Quankui Lin

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.

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.

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.

Hydrophilic modification of intraocular lens via surface initiated reversible addition-fragmentation chain transfer polymerization for reduced posterior capsular opacification

Phacoemulsification followed with intraocular lens (IOL) implantation is the most effective clinical surgeries in treating cataracts. However, posterior capsular opacification (PCO), a common complication of this surgery, may cause vision decrease after surgery. PCO is mainly caused by the adhesion, proliferation and trans-differentiation of the residual lens epithelial cells (LEC) after surgery. Surface modification of IOL to reduce the LEC adhesion is of great importance in PCO prevention. Herein, surface initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization was utilized to modify the IOL materials for generating a comb-like polyethylene glycol (PEG) brush coating on the surface. The ATR-FTIR, XPS, and contact angle characterizations indicate the successful immobilization of the RAFT agent, as well as the subsequent SI-RAFT polymerization of PEG macromonomer. More interestingly, the PEG brush coating shows excellent hydrophilicity on the surface. The in vitro LEC culture and bacteria adhesion results show that the hydrophilic modification can effectively reduce the bio-adhesion. The in vivo implantation results show that the PEG brush modified IOL presents good biocompatibility, and significantly decreases the posterior capsular hyperplasia. These results demonstrate that the surface modification of IOL with excellent hydrophilic brush via SI-RAFT may provide a good alternative for IOL anti-PCO modification.

Bottom-up fabrication of zwitterionic polymer brushes on intraocular lens for improved biocompatibility

Intraocular lens (IOL) is an efficient implantable device commonly used for treating cataracts. However, bioadhesion of bacteria or residual lens epithelial cells on the IOL surface after surgery causes postoperative complications, such as endophthalmitis or posterior capsular opacification, and leads to loss of sight again. In the present study, zwitterionic polymer brushes were fabricated on the IOL surface via bottom-up grafting procedure. The attenuated total reflection-Fourier transform infrared and contact angle measurements indicated successful surface modification, as well as excellent hydrophilicity. The coating of hydrophilic zwitterionic polymer effectively decreased the bioadhesion of lens epithelial cells or bacteria. In vivo intraocular implantation results showed good in vivo biocompatibility of zwitterionic IOL and its effectiveness against postoperative complications.