SWEDISH LIFE SCIENCES PROFILE A powerful solution for better bone

AddBIO has developed the Zolidd® technology – a proprietary bioactive nanolayer with a bone strengthening drug

the population in the developed ASworld ages and the baby boom generation enters old age, oral health issues such as and adult loss are an increasing problem. Today, dental caries is one of the most common chronic diseases in the world, often leading to the need for tooth extraction if left untreated or treated improperly. Globally, as many as 90% of school children and up to 100% of adults suffer from some extent of Fig. 1 The release of the drug from the implant to the surrounding in the bone primary or secondary caries. In addition, severe periodontal (gum) disease, which may result in Implant manufacturers are constantly trying to The more compromised the bone quality, the , is found in 15-20% of middle-aged outdo each other in their efforts to increase longer it takes to heal the bone and restore full load on the implanted tooth. At the same time, (35-44 years) adults. Moreover, as indicated by the the success rate of the procedure in patients manufacturers seek methods that allow World Health Organization, globally about 30% of with unfavourable health conditions. Therefore, immediate implant loading and limit the people aged 65-74 have no natural teeth.1 In manufacturers develop various shapes and post-surgical inconvenience to a minimum. As a Europe edentulism (total or partial ) is surfaces of implants to improve their functions. result, cases of implant loosening or implant less common than in the rest of the world, but tooth Current advancements in failure are quite frequent, causing pain, need for loss is still an important health issue. design has concentrated on the implant re-operation and generating additional costs for design; the length, width, amount of thread Increasing use of dental patients, dentists and healthcare systems. used and different implant surfaces in order to implant forces innovations improve stability. In its efforts to provide a solution that addresses Today dental implants have largely replaced these problems, AddBIO has used an approach (‘false teeth’) as the go-to solution when Unfortunately, the problem of poor implant unlike any other dental implant manufacturer treating edentulism. With a wealthier population, fixation in high-risk patients remains. In addition, today. Rather than just another variation of an new dental technologies, methods and materials some of the trends in implant development have implant’s geometry, surface type and material are introduced every year. The increasing use of been shown to be counterproductive. For (which only improves implant stability), the dental implants is partially the result of a growing instance, the development of rougher surfaces company has created a unique method of pool of potential patients. In the not too distant has been shown to improve initial fixation. adding a drug coating to virtually any given type past dental implants were limited to a select group However, they have also been shown to harvest of dental implant. As a result, AddBIO’s of patients. Today, implants are commonly used , causing infections (periimplantitis) and technology is the world’s first solution that on a wider group of high-risk patients with loss of bone around the implant long term. improves bone stability. compromised bone quality, such as smokers, Another drawback of lowering the inclusion Our solution: Zolidd® patients with bruxism (teeth grinding and criteria for implantation is an increase in the The Zolidd technology uses a multilayer protein clenching), diabetes, etc. required recovery time. film of fibrinogen as a bonding agent between

154 Health Europa Quarterly 05 www.healtheuropa.eu PROFILE SWEDISH LIFE SCIENCES the implant surface and drug particles. In its natural form, fibrinogen is a glycoprotein in vertebrates that helps the formation of blood clots. Blood proteins have long been regarded as key factors determining the in vivo acceptance of implants.

The Zolidd technology uses a biochemical treatment to create a multilayer layer of fibrinogen that is covalently bound to the metal surface of an implant and is able to absorb particles of other compounds. The drug used in AddBIO’s coating is zoledronate (zoledronic acid) – a bisphosphonate commonly used to prevent osteoporotic loss of bone mass. The addition of bisphosphonate to the fibrinogen matrix creates a strong synergistic effect on bone regeneration, increasing the bone volume significantly.

By combining a fibrinogen multilayer with bisphosphonate and designing a manufacturing © iStock/GuidoVrola process of coating implants with this compound, AddBIO paves the way for a new standard in Commercial and regulatory strategy AddBIO was founded in 2008 with the aim to dental implantology. To date, dental implant AddBIO is currently following a medical device solve the central problem of the implant industry manufacturers have avoided joining implants with – weak bone. Professor Per Aspenberg, pathway for CE marking and FDA approval. The pharmaceuticals, due to increased safety Linköping University, Sweden, had been working Zolidd One ExHex is AddBIO’s first product and a requirements imposed on drug/device medical with bone healing for many years. Professor result of many years of research within the products (e.g. need for clinical validation studies). Pentti Tengvall, Gothenburg University, Sweden, company. Zolidd One ExHex is currently evaluated was interested in biomaterials with special AddBIO is, however, better placed to explore this in a clinical study required for CE marking of Class interest on surface modifications. sector of industry, as it offers scientific III Medical Devices. background and expertise in doing clinical A collaboration between the two scientists led The recruitment of patients for the clinical study to the development of a technology to coat a validation studies – skills lacking in other dental has been completed and the outcome will be titanium surface with a drug using a protein implant manufacturers. evaluated during 2018. AddBIO plan to matrix. In 2012, Aspenberg and Tengvall The Zolidd prototype has been evaluated in a commercialise a full dental platform with Zolidd- published the first human clinical trial showing improved implant fixation using a five-year radiographic follow-up trial.2 The study coated implants in 2019. The implants will be fully coating with bone-strengthening drugs concluded that low doses of bisphosphonate, compatible with commonly used dental crowns, (bisphosphonates).3 Based on the technology and dental technology. locally delivered from a fibrinogen matrix indeed developed by Aspenberg and Tengvall, AddBIO improves early implant fixation with persistent Implants with the Zolidd technology is therefore has established a platform technology effect after years of loading and that the coating expected to become a game changer for dentistry, designed for local availability of drugs from has not imposed any complications. Hence, in disrupting the market for dental implants. The medical implants – Zolidd®. contrast with other state-of-the-art implants, Zolidd coating has a proven local bone Zolidd coated implants allows for earlier strengthening effect and enhances implant stability. implant loading, whilst decreasing the risk of Better implant stability will enable better implant post-surgical complications. Furthermore, Zolidd function and reduce the risk of complications. coated implants allow for smoother surface References 1 World Health Organization: Oral health, Information sheet, implants, that significantly reduce the rate of April 2012 http://www.who.int/oral_health/publications/ Ulf Sewerin periimplantitis, enabling long-term implant factsheet/en/ CEO AddBIO AB retention both in the general public and amongst 2 Randomised trial of bisphosphonate-coated implant: Radiographic follow-up after 5 years of loading. Abtahi J Linköping, Sweden individuals with compromised bone quality et al. Int J Oral Maxillofac Surg. Dec 2016 ;45, (12), +46 708 79 79 88 ( patients, diabetics and smokers). The 1564–1569 Zolidd-coated implants do not impact present 3 A bisphosphonate-coating improves the fixation of metal [email protected] implants in human bone. A randomized trial of dental http://www.addbio.se surgical procedures. implants. Abtahi J et al. Bone. 2012 May;50(5):1148-51 www.healtheuropa.eu Health Europa Quarterly 05 155