Short-term evaluation of thromboresistance of a poly(ether ether ketone) (PEEK) mechanical heart valve with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted surface in a porcine aortic valve replacement model.

Improved thromboresistance of mechanical valves is desired to decrease the risk of thromboembolism and thrombosis and reduce the dosage of anticoagulation with a vitamin K antagonist (e.g., warfarin). For several mechanical valves, design-related features are responsible for their improved thromboresistance. However, it remains unclear whether material-related features provide a practical level of thromboresistance to mechanical valves. Here, we studied the effect of a bileaflet valve made of poly(ether ether ketone) (PEEK) with a poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted surface (PEEK-g-PMPC). PMPC is a well-known thromboresistant polymeric material. A short-term (<26 h) porcine aortic valve replacement model using neither an anticoagulant nor an antiplatelet agent showed that the PEEK-g-PMPC valve opened and closed normally with an allowable transvalvular gradient. Unlike an untreated PEEK valve, no thrombus formed on the PEEK-g-PMPC valves on gross anatomy examination in addition to the absence of traveled thrombi in the kidney and lung tissues. Material (PEEK-g-PMPC)-related thromboresistance appeared to decrease the risk of thromboembolism and thrombosis for patients with mechanical valves. However, thromboresistance of the PEEK-g-PMPC valve requires improvement because fibrous fouling was still observed on the leaflet. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1052-1063, 2019.

Wear resistance of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted carbon fiber reinforced poly(ether ether ketone) liners against metal and ceramic femoral heads.

Younger, active patients who undergo total hip arthroplasty (THA) have increasing needs for wider range of motion and improved stability of the joint. Therefore, bearing materials having not only higher wear resistance but also mechanical strength are required. Carbon fiber-reinforced poly(ether ether ketone) (CFR-PEEK) is known as a super engineering plastic that has great mechanical strength. In this study, we focused on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted CFR-PEEK and investigated the effects of PMPC grafting and the femoral heads materials on the wear properties of CFR-PEEK liners. Compared with untreated CFR-PEEK, the PMPC-grafted CFR-PEEK surface revealed higher wettability and lower friction properties under aqueous circumstances. In the hip simulator wear test, wear particles generated from the PMPC-grafted CFR-PEEK liners were fewer than those of the untreated CFR-PEEK liners. There were no significant differences in the size and the morphology of the wear particles between the differences of PMPC-grafting and the counter femoral heads. Zirconia-toughened alumina (ZTA) femoral heads had significantly smoother surfaces compared to cobalt-chromium-molybdenum alloy femoral heads after the hip simulator test. Thus, we conclude that the bearing combination of the PMPC-grafted CFR-PEEK liner and ZTA head is expected to be a lifelong bearing interface in THA. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1028-1037, 2018.

High-efficiency preparation of poly(2-methacryloyloxyethyl phosphorylcholine) grafting layer on poly(ether ether ketone) by photoinduced and self-initiated graft polymerization in an aqueous solution in the presence of inorganic salt additives.

UNLABELLED: A highly efficient methodology for preparing a poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer on the surface of poly(ether ether ketone) (PEEK) was examined by photoinduced and self-initiated graft polymerization. To enhance the polymerization rate, we demonstrated the effects of inorganic salt additives in the feed monomer solution on thickness of grafted PMPC layer. Photoinduced polymerization occurred and the PMPC graft layer was successfully formed on the PEEK surface, regardless of inorganic salt additives. Moreover, it was clearly observed that the addition of inorganic salt enhanced the grafting thickness of PMPC layer on the surface even when the photoirradiation time was shortened. The addition of inorganic salt additives in the feed monomer solution enhanced the polymerization rate of MPC and resulted in thicker PMPC layers. In particular, we evaluated the effect of NaCl concentration and how this affected the polymerization rate and layer thickness. We considered that this phenomenon was due to the hydration of ions in the feed monomer solution and subsequent apparent increase in the MPC concentration. A PMPC layer with over 100-nm-thick, which was prepared by 5-min photoirradiation in 2.5mol/L inorganic salt aqueous solution, showed good wettability and protein adsorption resistance compared to that of untreated PEEK. Hence, we concluded that the addition of NaCl into the MPC feed solution would be a convenient and efficient method for preparing a graft layer on PEEK. STATEMENT OF SIGNIFICANCE: Photoinduced and self-initiated graft polymerization on the PEEK surface is one of the several methodologies available for functionalization. However, in comparison with free-radical polymerization, the efficiency of polymerization at the solid-liquid interface is limited. Enhancement of the polymerization rate for grafting could solve the problem. In this study, we observed the acceleration of the polymerization rate of MPC in an aqueous solution by the addition of inorganic salt. The salt itself did not show any adverse effects on the radical polymerization; however, the apparent concentration of the monomer in feed may be increased due to the hydration of ions attributed to salt additives. We could obtain PMPC-grafted PEEK with sufficient PMPC thickness to obtain good functionality with only 5-min photoirradiation by using 2.5mol/L NaCl in the feed solution.

Clinical and radiographic outcomes of total hip replacement with poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners: three-year results of a prospective consecutive series.

OBJECTIVES: This study aimed to evaluate the clinical safety and wear-resistance of the novel highly cross-linked polyethylene (HXLPE) acetabular liner with surface grafting of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) at 3 years after total hip replacement (THR). METHODS: Eighty consecutive patients underwent cementless THR using a 26-mm diameter cobalt-chromium-molybdenum alloy femoral head and a PMPC-grafted HXLPE liner for the bearing couplings. We evaluated the clinical and radiographic outcomes of 76 patients at 3 years after the index surgery. RESULTS: The clinical results at 3 years were equivalent to a Harris hip score of 95.6 points. No adverse events were associated with the implanted PMPC-grafted HXLPE liner, and no periprosthetic osteolysis was detected. The mean femoral head penetration rate was 0.002 mm/year, representing marked reduction compared with other HXLPE liners. CONCLUSIONS: A PMPC-grafted HXLPE liner is a safe option in THR and probably reduces the generation of wear particles.

Reduced platelets and bacteria adhesion on poly(ether ether ketone) by photoinduced and self-initiated graft polymerization of 2-methacryloyloxyethyl phosphorylcholine.

Aromatic poly(ether ether ketone) (PEEK) is a super engineering plastic, which has good mechanical properties and is resistant to physical and chemical stimuli. We have, therefore, attempted to use PEEK in cardiovascular devices. Synthetic cardiovascular devices require both high hemocompatibility and anti-inflammatory activity in addition to the mechanical properties. We modified the PEEK surface by photoinduced and self-initiated graft polymerization with 2-methacryloyloxyethyl phosphorylcholine (MPC; PMPC-grafted PEEK) for obtaining good antithrombogenicity. Polymerization was carried out on the surface of PEEK under radiation of ultraviolet (UV) light during which we controlled monomer concentrations, temperatures, and UV intensities. The biological performance of the PMPC-grafted PEEK was examined and compared with that of unmodified PEEK. With increase in the thickness of the PMPC layer, the amount of fibrinogen adsorption decreased significantly in comparison to that in the case of unmodified PEEK. When placed in contact with human platelet-rich plasma, surface of the PMPC-grafted PEEK clearly showed inhibition of platelet adhesion and activation. Also, bacterial adhesion was reduced dramatically on the PMPC-grafted PEEK. Thus, the PMPC grafting on PEEK improved the antithrombogenicity.

Poly(ether-ether-ketone) orthopedic bearing surface modified by self-initiated surface grafting of poly(2-methacryloyloxyethyl phosphorylcholine).

We investigated the production of free radicals on a poly(ether-ether-ketone) (PEEK) substrate under ultraviolet (UV) irradiation. The amount of the ketyl radicals produced from the benzophenone (BP) units in the PEEK molecular structure initially increased rapidly and then became almost constant. Our observations revealed that the BP units in PEEK acted as photoinitiators, and that it was possible to use them to control the graft polymerization of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC). This "self-initiated surface graft polymerization" method is very convenient in the absence of external photoinitiator. We also investigated the effects of the monomer concentration and UV irradiation time on the extent of the grafted PMPC layer. Furthermore, as an application to improving the durability of artificial hips, we demonstrated the nanometer-scale photoinduced grafting of PMPC onto PEEK and carbon fiber-reinforced PEEK (CFR-PEEK) orthopedic bearing surfaces and interfaces. A variety of test revealed significant improvements in the water wettability, frictional properties, and wear resistance of the surfaces and interfaces.

Reduction of Peritendinous adhesions by hydrogel containing biocompatible phospholipid polymer MPC for tendon repair.

BACKGROUND: Peritendinous adhesions are serious complications after surgical repair of tendons. As an anti-adhesion material, we focused on 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, our original biocompatible polymer, and prepared an aqueous solution of MPC-containing polymer called poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid) (PMBV), which can be formed into hydrogel properties by mixture with another aqueous polymer, poly(vinyl alcohol) (PVA). The objective of the present study was to examine the possible application of the MPC hydrogel for the reduction of peritendinous adhesions. METHODS: the effects of the hydrogel on peritendinous adhesions and tendon healing were examined by means of histological and mechanical analyses in a rat Achilles tendon model and a rabbit flexor digitorum profundus tendon model. Cell migration and viability were examined with use of fibroblastic NIH3T3 cells cultured in a double chamber dish. RESULTS: among the concentrations examined, 2.5% and 5.0% PMBV formed hydrogel properties immediately after mixing with 2.5% PVA and maintained a honeycomb microstructure with nanometer-scaled pores for three weeks after implantation. In animal models, the hydrogel formed from 5.0% PMBV remained at the sutured site during the critical period up to three weeks and disappeared by six weeks. The MPC hydrogel reduced the peritendinous adhesions histologically and mechanically by >25% at three weeks, without impairing tendon healing as determined with mechanical analyses. In the cell culture, cell migration was reduced by the MPC hydrogel, although cell viability was unaffected, indicating physical prevention, rather than cytotoxicity, to be the anti-adhesion mechanism. CONCLUSIONS: the MPC hydrogel that was formed by a local injection and mixture of two aqueous solutions, 5.0% PMBV and 2.5% PVA, reduced peritendinous adhesions without impairing tendon healing. This effect may be due to its excellent biocompatibility without a foreign-body reaction and the formation of a microstructure that physically prevents passage of cells but allows cytokines and growth factors to pass for healing. CLINICAL RELEVANCE: this nanotechnology could potentially improve the quality of surgical repair of tendon, especially the zone-II area of the digital flexor tendon.

The prevention of peritendinous adhesions by a phospholipid polymer hydrogel formed in situ by spontaneous intermolecular interactions.

Preventing peritendinous adhesions after surgical repair of tendon is difficult. In order to establish an ideal anti-adhesion material, we prepared a spontaneously forming hydrogel by mixing the aqueous solutions of two polymers, poly(MPC-co-methacrylic acid) (PMA) and amphiphilic poly(MPC-co-n-butyl methacrylate) (PMB), in the presence of Fe(3+). This PMA/PMB/Fe(3+) hydrogel (MPC polymer hydrogel) had a honeycomb microstructure with nanometer-scale pores, which resist cell invasion but allow the passage of cytokines and growth factors for tendon healing. The dissociation rate of the hydrogel could be controlled by changing Fe(3+) concentration, and by examining the viscoelasticity of the hydrogel, we determined the optimal Fe(3+) concentration to be 0.05 M. We then examined the effects of the in situ application of this MPC polymer hydrogel containing 0.05 M Fe(3+) by using two animal models: the rat Achilles tendon model and the chicken flexor digitorum profundus tendon model. In both models, macroscopic and histological observation revealed that peritendinous adhesions were significantly decreased by the hydrogel application. Mechanical analyses revealed that the hydrogel prevented peritendinous adhesions but did not affect the tendon healing. Because of its characteristic microstructure and excellent biocompatibility, we believe that the MPC polymer hydrogel will be ideal for preventing peritendinous adhesions.

Self-initiated surface grafting with poly(2-methacryloyloxyethyl phosphorylcholine) on poly(ether-ether-ketone).

Poly(ether-ether-ketone) (PEEK)s are a group of polymeric biomaterials with excellent mechanical properties and chemical stability. In the present study, we demonstrate the fabrication of an antibiofouling and highly hydrophilic high-density nanometer-scaled layer on the surface of PEEK by photo-induced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) without using any photo-initiators, i.e., "self-initiated surface graft polymerization." Our results indicated that the diphenylketone moiety in the polymer backbone acted as a photo-initiator similar to benzophenone. The density and thickness of the poly(MPC) (PMPC)-grafted layer were controlled by the photo-irradiation time and monomer concentration during polymerization, respectively. Since MPC is a highly hydrophilic compound, the water wettability (contact angle <10 degrees) and lubricity (coefficient of dynamic friction <0.01) of the PMPC-grafted PEEK surface were considerably lower than those of the untreated PEEK surface (90 degrees and 0.20, respectively) due to the formation of a PMPC nanometer-scale layer. In addition, the amount (0.05 microg/cm(2)) of BSA adsorbed on the PMPC-grafted PEEK surface was considerably lower, that is more than 90% reduction, compared to that (0.55 microg/cm(2)) for untreated PEEK. This photo-induced polymerization process occurs only on the surface of the PEEK substrate; therefore, the desirable mechanical properties of PEEK would be maintained irrespective of the treatment used.

[Progress of research in osteoarthritis. Invention of longer lasting artificial joints].

In the advent of the aging society, the lifetime of artificial joints is a matter of concern. The major cause of revision surgery is periprosthetic osteolysis caused by polyethylene wear particles. To prevent osteolysis, both the reduction of wear and the suppression of osteoclast induction are necessary. For these purposes, we developed a new technology for grafting 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer on the surface of polyethylene liners. On the basis of encouraging results of the preclinical studies, we have started a large-scale clinical trial of new artificial hip joints since 2007.

Self-initiated surface graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on poly(ether ether ketone) by photoirradiation.

In the present paper, we reported the fabrication of a highly hydrophilic nanometer-scale modified surface on a poly(ether ether ketone) (PEEK) substrate by photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) in the absence of photoinitiators. Photoirradiation results in the generation of semibenzopinacol-containing radicals of benzophenone units in the PEEK molecular structure, which acts as a photoinitiator during graft polymerization. The poly(MPC)-grafted PEEK surface fabricated by a novel and simple polymerization system exhibited unique characteristics such as high wettability and high antiprotein adsorption, which makes it highly suitable for medical applications.

Antidegenerative effects of partial disc replacement in an animal surgery model.

STUDY DESIGN: In vivo degenerative changes of rabbit intervertebral discs after partial disc replacements were evaluated radiologically and histologically in a controlled trial. OBJECTIVE: To demonstrate the therapeutic effects of partial disc replacement in an animal surgical model. SUMMARY OF BACKGROUND DATA: Although some authors reported that partial disc replacements have beneficial clinical outcomes, there are few controlled animal studies in which the therapeutic effects of this procedure have been demonstrated. METHODS: The implants for partial disc replacements were made of poly (vinyl alcohol) hydrogel and rod-shaped. The L2-L3 or L3-L4 intervertebral discs of Japanese white rabbits were pierced with a 2.0-mm Kirschner wire and implants were inserted into the holes. For comparative purposes, the adjacent discs underwent sham treatments or control treatments in which the disc was pierced but no implant was inserted. Sixty discs from 30 rabbits were analyzed radiologically and histologically for degenerative changes at 1, 3, or 6 months after surgery. RESULTS: Radiologic analysis revealed that significantly less disc height was lost with the replacement treatment than with the control treatment. Change in disc height after the replacement treatment was not significantly different from that after the sham treatment. Histologic degeneration of the replaced discs was delayed in comparison with that of the control discs but progressed with time. CONCLUSIONS: The antidegenerative effects of partial disc replacement surgery were demonstrated by quantitative radiologic and histologic analyses. Degeneration of the anulus fibrosus after the replacement treatment was delayed by preserving disc height and occupying the space of the nucleus pulposus. Properly designed implants and minimally invasive techniques are necessary for long-term success.

Change in UHMWPE properties of retrieved ceramic total knee prosthesis in clinical use for 23 years.

The alumina-ceramic total knee prosthesis developed by Kyocera Corp. was implanted in 1979, and was in clinical use for 23 years until total knee arthroplasty revision surgery in January 2002. It is believed that this is the longest clinical period of a ceramic total knee prosthesis reported to date in the world. In the present study, we gave consideration to the long-term clinical stability of the alumina-ceramic femoral component as well as the mechanism of in vivo degradation of ultrahigh molecular weight polyethylene (UHMWPE) based on the evaluated wear, oxidation, and fracture toughness of the retrieved UHMWPE. We concluded that the degradation of UHMWPE by progressive oxidation is an issue to be solved in the future. To moderate stress concentration, use of a thin UHMWPE insert should be avoided. The low wear rate and the mild wear pattern observed this time suggest the possibility of reduced wear of the UHMWPE against the alumina-ceramic femoral component, and the usefulness of the alumina-ceramic total knee prosthesis component was recognized even after long clinical use.