INNOVATIVE BIORESORBABLE MESH DEVICE FOR BONE AUGMENTATION IN DENTAL APPLICATIONS

The problem related to an insufficient quantity of bone to steadily place dental implants has been investigated in dentistry and maxillofacial surgery since 1970. This may happen because of the patient age, eventual pathologies or also as a consequence of traumatic events like car crash or industrial and sport accidents. Many techniques were attempted with particular attention to the autografts, removing a portion of bone from one site of the skeleton and placing on the same patient in the district where the augmentation was required. I have started my practice as oral surgeon specialist in 1999 and through these past years several concerns arose both about the filling techniques as well as the outcomes which are not always predictable. Many other specialists have tried to describe the complexity of the bone healing after an augmentation procedure, but, at the end, none of the investigated approaches was clearly identified as the solution to be employed with safety, minor invasivity and better outcome in terms of quantity of regenerated bone and this is still the present condition. The main problem could be split in two separated items: • What to use as optimum augmentation material • How to protect the insertion during the time, usually 4 up to 6 months, that it takes to stabilize the new condition While the first sub-item is widely debated and discussed in the international biomaterials communities (i.e. European Society for Biomaterials, TERMIS) the second issue is usually left back as a “technological” step over which no innovation could be applied. At the moment the usual way to proceed is through an artificial device, called “mesh”, ideally represented as a metallic/polymeric lamina shaped on site by the dentist to copy at best the patient jaw profile. This device is placed to protect and store the “artificial” bone used as effective augmentation material. After few months, normally 4 up to 6, this “mesh” has no more duties and must be removed, not being created to work as a permanent implant. This fact causes the necessity to perform a second surgery to extract the item. This step is even more complicated than the first installation phase. The sum of two surgeries within the extraction procedure greatly affect the overall result, that has still to be further finalized by the proper implant insertion phase and sequent post surgery recovery. Therefore, based on the surgical experience and especially knowing which are the critical aspects that the operator may encounter during the intervention, I have decided to look at the problem from the perspective of the materials, trying to identify a new model/solution, which can bring together the following advantages: • more efficient interaction with the tissues: I looked for a “place and forget” solution. • precise : avoiding the intra-surgical modification of the material to be grafted • faster: reducing surgical times means reducing risk of infection of the surgical site • less invasive: avoiding the need of a second surgery to remove the device used for the augmentation. The advantages of the actually available innovative customized devices generated by SLM metal additive manufacturing technique have resolved the first aspect related to the precision, but achieved only a partial reduction of the surgical times, while the need of a second surgical intervention to remove the titanium alloy mesh is still present and does not match completely with the present PhD goals mentioned above. This thesis moved from a preliminary analysis of the material used for customized titanium meshes alloy to sharply define the mesh mechanical properties and highlight the eventual modifications that the device can encounter after a period of 4 to 6 months after the implantation in the human oral cavity. This is a point that recently became of interest in the scenario of possible metal pollution disease, that in the last ten years became a serious item in the orthopedic field (see Metal-on-Metal hip prosthesis issues. In dental applications no friction 2 exist, as what happens in the femoral head vs. acetabular cup, anyhow many patients are even more frequently asking for “metal free” dental solution) To light up this last endpoint a comparison between samples produced with the same alloy and technique of the implantable devices by partner Companies of this PhD programs and some explanted titanium meshes, used and extracted from my patients, was performed. This analysis basically consisted in SEM inspection of the surface and mostly of the bulk of the specimens and the explanted meshes to observe modifications and defects generated both from the production and the exposure in the human body. In the view to reduce invasivity and social costs related to the second surgery, the core of this PhD program was addressed to change the usual dentistry protocol and move to the adoption of resorbable polymeric materials. Polymers have been employed in medicine since many years especially for the creation of sutures and drug delivery devices, but the literature about their use in dentistry especially combined with the 3D printing, is still not common. The final endpoint of this Thesis was therefore to reinvent the protective support (mesh) in order to greatly simplify the way to use it and reduce the evident actual disadvantages. 3D printing machines commercially available were chosen from the most common and already commercialized ones in order to assume a usual professionals’ viewpoint. All known available composites polymer/ceramic materials already fitting with the printers need were tested but this drove me to the awareness that their functional properties were not sufficient. I therefore studied the chance to create an innovative material moving from already certified “precursors” in order to maximize the commercial printers capabilities and look for a high TRL solution. To scale up this proposal and push it into a possible commercial scale testing phase a fruitful collaboration with a specialized Company was created, in order to produce in a semi-industrial way what I finalized in this Thesis. The Company collaborated with me and DICCA Material lab, following precisely my instructions related to the type of polymers to be used as well as the percentages of the osteoconductive filling material. All the samples were printed at DICCA laboratory in Genova with three different polymers (PDLA –poly D lactic acid; PLLA – poly L lactic acid; PCL- polycaprolactone). The printed composites materials were set as 10% of hydroxyapatites and 20% of beta-tricalcium phosphate, which were the maximum percentages to allow a correct printing process with the conventional 3D printers. Mechanical tests were performed always both with the material immediately after printing and also after the sterilization process, in order to observe any possible different behavior generated by this necessary step. As further investigation the infrared analysis of the samples was done to observe the incorporation of sterilizing agents and the possible modification of the chemical structure of the polymeric matrix, which will be extensively described in chapter 5, together with the final results. As final investigation, the composite material samples were studied on the biological point of view to observe if and how preosteoblast human derived cells can adhere and differentiate on the substrates. This last analysis was done with the Biology Department of University of Camerino with whom I cooperate since many years for other published researches on bone cells growth and maturation. Preosteoblasts behavior on the printed composite specimens showed an intense adhesion and growth, therefore the next steps of the research will be addressed to in vivo animal study and human implantation, when the material will be classified as Medical Grade. Although the biological tests results show a great performance of the tested material the expected reactions by the medical world may be on a different scale. Operators and mainly dentists are afraid to discover new possibilities for their daily practice, both because of a lack of knowledge of the evidence-based literature and also for the fear of possible legal issues in case of complications. Surely the legal matter is becoming more pressing in dental community than before. It is relevant the sentence nr. 3612 Tribunale Napoli sez. VIII, 22/05/2020 which demonstrates the limitations of the contractual responsibility of dentist toward the patient. This sentence clearly expresses that the professional operator is obliged to use the highest 3 diligence to pursue not the expected result but the predictable one, and the reach the level of the predictability human controlled studies will be mandatory as future steps. All the work that I have done during this PhD program generated a perfect match between materials and 3D printing to be used with commercial printers, in order to support and shift the paradigms and the technique used for dental and maxillo- facial surgery. The solution developed and shaped in this PhD Thesis was adopted to file in collaboration with Unige an Italian patent procedure actually pending. (N. 102022000023112 - 09 /11/ 2022) *