3D printed dental implants with anti-biofouling surface

Dr Tsoi Kit Hon   (Co-Investigator)

Dr Pow Edmond Ho Nang   (Co-Investigator)

Professor Burrow Michael Francis   (Co-Investigator)

Professor Su Yuxiong   (Co-Investigator)

Dr Chu Zhiqin   (Co-Investigator)

17

2021-06-30

150000

3D printed dental implants with anti-biofouling surface

3D printing, antibiofilm, dental implants, nano diamonds

Dentistry,Biomaterials

202010160015

Seed Fund for PI Research – Translational and Applied Research

2020

On-going

PROBLEMS BEING ADDRESSED: Titanium implants are an indispensable solution in craniomaxillofacial reconstructive surgery including tooth replacements. Although implants are a costly treatment, they have been shown to improve function and appearance of patients, thereby dramatically improving their quality of life. However, one of the most common causes of failure of implants is infection, which leads to poor integration with the surrounding bone (Costerton et al. 2005). In either case, microbial infection and the ensuing tissue destruction cause inflammation of the surrounding human tissues, loosening and the subsequent loss of implants. It is critical to develop novel implant materials that can prevent such microbial infections, and such a development is non-existent in dental implants, demonstrating a major translational void (Rifai et al. 2019). KEY ISSUES: The oral cavity, including the periodontal and peri-implant niches contain a vast number of microbial species, including pathogens and health-associated commensals. Bacterial contamination during surgery or due to the attachment of free-floating bacteria on the implant surface results in the formation of highly adherent communities called biofilms, which demonstrate remarkable resistance and tolerance to antimicrobials (Hall-Stoodley et al. 2004, Rifai et al. 2019). The role of biofilm is central on peri-implantitis etiology (Lafaurie et al. 2017): it is recognized as a complex infection of peri-implant tissues that are colonized by Gram-positive and Gram-negative bacteria. Biofilms can compromise the host immune system in the inflammatory phase, ultimately resulting in implant failure. Another problem which is linked to failure of implants is reduced osseointegration. The formation of implant wear particles and subsequent aseptic loosening of the prosthesis stimulate macrophages to release inflammatory mediators that cause bone resorption and a reduction in osseointegration (Landgraeber et al. 2014). To mitigate these effects, one approach is to develop secondary implant coatings to inhibit biofilm formation and improve the process of osseointegration, hence preventing the possibility of implant failure. However, such a coating process has been shown to have several problems including the lack of uniformity and increased roughness. Recently, nanoparticles have become popular across many industries including medicine and oral health due to their interesting properties such as the ability to modify surfaces of materials after the particles have been embedded or coated on a surface. Nanodiamonds are nanometer-sized carbon-based particles, and they are an exciting development in the nanotechnology filed due to their remarkable biocompatibility, bioactivity and ability to serve as carriers for several type of molecules (Zhang et al., submitted). ""Bespoke"" implants represent an important frontier for improving outcomes in reconstructive surgeries. By tailoring implants to the particular physiology of a given patient, it is possible to reduce pain, improve cosmetic outcomes, and ideally reduce the burden of surgery by decreasing the need for secondary replacement procedures being undertaken. One key technology for bespoke implants is through the application of computer aided additive manufacturing methods, which involves the use of three-dimensional (3D) printing technologies (Shidid et al. 2016, Zhu et al. 2017). To construct metal implants, selective laser melting (SLM) is one of the preferred technologies of choice. A variety of metals can be used for SLM, but biomedical implant materials are predominantly limited to stainless steel, cobalt chromium, and titanium. This is mainly due to their biocompatibility and mechanical stability enabling a high strength-to-weight ratio in the implant. SLM can reduce the cost of production and minimize the number of parts required for implant assembly while maintaining the integrity of the implant (Kruth et al. 2004). A previous study developed Nanodiamond coatings on titanium implants used for orthopedic applications and confirmed that it inhibited biofilms of one type of bacteria. However, in real life situations, biofilms have a mixture of several microbes. Furthermore, the effectiveness of nanodiamond coatings on dental implants, their potential to inhibit peri-implant biofilms and improve the attachment and differentiation of cells in this specific niche have never been investigated to date. PURPOSE OF THE PROPOSED PROJECT: Initial research by our group has synthesised high pressure high temperature nanodiamonds (ND) and showed that they can inhibit the biofilm formation by a number of bacteria or fungi associated with dental implant diseases (Zhang et al., submitted). Furthermore, these nanodiamonds were shown to be highly biocompatible to dental stem cells in our preliminary study. The current study proposes to use nanodiamonds incorporated as implant coatings to prevent the formation of microbial biofilms and enhance tissue differentiation on implant surfaces. Based on this robust pilot data, we seek funding to develop ND coated three-dimensional selective laser melted titanium (SLM-Ti) plates to improve its interfacial properties. OBJECTIVES: First, we will evaluate the coating methodologies in suspensions with different carefully chosen ND concentrations and evaluate the effect of surface coverage on the properties of the substrata (SLM-Ti). Then, we will test the hypothesis that the ND-SLM-Ti can synergistically promote antifouling (prevent bacterial adhesion and biofilm formation) and osteointegration. To test this hypothesis, we will investigate and compare the effects of the ND-SLM-Ti and SLM-Ti substrates on the adhesion and growth of a multi-species biofilm based on our well-established protocols. Then, we will determine the viability, growth and differentiation of human periodontal ligament stem cells, human dermal fibroblasts and osteoblasts. References: Costerton JW, Montanaro L, Arciola CR. Biofilm in implant infections: its production and regulation. Int J Artif Organs 2005; 28:1062-8 Landgraeber S, Jäger M, Jacobs JJ, Hallab NJ. The pathology of orthopedic implant failure is mediated by innate immune system cytokines. Mediators Inflamm 2014;2014:185150. Lafaurie GI, Sabogal MA, Castillo DM, Rincón MV, Gómez LA, Lesmes YA, et al. Microbiome and microbial biofilm profiles of peri-implantitis: a systematic review. J Periodontol. 2017;88(10):1066–89 Rifai A, Tran N, Reineck P, Elbourne A, Mayes E, Sarker A, Dekiwadia C, Ivanova EP, Crawford RJ, Ohshima T, Gibson BC, Greentree AD, Pirogova E, Fox K. Engineering the interface: nanodiamond coating on 3d-printed titanium promotes mammalian cell growth and inhibits Staphylococcus aureus colonization. ACS Appl Mater Interfaces 2019;11:24588-24597 Zhang T, Kalimuthu S, Rajasekar V, Xu F, Yiu YC, Hui TKC, Neelakantan P, Chu Z. Biofilm inhibition in oral pathogens by nanodiamonds. Submitted for publication.