Yuemei Han

Hydrophobic modification of polymethyl methacrylate as intraocular lenses material to improve the cytocompatibility

The development of posterior capsule opacification (PCO) after intraocular lenses (IOL) implantation for dealing with cataract is mainly due to the severe loss of the human lens epithelial cells (HLECs) during surgery contact. A novel poly (hedral oligomeric silsesquioxane-co-methyl methacrylate) copolymer (allyl POSS-PMMA) was synthesized by free radical polymerization method to promote the adhesion of HLECs. FT-IR and (1)H NMR measurements indicated the existence of POSS cage in the product, which demonstrated the successful synthesis of allyl POSS-PMMA copolymer. Effect of allyl POSS in the hybrids on crystal structure, surface wettability and morphology, optical transmission, thermodynamic properties and cytocompatibility was investigated in detail. X-ray diffraction peaks at 2θ∼11° and 12° indicated that POSS molecules had aggregated and crystallized. Thermogravimetric analysis-differential scanning calorimeter and optical transmission measurements confirmed that the allyl POSS-PMMA copolymer had high glass transition temperatures (more than 100°C) and good transparency. The hydrophilicity and morphology of PMMA and copolymers surfaces were characterized by static water contact angle and atomic force microscopy. The results revealed that the surface of the allyl POSS-PMMA copolymer displayed higher hydrophobicity and higher roughness than that of pure PMMA. The surface biocompatibility was evaluated by morphology and activity measurement with HLECs in vitro. The results verified that the surface of allyl POSS-PMMA copolymer films had more HLECs adhesion and better spreading morphology than that of PMMA film.

Surface modification of intraocular lenses with hyaluronic acid and lysozyme for the prevention of endophthalmitis and posterior capsule opacification

Posterior capsule opacification is one of the complications of cataract surgery caused by the adhesion and reproduction of residual human lens epithelial cells (HLECs) on the posterior capsule. Infectious endophthalmitis is another common complication due to bacterial colonization and biofilm formation. Hyaluronic acid–lysozyme (HA–lysozyme) composite coating was covalently grafted on the surface of PMMA intraocular lenses by reaction with N-hydroxysuccinimide (NHS) and 1-etil-3-(3-dimetilaminopropil) carbodiimida (EDC). Measurements of water contact angle and AFM revealed that the coating created a highly hydrophilic surface with low roughness. Adherences of S. aureus and HLECs on PMMA with HA or HA–lysozyme coating were significantly reduced due to the hydrophilic property of HA. Bactericidal activity of HA–lysozyme coatings, measured by SEM and LIVE/DEAD bacterial viability kit, was remarkably effective against S. aureus owing to the component of lysozyme. The achievement of the HA–lysozyme composite coating with anti-adhesive and antibacterial properties can potentially be widely used on surface modification of PMMA intraocular lenses and other biomedical implants.

Synthesis of MA POSS–PMMA as an intraocular lens material with high light transmittance and good cytocompatibility

Poly(methyl methacrylate) (PMMA) has been widely used for intraocular lenses (IOL) but may lead to posterior capsule opacification (PCO) after implantation due to its undesirable hydrophilicity and surface morphology. A novel methacrylisobutyl polyhedral oligomeric silsesquioxane-co-poly methyl methacrylate copolymer (MA POSS–PMMA) was synthesized by a free radical polymerization method to improve its material properties and cytocompatibility. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and proton nuclear magnetic resonance spectroscopy (1H NMR) measurements demonstrated the successful synthesis of MA POSS–PMMA copolymer. The incorporation of MA POSS greatly changed the crystal structure, surface wettability, optical transmission and cytocompatibility of PMMA. XRD peaks at 2θ ∼ 38.5, 44.7 and 66.1° indicated that a portion of the MA POSS molecules had aggregated and crystallized. Furthermore, larger aggregates are formed at higher MA POSS contents. The optical transmission of the copolymers was up to 99%, which was better than pure PMMA. The hydrophilicity and morphology of the IOL surface were characterized by static water contact angle and atomic force microscopy. Results revealed that MA POSS rendered the surface more hydrophobic and with higher roughness than the pure PMMA. Biocompatibility of copolymers with human lens epithelial cells (HLECs) was further evaluated by morphology and activity measurements in vitro. More HLECs adhesion and better spreading morphology on the surfaces of MA POSS–PMMA copolymers than that on PMMA was shown.

Surface-initiated RAFT polymerization of p (MA POSS-co-DMAEMA+) brushes on PDMS for improving antiadhesive and antibacterial properties

ABSTRACT Poly (dimethylsiloxane) (PDMS) silicones, as a common intraocular lenses material, often lead to the happen of posterior capsule opacification due to the adhesion and reproduction of residual human lens epithelial cells (HLECs) on the posterior capsule after surgery. Bacterial infection is a potentially catastrophic complication of cataract surgery, which occurs within several days after implantation of the lens. A novel poly (methacrylisobutyl polyhedral oligomeric silsesquioxane-co-2-(dimethylamino)-ethyl methacrylate) (p (MA POSS-co-DMAEMA)) brush was synthesized by reversible addition–fragmentation chain-transfer (RAFT) polymerization. After being quaternized treatment by 1-bromo-heptane, p (MA POSS-co-DMAEMA+) brushes with bactericidal function were obtained. The optical transmission of the brushes functionalized PDMS was better than p (DMAEMA+) coating modified PDMS, which may be due to the similar chemical composition of MA POSS and PDMS. Measurements of water contact angle, spectroscopic ellipsometry, and atomic force microscope were used to characterize hydrophilicity, thickness, and morphology of the brushes. Results revealed that brushes rendered PDMS surface more hydrophilicity and higher roughness. Adherences of bovine serum albumin and HLECs on the p (MA POSS-co-DMAEMA+) brushes were significantly reduced due to the hydrophilic property and cytotoxicity of the brushes. Bactericidal activity of the brushes, measured by shake-flask culture and LIVE/DEAD bacterial viability kit staining methods, was remarkably effective against S. aureus owing to the component of p (DMAEMA+). GRAPHICAL ABSTRACT

Development of antibacterial and high light transmittance bulk materials: Incorporation and sustained release of hydrophobic or hydrophilic antibiotics

Infection associated with medical devices is one of the most frequent complications of modern medical biomaterials. Bacteria have a strong ability to attach on solid surfaces, forming colonies and subsequently biofilms. In this work, a novel antibacterial bulk material was prepared through combining poly(dimethyl siloxane) (PDMS) with either hydrophobic or hydrophilic antibiotics (0.1-0.2 wt%). Scanning electron microscopy, water contact angle and UV-vis spectrophotometer were used to measure the changes of surface topography, wettability and optical transmission. For both gentamicin sulfate (GS) and triclosan (TCA), the optical transmission of the PDMS-GS and PDMS-TCA blend films was higher than 90%. Drug release studies showed initial rapid release and later sustained release of GS or TCA under aqueous physiological conditions. The blend films demonstrated excellent bactericidal and sufficient biofilm inhibition functions against Gram-positive bacteria (Staphylococcus aureus, S. aureus) measured by LIVE/DEAD bacterial viability kit staining method. Kirby-Bauer method showed that there was obvious zone of inhibition (7.5-12.5mm). Cytocompatibility assessment against human lens epithelial cells (HLECs) revealed that the PDMS-GS blend films had good cytocompatibility. However, the PDMS-TCA blend films showed certain cytotoxicity against HLECs. The PDMS-0.2 wt% GS blend films were compared to native PDMS in the rabbit subcutaneous S. aureus infection model. The blend films yielded a significantly lower degree of infection than native PDMS at day 7. The achievement of the PDMS-drug bulk materials with high light transmittance, excellent bactericidal function and good cytocompatibility can potentially be widely used as bio-optical materials.

Hydrated polysaccharide multilayer as an intraocular lens surface coating for biocompatibility improvements

Posterior capsule opacification (PCO) is a significant complication of intraocular lens (IOL) implantation in cataract surgery, in which the adhesion and proliferation of lens epithelial cells (LECs) on the IOL surface play important roles. In the present study, a highly swollen hyaluronic acid (HA)/chitosan (CHI) polyelectrolyte multilayer was fabricated on the IOL surface via the layer by layer technique. Quartz crystal microbalance with dissipation (QCM-D) results not only show the successful construction of the multilayer, but also indicate its hydrogel-like swollen property. The water content of the (HA/CHI)5 multilayer is around 400%, as obtained by thermogravimetry (TG) analysis. Compared with a pristine IOL, the polysaccharide multilayer modification does not influence its optical property, whereas the adhesion and proliferation of LECs are greatly inhibited. In vivo ocular implantation results show that such a polysaccharide multilayer modification presents good in vivo biocompatibility, and has positive effects on reducing PCO development.

Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization

Infections after surgery or endophthalmitis are potentially blinding complications caused by bacterial adhesion and subsequent biofilm formation on the intraocular lens. Neither single-function anti-adhesion surface nor contacting killing surface can exhibit ideal antibacterial function. In this work, a novel (2-(dimethylamino)-ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) (p (DMAEMA-co-MPC)) brush was synthesized by “grafting from” method through reversible–addition fragmentation chain transfer polymerization. 1-Bromoheptane was used to quaternize the p (DMAEMA-co-MPC) brush coating and to endow the surface with bactericidal function. The success of the surface functionalization was confirmed by atomic force microscopy, water contact angle, and spectroscopic ellipsometry. The quaternary ammonium salt units were employed as efficient disinfection that can eliminate bacteria through contact killing, whereas the 2-methacryloyloxyethyl phosphorylcholine units were introduced to suppress unwanted nonspecific adsorption. The functionalized poly(dimethyl siloxane) surfaces showed efficiency in reducing bovine serum albumin adsorption and in inhibiting bacteria adhesion and biofilm formation. The copolymer brushes also demonstrated excellent bactericidal function against gram-positive (Staphylococcus aureus) bacteria measured by bacteria live/dead staining and shake-flask culture methods. The surface biocompatibility was evaluated by morphology and activity measurement with human lens epithelial cells in vitro. The achievement of the p (DMAEMA+-co-MPC) copolymer brush coating with nonfouling, bactericidal, and bacteria corpse release properties can be used to modify intraocular lenses.

Ocular biocompatibility evaluation of POSS nanomaterials for biomedical material applications

The tremendous advancement of polyhedral oligomeric silsesquioxanes (POSSs) has been focused on the field of biomaterial applications including tissue engineering, drug delivery, biomedical devices and biosensors. More recently, POSSs have been used in components of ophthalmic biomedical devices, such as contact lenses and intraocular lenses due to their chemical inertness and transparency. A systematic biocompatibility evaluation of POSS nanomaterials is thus essential. Herein, the ocular biocompatibility and cytotoxicity of POSS nanomaterials were investigated both in vitro and in vivo. Three types of commercial POSS nanomaterials with different functional groups were utilized in this research, including aminoethylaminopropylisobutyl-POSS (NH2-POSS), mercaptopropylisobutyl-POSS (SH-POSS) and octahydroxypropyldimethylsilyl-POSS (HO-POSS). The cellular metabolic activity, membrane integrality, cell apoptosis and oxidative damage were tested on human lens epithelial cells (HLECs) under different concentrations of POSS nanomaterial exposure. The ocular irritation on rabbit eyes was measured as well. The results show that the studied POSS nanomaterials do not exhibit any significant toxicity to cell growth and proliferation in most cases, except for the NH2-POSS, which decreases the cellular viability at high concentration. All of the POSS nanomaterials slightly induced oxidative stress as a result of an increase in reactive oxygen species (ROS), however they did not generate cell apoptosis. The animal experiment results also show that no acute ocular irritation can be detected after POSS nanomaterial administration. These results indicate the good ocular biocompatibility of the POSS nanomaterials in most cases, which have great potential in ocular biomedical applications.

Surface PEGylation of intraocular lens for PCO prevention: An in vivo evaluation.

Posterior capsular opacification (PCO) is a common complication in cataract surgery. The development of PCO is attributed to the combination of adhesion, migration, proliferation, and transdifferentiation of the residual lens epithelial cells (LEC) onto the interface of intraocular lens (IOL) material and lens posterior, in which the initial adhesion is the beginning step and plays important roles. In the present study, hydrophilic polyethylene glycol (PEG) was immobilized onto IOL surface via plasma-aided chemical grafting procedure. The attenuated total reflection – Fourier transform infrared (ATR-FTIR) and contact angle (CA) – measurements indicate the successful surface PEGylation, as well as the excellent hydrophilicity of the surfaces. Compared with pristine IOL, the PEGylation does not influent its optical property, whereas the initial adhesion of LEC is greatly inhibited. In vivo ocular implantation results show that the PEGylated IOL presents good in vivo biocompatibility, and can effectively prevent the PCO development.

Anti-CD34 Antibody Functionalized Swollen Polymeric Coating for Endothelial Cell Rapid Selectively Capture

A swollen and hydrogel-like polyelectrolyte multilayer composed of polysaccharide heparin and chitosan was constructed via layer-by-layer self-assembly. The ECs targeting antibody anti-CD34 was subsequently immobilized onto the surface. The culture of primary human vascular ECs and SMCs indicates that the swollen polysaccharide multilayer possesses excellent nonspecifically cell-resistant property. A rapid ECs specifically selective attachment property was obtained after the anti-CD34 antibody functionalization. Such surface modification with rapid EC selectively attachment might have prospective potential for the in situ endothelialization of the cardiovascular implantable materials. GRAPHICAL ABSTRACT