Table of Contents      
INVITED REVIEW
Year : 2015  |  Volume : 7  |  Issue : 3  |  Page : 40-47

Dynamics of bone graft healing around implants


1 Department of Oral Pathology, Oxford Dental College, Banglore, Karnataka, India
2 Department of Periodontics, Sudha Rustagi College of Dental Sciences and Research, Faridabad, Haryana, India
3 Department of Oral and Maxillofacial Surgery, Sudha Rustagi College of Dental Sciences and Research, Faridabad, Haryana, India
4 Department of Periodontics, Rajiv Gandhi Dental College, Banglore, Karnataka, India

Date of Web Publication31-Dec-2015

Correspondence Address:
Sumidha Bansal
363, Sector 19, Faridabad, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0754.172930

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   Abstract 

Bone is a highly dynamic tissue undergoing constant adaptation to the mechanical and metabolic demands of the body by bone regeneration and repair. In order to facilitate or promote bone healing, bone grafting materials have been placed into bony defects. The advantages of using bone grafts are space maintenance, inhibiting collapse of defect and acting (at least) as osteoconductive scaffold (though they can be osteoinductive or osteogenic also). After their successful use around teeth afflicted by periodontal disease, in ridge augmentations, and in socket preservations, we now look forward to their use around implants during the osseointegration phase.
A few questions arise pertaining to the use of bone grafts along with implants are whether these are successful in approximation with implant. Do they accelerate bone regeneration? Are all defects ultimately regenerated with new viable bone? Is the bone graft completely resorbed or integrated in new bone? Does the implant surface characteristic positively affect osseointegration when used with a bone graft? What type of graft and implant surface can be used that will have a positive effect on the healing type and time? Finally, what are the dynamics of bone graft healing around an implant? This review discusses the cellular and molecular mechanisms of bone graft healing in general and in vicinity of another foreign, avascular body, namely the implant surface, and further, the role of bone grafts in osseointegration and/or clinical success of the implants.

Keywords: Bone graft healing, endosseous dental implants, immediate implant placement, osseointegration, sinus lift


How to cite this article:
Venkataraman N, Bansal S, Bansal P, Narayan S. Dynamics of bone graft healing around implants. J Int Clin Dent Res Organ 2015;7, Suppl S1:40-7

How to cite this URL:
Venkataraman N, Bansal S, Bansal P, Narayan S. Dynamics of bone graft healing around implants. J Int Clin Dent Res Organ [serial online] 2015 [cited 2018 Nov 15];7, Suppl S1:40-7. Available from: http://www.jicdro.org/text.asp?2015/7/3/40/172930


   Introduction Top


High success rates of dental rehabilitation with endosseous implants have prompted its use in more challenging clinical situations, the most common being insufficient bone volume at recipient sites. These days implants are regularly being accommodated in treatment plans, to be further placed in extraction sockets as a part of immediate implant placement, or in areas requiring sinus lift to increase the local bone stock. Similarly, the loading schedule of implants is increasingly getting shortened to weeks, days or even hours.[1] These changes have been possible though evolution of knowledge in different fields such as surgical procedures related to implants, implant surface and design characteristics, and the concepts and mechanisms of periimplant bone healing.

The understanding of science of bone grafting is continuously developing with the principles of cellular and molecular biology being incorporated in osseous healing. With the increased demand of use of bone grafting in implantology, a review of biologic events of healing of various bone grafts around implant surface seems essential.

The first documented xenograft was done by Job van Mee'kren in 1600.[2] Allografting was introduced by Sir William MacEwen in 1879.[3] The physiological properties of osteogenesis, osteoconduction, and osteoinduction possessed by bone grafts is one of the most important factors that affect the dynamics of bone graft healing. While osteogenesis is the ability of graft to produce new bone owing to the presence of viable osteoprogenitor/osteogenic precursor cells, osteoinduction is the ability of the graft to induce stem cells to differentiate into mature bone cells owing to the presence of bone growth factors. Osteoconduction is just a physical property that enables a graft to serve as a scaffold and allow the ingrowth of neovasculature and infiltration of osteogenic precursor cells into the graft site.[4]

Several local factors that influence graft incorporation positively are good vascular supply at graft site, large surface area, mechanical stability and loading, growth factors, and electrical stimulation; while radiation, bone disease, infection, mechanical instability, and denervation affect it negatively.[5] A major factor when considering a bone graft material is the aim of the surgeon regarding repair or regeneration. Repair is the replacement of a part with something that is physically but not biologically or physiologically similar to the original structure, and regeneration is natural renewal of a structure, produced by growth and differentiation of new cells and intercellular substances to form new tissues or parts in all ways identical to what was lost.[6]

Concept of osseointegration

Endosseous wound healing comprises of stages of hematoma formation, clot resolution, and osteogenic cell migration, which lead to the formation of new bone. The osseous healing phase consists of:

  1. Osteoconduction that relies on recruitment and migration of osteogenic cells to implant surface.
  2. de novo bone formation.
  3. Bone remodeling.


Osseointegration was defined by Brånemark [7] as a direct structural and functional connection between ordered living bone and the surface of a load-carrying implant. Osborn and Newesley [8] proposed the concept of contact or distance osteogenesis. While the former involves de novo bone formation directly on the implant surface, the latter is formation of new bone on the surfaces of existing periimplant bone. Immediately after implantation serum proteins adhere, and during the first three days mesenchymal cells attach and proliferate. Osteoid formation and matrix calcification occur by 6 days and 14 days respectively. Remodeling starts by 3 weeks.[9]

Rationale of using bone graft with implants

Bone grafts are used along with implants in procedures such as sinus lift, immediate implant placement in extraction sockets, and ridge augmentation. Bone grafts serve as support for the sinus membrane to prevent its collapse and hence maintain space, and may at the same time promote bone formation.[10]

According to Schmitz and Hollinger,[11] a critical-size defect does not heal spontaneously without placement of the graft during the healing period. Thus bone augmentation is recommended in the gaps wider than 2 mm left between the socket wall and the coronal neck of the implant during immediate implant placement. All grafts have their unique properties owing to which they are usable in different conditions. Autogenous grafts, although the gold standard in reconstructive surgery, have the disadvantages of donor site morbidity and limited available bone volume. Dense, crystalline hydroxyapatite (HA) is used in the denture support region to maintain contour and volume and not in socket preservation as it is almost thrice as hard as bone and nonresorbable. While β-tricalcium phosphate (β-TCP) is considered useful in a contained type defect owing to the favorable substitution rate in a standardized bone defect, its usefulness in onlay grafting and as volume expander around autogenous onlay blocks is questionable due to the same reason. Anorganic bovine bone (ABB) shows osseous integration in mature bone but without evidence of substitution of graft particles, thus showing partial nonresorbability.[12] Hence the choice of graft material is based on its application and macromolecular and biochemical profile.

Structure and biochemical properties of different grafts

Autografts

These contain properties of osteoinductivity [due to bone morphogenetic protein (BMP)], osteoconductivity (bone mineral and collagen), and osteogenicity (osteoblastic cells, preosteoblastic precursor cells). Insufficient amount, morbidity, and cost are the drawbacks. Autografts can be of three types: bone marrow, cancellous, and cortical.[5]

Allografts

These are the graft materials harvested from different individuals of the same species and require processing in order to lessen antigenicity and disease transfer. They are osteoconductive and osteoinductive. Immunogenicity is decreased when grafts are deep-frozen and even more when freeze-dried.[5]

Xenografts

These are obtained from the bone of individuals of other species, their composition and biomechanical properties being almost similar to bone. Two illustrations of xenografts used in dentistry are i) coral-derived bone substitutes having geometry similar to that of human cancellous bone interconnected macropores (200-600 µm) and ii) demineralized bovine bone grafts, biocompatible and osteoconductive. There are two types of demineralization:

  1. High temperatures and
  2. Chemical extraction of calcium and other minerals.[13]


Alloplastic materials

Calcium phosphates

These are synthetic osteoconductive materials with composition similar to bone. They are HA (calcium/phosphate: 1.67) and β-TCP: (calcium/phosphate: 1.5). Due to this biochemical difference in the composition, β-TCP resorbs faster and is generally replaced by natural bone in a 3-24 month period depending on the type of bone. HA resorption is slow/very slow (years, decades). Calcium phosphates are available as porous blocks or granules. The molecular mechanism of action in vivo is not yet defined. Regulation of bioactivity is based only on the HA/TCP ratio. The mechanism of resorption involves chemical dissolution and osteoclastic resorption.[14]

Bioactive glasses

Bioactive glasses are a group of synthetic silica-based bioactive materials with unique bone-bonding properties first discovered by Hench.[15] They are composed of calcium and phosphates along with sodium and silicon salts that promote bone mineralization. They are available as granules or sintered porous blocks, fibers, and woven structures; they are osteopromotive and form chemical bonding with ongrowing new bone. They induce high local bone turnover. Bioactive glasses have different rates of bioactivity and resorption rates, which can be regulated by modifying the chemical composition. The most rapid bonding is achieved with bioactive glasses containing 45-52% in weight of SiO2 (silicon dioxide). They are found to be superior to calcium phosphates owing to the relatively quick rate of reaction with host cells, ability to bond to collagen found in connective tissue, and ability to bond to hard and soft tissue. The mechanism of resorption is through chemical dissolution. They are also known to inhibit bacterial growth in vitro, depending on chemical composition.[14]

Hard tissue replacement (HTR) polymer

It is a microporous composite with calcium hydroxide graft surface. It is slow-resorbing, healing by osteoconduction.[16]

Cellular and molecular events after bone grafting

Autograft

An autograft is very osteogenic, easily revascularized, and rapidly incorporated. It lacks mechanical strength, but this is balanced by early production of new bone. Active bone formation and resorption occurs by 4 weeks of graft placement. In the secondary phase, osteoblasts lay down seams of the osteoid that surrounds the core of dead bone. The most important difference between cortical and cancellous grafts is in the rate of vascularization and degree of osteoinduction, which is less in the former due to the dense architecture and lower number of endosteal cells.

For osseointegration of the graft to proceed successfully, the host tissue must have sufficient vascularity to diffuse nutrients to the cells before revascularization occurs and bud new capillaries into the graft to create a more permanent vascular network. Osteogenesis is activated by surgical trauma, which releases a large quantity of cytokines with osteogenic effects, such as BMP-2, platelet-derived growth factor (PDGF), tumor growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF). This repair reaction with the formation of woven bone originates from the bone walls subjected to trauma, which stimulates the osteoblastic precursors, due to exposure of the bone matrix, and also acts as a solid wall for attachment of the osteoblasts. Placement of the graft with autogenous endosteal osteoblasts embedded within creates a biochemical environment at the recipient site that is hypoxic (O2 tension of 3-10 mmHg), acidotic (pH 4.0-6.0), and rich in lactate. Osteoblasts survive the first 3-5 days after transplant to the host site because of their surface positioning and ability to absorb nutrients from recipient sites. The platelets trapped in the clot degranulate within hours and release the PDGF depending on the oxygen gradient of the graft incorporated, with mitogenesis of osteocompetent cells and angiogenesis of the capillaries at the recipient site. By 3 days, budding capillaries are seen outside the surface of the graft, which penetrate the graft and form a vascular network by 10-14 days. PDGF is then replaced by macrophage-derived growth factor (MDGF) and other mesenchymal tissue stimulators from the TGF-β family. During the initial week of graft placement only minimal osteoid deposition is noted, but after established vascular network formation, due to abundant oxygen and nutrient availability, acceleration in bone healing is noticeably seen. Consolidation of the graft during the first 3-4 weeks by the chemical and cellular phase activity of bone healing enables formation of a scaffold framework for initiation of the osteoconductive phase of healing. This phase of bone healing with cellular regeneration is referred to as phase-I bone regeneration, where disorganized woven bone similar to fracture callus is formed. The addition of certain growth factors to the material, such as PDGF, recombinant human BMP (rhBMP), TGF-β, and insulin growth factor (IGF), increases the speed and quantity of bone regeneration. Phase-I bone undergoes resorption and remodeling until its eventually replacement by less cellular, more mineralized and structurally organized phase-II bone forms. Phase-II bone is initiated by osteoclasts that arrive at the graft site through the newly developed vascular network. This bone forms as in response to demands placed by the jaw and graft working in function. This bone develops into mature Haversian systems and lamellar bone that can withstand normal shear forces from the jaw and impact compressive forces that are typical of dentures and implant-supported prostheses.[16]

Allograft

Cancellous allograft is a poor promoter of bone healing compared to autograft. Allografts are incorporated faster than their cortical counterparts. They act as a scaffold onto which host bone is laid. They are never completely resorbed and thus remain entrapped in the host bone.[5]

Bone formation starts from the defect walls and progresses toward the center. Along the interface, spots of apparent mineral deposition arise between the mineralized woven bone and the demineralized matrix [demineralized freeze-dried bone allografts (DFDBA)], which are spherical and cylindrical precipitates having diameters 3-5pm at around 4 weeks, as seen in an animal study on minipigs.[17] Recalcification of DFDBA is restricted to areas where new mineralizing bone matrix is deposited on their surface. Sites where the particle surface faces the marrow tissue stay nonmineralized. At 12 weeks, bone formation spreads over the whole defect area, but it still includes a considerable amount of the grafted material and represents a composite of partially recalcified DFDBA, woven bone, and most superficially, lamellar bone deposits. Remodeling starts and osteoclastic resorption extends along bony surfaces as well as on recalcified DFDBA particles [Figure 1]a and [Figure 1]b.
Figure 1: (a) histologic sections of grafted bone 9 months after grafting with alloplast graft material. graft particles (GP) are surrounded by vital newly formed bone (NB) and bone marrow (BM). lining osteoblasts (OB) are clearly observed at the interface (hematoxylin and eosin stain; original magnification, 40×) (b) image processing of the biopsy in identifies new bone (red), graft particles (blue), and connective tissue (yellow)[37]

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Xenograft

Coral-derived HA

According to the study on minipigs mentioned above,[17]at 4 weeks the rather compact coral-derived HA granules are evenly dispersed in the defect sites and are invaded by dense fibrous tissue and bony trabeculae. Thin layers of woven bone cover the outer surface of the granules as well as the lining of their pores. At 12 weeks, the bony filling of pores and interspaces becomes much denser. Half of the newly formed bone still consists of woven bone, reinforced by parallel-fibered and lamellar bone. The overall remodeling activity, however, is low. At 24 weeks, the composite of coralline filler and bony regenerate seems the same except for the maturity of the bone structure. Enhanced remodeling replaces much of woven bone with lamellar bone but is restricted to the bone compartment, not extending into the adjacent coralline material [Figure 2]a and [Figure 2]b.
Figure 2: image showing μCT in which the substitute material HA (grey) is completely surrounded by bone (green)[36]

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ABB

Defects grafted with ABB show newly formed bone, although smaller and less mature than with autograft, at 4 weeks in minipigs.[12] The stark difference when compared to other grafts is its stability and resistance to resorption. At 8 weeks, too, it shows osseous integration that creates a dense, hard tissue network, which provides biological support to loaded dental implants that is comparable to or even in excess of native bone.[18]

Alloplast

Calcium phosphate-based graft materials

Several calcium phosphate parameters can affect cellular activity: dissolution, composition, topography, surface energy. After colonization of the substrate by monocytes/macrophages that are recruited during the inflammatory reaction following surgery, osteoclasts are responsible for bone resorption. They degrade calcium phosphate ceramics in a similar way to bone mineral: osteoclasts attach firmly to the substrate-sealing zone. In the center of this sealing zone, they secrete H + leading to a local pH = 4-5. In vivo, osteoclasts participate partially in the degradation of calcium phosphate ceramics into the minerals available for the bone regeneration by providing the space required for bone formation.[19] Defects grafted with β-TCP in minipigs showed newly formed bone throughout the defects at 4 weeks, but the amount and maturity was less than that seen with autograft. Graft particles had almost disappeared, also, and were substituted by bone. At 8 weeks complete trabecular bone filling is seen, with β-TCP almost resorbed by dissolution rather than cellular resorption.[12]

Bioactive glasses

Undifferentiated mesenchymal tissue surrounds the bioactive glass microspheres during the first 2 weeks of primary bone response and differentiate into an immature woven-bone structure. Histomorphometric analysis has revealed that bioactive glass filling induces a constant time-related increase of new bone. Formation of the silicon-rich layer is known to be a crucial stage in bone bonding as it acts as a template for calcium phosphate precipitation. The calcium phosphate layer then directs new bone formation together with absorbing proteins. The extracellular proteins attract macrophages, and mesenchymal stem cells and osteoprogenitor cells with generation and further crystallization of matrix.[14] The results of a study by Mahesh et al.[20] suggest that ridge preservation using a putty calcium phosphosilicate alloplastic (CPS) bone substitute demonstrates more timely graft substitution and increased bone regeneration when compared to an ABB xenograft. Moreover, implant stability seems to be higher in sockets grafted with CPS, as determined by periotest, compared to nongrafted sites, which suggests enhancement in bone quality for implant placement [21] [Figure 3]a and [Figure 3]b.
Figure 3: image showing immunohistochemical technique for studying bone healing. immuno-labeled proteins (arrows) such as (osteoprotegerin) OPG; receptor activator of nuclear factor kB (RANKL); alkaline phosphatase (ALP); osteopontin (OPN); vascular endothelial growth factor (VEGF); tartrate-resistant acid phosphatase (TRAP); type 1 collagen (COL I); and osteocalcin (OC)[38]

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Effects of various bone grafts on osseointegration

The type of bone graft used does not seem to be associated with success of the procedure as well as implant survival according to a systematic review pertaining to the determination of any advantage of using autogenous graft over bone substitutes in sinus floor augmentation. The results of this review are not changed even by considering length of the healing period, simultaneous or staged implant placement, sinusitis or graft loss.[22]

In a human randomized control trial (RCT),[23] comparing alloplast (synthetic biphasic calcium phosphate, i.e., BCP) and xenograft (deproteinized bovine bone, i.e., DBB), new bone formation, and bone-to-implant contact around microimplants with sand-blasted, acid-etched surface was found to be equivalent between sinuses augmented with either material.

Nortan et al.[24] have studied the 3-year clinical outcome of implants placed in bioactive glass-grafted sites. They concluded that although a long healing time is required to achieve even a small amount of new bone incorporation into the graft histologically, there is still a high rate of osseointegration that is achieved, resulting in implant success. It is likely that initial integration comes from native bone in contact but also that the graft material does not prohibit osseointegration and does conduct new bone growth, though quite slowly.

Polyzois et al.[25] studied the effect of gap width and graft placement on bone healing around implants in dogs and concluded that wider gaps (≥2.37 mm) around implants without bone graft give less favorable histological results at short time intervals (4 months) than do gaps grafted with xenograft (ABB), which showed more bone implant contact (BIC) and more bone inside the threads. Choo et al.[26] in their 4-week animal (sheep) study using resorbable barrier membrane, examining the effect of β-TCP with recombinant human platelet-derived growth factor BB (rhPDGF-BB) (300 μg/mL) and β-TCP alone in circumferential critical size (3.25 mm) defects on bone healing, found out that the former enhanced bone regeneration almost twice as much, while the latter, although maintaining space and preventing collapse of soft tissue, showed inhibition in bone healing at the end of the study. Moreover, it was also suggested that the rate of resorption of β-TCP was retarded in the presence of rhPGDD-BB and that a greater amount of new bone formation, both from the bottom of the defect as well as the lateral walls (that too in contact with implant surface) was seen when a combination graft was used.

Role of implant surface in osseointegration

Among the implant-related factors, importance is given to material, shape, surface topography, and chemistry.[27]

Topography

This is achieved by additive (plasma spraying, HA coating, magnetron sputter, calcium phosphate coatings, biologic molecules) and subtractive methods (abrasion through blasting, grit or sandblasting with aluminous oxides, blasting and etching with hydrogen sulfate or chloride). Other treatments are anodizing, cold working, and sintering and bead compaction. Surface energy, topography, composition, and roughness are supposed to be important factors governing bone formation and apposition.

Chemistry

Charge affects the hydrophilic and hydrophobic properties of a surface. A hydrophilic surface is assumed to be more favorable in the initial stages of osseointegration. Topography also alters its chemistry. Turned surfaces are found to have more carbon and less titanium than roughened ones and acid etching removes most of the carbon contaminant.

Both iliac bone marrow-grafting and demineralized bone matrix (DBM) have been shown to enhance biological fixation in porous implants. Among different pore sizes, pore size above 80 μm is associated with improved bone ingrowth in both HA and tricalcium phosphate materials. Bone allograft, bone graft substitutes, and biological coatings have been used to induce osseointegration.[28] Calcium phosphate ceramics not only increase implant surface but also favor platelet adhesion activation and fibrin binding by increasing protein adsorption. Several growth factors such as BMPs, including BMP-2 and BMP-7 [also known as osteogenic protein-1 (OP-1)], PDGF, insulin-like growth factor 1 (IGF-1), and other biologic coatings such as collagen and extracellular matrix proteins, including fibronectin and vitronectin, have been used to enhance osseointegration.

Rough surface implants yield higher survival rates than machined surface implants when placed in grafted sinuses.[29] Tellemanet al. compared nanotite (dual acid-etched surface modified with nanometer-sized calcium phosphate) and osseotite (dual acid-etched surface) implant surfaces in humans and demonstrated that endosseous healing in the former was superior to that in the latter in native bone, suggesting that the more complex nanotopography and/or CaP deposits may lead to a better osteogenic process but not in the autograft area, which they attributed to slower remodeling process of graft and the shorter study period of 3 months.[30] Menicucciet al. presented similar results in his 12-month human study with ABB graft, the result being ascribed to clot detachment from an inflexible implant surface in the grafted area.[31] Moreover, strain signals responsible for biomineral formation were missing in this area. Schuler et al.[32] described in their 4-week dog study maximum bone-to-implant BIC in 1-mm marginal defects (5 mm deep) around AO implants (i.e., porous oxide surface prepared by anodic oxidation) with autograft as compared to T implants (turned surface) with autograft and even surpassed the effect of AO surface alone. The highest point of the first BIC was also seen in the AO + autograft group. This shows that the effect of the surface can be enhanced by bone grafting. Histologically the researchers showed the presence of new formed bone surrounding the nonvital bone graft particles and these (nonvital bone) particles were never found in contact with the implant surface. Apart from histological determination of BIC, cytodetachment technology might represent a new parameter to judge implant surface properties as it calculates the force required to detach osteoblasts from different implant surfaces.[33]

Thus it may be concluded that surfaces considered superior for osseointegration show conflicting results in terms of osseointegration in the presence of a bone graft.

Study methods of bone healing

Histological and histomorphometric analysis of graft healing

Histological analysis gives the qualitative data regarding the bone healing, while histomorphometric analysis focuses on the quantitative data. Hockers et al.[34] performed a histological and histomorphometric analysis of new bone formation in large bone defects (4 mm apicocronally, 6 mm both mesiodistally and buccolingually) around implants in beagle dogs using bioresorbable membrane along with xenograft or autograft. After 4 months they concluded that both the graft materials appeared to be integrated equally well in regenerating bone, with no clinically or statistically significant differences in terms of vertical bone regeneration, new bone-to-implant contact, area density of bone near the graft, and bone-to-graft contact. No contact was seen between grafts and implant surface, and only a minimal part of regenerated bone was in contact with implant. In another, 8-week-long study by Jensen et al.[12] on minipigs, it was seen that both ABB and β-TCP seem to decelerate bone regeneration as compared to autograft in the early healing phase, but finally all defects regenerate with newly formed bone and developing bone marrow.

Radiographic

Technetium-99 scan

99m Tc-labeled diphosphonates [technetium-99m-methyl diphosphonate (99m Tc-MDP) and technetium-99m-hydroxymethylene diphosphonate(99m Tc-HMDP)] and fluorine-18 sodium fluoride (18 F-NaF) are essentially markers of both bone perfusion and bone turnover. After intravenous administration, the principal uptake mechanism of bone-seeking radiotracers involves adsorption onto or into the crystalline structure of HA.99m Tc-MDP undergoes protein binding in blood, which increases over time from around 25% at injection to about 50% at 4 h after injection. Only unbound tracer will be available for bone uptake. The mechanism of binding of extravascular 99m Tc diphosphonates to bone is due to physicochemical adsorption (chemisorption) to the HA structure of bone tissue.[35]

Microcomputed tomography (μCT)

μCT is a nondestructive radiographic procedure that provides three-dimensional (3D) radiographs of hard tissues with a spatial resolution of up to 6 × 6 × 6 μm 2. As μCT has been used successfully to characterize the 3D structure of bone with morphometric precision comparable to that of classic histomorphometry, μCT is also suitable for evaluation of the remodeling of bone substitute material after healing in the human jaw.[36]

Immunohistochemical staining

Immunohistochemistry (IHC) is a widely used biological technique that combines anatomy, physiology, immunology, and biochemistry. Developed from the antigen-antibody binding reaction, HC can be considered as a method that visualizes distribution and localization of specific antigen or cellular components in separated tissues, or tissue sections.

Major components in a complete IHC experiment:





  1. Primary antibody binds to specific antigen;
  2. The antibody-antigen complex is formed by incubation with a secondary, enzyme-conjugated antibody;
  3. With presence of substrate and chromogen, the enzyme catalyzes to generate colored deposits at the sites of antibody-antigen binding.


In graft healing analysis, antibodies generated against growth factors in the bone and specific cell receptors for bone remodeling are impregnated into the core sample of the bone to be analyzed. Later, these antibodies combine with their specific antigen and form a complex that can be illustrated under the microscope with the help of chromogen impregnated in the antibody.[37]


   Conclusion Top


Perusal of the literature reveals many limitations pertaining to the subject being reviewed. According to long-term studies on implants (staged placement) in grafted bone, incorporation of nonvital, non- or slow-resorbing particles may not make a difference in their clinical success, although studies done on fully resorbable materials support earlier placement of dental implants. As far as immediate implant placement is concerned, most of the results are from animal studies, which have to be applied with caution to human beings. These studies do provide histological and histomorphometric evidence of new bone formation, but do not render any information about the strength of shear forces between implant and new bone containing different graft materials. Moreover, turnover rates of various graft materials such as DBB mineral and autogenic transplanted bone are presently not known and need to be determined in future studies. Furthermore, the biologic responses to the physical nature of different implant surfaces may affect grafting materials differently. Histologic studies describing bone graft healing in the vicinity of immediately placed as well as immediately loaded implants are also lacking. More studies are required comparing different implant surfaces with the same graft materials to see the actual effect of surface on bone graft healing.

A better understanding of the complex biological events occurring at the bone/implant interface continues to develop and will lead to improved, biologically driven strategies for endosseous implants.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[38]

 
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[Figure 2]: (courtesy) Kühl S, Götz H, Hansen T, Kreisler M, Behneke A, Heil U, et al. Three-dimensional analysis of bone formation after maxillary sinus augmentation by means of microcomputed tomography: A pilot study. Int J Oral Maxillofac Implants. 2010 Sep-Oct:25(5):930-8.  Back to cited text no. 36
    
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[Figure 3]: (courtesy) Pedrosa Jr WF, Okamoto R, Faria PEP, Arnez MFM, Xavier SP, Salata LA. Immunohistochemical, tomographic and histological study on onlay bone grafts remodeling. Part II: Calvarial bone. Clin Oral Impl Res 2009;20:1254-64.  Back to cited text no. 38
    


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