Examining the etiological factors resulting in retinal detachment following prophylactic vitrectomy in the context of acute retinal necrosis syndrome.

OBJECTIVE: The aim of this study is to elucidate the factors contributing to the occurrence of retinal detachment (RD) following prophylactic vitrectomy in cases of acute retinal necrosis (ARN) syndrome. METHODS: A retrospective examination was undertaken, encompassing the medical records of patients diagnosed with ARN who underwent prophylactic vitreous intervention at the Ophthalmology Department of Wuhan University Renmin Hospital East Campus between October 2019 and September 2023. Subsequently, patients who manifested RD in the postoperative period were identified, and a comprehensive analysis was conducted to ascertain the factors underlying the occurrence of RD post-surgery. RESULTS: This study comprised 14 cases (involving 14 eyes) of patients diagnosed with ARN who underwent prophylactic vitreous intervention. The findings revealed that 4 patients experienced postoperative RD, resulting in an incidence rate of 28.57%. Notably, among these cases, 3 cases of RD manifested in the presence of silicone oil, while 1 case occurred subsequent to the removal of silicone oil. All 4 cases of RD exhibited varied degrees of proliferative vitreoretinopathy. Following the occurrence of RD, all patients underwent a secondary vitreous intervention coupled with silicone oil tamponade, leading to successful reattachment of the retina. However, despite these interventions, there was no significant enhancement observed in postoperative visual outcomes when compared to preoperative levels. CONCLUSION: RD following prophylactic vitrectomy in cases of ARN is not an infrequent occurrence and is primarily linked to the postoperative onset of proliferative vitreoretinopathy.

Cross-Linkable Polyion Complex Micelles from Polypept(o)ide-Based ABC-Triblock Copolymers for siRNA Delivery.

ABC-type triblock copolymers are a rising platform especially for oligonucleotide delivery as they offer an additional functionality besides the anyhow needed functions of shielding and complexation. The authors present a polypept(o)ide-based triblock copolymer synthesized by amine-initiated ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs), comprising a shielding block A of polysarcosine (pSar), a poly(S-ethylsulfonyl-l-cystein) (pCys(SO2 Et)) block B for bioreversible and chemo-selective cross-linking and a poly(l-lysine) (pLys) block C for complexation to construct polyion complex (PIC) micelles as vehicle for small interfering RNA (siRNA) delivery. The self-assembly behavior of ABC-type triblocks is investigated to derive correlations between block lengths of the polymer and PIC micelle structure, showing an enormous effect of the ß-sheet forming pCys(SO2 Et) block. Moreover, the block enables the introduction of disulfide cross-links by reaction with multifunctional thiols to increase stability against dilution. The right content of the additional block leads to well-defined cross-linked 50-60 nm PIC micelles purified from production impurities and determinable siRNA loading. These PIC micelles can deliver functional siRNA into Neuro2A and KB cells evaluated by cellular uptake and specific gene knockdown assays.

Extracellular matrix-based biomaterials for cardiac regeneration and repair.

The spectrum of ischemic heart diseases, encompassing acute myocardial infarction to heart failure, represents the leading cause of death worldwide. Although extensive progress in cardiovascular diagnoses and therapy has been made, the prevalence of the disease continues to increase. Cardiac regeneration has a promising perspective for the therapy of heart failure. Recently, extracellular matrix (ECM) has been shown to play an important role in cardiac regeneration and repair after cardiac injury. There is also evidence that the ECM could be directly used as a drug to promote cardiomyocyte proliferation and cardiac regeneration. Increasing evidence supports that applying ECM biomaterials to maintain heart function recovery is an important approach to apply the concept of cardiac regenerative medicine to clinical practice in the future. Here, we will introduce the essential role of cardiac ECM in cardiac regeneration and summarize the approaches of delivering ECM biomaterials to promote cardiac repair in this review.

Foldable Glistening-Free Acrylic Intraocular Lens Biomaterials with Dual-Side Heterogeneous Surface Modification for Postoperative Endophthalmitis and Posterior Capsule Opacification Prophylaxis.

Hydrophobic acrylic intraocular lenses (IOLs) are widely used in cataract treatment for posterior capsule opacification (PCO) prophylaxis. However, undesired glistening and postoperative endophthalmitis are two major potential risks. Hence, a series of poly(2-phenoxyethyl methacrylate-co-2-phenoxyethyl acrylate-co-2-ethylhexyl methacrylate) (PPPE) acrylic IOL materials were synthesized for "glistening-free" optimization. The selected PPPE with 2% 2-ethylhexyl methacrylate showed excellent optical, foldable, and thermomechanical properties. The anterior surface of PPPE was coated with polydopamine followed by gentamycin conjugation (PDA/GS). It inhibited bacterial adhesion by 74% and decreased the biofilm thickness by 87%. In inflammatory mimicking conditions, bacterial proliferation was restrained, with acidic-dependent GS release behavior. The surface of PPPE toward the posterior capsule remained hydrophobic. It was conducive to human lens epithelial cell adhesion, collagen IV and fibronectin adsorption, and the following "sealed sandwich structure" formation. In summary, the PPPE with a dual-side heterogeneous surface displayed good application prospects in postoperative endophthalmitis and PCO prevention.

Artificial Organelles Based on Cross-Linked Zwitterionic Vesicles.

Artificial organelles (AOs) are typical microcompartments with intracellular biocatalytic activity aimed to replace missing or lost cellular functions. Currently, liposomes or polymersomes are popular microcompartments to build AOs by embedding channel proteins in their hydrophobic domain and entrapping natural enzymes in their cavity. Herein, a new microcompartment is established by using monolayer cross-linked zwitterionic vesicles (cZVs) with a carboxylic acid saturated cavity. The monolayer structure endows the cZVs with intrinsic permeability; the cavity supplies the cZVs ability of in situ synthesis of artificial enzymes, and the pH-dependent charge-change property makes it possible to overcome the biological barriers. Typically, nanozymes of CeO2 and Pt NPs were synthesized in the cZVs to mimic peroxisome. In vitro experiments confirmed that the resulting artificial peroxisome (AP) could resist protein adsorption, endocytose efficiently, and escape from the lysosome. In vivo experiments demonstrated that the APs held a good therapeutic effect in ROS-induced ear-inflammation.

Specially-Made Lipid-Based Assemblies for Improving Transmembrane Gene Delivery: Comparison of Basic Amino Acid Residue Rich Periphery.

Cationic lipid based assemblies provide a promising platform for effective gene condensation into nanosized particles, and the peripheral properties of the assemblies are vital for complexation and interaction with physical barriers. Here, we report three cationic twin head lipids, and each of them contains a dioleoyl-glutamate hydrophobic tail and a twin polar head of lysine, arginine, or histidine. Such lipids were proven to self-assemble in aqueous solution with well-defined nanostructures and residual amino-, guanidine-, or imidazole-rich periphery, showing strong buffering capacity and good liquidity. The assemblies with arginine (RL) or lysine (KL) periphery exhibited positive charges (∼+35 mV) and complete condensation of pDNA into nanosized complexes (∼120 nm). In contrast, assemblies composed of histidine-rich lipids (HL) showed relatively low cationic electric potential (∼+10 mV) and poor DNA binding ability. As expected, the designed RL assemblies with guanidine-rich periphery enhanced the in vitro gene transfection up to 190-fold as compared with the golden standard PEI25k and Lipofectamine 2000, especially in the presence of serum. Meanwhile, interaction with cell and endo/lysosome membrane also revealed the superiority of RL complexes, that the guanidine-rich surface efficiently promoted transmembrane process in cellular internalization and endosomal disruption. More importantly, RL complexes also succeeded beyond others in vivo with significantly (∼7-fold) enhanced expression in HepG2 tumor xenografts in mice, as well as stronger green fluorescence protein imaging in isolated tumors and tumor frozen sections.

Liposomes as a Novel Ocular Delivery System for Brinzolamide: In Vitro and In Vivo Studies.

The objective of this study was to investigate the potential of liposomes as an ophthalmic delivery system for brinzolamide (Brz) to enhance the local glaucomatous therapeutic effect. The liposomes of Brz (Brz-LPs) were produced by the thin-film dispersion method with a particle size of 84.33 ± 2.02 nm and an entrapment efficiency of 98.32 ± 1.61%. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) analysis proved that Brz was successfully entrapped into Brz-LPs. Brz-LPs displayed a biphasic release pattern in vitro with burst release initially and sustained release afterwards. The corneal permeability was measured using modified Franz-type diffusion cells, and Brz-LPs showed 6.2-fold increase in the apparent permeability coefficient when compared with the commercial available formulation (B rz-Sus). Moreover, Brz-LPs (1 mg/mL Brz) showed a more sustained and effective intraocular pressure reduction (5-10 mmHg) than Brz-Sus (10 mg/mL Brz) in white New Zealand rabbits. Therefore, Brz-LPs were a hopeful formulation of Brz for glaucoma treatment and worthy of further investigation.

A whole-course-repair system based on ROS/glucose stimuli-responsive EGCG release and tunable mechanical property for efficient treatment of chronic periodontitis in diabetic rats.

Elevated glucose levels, multiple pro-inflammatory cytokines and the generation of excessive reactive oxygen species (ROS) are pivotal characteristics within the microenvironments of chronic periodontitis with diabetes mellitus (CPDM). Control of inflammation and modulation of immune system are required in the initial phase of CPDM treatment, while late severe periodontitis requires a suitable scaffold to promote osteogenesis, rebuild periodontal tissue and reduce alveolar bone resorption. Herein, a whole-course-repair system is introduced by an injectable hydrogel using phenylboronic acid functionalized oxidized sodium alginate (OSA-PBA) and carboxymethyl chitosan (CMC). Epigallocatechin-3-gallate (EGCG) was loaded to simultaneously adjust the mechanical property of the OSA-PBA/CMC + EGCG hydrogel (OPCE). This hydrogel has distinctive adaptability, injectability, and ROS/glucose-triggered release of EGCG, making it an ideal drug delivery carrier. As expected, OPCE hydrogel shows favourable antioxidant and anti-inflammatory properties, along with a regulatory influence on the phenotypic transition of macrophages, providing a favourable immune microenvironment. Apart from that, it provides a favourable mechanical support for osteoblast/osteoclast differentiation regulation at the late proliferation stage of periodontal regeneration. The practical therapeutic effects of OPCE hydrogels were also confirmed when applied for treating periodontitis in diabetic rats. In summary, OPCE hydrogel may be a promising whole-course-repair system for the treatment of CPDM.

pH-responsive size-adjustable liposomes induce apoptosis of fibroblasts and macrophages for rheumatoid arthritis treatment.

In rheumatoid arthritis (RA), macrophages infiltrate joints, while fibroblast-like synovial cells proliferate abnormally, forming a barrier against drug delivery, which hinders effective drug delivery to joint focus. Here we firstly designed a pH-responsive size-adjustable nanoparticle, composed by methotrexate (MTX)-human serum albumin (HSA) complex coating with pH-responsive liposome (Lipo/MTX-HSA) for delivering drugs specifically to inflamed joints in acidic environments. We showed in vitro that the nanoparticles can induce mitochondrial dysfunction, promote apoptosis of fibroblast-like synoviocytes and macrophages, further reduce the secretion of inflammatory factors (TNF-α, IL-1ß, MMP-9), and regulate the inflammatory microenvironment. We also demonstrated similar effects in a rat model of arthritis, in which Lipo/MTX-HSA accumulated in arthritic joints, and at low pH, liposome phospholipid bilayer cleavage released small-sized MTX-HSA, which effectively reduced the number of fibroblast-synoviocytes and macrophages in joints, alleviated joint inflammation, and repaired bone erosion. These findings suggest that microenvironment-responsive size-adjustable nanoparticles show promise as a treatment against rheumatoid arthritis. STATEMENT OF SIGNIFICANCE: Abnormal proliferation of fibroblast synoviocytes poses a physical barrier to effective nanoparticle delivery. We designed size-adjustable nano-delivery systems by preparing liposomes with cholesterol hemisuccinate (CHEM), which were subsequently loaded with small-sized albumin nanoparticles encapsulating the cytotoxic drug MTX (MTX-HSA), termed Lipo/MTX-HSA. Upon tail vein injection, Lipo/MTX-HSA could be aggregated at the site of inflammation via the ELVIS effect in the inflamed joint microenvironment. Specifically, intracellular acidic pH-triggered dissociation of liposomes promoted the release of MTX-HSA, which was further targeted to fibroblasts or across fibroblasts to macrophages to exert anti-inflammatory effects. The results showed that liposomes with adjustable particle size achieved efficient drug delivery, penetration and retention in joint sites; the strategy exerted significant anti-inflammatory effects in the treatment of rheumatoid arthritis by inducing mitochondrial dysfunction to promote apoptosis in fibrosynoviocytes and macrophages.

Effectiveness and safety of n-butyl-2-cyanoacrylate medical adhesive for noninvasive patch fixation in laparoscopic inguinal hernia repair.

BACKGROUND: Our purpose was to compare the recurrence rate and other clinical outcomes of laparoscopic (LS) transabdominal preperitoneal (TAPP) inguinal hernia repair using n-butyl-2-cyanoacrylate (NBCA) for mesh fixation with those of no mesh fixation and mesh fixation with titanium spiral tacks (ST). METHODS: The medical records of patients who received LS TAPP inguinal hernia repair between 2009 and 2012 at our institution were reviewed. Patients were included if the received LS TAPP with either no mesh fixation, mesh fixation with NBCA only, fixation with ST only, or fixation with NBCA + ST. Outcome measures were operation time, postoperative length of stay, visual analogue scale (VAS) pain score 24 h after surgery, postoperative complications, and hernia recurrence. RESULTS: A total of 1,027 TAPP cases were included. In 552 cases, meshes were fixed with NBCA only, in 89 cases only ST were used, in 47 cases ST and NBCA were used, and in 339 cases meshes were not fixed. The groups were comparable with respect to demographic and clinical characteristics. No surgical complications occurred in any group. VAS pain scores were significantly lower in the nonfixation and NBCA only groups (1.4 ± 0.6 and 1.3 ± 0.6, respectively) than in the ST and NBCA + ST groups (2.2 ± 0.9 and 2.2 ± 0.7, respectively; P = 0.001). The mean follow-up duration was ~19 months. At the final follow-up, no wound infections or hernia recurrences had occurred in any of the groups. No occurrence of chronic pain was noted in the nonfixation and NBCA only groups, whereas two cases (2.2%) were noted in the ST group and one case (2.1%) in the NBCA + ST group (P = 0.005). CONCLUSIONS: The use of NBCA medical adhesive for noninvasive patch fixation in laparoscopic hernia repair (TAPP) is effective and safe.

Supramolecular Polymer-Nanomedicine Hydrogel Loaded with Tumor Associated Macrophage-Reprogramming polyTLR7/8a Nanoregulator for Enhanced Anti-Angiogenesis Therapy of Orthotopic Hepatocellular Carcinoma.

Anti-angiogenic therapies targeting inhibition of vascular endothelial growth factor (VEGF) pathway show clinical benefit in hypervascular hepatocellular carcinoma (HCC) tumors. However, HCC expresses massive pro-angiogenic factors in the tumor microenvironment (TME) in response to anti-angiogenic therapy, recruiting tumor-associated macrophages (TAMs), leading to revascularization and tumor progression. To regulate cell types in TME and promote the therapeutic efficiency of anti-angiogenic therapy, a supramolecular hydrogel drug delivery system (PLDX-PMI) co-assembled by anti-angiogenic nanomedicines (PCN-Len nanoparticles (NPs)) and oxidized dextran (DX), and loaded with TAMs-reprogramming polyTLR7/8a nanoregulators (p(Man-IMDQ) NRs) is developed for orthotopic liver cancer therapy. PCN-Len NPs target tyrosine kinases of vascular endothelial cells and blocked VEGFR signaling pathway. p(Man-IMDQ) NRs repolarize pro-angiogenic M2-type TAMs into anti-angiogenic M1-type TAMs via mannose-binding receptors, reducing the secretion of VEGF, which further compromised the migration and proliferation of vascular endothelial cells. On highly malignant orthotopic liver cancer Hepa1-6 model, it is found that a single administration of the hydrogel formulation significantly decreases tumor microvessel density, promotes tumor vascular network maturation, and reduces M2-subtype TAMs, thereby effectively inhibiting tumor progression. Collectively, findings in this work highlight the great significance of TAMs reprogramming in enhancing anti-angiogenesis treatment for orthotopic HCC, and provides an advanced hydrogel delivery system-based synergistic approach for tumor therapy.

High Strength Titanium with Fibrous Grain for Advanced Bone Regeneration.

Pure titanium is widely used in clinical implants, but its bioinert properties (poor strength and mediocre effect on bone healing) limit its use under load-bearing conditions. Modeling on the structure of collagen fibrils and specific nanocrystal plane arrangement of hydroxyapatite in the natural bone, a new type of titanium (Ti) with a highly aligned fibrous-grained (FG) microstructure is constructed. The improved attributes of FG Ti include high strength (≈950 MPa), outstanding affinity to new bone growth, and tight bone-implant contact. The bone-mimicking fibrous grains induce an aligned surface topological structure conducive to forming close contact with osteoblasts and promotes the expression of osteogenic genes. Concurrently, the predominant Ti(0002) crystal plane of FG Ti induces the formation of hydrophilic anatase titanium oxide layers, which accelerate biomineralization. In conclusion, this bioinspired FG Ti not only proves to show mechanical and bone-regenerative improvements but it also provides a new strategy for the future design of metallic biomaterials.

Fabrication of Janus-type nanocomposites from cellulose nanocrystals for self-healing hydrogels' flexible sensors.

Janus bio-nanomaterials have great application potential in functional solid surfactants, probes and flexible sensors. In this manuscript, the sustainable Janus cellulose nanocrystals-type (CNCs-type) nanomaterials were prepared by Pickering emulsion template method. The asymmetric functionalism of Janus nanorods was realized by asymmetrically grafting polypyrrole (PPy) and polydopamine (PDA) onto different sides of CNCs (Janus CNCs-PPy /PDA (JCNs)). JCNs was successfully applied to self-healing nanocomposite hydrogels and further applied to the development of flexible sensors. The self-healing efficiency of nanocomposite hydrogels was 87.2%, and the stress and strain reached 3.50 MPa and 453.45%, respectively. It is worth noting that flexible sensors have been widely used in the field of wearable electronic sensing for real-time monitoring of human movement due to their high sensitivity (gauge factor (GF) = 9.9) and fast response time (260 ms).

Gene delivery of chitosan-graft-polyethyleneimine vectors loaded on scaffolds for nerve regeneration.

As an important transcription factor, c-Jun could upregulate growth factors expression in Schwann cells (SCs). Arginine-Glycine-Aspartate (RGD)-functionalized chitosan-graft-polyethyleneimine (RCP) gene vectors were prepared through the maleic anhydride & the carbodiimide methods, and electrostatically bound with c-Jun plasmids (pJUN), finally loaded on poly-L-lactic acid/silk fibroin parallel fiber films to fabricate nerve scaffold (RCP/pJUN-PSPF@PGA), which could locally deliver c-Jun plasmids into SCs via the mediation of RGD peptides, and upregulate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in SCs. After the scaffold was bridged in sciatic nerve defect, the delivery of c-Jun plasmids from RCP/pJUN-PSPF@PGA facilitated SCs to sustain the expressions of NGF, BDNF and vascular endothelial growth factor in the injury field, promoting myelination, axonal growth and microvascular generation and nerve regeneration, muscle reinnervation and functional recovery. These results suggested that RCP/pDNA-PSPF@PGA, as an effective gene delivery platform, could provide a local gene therapy to improve nerve regeneration.

Epidermal growth factor-PEG functionalized PAMAM-pentaethylenehexamine dendron for targeted gene delivery produced by click chemistry.

Aim of this study was the site-specific conjugation of an epidermal growth factor (EGF)-polyethylene glycol (PEG) chain by click chemistry onto a poly(amido amine) (PAMAM) dendron, as a key step toward defined multifunctional carriers for targeted gene delivery. For this purpose, at first propargyl amine cored PAMAM dendrons with ester ends were synthesized. The chain terminal ester groups were then modified by oligoamines with different secondary amino densities. The oligoamine-modified PAMAM dendrons were well biocompatible, as demonstrated in cytotoxicity assays. Among the different oligoamine-modified dendrons, PAMAM-pentaethylenehexamine (PEHA) dendron polyplexes displayed the best gene transfer ability. Conjugation of PAMAM-PEHA dendron with PEG spacer was conducted via click reaction, which was performed before amidation with PEHA. The resultant PEG-PAMAM-PEHA copolymer was then coupled with EGF ligand. pDNA transfections in HuH-7 hepatocellular carcinoma cells showed a 10-fold higher efficiency with the polyplexes containing conjugated EGF as compared to the ligand-free ones, demonstrating the concept of ligand targeting. Overall gene transfer efficiencies, however, were moderate, suggesting that additional measures for overcoming subsequent intracellular bottlenecks in delivery have to be taken.

Enhancing the antibacterial activity of biomimetic HA coatings by incorporation of norvancomycin.

BACKGROUND: Bacterial infections associated with the use of biomaterials remain a great challenge for orthopedic surgery. The main purpose of the work discussed in this paper was to improve the antibacterial activity of a biomimetic calcium phosphate (CP) coating widely used in orthopedic biomaterials by incorporation of norvancomycin in the biomimetic process. METHODS: CP coating and CP coating containing norvancomycin were produced on a titanium alloy (Ti6Al4V) surface by a biomimetic process. The morphology, surface crystal structure, and concentrations of elements in the coatings were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDX), respectively. The amount of norvancomycin and its release were investigated by UV-visible spectroscopy. MTT was used to investigate cell behavior. The morphology of adhered bacteria was observed by SEM. Antibacterial activity was expressed as inhibition zone by using Staphylococcus aureus (ATCC 25923) as model bacteria. RESULTS: Results from SEM, EDX, and XRD revealed formation of a hydroxyapatite (HA) coating. The amount of antibiotic in the CP coating increased with increasing concentration of norvancomycin in the coating solution, followed by a plateau when the concentration of norvancomycin in the coating solution reached 600 mg/l. Approximately 2.16 µg norvancomycin per mg coating was co-precipitated with the CP layer onto titanium alloy discs when 600 mg/l norvancomycin coating solution was applied. The norvancomycin had a fast release profile followed by slow release. The MTT test of osteoblast cell cultures suggested that coatings containing norvancomycin did not cause any cytotoxicity compared with the CP coating and control titanium plate. The antibacterial activity test showed that the norvancomycin released from the coatings inhibited the growth of Staphylococcus aureus; more bacteria were found on the CP coating than on the norvancomycin-loaded coating. CONCLUSIONS: A norvancomycin-loaded HA-like coating was successfully obtained on titanium surfaces. The norvancomycin incorporated had no negative effects on osteoblast cell behavior. The released norvancomycin results in excellent antibacterial activity of Ca-P coatings. Therefore, incorporation of norvancomycin can enhance antibacterial activity and the norvancomycin-loaded CP coating can be used to inhibit post-surgical infections in orthopaedics.

A Gd-doped polydopamine (PDA)-based theranostic nanoplatform as a strong MR/PA dual-modal imaging agent for PTT/PDT synergistic therapy.

Based on widely used photoacoustic imaging (PAI) and photothermal properties of polydopamine (PDA), a multifunctional Gd-PDA-Ce6@Gd-MOF (GPCG) nanosystem with a core-shell structure and strong imaging ability was constructed. Benefitting from the metal-organic framework (MOF) structure, GPCG nanoparticles (NPs) showed enhanced magnetic resonance imaging (MRI) ability with high relaxation rates (r1 = 13.72 mM-1 s-1 and r2 = 216.14 mM-1 s-1). The MRI effect of Gd ions combined with the PAI effect of PDA, giving GPCG NPs a dual-modal imaging ability. The core, mainly composed of PDA and photodynamic photosensitizer chlorin e6 (Ce6), achieved photothermal/photodynamic therapy (PTT/PDT) synergistic performance. Besides, to overcome the unexpected release of Ce6, the MOF shell realized pH-sensitive release and a high local concentration. Through in vivo studies, we concluded that GPCG NPs show a good inhibitory effect on tumor growth. In conclusion, we successfully obtained a GPCG theranostic nanoplatform and paved the way for subsequent design of imaging guided therapeutic nanostructures based on metal-doped PDA.

Drug-loaded and Blue-ray Filtered Hydrogel as a Potential Intraocular Lens for Cataract Treatment.

BACKGROUND: Indomethacin (IND) is a class of non-steroidal, anti-inflammatory drugs, which is used to treat various kinds of ocular inflammation, and has been reported to prevent posterior capsule opacification (PCO) by inhibiting the mitosis and collagen synthesis of human lens epithelial cells (LECs). In addition, the specific absorption spectrum of indomethacin shows the effect of absorbing short-wavelength blue-violet light. OBJECTIVE: We prepared an indomethacin-loaded hydrogel as a potential intraocular lens (IOLs) material to prevent endophthalmitis, PCO and filter harmful blue light. METHODS: Indomethacin prodrugs (HEMA-IND) (HI) were prepared by esterification of indomethacin and 2-hydroxyethyl methacrylate (HEMA), and poly (HEMA-co-MAA-co-MMA-co- HI) (HAMI) hydrogels were prepared by free-radical polymerization of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), methacrylic acid (MAA) and HI. The physical and chemical properties of obtained hydrogel were detected, including optical, morphology, thermomechanical and surface properties, equilibrium water content, drug release behaviors and cytotoxicity. RESULTS: HAMI hydrogels can filter harmful short-wavelength blue light and show other necessary properties like visible light transparency, glass transition temperatures, mechanical strength, and biocompatibility for making intraocular lenses. Meanwhile, MAA increases the hydrophilicity of the hydrogels, resulting in a lower water contact angle and controllable drug release from the hydrogels. CONCLUSION: In summary, HAMI hydrogels show a great potential as IOL biomaterials that can maintain the sustained release of indomethacin and filter harmful blue light after cataract surgery. Lay Summary: People with cataract surgery can be at high risk of postoperative complications, such as PCO and postoperative endophthalmitis. Moreover, early IOLs allowed all ultraviolet (UV) and visible light to pass through retina without restriction, thus to damage the retina and the retinal pigment epithelium, which may lead to retinopathy and age-related macular degeneration (AMD). Herein, we sought to design and prepare a kind of IOLs loaded with indomethacin to mitigate those postoperative complications and filter harmful blue light to improve the treatment prognosis.

Stable Fabrication of Zwitterionic Coating Based on Copper-Phenolic Networks on Contact Lens with Improved Surface Wettability and Broad-Spectrum Antimicrobial Activity.

Ocular dryness and contact lens(CL)-related microbial keratitis (MK) are two major risks of wearing CLs. The development of multifunctional surface coating for CLs with excellent hydrating and antimicrobial properties is a practical strategy to improve the comfort of CL wearers and to prevent corneal infection. Here, we develop zwitterionic and antimicrobial metal-phenolic networks (MPNs) based on the coordination of copper ions (CuII) and the poly(carboxylbetaine-co-dopamine methacrylamide) copolymer (PCBDA), which can be easily one-step prepared onto CLs due to the near-universal adherent properties of catechol groups. The zwitterionic and antifouling carboxybetaine (CB) groups of the CuII-PCBDA coating can significantly increase the wettability of CLs and reduce their protein adsorptions, resulting in a lens surface that is more water retentive and with lower protein binding to prevent tear film evaporation and eye dryness. In addition, since the immobilized copper ions in the MPNs impart them with ion-mediated antimicrobial activity, the CuII-PCBDA coating exhibits a strong and broad-spectrum antimicrobial activity against MK related pathogenic microbes, including bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and fungi, such as Candida albicans. Compared with a pristine CL, the CuII-PCBDA-coated CL effectively inhibited biofilm formation even after daily exposure to the above microbial environment for 14 days. Notably, the CuII-PCBDA coating developed in this study is not only biocompatible with 100% cell viability following direct contact with human corneal epithelial cells (HCECs) for 48 h but also maintains the optical clarity of the native CLs. Thus, the CuII-PCBDA coating has a great application potential for the development of a multifunctional surface coating for CLs for increased CL comfort and prevention of MK.

Synthesis, characterization and transfection of a novel folate-targeted multipolymeric nanoparticles for gene delivery.

Novel folate-conjugated biodegradable multipolymeric nanoparticles (NPs) were constructed and evaluated for potential use in gene delivery to human cervical carcinomas Hela cells, which overexpressed folate receptors. Folate-poly(ethylene glycol)-poly(D: , L: -lactic-co-glycolic acid) (PELGA-F) was synthesized and collaborated with poly-L: -lysine (PLL) to form polymer-polycationic peptide-DNA (PPD) NPs. Fluorescein sodium and polylysine-condensed DNA (PD) were encapsulated in both PELGA nanoparticles (PELGA-NPs) and folate modified nanoparticles (PELGA-F-NPs), which were prepared by a modified solvent extraction/evaporation method. Effects of the folate conjugation and PLL introduction on the uptake of NPs was qualified by fluorescent invert microscopy and quantified by spectrofluorometric measurement, while effect on the gene expression was measured by X-gal staining and luciferase assay, both using Hela cells as an in vitro model. Results showed that cellular uptake of NPs was enhanced by folate modification, but had no difference after PLL encapsulation. In transfection tests, increased gene expression also confirmed the different functions of folate and PLL introduction. It is feasible that folate-linked multipolymeric NPs should be an efficient targeted carrier for gene delivery.