Effects of a human amniotic membrane extract on ARPE-19 cells.

BACKGROUND: Human Amniotic Membrane (hAM) is endowed with several biological activities and might be considered an optimal tool in surgical treatment for different ophthalmic pathologies. We pioneered the surgical use of hAM to treat retinal pathologies such as macular holes, tears, and retinal detachments, and to overcome photoreceptor damage in age-related macular degeneration. Although hAM contributed to improved outcomes, the mechanisms of its effects are not yet fully understood. The characterization and explanation of the effects of hAM would allow the adoption of this new natural product in different retinal pathologies, operative contexts, and hAM formulations. At this end, we studied the properties of a hAM extract (hAME) on the ARPE-19 cells. METHODS AND RESULTS: A non-denaturing sonication-based technique was developed to obtain a suitable hAME. Viability, proliferation, apoptosis, oxidative stress, and epithelial-mesenchymal transition (EMT) were studied in hAME-treated ARPE-19 cells. The hAME was able to increase ARPE-19 cell viability even in the presence of oxidative stress (H2O2, TBHP). Moreover, hAME prevented the expression of EMT features, such as EMT-related proteins, fibrotic foci formation, and migration induced by different cytokines. CONCLUSIONS: Our results demonstrate that the hAME retains most of the properties observed in the whole tissue by others. The hAME, other than providing a manageable research tool, could represent a cost-effective and abundant drug to treat retinal pathologies in the future.

Adiponectin and visfatin expression profile in extra-embryonic annexes and role during embryo development in layer and broiler chickens.

Some evidence showed differences between layer and broiler embryo development. We recently showed that two adipokines, adiponectin and visfatin are expressed in the extra embryonic membranes and fluids. However, their role in the embryo development is unknown. Thus, our objectives were 1. to compare the expression of AdipoQ and its receptors AdipoR1 and AdipoR2 and visfatin in extra-embryonic annexes in broiler and layer breeders during the embryo development and 2. to investigate the role of two adipokines in embryo development in both broiler and layer breed after in ovo injection of blocking antibodies against chicken adiponectin or visfatin. We found that adiponectin, AdipoR1, AdipoR2 and visfatin were mainly more expressed in the allantoic that in amniotic membranes. In addition, these expressions increased according the stage of embryo development. We observed a higher expression in layer than in broiler of AdipoQ in allantoic membranes at ED14 and ED18, of AdipoR1 and AdipoR2 in both allantoic and amniotic membranes at ED7 and ED14 and of visfatin only in allantoic membrane from ED7 to ED18. AdipoQ and visfatin were absent in amniotic fluid at ED7 but present at ED14 or ED18 where higher concentrations were detected in layer than in broiler. Interestingly, we showed a strong positive correlation between Adipo and visfatin concentration in amniotic fluid and the body weight of embryo in both breeds. However, after in ovo injection of Adipo antibodies we did not observe any effect on the embryo mortality whereas injection of visfatin antibodies increased in a dose dependent manner the embryo mortality in both breeds. Taken together, Adipo and visfatin are higher expressed in layer than broiler in extra-embryonic membranes and amniotic fluid. Our data suggest also that visfatin could be a main regulator of embryo development.

Biological ultrathin amniotic membrane flap to close refractory macular holes associated with high myopia.

PURPOSE: To propose an ultrathin biological amniotic membrane (btAM) thinner than 10 µm as the graft to treat highly myopic macular holes (MH). METHODS: This pilot study included 14 patients affected by refractory macular holes associated with high myopia. btAM was used as a bandage covering the holes. The best-corrected visual acuity (BCVA), fundus photography, and optical coherence tomography (OCT) before and after surgery were compared. RESULTS: The mean MH size was 865.93 ± 371.72 µm and all the MHs achieved anatomical closure. The btAM located centrally and fully on MHs from fundus photography yet no obvious visual masking was complained. The average BCVA 1 month, 3, and 6 months after surgery were 0.95 ± 0.24, 0.92 ± 0.23, 0.92 ± 0.23 logMAR, respectively, improved significantly compared to pre-operative BCVA (1.24 ± 0.42 logMAR, all P < 0.05). Ten out of 14 (71.4%) exhibited 2C closure patterns (formally closed and no bare RPE) on OCT. CONCLUSION: The btAM thinner showed a favorable anatomical success with less risk of parafoveal atrophy or iatrogenic injuries and shortened the dissolving time.

The effect of different pterygium surgery techniques on the ocular surface parameters in different durations: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of different pterygium surgery techniques on ocular surface (OS) in different follow-up periods. METHODS: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, and China Biology Medicine disc were searched for studies reporting pre- and post-operative OS parameters in pterygium. RESULTS: A total of 33 articles were finally included. Three OS parameters showed relatively consistent changing trends after surgery including ocular surface disease index (OSDI), tear film break-up time (BUT), and score of corneal fluorescein staining (SCFS). They worsened significantly at 1w post-operation and then gradually improved: OSDI and BUT showed obvious improvement in 1 m post-operation (SMD = - 0.58, 95%CI = [- 1.04, - 0.13]; SMD = 0.42, 95%CI = [0.06, 0.78]); SCFS was restored to preoperative levels in 3 m after surgery (SMD = - 0.54, 95%CI = [- 1.16, 0.07]). Another parameter, Schirmer test without anesthesia (SIT), presented transient increase at 1w post-operation (SMD = 0.87, 95%CI = [0.27, 1.47]) and presented a relatively stable improvement after 1 m post-operation (SMD = 0.52, 95%CI = [0.16, 0.89]). All parameters in amniotic membrane graft (AMT) showed better improvement in early stage and they showed non-inferior improvements in the long term compared with conjunctival autograft (CAG). Limbal-conjunctival autograft (LCAG) made excellent improvement to OS in the long term while pterygium excision (PE) showed the worst OS. The type of pterygium (primary and secondary), diabetes mellitus (DM) status, and fixation method had certain effects on the results. CONCLUSIONS: OS of pterygium is deteriorated at 1w post-operation then gradually improved to preoperative levels after 1 m post-operation. Among various surgery techniques, LCAG had the best improvement to OS which especially displayed in the long-term outcomes.

Amniotic miracle: Investigating the unique development and applications of amniotic membrane in wound healing.

BACKGROUND: The perfect repair of damaged skin has always been a constant goal for scientists; however, the repair and reconstruction of skin is still a major problem and challenge in injury and burns medicine. Human amniotic membrane (hAM), with its good mechanical properties and anti-inflammatory, antioxidant and antimicrobial benefits, containing growth factors that promote wound healing, has evolved over the last few decades from simple skin sheets to high-tech dressings, such as being made into nanocomposites, hydrogels, powders, and electrostatically spun scaffolds. This paper aims to explore the historical development, applications, trends, and research hotspots of hAM in wound healing. METHODS: We examined 2660 publications indexed in the Web of Science Core Collection (WoSCC) from January 1, 1975 to July 12, 2023. Utilizing bibliometric methods, we employed VOSviewer, CiteSpace, and R-bibliometrix to characterize general information, identify development trends, and highlight research hotspots. Subsequently, we identified a collection of high-quality English articles focusing on the roles of human amniotic epithelial stem cells (hAESCs), human amniotic mesenchymal stem cells (hAMSCs), and amniotic membrane (AM) scaffolds in regenerative medicine and tissue engineering. RESULTS: Bibliometric analysis identified Udice-French Research Universities as the most productive affiliation and Tseng S.C.G. as the most prolific author. Keyword analysis, historical direct quotations network, and thematic analysis helped us review the historical and major themes in this field. Our examination included the knowledge structure, global status, trends, and research hotspots regarding the application of hAM in wound healing. Our findings indicate that contemporary research emphasizes the preparation and application of products derived from hAM. Notably, both hAM and the cells isolated from it - hADSCs and hAESCs are prominent and promising areas of research in regenerative medicine and tissue engineering. CONCLUSION: This research delivers a comprehensive understanding of the knowledge frameworks, global dynamics, emerging patterns, and primary research foci in the realm of hAM applications for wound healing. The field is rapidly evolving, and our findings offer valuable insights for researchers. Future research outcomes are anticipated to be applied in clinical practice, enhancing methods for disease prevention, diagnosis, and treatment.

Silica nanoparticles enhance the cyto- and hemocompatibility of a multilayered extracellular matrix scaffold for vascular tissue regeneration.

PURPOSE: The limited availability of autologous vessels for vascular bypass surgeries is a major roadblock to treating severe cardiovascular diseases. Based on this clinical priority, our group has developed a novel engineered vascular graft by rolling human amniotic membranes into multilayered extracellular matrixes (ECM). When treated with silica nanoparticles (SiNP), these rolled scaffolds showed a significant improvement in their structural and mechanical properties, matching those from gold standard autologous grafts. However, it remained to be determined how cells respond to SiNP-treated materials. As a first step toward understanding the biocompatibility of SiNP-dosed biomaterials, we aimed to assess how endothelial cells and blood components interact with SiNP-treated ECM scaffolds. METHODS: To test this, we used established in vitro assays to study SiNP and SiNP-treated scaffolds' cyto and hemocompatibility. RESULTS: Our results showed that SiNP effects on cells were concentration-dependent with no adverse effects observed up to 10 µg/ml of SiNP, with higher concentrations inducing cytotoxic and hemolytic responses. The SiNP also enhanced the scaffold's hydrophobicity state, a feature known to inhibit platelet and immune cell adhesion. Accordingly, SiNP-treated scaffolds were also shown to support endothelial cell growth while preventing platelet and leukocyte adhesion. CONCLUSION: Our findings suggest that the addition of SiNP to human amniotic membrane extracellular matrixes improves the cyto- and hemocompatibility of rolled scaffolds and highlights this strategy as a robust mechanism to stabilize layered collagen scaffolds for vascular tissue regeneration.

Amniotic membrane dressings for treatment of aplasia cutis in newborns.

BACKGROUND: Aplasia cutis congenita (ACC) is a rare congenital skin defect characterized by a focal or extensive absence of the epidermis, dermis, and occasionally, subcutaneous tissue. When the wound caused by this defect is wide or deep, various treatments are used, including skin grafting. The amniotic membrane (AM) is a biological dressing that facilitates re-epithelialization as it contains mesenchymal cells and numerous growth factors. OBJECTIVE: To report the efficacy of AM dressings in treating the skin defects of ACC. METHOD: This study was conducted on five neonates diagnosed with ACC born between 2018 and 2022, referred to the Children's Medical Center in Tehran, Iran. AM dressings were applied on wounds larger than 1 cm2. The wounds were assessed weekly and, if required, an additional AM dressing was applied. RESULTS: The skin defects gradually re-epithelialized after application of the AM. The complete healing process took around 3.5 weeks on average. No hypertrophic scarring was observed. CONCLUSION: The application of AM dressing resulted in satisfactory cosmetic outcomes, with no hypertrophic scar formation. Complete healing occurred in all cases except one. The length of the hospital stay ranged from 2 to 6 weeks, depending on the size of the wound.

Comparison of proteomic profiles and biological properties for corneal wound healing of canine amniotic membrane and its extracts.

OBJECTIVE: The application of canine amniotic membrane (cAM) for corneal reconstruction is widely used in the veterinary field. However, the information on biological properties and alternative forms of cAM for corneal wound healing is limited. This study aimed to investigate the proteomic profiles and corneal wound healing properties of cAM, cAM extract (cAME), and lyophilized cAM extract (cAMX). ANIMAL STUDIED: A total number of 14 cAMs were sterilely harvested from healthy full-term puppies and randomly divided into three different forms: cAM (n = 14), cAME (n = 14), and cAMX (n = 14). PROCEDURES: Each form of cAMs was subjected to proteomic analysis using label-free liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), followed by bioinformatic analysis. The proteins were classified into properties by comparing them with the literature search on human amniotic membrane (hAM) properties and the effect on corneal wound healing when given topically. RESULTS: The analyses identified 8136 proteins in cAM, 8211 proteins in cAME, and 7093 proteins in cAMX. A total number of 100 proteins were matched with proteins in hAM properties and were classified into anti-inflammatory, anti-fibrotic, anti-microbial, anti-angiogenic, promotion of epithelialization, analgesic, and support cell adhesion and growth properties. Furthermore, proteins with corneal wound healing effects were identified in cAME and cAMX. CONCLUSIONS: cAM and its extracts contain numerous proteins, including proteins related to corneal wound healing properties. Additionally, cAME and cAMX showed proteins involved in corneal wound healing and their potential benefits for topical use in ophthalmology.

Amniotic membrane in wound healing: new perspectives.

There are several reasons for skin damage, including genetic factors, disorders, acute trauma, hard-to-heal wounds, or surgical interventions. Whatever the cause, wounds have a substantial impact on people who experience them, their caregivers and the healthcare system. Advanced wound care products have been researched and developed, providing an opportunity for faster and more complete healing. Tissue engineering (TE) is a promising strategy that can overcome limitations when choosing a graft for a wound. Amniotic membrane is a highly abundant, readily available, and inexpensive biological tissue that does not raise ethical concerns, with many applications in different fields of TE and regenerative medicine. It has attractive physical characteristics, such as elasticity, rigidity and mechanical strength, among others. The effects can also be potentiated by association with other substances, such as hyaluronic acid and growth factors. This paper describes new perspectives involving the use of amniotic membranes.

Use of amniotic membrane in hard-to-heal wounds: a multicentre retrospective study.

OBJECTIVE: Hard-to-heal (chronic) wounds negatively impact patients and are a source of significant strain on the healthcare system and economy. These wounds are often resistant to standard of care (SoC) wound healing approaches due to a diversity of underlying pathologies. Cellular, acellular, and matrix-like products, such as amniotic membranes (AM), are a potential solution to these challenges. A growing body of evidence suggests that AM may be useful for treatment-resistant wounds; however, limited information is available regarding the efficacy of dehydrated amniotic membrane (DHAM) on multi-aetiology, hard-to-heal wounds. Therefore, we analysed the efficacy of DHAM treatment in reducing the size of hard-to-heal diabetic and venous leg ulcers (VLUs) that had failed to improve after SoC-based treatments. METHOD: In this multicentre retrospective study, we analysed wound size during clinic visits for patients being treated for either diabetic or VLUs. During each visit, the treatment consisted of debridement followed by application of DHAM. Each wound was measured after debridement and prior to DHAM application, and wound volumes over time or number of DHAM applications were compared. RESULTS: A total of 18 wounds in 11 patients were analysed as part of this study. Wounds showed a significant reduction in volume after a single DHAM application, and a 50% reduction in wound size was observed after approximately two DHAM applications. These findings are consistent with reports investigating DHAM treatment of diabetic ulcers that were not necessarily resistant to treatment. CONCLUSION: To our knowledge, this study is the first to directly compare the efficacy of standalone DHAM application to hard-to-heal diabetic and venous leg ulcers, and our findings indicate that DHAM is an effective intervention for resolving these types of wounds. This suggests that implementing this approach could lead to fewer clinic visits, cost savings and improved patient quality of life. DECLARATION OF INTEREST: This research was supported in part by Merakris Therapeutics, US, and facilitated access to deidentified patient datasets, which may represent a perceived conflict of interest; however, the primary data analysis was performed by FSB who is unaffiliated with Merakris Therapeutics. TCB is a founder, employee of and shareholder in Merakris Therapeutics; WSF is a co-founder of, consultant for, and shareholder in Merakris Therapeutics, and was also supported by the National Institutes of Health National Center for Advancing Translational Sciences Clinical and Translational Science Awards Grant KL2 Scholars Program (KL2TR001441). The research was also supported through endowments to WSF from the University of Texas Medical Branch Mimmie and Hallie Smith Endowed Chair of Transplant Research and the John L Hern University Chair in Transplant Surgery.

Management of post-Mohs surgical wounds with a hypothermically stored amniotic membrane: a case series.

OBJECTIVE: The aim of this case series is to present an alternative approach to managing post-Mohs Micrographic Surgery (Mohs) wounds with hypothermically stored amniotic membrane (HSAM). METHOD: A case series of patients with post-Mohs wounds is presented, with four patients referred for hard-to-heal wounds following a Mohs procedure that was performed 1-3 months previously. All wounds underwent weekly assessment, debridement, and application of HSAM and secondary dressings. Treatment also included management of bioburden, proper skin care and compression therapy for lower extremity wounds. RESULTS: This case series of seven wounds consisted of four females and three males with a mean age of 87.6 years. Mean wound size at first application of HSAM was 1.34±1.20cm2. All wounds closed, with an average time to wound closure of 43.7±27.1 days. Patients received an average of 4.6±2.5 HSAM applications. The four post-Mohs wounds with a history of being hard-to-heal had an average time to wound closure of 35.5±16.3 days, with an average duration of 86.5±32.4 days prior to the first HSAM application. CONCLUSION: The results of this case series suggest that use of HSAM may provide an alternative approach to managing post-Mohs wounds. In addition, these findings suggest that HSAM may be of greatest benefit when applied early after Mohs surgery.

Use of hypothermically stored amniotic membrane on diabetic foot ulcers: a multicentre retrospective case series.

OBJECTIVE: The aim of this retrospective case series was to report on the outcomes of diabetic foot ulcers (DFUs) managed with hypothermically stored amniotic membrane (HSAM). METHOD: Deidentified case data of patients who received HSAM were obtained from wound care sites across the US. Data were collected, beginning at the first patient visit to the wound care site (first presentation), at the visit in which the first HSAM application occurred (baseline), and at each subsequent visit over 12 weeks of treatment (follow-up). All patients received standard of care (SoC) between first presentation and baseline. RESULTS: Of the 50 patients in the study, 68% were male. Mean age of the entire cohort was 66.7 years. Of the DFUs, 88% were present for <6 months at first presentation. Mean wound area was 3.5cm2, and mean percentage area reduction was -68.3% from first presentation to baseline. The mean number of HSAM applications was 5.5, and mean number of days between applications was 7.5. A >60% area reduction was attained in 96.0% of DFUs, and 78% attained complete wound closure (CWC) by week 12. The median time to CWC was 55 days. CONCLUSION: The results of this retrospective case series suggest positive outcomes for DFUs managed with HSAM. A reduction in time to CWC may lead to lesser financial burden and improved quality of life for DFU patients. DECLARATION OF INTEREST: The authors have no conflicts of interest.

An important detail that is still not clear in amniotic membrane applications: How do we store the amniotic membrane best?

The use of fresh amniotic membrane (AM) is not a viable option, as it has many disadvantages. Preserving the AM reduces the risk of cross-infection and maintains its effectiveness for a long time. In order to maximize the therapeutic effects of the AM, the basic need is to preserve its vitality and the bioactive molecules it contains. However, the effect of preservation procedures on cell viability and growth factors is a still matter of debate. Optimum preservation method is expected to be cost-effective, easily-accessible, and most importantly, to preserve the effectiveness of the tissue for the longest time. However, each preservation technique has its advantages and disadvantages over the other, and each one compromises the vitality and bioactive molecules of the tissue to some extent. Therefore, the best method of preservation is still controversial, and the question of 'how to preserve the AM best?' has not yet been definitively answered.

Comparison of the effects of preservation methods on structural, biological, and mechanical properties of the human amniotic membrane for medical applications.

Amniotic membrane (AM), the innermost layer of the placenta, is an exceptionally effective biomaterial with divers applications in clinical medicine. It possesses various biological functions, including scar reduction, anti-inflammatory properties, support for epithelialization, as well as anti-microbial, anti-fibrotic and angio-modulatory effects. Furthermore, its abundant availability, cost-effectiveness, and ethical acceptability make it a compelling biomaterial in the field of medicine. Given the potential unavailability of fresh tissue when needed, the preservation of AM is crucial to ensure a readily accessible and continuous supply for clinical use. However, preserving the properties of AM presents a significant challenge. Therefore, the establishment of standardized protocols for the collection and preservation of AM is vital to ensure optimal tissue quality and enhance patient safety. Various preservation methods, such as cryopreservation, lyophilization, and air-drying, have been employed over the years. However, identifying a preservation method that effectively safeguards AM properties remains an ongoing endeavor. This article aims to review and discuss different sterilization and preservation procedures for AM, as well as their impacts on its histological, physical, and biochemical characteristics.

Management of grade II and III furcation defects with intramarrow penetration along with indigenously prepared DFDBA and amniotic membrane: a clinical and radiographic study.

Managing furcation defects constitutes a problem in successful periodontal therapy. Guided tissue regeneration (GTR) is the mainstay for the management of such defects but is expensive. This study makes use of indigenously prepared demineralized freeze-dried bone allograft (DFDBA) and amniotic membrane (AM) as a cost-effective alternative. The purpose of the study was to compare the clinical outcome of grade II and III furcation defects with and without using indigenous DFDBA and AM prepared at Central Tissue Bank, MAIDS. 18 systemically healthy patients with chronic periodontitis displaying either grade II or III furcation defects were treated with open flap debridement (OFD) + intramarrow penetration (IMP) (control group) and OFD + IMP + DFDBA + AM (test group). The clinical and radiographic parameters were recorded at 3 and 6 months postoperatively. All parameters were statistically analyzed. Both treatment modalities resulted in improvement in all clinical variables evaluated. Radiographic dimensions evaluating bone fill showed a statistically significant difference in the test group compared to the control group. Within the limitations of this study, data suggest GTR using indigenously prepared DFDBA and amniotic membrane to be an economical and viable option for treating furcation defects.

Cryopreserved amniotic membrane in chronic nonhealing wounds: a series of case reports.

A case series of the use of amniotic membrane (AM) for treating chronic nonhealing wounds. It presents five cases of polymorbid patients with a total of nine chronic nonhealing wounds. The patient group consisted of four men and one woman with various comorbidities, aged 45-72 years. The mean initial wound size was 15.8 cm2, and the mean time from the onset of the wound to the first application of AM was 122 weeks. The wounds were caused by chronic venous insufficiency and/or peripheral arterial disease. Wounds were treated in a standardized protocol. AM was applied weekly in the first month and then every two weeks. Photo documentation of the wound and microbiological colonization was carried out at each visit. In three out of five patients, the AM treatment effectively promoted healing up to complete wound closure. In two cases, the wounds stayed unhealed despite numerous AM applications. Pain relief was noted in all patients. The success of the treatment was closely tied to patient factors, such as adherence to the prescribed treatment regimen and individual patient characteristics. In some cases, treatment failure was observed, possibly due to underlying comorbidities, wound parameters, or poor patient compliance. AM treatment has the potential to become a viable treatment option for these nonhealing wounds. However, the effectiveness of the treatment may be influenced by various patient factors and the underlying cause of the wound. Therefore, it is crucial to have an individualized treatment plan that considers these particular factors.

Stable Housekeeping Genes in Bone Marrow, Adipose Tissue, and Amniotic Membrane-Derived Mesenchymal Stromal Cells for Orthopedic Regenerative Medicine Approaches.

The therapeutic effect of mesenchymal stromal cells (MSCs) has been described for a variety of disorders, including those affecting musculoskeletal tissues. In this context, the literature reports several data about the regenerative effectiveness of MSCs derived from bone marrow, adipose tissue, and an amniotic membrane (BMSCs, ASCs, and hAMSCs, respectively), either when expanded or when acting as clinical-grade biologic pillars of products used at the point of care. To date, there is no evidence about the superiority of one source over the others from a clinical perspective. Therefore, a reliable characterization of the tissue-specific MSC types is mandatory to identify the most effective treatment, especially when tailored to the target disease. Because molecular characterization is a crucial parameter for cell definition, the need for reliable normalizers as housekeeping genes (HKGs) is essential. In this report, the stability levels of five commonly used HKGs (ACTB, EF1A, GAPDH, RPLP0, and TBP) were sifted into BMSCs, ASCs, and hAMSCs. Adult and fetal/neonatal MSCs showed opposite HKG stability rankings. Moreover, by analyzing MSC types side-by-side, comparison-specific HKGs emerged. The effect of less performant HKG normalization was also demonstrated in genes coding for factors potentially involved in and predicting MSC therapeutic activity for osteoarthritis as a model musculoskeletal disorder, where the choice of the most appropriate normalizer had a higher impact on the donors rather than cell populations when compared side-by-side. In conclusion, this work confirms HKG source-specificity for MSCs and suggests the need for cell-type specific normalizers for cell source or condition-tailored gene expression studies.

Photosealed Neurorrhaphy Using Autologous Tissue.

Photochemical sealing of a nerve wrap over the repair site isolates and optimizes the regenerating nerve microenvironment. To facilitate clinical adoption of the technology, we investigated photosealed autologous tissue in a rodent sciatic nerve transection and repair model. Rats underwent transection of the sciatic nerve with repair performed in three groups: standard microsurgical neurorrhaphy (SN) and photochemical sealing with a crosslinked human amnion (xHAM) or autologous vein. Functional recovery was assessed at four-week intervals using footprint analysis. Gastrocnemius muscle mass preservation, histology, and nerve histomorphometry were evaluated at 120 days. Nerves treated with a PTB-sealed autologous vein improved functional recovery at 120 days although the comparison between groups was not significantly different (SN: -58.4 +/- 10.9; XHAM: -57.9 +/- 8.7; Vein: -52.4 +/- 17.1). Good muscle mass preservation was observed in all groups, with no statistical differences between groups (SN: 69 +/- 7%; XHAM: 70 +/- 7%; Vein: 70 +/- 7%). Histomorphometry showed good axonal regeneration in all repair techniques. These results demonstrate that peripheral nerve repair using photosealed autologous veins produced regeneration at least equivalent to current gold-standard microsurgery. The use of autologous veins removes costs and foreign body concerns and would be readily available during surgery. This study illustrates a new repair method that could restore normal endoneurial homeostasis with minimal trauma following severe nerve injury.

Available Therapeutic Options for Corneal Neovascularization: A Review.

Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-ß) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-ß-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.

In Vivo Wound Healing Potential and Molecular Pathways of Amniotic Fluid and Moringa Olifera-Loaded Nanoclay Films.

Cutaneous wounds pose a significant health burden, affecting millions of individuals annually and placing strain on healthcare systems and society. Nanofilm biomaterials have emerged as promising interfaces between materials and biology, offering potential for various biomedical applications. To explore this potential, our study aimed to assess the wound healing efficacy of amniotic fluid and Moringa olifera-loaded nanoclay films by using in vivo models. Additionally, we investigated the antioxidant and antibacterial properties of these films. Using a burn wound healing model on rabbits, both infected and non-infected wounds were treated with the nanoclay films for a duration of twenty-one days on by following protocols approved by the Animal Ethics Committee. We evaluated wound contraction, proinflammatory mediators, and growth factors levels by analyzing blood samples. Histopathological changes and skin integrity were assessed through H&E staining. Statistical analysis was performed using SPSS software (version 2; Chicago, IL, USA) with significance set at p < 0.05. Our findings demonstrated a significant dose-dependent increase in wound contraction in the 2%, 4%, and 8% AMF-Me.mo treatment groups throughout the study (p < 0.001). Moreover, macroscopic analysis revealed comparable effects (p > 0.05) between the 8% AMF-Me.mo treatment group and the standard treatment. Histopathological examination confirmed the preservation of skin architecture and complete epidermal closure in both infected and non-infected wounds treated with AMF-Me.mo-loaded nanofilms. RT-PCR analysis revealed elevated concentrations of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF), along with decreased levels of tumor necrosis factor-alpha (TNF-α) in AMF-Me.mo-loaded nanofilm treatment groups. Additionally, the antimicrobial activity of AMF-Me.mo-loaded nanofilms contributed to the decontamination of the wound site, positioning them as potential candidates for effective wound healing. However, further extensive clinical trials-based studies are necessary to confirm these findings.