Bone Biology & Physiology, Selection Of Grafting Materials .

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Implant SiteDevelopmentand ExtractionSite GraftingBone Biology & Physiology,Selection of Grafting Materials,Selection of Barrier Membranesand Surgical TechniqueBarry Kyle Bartee DDS, MDS I M P L E P R E D I C TA B L E P R A C T I C A L

Presented byOsteogenics Biomedical, Inc.Toll-free (888) 796.1923International calls (806) ducational DisclaimerThe authors, editors and publisher haveexerted considerable care to ensure that drug,device and material selection and applicationsset forth in this publication are in accordancewith current recommendations and practiceat the time of publication. However, in viewof ongoing research, changes in governmentregulations, and the constant flow of information related to implant procedures, graftingand implant materials and techniques, thereader is urged to check the package insert,prior to use, for any material discussed forany changes in indications and dosage and foradditional warnings and precautions. This isparticularly important when the recommendedagent is new or infrequently employed.Readers need to be aware of the potentialrisks of using limited knowledge when integrating techniques and procedures that arenew to them into their practices, particularly iftheir training has not included supervised clinical experience to ensure that participants haveattained competence. Treatment decisions arepersonal choices made by individual dentistsexercising their own professional judgment ineach situation. Readers need to consult theirown professional colleagues and advisers forprofessional advice. Osteogenics Biomedical,Inc. does not warrant the accuracy, completeness or timeliness of the informationpresented and is not responsible for anyclaim, injury, damage or loss arising from theuse of or reliance upon the material presentedor techniques demonstrated, whether thoseclaims are asserted by members of the healthcare professions or any other person. Copyright 2012 by Osteogenics Biomedical, Inc. AllRights Reserved. No part of this manual may be reproduced by any means without prior written permission.For information contact Osteogenics Biomedical,4620 71st Street, Building 78, Lubbock, Texas 79424

Table of Contents5566799910101011131618192022232526Section 1:Bone Grafting Biology &PhysiologyBone Structure and FunctionCellular ComponentsBone as a Dynamic TissueAlveolar Bone LossSection 2:Bone Grafting MaterialsMechanisms of Graft HealingClassification of MaterialsRelated Concepts and TermsClassification of Grafting MaterialsAutogenous BoneAllograftsAlloplastsXenograftsSection 3:Guided Tissue RegenerationMembranesNon-resorbable MembranesResorbable MembranesSection 4:Extraction SiteGrafting ProcedureGraft Material Selection Based onProsthetic OutcomeCytoplast Ridge PreservationTechniquePatient Management28Case Study:Extraction, ImmediateImplant Placement andGuided Bone RegenerationUsing a Flapless Approach30Case Study:Use of Titanium-Reinforceddense PTFE Membrane forImmediate Socket Reconstruction32Appendix A:Cytoplast PTFE MembraneProduct Description34Appendix B:References36Appendix C:Selection of Abstracts

Osteogenics Biomedical, Inc.4620 71st Street Bldg 78Lubbock, TX 79424888.796.1923osteogenics.comCytoplast Regenerative Membrane ProductsCytoplast PTFE SuturePro-Fix Precision Fixation SystemenCore Combination AllograftVitala Porcine Derived Collagen MembraneZcore Porcine Xenograft ParticulateNovabone Dental PuttyResorba Sutures

The Biology of Bone Grafting SECTION 1The loss of bone following tooth extraction is a significant clinicalproblem in implant dentistry as well as conventional restorativedentistry. Clinical studies indicate that in the first few monthsfollowing tooth extraction as much as 1-3 mm in alveolar ridgeheight and 3-5 mm in ridge width may be lost due to the resorptive nature of the healing process. Unfortunately, this bone lossis permanent and has severe consequences in terms of potentialimplant support. Moreover, in the esthetic zone, bone loss canseverely impact the appearance of implant restorations due tosubsequent loss of interdental papillae, facial soft tissue recession, or loss of soft tissue volume which is essential in providingcamouflage of abutments and restorative components.3.Cells: osteoprogenitor cells osteoblasts osteocytes osteoclasts4.Vascular & Nutrient Distribution: bone receives 5 - 10% of cardiac output arterial supply microcirculation, extracellular fluid lymphatics venous returnThe literature has shown that early bone loss can be significantlyreduced by advanced socket management techniques combinedwith atraumatic tooth extraction. The process of socket graftingis not technically difficult, but does require an understanding ofwound healing and an appreciation of the biological properties ofthe products available for socket grafting. The use of a standardized clinical technique and material selection protocol is alsoimportant if predictable results are to be achieved.5.Neurological: autonomic neurosensory6.Marrow: serves both hematopoietic andosteogenic functionsWith these goals in mind, this manual will guide the readerthrough a logical process of understanding the selection and useof particulate grafting materials as well as the various membranesavailable for socket grafting. The subtle differences in augmentation materials, and the effect that material properties have onclinical outcome will be discussed. Finally, a technique of socketgrafting developed by the author will be presented. It is our intentto provide the reader with a scientific, standardized and provenapproach to socket grafting which will yield predictable results.7.Periosteum: a source of osteoprogenitor cells,neurovascular distribution, blood supply8. Endosteum: "inner osteogenic layer" a source of osteoprogenitor cells9.Communication System: a network including Haversian and Volksmann's canals,canaliculi, lacunae and extracellular fluid.Bone as an Organ SystemStructural ClassificationBone is a dynamic and highly ordered structure on the macroscopic, microscopic, cellular and molecular levels. Conceptually,bone is described within the framework of the following anatomical and functional components.Compact BoneThis is a clinical term referring to the dense, solid bone found atthe outer cortical layer of the maxilla or mandible or the corticalplate of the extraction socket. Composed primarily of mineralized matrix, it is designed for load bearing and protection withrelatively few cells and blood vessels.1.2.Organic matrix: 40% of the dry weight of bone composed of 90% Type I collagen non-collagenous proteins ground substance/H20 proteoglycans, cytokines, & growth factorsMineralized matrix: 60% of the dry weight of bone hydroxylapatite crystals: Ca10(PO4)6(OH)2Trabecular boneThis is a clinical term referring to the less dense bone locatedbetween the cortical plates of the maxilla or mandible. Trabecularbone may also be referred to as spongy or cancellous bone. Clinically, trabecular bone may vary in density and may be composedof thick or relatively thin trabeculae.5

Section 1 The Biology of Bone GraftingLamellar BoneOn the microscopic level, this term describes a highly organized, secondary structureof bone arranged in a typical layered fashion. Lamellar bone may be arranged in concentric Haversian systems such as seen in dense compact bone, or it may be foundas circumferential or endosteal lamellae located immediately beneath the periosteum.This is the principal load-bearing bone of the body and is the predominant componentof mature cortical and trabecular bone.Woven (embryonic) BoneIn distinct contrast to the highly organized structure of lamellar bone, on the lightmicroscopic level the term woven bone describes a highly cellular, less organized,poorly mineralized bone that is formed in response to growth or injury. For example,woven bone is the first type of bone observed in a healing extraction site, or foundimmediately adjacent to a dental implant in the first few weeks following implantation.Woven bone is initially very weak. However, it is eventually remodeled into highlyorganized, load bearing, lamellar bone with increased mineral density. Woven bone isnot typically found in the adult skeleton except in response to fracture or injury.Cellular ComponentsThere are four major cell types that we are concerned with in the context of socketgrafting, implantology and ridge augmentation.Osteoprogenitor CellsThese cells may also be referred to as undifferentiated stem cells, pluripotential cells,stem cells, or bone marrow stromal cells. Osteoprogenitor cells, which are initiallyfibroblastic in appearance, differentiate into preosteoblastic and mature osteoblasticcells found lining the endosteal surfaces of bone.Figure 1WLFigure 2Histology from a bone core taken by the author froman extraction site grafted with tricalcium phosphate at6 months (Fig.1). The application of polarized light onthe same sample (Fig. 2) demonstrates the differencein organization between lamellar and woven bone. Inthis section, focal zones of lamellar bone are seen (L)as well as less organized, woven bone (W). (Histologyby Dr. Michael D. Rohrer, University of Minnesota.)6The OsteoblastThe osteoblast is the "bone forming" cell responsible for deposition and calcification ofthe extracellular bone matrix. They are initially derived from mesenchymal pluripotential/stem cells in the bone marrow. Depending on the microenvironment and exposure to various growth factors, it may also differentiate into fat, cartilage or muscle(Owen & Ashton, 1986. Beresford, 1989). Mature osteoblasts are polarized andsecretorily active, synthesizing collagen and other proteins such as growth factors.Once osteoblasts have done their work, they may be known as "resting surface cells"or if they are encircled in bone, are referred to as osteocytes.The OsteocyteThe osteocyte is a mature, fully differentiated osteoblast which has been surroundedby mineralized bone matrix. While it is no longer active in terms of forming bone matrix, it does play a role in cell to cell communication via fluid flow in the lacunar-canalicular system. This communication is believed to be involved in the response of boneto load or injury and in regulating the response of bone to the mechanical environment(Skerry et al., 1989).The OsteoclastThis "bone resorbing" cell is responsible for the resorptive aspect of bone modeling andremodeling. This large, motile, multinucleated cell elaborates enzymes such as collagenase, lysozomal enzymes, and acids at the "ruffled border" of the cell, which is the sitefor resorption of mineralized bone matrix and collagen degradation (Baron, 1989). Thecomplex actions of this cell are under hormonal control (PTH, D3, calcitonin, glucocortocoids, prostaglandins, ILGF, TNF, TGFb, androgens, thyroid hormones, bisphosphonates) and are influenced by local factors as well (vascular/NO2, stress, strain).

Section 1 The Biology of Bone GraftingBone as a Dynamic TissueIn the human body, bone plays an important structural role, providing the framework forand the protection of vital organs. Throughout the body, bone is important in facilitatinglocomotion and other complex functional movements such as mastication. In addition,bone plays an important role in metabolism, serving as a reservoir of lipids, calcium andphosphate. In the adult, bone is also important in the production of blood cells (erythrocytes, differentiated granulocytes, platelets) which are derived from pluripotentialhematopoietic stem cells in the bone marrow.Structurally, bone is a complex and constantly changing tissue which is capable of selfrepair and adaptation to new loads. Two fundamental concepts, modeling and remodeling, are used to describe the dynamic nature of bone.Modeling is the process whereby, in response to some stimulus or physical force, abone may change in three-dimensional size or shape. An example is the change observed in alveolar bone following the loss of teeth. In this case, osteoclastic resorptionbecomes uncoupled from and outpaces osteoblastic deposition, resulting in a net lossin bone mass. Clinically, this phenomenon is manifest as alveolar ridge resorption.In contrast to a visible three-dimensional change, the concept of remodeling refersto the internal turnover of bone. Remodeling is a coupled process where osteoclasticresorption and osteoblastic formation are more or less balanced. Similar to the constant regeneration and replacement of the epidermis, remodeling helps maintain theskeleton in a healthy state ready to carry load. Remodeling also plays a role in maintaining calcium homeostasis and in the repair of microtrauma to bone. A clinical exampleof remodeling is the development and long-term maintenance of healthy bone at thebone-implant interface in response to appropriate physiologic loading.The rate of remodeling may vary from location to location and from one type of bone toanother. Because remodeling is a surface-level phenomenon, and since trabecular bonehas a much greater surface area than cortical bone, the rate of remodeling is six timesgreater in trabecular bone than in cortical bone. Thus, more rapid loss will typically beobserved first in areas rich in trabecular bone, such as the vertebral bodies and dentalalveolus, and later in cortical bone sites.It is clear that bone formation and resorption is under cellular control, and that theseprocesses are mediated by molecular messengers. The extracellular fluid within thecanalicular system is the medium through which cell to cell communication occurs; presumably by exchange of biochemical mediators produced in response to stress, strain,inflammation or other environmental cues. These mediators interact with the bonecells via cell surface receptors, causing release of "second messenger" cell signalingmolecules. In turn, DNA and protein synthesis is "turned on" within the cell, manifest aschanges in cellular behavior or differentiation.Figure 3. A sample bone core taken by the author froman extraction site grafted with demineralized bone at4 months. Osteocytes (1) are seen encased in islandsof newly formed mineralized bone. Osteoblasts andpre-osteoblasts (2) are observed on the leading edgeof bone formation. An osteoclast is observed (3) incontact with and actively resorbing a fragment of residual allograft. (Histology by Dr. John M. Wright, TexasA&M Baylor College of Dentistry.)Alveolar Bone LossIn addition to physiological remodeling, in implant dentistry we must be concerned withthe ongoing response of bone to loading. It is well accepted that mechanical overloadof implants can result in bone resorption, and that dynamic mechanical loading withinphysiological limits tends to result in maintenance of bone mass and functional trabecular orientation. In contrast, inadequate mechanical stimulation or the application of highstatic loads can result in reduced bone mass through resorptive modeling.How do bone cells communicate with the outside environment? The concept ofmechanotransduction; the translation of mechanical signals into biochemical response,provides some insight. Integrins, a group of specialized transmembrane receptor7

Section 1 The Biology of Bone GraftingNOTESmolecules found on the bone cell, enable the cell to sense and respond to changes inthe local environment through simultaneous contact with the extracellular matrix andthe actin cytoskeleton inside the cell membrane. Through the coupling of mechanicalcues with a tightly regulated, complex intracellular and nuclear biochemical cascade,events such as proliferation, migration, and adhesion can be affected.The loss of bone following tooth extraction provides a good example of the complexinteraction between the environment and cellular behavior and response. A recentstudy found that disuse atrophy in bone is related to acquired resistance of bone cellsto the effects of insulin like growth factor (IGF-1). In this investigation, cells whichwere protected from mechanical loading showed reduced expression of integrins andtherefore a reduced ability to respond to the effects of the growth factor.Similarly, loss of the natural dentition results in reduced physical loading of alveolarbone. Shortly thereafter, resorptive modeling of the alveolus occurs. Certainly, theprocess of post-extraction bone loss is complex and many factors are involved.While it is interesting to speculate on the cellular and molecular mechanisms involvedin alveolar bone loss, the central question remains: can anything be done clinically toeliminate or reduce this phenomenon?Let's look at the available evidence. Over 20 years ago, it was shown that root-shapedcones made from hydroxylapatite, when placed into fresh extraction sites, resulted ina reduction in bone loss (Quinn and Kent). Later, hydroxylapatite particles were usedin the same fashion by the same authors with some success in animal studies (Blockand Kent, 1986). Unfortunately, the use of cones and particles was never widelyaccepted, and interest in these procedures declined due to premature exposure andloss of graft materials during the early healing phase.With the advent of guided tissue regeneration (GTR) in periodontics, the concept ofusing barrier membranes to improve socket healing was explored. The use of guidedtissue regeneration membranes placed over extraction sockets, even without underlying graft materials was shown to result in a reduction of ridge resorption (Nemcovsky1996. Lekovic 1997, 1998).Recently, immediate implant placement into extraction sites has been suggested asone method to reduce bone loss (Schropp 2003, Covani 2003, Boticelli 2004). It hasfurther been suggested that if the gap between the implant and buccal socket wall is2.0 mm or less, that no additional intervention in the form of adjunctive graft materials or membranes is required. However, a careful analysis of the data reveals thatwhile osseointegration was indeed successful, a substantial reduction in bone widthoccurred, up to 56% in one report (Boticelli 2004).Therefore, we can draw several conclusions from the available evidence in thesesocket grafting studies.1. The use of a guided tissue regeneration membrane alone, with no underlying graftmaterial, results in a reduction in bone loss.2. The use of a particulate material alone with no membrane results in a reduction inbone loss, but particle loss reduces the predictability of the procedure.3. Implants placed immediately into extraction sockets integrate predictably. However, if no graft material is placed into the gap between the facial aspect of the implantand the buccal plate, bone loss occurs similar to untreated extraction sites.4. Particulate grafting materials differ in terms of their resorption profile and have thepotential, if not used appropriately, to actually interfere with normal bone formation. n8

Bone Grafting Materials SECTION 2Mechanisms of Bone Formationand Graft HealingImplantation of a graft material, whether natural or synthetic,results in a host response. There are effects at the tissue, cellular, and molecular level resulting from the interaction of the hosttissue with the implanted material. These effects are chieflydependent on the morphology, chemical composition, porosityand particle size of the material. In addition, materials whichcontain biomimetic or bioactive molecules may accelerate thenormal wound healing kinetics by modulation of normal cellularprocesses. Even inert biomaterials - which may appear to dolittle more than take up space - may cause significant biologiceffects through mechanical interaction with host tissue.When selecting a bone graft material for a given clinical situation, several questions arise: What is the clinical outcomedesired? Do we want vital bone for the future placement ofimplants, or do we want long-term, stable preservation of apontic site? Will the implantation o

Implant Site Development and Extraction Site Grafting Bone Biology & Physiology, Selection of Grafting Materials, Selection of Barrier Membranes and Surgical Technique Barry Kyle Bartee DDS, MD. Presented by Osteogenics Biomedical, Inc. Toll-free (888) 796.1923 International calls (806) 796.1923

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