The bone healing process in people can be affected by diseases such as Crohn’s disease, diabetes and colitis. It can also be affected by drugs such as bisphosphonates, which are used to treat weak bones in people with osteoporosis, Paget's disease and certain cancers. The role of animal models is enormous for investigating these disease conditions as well as other “risk factors” for compromised healing, such as radiotherapy, which is being increasingly used as early treatment of cancer in the community rises. Diabetes and intestinal disorders can be induced in rats, often using chemicals with toxic effects, but the diseases can take some time to develop. This chapter gives guidance on various timeframes for evaluating inflammatory processes, osseointegration and collagen cross-linking, and gives details on mechanical strength testing of dental implants and other candidate therapies. Different aspects of the compromised bone healing response can be observed using both the long bones (tibia and femur) and the maxilla of rats. This chapter also describes an adaptable study protocol for new investigators, with suitable endpoints such as bone to tissue ratio and bone to implant contact, to contribute to the body of knowledge on patients with compromised bone healing who are increasingly encountered in dental practice.

Objectives: Bone grafts with both antibacterial and osteoinductive abilities are greatly needed for treatment of infected bone defects. In this study we developed such a bone graft with a sequential release system: burst release of the powerful antimicrobial agent, hydroxypropyltrimethylammonium chloride chitosan (HACC), followed by sustained release of the osteoinductive agent, BMP-2. Our hypothesis was that this would kill infection-associated bacteria and eventually induce osteogenesis to repair an infected bone defect. Methods: The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time–kill curve of HACC against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. The influence of HACC at concentrations of 1000, 200 or 40μg/mL on the proliferation of pre-osteoblasts was evaluated by measuring cell viability. The influence of 40μg/mL HACC on the BMP-2-induced differentiation of pre-osteoblasts was evaluated by assessing activity of alkaline phosphatase (ALP) , osteocalcin (OCN) expression and mineralisation. BMP-2 was first internally incorporated into biomimetic calcium phosphate granules to form BMP-2-BioCaP. HACC solution was then adsorbed onto its surface to obtain a BMP-2-BioCaP/HACC complex. Confocal laser scanning microscopy (CLSM) was used to observe the structure of BMP-2-BioCaP/HACC using FITC-BSA as a substitute for BMP-2 and staining HACC solution with rhodamine B. The release kinetics of FITC-BSA and rhodamine B were determined by quantitative spectrophotometric analysis. To evaluate osteoinductivity of the complex and to optimise the HACC concentration in vivo, the following groups (n=6) were randomly implanted into subcutaneous pockets in rats: (i) BMP-2-BioCaP/HACC complex (BMP-2-BioCaP/HACC-20, BMP-2-BioCaP/HACC-4 and BMP-2-BioCaP/HACC-0.8 according to content of 20, 4 or 0.8μg HACC); (ii) BMP-2-BioCaP; (iii)BioCaP/HACC; (iv) BioCaP. Five weeks after implantation, samples were retrieved for histological and histomorphometric analysis. Results: The MIC and MBC of HACC for MRSA were 40μg/mL. BioCaP/HACC completely eliminated MRSA within 24 hours. HACC at levels of 1000μg/mL and 200μg/mL (but not 40μg/mL) significantly suppressed cell viability. HACC at a level of 40μg/mL did not significantly influence BMP-2-induced ALP, OCN or mineralisation. Microscopy showed that BMP-2 homogenously distributed throughout BMP-2-BioCaP granules within BMP-2-BioCaP/HACC complex, forming a thin layer of HACC along the surface. The in vitro release profile showed rapid release of HACC, which was completely exhausted after 3 days; BMP-2 was gradually and slowly released, with only about 20% depletion after 30 days. Bone formation was observed only in the BMP-2-containing groups in the in vivo pro-fibrotic environment (subcutaneous sites). In comparison with the positive control group (BMP-2-BioCaP), BMP-2-BioCaP/HACC-4 and BMP-2-BioCaP/HACC-0.8 complexes resulted in similar levels of new bone formation, while BMP-2-BioCaP/HACC-20 was associated with significantly less new bone formation. Conclusions: BMP-2-BioCaP/HACC-4 complex can rapidly eliminate antibiotic-resistant bacteria and efficiently promote new bone formation both in vitro and in vivo – making this a promising material for repairing infected bone defects. HACC is a strong antibiotic that can be readily combined with other bone substitutes, such as Bio-OssTM/® to provide in situ antibacterial activity for bone regeneration associated with infection.

On the occasion of the Osteology Board Meeting on June 22, 2015 in Zurich, the presidency of the Osteology Foundation was officially handed over from Christoph Hmmerle to Mariano Sanz. Professor Christoph Hmmerle served as president of the Osteology Foundation for 12 years, ever since it was established. Looking back at his term of office, he said in an interview prior to the meeting in Zurich: The Osteology Foundation has grown to be a highly respectable organization over recent years. I think the key elements for this success have been the excellent teamwork among the members of the Foundation Board, the dedication of those working in the office and, very importantly, the support and the academic freedom granted by the Founder. Read the full interview with Christoph Hmmerle Even though his term of office as president of the Osteology Foundation has ended, Christoph Hmmerle will remain a member of the Board for two more years, contributing to the development of the Foundation and its activities with his great experience and knowledge. Professor Mariano Sanz, who in Zurich officially took over as new president of the Osteology Foundation, has been a member of the Board for 12 years, he also served as Chairmen of the Education Committee and Member of the Executive Board for several years. For him, the Foundation and its activities are therefore already familiar - with Mariano Sanz, the Osteology Foundation is in the best hands, said Christoph Hmmerle. Mariano Sanz thanked him, and said that in the past 12 years Christoph Hmmerle has done a superb job. Not only as a result of his vision and work, but also through his personal and social skills has the Foundation become a friendly family of leaders all striving for the same objective, which is to fulfil the mission of the Osteology Foundation. Mariano Sanz does not intend to change the strategy of the Osteology Foundation. We will continue the successful work, and wherever possible extend it to other parts of the world, he said in an interview, and added: we shall consolidate our accomplishments, but at the same time open up to new technologies and improve communications media with the goal of widening our reach in order to better fulfil our mission. Read the full interview with Mariano Sanz