DESIGN, DEVELOPMENT AND CHARACTERIZATION OF NOVEL BIOMATERIALS FOR PERIODONTAL TISSUE ENGINEERING

Periodontium is a complex system of different tissues, such as connective tissue, cartilage and bone, which work together to sustain the tooth. Gingivitis and periodontitis are devastating diseases that could affect the structure and function of the periodontal tissue. When the gingivitis are not treated and controlled with a correct oral hygiene, they could evolve in periodontitis, which could seriously damage the tissue surrounding the tooth and lead tooth loss. The main objective of periodontal tissue engineering is to regenerate the tooth’s supporting tissues. Periodontal tissue regeneration involves formation of new connective tissue (cementum and periodontal ligament) and new alveolar bone. The restoration of tooth by using a titanium dental implant is nowadays a quite common procedure. However, the positive fate of a surgical procedure that involves an insertion of titanium screw depends on the quality and quantity of alveolar bone which is present in the extraction site. The main objective of this doctoral thesis is to develop a set of novel biomaterials, designed to improve periodontal bone regeneration in patients and to control or prevent the bacterial infection in the wound site, via a sustained in situ drug release. Three different materials have been developed and characterized: 1. Three-dimensional porous scaffold coated with a polyelectrolyte complex for periprosthetic infection prevention 2. Bioceramic-reinforced hydrogel for alveolar bone regeneration 3. Antiadhesive guided tissue regeneration membrane The results demonstrated that they could be used in periodontal tissue engineering with predictable and excellent outcomes. With this set of biomaterials it is possible to control or prevent possible bacterial growth, achieve the correct alveolar bone quantity and quality and guide the tissue regeneratio

Potentials of Polyphenols in Bone-Implant Devices

Knowledge of bioactive plant-derived polyphenols is growing to such an extent that science interest is looking at development of different applications in regenerative medicine through new and state-of-the-art tissue engineering technologies. Due to their well-established and demonstrated antioxidant and anti-inflammatory beneficial properties, polyphenols have been extensively investigated to the extent that they provide benefits to different pathological conditions, including cardiovascular and bone diseases, neurodegenerative disorders, and cancer. By taking into account the main molecular pathways of polyphenols’ action, we want to focus this chapter on applications of polyphenols in bone-implant devices. In particular, results of polyphenols’ effects on bone cells and tissues following local delivery from innovative biomaterials will be discussed, together with preliminary in vivo tests. Purpose of the dissertation is to provide the reader new insights into knowledge of polyphenols not only regarding the different molecular mechanisms involved in their action but also the biological responses deriving from local applications

New collagen‐coated calcium phosphate synthetic bone filler (Synergoss®): A comparative surface analysis

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Evaluation of Bone Regeneration Efficacy in a Rabbit Model of Femoral Condyles Defect by Polyphenols-Containing Bone Filler

[EN] The purpose of this study was to evaluate the local biological effects and bone regeneration efficacy of a polyphenols-enriched ceramic bone filler. To this end, a test article (NBR_Purple) a biphasic phosphate ceramic plus polyphenols from grape pomace and the same material without polypohenols (NBR_White), were implanted in the medial condyle of the femur bone of rabbits for 56 days. A control article of clinical use (Ostim ®), was implanted as the first control condition. There was a second control by performing the same defect at the same location but without any implanted material (void condition). Histological examination at the end of the test period shows statistically significant improvement of bone regeneration by the polyphenolenriched material over the same material without polyphenols, supporting literature data on the involvement of polyphenol molecules in bone regeneration pathways.Iviglia, G.; Cassinelli, C.; Peris Serra, JL.; Primo Capella, V.; Morra, M. (2020). Evaluation of Bone Regeneration Efficacy in a Rabbit Model of Femoral Condyles Defect by Polyphenols-Containing Bone Filler. Journal of Oral & Maxillofacial Research. 3(3):1-8. https://doi.org/10.31038/JDMR.2020334S183

The incorporation of strontium to improve bone-regeneration ability of mesoporous bioactive glasses

Over the recent years, mesoporous bioactive glasses (MBGs) gained interest as bone regeneration systems, due to their excellent bioactivity and ability to release therapeutic molecules. In order to improve the bone regeneration ability of MBGs, the incorporation of Sr2+ ions, due to its recognized pro-osteogenenic potential, represents a very promising strategy. In this study, MBGs based on the SiO₂⁻CaO system and containing different percentages (2 and 4 mol %) of strontium were prepared by two synthesis methods, in the form of microspheres and nanoparticles. Sr-containing MBGs were characterized by FE-SEM, XRD and N₂ adsorption/desorption analysis. The in vitro bioactivity in SBF resulted excellent. The assessment of fibroblast cell (line L929) viability showed that Sr-containing MBGs were biocompatible both in form of micro- and nanoparticles. The osteogenic response of osteoblast-like SAOS-2 cells was investigated by analysing the expression of GAPDH, COL1a1, RANKL, SPARC, OPG and ALPL genes, as cell differentiation markers. The results indicate that the incorporation of Sr into MBG is beneficial for bone regeneration as promotes a pro-osteogenic effect, paving the way to the design of advanced devices enabled by these nanocarriers also in combination with drug release, for the treatment of bone pathologies, particularly in patients with osteoporosis

Engineering Interfacial Environment of Epigallocatechin Gallate Coated Titanium for Next-Generation Bioactive Dental Implant Components

In view of endowing the surface of abutments, a component of titanium dental implant systems, with antioxidant and antimicrobial properties, a surface layer coated with epigallocatechin gallate (EGCg), a polyphenol belonging to the class of flavonoids, was built on titanium samples. To modulate interfacial properties, EGCg was linked either directly to the surface, or after populating the surface with terminally linked polyethyleneglycol (PEG) chains, Mw ~1600 Da. The underlying assumption is that fouling-resistant, highly hydrated PEG chains could reduce non-specific bioadhesion and magnify intrinsic EGCg properties. Treated surfaces were investigated by a panel of surface/interfacial sensitive techniques, to provide chemico–physical characterization of the surface layer and its interfacial environment. Results show: (i) successful EGCg coupling for both approaches; (ii) that both approaches endow the Ti surface with the same antioxidant properties; (iii) that PEG-EGCg coated surfaces are more hydrophilic and show a significantly higher (>50%) interaction force with water. Obtained results build up a rationale basis for evaluation of the merits of finely tuning interfacial properties of polyphenols coated surfaces in biological tests

Biomaterials, Current Strategies, and Novel Nano-Technological Approaches for Periodontal Regeneration

Periodontal diseases involve injuries to the supporting structures of the tooth and, if left untreated, can lead to the loss of the tooth. Regenerative periodontal therapies aim, ideally, at healing all the damaged periodontal tissues and represent a significant clinical and societal challenge for the current ageing population. This review provides a picture of the currently-used biomaterials for periodontal regeneration, including natural and synthetic polymers, bioceramics (e.g., calcium phosphates and bioactive glasses), and composites. Bioactive materials aim at promoting the regeneration of new healthy tissue. Polymers are often used as barrier materials in guided tissue regeneration strategies and are suitable both to exclude epithelial down-growth and to allow periodontal ligament and alveolar bone cells to repopulate the defect. The problems related to the barrier postoperative collapse can be solved by using a combination of polymeric membranes and grafting materials. Advantages and drawbacks associated with the incorporation of growth factors and nanomaterials in periodontal scaffolds are also discussed, along with the development of multifunctional and multilayer implants. Tissue-engineering strategies based on functionally-graded scaffolds are expected to play an ever-increasing role in the management of periodontal defects

Functionalization with a Polyphenol-Rich Pomace Extract Empowers a Ceramic Bone Filler with In Vitro Antioxidant, Anti-Inflammatory, and Pro-Osteogenic Properties

Oral diseases and periodontitis in particular are a major health burden worldwide, because of their association with various systemic diseases and with conditions such as peri-implantitis. Attempts have been made over the years to reverse bone loss due to the host disproportionate inflammatory response and to prevent failure of dental implants. To this end, the use of biomaterials functionalized with molecules characterized by anti-inflammatory and antioxidant properties could represent a new frontier for regenerating functional periodontal tissues. In this study, a new ceramic granulated biomaterial, named Synergoss Red (SR), functionalized with a polyphenolic mixture extracted from pomace of the Croatina grape variety, is introduced. Following a preliminary in-depth characterization of the extract by HPLC analysis and of the biomaterial surface and composition, we performed evaluations of cytocompatibility and a biological response through in vitro assays. The anti-inflammatory and antioxidant properties of the identified phenolic molecules contained in SR were shown to downregulate inflammation in macrophages, to stimulate in osteoblast-like cells the expression of genes involved in deposition of the early bone matrix, and to mitigate bone remodeling by decreasing the RANKL/OPG ratio. Thanks to its cytocompatibility and assorted beneficial effects on bone regeneration, SR could be considered an innovative regenerative approach in periodontal therapy

Biomimetic Surfaces Coated with Covalently Immobilized Collagen Type I: An X-Ray Photoelectron Spectroscopy, Atomic Force Microscopy, Micro-CT and Histomorphometrical Study in Rabbits

Background: The process of osseointegration of dental implants is characterized by healing phenomena at the level of the interface between the surface and the bone. Implant surface modification has been introduced in order to increase the level of osseointegration. The purpose of this study is to evaluate the influence of biofunctional coatings for dental implants and the bone healing response in a rabbit model. The implant surface coated with collagen type I was analyzed through X-ray Photoelectron Spectroscopy (XPS), Atomic Force Microscopy (AFM), micro-CT and histologically. Methods: The sandblasted and double acid etched surface coated with collagen type I, and uncoated sandblasted and double acid etched surface were evaluated by X-ray Photoelectron Spectroscopy (XPS) and Atomic Force Microscopy (AFM) analysis in order evaluate the different morphology. In vivo, a total of 36 implants were positioned in rabbit articular femoral knee-joint, 18 fixtures for each surface. Micro-CT scans, histological and histomorphometrical analysis were conducted at 15, 30 and 60 days. Results: A histological statistical differences were evident at 15, 30 and 60 days (p < 0.001). Both implant surfaces showed a close interaction with newly formed bone. Mature bone appeared in close contact with the surface of the fixture. The AFM outcome showed a similar roughness for both surfaces. Conclusion: However, the final results showed that a coating of collagen type I on the implant surface represents a promising procedure able to improve osseointegration, especially in regions with a low bone quality