Abstract
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.
Highlights
In the last decades, the development of grafting materials has aroused great interest [1].In particular, synthetic ceramic materials such as tricalcium phosphate and hydroxyapatite (HA) have been widely used thanks to their good reproducibility, biocompatibility, and non-immunogenicity, in addition to their high similarity to components of the native bone mineral phase [2,3]
Croatina Polyphenol-Rich Pomace Extracts (PRPE) reduced radicals by 72.8%, which suggests a high antioxidant power of the polyphenolic molecules contained in the extract
By comparing expression of RANKL with that of its decoy receptor OPG (Figure 9b), it is evident that cells incubated with the bone filler control or Synergoss Red behave in a different manner; the bone filler control induced a progressive increase in OPG transcript levels, as compared to polystyrene at 72 h (72 h: 1-fold; 5 d: 2-fold; 7 d: 3-fold), but similar to OPG expression levels in polystyrene at the same time point, whereas Synergoss Red induced an early significant increase at 72 h (p < 0.01), with a further downregulation at 5 and 7 d (72 h: 2.1-fold; 5 d: 1.1-fold; 7 d: 1.3-fold)
Summary
Synthetic ceramic materials such as tricalcium phosphate (βTPC) and hydroxyapatite (HA) have been widely used thanks to their good reproducibility, biocompatibility, and non-immunogenicity, in addition to their high similarity to components of the native bone mineral phase [2,3]. The mode of action of biomaterials currently available on the market for bone grafting applications mainly relies on a mechanical support and is limited to providing a functional scaffold for cell adhesion. Coupling bone grafting and titanium implants is still one of the best available solutions to replace bone and dental tissue loss [4]. Tooth replacement with titanium dental implants is currently a routine procedure with a success rate around 98% [4]. Diseases resulting from failures of dental implants are still reported [5]; recent studies found peri-implantitis to occur in 2.7% to 47.1% of implants [6]
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