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Clinical Science and Techniques

Implant Surface Treatment Using Biomimetic Agents

Avila, Gustavo DDS, PhD*; Misch, Kelly DDS*; Galindo-Moreno, Pablo DDS, PhD; Wang, Hom-Lay DDS, MSD, PhD

Author Information
doi: 10.1097/ID.0b013e318192cb7d
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Abstract

Our way of understanding implant dentistry has changed substantially because Branemark et al1,2 introduced osseointegrated implants. Clinicians not only use implants to replace missing teeth, but also as an anchor for orthodontic tooth movement.3,4 The advance of research in this field has been relentless. This has led to a high degree of excellence in treatments. Thus, dental implant therapy is now regarded as extremely reliable with a high predictable success rate, making it possible to meet the expectations of all parties involved.

Titanium has been widely used in dental implants because of its excellent physical properties including high resistance to corrosion, low module of elasticity, and considerable fatigue strength. It also possesses excellent biocompatibility because of spontaneous formation of a dense 4-nm layer of titanium dioxide (TiO2) when it is exposed to air. This layer increases calcium deposition and the consequent primary adsorption of adhesive proteins, e.g., glycosaminoglycans or albumin,5 one of the most important events of the initial phase of osseointegration.

A wide range of materials has been studied in search for an alternative to titanium. These materials include metals (e.g., tantalum,6 niobium,7 or cobalt-chromium alloy8), ceramic materials (e.g., hydroxyapatite [HA] and other calcium phosphate salts9), and aluminum oxide.10 Nevertheless, it is universally recognized that titanium of commercial purity (99.67% by weight) or titanium alloys (contain small proportions of vanadium and aluminum, e.g., Ti6Al4V) are the material of choice for the preparation of dental implants.11

Advances in Osseointegration

Despite titanium biocompatibility, a positive modulation of biological processes is somehow limited because titanium per se is unable to induce bone apposition (osteoinduction). Hence, recent researches have been focused in improving surface treatments to promote early integration thus to shorten overall treatment time needed.12

Wound healing around implants is similar to bone healing noted after bone trauma/fracture.13 Osseointegration is comparable with direct ossification after fracture or trauma but with a small difference; osseointegration involves the union of bone to a foreign material (implant surface), not to bone.10 Early events related to the hemorrhage that follows implant placement, e.g., vasoconstriction and retraction of the blood clot, play an essential role in implant wound healing. An interaction between biological components and implant surface was noted. This includes binding of ions, lipids, and adhesive macromolecules (e.g., albumin, fibrin, and fibronectin).14 This adsorption of proteins on the implant surface is considered to be the earliest stage of osseointegration, and is rapidly followed by adhesion of platelets on the implant surface.15 The platelets release biological mediators, including chemotactic factors for osteogenic cells. It can, therefore, be appreciated that the surface properties of the implant will have a critical influence on the initiation of osseointegration.

Biomimetics: New Perspectives in Implant Dentistry

Since the 1980s, research efforts to improve implant surface properties have centered on HA, studying how morphologic changes to the surface might enhance osseointegration. A promising and novel research field has now emerged in implant dentistry; that is, biomimetics. It is the investigation of the addition of bioactive agents to the titanium implant surfaces. Coating an implant surface with these materials/agents is intended to speed up the healing events and thus reduce the overall healing/treatment time required. A biomimetic agent is that material that has been designed to elicit specified cellular responses mediated by interactions with scaffold-tethered peptides from extracellular matrix (ECM) proteins; essentially, by the incorporation of cell-binding peptides into biomaterials via chemical or physical modification.16 It is simplified to an agent/material “able to replicate or imitate a body structure (anatomy) and/or function (physiology)” that is defined by the glossary of implant dentistry.17

Biomimetic agents applied to the implant surfaces should possess the following characteristics: (1) Ability to induce differentiation of the appropriate cells for enhancing new bone formation; (2) easy synthesis or production, avoiding extraction from allografts to eliminate the risk of transmission of infectious-contagious diseases; (3) resorbability in response to osteogenic action, avoiding problems of implant loss due to delamination of the coating; (4) no production of immune reactions in the receptor; (5) chemical stability until placement of the implant in the surgical socket; and (6) a good cost-effectiveness ratio.18 Based on these premises, the development of and research into biomimetic implant surface treatments should be focused on the following aspects: selection proper surface and remains to be effective; and identification of the appropriate biomimetic agents. So far, none of available materials could fulfill all these requirements. Currently, an implant surface can be treated with 4 major categories of agents: biocompatible ceramics, bioactive proteins, ions, and polymers (Table 1). All above agents will be thoroughly discussed later.

Table 1
Table 1:
Agents With Potential to be Applied for Biomimetic Purposes

Bioceramics

The most widely used bioceramics in medicine and dentistry are calcium phosphate salts, with variations in their final chemical composition, crystalline structure, and porosity.19 Phosphocalcic HA, formula Ca10 (PO4)6 (OH)2, is the main inorganic component of bone and has been the most widely used calcium phosphate as a ceramic biomaterial and bone substitute in medicine. The biological principles underlying the use of biomaterials coated with bioactive ceramics for therapeutic purposes have long been investigated.8 HA was the first surface modification agents published, and it was initially used in the hip prosthesis setting.20 Implant dentistry has been slow in incorporating this therapeutic modality into their design. Nonetheless, the addition of HA to the surface of titanium implants can be regarded as the first improvement in implant surface conditions that favors quick osseointegration.21

The clinical value of these materials derives in part from biocompatibility when applied to living bone and in part from bioactivity (i.e., their capacity to improve bone regeneration conditions).22 The contribution of calcium and phosphorus to reossification and the structural similarity of HA and other bioceramics to the inorganic component of bone explain this high biocompatibility and the early interaction of these materials with the bone. In an experimental study on rabbit femurs, implants with HA-coated surface were compared with titanium plasma-coated surfaces.23 Although osseointegration and bone maturation were similar around both surfaces at 12 months, higher fixation and bone formation rates were observed in the HA-coated half at initial stages (first 3 weeks). These data suggested that HA favors an early chemical interaction between implant surface and living bone. This early bone bonding is based on a series of biological events that include a rapid initial dissolution of the coating surface, followed by precipitation and ionic exchange phenomena until the coating is replaced by mature living bone.

HA was first added by electrophoresis22 and then by other methods including plasma spraying or ion beam-assisted deposition. However, these HA-coating methods have been criticized because of difficulty in obtaining a homogeneous degree of crystallization that may allow a complete absorption in a normal biological environment.24 To overcome these shortfalls, other physiologic deposition methods have, therefore, been developed. These include, but not limited to, electrolytic deposition or implant immersion in stimulated body fluids. Stimulated body fluids are rich in calcium, phosphorus, and other elements and are prepared under specific conditions designed to obtain a 30- to 50-mm layer of phosphate salt crystals by gradual precipitation.25

Many authors have reported the benefits of placing implants coated with bioceramics largely because of their ability in achieving early interaction and a bond between HA and bone.26–30 Nevertheless, other studies have reported some shortcomings, such as resorption of the material and detachment of the implant because of lack of strong bonding between coating and implant; and the tendency to harbor more bacterial colonization due to surface roughness and their porosity, of these implants.31

If absorption of the coating was one of the causes of failure with this type of implant, the success rate should diminish with time. This has not been observed in 5- and 10-year follow-up studies.32 Although Gottlander and Albrektsson33 observed that fragments of HA coating separated from some areas of the implant surface in an in vivo rabbit study, no author has related absorption or separation of the HA coating to the failure of osseointegrated implants. Separation does not occur in coatings with other phases of calcium phosphate, which are almost completely absorbed due to their high solubility in body fluids and physiologic mimetism. A further aspect is that bacterial adhesion increases with the higher porosity of a material,34 and bioceramic materials are porous. Meticulous hygiene measures and postimplantation antibiotic treatment have been proposed to prevent infection around bioceramic-coated implants.35,36

In summary, bioceramic-coated dental implants are a valid therapeutic option. This type of coating has a high biocompatibility and shows a good long-term success rate.32

Bioactive Proteins

Bone morphogenetic proteins.

The high biological potential of bone morphogenetic proteins (BMPs) as osteoinductive agents has been widely recognized.37 The ability to immobilize BMPs on titanium surfaces has opened their application in implants.38 BMP is the generic name of a family of proteins, originally identified in extracts of demineralized bone, that are capable of inducing bone formation at ectopic sites. BMPs are found in minute amounts in bone material (∼1 μg/kg dry weight of bone). The designation BMP only describes one particular function of these proteins, which have been implicated in embryonic development.39 BMPs are not only present in the bone matrix, but can also be synthesized by cells of other lineages (e.g., macrophages).

To date, 20 types and subtypes of BMPs have been reported. Except for BMP-1 that is classified as a metalloproteinase, all BMPs belong to the transforming growth factor-β (TGF-β) superfamily.40 BMP-2 and BMP-7 have been the most widely studied types, thanks to their interesting biological properties revealed by experimental studies. BMP-2 (BMP-2-α) is a protein of 114 amino acids, and the amino acid sequence is identical in humans, mice, and rats. BMP-7 has 139 amino acids and is identical to osteogenic protein-1 (also known as Vg-1); mouse and human proteins are 98% identical.

Over the past decade, recombinant human bone morphogenetic protein-2 (rhBMP-2) has been studied as a bone-modulating agent for application as coadjuvant therapy in dentistry, oral and maxillofacial surgery, and other biomedical settings.25,41 Animal model studies of the capacity of rh-BMP-2 to induce bone formation around intraosseous implants have yielded very favorable results,42 and the bone formed has demonstrated long-term stability after placement of loaded implants.

To be suitable for clinical use, a BMP carrier must be dimensionally stable and capable of resisting compression forces if placed in supra-alveolar areas, and the properties of these molecules must not be altered in the addition process. It can be affirmed that the characteristics and properties of an implant treated with rh-BMP-2 can clearly influence the release and action of this protein when used as a biomimetic agent. A study has shown a promising method that uses allylamine to immobilize bioactive peptides, including BMPs, on the surface of bioinert materials (e.g., titanium), as an alternative to the silane method used in other studies.38

These proteins may offer the following advantages when applied as biomimetic agents. They can be applied on all types of implant material, including polymers and they can adhere under physiologic temperature and pH conditions. Therefore, the molecule retains its properties until its therapeutic use; and BMPs have high osteogenic potential, suggesting that small doses of the agent can produce significant amount of peri-implant osteogenesis.43 Major drawbacks of these proteins are their extremely high cost and the possibility of inducing ectopic or uncontrolled bone formation.

BMPs are the most promising group with greatest therapeutic potential among proteins with bioactive capacity for application in biomimetics. Nonetheless, further experimental research is required before a BMP-enriched implant becomes commercially available.

Growth factors.

Cytokines are polypeptide protein factors of low molecular weight (<80 KDa) with pleiotropic action that are produced in most nucleated cells of the organism. Hence, its targets (in this case the cells) are multiple, and different and varied effects are produced that frequently interact with each other. Cytokines, therefore, behave as mediators of complex interactions among different cell types and play a key role in the cell coordination of the organism. The cytokine group includes growth factors (GFs), a heterogeneous family of proteins involved in a wide variety of biological processes related to the proliferation, differentiation, and chemotactism of cells.44

Platelet-rich plasma (PRP) was proposed for use in oral and maxillofacial surgery, due to its high content of GFs.45,46 However, many questions remain unanswered about its true regenerative capacity, biochemical composition, and the biological safety.47 From a biomimetic standpoint, the possibility of impregnating the implant with PRP clot can be very attractive. Because PRP can enhance regeneration mediated by the releasing of GFs, such as TGF-β, platelet-derived growth factor (PDGF), and especially insuline-like growth factor-1 (IGF-1), that are present inside of the α- granules of platelets. However, the major question of coating PRP to implant surface is as follows: how to properly distribute GFs homogeneously to the implant surface? Other challenge includes short half-life of GFs.48 This is contradictory to the basic requirements for a biomimetic agent as a coating agent. Further studies are required to develop effective methods of adding GFs onto titanium implant surfaces as well as to control their action in the target area.

Type I collagen.

The reasons why type I collagen have been considered for implant surface coating is because its high dimensional stability, essential component for ECM development and its presence in all hard and soft tissues. Collagen is the major protein of the human body and plays an essential role in tissue repair and regeneration. Type 1 collagen, largely produced by osteoblasts, is the most abundant protein in bone tissue and serves as a scaffolding for bone neoformation. Hence, type 1 collagen was considered to be a biomimetic agent for implant surface coating.

In vitro studies have shown that type 1 collagen-coated implants promote osteoblast adhesion and proliferation.49 Similar results were later found in many animal studies.50 Biomimetic properties of type 1 collagen to promote early implant osseointegration may be attributed to an early interaction between coated collagen and adjacent cells. These phenomena are influenced by the chemical stability of the type I collagen coating via its fibrillar assembly and crosslinking.51 Nevertheless, despite its high biocompatibility and proven osteoconductive properties, there has been little investigation into the application of collagen on titanium surfaces to improve implant osseointegration in human. Many studies in this field are currently being tested in different laboratory.

RGD peptide.

RGD or Arg-Gly-Asp (Arginine-glycine-aspartic acid) is expressed in several of these ECM proteins. It has been known that this sequence has a high affinity for some proteins of the integrin family and is of great importance in the binding of cells to the ECM.52 It has been observed that early adhesion of human osteoblast-like cells to homogeneous surfaces of RGD peptides is determined by integrins with affinity for collagen.53 This has led to the development of RGD peptides as a potential biomimetic agent for implant surface coating. It is hoped that this coating will improve selective osteoblasts binding to the implant thus favoring early osseointegration. Roessler et al54 found an increased binding of animal osteoblasts to titanium surfaces pretreated with RGD peptides. In the same research line, interesting results have been published supporting the use of RGD peptides to improve the properties of other coatings for biomaterials such as HA. These findings lead to very interesting possibilities.

The first in vivo studies in this field have yielded promising results. Rats showed a significant increase in bone tissue at 2 and 4 weeks around implants with surfaces treated RGD peptides compared with untreated implants.55 In addition, a greater bone-to-implant contact was demonstrated for RGD peptide-treated titanium implants compared with controls. In another study, greater bone formation was observed on titanium fiber mesh treated with cyclic RGD peptides than on untreated mesh.56 Despite these highly positive results, another in vivo study found that the presence of the RGD sequence did not improve the adhesion on titanium.57 These findings were in line with other in vivo animal studies (Beagle dogs) that had been unable to confirm increased bone regeneration or bone-to-implant contact around titanium transplants treated with RGD peptides.58 The earlier studies suggest that the application of RGD peptides may have potential to act as a surface coating agent for implants. Nevertheless, further in vivo and in vitro research is necessary to elucidate interactions between these RGD peptides and the cells involved in osteogenesis and to establish the optimal application conditions and most appropriate protein(s) for each clinical situation.

Ions—Fluoride

To improve the biocompatibility of titanium, few authors have used chemical modification that binds the essential elements (e.g., fluoride) of bone to an implant surface to promote osteogenesis.59 In fact, there are implants treated with fluorine as biomimetic agent currently available for the clinician to use (OsseoSpeed, Astra Tech, Mölndal, Sweden). The mechanism of how this works is based upon the following: formation of fluorapatite, then promotion of osteoblasts’ proliferation and stimulation of alkaline phosphatase activity.

Fluoride is the halogen family member with the lowest atomic number and weight. In aqueous solutions, it appears in the form of fluoride ion (F), a highly reactive ion with considerable capacity to form very stable compounds with other elements. These properties allow fluoride to interact with HA present in bone tissue or teeth and give rise to fluorapatite or fluoridated HA, with an improved crystallinity and lower dissolution rate in comparison with HA.60 Hence, a tight junction between bone and implant was noted.

Farley et al61 studied the effect of fluoride on osteoblasts in an in vitro model of avian cells. They reported that fluoride increases in osteoblasts’ proliferation and alkaline phosphatase activity. These findings were later confirmed by others.62,63 Results from these studies suggest fluoride application can facilitate a highly specific stimulus on osteoblasts that leads to an increase in the bone apposition rate in early phases of osteogenesis.

Although we do not know, in detail, the mechanisms that give rise to the beneficial effects of fluoride on bone tissue, its application as a biomimetic agent to modify the surface of osseointegrated implants have shown good results.64 Nevertheless, more research is still needed to enhance our understanding of how fluoride actually promotes fast osseointegration.

Polymers—Chitosan

Chitosan is a polysaccharide of natural origin that is formed of copolymers of glucosamine and N-acetyl glucosamine. It is obtained by the partial deacetylation of chitin, the second most abundant marine organic polymer in nature. Chitosan has numerous amino groups bound to its main chain that allow it to react chemically with an anionic environment.65 The beneficial chemical and structural properties of chitosan have prompted proposals for several therapeutic applications, e.g., as a hemostatic or cholesterol-lowering agent, and dental implant coating, which has been studied in animal models.66 The remarkable regeneration results observed with the use of chitosan as a wound dressing made it an obvious candidate for investigation as an agent to enhance tissue regeneration. Thus, Ueno et al67, in an in vitro study of epidermal tissue, observed that chitosan was able to increase the proliferation and chemotactism of fibroblasts and their production of collagen, among other biological effects.

With regard to bone tissue, it has been reported that chitosan can act as an effective scaffold for osteoblasts, permitting apposition of ECM, and can enhance differentiation of preosteoblastic cells into osteoblasts.68 These observations suggest that chitosan may have osteoconductive properties with moderate osteoinductive potential. In vitro studies were recently published on the application of chitosan to titanium surfaces in combination with either calcium phosphate or protein gels.69 They reported that chitosan can enhance biological bone regeneration processes, paving the way for further research into the true potential of chitosan as a biomimetic agent for coating titanium implants.

Conclusions

Implants with biomimetic properties, whose surfaces have been treated with bioceramics or ions, are commercially available and have shown faster speed of osseointegration. Nevertheless, there are other promising bioactive agents, such as BMPs, chitosan, or hormones, whose true potential for application as biomimetic agents has yet to be established (properties summarized in Table 2). Research lines are warranted to increase our understanding of the manner in which these substances might improve osseointegration so as to increase the reliability and prognosis of osseointegrated implantation.

Table 2
Table 2:
Comparison of the Main Properties of the Biomimetic Agents Proposed in This Review

Disclosure

The authors claim to have no financial interests, either directly or indirectly, in the products listed in the study.

Acknowledgments

This study was partially supported by the University of Michigan, Periodontal Graduate Student Research Fund.

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Abstract Translations

GERMAN / DEUTSCH

AUTOR(EN): Gustavo Avila, DDS, PhD, Kelly Misch, DDS, Pablo Galindo-Moreno, DDS, PhD, und Hom-Lay Wang, DDS, MSD, PhD. Korrespondenz an: Hom-Lay Wang, DDS, MSD, PhD, Professor und Leiter des Graduiertenkollegs Parodontie (Professor and Director of Graduate Periodontics), Abteilung für Parodontie und Oralmedizin (Department of Periodontics and Oral Medicine), zahnmedizinische Fakultät (School of Dentistry), Universität von Michigan (University of Michigan), 1101 N. Universität, Ann Arbor, MI 48109-1078. Telefon: 734-763-3383, Fax: 734-936-0374. eMail:[email protected]

Oberflächenbehandlung von Implantaten mit biomimetischen Wirkstoffen

ZUSAMMENFASSUNG: Um eine schnellere Knochengewebsintegration zu erzielen und damit den gesamten Behandlungsprozess zu beschleunigen, stellt die Verwendung biomimetischer Wirkstoff einen zunehmend interessanten Wirkungsbereich zur Forschung für die Implantatzahnheilkunde dar. Das vorliegende Dokument umreißt vier Kategorien an bioaktiven Wirkstoffen, die zur Beschichtung der Titanoberfläche von Implantaten verwendet werden könnten: (1) biokompatible Keramiken, (2) bioaktive Proteine, (3) Ionen, und (4) Polymere, sowie ihre entsprechende Bedeutung für die frühen Phasen der Knochengewebsintegration. Die potentiellen bioaktiven Wirkstoffe, die untersucht wurden, umschließen unter anderem morphogenetische Knochenproteine (BMPs), Wachstumsfaktoren (GFs), Typ-I-Kollagen, RGD-Peptide, Fluoride sowie Chitosan. Es werden die idealen Eigenschaften, über die biomimetische Wirkstoffe verfügen sollten sowie die Faktoren, die ihre Wirksamkeit beeinflussen könnten, beobachtet und untersucht. Dazu gehören die Oberflächentextur, das Zeitbasierte Abgabemedium sowie die Fähigkeit des Wirkstoffs, sein Ziel zu erreichen. Einige dieser Wirkstoffe, wie beispielsweise Biokeramiken (Kalziumphosphatsalze) oder Ionen (Fluoride) sind bereits allgemein im Handel erhältlich und haben sich in ihrer klinischen Anwendung als erfolgreich erwiesen. Andere, wie beispielsweise BMPs, scheinen sehr viel versprechend zu sein und verfügen über ein hervorragendes therapeutisches Potential. Eine spezielle Oberflächenbeschichtung bei Implantaten könnte dazu beitragen, den Prozentsatz an Knochen-Implantat-Kontakt sowie die Geschwindigkeit der Knochengewebsintegration zu erhöhen. Damit stünde den behandelnden Ärzten ein gutes Mittel zur Verfügung, um vielen klinischen Szenarien mit hohen Anforderungen adäquat zu begegnen.

SCHLÜSSELWÖRTER: zahnimplantat, knochengewebsintegration, titan, oberflächenbearbeitung, knochengewebsbildung

SPANISH / ESPAÑOL

AUTOR(ES): Gustavo Avila, DDS, PhD, Kelly Misch, DDS, Pablo Galindo-Moreno, DDS, PhD, Hom-Lay Wang, DDS, MSD, PhD. Correspondencia a: Hom-Lay Wang, DDS, MSD, PhD, Professor and Director of Graduate Periodontics, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1101 N. University, Ann Arbor, MI 48109-1078. Teléfono: 734-763-3383, Fax: 734-936-0374. Correo electrónico:[email protected]

Tratamiento de la superficie del implante usando agentes biomiméticos

ABSTRACTO: Ante el intento de lograr una oseointegración más rápida para poder acelerar el proceso general del tratamiento, el uso de agentes biomiméticos representa un campo de investigación en expansión en la odontología de implantes. Este trabajo reseña cuatro categorías de agentes bioactivos que pueden aplicarse para cubrir la superficie de un implante de titanio: (1) cerámicas biocompatibles, (2) proteínas bioactivas, (3) iones, y (4) polímeros y su importancia respectiva en las primeras etapas de la oseointegración. Los agentes bioactivos potenciales investigados incluyen las proteínas de hueso morfogenético (BMP por sus siglas en inglés), factores de crecimiento (GF por sus siglas en inglés), colágeno Tipo-I, péptidos RGD, fluoruro, o quitosano, entre otros. Se evalúan las características ideales que retienen los agentes biomiméticos y los factores que podrían influenciar su eficacia. Los mismos incluyen la textura de la superficie del implante, vehículos de entrega orientados hacia el tiempo y la capacidad del agente de alcanzar la meta. Algunos de estos agentes, tales como las biocerámicas (sales de fosfato de calcio) o iones (fluoruro) ya están disponibles comercialmente y han demostrado ser clínicamente exitosos. Otros, tales como los BMP son muy prometedores, con un excelente potencial terapéutico. Un recubrimiento específico de la superficie del implante podría mejorar el porcentaje del contacto entre el hueso y el implante así como acelerar la oseointegración que permite a los clínicos superar muchos escenarios clínicos complicados

PALABRAS CLAVES: implante dental, oseointegración, titanio, modificación de la superficie, formación de hueso

PORTUGUESE / PORTUGUÊS

AUTOR(ES): Gustavo Avila, Cirurgião-Dentista, PhD, Kelly Misch, Cirurgiã-Dentista, Pablo Galindo-Moreno, Cirurgião- Dentista, PhD, Hom-Lay Wang, Cirurgião-Dentista, Mestre em Odontologia, PhD. Correspondência para: Hom-Lay Wang, DDS, MSD, PhD, Professor and Director of Graduate Periodontics, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1101 N. University, Ann Arbor, MI 48109-1078. Telefone: 734-763-3383 Fax: 734-936-0374. e-mail:[email protected]

Tratmento de Superficie de Implante usando Agentes Biominéticos

RESUMO: Com uma tentativa de alcançar osseointegração mais rápida a fim de apressar o processo geral de tratamento, o uso de agentes biomiméticos representa uma área crescente de pesquisa em odontologia de implante. Este artigo delineia quatro categorias de agentes bioativos que podem ser aplicados para cobrir a superfície de implante de titânio: (1) cerâmica biocompatível, (2) proteínas bioativas, (3) íons, e (4) polímeros e sua respectiva importância nos estágios iniciais da osseointegração. Os agentes bioativos potenciais pesquisados incluem proteínas morfogenéticas do osso (BMPs), fatores de crescimento (GFs), colágeno Tipo-I, RGD peptídeo, fluoreto ou chitosan, entre outros. As características ideais que os agentes biomiméticos deveriam preservar e os fatores que podem influenciar sua eficácia são revistos. Elas incluem textura de superfície de implante, veículo de entrega orientada a tempo e a capacidade do agente atingir uma meta. Alguns desses agentes, tais como biocerâmica (sais de fosfato de cálcio) ou íons (fluoreto) já estão disponíveis comercialmente e têm mostrado sucesso clínico. Outros tais como BMPs são muito promissores, com um excelente potencial terapêutico. Uma cobertura específica de superfície de implante pode aumentar a porcentagem de contato osso-implante, bem como a velocidade da osseointegração que permite que os clínicos superem muitos cenários clínicos desafiadores

PALAVRAS-CHAVE: implante dentário, osseointegração, titânio, modificação de superfície, formação de osso

RUSSIAN / SYMBOL

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АВТОРЫ: Gustavo Avila, доктор Џequals;ирургичeской стоматологии, доктор философии, Kelly Misch, доктор Џequals;ирургичeской стоматологии, Pablo Galindo-Moreno, доктор Џequals;ирургичeской стоматологии, доктор философии и Hom-Lay Wang, доктор Џequals;ирургичeской стоматологии, магистр стоматологии, доктор философии. Адрeс для коррeспондeнции: Hom-Lay Wang, DDS, MSD, PhD, Professor and Director of Graduate Periodontics, Dept. of Periodontics and Oral Medicine, University of Michigan, School of Dentistry. 1101 N. University, Ann Arbor, MI 48109-1078. Тeлeфон: 734-763-3383, Факс: 734-936-0374, Адрeс элeктронной почты:[email protected].

Обработка повeрЏequals;ности имплантата при помощи биомимeтичeскиЏequals; матeриалов

РEЗЮМE: Примeнeниe биомимeтичeскиЏequals; матeриалов в дeнталЏrsquo;ной имплантологии прeдставляeт собой интeнсивно развивающуюся областЏrsquo; исслeдований в связи с нeобЏequals;одимостЏrsquo;ю ускоритЏrsquo; процeсс остeоинтeграции и общий процeсс лeчeния. В данной работe рассматриваются чeтырe катeгории биоактивныЏequals; матeриалов, которыe можно примeнятЏrsquo; для покрытия титановой повeрЏequals;ности имплантатов: 1) биосовмeстимая кeрамика, 2) биоактивныe протeины, 3) ионы и 4) полимeры; а такжe значимостЏrsquo; каждого из этиЏequals; видов матeриалов на ранниЏequals; стадияЏequals; остeоинтeграции. Срeди исслeдуeмыЏequals; потeнциалЏrsquo;ныЏequals; биоактивныЏequals; матeриалов в данной работe прeдставлeны костныe морфогeнeтичeскиe протeины (BMPs), факторы роста (GFs), коллагeн I типа, RGD-содeржащий пeптид, фторид и Џequals;итозан. Рассматриваются оптималЏrsquo;ныe свойства, которыми должны обладатЏrsquo; биомимeтичeскиe матeриалы, и факторы, влияющиe на иЏequals; эффeктивностЏrsquo;. к ним относится тeкстура повeрЏequals;ности имплантата, срeдство доставки с учeтом врeмeни и способностЏrsquo; матeриала достигатЏrsquo; цeли. Нeкоторыe из данныЏequals; матeриалов, такиe как биокeрамика (калЏrsquo;циeво-фосфатныe соли) или ионы (фторид), ужe доказали свою клиничeскую эффeктивностЏrsquo; и прeдставлeны на рынкe. Другиe матeриалы, такиe как костныe морфогeнeтичeскиe протeины (BMPs), являются вeсЏrsquo;ма пeрспeктивными, обладая отличным тeрапeвтичeским потeнциалом. Особоe покрытиe повeрЏequals;ности имплантата можeт улучшитЏrsquo; контакт костЏrsquo;-имплантат и способствоватЏrsquo; ускорeнию остeоинтeграции, что позволит врачам избeжатЏrsquo; многиЏequals; отрицатeлЏrsquo;ныЏequals; клиничeскиЏequals; послeдствий

кЛЮХEВЫE СЛОВА: зубной имплантат, остeоинтeграция, титан, модификация повeрЏequals;ности, костeобразованиe.

TURKISH / TÜRKÇE

YAZARLAR: Gustavo Avila, DDS, PhD, Kelly Misch, DDS, Pablo Galindo-Moreno, DDS, PhD, Hom-Lay Wang, DDS, MSD, PhD. Yazışma için: Hom-Lay Wang, DDS, MSD, PhD, Professor and Director of Graduate Periodontics, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1101 N. University, Ann Arbor, MI 48109-1078 ABD. Telefon: 734-763-3383, Faks: 734-936-0374. e-posta:[email protected]

Biyo-mimetik Ajanlar Kullanarak İmplant Yüzeyinin Kaplanması

ÖZET: Genel tedavi sürecini hızlandırmak amacıyla daha süratli osseoentegrasyon sağlamak için biyomimetik ajanların kullanımı, implant dişçiliğinin halen büyümekte olan bir alanıdır. Bu çalışma, titanyum implant yüzeyini kaplamak için uygulanabilecek biyo-aktif ajanların dört kategorisini sunmaktadır: (1) biyo-uyumlu seramikler, (2) biyo-aktif proteinler, (3) iyonlar, ve (4) polimerler ve bunların osseoentegrasyonun erken evrelerindeki önemi. Araştırılan olası biyo-aktif ajanlar arasında kemik morfogenetik proteinleri (KMP), büyüme faktörleri (BF), Tip I kollajen, RGD peptid, florür, veya chitosan, ve diğerleri yer aldı. Bu çalışmada biyo-mimetik ajanların ideal özellikleri ve bunların etkinliğini etkileyen faktörler incelendi. Bu özellikler arasında implant yüzeyinin dokusu, zamana ilişkin dağıtım aracı ve ajanın hedefine ulaşabilme yeteneği sayılabilir. Biyo-seramikler (kalsiyum fosfat tuzları) veya iyonlar (florür) gibi bazı ajanlar piyasada mevcut olup, klinik başarı göstermişlerdir. KMP gibi diğer ajanlar, mükemmel terapötik potansiyelleri nedeniyle ümit verici kabul edilmektedir. Özel bir implant yüzeyi kaplaması, kemiğin implant ile temas yüzdesini arttırabileceği gibi, diş hekimlerinin birçok çetin klinik senaryoları yenmelerine olanak sağlamak üzere osseoentegrasyon hızını da arttırabilir.

ANAHTAR KELİMELER: dental implant, osseoentegrasyon, titanyum, yüzeyde değişiklik, kemik oluşumu

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CHINESE / SYMBOL

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KOREAN / SYMBOL

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Keywords:

dental implant; osseointegration; titanium; surface modification; bone formation

© 2009 Lippincott Williams & Wilkins, Inc.