De Luise, Adriana (2017) Electrospun membranes loading osteogenic bioactive molecules for guided bone regeneration in dental implantology. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Electrospun membranes loading osteogenic bioactive molecules for guided bone regeneration in dental implantology
Creators:
CreatorsEmail
De Luise, Adrianaadriana.deluise@hotmail.it
Date: 6 April 2017
Number of Pages: 98
Institution: Università degli Studi di Napoli Federico II
Department: Scienze Mediche Traslazionali
Dottorato: Medicina clinica e sperimentale
Ciclo di dottorato: 29
Coordinatore del Corso di dottorato:
nomeemail
Marone, Giannigianni.marone@unina.it
Tutor:
nomeemail
Rengo, SandroUNSPECIFIED
Peluso, GianfrancoUNSPECIFIED
Date: 6 April 2017
Number of Pages: 98
Uncontrolled Keywords: Resveratrol; elettrospinning
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/28 - Malattie odontostomatologiche
Date Deposited: 02 May 2017 08:04
Last Modified: 13 Mar 2018 10:31
URI: http://www.fedoa.unina.it/id/eprint/11551
DOI: 10.6093/UNINA/FEDOA/11551

Abstract

The resorption and remodeling of the alveolar ridge after tooth removal due to trauma, periodontal disease, periapical pathology, etc. is a natural healing phenomenon which can negatively impact to the future placement of a dental implant. Because the ridge dimensions are so crucial for decreasing patient morbidity, it is advantageous to preserve the dimension of the post-extraction ridge instead of reconstructing it thereafter, and to maintain its ideal vertical and horizontal dimensions. In order to preserve the ridge volume within the bony envelope existing at the time of extraction, various techniques have been proposed, such as the placement of a bone graft/substitute material into the extraction sockets. However, the quality of the new tissue formed within the socket may vary due to different healing patterns within the alveolar socket with different bone substitute materials. In this context, not only is the amount of the newly formed bone important in these grafted sites, but also the quality of osseous tissues in the socket area is essential, especially when the justification of ridge preservation is to facilitate the placement of a dental implant. Biocompatible materials with high resorption rates, such as poly-lactic acid (PLA), and poly-caprolactone (PCL) allow the formation of bone with no residual graft particles at the time of implant placement, but they are able to limit but not eliminate the post-extraction alveolar ridge resorption to a certain extent. The present study has been designed to synthesize and evaluate the performance of a new flexible, moldable, electrospun cotton wool-like nanocomposite. This nanocomposite incorporates resveratrol (RSV) into a biodegradable synthetic poly-caprolactone (PCL) or poly-lactic acid (PLA) polymer, and it is prepared through an electrospinning process, which gives it the typical cotton wool-like appearance. This characteristic of the material allows easy proportioning, handling and adaption to a bone defect. In addition, the delivery of RSV, embedded in the polymer, can give new osteoinductive properties to the material. Indeed, RSV has been shown to have physiological properties that could be useful in regenerative medicine. RSV is a naturally polyphenolic compound present in red wine and in numerous plants and it has been shown to direct mesenchimal stem cells (MSCs) differentiation towards the osteoblast lineage and to stimulate the proliferation and activity of pre-osteoblasts. Moreover, RSV inhibits RANKL-induced osteoclast differentiation and induces apoptosis of differentiated osteoclasts. Although RSV has potential therapeutic application, it is rapidly metabolized and excreted from the body as sulfated and monoglucuronide derivatives, therefore, controlled release of RSV directly at the target site would be more efficient. Since site specific drug delivery is the best suitable option for bioactive compounds characterized by poor availability, we have developed non-woven RSV loaded and biodegradable nanofiber composite with inbuilt property of high surface area to volume ratio. PCL and PLA have been used specifically as the polymer since they possess remarkable properties like promoting the deposition of extracellular matrix supporting tissue regeneration. Moreover, both polymers can be electrospun efficiently also in the presence of high percentage of RSV, as they show very low viscosity at very high polymer concentration. Electrospinning conditions were setup to produce a final material composed of individual fibers without any bead formation. The scanning electron microscope (SEM) analysis has suggested that RSV is well dispersed into the materials, resulting in electrospun nanofibers with average diameter around 0.3-0.9 micron. Normally, drugs encapsulated in nanofibers synthesized through single step electrospinning tend to give initial burst release which may cause reduction in drug therapeutic efficiency. The in vitro drug release profile of the RSV- loaded PCL or PLA nanofibers was studied to test their potential application as Drug Delivery System. The release studies were carried out for a time period of 30 days and the cumulative release behaviors of the drug from the composite nanofibers were analyzed by HPLC. The release pattern for electrospun nanofibers were studied at two stages: an initial burst release (stage I), followed by decelerate and constant release (stage II). RSV displayed a small initial release of 8,1 % for PCL-RSV and 13,5 % for PLA-RSV within the first 24 hours and thereafter showed a sustained release profile (32 % and 44 % at 30 days). The in vitro osteoinductive efficiency of RSV-released nanofiber on Dental Puls Stem Cells (DPSCs) was evaluated analyzing specific differentiation markers such as runt-related transcription factor 2 (RUNX2), osterix (OSX), osteocalcin (OCN), osteonectin (ONN), osteopontin (OPN) and bone sialoprotein (BSP). Furthermore, the ability of RSV to inhibit osteoclastogenesis was confirmed by the reduction of RANKL-induced osteoclast differentiation. In conclusion, our results provide evidence that resveratrol dispersed into electrospun fibers generates bioactive materials able to promote the osteogenic differentiation of mesenchymal stem cells and to inhibit osteoclastogenesis, so they can be useful to improve GBR surgical procedure.

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