Photofunctionalization

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1 Photofunctionalization One and only technology to overcome the biological aging of titanium Scientific brochure of photofunctionalization Volume 1, Issue 1, 2013 published by Global Network for Photofunctionalized Implants and Regenerative Medicine (GNPIRM) and Japanese Society of Photofunctionalized Implants and Regenerative Medicine (JSPIRM) Problem-solving Patient-centered Scientifically driven Biologically proven Clinically inspiring Introducing the next generation implant surface technology and sience

2 Innovation Clinically inspiring. Photofunctionalization technology you can see As-received Photofunctionalized Newly developed, rapid, chairside conditioning of dental implants using cutting-edge LIGHT technology. Imagine if osteogenic cells you want are located in the white circles. The consequence of osseointegration would be different between the as-received and photofunctionalized implants. As-received Photofunctionalized Anyone. Anything. Anywhere. On demand readiness. A conversion from hydrophobic to superhydrophilic surfaces by a fully programmed chairside conditioning in just a short time. Versatility. The optimized conditioning program makes the unprecedented difference for all implants tested. The application is expanding beyond dentistry.

3 Clinically inspiring. Multipurpose photofunctionalization beyond implant fixtures As-received Photofunctionalized As-received Photofunctionalized Solutions and opportunities for many Because of the established principles and mechanisms as well as simplicity of photofunctionalization, the technology is being applied for versatile titanium-based biomaterials to generate clean, hydrophilic interfaces for better tissue compatibility.

4 BIOLOGY Biologically proven. Osseointegration beyond osseointegration Biological cascades accelerated and enhanced by photofunctionalization As-received Photofunctionalized Regeneration of hemophilicity that allows proteins and cells to reach implant surfaces without creating voids and defects of biological resources. Considerably increased recruitment and attachment and accelerated settlement and spread and reinforced retention of osteogenic cells on photofunctionalized surface. These enhanced biological events effectively and synergistically lead to a new level of osseointegration and enable a near maximum bone implant integration (98.2 % BIC) obtained in an animal model as opposed to 53 % for as-received implants.

5 Because of the increased BIC nearing 100 % as well as the near-complete control of soft tissue intervention, the peri-implant osteogenesis around photofunctionalized implants is defined as super osseointegration, where super is a scientific prefix to represent minimum resistance. In this context, the resistance denotes the soft tissue intervention, which has been considered unavoidable to some degree till date.

6 SCIENCE Scientifically driven. Mechanisms of photofunctionalization there are reasons for the super osseointegration Carbon removable Promotes adhesion and spread of cells Superhydrophilicity regeneration Provides access for proteins and cells Photofunctionalization regains the prerequisites for osseointegration that have been lost or substantially compromised during the biological aging of titanium. The prerequisites are established at even higher degree than the original surfaces after photofunctionalization. Electrostatic optimization Works as attractants for proteins and cells A triad in determining osseointegration capability. Photofunctionalization improves implant surfaces fundamentally by (1) removing surface carbon that was unavoidably accumulated on the surface during their biological aging of titanium, (2) regenerating superhydrophilicity that had been lost during the biological aging of titanium, and (3) optimizing the electrostatic status of the surface. Therefore, the presence of hydrophilicity alone does not improve the osteoconductivity of implants as significantly as when the triad of osseointegration are met.

7 Breakthrough Photofunctionalization Problem-solving, patient-centered technology. The biological aging of titanium a degrading capability of osseointegration over time Spreading behavior of 10 µl water on new and aged titanium surfaces New titanium 1-day-old 1-week-old 3-month-old The biological aging of titanium A series of recent studies uncovered that titanium surfaces, whether for experimental or commercial use, are chemically contaminated with hydrocarbon that unavoidably accumulates in a time-dependent manner. In other words, titanium surfaces degrade chemically as they age, which compromises their osseointegration capability; this phenomenon is defined as the biological aging of titanium. Data indicate that as much as 50 % or more area of titanium surfaces are covered by carbon-containing organic-molecules within 4 weeks after the surface is exposed to the atmosphere. Accordingly, as shown in the images, hydrophilicity disappears over time, which is also a part of the biological aging of titanium. Photofunctionalization one and only technology to overcome the biological aging of titanium In the face of this unprecedented challenge, photofunctionalization cleanses these surfaces by removing hydrocarbon through TiO 2 -mediated photocatalysis and direct decomposition by UV. Because of this chemical cleaning, super-hydrophilicity that was lost on sufficiently aged titanium surfaces can be regained. Arbitrarily aged titanium As-is Photofunctionalized Recovery from any levels of aging

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9 Evidence Milestones of the scientifically driven and biologically proven technology The principle, biological effects, and clinical effectiveness and significance of photofunctionalization are supported by a total impact factor of more than 100. Research papers and projects on photofunctionalization received a number of awards from international and national scientific societies and conferences, such as Academy of Osseointegration William R. Raney Award. Photofunctionalization is described in nationlevel syllabus in Germany, Switzerland and Austria (Implantat-Werkstoffe, Curriculum Prothetik III). Key articles and summaries The effect of ultraviolet functionalization of titanium on integration with bone. Aita H, Hori N, Takeuchi M, Suzuki T, Yamada M, Anpo M, et al. Biomaterials 2009;30: UV-photofunctionalization increases the strength of bone-implant integration 3 times at the early stage of healing in a rat model. Along the course of developing implant stability, photofunctionalization accelerated the bone-implant integration 4 times. In vitro studies showed that the amount of proteins and osteoblasts attached during the early stage was increased by 3-5 times by photofunctionalization. Regenerated superhydrophilicity and reduced amount of surface carbon were responsible for the enhanced osseointegration capability of photofunctionalized implants. Enhancement of bone-titanium integration profile with UV-photofunctionalized titanium in a gap healing model. Ueno T, Yamada M, Suzuki T, Minamikawa H, Sato N, Hori N, et al. Biomaterials 2010;31: Implants were placed in the site with a 0.5 mm gap without cortical support in an animal model. These implants showed approximately one fourth of the strength of bone-implant integration compared with implants with cortical support. However, when the implants were photofunctionalized in advance, the strength of bone-implant integration was recovered to the level equivalent to the one for implants with cortical support. Osteogenesis around photofunctionalized implants was initiated at the interface and spread to the remote cortical bone, whereas the osteogenesis around untreated implants started at the remote cortical bone and slowly approached the interface.

10 Evidence Effect of ultraviolet photoactivation of titanium on osseointegration in a rat model. Ueno T, Yamada M, Hori N, Suzuki T, Ogawa T. Int J Oral Maxillofac Implants 2010;25: Implants in 40 % shorter length were placed in an animal model. The strength of osseointegration for these implants was 50 % lower than the one for standard-length implants. When the 40 % shorter implants were photofunctionalized, the strength of osseointegration was even higher than the standard-length implants by 100 % in the early stage of healing. The short photofunctionalized implants maintained the level of osseointegration equivalent to the untreated standard-length implants even at the late stage of healing. Photofunctionalized dental implants: A case series in compromised bone Funato A, Ogawa T. submitted Seven photofunctionalized implants were placed into complex cases of either a fresh extraction socket, vertically augmented bone, simultaneous sinus-lifted site, or site of a failing implant. At a 1-year follow-up, all implants remained functional and healthy, despite a substantially earlier loading protocol applied than reported for similar cases. The average marginal bone level significantly increased during the 1-year after crown placement; the bone level progressed coronally in some cases even exceeding the platform level. Time-dependent degradation of titanium osteoconductivity: an implication of biological aging of implant materials. Att W, Hori N, Takeuchi M, Ouyang J, Yang Y, Anpo M, et al. Biomaterials 2009;30: This study revealed the time-dependent degradation of osteoconductivity of titanium. Implants stored for 4 weeks after processing showed a 50 % reduced strength of osseointegration compared with implants immediately after processing. The 4-week-old implants showed significantly decreased capability of recruiting cells and letting them to attach and settle compared with new implants. The study identified changes of surface factors with time, i.e., there found a loss of hydrophilicity and an accumulation of surface carbons in correlation with the age of titanium surfaces. Implant stability change and osseointegration speed of immediately loaded photofunctionalized implants Suzuki S, Kobayashi H, Ogawa T. Implant Dentistry. in press A cohort design was employed to evaluate implants placed in the maxilla and immediate loaded. The rate of establishing implant stability substantially increased in photofunctionalized implants when their initial stability was low. When the initial stability was high, the ISQ was maintained at a high value, eliminating any stability dip. In both cases, the degree of implant stability achieved by photofunctionalization was considerably higher than reported data in literature.

11 Biological aging of implant surfaces and their restoration with ultraviolet light treatment: a novel understanding of osseointegration. Att W, Ogawa T. Int J Oral Maxillofac Implants 2012;27: This review article summarizes the principles and supporting findings about the biological aging of implant materials as well as the discovery of UVmediated photofunctionalization as a solution for this phenomenon. It also provides a novel understanding of osseointegration by identifying prerequisites for osseointegration and calls for immediate attention to a new avenue of exploration in the science and therapeutics of implant dentistry. UV photofunctionalization of titanium implants Ogawa T. J Craniofac Tissue Eng 2012;2: This review paper summarizes the findings from recent in vitro and in vivo studies related to UVphotofunctionalization of titanium as well as clinical relevancy and practicality of the technology. UV-photofunctionalization is defined as an overall phenomenon of surface modification on titanium surfaces occurring after UV treatment, including the alteration of physicochemical properties and the enhancement in biological capabilities. The UV treatment is simple and low-cost, and has been proven effective in all titanium surface types tested. These suggest that UV photofunctionalization can be a novel effective measure to improve current implant therapies and to meet its growing demands in dental and orthopedic fields. Success rate, healing time, and implant stability development of photofunctionalized dental implants Funato A, Yamada M, Ogawa T. Int J Oral Maxillofac Implants. in press This 2.5 year-follow-up study analyzed 95 consecutive patients who received untreated implants and 70 patients who received photofunctionalized implants. The healing time before functional loading was substantially decreased in patients who received photofunctionalized implants (less than half period of time) compared with that in patients who received untreated implants. Despite this substantially shortened protocol, the success rate of photofunctionalized implants was as high as untreated implants. The ISQ increase per month for photofunctionalized implants was considerably higher than that of as-received surfaces reported in the literature. The average length and diameter for photofunctionalized implants were significantly smaller than those for untreated implants. The biological aging of titanium implants. Lee JH, Ogawa T. Imp Dent 2012;21: This review article introduces the recently reported time-dependent reduction in osteoconductivity and other biological capabilities of titanium since processing as referred as the biological aging of titanium. Various findings from a set of comprehensive in vitro and in vivo approaches as well as clinically relevant interpretation and discussion are described. Additionally, the paper introduces a profound insight and strategy to utilize this discovery toward the development of new technologies to improve implant surfaces for better osseointegration.

12 Discover it by yourself Global Scenes of Photofunctionalized Dental Implants Accelerate yourself, Distinguish yourself simply deriving the best possible of implants of your choice An academic website is now open for dentists, physicians, researchers, students, and patients interested in implants therapy and sience of tomorrow. GNPIRM Global Network for Photofunctionalized Implants and Regenerative Medicine. JSPIRM Japanese Network for Photofunctionalized Implants and Regenerative Medicine. Status: June 2013

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