Bone grafts in dentistry.

Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

Ridge defects develop as a result of surgery, trauma, infection, or congenital malformations. The goals of osseous replacement are maintenance of contour, elimination of dead space, and reduce postoperative infection; and thus enhance bony and soft tissue healing. The insufficient quantity of bone is due to tooth loss which results in rapid resorption of alveolar bone due to lack of intraosseous stimulation by periodontal ligament (PDL) fibers, for example, pneumatization of maxillary sinus following tooth loss.

Bone grafting is a surgical procedure that replaces missing bone with material from patient′s own body, an artificial, synthetic, or natural substitute. Bone grafting is possible because bone tissue has the ability to regenerate completely if provided the space into which it has to grow. As natural bone grows, it generally replaces the graft material completely, resulting in a fully integrated region of new bone.

Classification of bone grafts based on material groups:[1]

Allograft-based bone graft involves allograft bone, used alone or in combination with other materials (e.g., Grafton, OrthoBlast).

Factor-based bone graft are natural and recombinant growth factors, used alone or in combination with other materials such as transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), fibroblast growth factors (FGF), and bone morphogeneic protein (BMP).

Cell-based bone grafts use cells to generate new tissue alone or are added onto a support matrix, for example, mesenchymal stem cells.

Ceramic-based bone graft substitutes include calcium phosphate, calcium sulphate, and bioglass used alone or in combination; for example, OsteoGraf, ProOsteon, OsteoSet.

Polymer-based bone graft uses degradable and nondegradable polymers alone or in combination with other materials, for example, open porosity polylactic acid polymer.

The biologic mechanisms that provide a rationale for bone grafting are osteoconduction, osteoinduction, and osteogenesis.[2]

Osteoconduction

Occurs when bone graft material serves as a scaffold for new bone growth, which is perpetuated by the native bone. Osteoblasts from the margin of defect that is being grafted, utilize the bone graft material as a framework upon which to spread and generate new bone.[1] In the very least, a bone graft material should be osteoconductive.

Osteoinduction

Involves stimulation of osteoprogenitor cells to differentiate into osteoblasts and then begins formation of new bone. The most widely studied type of osteoinductive cell mediators are BMPs.[2] A bone graft material that is osteoconductive and osteoinductive will not only serve as a scaffold for currently existing osteoblasts but will also trigger formation of new osteoblasts, promoting faster integration of the graft.

Osteopromotion

Involves enhancement of osteoinduction without possession of osteoinductive properties. For example, enamel matrix derivative enhances the osteoinductive effect of demineralized freeze-dried bone allograft (DFDBA), but will not stimulate bone growth alone.[2]

Osteogenesis

It occurs when vital osteoblasts originating from bone graft material contributes to the growth of new bone along with bone formation.

Types and Tissue Sources

Autograft

Autologous or autogenous bone grafting involves utilizing bone obtained from same individual receiving the graft. Bone can be harvested from nonessential bones, such as from iliac crest, mandibular symphysis (chin area), and anterior mandibular ramus (coronoid process). When a block graft will be performed, autogeneous bone is the most preferred because there is less risk of graft rejection as the graft is originated from the patient′s body.[3] It would be osteoinductive and osteogenic, as well as osteoconductive. Disadvantage of autologous grafts is that additional surgical site is required, another potential location for postoperative pain and complications.[3]

All bones require blood supply in the transplanted site. Depending on where the transplant site is and size of the graft, an additional blood supply may be required. For these types of grafts, extraction of the part of the periosteum and accompanying blood vessels along with the donor bone is required. This kind of graft is known as a free flap graft.

Allografts

Allograft is derived from humans. The difference is that allograft is harvested from an individual other than the one receiving the graft. Allograft bone is taken from cadavers that have donated their bone so that it can be used for living people who are in need of it; it is typically sourced from a bone bank.

There are three types of bone allograft available:[4]

Fresh or fresh-frozen bone

FDBA

DFDBA

The use of allografts for bone repair often requires sterilization and deactivation of proteins normally found in healthy bone. Contained in the extracellular matrix of bone tissue are the full cocktail of bone growth factors, proteins, and other bioactive materials necessary for osteoinduction and successful bone healing; the desired factors and proteins are removed from the mineralized tissue by using a demineralizing agent such as hydrochloric acid. The mineral content of the bone is degraded, and the osteoinductive agents remain in a demineralized bone matrix (DBM).

Synthetic variants

Flexible hydrogel-hydroxyapatite (HA) composite which has a mineral to organic matrix ratio, approximating that of human bone.

Artificial bone can be created from ceramics such as calcium phosphates (e.g., HA and tricalcium phosphate), bioglass, and calcium sulphate are biologically active depending on solubility in physiological environment.[5] These materials combine with growth factors, ions such as strontium or mixed with bone marrow aspirate to increase biological activity. The presence of elements such as strontium can result in higher bone mineral density (BMD) and enhanced osteoblast proliferation.

Xenograft

Xenogratfs are bone grafts from a species other than human, such as bovine and are used as a calcified matrix.

Alloplastic grafts

Alloplastic grafts may be made from hydroxyapatite, a naturally occurring mineral (main mineral component of bone), made from bioactive glass. Hydroxyapatite is a synthetic bone graft, which is the most used now due to its osteoconduction, hardness, and acceptability by bone. Some synthetic bone grafts are made of calcium carbonate, which start to decrease in usage because it is completely resorbable in short time and makes breaking of the bone easier. Finally used is the tricalcium phosphate in combination with hydroxyapatite and thus giving effect of both, osteoconduction and resorbability.

Growth factors

Growth factors enhanced grafts are produced using recombinant DNA technology. They consist of either human growth factors or morphogens (BMPs in conjunction with a carrier medium, such as collagen).

The factors and proteins that exist in bone are responsible for regulating cellular activity. Growth factors bind to receptors on cell surfaces and stimulate intracellular environment to act. Generally, this activity translates to a protein kinase that induces a series of events resulting in transcription of messenger ribonucleic acid (mRNA) and ultimately into the formation of a protein to be used intracellularly or extracellularly. The combination and simultaneous activity of many factors results in controlled production and resorption of bone. These factors, residing in extracellular matrix of bone, include TGF-beta, insulin like growth factors I and II, PDGF, FGF, and BMPs.[67] Cell-based bone graft substitutes: Stem cells are cultured in the presence of various additives such as dexamethasone, ascorbic acid, and β-glycerophosphate to direct the undifferentiated cell towards osteoblast lineage.

The addition of TGF-beta and BMP-2, BMP-4, and BMP-7 to the culture media can also influence the stem cells towards osteogenic lineage. Mesenchymal stem cells have also been seeded onto bioactive ceramics conditioned to induce differentiation to osteoblasts.

Ceramic-based bone graft substitutes

Majority of bone grafts available involve ceramics, either alone or in combination with another material (e.g., calcium sulfate, bioactive glass, and calcium phosphate). The use of ceramics, like calcium phosphates is calcium hydroxyapatite which is osteoconductive and osteointegrative; and in some cases, osteoinductive. They require high temperatures for scaffold formation and have brittle properties.

Calcium sulfate is also known as plaster of Paris. It is biocompatible, bioactive, and resorbable after 30-60 days. Significant loss of its mechanical properties occurs upon its degradation; therefore, it is a questionable choice for load-bearing applications:

OsteoSet is a tablet used for defect packing. It is degraded in approximately 60 days.

Allomatrix is Osteoset combined with DBM, forms a putty or injectable paste. OsteoSet is a calcium sulfate tablet used for bone defect sites, whereas allomatrix is a combination of calcium sulfate and DBM that forms an injectable paste or fable putty.

Bioactive glass (bioglass) is a biologically active silicate-based glass,[8] having high modulus and brittle nature; it has been used in combination with polymethylmethacrylate to form bioactive bone cement and with metal implants as a coating to form a calcium-deficient carbonated calcium phosphate layer which facilitates the chemical bonding of implants to the surrounding bone. Different types of calcium phosphates are tricalcium phosphate, synthetic hydroxyapatite, and coralline hydroxyapatite; available in pastes, putties, solid matrices, and granules.

Such calcium phosphates products include Bio-Oss and OsteoGraft. Both products use hydroxyapatite, either as a particulate (Bio-Oss) or as blocks and particulates (OsteoGraft). Pro-Osteon is a unique product based on sea coral, which is converted from calcium carbonate to calcium hydroxyapatite. The advantage of this material is that the structure of coral, which is similar to that of trabecular bone.

Polymer-based bone graft substitutes

This can be divided into natural polymers and synthetic polymers. Subclassified into degradable and nondegradable types. Polymer-based bone graft substitutes include the following:

Healos is a natural polymer-based product, a polymer-ceramic composite consisting of collagen fibers coated with hydroxyapatite and indicated for spinal fusions.

Cortoss is an injectable resin-based product with applications for load-bearing sites.

Degradable synthetic polymers, like natural polymers are resorbed by the body. The benefit of having the implant resorbed by the body is that, the body is able to heal itself completely without remaining foreign bodies.

Uses

The most common use of bone grafting is in application of dental implants, in order to restore edentulous area of a missing tooth. In general, bone grafts are either used in block (such as from chin or ascending ramus area of lower jaw) or particulated, in order to be able to adapt it better to a defect. The grafted, vascularized fibulas have been used to restore skeletal integrity to long bones of limbs in which congenital bone defects exist and to replace segments of bone after trauma or malignant tumor invasion. The periosteum and nutrient artery are generally removed with piece of bone so that the graft will remain alive and grow when transplanted into new host site. Once the transplanted bone is secured into its new location, it generally restores blood supply to the bone on which it has been attached.

Besides the main use of bone grafting in dental implants, this procedure is used to fuse joints to prevent movement, repair broken bones that have bone loss, and repair broken bone that has not yet healed.[9]