Brian Wong, Vice President of Commercial Development at Theradaptive, explains why dentists and periodontists need better therapies to regenerate bone.
Dentists, periodontists, and craniomaxillofacial surgeons transform the lives of patients in countless ways, though their contributions may often go unnoticed. While many of us take our dental and oral health for granted, our ability to enjoy our food without a second thought is dependent on maintaining healthy teeth and gums. At some point we have all experienced frustration from even minor dental issues interrupting our daily eating habits. From routine dental cleanings and fillings to complex oral surgeries and reconstructions, dental professionals play a crucial role in a patient’s quality of life. Beyond basic oral health, in more severe cases, these healthcare professionals are sometimes required to rebuild a portion of a patient’s jaw, in traumatic injuries, or due to implications from oral cancer, by performing major bone segment repair and augmentations. These procedures trigger the need to regenerate bone in the jaw, which has proven to be an essential, and growing part of development in the dental field. Recent advancements in protein engineering and delivery methods hold promise for improving efficacy of bone regeneration techniques, revolutionizing the current standard of care.
Despite advances in the field, the ability of practitioners to consistently regrow bone and tissue within surgical sites is still inadequate. Oral diseases such as oral cancer, tooth decay, and periodontal disease continue to plague cases where viable treatment is limited.
Periodontal disease is a chronic inflammatory condition that affects the gums and bone supporting the teeth. When a tooth is badly infected by periodontal disease to the point where it is beyond saving with a filling or a crown, it must be extracted and replaced with a dental implant. The gap where the tooth once was is usually filled with allograft bone filler to permit the formation of new bone. The implant is then drilled into the new bone. However, when the bone and gum around the implant become infected or inflamed, a condition referred to as peri-implantitis occurs. This causes bone and tissue to recede, preventing the implant from staying in place, progressively loosening, and sometimes falling out completely. There are approximately 650,000 cases of peri-implantitis every year in the United States and in some categories of patient the dental implant failure rate is as high as 20%. The patients most at risk of peri-implantitis or an implant failing include those who smoke, elderly patients, patients with diabetes, and patients with gum disease.
Peri-implantitis often results from the body’s response to periodontitis. Macrophages that normally target microorganisms and remove dead cells can also inadvertently contribute to bone resorption. Periodontists seek to counteract this by debriding and disinfecting the bone and eliminating bacteria. Once disinfected they often fill the area with a void filler to promote new bone growth. The alveolar bone ridge quickly narrows once a tooth has been lost, making it difficult to find a flat surface for implantation, especially in the case of elderly patients, smokers, and diabetics. As a result, periodontists may use an inert ceramic bone filler, autograft harvested from another area of the body, or allograft from a human tissue bank to rebuild the bone where the damaged tooth has been extracted.
Each of these fillers, unfortunately, has major shortcomings. Allograft and ceramic fillers often struggle to generate enough bone. Autograft has a better record of bone regeneration, but it can cause donor site pain and other unwanted side effects when it is harvested. Periodontists and their patients need a new kind of osteoinductive material that can promote bone formation with anatomical precision and without the usual safety concerns or risk of infection.
Thankfully, this is not an unrealistic goal. There are already a limited number of osteo-inductive agents on the market, albeit still in an imperfect form. Growth factors such as rhBMP-2 and rhPDGF are both commercially available to promote bone growth on the alveolar ridge and the sinus ridge.
These kinds of products are still problematic however, due to their lack of precision. Rather than remaining at the site where clinicians want to promote bone generation, these agents can diffuse away to surrounding areas, in some cases causing swelling, inflammation and off-target bone growth. This is particularly concerning when inflammation and swelling occur around the sinus ridge, potentially affecting a patient’s breathing. The lack of precise delivery also necessitates a large dose to be efficacious, resulting in a substantial cost that is not usually covered by a patient’s insurance. For this reason, it has not achieved widespread use among dentists, periodontists, or craniomaxillofacial surgeons.
Recent technological advancements are changing the landscape significantly. Protein engineering is creating new opportunities to adapt biologics in a manner that overcomes their limitations in precise delivery. This breakthrough has made it possible to deliver potent osteo-inductive proteins in a targeted manner, allowing therapeutic biologic to remain only where it is required. This results in a much safer lower dose at a significantly lower cost while mitigating any off-target effects that come from systemic delivery. While native BMP-2 dissipates quickly and does not have a long-lasting effect, we have designed variants of BMP2 that bind to bone substitutes that can be implanted where bone needs to grow, allowing it to persist and have the effect in the location it is needed. One of these variants, AMP2, has shown significant promise, and has beaten the standard of care in all preclinical studies to date.
The ability to precisely deliver therapeutic proteins without any side effects will have tremendous promise for improving dental implantations and other facial reconstruction operations that require consistent, high quality bone regeneration. For instance, in the challenging situations such as peri-implantitis, where being able to regrow bone on the alveolar ridge is difficult, this type of treatment could provide a powerful new tool for dentists to augment or replace current standard treatments that are imperfect.
The continued development and implementation of protein engineering and targeted therapeutic delivery holds enormous potential to improve the lives of patients, offering better options for conditions with limited therapeutic alternatives.