The use of light/chemically hardened polymethylmethacrylate, polyhydroxyethylmethacrylate, and calcium hydroxide graft material in combination with polyanhydride around implants in minipigs: part I: immediate stability and function.

BACKGROUND: The present study is designed as a proof-of-concept study to evaluate light/chemical hardening technology and a newly formulated polymethylmethacrylate, polyhydroxyethylmethacrylate, and calcium hydroxide (PPCH) plus polyanhydride (PA) (PPCH-PA) composite graft material as a bone substitute compared to positive and negative controls in a minipig model. METHODS: PPCH-PA (composite graft); PPCH alone (positive control), PA alone (positive control), and no graft (negative control) were compared. Four mandibular premolar teeth per quadrant were extracted; a total of 48 implants were placed into sockets in three minipigs. Abutments were placed protruding into the oral cavity 4 mm in height for immediate loading. Crestal areas and intrabony spaces were filled with PPCH-PA, PPCH, or PA using a three-phase delivery system in which all graft materials were hardened by a light cure. In the negative control group, implant sites were left untreated. At 12 weeks, block sections containing implants were obtained. Evaluations included periodontal probing, pullout-force load, and stability measurements to determine implant stability, radiographs to examine bone levels, and scanning electron microscopy (SEM)-energy-dispersed spectroscopy to determine bone-to-implant contact. RESULTS: Probing measurements did not reveal any pathologic pocket formation or bone loss. Radiographs revealed that immediate implant placement and loading resulted in bone at or slightly apical to the first thread of the implant in all groups at 12 weeks. Stability test values showed a relative clinical stability for all implants (range: -7 to +1); however, implants augmented with PPCH-PA exhibited a statistically significantly greater stability compared to all other groups (P <0.05). The newly formed bone in PPCH-PA-treated sites was well organized with less marrow spaces and well-distributed osteocytes. SEM revealed a tighter implant-socket interface in the PPCH-PA group compared to other groups with reduced microfissures and implant-bone interface fractures during pullout testing, whereas implants treated with PA or no graft showed ≈ 10-µm microfissures between the implant and bone with fractures of the intrathread bone. CONCLUSIONS: The newly formulated chemically hardened graft material PPCH-PA was useful in immediate implant placement after tooth extraction and resulted in greater stability and a well-organized implant-bone interface with immediate loading, especially in those areas where cancellous bone was present. The results of this proof-of-concept study warranted further research investigating different healing times and longer durations.

Swelling response of radiation synthesized 2-hydroxyethylmethacrylate-co-[2-(methacryloyloxy)ethyl] trimethylammonium chloride hydrogels under various in vitro conditions.

High-energy (60)Co gamma radiation has been used to synthesize 2-hydroxyethylmethacrylate-co-[2-(methacryloyloxy)ethyl]trimethylammonium chloride (HEMA-co-MAETC) polyelectrolyte hydrogels. HEMA-co-MAETC co-polymer gels were characterized and investigated for swelling behaviour in different swelling conditions. Fourier transformed infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) techniques were used to characterize the co-polymer gels. Swelling extent of the gels was found to be a linear function of MAETC content in the gels. The effect of ionic strength, temperature, pH, some solutes of biological importance like glucose, urea, and surfactants such as Triton-X and deoxycholic acid on swelling behavior have been reported. The swelling of gels at higher temperature enhanced the swelling rates but not the swelling extent. HEMA-co-MAETC hydrogel exhibited an excellent responsive characteristic to the ionic strength of the swelling medium. It was found that the swelling of the co-polymer gel at 60 degrees C reduced the swelling-deswelling cycle time by approx. 30% without altering the swelling extent. The gels were also investigated for their swelling in aqueous solutions of anionic dyes, acid blue 25 (AB25), acid blue (AB74) and acid yellow 99 (AY99), and were found to be suitable for dye uptake applications.

Effect of gamma-irradiation on the structure of poly(ethyl acrylate-co-hydroxyethyl methacrylate) copolymer networks for biomedical applications.

The effect of the sterilization process by gamma-irradiation on the structure of poly(ethyl acrylate-co-hydroxyethyl methacrylate) copolymer networks, P(EA-co-HEMA) is studied for a broad dose range (7, 15, 25 and 50 kGy) and copolymer composition interval (0, 0.3, 0.5, 0.7 and 1 weight fraction of HEMA in the copolymer). gamma-irradiation promotes chain scission in PHEMA homopolymer but induces new crosslinking points in PEA homopolymer. Both effects are present in the copolymers, with a net result that depends on composition. For copolymers with high HEMA fractions chain scission predominates, while, as the amount of EA in the copolymer increases, the situation changes and the net effect turns out to be an increase in the number of elastically active chains. Further, gamma-irradiation strengthens the gamma relaxation in PHEMA homopolymer, what suggest that the number of interchain hydrogen bonds decreases. FTIR spectroscopy reveals no oxidation as a consequence of the sterilization process.

Poly(2-hydroxyethyl methacrylate) wound dressing containing ciprofloxacin and its drug release studies.

An improved wound dressing with a long-term drug diffusion-efficacy has been developed by UV-radiation technique. It involves incorporation of ciprofloxacin (CIP), at the concentration of 0.5-2.0% (w/v), into a water mixture of 2-hydroxymethacrylate (HEMA) monomer, benzoin isobutyl ether (BIE) initiator and different content of ethylene glycol dimethacrylate (EGDMA) cross-linker. Increasing the concentration of EGDMA would reduce the releasing ratio of CIP from pHEMA. T1/2 is increased from 2.64 to 45.67 h when the EGDMA is added from 1 to 8%. In the ranges of 0< or = F < or = 0.6, the n value of 1%CIP-pHEMA membranes is increased from 0.48 to 0.81. It indicates that the mechanism of drug release falls between the Fickian and Case II diffusion model. The antibacterial activity of the drug impregnated into the membrane was evaluated by in vitro drug kinetic agar plate method. Higher concentration of EGDMA, up to 8% of the cross-linker, extends the drug release. Comparison with the drug-soaked membranes, the newly synthesized 1% CIP-pHEMA membrane (cross-linked with 4% EGDMA) sustains the release of the entrapped drug and maintains the antibacterial activity up to 12 days.

Preparation of macroporous poly(2-hydroxyethyl methacrylate) hydrogels by enhanced phase separation.

Macroporous poly(2-hydroxyethyl methacrylate) (p(HEMA)) hydrogels were prepared in the presence of a 0.3-0.7 M NaCl solution. The pore morphology of the p(HEMA) hydrogels was dependent on the concentration of NaCl for a constant monomer solution to aqueous solution ratio. Swelling studies showed an increase in equilibrium water content and hydrogel porosity as the NaCl concentration in the polymerization medium increased from 0 to 0.7 M. The equilibrium water content, however, decreased as the NaCl concentration in the swelling medium increased. The frozen water content increased and non-frozen water decreased with an increase in the NaCl concentration in the polymerization medium. Mechanical testing indicated that the elastic modulus of the hydrogels was not affected by the increased porosity until the pores became interconnected. These data suggest that the addition of NaCl to the polymerization medium results in a multi-phase separation during fabrication that produces macroporous hydrogels of controlled morphology.

Photopolymerization of multilaminated poly(HEMA) hydrogels for controlled release.

A novel approach to immobilize nonuniform initial drug concentration profiles in multilaminated matrix devices utilizing photopolymerization techniques is presented. Solution polymerization of 2-hydroxyethyl methacrylate (HEMA) and diethylene glycol dimethacrylate (DEGDMA) in the presence of a model compound, acid orange 8 (AO8), was conducted using UV light and photoinitiators to construct a laminated matrix device. In this process, each layer was polymerized with a different AO8 concentration to form a nonuniform initial concentration profile in the matrix devices. The AO8 diffusion coefficients measured in this work were used in a concurrently developed model to predict the effects of nonuniform AO8 concentration profiles on AO8 release patterns. The release data predicted by the model agreed well with the experimentally determined data. The results indicate that a zero-order release pattern can be approximated by employing a suitable nonuniform initial drug concentration profile.

Laser-induced damage to transparent polymers: chemical effect of short-pulsed (Q-switched) Nd:YAG laser radiation on ophthalmic acrylic biomaterials. I. A review.

The use of short-pulsed lasers in ophthalmic surgery inspired and called for research on the damage inflicted by the laser radiation upon the acrylic polymers from which artificial intraocular lenses are made. The possible release of toxic monomers by laser-induced depolymerization is of great concern but past investigations of this phenomenon have been very limited. The present knowledge of various types of laser-induced damage to transparent polymers is reviewed with particular emphasis on the acrylic materials and intraocular lenses.

Laser-induced damage to transparent polymers: chemical effect of short-pulsed (Q-switched) Nd:YAG laser radiation on ophthalmic acrylic biomaterials. II. Study of monomer release from artificial intraocular lenses.

Commercial intraocular lenses and polymer specimens, both poly(methyl methacrylate) (PMMA) and poly(2-hydroxyethyl methacrylate) p(HEMA), were subjected to various levels of irradiation from a Q-switched Nd:YAG laser, and then to extraction and sample-enrichment techniques. The extracts were analysed by capillary gas chromatography. In PMMA samples, residual contents of 0.05-0.89% (wt) MMA were found and it appeared that the laser radiation did not cause a detectable increase of the monomer content. No residual HEMA could be found in p(HEMA) samples before or after laser bombardment. It is concluded that the accidental exposure of lenses to Nd:YAG laser cannot produce a significant release of monomers. Depolymerization induced by laser is a process unlikely to occur at the energy levels used in ophthalmic surgery.

Studies of the slow releasing of testosterone from radiation-polymerized testicular prostheses implanted subcutaneously in the back of castrated rabbits.

A controlled release testicular prosthesis containing testosterone, which was previously dissolved in 2-hydroxyethyl methacrylate (HEMA) at a temperature of 80 degrees C, was prepared by radiation-induced polymerization in the supercooled state at a low temperature. The daily dose of testosterone released in vitro from the poly(HEMA) testicular prosthesis was kept constant at a rate of 5.5 +/- 1.5 mg/d throughout an experimental period of 900 d. In the in vivo experiments, the poly(HEMA) testicular prosthesis was implanted subcutaneously in the back of castrated rabbits over a maximum period of 11 mnth. The cumulative amounts of testosterone released in vitro and in vivo from the poly(HEMA) testicular prosthesis for a period of 11 mnth were found to be 2.1 g (30.0 wt% of initial drug) and 0.9 g (12.8 wt% of initial drug), respectively. The serum testosterone level in castrated rabbits with a poly(HEMA) testicular prosthesis rapidly decreased for periods up to 2 mnth (after increasing during the first 2 wk), then showed a moderate decrease for a few months, and finally held constant at a level of 10 ng/ml throughout the experimental period. It was concluded that a slight amount of testosterone is continuously released in vivo from the radiation-polymerized poly(HEMA) testicular prosthesis over a long period analogous with that in vitro.

UV versus chemical polymerization of glycol methacrylate (GMA) in enzyme histochemistry.

The influence of the mode of polymerization of GMA on the enzyme activities of differently fixed rat livers was studied. It was found that with increasing time of UV-polymerization several enzyme activities were inhibited whereas chemical polymerization was comparatively less harmful. The histochemical reactivity of substrates such as glycogen was not impaired by the mode of polymerization, which is in contrast to the increased basophilia of DNA and RNA after UV-polymerization.