A Healthy Foundation: Regeneration Advances in Dental Implant Therapy

In order to recognize the need for regeneration around an implant, an understanding of a healthy foundation is required. Healthy peri-implant mucosa is either a keratinized (masticatory mucosa) or non-keratinized (lining mucosa) epithelium with underlying connective tissue, according to the 2017 World Workshop on peri-implant health.¹ These same authors stated that peri-implant health features the absence of inflammation, erythema, swelling, and bleeding on probing (BOP).

Bony defects in the jaw can vary in size from a trough-like defect around the dental implant caused by peri-implantitis to a large alveolar defect that extends both vertically and horizontally in part of or the entire arch due to trauma or removal of teeth with severe periodontitis. The aim of regeneration is to obtain ideal bone quality and create a predictable means for restoring these defects to ideal height and width.

Up to 40% of patients with dental implants can be affected by peri-implantitis after at least 1 year in function.² It is best to treat peri-implant defects in the early stages, as the larger the defect, the more difficult it is to treat. Dental implants should be probed as part of a patient's yearly examination.³ Once BOP is detected, the diagnosis is peri-implant mucositis and a recommendation must be made to the patient on how to correct the inflammation, whether by improving home care, bacterial biofilm removal, and/or laser therapy.⁴ Yearly radiographic changes have to be assessed.⁵ A standardized vertical bitewing x-ray is taken at the time of insertion of the restoration to allow annual assessment of bony changes around the implant. Alveolar bone remodeling in the first year is well-documented and is dependent on the type of implant being used; however, it should not occur apical to the first thread of the implant. Therefore, it is important to be able to visualize the implant threads on the x-rays. Bone loss changes of 2 mm or more after the first year are a sign of peri-implantitis.⁶ As soon as bone loss is recognized, immediate therapy must be recommended to the patient to stop the disease process.

The patient's medical and nutritional status must also be carefully and thoroughly evaluated to ensure optimal healing. Blood cholesterol, glucose, anemia, and vitamin D play roles in bone regeneration.⁷ Vitamin D supplementation was shown to improve bone-to-implant contact (BIC) and mineralization around dental implants.⁸ The Vitamin D Council recommends optimum blood levels of 60 ng/ml to 80 ng/ml.⁹

Intrabony defects resulting from peri-implantitis tend to be circumferential and have a bacterial component due to poor oral hygiene, a poor crown margin, and/or the subgingival presence of cement. For regenerative treatment to be successful, the causative factors must be addressed. Improving oral hygiene via use of a water flosser, restoring healthy crown margins, and removing subgingival cement or replacing the cement-retained restoration with a screw-retained one whenever possible are important components of treating peri-implantitis. If left untreated, peri-implantitis can cause extensive bone loss and potentially implant loss.¹⁰

For a successful regenerative result, the microbial biofilm must be removed from the surface of the implant. Different techniques have been used for this, including chemical or mechanical methods, such as debridement with brushes, ultrasonics, and antiseptics (hydrogen peroxide or chlorhexidine), and lasers, such as Er:Cr:YSGG (erbium, chromium:yttrium, scandium, gallium, garnet).¹¹ There is no study that demonstrates one superior method of debridement. Ozone technology offers additional benefits when used to decontaminate implant surfaces prior to regenerative therapy. Ozone water can be easily obtained in the dental setting through the use of an ozone water generator (eg, BioSure, biosureozone.com) at 10 ppm. The antibacterial properties of ozone have been well-documented in medical studies, and recently ozone has garnered more attention in dentistry because of the challenges clinicians face in removing pathogenic biofilm from contaminated peri-implant surfaces.¹² Ozone water debridement of implant surfaces has been shown to add a significant benefit in surgical treatment of peri-implantitis by improving inflammatory markers such as interleukin (IL)-6, IL-8, and IL-17, probing depth, and clinical attachment level measured at 12 months post-treatment.^13,14

Laser treatment of a peri-implant pocket offers several benefits, including minimal invasiveness, hemostasis, photobiostimulation, microbial destruction, and precise degranulation.¹⁵ The results of a 2014 study with Er,Cr:YSGG laser in the nonsurgical treatment of peri-implantitis showed a 91% resolution of inflammation and pocket depth reduction. The treatment was nonresponsive in three of 28 implants that had no keratinized tissue, which most likely affected the treatment outcome.¹⁶

The Er:YAG (erbium:yttrium, aluminum, garnet) laser also has been shown to restore bone loss around dental implants by improving BIC.¹⁷ An 18-month study showed that Er,Cr:YSGG laser can effectively decontaminate the implant surface during surgical regenerative procedures, with results showing successful bone regeneration around these implants.¹⁸

Not all lasers are suited to treat implant surfaces due to the potential increase in surface temperature of the implant, which can alter the implant surface and create cellular damage producing an environment that is less favorable for bone attachment.¹⁹ A review concluded that the Er,Cr:YSGG laser can be safely and effectively used in the treatment of peri-implantitis in a noncontact mode for up to 2 minutes, respectively, with air and water spray.²⁰

Tissue engineering/regenerative medicine (TE/RM) is a relatively new field of research that spans across multiple disciplines, such as medicine, manufacturing, stem cell research, chemistry, and dentistry. The purpose of TE/RM is to promote regeneration of tissues by either implanting biomaterials for in vivo regeneration or creating in vitro substitutions.²¹ Nanotechnology advances are being studied in the reconstruction of peri-implant defects to achieve more predictable bone regeneration. This is an exciting field to be aware of, and products should soon become commercially available for use in dentistry.

Biomaterial used in peri-implant regeneration can be divided into three categories: bone grafts, to replace missing bone; barriers, to protect the graft from epithelial invasion; and biologics, which release growth factors or stem cells.²²

Bone grafts can be classified based on their origin: autogenous, allogenic (cadaveric), xenogeneic (animal), and synthetic.²³ Autogenous bone grafts remain the "gold standard" because the cells are alive and come from the patient. For large defects, a membrane or titanium mesh is used to cover the bone graft and act as a physical barrier in guided tissue regeneration. Barriers are also classified as autogenous, allogenic (placenta), xenogeneic (animal), and synthetic (titanium mesh or polytetrafluoroethylene).²²

Biologics, such as products with growth factor release and stem cells, are a more recent addition to bone regeneration techniques. Bone morphogenic proteins (BMPs), specifically BMP-2, are used for ridge augmentation in dental implant treatment.²⁴ Because of the high cost of BMP-2, it is not widely utilized in dentistry and is used mostly in orthopedics.

Critical factors impacting long-term stability following bone regeneration in peri-implantitis cases include biofilm removal, access for good oral hygiene postoperatively, effective plaque control, and the use of growth factors.²⁵

Platelet-rich fibrin (PRF) therapy has been a useful addition to the armamentarium to enhance healing of wound regeneration in implant dentistry. PRF is prepared from whole blood, which is spun in a centrifuge, which then aggregates the platelets and leukocytes in a clot-like layer. PRF can be pressed into a membrane or used as an injectable (i-PRF) to mix with bone graft material.²⁶ When used for alveolar ridge preservation, PRF has been shown to increase radiographic bone fill after tooth extraction as well as preserve horizontal and vertical ridge dimensions following extraction.²⁷ It also has been shown to provide pain relief within the first 3 days when compared to controls and improve soft-tissue healing.²⁸ In a study treating peri-implantitis defects through open-flap debridement, it was shown that when PRF was used, there was greater probing depth reduction and reduced recession after 3 and 6 months.²⁹ Also, interestingly, PRF products have antimicrobial properties, and titanium surfaces exposed to bacterial biofilm display a significant reduction in bacterial counts when treated with PRF.³⁰

In the past decade, research on the use of teriparatide, a drug composed of 34 amino acids of the parathyroid hormone, has shown increased bone regeneration around dental implants. Teriparatide is mainly used in the treatment of osteoporosis and healing fractures. To improve bone regeneration orally, teriparatide is given as a daily subcutaneous injection to increase preosteoblast proliferation and decrease osteoblast apoptosis.³¹

While many advances have been made in peri-implant regeneration, there is no universally accepted protocol to resolve peri-implantitis. It is the clinician's responsibility to stay informed regarding available advances and techniques and make the appropriate clinical decision in treating peri-implantitis. Nevertheless, it is universally agreed that peri-implant disease must be recognized and treated as early as possible, preferably before bone loss is noted.

Sanda Moldovan, DDS, MS, CNS
Private Practice, Beverly Hills, California; Diplomate, American Academy of Periodontology