Understanding The Science of Biocompatibility of Dental Implants: Biomechanical, Pre-Clinical and Clinical Validation of New Design Concepts

Abstract

Dental implants, a prominent field of research, have evolved from prehistoric times to the present. Despite this long history, many aspects still require improvement, particularly in understanding primary stability and placing implants in challenging sites of the jawbone. While addressing the limitations of existing implant systems, this thesis focuses on developing a new dental implant system featuring a novel combination of hybrid threads to enhance primary stability and to reduce the healing period. In particular, dissertation reports on the design and comprehensive development of a three-piece tapered Ti6Al4V dental implant system, and some initial findings on one-piece zirconia dental implants. The innovative combination of hybrid external threads on the Ti6Al4V implant includes micro-V threads of optimal pitch and depth to minimize marginal bone loss, while buttress threads in the tapered apical region improve primary stability. The apical end features bone-cutting active V-threads to facilitate bone cutting during propagation in the osteotomy, especially in high-density bones such as D1 or D2. This knowledge has contributed to optimizing the implant design, enhancing its clinical functionality. Finite element analysis (FEA) was employed to study the biomechanical aspects such as stress in the implant, stress and strain in the bone, and micromotion at the bone-implant interface and its impact on bone remodeling. In parallel, biomechanical studies were conducted to understand bone remodeling of zirconia-based one-piece dental implants with new design concepts. The results indicated that the biomechanics of these implants support bone remodeling with minimal micromovement at the bone-implant interface. Further, performance assessment studies, particularly relevant to clinical dentistry, were conducted to understand clinical implications. The primary stability of the metallic implant was evaluated in various polyurethane foams simulating different bone densities and in natural bones (porcine bone and human cadaver bone) by measuring insertion and removal torque, and it was benchmarked against commercially available implants. The results showed that the newly designed implants can provide improved or comparable primary stability. Also, the fatigue life of the dental implant assembly was tested according to ISO 14801, and the assembly withstood 2 million cycles. To achieve clinically relevant surface roughness, the implant was modified using sandblasting and dual acid-etching techniques to attain a surface roughness (Ra) of approximately 2 μm. Cytocompatibility of the surface-modified substrates was tested using human gingival fibroblasts, and more importantly, the differentiation of human mesenchymal stem cells (hMSCs) was studied using an indirect co-culture method with osteoblasts, which showed signs of in vitro bone mineralization. Further, the osseointegration of the implants was evaluated in a rabbit model over 12 weeks and benchmarked against commercially available implants. The new implant demonstrated superior osseointegration histologically, which was further cross-validated by the upregulation of several osteogenic and angiogenic genes. Currently, the implant assembly is being tested in human subjects as part of a multicentric clinical study and towards the last part of the thesis, a few clinical cases will be discussed with immediate post-operative clinical outcomes. Overall, this dissertation marks a significant advancement in the development of new dental implant systems while adopting bench-to-bedside translational approach. Apart from the scientific outcomes of pedagogical relevance, this dissertation allows the candidate to learn the entire spectrum from design to clinical studies of the medical device.