCL) to develop composite membranes, namely, PCL/hAM and PCL/hAM/PCL. Composite membranes were compared for physical, biological, and mechanical properties with the native counterpart. PCL/hAM and PCL/hAM/PCL displayed improved stability and delayed degradation, which further synergically improved the rapid wound healing property of hAM, driven primarily by wound closure analysis and histological assessment. Moreover, PCL/hAM displayed a comparable cellular interaction to hAM. On application as a wound dressing, histological analysis demonstrated that hAM and PCL/hAM promoted early epidermis and dermis formation. Studies on wound healing revealed that although hAM accelerates cell development, the overall wound healing process is similar in PCL/hAM. This finding is further supported by the immunohistochemical analysis of COL-1/COL-3, CD-31, and TGF-β. Overall, this conjugated PCL and hAM-based membrane has considerable potential to be applied in skin wound healing. The facile fabrication of the PCL/hAM composite membrane provided the self-regenerating wound dressing with the desired mechanical strength as an ideal regenerative property for skin tissue regeneration.
Topics: Wound Healing; Polyesters; Amnion; Humans; Animals; Biocompatible Materials; Skin; Membranes, Artificial
PubMed: 38754076
DOI: 10.1021/acsbiomaterials.3c01740 -
Advances in Wound Care May 2024Chronic wounds can lead to poor outcomes for patients, with risks including amputation and death. In the United States, chronic wounds affect 2.5% of the population and...
SIGNIFICANCE
Chronic wounds can lead to poor outcomes for patients, with risks including amputation and death. In the United States, chronic wounds affect 2.5% of the population and cost up to $28 billion per year in primary healthcare costs.
RECENT ADVANCES
Allograft tissues (dermal, amnion, and amnion/chorion) have shown efficacy in improving healing of chronic, recalcitrant wounds in human patients, as evidenced by multiple clinical trials. Their mechanisms of actions have been relatively understudied, until recently. Research in murine models has shown dermal allografts promote re-epithelialization, amnion allografts promote granulation tissue formation and angiogenesis, and amnion/chorion allografts support all stages of wound healing. These findings not only confirm effectiveness, but they shed light on mechanisms of action responsible for their therapeutic utility in patients.
CRITICAL ISSUES
Despite the promise of allografts in chronic wound care, a gap exists in understanding which allografts are most effective during each wound healing stage. The variable efficacy among each type of allograft suggests a mechanistic approach towards a proposed clinical treatment algorithm, based on wound characteristics and patient's needs, may be beneficial.
FUTURE DIRECTIONS
Recent advances in allografts provide a framework for further investigations on how allograft selection can be based on specific needs of individual patients. This requires additional research to identify which allografts support the best outcomes during each stage of the wound healing process as well as utility in specific wound types. Longitudinal human studies investigating the long-term impacts of allografts, particularly in the remodeling phase, are also essential to developing a deeper understanding of their role in sustained wound repair and recovery.
PubMed: 38753722
DOI: 10.1089/wound.2023.0139 -
BMC Pregnancy and Childbirth May 2024Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal...
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without.
METHODS
A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without.
RESULTS
Overall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p < 0.001 for all). Women in the ADHD group, compared to those without, had a higher rate of hypertensive disorders of pregnancy (HDP) (aOR 1.36, 95% CI 1.28-1.45, p < 0.001), cesarean delivery (aOR 1.19, 95% CI 1.13-1.25, p < 0.001), chorioamnionitis (aOR 1.34, 95% CI 1.17-1.52, p < 0.001), and maternal infection (aOR 1.33, 95% CI 1.19-1.5, p < 0.001). Regarding neonatal outcomes, patients with ADHD, compared to those without, had a higher rate of small-for-gestational-age neonate (SGA) (aOR 1.3, 95% CI 1.17-1.43, p < 0.001), and congenital anomalies (aOR 2.77, 95% CI 2.36-3.26, p < 0.001).
CONCLUSION
Women with a diagnosis of ADHD had a higher incidence of a myriad of maternal and neonatal complications, including cesarean delivery, HDP, and SGA neonates.
Topics: Humans; Female; Attention Deficit Disorder with Hyperactivity; Pregnancy; Adult; Retrospective Studies; Pregnancy Complications; Infant, Newborn; Pregnancy Outcome; United States; Databases, Factual; Young Adult; Cesarean Section; Delivery, Obstetric; Hypertension, Pregnancy-Induced
PubMed: 38750437
DOI: 10.1186/s12884-024-06561-5 -
Cytokine Aug 2024The risk of various complications, such as neonatal death, early onset sepsis, and chronic lung disease, is increased in infants born to mothers with chorioamnionitis...
BACKGROUND
The risk of various complications, such as neonatal death, early onset sepsis, and chronic lung disease, is increased in infants born to mothers with chorioamnionitis (CAM). However, predicting the diagnosis of histological CAM (hCAM) in the early postnatal period is challenging for clinicians due to pathological considerations. Therefore, an early diagnostic tool for hCAM is needed. Gastric fluid at birth is considered a suitable biomarker for predicting the intrauterine environment because most of its components are from amniotic fluid, and the sampling technique is less invasive. This study aimed to evaluate the clinical utility of cytokines in the gastric fluid of preterm infants at birth as predictors of hCAM.
METHODS
We retrieved gastric fluid and serum from 21 preterm infants with a gestational age of ≤ 32 weeks within 1 h after birth and used cytometric bead array to measure the concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma. We compared the cytokine concentrations in the gastric fluid and serum of the preterm infants born to mothers with or without hCAM.
RESULTS
The gastric fluid, serum IL-6, and serum IL-10 concentrations were significantly higher in the hCAM group than that in the non-hCAM group. The best cutoff values for predicting hCAM was > 2,855 pg/mL and > 315 pg/mL for IL-6 in the gastric fluid and serum, respectively. Receiver operating characteristic curves showed that gastric fluid IL-6 concentrations correlated more strongly with the presence of hCAM than serum IL-6 concentrations.
CONCLUSION
IL-6 in the gastric fluid at birth may be a more promising biomarker for predicting the presence of hCAM than that in serum. IL-6 concentration analysis in the gastric fluid at birth might help to diagnose hCAM immediately after birth and improve the prognosis of preterm infants.
Topics: Humans; Female; Chorioamnionitis; Pregnancy; Infant, Premature; Infant, Newborn; Cytokines; Male; Biomarkers; Gastric Juice; ROC Curve; Gestational Age; Adult; Amniotic Fluid; Interleukin-6
PubMed: 38749278
DOI: 10.1016/j.cyto.2024.156642 -
Placenta Jul 2024Placental abnormalities can precipitate preterm birth (PTB), a principal contributor to neonatal morbidity and mortality. This study targets understanding placental...
UNLABELLED
Placental abnormalities can precipitate preterm birth (PTB), a principal contributor to neonatal morbidity and mortality. This study targets understanding placental variations among different gestational age-based categories of PTB.
METHODS
A three-year retrospective study conducted a detailed clinicopathological analysis of PTB placentas categorized by gestational age: extremely preterm (EPTB,<28 weeks), very preterm (VPTB, 28 to 31 + 6 weeks), moderate preterm (MPTB, 32 to 33 + 6 weeks), and late preterm (LPTB, 34 to 36 + 6 weeks). Macroscopic parameters sourced from pathology records and microscopic examination assessed for maternal and fetal stromal-vascular lesions, inflammatory and hypoxic lesions and others. Stillbirths/intrauterine demise and multifetal gestation were excluded. Clinical data were gathered from medical records.
RESULTS
A total of 645 preterm placentas were received and 538 were included. The majority were LPTB(46.3 %), while EPTB, VPTB and MPTB accounted for 5.8 %, 28.4 % and 19.5 % respectively. Low birth weight and low Apgar were prevalent in EPTB(p < 0.001), while obstetric complications were higher in other PTB categories. Placental infarction was higher in VPTB and MPTB(p = 0.006). On microscopy, maternal (48.4 %), fetal (29 %) inflammatory response and villous edema (48.4 %) was higher in EPTB(p = 0.04 & p < 0.001 respectively), while maternal stromal-vascular lesions were higher in VPTB and MPTB(67.3 % & 64.8 %, p < 0.001). Delayed villous maturation (17.7 %,p = 0.02), chronic chorioamnionitis (11.3 %,p = 0.02), membrane hypoxia (38.6 %,p = 0.007), and massive fibrin deposition (10.8 %,p < 0.001) featured higher in LPTB.
DISCUSSION
Acute inflammatory pathology was common in EPTB, strongly suggesting inflammation in triggering parturition. Frequent obstetric complications and maternal stromal-vascular lesions in VPTB and MPTB may underscore maternal vascular compromise in this group. Villous maturation defects, chronic chorioamnionitis, massive fibrin deposition and membrane hypoxia in LPTB, likely contribute to long-term neonatal morbidity.
Topics: Humans; Female; Pregnancy; Placenta; Retrospective Studies; Premature Birth; Gestational Age; Adult; Infant, Newborn; Placenta Diseases
PubMed: 38744037
DOI: 10.1016/j.placenta.2024.05.124 -
Case Reports in Pediatrics 2024Home high-flow nasal cannula (HFNC) use in the neonatal field has become prevalent as a noninvasive respiratory support, but its application in home care remains rare....
Home high-flow nasal cannula (HFNC) use in the neonatal field has become prevalent as a noninvasive respiratory support, but its application in home care remains rare. We report two cases in which a home HFNC was effective in managing extremely low-birth-weight infants with severe bronchopulmonary dysplasia (BPD). Case 1 was a male infant born at 22 weeks' gestation weighing 435 g. Case 2 was a female infant born at 23 weeks' gestation weighing 450 g. Both patients had mothers with chronic placental abruption or chorioamnionitis. They transitioned from invasive mechanical ventilation to nasal CPAP (nCPAP) at 45 days (case 1) and 50 days (case 2) old. Subsequently, at 324 days (case 1) and 90 days (case 2) old, they transitioned to a HFNC, demonstrating stable oxygenation and ventilation, but faced difficulty in removal. Considering the drawbacks of prolonged hospitalization, the patients were discharged using a home HFNC at 404 days (case 1) and 391 days (case 2) old. For case 1, the HFNC was set at 4 L/min of room air and 2 L/min of oxygen, whereas for case 2, it was set at 5 L/min of room air and 1 L/min of oxygen. These settings maintained an SpO above 90% and a pCO below 60 mmHg. An HFNC offers advantages over nCPAP owing to its lower invasiveness and reduced discomfort for long-term use. However, reports on the use of a home HFNC for BPD are scarce. In recent years, while premature infant mortality has decreased worldwide, the incidence of BPD has risen, necessitating preparedness for prolonged ventilation in preterm infants. Home ventilators represent a strategy to prevent extended hospitalization, and based on our cases, home HFNC for BPD appears safe and effective, making it potentially useful for managing preterm infants requiring prolonged respiratory support in the future.
PubMed: 38741929
DOI: 10.1155/2024/3266928 -
Cureus Apr 2024Background Advancements in regenerative techniques have been utilized in placental amnion and chorion for a variety of purposes. Their ability to regenerate tissues has...
Background Advancements in regenerative techniques have been utilized in placental amnion and chorion for a variety of purposes. Their ability to regenerate tissues has led to their usage in tissue engineering, wound healing, and other therapeutic applications. This study aims to evaluate and compare the efficacy of amnion and chorion in facial tissue wound healing. Methodology The study was an observational comparative study conducted in the Department of Oral and Maxillofacial Surgery, involving 20 participants divided into two groups (Group I and Group II). Study groups were selected according to the inclusion and exclusion criteria. A dehydrated human amnion/ chorion membrane was applied to the affected site of each group respectively. Its efficacy in wound healing was analyzed in the first, third, seventh day, and second week. Statistical analysis was done using SPSS software (IBM Corp., Armonk, NY). Results Patients treated with amnion membrane showed a decrease in wound size and the wound was completely healed by second week with mean scores of wound sizes of 0.00 whereas the wound remained unhealed by second week with mean of 1.70 to those treated with chorion membrane. Conclusion Amnion showed superior efficacy in wound healing at two-week intervals when compared to the chorion. Hence, this could be used in regenerative medicine as a graft to induce healing in facial wounds.
PubMed: 38741866
DOI: 10.7759/cureus.58160