External limiting membrane angle as a composite predictive index for post-operative ELM closure in full thickness macular holes.

AIM: To evaluate pre-operative qualitative and quantitative parameters of external limiting membranes (ELM) and other associated full thickness macular holes (FTMH) features and their predictive values for post-operative anatomical and functional outcomes. METHODS: This was a retrospective study of 48 eyes that underwent vitrectomy with internal limiting membrane (ILM) peeling for FTMH and had type 1 closure. All subjects underwent optical coherence tomography (SDOCT, Heidelberg, Spectralis), and the eyes were divided into complete ELM closure (CEC) and incomplete ELM closure (IEC) groups based on the post-operative OCTs within 2 months, and ROC curves were used to estimate which of the pre-operative parameters could best predict eyes falling in the CEC group. RESULTS: The mean pre-op ELM defect was smaller in CEC group (594 µm vs 1126 µm, p < 0.001) and so was the pre-op EZ defect (770 µm vs 1186 µm, p = 0.001). The mean ELM angle also was smaller in the CEC group (51.6° vs 102.5°, p < 0.001) and so was the mean hole inlet distance (353 µm vs 596 µm, p < 0.001). The post-operative ELM defect showed a significant negative correlation with visual acuity (r = - 0.319; p = 0.027). The ELM angle was most predictive with an AUROC of 0.958, and a cut-off of 68.3° had a sensitivity of 90% and a specificity of 89%. CONCLUSION: Our study introduces a novel parameter called the ELM angle and proves that it has a high sensitivity and specificity in predicting complete ELM reformation post-surgery in the short term as well as the long term.

Dual growth factor entrapped nanoparticle enriched alginate wafer-based delivery system for suppurating wounds.

We have investigated the wound healing efficiency of calcium alginate wafer embedded with growth factor entrapped PLGA nanoparticle. Herein, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) entrapped PLGA nanoparticles were synthesized and embedded in a sodium alginate gel by freeze-drying technique. The synthesized dressing exhibited a high degree of swelling and appropriate porosity. The scaffold was characterized by Scanning Electron Microscopy (SEM) showing a highly porous morphology. Also, incorporation of growth factor loaded nanoparticles in a wafer-based delivery system resulted in localized growth factor delivery at the site of the wound in a sustained manner. The biocompatibility of the scaffold was evaluated by MTT assay, which showed a higher cell proliferation in the proposed scaffold as compared to the control. In vivo wound healing efficiency of the scaffold was evaluated using a full thickness murine wound model, which showed improved re-epithelialization, collagen deposition, and angiogenesis. These results suggest the use of the scaffold as a promising wound dressing material.

ECM-mimicking nanofibrous scaffold enriched with dual growth factor carrying nanoparticles for diabetic wound healing.

Polymeric nanofibrous scaffolds provide fine-tuned structures with inter-connecting pores resembling the natural extracellular matrix (ECM) in tissues, and show good potential in assisting the creation of artificial functional tissue. Additional application of growth factors helps to regulate the cellular behaviors and tissue assembly in the scaffolds, which eases the healing process. In this study, we synthesized an electrospun polymer scaffold system enriched with nanoparticles containing growth factors for accelerated healing of diabetic wounds. BSA nanoparticles were synthesized by cross-linking with PEG aldehyde. To free the amino group of BSA, heparin was conjugated by EDC/NHS chemistry. The angiogenic growth factors bFGF and VEGF were bound to heparin by electrostatic interaction. These nanoparticles were adsorbed on to electrospun collagen/PLGA/chitosan nanofibers. The synthesized nanofiber system was evaluated in vitro for its cell viability and proliferation. In vivo experiments conducted in a streptozotocin-induced diabetic mice model showed accelerated wound healing. The excellent healing efficiency of this ECM-mimicking nanofiber scaffold makes it a great candidate for therapeutic application in diabetic wounds.

PEG grafted chitosan scaffold for dual growth factor delivery for enhanced wound healing.

Application of growth factors at wound site has improved the efficiency and quality of healing. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) induce proliferation of various cells in wound healing. Delivery of growth factor from controlled release systems protect it from degradation and also result in sustained delivery of it at the site of injury. The goal of the study was to develop a Polyethylene glycol (PEG) cross-linked cotton-like chitosan scaffold (CS-PEG-H) by freeze-drying method and chemically conjugate heparin to the scaffold to which the growth factors can be electrostatically bound and evaluate its wound healing properties in vitro and in vivo. The growth factor containing scaffolds induced increased proliferation of HaCaT cells, increased neovascularization and collagen formation seen by H and E and Masson's trichrome staining. Immunohistochemistry was performed using the Ki67 marker which increased proliferation of cells in growth factor containing scaffold treated group. Frequent dressing changes are a major deterrent to proper wound healing. Our system was found to release both VEGF and bFGF in a continuous manner and attained stability after 7 days. Thus our system can maintain therapeutic levels of growth factor at the wound bed thereby avoiding the need for daily applications and frequent dressing changes. Thus, it can be a promising candidate for wound healing.

Multiple cargo deliveries of growth factors and antimicrobial peptide using biodegradable nanopolymer as a potential wound healing system.

BACKGROUND: Treatment of wounds with the help of nanoparticles (NPs) is more effective and superior in comparison to traditional wound healing methods as it protects and sustains active drug release at the wound site thus enhancing the safety of the drug and reducing the possibility of side effects. The advantages of this method are the possibility of allowing a reduction in administered dose, limiting toxicity levels to the minimum, and increasing safety of topical delivery of the drug. MATERIALS AND METHODS: We report the synthesis of a novel poly (lactic-co-glycolic acid) (PLGA) NP-based multicargo delivery system for growth factors and antimicrobial peptide. Growth factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were entrapped in PLGA NPs by solvent diffusion method and an antimicrobial peptide (K4) was conjugated to the NP by carbodiimide chemistry. The developed multiple cargo delivery systems with growth factors (VEGF and bFGF) and an antimicrobial peptide (K4) were investigated and optimized for potential wound healing. RESULTS: The system showed a sustained release of growth factors and was evaluated for cytotoxicity by MTT and live/dead assay, which revealed that the bioactivity of the growth factor-entrapped NPs was higher than that of free growth factors, and it also induced enhanced cell proliferation in vitro. CONCLUSION: The development of a system for the codelivery of growth factors (VEGF and bFGF) and an antimicrobial peptide (K4) was investigated for potential wound healing application. The entrapment of growth factors with very high efficiency is an advantage in this method along with its sustained release from the nanoparticulate system, which will enhance the angiogenesis. Our system also displayed broad-spectrum antimicrobial activity against both gram-positive and gram-negative bacteria.