Characteristics of Large Animal Models for Current Cell-Based Oral Tissue Regeneration.
Tissue engineering. Part B, Reviews
The recent advances in the field of cell-based therapeutics open promising perspectives for oral tissue regeneration. The development of large animal models, which overcome the limits of the rodent models and allow to emulate clinical situations, is crucial for the validation of regenerative strategies to move toward clinical application. Currently, porcine, canine, and ovine models are mainly developed for oral regeneration and their specific characteristics have an impact on the outcomes of the studies. Thus, this systematic review investigates the application of porcine, canine, and ovine models in present cell-based oral regeneration, according to the species characteristics and the targeted tissue to regenerate. A customized search of PubMed, EMBASE, Scopus, and Web of Science databases from January 2015 to March 2020 was conducted. Relevant articles about cell-based oral tissues engineering in porcine, canine, and ovine models were evaluated. Among the evaluated articles, 58 relevant studies about cell-based oral regeneration in porcine, canine, and ovine models matched the eligibility criteria and were selected for full analysis. Porcine models, the most similar species with humans, were mostly used for bone and periodontium regeneration; tooth regeneration was reported only in pig, except for one study in dog. Canine models were the most transversal models, successfully involved for all oral tissue regeneration and notably in implantology. However, differences with humans and ethical concerns affect the use of these models. Ovine models, alternative to porcine and canine ones, were mainly used for bone and, scarcely, periodontium regeneration. The anatomy and physiology of these animals restrain their involvement. If consistency was found in defect specificities and cell trends among different species animal models of bone, dentin-pulp complex, or tooth regeneration, variability appeared in periodontium. Regeneration assessment methods were more elaborate in porcines and canines than in ovines. Risk of bias was low for selection, attrition and reporting, but unclear for performance and detection. Overall, if none of the large animal models can be considered an ideal one, they are of deemed importance for oral cell-based tissue engineering and researchers should consider their relevance to establish favorable conditions for a given preclinical cell-based therapeutics. Impact statement This systematic review investigates porcine, canine, and ovine models for current oral cell-based regeneration procedures, and researchers could refer to it for the choice of the most pertinent preclinical model for a given cell-based therapeutics.
10.1089/ten.TEB.2020.0384
Design and development of electrospun SPEEK incorporated with aminated zirconia and curcumin nanofibers for periodontal regeneration.
Ekambaram Rajalakshmi,Paraman Vikas,Raja Lokeshwar,Suresh Manoj Kumar,Dharmalingam Sangeetha
Journal of the mechanical behavior of biomedical materials
Periodontal disease disturbs the supportive tissues around the teeth such as connective tissue, gingival tissue, periodontal ligaments and alveolar bone. Previously, treatment of periodontitis was embattled by repopulating the affected site with cells that has capacity to regenerate damaged tissue by endorsing the perception of guided tissue regeneration but it entails additional surgery owing to non-biodegradability. Biodegradable polymeric nanofibrous scaffold imitating extracellular matrix (ECM) delivering functionalized nanoparticles loaded with therapeutic drug have the ability to support cellular functions thereby enhancing regeneration. Present study explores novel amine functionalized zirconia nanoparticle loaded curcumin incorporated SPEEK nanofibrous scaffolds to address periodontal regeneration. Zirconia - crown of dental therapeutics, its amine functionalization further enhanced the strength and cyto-compatibility. Carbon-Silica NMR (59.9 and 69.8 ppm), FT-IR (3426 cm), EDAX and XRD (28.9° 31.6° and 38.2° pertaining to [-1 1 1], [1 1 1] and [1 2 0] planes) analysis confirmed the effective functionalization of the zirconia nanoparticle with the amine group. Electrospinning was carried out at a voltage of 20 kV and flow rate of 0.05 ml/h. Fabricated nanofibers were highly dense, porous with interconnected fibrous structures that bio-mimic ECM. They exhibited an average diameter of 187 ± 2 nm (SPEEK), 192 ± 2 nm (SPEEK + NH-ZrO), and 256 ± 17 nm (SPEEK + NH-ZrO+Cur). Extensively discovered anti-bacterial traits of curcumin supplemented the advantage for the treatment of periodontitis. Incorporated materials improve the physico-chemical, mechanical and biological characteristics of nanofibers. FT-IR, EDAX and XRD analysis of the fabricated nanofibrous scaffold demonstrated the effective incorporation of aminated zirconia loaded curcumin. Results of cyto-compatibility analysis of SPEEK + NH-ZrO+Cur nanofibrous scaffold depicted a cell viability of 100 ± 1.62%. Results of anti-bacterial assay with zone of inhibition was 6.5 ± 0.5 mm (SPEEK), 7.5 ± 1 mm (SPEEK + NH-ZrO), and 8 ± 1 mm (SPEEK + NH-ZrO+Cur). Thus, the fabricated bio-material is cyto-compatible, non-toxic and effective against pathogens exploiting higher potential for periodontal regeneration applications.
10.1016/j.jmbbm.2021.104796
Effects of PIN on Osteoblast Differentiation and Matrix Mineralization through Runt-Related Transcription Factor.
Park Kyung-Ran,Kim SooHyun,Cho MyoungLae,Kang Sang Wook,Yun Hyung-Mun
International journal of molecular sciences
Sieb. et Zucc. has been used as traditional medicine in inflammatory diseases, and isolated compounds have shown pharmacological activities. Pinoresinol glucoside (PIN) belonging to lignins was isolated from the stem bark of This study aimed to investigate the biological function and mechanisms of PIN on cell migration, osteoblast differentiation, and matrix mineralization. Herein, we investigated the effects of PIN in MC3T3-E1 pre-osteoblasts, which are widely used for studying osteoblast behavior in in vitro cell systems. At concentrations ranging from 0.1 to 100 μM, PIN had no cell toxicity in pre-osteoblasts. Pre-osteoblasts induced osteoblast differentiation, and the treatment of PIN (10 and 30 μM) promoted the cell migration rate in a dose-dependent manner. At concentrations of 10 and 30 μM, PIN elevated early osteoblast differentiation in a dose-dependent manner, as indicated by increases in alkaline phosphatase (ALP) staining and activity. Subsequently, PIN also increased the formation of mineralized nodules in a dose-dependent manner, as indicated by alizarin red S (ARS) staining, demonstrating positive effects of PIN on late osteoblast differentiation. In addition, PIN induced the mRNA level of BMP2, ALP, and osteocalcin (OCN). PIN also upregulated the protein level of BMP2 and increased canonical BMP2 signaling molecules, the phosphorylation of Smad1/5/8, and the protein level of Runt-related transcription factor 2 (RUNX2). Furthermore, PIN activated non-canonical BMP2 signaling molecules, activated MAP kinases, and increased β-catenin signaling. The findings of this study indicate that PIN has biological roles in osteoblast differentiation and matrix mineralization, and suggest that PIN might have anabolic effects in bone diseases such as osteoporosis and periodontitis.
10.3390/ijms21249579
Histological evaluation of the repair process of replanted rat teeth after storage in resveratrol dissolved in dimethyl sulphoxide.
Dental traumatology : official publication of International Association for Dental Traumatology
BACKGROUND/AIM:The storage media is directly related to the prognosis of avulsed teeth, with resveratrol drawing attention due to its antioxidant and anti-inflammatory proprieties. The aim of this study was to evaluate the repair process in rat teeth following delayed replantation after storage in resveratrol (R) dissolved in dimethyl sulphoxide (DMSO). MATERIALS AND METHODS:The upper right central incisors of 36 rats were divided into 4 groups. In group I, the teeth were extracted and immediately replanted. Group II teeth were stored in 50 mL R+DMSO (0.0512 g/mL), whereas group III teeth were stored in 50 mL pure DMSO, both for a period of 60 minutes. The teeth of group IV were stored dry for 60 minutes. The teeth of groups II, III and IV were then replanted, and the animals were euthanized after 60 days. Longitudinal histological cuts were HE stained for histomorphometric analysis of the periodontal ligament, alveolar bone, cementum and dentin. RESULTS:The analysis of HE stained histological sections showed the following statistical differences: the acute inflammatory process in the epithelial insertion was less prominent in group II than in group III; the organization of the periodontal ligament was better in group I, while the intensity and extension of acute inflammation in the periodontal ligament were better in group I, and worse in group III; the chronic inflammatory infiltrate was less in groups I and IV, and the depth and extent of resorption, as well as the repair of root resorption, were better in group I. CONCLUSIONS:Storage in R+DMSO solution did not inhibit root resorption after delayed replantation in rat teeth. It is concluded that pure DMSO is not a suitable transport medium for avulsed teeth.
10.1111/edt.12402
Buccal Resveratrol Delivery System as a Potential New Concept for the Periodontitis Treatment.
Paczkowska-Walendowska Magdalena,Dvořák Jakub,Rosiak Natalia,Tykarska Ewa,Szymańska Emilia,Winnicka Katarzyna,Ruchała Marek A,Cielecka-Piontek Judyta
Pharmaceutics
The health benefits of resveratrol have been proven to inhibit the development of numerous diseases. A frequent limitation in its use is a low bioavailability stemming from a poor solubility and fast enterohepatic metabolism. Thus, the aim of the research was to investigate the possibility to formulate mucoadhesive cyclodextrin- and xanthan gum-based buccal tablets in order to increase the solubility of resveratrol and to eliminate bypass enterohepatic metabolism. Systems of resveratrol with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) prepared by the dry mixing method (ratio 1:1) were selected for the of tablets where xanthan gum was used as a mucoadhesive agent. They were identified on the basis of PXRD, FT-IR analysis. Tablets F1 (with α-CD), F2 (with β-CD) and F3 (with γ-CD) were characterized by the highest compactibility as well as by favorable mucoadhesive properties. Resveratrol release from these tablets was delayed and controlled by diffusion. The tablets prepared in the course of this study appear to constitute promising resveratrol delivery systems and are recommended to increase the effectiveness of the treatment in many diseases, particularly periodontitis.
10.3390/pharmaceutics13030417
Dual drug loaded coaxial electrospun PLGA/PVP fiber for guided tissue regeneration under control of infection.
He Ping,Zhong Quan,Ge Yao,Guo Zhenzhao,Tian Jinhuan,Zhou Yehui,Ding Shan,Li Hong,Zhou Changren
Materials science & engineering. C, Materials for biological applications
Electrospinning promisingly fabricate mats for Guided Tissue Regeneration (GTR). Due to a chronic inflammatory pathology in periodontal, it is highly desirable to develop a novel GTR mats to realize tissue regeneration under control of infection. In the study, coaxial electrospinning was firstly conducted to fabricate dual drug loaded fiber mats with core/shell structure. Naringin-loaded polyvinylpyrrolidone was designed as core fiber to enrich tissue regeneration and metronidazole-loaded poly(lactic-co-glycolic acid) as shell fiber to inhibit bacterial. TEM revealed that the fibers with distinct core/shell structure were in an outer diameter of 1.5-1.7 μm with an inner diameter of <1.0 μm. The loading of dual drug decreased the tensile strength and elongation of the coaxial fiber mats. On in vitro assessment, metronidazole had a short-term release while naringin had a long-term release behavior in all the coaxial mats. The colonization of anaerobic bacteria on the mats effectively were inhibited over 21 days. Furthermore, the dual drug loaded coaxial fiber mats were observed to positively supported the adhesion and proliferation of MC3T3-E1 and was conductive to high alkaline phosphatase express. Thus, a simple and effective coaxial electrospinning approach was demonstrated for the fabrication of anti-infective GTR mats with promoting tissue regeneration.
10.1016/j.msec.2018.04.014
The effect of (-)-epigallocatechin gallate as an adjunct to non-surgical periodontal treatment: a randomized clinical trial.
Trials
BACKGROUND:EGCG is proven to be of good effect to relieve periodontal inflammation, but it has not been applied as a local delivery medicine in patients with periodontitis widely. The aim of this clinical trial was to evaluate the adjunctive effect of (-)-epigallocatechin gallate (EGCG) aqueous solution as a coolant during scaling and root planing in the management of chronic periodontitis. METHODS:A double-blind, randomized controlled study was performed on 15 patients with moderate to severe chronic periodontitis. The bilateral maxillary teeth were randomly divided into the test side and the control side on every individual. On the control side, the periodontal therapy was routinely performed. And on the test side, in the process of periodontal therapy, the distilled water in the ultrasonic scaler was replaced with a 5-mg/mL EGCG solution. The probing depth (PPD), clinical attachment level (CAL), bleeding index (BI), gingival index (GI), and plaque index (PI) were recorded at baseline and 6 and 12 weeks after the treatment. RESULTS:PPD, CAL, BI, GI, and PI generally improved after treatment in both groups. At the sixth week and the twelfth week of review, PPD, CAL, GI, and PI had no statistical difference (p >0.05) between the two groups. At the review of the twelfth week, BI on the test side decreased significantly (p <0.05). CONCLUSIONS:Using EGCG solution as the irrigant instead of water has an additional benefit on the bleeding index at the 12-week review. However, the rest clinical parameters had no additional benefit. TRIAL REGISTRATION:ClinicalTrials.gov ChiCTR2000029831 , date of registration: Feb 15, 2020.
10.1186/s13063-022-06298-6
Effects of Lactobacillus salivarius WB21 combined with green tea catechins on dental caries, periodontitis, and oral malodor.
Higuchi Takuya,Suzuki Nao,Nakaya Seigo,Omagari Sami,Yoneda Masahiro,Hanioka Takashi,Hirofuji Takao
Archives of oral biology
OBJECTIVE:To evaluate the combined use of Lactobacillus salivarius WB21 and (-)-epigallocatechin gallate (EGCg) for oral health maintenance. DESIGN:The effects of L. salivarius WB21 on growth of Streptococcus mutans, the insoluble glucan produced by S. mutans, and on growth of Porphyromonas gingivalis were evaluated in vitro. In addition, the susceptibility of five oral pathogenic bacteria and L. salivarius WB21 to EGCg, the inhibiting effect of EGCg on methyl mercaptan, and the effects of L. salivarius WB21 and EGCg in combination on growth of P. gingivalis were examined. RESULTS:Lactobacillus salivarius WB21 showed concentration-dependent inhibition of the growth of S. mutans. Addition of L. salivarius WB21 inhibited production of the insoluble glucan by S. mutans (p < 0.001). A filtrate of L. salivarius WB21 culture solution inhibited growth of P. gingivalis (p < 0.001 vs. control), and this effect was enhanced when it was used in combination with EGCg (p < 0.001 vs. the addition of L. salivarius WB21). In addition, EGCg directly inhibited methyl mercaptan in a concentration-dependent manner (p < 0.001). Concerning bacterial susceptibility to EGCg, growth of P. gingivalis, Prevotella intermedia, and Fusobacterium nucleatum was inhibited at 2.5 mg/mL of EGCg, while that of L. salivarius WB21 was inhibited at 25 mg/mL EGCg. CONCLUSIONS:Our results imply that L. salivarius WB21 may be useful for controlling dental caries, periodontitis, and oral malodor. In addition, the effects of L. salivarius WB21 on periodontitis and oral malodor may be synergistically enhanced by use in combination with EGCg.
10.1016/j.archoralbio.2018.11.027
Effects of quercetin on antioxidant potential in the experimental periodontitis development.
Interventional medicine & applied science
The results of experimental research of antioxidant system are presented in this article. Superoxide dismutase activity, catalase, and ceruloplasmin have been determined on the 7 and 14 days of experimental periodontitis development both without correction and with the injection of a water-soluble quercetin drug (corvitin). Hence, there was a decrease in superoxide dismutase activity, intensive increase in catalase activity, and ceruloplasmin maintenance in the blood serum during acute period of inflammatory process. The usage of flavonoid for 7 days resulted in stabilization of radical oxidation due to reduction of superoxide dismutase activity, maintenance at the high-level catalase activity, and ceruloplasmin concentration in the rat's blood plasma with experimental bacterial-immune periodontitis.
10.1556/1646.11.2019.06
The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling pathway.
Zhu Chunhui,Zhao Ying,Wu Xiaoyan,Qiang Cui,Liu Jin,Shi Jianfeng,Gou Jianzhong,Pei Dandan,Li Ang
Journal of periodontal research
BACKGROUND AND OBJECTIVE:Oxidative stress has been suggested as an important pathogenic factor contributing to chronic periodontitis with diabetes mellitus (CPDM). Previous studies have revealed the potential therapeutic properties of baicalein (BCI) in oxidative stress-related diseases; however, the antioxidant effects of BCI on therapy for individual with CPDM remain largely unexplored. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in cellular defence against oxidative stress. In this study, we aim to determine whether BCI prevents diabetes-related periodontal tissue destruction by regulating Nrf2 signaling pathway. MATERIAL AND METHODS:Human gingival epithelial cells (hGECs) were challenged with high glucose (HG, 25 mmol/L) and/or lipopolysaccharide (LPS, 20 µg/mL). Reactive oxygen species (ROS) were detected by fluorescence-activated cell sorting. The changes of antioxidant-related genes, including Nrf2, catalase (Cat), glutamate-cysteine ligase catalytic subunit (Gclc), superoxide dismutase 1 (Sod1), and superoxide dismutase 2 (Sod2), were quantified by real-time PCR. The localization of phospho-Nrf2 (pNrf2, S40) in the nucleus was detected by immunofluorescence staining and laser scanning confocal microscope (LSCM). PNrf2 and total form of Nrf2 were determined using western blot. The above indicators together with mitochondrial membrane potential (MMP) were further investigated in hGECs pre-treated with different concentrations of BCI (0.01, 0.1, or 0.5 µg/mL) before stimulated with HG plus LPS (GP). Finally, the role of BCI in activating Nrf2 signaling pathway and relieving the alveolar bone absorption was examined in the CPDM model of Sprague Dawley rats. CPDM rats were oral gavaged with BCI (50, 100, or 200 mg/kg daily). The pNrf2 was detected by immunohistochemistry, and the alveolar bone absorption was examined by microcomputed tomography. RESULTS:Our results showed that ROS were significantly increased in both groups of HG and LPS, with the strongest generation in the GP group. In terms of ROS-related gene expression, we found that the mRNA levels of Nrf2, Cat, Gclc, Sod1, and Sod2 were significantly decreased in HG and LPS groups. In consistent with the strongest induction of ROS in GP group, the gene expression in GP group was further decreased as compared to those of HG and LPS groups. Also, the expression of pNrf2 exhibited the same trend with the expression of those antioxidant genes. However, the generation of ROS and the loss of mitochondrial membrane potential induced by GP were abolished by pre-treatment with different concentrations of BCI (0.01, 0.1, or 0.5 µg/mL). Interestingly, we observed that BCI promoted the nucleus translocation of pNrf2, as well as the gene expression levels of pNrf2 and its target genes (Cat, Gclc, Sod1, and Sod2). Finally, in the CPDM animal model, we found that BCI (at concentrations: 50, 100, and 200 mg/kg) markedly increased the number of pNrf2-positive cells in periodontal tissue and mitigated the alveolar bone loss. CONCLUSIONS:Our data revealed a potential role for clinic application of BCI under CPDM conditions, suggesting a new therapeutic drug for CPDM patients.
10.1111/jre.12722
Study on proanthocyanidins crosslinked collagen membrane for guided bone tissue regeneration.
Yang Hongfa,Liu Wai-Ching,Liu Xinrui,Li Yunqian,Lin Chingpo,Lin Yu-Min,Wang An-Ni,Nguyen Thu-Trang,Lin Yu-Chien,Chung Ren-Jei
Journal of applied biomaterials & functional materials
The goal of this study is to understand the ability of a newly developed barrier membrane to enhance bone tissue regeneration. Here in this study we present the in vitro characterization of the barrier membrane made from type I collagen and crosslinked by oligomeric proanthocyanidins (OPCs). The effects of the membrane (P-C film) on cell cycle, proliferation, alkaline phosphatase activity, and mineralization were evaluated using the human osteoblast cell line MG-63, while the barrier ability was examined using MG-63 cells, as well as the human skin fibroblast cell line WS-1. The pore size is one of the factors that plays a key role in tissue regeneration, therefore, we evaluated the pore size of the membrane using a capillary flow porometer. Our results showed that the mean pore size of the P-C film was approximately 7-9 µm, the size known to inhibit cell migration across the membrane. The P-C film also demonstrated excellent cell viability and good biocompatibility, since the cell number increased with time, with MG-63 cells proliferating faster on the P-C film than in the cell culture flask. Furthermore, the P-C film promoted osteoblast differentiation, resulting in higher alkaline phosphatase activity and mineralization. Therefore, our results suggest that this P-C film has a great potential to be used in guided bone regeneration during periodontal regeneration and bone tissue engineering.
10.1177/22808000211005379
More natural more better: triple natural anti-oxidant puerarin/ferulic acid/polydopamine incorporated hydrogel for wound healing.
Ou Qianmin,Zhang Shaohan,Fu Chuanqiang,Yu Le,Xin Peikun,Gu Zhipeng,Cao Zeyuan,Wu Jun,Wang Yan
Journal of nanobiotechnology
BACKGROUND:During wound healing, the overproduction of reactive oxygen species (ROS) can break the cellular oxidant/antioxidant balance, which prolongs healing. The wound dressings targeting the mitigation of ROS will be of great advantages for the wound healing. puerarin (PUE) and ferulic acid (FA) are natural compounds derived from herbs that exhibit multiple pharmacological activities, such as antioxidant and anti-inflammatory effects. Polydopamine (PDA) is made from natural dopamine and shows excellent antioxidant function. Therefore, the combination of natural antioxidants into hydrogel dressing is a promising therapy for wound healing. RESULTS:Hydrogel wound dressings have been developed by incorporating PUE or FA via PDA nanoparticles (NPs) into polyethylene glycol diacrylate (PEG-DA) hydrogel. This hydrogel can load natural antioxidant drugs and retain the drug in the gel network for a long period due to the presence of PDA NPs. Under oxidative stress, this hydrogel can improve the activity of superoxide dismutase and glutathione peroxidase and reduce the levels of ROS and malondialdehyde, thus preventing oxidative damage to cells, and then promoting wound healing, tissue regeneration, and collagen accumulation. CONCLUSION:Overall, this triple antioxidant hydrogel accelerates wound healing by alleviating oxidative injury. Our study thus provides a new way about co-delivery of multiple antioxidant natural molecules from herbs via antioxidant nanoparticles for wound healing and skin regeneration.
10.1186/s12951-021-00973-7
Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo.
International journal of molecular sciences
This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.
10.3390/ijms22063223
Hesperetin suppresses RANKL-induced osteoclastogenesis and ameliorates lipopolysaccharide-induced bone loss.
Liu Hui,Dong Yonghui,Gao Yutong,Zhao Liming,Cai Cong,Qi Dahu,Zhu Meipeng,Zhao Libo,Liu Changyu,Guo Fengjing,Xiao Jun,Huang Hui
Journal of cellular physiology
Destructive bone diseases caused by osteolysis are increasing in incidence. They are characterized by an excessive imbalance of osteoclast formation and activation. During osteolysis, the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways are triggered by receptor activator of NF-κB ligand (RANKL), inflammatory factors, and oxidative stress. Previous studies have indicated that the common flavanone glycoside compound hesperetin exhibits anti-inflammatory and antioxidant activity by inhibition of NF-κB and MAPK signaling pathways. However, the direct relationship between hesperetin and osteolysis remain unclear. In the present study, we investigated the effects of hesperetin on lipopolysaccharide (LPS)-induced osteoporosis and elucidated the related mechanisms. Hesperetin effectively suppressed RANKL-induced osteoclastogenesis, osteoclastic bone resorption, and F-actin ring formation in a dose-dependent manner. It also significantly suppressed the expression of osteoclast-specific markers including tartrate-resistant acid phosphatase, matrix metalloproteinase-9, cathepsin K, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1. Furthermore, it inhibited osteoclastogenesis by inhibiting activation of NF-κB and MAPK signaling, scavenging reactive oxygen species, and activating the nuclear factor E2 p45-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway. Consistent with in vitro results, hesperetin effectively ameliorated LPS-induced bone loss, reduced osteoclast numbers, and decreased the RANKL/OPG ratio in vivo. As such, our results suggest that hesperetin may be a great candidate for developing a novel drug for destructive bone diseases such as periodontal disease, tumor bone metastasis, rheumatoid arthritis, and osteoporosis.
10.1002/jcp.27924
Expression of silent information regulator 2 homolog 1 (SIRT1) in periapical granulomas.
Kudo Hiroshi,Takeichi Osamu,Makino Kosuke,Hatori Keisuke,Ogiso Bunnai
Journal of oral science
Silent information regulator 2 homolog 1 (SIRT1) inhibits oxidative injury and has anti-inflammatory effects. SIRT1 may be involved in healing of periapical periodontitis; however, SIRT1 expression in periapical periodontitis lesions has not been investigated. This study evaluated SIRT1 expression and a marker of oxidative stress-8-hydroxy-2'-deoxyguanosine (8-OHdG)-in periapical granulomas. First, we used real-time polymerase chain reaction to determine whether U-937 monocytes express SIRT1. U-937 cells treated with the SIRT1 activator resveratrol exhibited the highest SIRT1 mRNA level after 6-h incubation. By contrast, treating cells with the SIRT1 inhibitor sirtinol returned SIRT1 expression level to that of the control. In addition, immunocytochemical analysis using cytospin specimens showed that U-937 cells co-expressed SIRT1 and Ki-67. Dual-color immunofluorescence imaging showed that round cells in periapical granulomas co-expressed SIRT1 and 8-OHdG; however, neither was expressed in healthy gingival tissues. The number of 8-OHdG-expressing cells was significantly greater than the number of SIRT1-expressing cells. Our findings suggest that macrophages express SIRT1 and that wound healing in periapical granulomas is enhanced by a SIRT1-mediated reduction in the level of oxidative stress.
10.2334/josnusd.17-0412
Efficacy of (-)-epigallocatechin gallate delivered by a new-type scaler tip during scaling and root planing on chronic periodontitis: a split-mouth, randomized clinical trial.
Wang Yanfeng,Zeng Jiajun,Yuan Qiao,Luan Qingxian
BMC oral health
BACKGROUND:(-)-Epigallocatechin Gallate (EGCG) as green tea catechins possessed antibacterial and anti-inflammatory effects on periodontal disease. This study was designed to evaluate the clinical and microbiological efficacy of scaling and root planing (SRP) using EGCG aqueous solution as coolants through a new-type ultrasonic scaler tip on chronic periodontitis. METHODS:This split-mouth, randomized clinical trial included 20 patients (2 drop-outs) with chronic periodontitis and the maxillary contra-lateral sides were allocated into test and control groups randomly. Through the new-type scaler tip, 762 sites with probing depth (PD) ≥ 4 mm were treated by SRP using EGCG solution or distilled water as coolants respectively. Clinical parameters and red complex pathogens in subgingival microbiome were evaluated at baseline, 3 and 6 months after treatments. RESULTS:During 6 months, the SRP plus EGCG medication contributed to additional PD reduction as 0.33 mm and gain of clinical attachment level as 0.3 mm compared with SRP alone, and approximate 8% more sites obtained PD reduction ≥ 2 mm (p < 0.05). Meanwhile, the mean relative abundance of Tannerella forsythia was significantly lower in the combined treatment group (p < 0.05). CONCLUSION:The purified EGCG showed the potential to improve the outcome of periodontal non-surgical treatment and the new-type scaler tip provided an alternative vehicle for subgingival medication. Trial registration The trial was registered in Chinese Clinical Trial Registry on 15 February 2020 (No.: ChiCTR2000029831, retrospectively registered). http://www.chictr.org.cn/showprojen.aspx?proj=49441 .
10.1186/s12903-021-01418-1
The Antioxidant Effect of Curcumin and Rutin on Oxidative Stress Biomarkers in Experimentally Induced Periodontitis in Hyperglycemic Wistar Rats.
Iova Gilda M,Calniceanu Horia,Popa Adelina,Szuhanek Camelia A,Marcu Olivia,Ciavoi Gabriela,Scrobota Ioana
Molecules (Basel, Switzerland)
BACKGROUND:There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. METHODS:Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)-control group, (2) (DPP)-experimentally induced diabetes mellitus and periodontitis, (3) (DPC)-experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)-experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)-experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. RESULTS:The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. CONCLUSIONS:The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.
10.3390/molecules26051332
Development and Evaluation of Thermosensitive Hydrogels with Binary Mixture of Extract and Chitosan for Periodontal Diseases Treatment.
Chanaj-Kaczmarek Justyna,Osmałek Tomasz,Szymańska Emilia,Winnicka Katarzyna,Karpiński Tomasz M,Dyba Magdalena,Bekalarska-Dębek Marta,Cielecka-Piontek Judyta
International journal of molecular sciences
root displays anti-inflammatory and antibacterial properties due to the presence of flavonoids, particularly baicalin, baicalein, and wogonin. Our work aimed at developing thermosensitive hydrogels containing a binary mixture of lyophilized extract and chitosan as a novel approach for periodontal diseases treatment. Two types of chitosan were employed in preliminary studies on binary mixtures with lyophilized extract standardized for baicalin, baicalein, and wogonin. Thermosensitive hydrogels were prepared of poloxamer 407, alginate sodium, and cellulose derivatives and evaluated in terms of rheological and mucoadhesive behavior. The presence of chitosan altered the release profile of active compounds but did not affect their in vitro permeation behavior in PAMPA assay. The synergistic effects of lyophilized extract and chitosan toward ferrous ion-chelating activity, inhibition of hyaluronidase, and pathogen growth were observed. The thermosensitive gelling system showed shear-thinning properties, gelation temperature between 25 and 27 °C, and favorable mucoadhesiveness in contact with porcine buccal mucosa, which was enhanced in the presence of binary mixture of extract and chitosan. The release tests showed that baicalin and baicalein were liberated in a prolonged manner with a fast onset from hydrogel formulations.
10.3390/ijms222111319
Citrus polyphenol for oral wound healing in oral ulcers and periodontal diseases.
Tsai Hsiao-Cheng,Li Yi-Chen,Young Tai-Horng,Chen Min-Huey
Journal of the Formosan Medical Association = Taiwan yi zhi
BACKGROUND/PURPOSE:Various polyphenolic compounds from plants have been confirmed to have different pharmaceutical functions. The purpose of this study was to evaluate citrus polyphenol (CP) for dental applications. A medium with CP was developed to improve oral wound healing. The CP could be used as a supplemental compound in mouthwash for periodontal diseases. METHOD:In this study, the metabolic activity and cell toxicity of CP (1%, 0.1%, and 0.01%) for fibroblasts were investigated by MTT and lactate dehydrogenase assays (n = 6). The effect of CP on motility of fibroblast was also evaluated via a wound healing model. RESULTS:The growth of Hs68 cells on TCPS was greatly increased in the presence of 0.01% CP. In addition, the significant difference (p<0.01) of cell toxicity of fibroblast was observed after 6 days in 0.01% CP medium. Using the wound healing model, it was also found that CP could enhance the migratory ability of fibroblasts. CONCLUSION:The results confirm the feasibility of CP be a supplemental compound in mouthwash for treatment of periodontal diseases in dental application to improve wound healing in the mouth.
10.1016/j.jfma.2015.01.003
Quercetin potentiates antiradical properties of epigallocatechin-3-gallate in periodontium of rats under systemic and local administration of lipopolisaccharide of salmonella typhi
Yelins’ka Alina M.,Liashenko Lilia I,Kostenko Vitalii O
Wiadomosci lekarskie (Warsaw, Poland : 1960)
Introduction:There has been demonstrated that pharmaceutical effect of epigallocatechin-3-gallate (EGCG), a polyphenol, which is found in green tea (Camellia sinensis), is implemented through the activation of Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2).The importance of Keap1 / Nrf2 / antioxidant response element (ARE) system is determined by the fact that the state of NF-κB- and АР-1-associated pathways depends on its activity. Recent studies have demonstrated the property of quercetin to suppress ubiquitin-dependent proteolysis of complex of NF-κB and its inhibitory protein IκB. All this provides preconditions to eliminate the potentiality of NF-κB-dependent expression of the number of genes of pro-oxidant and pro-inflammatory proteins. However, co-effect produced by quercetin and EGCG on the oxidative nitrosative stress markers in the periodontal tissues is still unclear. The aim:To investigate the co-effect produced by quercetin and an inducer of the Keap1 / Nrf2 / ARE epigallocatechin-3-gallate on markers of oxidative-nitrosative stress in rats’ periodontium under the systemic and local administration of Salmonella typhi lipopolysaccharide (LPS). Material and methods:The studies were conducted on 30 white rats of the Wistar line, divided into 5 groups: the 1st included intact animals, the 2nd was made up of animals after their exposure to combined systemic and local LPS administration, the 3rd and 4th groups included animals, which were given injections with water-soluble form of quercetin (corvitin) and EGCG respectively, and the 5th group involved rats, which were injected with co-administered corvitin and EGCG. The formation of superoxide anion radical (.О-2 ) was evaluated by a test with nitro blue tetrazolium using spectrophotometry of the periodontal soft tissue homogenate. The total activity of NO-synthase and concentration of peroxynitrite in the homogenate of the soft components of periodontium were evaluated spectrophotometrically. Results:Co-effect produced by corvitin and EGCG under systemic and local LPS administration is accompanied with reduced О-2 production by NADPH-dependent electron transport chains (microsomal and NOS) by 20.0 % (p <0.05) compared with values for the animals received separate corvitin during the experiment. .О-2 generation by the mitochondrial respiratory chain yielded to comparable data of the 3rd and 4th groups by 27.6 % (p <0.01) and 23.8 % (p <0.05) respectively. No differences were found between the groups exposed to combined or separate action of the above mentioned agents in the experiment when assessing О-2 generation by leukocyte NADPH-oxidase. Combined effect of corvitin and EGCG during systemic and local LSP administration showed the decrease in NOS activity and peroxynitrite concentration in periodontal tissues by 53.3 % (p <0.001) and 27.0 % (p <0.02) compared with the findings in the 3rd group, and by 42.0 % (p <0.01) and 22.3 % (p <0.01) in the 4th group. Conclusions:The co-administration of water-soluble form of quercetin and epigallocatechin-3-gallate under systemic and local introducing of lipopolysaccharide Salmonella typhi has been proven to be more effective means for preventing and correcting oxidative-nitrosative stress in the periodontal tissues than this occurs at separate administration of each of the polyphenols.
Design, characterization and in vitro evaluation of thin films enriched by tannic acid complexed by Fe(III) ions.
Kaczmarek B,Mazur O,Miłek O,Michalska-Sionkowska M,Das A,Jaiswal A,Vishnu J,Tiwari K,Sionkowska A,Osyczka A M,Manivasagam G
Progress in biomaterials
Materials based on carbohydrate polymers may be used for biomedical application. However, materials based on natural polymers have weak physicochemical properties. Thereby, there is a challenge to improve their properties without initiation of toxicity. The alternative method compared to toxic chemical agents' addition is the use of metal complexation method. In this study, chitosan/tannic acid mixtures modified by Fe(III) complexation are proposed and tested for potential applications as wound dressings. Thereby, surface properties, blood compatibility as well as platelet adhesion was tested. In addition, the periodontal ligament stromal cells compatibility studies were carried out. The results showed that the iron(III) addition to chitosan/tannic acid mixture improves properties due to a decrease in the surface free energy and exhibited a reduction in the hemolysis rate (below 5%). Moreover, cells cultured on the surface of films with Fe(III) showed higher metabolic activity. The current findings allow for the medical application of the proposed materials as wound dressings.
10.1007/s40204-020-00146-z
Curcumin downregulates the PI3K-AKT-mTOR pathway and inhibits growth and progression in head and neck cancer cells.
Borges Gabriel Alvares,Elias Silvia Taveira,Amorim Bruna,de Lima Caroline Lourenço,Coletta Ricardo Della,Castilho Rogerio Moraes,Squarize Cristiane Helena,Guerra Eliete Neves Silva
Phytotherapy research : PTR
Curcumin, a polyphenol isolated from the rhizome of Curcuma longa, has been studied because of its antioxidant, antimicrobial, and antiinflammatory properties. This study aimed to evaluate the effects of curcumin on head and neck cancer (HNC) cell lines and how it modulates the PI3K-AKT-mTOR signaling pathway. Dose-response curves for curcumin were established for hypopharynx carcinoma (FaDu), tongue carcinoma (SCC-9), and keratinocytes (HaCaT) cell lines and IC values were calculated. Cell cycle and cell death were investigated through flow cytometry. Cytoskeleton organization was assessed through phalloidin+FITC staining. qPCR array and western blot were performed to analyze gene and protein expression. Curcumin reduced cell viability in a dose-dependent and selective manner, induced cell death on SCC-9 cells (necrosis/late apoptosis: 44% curcumin vs. 16.4% vehicle), and arrested cell cycle at phase G /M on SCC-9 and FaDu (G : SCC-9-19.1% curcumin vs. 13.4% vehicle; FaDu-37.8% curcumin vs. 12.9% vehicle). Disorganized cytoskeleton and altered cell morphology were observed. Furthermore, curcumin downregulated the PI3K-AKT-mTOR signaling pathway by modifying the expression of key genes and proteins. These findings highlight the promising therapeutic potential of curcumin to inhibit HNC growth and progression and to modulate the PI3K-AKT-mTOR pathway.
10.1002/ptr.6780
Functionalization with a Polyphenol-Rich Pomace Extract Empowers a Ceramic Bone Filler with In Vitro Antioxidant, Anti-Inflammatory, and Pro-Osteogenic Properties.
Iviglia Giorgio,Torre Elisa,Cassinelli Clara,Morra Marco
Journal of functional biomaterials
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.
10.3390/jfb12020031
An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model.
Bahar Bojlul,Singhrao Sim K
Molecular biology reports
Porphyromonas gingivalis triggers a range of innate immune responses in the host that may contribute to the development of periodontitis and dementing diseases including Alzheimer's disease (AD). This study aimed to assess the mode of action of trans-resveratrol in modulating the P. gingivalis lipopolysaccharide (PgLPS) induced metabolic inflammation in a neuronal cell model. Confluent IMR-32 neuroblastoma cells were treated with trans-resveratrol from Polygonum cuspidatum in the presence or absence of PgLPS. The abundance of messenger ribo-nucleic acid (mRNA) transcripts of a panel of 92 genes was quantitatively assessed through targeted transcriptome profiling technique and the biochemical pathways affected were identified through Ingenuity Pathway Analysis. Gene expression analysis revealed that trans-resveratrol down-regulated the mRNA of multiple gene markers including growth factors, transcription factors, kinases, trans-membrane receptors, cytokines and enzymes that were otherwise activated by PgLPS treatment of IMR-32 neuroblastoma cells. Pathway analysis demonstrated that the cellular oxidative stress caused by the activation of phosphoinositide-3-kinase/Akt1 (PI3K/Akt1) pathway that leads to the production of reactive oxygen species (ROS), chronic inflammatory response induced by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and nutrient utilization pathways were favourably modulated by trans-resveratrol in the PgLPS challenged IMR-32 cells. This study demonstrates the potential of trans-resveratrol as a bioactive compound with multiple modes of intracellular action further supporting its therapeutic application in neuroinflammatory diseases.
10.1007/s11033-020-06024-y
Protocatechualdehyde inhibits receptor activator of nuclear factor kappa-B ligand-induced osteoclastogenesis and attenuates lipopolysaccharide-induced inflammatory osteolysis.
Huang Hao,Jiang Wenli,Hong Kehua,Cai Jie,He Yongchao,Ma Xuming,Wu Peng,Lang Junzhe,Ma Yuegang,Huang Caiguo,Yuan Jiandong
Phytotherapy research : PTR
Inflammatory osteolysis as a consequence of chronic bacterial infection underlies several lytic bone conditions, such as otitis media, osteomyelitis, septic arthritis, periodontitis, periprosthetic infection, and aseptic loosening of orthopedic implants. In consideration of the lack of effective preventive or treatments options against infectious osteolysis, the exploitation of novel pharmacological compounds/agents is critically required. The present study assessed the effect of protocatechualdehyde (PCA), a natural occurring polyphenolic compound with diverse biological activities including but not limited to antibacterial and antiinflammatory properties, on nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and lipopolysaccharide (LPS)-induced bone loss in vivo. In the present study, it was found that PCA potently inhibited RANKL-induced osteoclast formation, fusion, and activation toward bone resorption in a dose-dependent manner via the suppression of the ERK/c-Fos/nuclear factor of activated T-cells, cytoplasmic 1 signaling axis. It was further demonstrated that the in vivo administration of PCA could effectively protect mice against the deleterious effects of LPS-induced calvarial bone destruction by attenuating osteoclast formation and activity in a dose-dependent manner. Collectively, these findings provided evidence for the potential therapeutic application of PCA in the prevention and treatment of infectious osteolytic conditions, and potentially other osteoclast-mediated bone diseases.
10.1002/ptr.7088
Quantum curcumin mediated inhibition of gingipains and mixed-biofilm of causing chronic periodontitis.
RSC advances
Periodontitis is a biofilm-associated irreversible inflammation of the periodontal tissues. Reports suggest the role of specific Arg- and Lys-specific proteinases in the orchestration of the initiation and progression of periodontal diseases. These proteinases are precisely termed as gingipains R and K. Curcumin is an active polyphenol that is extracted from the rhizomes of . However, the molecule curcumin owing to its high hydropathy index and poor stability has not been able to justify its role as frontline drug modality in the treatment of infectious and non-infectious diseases as claimed by several investigators. In the present study, at first, we synthesized and characterized quantum curcumin, and investigated its biocompatibility. This was subsequently followed by the evaluation of the role of quantum curcumin as an antimicrobial, anti-gingipains and antibiofilm agent against and select reference strains. We have successfully synthesized the quantum curcumin utilizing a top-down approach with the average size of 3.5 nm. Apart from its potent antimicrobial as well as antibiofilm properties, it also significantly inhibited the gingipains in a dose-dependent manner. At the minimal concentration of 17.826 μM, inhibition up to 98.7% and 89.4% was noted for gingipain R and K respectively. The data was also supported by the docking experiments which revealed high exothermic enthalpies (-7.01 and -7.02 cal mol). Besides, the inhibition constant was found to be 7.24 μM and 7.1 μM against gingipains R and K respectively. The results suggest that quantum curcumin is a potential drug candidate which needs further clinical validation.
10.1039/c8ra08435a
Resveratrol derivative-rich melinjo seed extract induces healing in a murine model of established periodontitis.
Ikeda Eri,Ikeda Yuichi,Wang Yongqiang,Fine Noah,Sheikh Zeeshan,Viniegra Ana,Barzilay Oriyah,Ganss Bernhard,Tenenbaum Howard C,Glogauer Michael
Journal of periodontology
BACKGROUND:Products of internal defense systems, like pro-inflammatory cytokines, reactive oxygen species, and leukocytes, are released which attack periodontal bacteria in periodontitis, but at the same time, lead to tissue destruction as well. We hypothesize that resveratrol derivative-rich melinjo seed extract (MSE), an edible plant extract that has antioxidant properties, should promote healing of periodontal bone loss and modulating immune-inflammatory systems that leads periodontal tissue destruction. METHODS:We used an experimentally induced periodontitis (EP) model in mice. Ligatures were placed first for development of EP (15 days). MSE was intraperitoneally administrated (0.001% (w/w)) to reverse bone loss that had already occurred in established EP and mice were then sacrificed (day 17, 20 and 22). RESULTS:Morphometric outcomes revealed lower bone-loss in the MSE groups compared to control. Immunohistochemistry assays demonstrated lower oxidative stress in MSE groups. MSE also inhibited M-CSF/sRANKL mediated osteoclast formation and down-regulated osteoclast activity. CONCLUSIONS:Treatment with MSE in EP actually caused healing of bone, and these effects are probably related to decreases in local oxidative damage and osteoclast activity. Given MSE's positive effects on osteodifferentiation as well, these findings suggest that MSE could be a useful therapeutic agent for the management of periodontitis.
10.1002/JPER.17-0352
Improvement of the Physical Properties of Guided Bone Regeneration Membrane from Porcine Pericardium by Polyphenols-Rich Pomace Extract.
Russo Nazario,Cassinelli Clara,Torre Elisa,Morra Marco,Iviglia Giorgio
Materials (Basel, Switzerland)
To achieve optimal performances, guided bone regeneration membranes should have several properties, in particular, proper stiffness and tear resistance for space maintenance, appropriate resorption time, and non-cytotoxic effect. In this work, polyphenol-rich pomace extract (PRPE), from a selected grape variety (Nebbiolo), rich in proanthocyanidins and flavonols (e.g., quercetin), was used as a rich source of polyphenols, natural collagen crosslinkers, to improve the physical properties of the porcine pericardium membrane. The incorporation of polyphenols in the collagen network of the membrane was clearly identified by infra-red spectroscopy through the presence of a specific peak between 1360-1380 cm. Polyphenols incorporated into the pericardium membrane bind to collagen with high affinity and reduce enzymatic degradation by 20% compared to the native pericardium. The release study shows a release of active molecules from the membrane, suggesting a possible use in patients affected by periodontitis, considering the role of polyphenols in the control of this pathology. Mechanical stiffness is increased making the membrane easier to handle. Young's modulus of pericardium treated with PRPE was three-fold higher than the one measured on native pericardium. Tear and suture retention strength measurement suggest favorable properties in the light of clinical practice requirements.
10.3390/ma12162564