Current Trends and Advances in Bone Augmentation for Dental Implant Placement

The Graftless Approach

A recent trend is toward minimally invasive surgical procedures to reduce complications, decrease discomfort, and facilitate faster recovery.¹ One way to accomplish this is by treatment planning to avoid the need for bone grafting or choosing a “graftless” approach.² Reduced-diameter or shorter implants may be utilized when minimal available bone volume is present. Today, with short implants, bone grafting the atrophic edentulous mandible is rarely needed.³ In the atrophic maxilla, tilted implants or zygomatic implants can be used to avoid the maxillary sinus, eliminating the need for sinus bone grafting.^2,4 As long as biomechanical support is not compromised, fewer implants may also be considered for a fixed prosthesis (4 to 6 versus 8 to 10).⁵ The dentist may elect extraction of compromised teeth for full-arch implant placement instead of augmenting the atrophic maxillary or mandibular posterior ridges. The introduction of cone-beam computed tomography to the dental office has been integral to this minimally invasive trend. The ability to more accurately diagnose available bone and visualize anatomy enables the clinician to manage cases with marginal conditions. It also permits the use of computer-guided surgery with a flapless approach to further decrease morbidity. Although patients may tend to prefer a minimally invasive approach, dentists should not disregard options that require bone grafting solely on this basis.⁶

Bone-Graft Materials

Today, clinicians have a much better understanding of the requirements for bone regeneration. The repair of an osseous defect primarily originates with the surrounding bony walls. As such, the morphology of a bone defect should influence the choice of material or technique. Sites with fewer surrounding osseous walls and greater jaw atrophy are more demanding and require materials and/or techniques that offer greater biologic activity and regenerative capacity. As a general rule, vertical bone augmentation is more biologically and clinically challenging than horizontal augmentation.

Autogenous bone has long been considered the gold standard of graft materials because of its superior biologic properties, including osteogenesis, osteoinduction, and osteoconduction. As such, the use of autograft for bone augmentation still has indications, including larger defects, vertical augmentation, and severe atrophy.⁷ However, inherent disadvantages exist, including morbidity from bone harvest, added surgical time, and limited bone supply. Bone grafts harvested from the local recipient site and the mandibular ramus have a low incidence of morbidity.⁸ There may be regeneration limitations when using primarily osteoconductive bone substitutes that rely on passive bone ingrowth. Demineralized freeze-dried bone allograft is weakly osteoinductive and requires a carrier to meet the other clinical objectives, such as scaffolding.⁹ Bone substitutes perform well in sites with favorable osseous morphology, including socket bone grafting, sinus bone grafting, localized implant repair, and modest horizontal augmentation.¹⁰ At present, bone allografts and bovine-derived bone mineral dominate the choices for particulate bone substitutes.¹¹ These materials have variations in particle size, type of graft (eg, cortical, cancellous, blends), and demineralized or mineralized forms. In the United States, alloplastic bone grafts (eg, ceramics, polymers) constitute a smaller share of the dental market.¹¹ Their use may well increase as tissue engineering becomes more advanced. The global dental bone graft market was valued at $456 million in 2013 and is expected to reach $884 million in 2020.¹¹

Tissue Engineering

The developing field of tissue engineering offers a strategy to replace the need for harvesting bone from the patient. Tissue engineering may be used to regenerate bone by combining cells from the body with growth factors and scaffold biomaterials.¹² This combination of cells, signaling molecules, and scaffold is often referred to as the tissue engineering triad.

Growth factors are naturally occurring signaling proteins that can recruit cells and stimulate cell proliferation and differentiation.¹² For many years, surgeons have used autologous blood-derived growth factors to enhance wound healing. The platelets contain several growth factors, including platelet-derived growth factor, transforming growth factor beta, and vascular endothelial growth factor.¹³ Various types of platelet concentrates have been developed, such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and plasma rich in growth factors (PRGF). Their production methods are diverse, and as such, cellular and cytokine compositions vary. No consensus is available regarding the preference or biologic superiority of one type of bloodborne product. The rationale for using platelet concentrates in bone augmentation is acceleration of graft revascularization, improved soft tissue healing, and enhanced bone formation.¹³ However, scientific evidence is insufficient to support that platelet concentrates significantly improve grafting outcomes when used with bone substitutes.^14,15 The fibrin within the plasma creates a gel consistency, improving the placement and containment of the graft. The amplification of soft-tissue healing over the graft site and improved graft handling properties may justify routine use of platelet concentrates.

Recombinant growth factors are genetically engineered versions produced in the laboratory that are identical in structure and action to the naturally occurring cytokines.¹⁶ Commercially available growth factors for clinical use in dentistry include recombinant platelet-derived growth factor (rhPDGF-BB) (Gem 21S®, Osteohealth, osteohealth.com) and recombinant bone morphogentic protein 2 (rhBMP-2) (Infuse® Bone Graft, Medtronic, medtronic.com). Gem 21S has been approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe periodontal intraosseous defects.¹⁷ Infuse Bone Graft has FDA approval for the repair of extraction socket defects and sinus bone grafting.^18,19 The use of these recombinant growth factors for ridge-augmentation procedures is considered an “off label” application.²⁰ Although the off-label designation does not prevent clinicians from considering their use for bone augmentation, dental teams should inform patients of this status, any alternative treatment options, and possible risks. Any adverse affects must also be well documented. Infuse Bone Graft has been the subject of some media attention regarding its off-label usage, high cost, and adverse events in spinal applications.^21,22

Platelet-derived growth factor (PDGF) is chemotactic for osteoblasts, cementoblasts, and periodontal ligament cells. It is also a potent mitogen that enhances cell proliferation and the induction of angiogenesis.¹² Although PDGF is a mitogen that does not actually induce bone formation, it may augment bone regeneration by improving the conditions for osseous regeneration. Findings from animal studies using mandibular defects have shown an increase in bone formation and defect repair.^23,24 To date, the only human studies on rhPDGF-BB for bone augmentation are clinical case reports using the growth factor in combination with bone substitutes.^25,26 A clinician should not assume that adding a growth factor, such as rhPDGF-BB, would necessarily improve augmentation outcomes.^27,28 So far, evidence does not support routine use in sinus lift procedures and socket healing or lateral/vertical augmentations of the alveolar crest.²⁹ A possible strategy for using rhPDGF-BB in bone augmentation may be to enhance wound healing and flap closure over the grafted site. Wound dehiscence is one of the most common complications with bone-augmentation procedures.³⁰ The growth factor can be applied to a collagen sponge and placed under the flaps during closure. Results from animal studies have shown decreased dehiscence of titanium mesh grafts with this technique.³¹

Bone morphogenetic proteins (BMPs) are naturally occurring osteoinductive growth factors found in bone. These cytokines are chemotactic for mesenchymal stem cells and induce their proliferation and differentiation into osteoblasts. In extraction sockets with significant buccal wall defects, rhBMP-2 has been shown to be effective in enhancing bone formation for implant placement.^19,32 Studies have also found rhBMP-2 is applicable to maxillary sinus floor augmentation.¹⁸ However, many surgeons have questioned the use of a more costly product when other less expensive bone substitutes have been shown to be as effective.³³ Although the absorbable collagen sponge (ACS) has been found to be an optimal carrier for the rhBMP-2 molecule, it has poor scaffolding properties to resist flap compression.¹⁶ When horizontal or vertical bone augmentation is needed, titanium mesh has been used as a method to provide space maintenance and protection of the rhBMP-2/ACS graft.^34-37 The addition of an osteoconductive matrix to the rhBMP-2/ACS complex, such as particulate allograft, has also been suggested as a strategy to provide additional scaffolding and matrix for cellular migration.^34-37 This also decreases the material cost as less BMP is needed. Outcomes of rhBMP-2 bone grafts with titanium mesh in lateral and vertical augmentations have been comparable to autografts.^34,36 The benefits for using a growth factor are significant, as there is no bone graft harvest and associated morbidity. The surgery may be performed in an office environment under sedation and local anesthesia instead of in an operating room under general anesthesia. Also, surgical time may be less. The disadvantages of the use of rhBMP-2 compared to autograft include greater postoperative edema, longer graft healing times, softer initial bone quality, and higher materials costs.^34,37

The Future of Bone Regeneration

Presently in dentistry, the main focus in tissue engineering has been on using growth factors. However, there are limitations to using one recombinant growth factor in a supraphysiologic dose at the time of surgery for early release in wound healing. Improvements may be attained by a combination of growth factors that are released at times that mimic the normal cascade of bone formation.³⁸ Another promising technique for growth factor delivery is the application of gene therapy.³⁹ Genetic material is transferred into the genome of the target cells, causing them to produce a functional protein, such as BMP, at physiologic amounts and timelines.

Research is ongoing to develop biodegradable scaffolds that maintain space, allow vascular ingrowth, and promote cell adhesion.³⁸ Dentistry is at the forefront for integrating radiographic imaging with CAD/CAM technology for fabricating custom devices. A CBCT scan of the jaw can be obtained for virtual planning of the reconstruction using software. It can also be used to produce a stereolithographic model of the jaw for reconstructive planning or creating made-to-order matrices.^40,41 Custom titanium meshes have been developed to protect and contain growth factor-enhanced grafts.⁴² At present, allogeneic and xenograft block bone grafts may be milled to custom fit an atrophic ridge.⁴³ In the future, custom-made resorbable scaffolds will routinely be fabricated using 3-dimensional printers.³⁸ The printed porous scaffold may then be seeded with osteoblasts or mesenchymal stem cells. Mesenchymal stem cells from bone marrow, adipose tissue, and cryopreserved umbilical cord blood have shown the ability to form new bone tissue.⁴⁴ Bone-marrow aspirate from the iliac crest may be centrifuged to produce a concentrate of mesenchymal stem cells for mixture with bone substitutes or seeding of a porous matrix. In vitro cultural expansion can further generate a larger number of progenitor cells.³⁸ Another strategy for customized bone reconstruction is to infuse a porous biodegradable scaffold with osteoinductive growth factors that recruit host cells and guide bone ingrowth.^38,44 The use of biologic agents on dental implant surfaces may be another alternative for encouraging bone formation in deficient sites.

Conclusion

We practice implant dentistry at a time when numerous ways are available to help us treat cases with bone deficiencies. No single clinical technique or biomaterial is optimum for every augmentation procedure. However, clinicians may be tempted to abandon traditional approaches for new and less complicated procedures that may not provide comparable results. Surgeons should consider the advantages and disadvantages of each alternative in a given clinical situation and select the material with lowest overall cost and morbidity and the highest likelihood of success.⁴⁵ Clinicians will need to weigh the higher costs of newer tissue engineering techniques against the benefits of simplified surgery, enhanced biologic response, and potential for reduced morbidity.

About the Author

Craig M. Misch, DDS, MDS
Private Practice
Oral & Maxillofacial Surgery and Prosthodontics
Sarasota, Florida
Clinical Associate Professor
Departments of Periodontics and Prosthodontics
University of Florida
Gainesville, Florida