scholarly journals Dentinogenic effects of extracted dentin matrix components digested with matrix metalloproteinases

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Motoki Okamoto ◽  
Yusuke Takahashi ◽  
Shungo Komichi ◽  
Paul R. Cooper ◽  
Mikako Hayashi

Abstract Dentin is primarily composed of hydroxyapatite crystals within a rich organic matrix. The organic matrix comprises collagenous structural components, within which a variety of bioactive molecules are sequestered. During caries progression, dentin is degraded by acids and enzymes derived from various sources, which can release bioactive molecules with potential reparative activity towards the dentin-pulp complex. While these molecules’ repair activities in other tissues are already known, their biological effects are unclear in relation to degradation events during disease in the dentin-pulp complex. This study was undertaken to investigate the effects of dentin matrix components (DMCs) that are partially digested by matrix metalloproteinases (MMPs) in vitro and in vivo during wound healing of the dentin-pulp complex. DMCs were initially isolated from healthy dentin and treated with recombinant MMPs. Subsequently, their effects on the behaviour of primary pulp cells were investigated in vitro and in vivo. Digested DMCs modulated a range of pulp cell functions in vitro. In addition, DMCs partially digested with MMP-20 stimulated tertiary dentin formation in vivo, which exhibited a more regular tubular structure than that induced by treatment with other MMPs. Our results indicate that MMP-20 may be especially effective in stimulating wound healing of the dentin-pulp complex.

2019 ◽  
Vol 19 (8) ◽  
pp. 647-656 ◽  
Author(s):  
Gatta Daniela Maria Pia ◽  
Franceschelli Sara ◽  
Felaco Mario ◽  
Speranza Lorenza

Medicinal plants and their natural bioactive molecules, are evaluated as the foundation for health preservation and care of humanity. The licorice root, known as “Radix Glycyrrhizae”, is a perennial plant that comes from Mediterranean countries, central to southern Russia, Asia, Turkey, Iraq and Iran. The licorice root has been used in traditional Chinese medicines for centuries and has been defined as "the progenitor of herbs". The name 'Licorice' is derived from the ancient Greek word Glukurrhiza, meaning 'sweet root'. It consists of approximately 30 species, however, the most common ones consist of Glycyrrhiza glabra L., Glycyrrhiza uralensis Fisch and Glycyrrhiza Inflata. In addition, the licorice root contains chalcones, which are a part of an important class of natural products and are precursors of flavonoids. Chemically, chalcones are composed of two aromatic rings associated with α, β-unsaturated α-carbon ketone, representing the prima nucleus of the structure. They have been classified, according to chemical structures, in Licochalcone A, B, C, D, E, F and G. This review aims to highlight all the in vitro and in vivo studies that have been conducted on the licochalcones, extracted from Glycyrrhiza species. The main effects are as follows: anti-inflammatory, antioxidant, anticancer, antimicrobial, antiviral, antiallergic, antidiabetic, hepatotoxic and osteogenic. It is important to implement the introduction of biologically active natural molecules from the bench (research) to the bedside (clinical practice). However, in the future, it is required to conduct additional studies to validate these biological effects.


2021 ◽  
Vol 8 ◽  
Author(s):  
Alfredo Ayala-Ham ◽  
Jorge López-Gutierrez ◽  
Mercedes Bermúdez ◽  
Maribel Aguilar-Medina ◽  
Juan Ignacio Sarmiento-Sánchez ◽  
...  

Regenerative therapy in dentistry has gained interest given the complexity to restore dental and periodontal tissues with inert materials. The best approach for regeneration requires three elements for restoring functions of affected or diseased organ tissues: cells, bioactive molecules, and scaffolds. This triad is capable of modulating the processes to replace lost or damaged tissues and restore function, as it has an impact on diverse cellular processes, influencing cell behavior positively to induce the complete restoration of function and morphology of such complex tissues. Hydrogels (HG) have shown advantages as scaffolds as they are soft and elastic three-dimensional (3D) networks formed from hydrophilic homopolymers, copolymers, or macromers. Besides simple or hybrid, HG show chemical, mechanical and biological activities such as the incorporation of cells in their structures, the retention of high-water content which enhances the transportation of cell nutrients and waste, and elastic and flexible characteristics that emulate the native extracellular matrix (ECM). HG can induce changes in cellular processes such as chemotaxis, proliferation, angiogenesis, biomineralization, and expression of specific tissue biomarkers, enhancing the regeneration process. Besides some of them have anti-inflammatory and anti-bacterial effects. This review aims to show an extensive overview of the most used hydrogels in tissue engineering, emphasizing those that are studied for the regeneration of oral tissues, their biological effects, and their clinical implications. Even though most of the HG are still under investigation, some of them have been studied in vitro and in vivo with outstanding results that may lead to preclinical studies. Besides there are HG that have shown their efficacy in patients such as hyaluronan HG that enhances the healing of gingival tissue.


2007 ◽  
Vol 86 (10) ◽  
pp. 968-973 ◽  
Author(s):  
J.S. Song ◽  
A. Wlodarska ◽  
H.J. Ko ◽  
W.J. Grzesik

The regeneration of structurally/functionally competent tooth root cementum is a critical step for the successful restoration of periodontal attachment. In this study, we tested whether a poly-glutamic acid-rich domain and glutamine-containing transglutaminase substrate can be used to target biologically active peptides to the mineralized root matrix and to bind such peptides covalently to the organic matrix. As a biologically active model molecule, the integrin-binding motif, RGD, was used. The effects of immobilization of such synthetic peptides to the dentin matrix on cementoblastic adhesion in vitro and cementogenesis in vivo were studied. In vitro, cementoblastic adhesion improved significantly when the dentin surface contained covalently bound peptides. In vivo, this bound peptide significantly increased cementum formation compared with that attained in control conditions. Transglutaminase-catalyzed covalent binding of bioactive peptides targeted to mineralized collagenous dentin matrix via the poly-glutamate domain can be readily achieved. This approach offers potential for clinical use in periodontal regeneration.


Materials ◽  
2019 ◽  
Vol 12 (6) ◽  
pp. 970 ◽  
Author(s):  
Witold Sujka ◽  
Zbigniew Draczynski ◽  
Beata Kolesinska ◽  
Ilona Latanska ◽  
Zenon Jastrzebski ◽  
...  

In spite of intensively conducted research allowing for the development of more and more advanced wound dressing materials, there is still a need for dressings that stimulate not only reparative and regenerative processes, but also have a positive effect on infected and/or difficult-to-heal wounds. Porous dressing materials based on butyric-acetic chitin co-polyester containing 90% of butyryl and 10% of acetyl groups (BAC 90/10) can also be included in the group mentioned above. Two types of dressings were obtained by the salt leaching method, i.e. a porous sponge Medisorb R and Medisorb Ag with an antibacterial additive. The aim of the study was to evaluate biological effects of porous Medisorb R and Medisorb Ag dressings under in vitro and in vivo conditions. In an in vitro biodegradation test, no mass loss of Medisorb R dressing was observed within 14 days of incubation in physiological fluids at 37 °C. However, on the basis of the FTIR (Fourier Transform Infrared Spectroscopy) tests, surface degradation of Medisorb R dressing was observed. Additionally, the antibacterial activity of the porous Medisorb Ag dressing containing microsilver as an antibacterial additive was confirmed. The in vivo studies included inflammatory activity, skin irritation and sensitisation tests, as well an assessment of local effect after contact with subcutaneous tissue up to 6 months and skin wounds up to 21 days. In the in vivo tests, the dressings exhibited neither effects of skin irritation nor sensitisation. Under macroscopic examination, in full thickness defects of subcutaneous tissue and skin, the dressings caused wound healing with no inflammation, undergoing the most gradual biodegradation between weeks 4 and 8, and the observed differences were statistically significant. In the histological assessment, a weakened, limited inflammatory process associated with degradation of the material has been observed. The process of skin wound healing under Medisorb R dressing in the early period was accelerated compared to that observed in the control group with a gauze dressing.


2019 ◽  
Vol 6 (10) ◽  
pp. 182104
Author(s):  
Qian Wu ◽  
Tiantian Shan ◽  
Manduo Zhao ◽  
Sui Mai ◽  
Lisha Gu

The biomimetic remineralization of collagen fibrils has increased interest in restoring the demineralized dentine generated by dental caries. Carboxyl-terminated polyamidoamine dendrimers (PAMAM-COOH), hyperbranched polymeric macromolecules, can act as non-collagenous proteins to induce biomimetic remineralization on a dentine organic matrix. However, in vivo remineralization is an extremely time-consuming process; before complete remineralization, demineralized dentine collagen fibrils are susceptible to degradation by host-derived matrix metalloproteinases (MMPs). Therefore, we examined the effect of fourth-generation PAMAM-COOH (G4-PAMAM-COOH) on the collagenolytic activities of endogenous MMPs, the interaction between G4-PAMAM-COOH and demineralized dentine collagen and the influence of G4-PAMAM-COOH pre-treatment on resin–dentine bonding. G4-PAMAN-COOH not only inhibited exogenous soluble rhMMP9 but also hampered the proteolytic activities of dentine collagen-bound MMPs. Cooperated with the results of G4-PAMAM-COOH absorption and desorption, FTIR spectroscopy provided evidence for the exclusive electrostatic interaction rather than hydrogen or covalent bonding between G4-PAMAM-COOH and dentine collagen. Furthermore, G4-PAMAM-COOH pre-treatment showed no damage to resin–dentine bonding because it did not significantly decrease the elastic modulus of the demineralized dentine, degree of conversion, penetration of the adhesive into the dentinal tubules or ultimate tensile strength. Thus, G4-PAMAM-COOH can effectively inactivate MMPs, retard the enzymolysis of collagen by MMPs and scarcely influence the application of resin–dentine bonding.


Foods ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Rosalba Leuci ◽  
Leonardo Brunetti ◽  
Viviana Poliseno ◽  
Antonio Laghezza ◽  
Fulvio Loiodice ◽  
...  

Secondary metabolites from plants and fungi are stimulating growing interest in consumers and, consequently, in the food and supplement industries. The beneficial effects of these natural compounds are being thoroughly studied and there are frequent updates about the biological activities of old and new molecules isolated from plants and fungi. In this article, we present a review of the most recent literature regarding the recent discovery of secondary metabolites through isolation and structural elucidation, as well as the in vitro and/or in vivo evaluation of their biological effects. In particular, the possibility of using these bioactive molecules in the prevention and/or treatment of widely spread pathologies such as cardiovascular and neurodegenerative diseases is discussed.


Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2319
Author(s):  
Ruth Naomi ◽  
Hasnah Bahari ◽  
Pauzi Muhd Ridzuan ◽  
Fezah Othman

Collagen (Col) and gelatin are most extensively used in various fields, particularly in pharmaceuticals and therapeutics. Numerous researchers have proven that they are highly biocompatible to human tissues, exhibit low antigenicity and are easy to degrade. Despite their different sources both Col and gelatin have almost the same effects when it comes to wound healing mechanisms. Considering this, the bioactivity and biological effects of both Col and gelatin have been, and are being, constantly investigated through in vitro and in vivo assays to obtain maximum outcomes in the future. With regard to their proven nutritional values as sources of protein, Col and gelatin products exert various possible biological activities on cells in the extracellular matrix (ECM). In addition, a vast number of novel Col and gelatin applications have been discovered. This review compared Col and gelatin in terms of their structures, sources of derivatives, physicochemical properties, results of in vitro and in vivo studies, their roles in wound healing and the current challenges in wound healing. Thus, this review provides the current insights and the latest discoveries on both Col and gelatin in their wound healing mechanisms.


Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 572
Author(s):  
Chunsong Yu ◽  
Myunggi An ◽  
Meng Li ◽  
Charles Manke ◽  
Haipeng Liu

Cell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug cargos. Noncovalent insertion of lipid-based amphiphilic molecules on the cell surface is a rapid and nontoxic approach for modifying cells with a variety of bioactive molecules without affecting the cellular functions and viability. A wide variety of lipid amphiphiles, including proteins/peptides, carbohydrates, oligonucleotides, drugs, and synthetic polymers have been designed to spontaneously anchor on the plasma membranes. These molecules typically contain a functional component, a spacer, and a long chain diacyl lipid. Though these molecular constructs appeared to be stably tethered on cell surfaces both in vitro and in vivo under static situations, their stability under mechanical stress (e.g., in the blood flow) remains unclear. Using diacyl lipid-polyethylene glycol (lipo-PEG) conjugates as model amphiphiles, here we report the effect of molecular structures on the amphiphile stability on cell surface under mechanical stress. We analyzed the retention kinetics of lipo-PEGs on erythrocytes in vitro and in vivo and found that under mechanical stress, both the molecular structures of lipid and the PEG spacer have a profound effect on the membrane retention of membrane-anchored amphiphiles. Our findings highlight the importance of molecular design on the dynamic stability of membrane-anchored amphiphiles.


2021 ◽  
Vol 11 (17) ◽  
pp. 7769
Author(s):  
Mohammad Foad Abazari ◽  
Shayan Gholizadeh ◽  
Shohreh Zare Karizi ◽  
Nazanin Hajati Birgani ◽  
Danya Abazari ◽  
...  

Application of wound-healing/dressing biomaterials is amongst the most promising approaches for wound repair through protection from pathogen invasion/contamination, maintaining moisture, absorbing exudates, modulating inflammation, and facilitating the healing process. A wide range of materials are used to fabricate wound-healing/dressing biomaterials. Active wound-healing/dressings are next-generation alternatives for passive biomaterials, which provide a physical barrier and induce different biological activities, such as antibacterial, antioxidant, and proliferative effects. Cellulose-based biomaterials are particularly promising due to their tunable physical, chemical, mechanical, and biological properties, accessibility, low cost, and biocompatibility. A thorough description and analysis of wound-healing/dressing structures fabricated from cellulose-based biomaterials is discussed in this review. We emphasize and highlight the fabrication methods, applied bioactive molecules, and discuss the obtained results from in vitro and in vivo models of cellulose-based wound-healing biomaterials. This review paper revealed that cellulose-based biomaterials have promising potential as the wound-dressing/healing materials and can be integrated with various bioactive agents. Overall, cellulose-based biomaterials are shown to be effective and sophisticated structures for delivery applications, safe and multi-customizable dressings, or grafts for wound-healing applications.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ahmed Alafnan ◽  
Swathi Sridharagatta ◽  
Hammad Saleem ◽  
Umair Khurshid ◽  
Abdulwahab Alamri ◽  
...  

Traditionally, plants of the genus Calotropis have been used to cure various common diseases. The present research work explores the chemical and biological characterization of one of the most common species of this genus, i.e., Calotropis gigantea (L.) Dryand (syn. Calotropis gigantea (L.) Dryand.), having multiple folklore applications. The ethanolic extract of leaves of Calotropis gigantea (L.) Dryand was analyzed for the phytochemical composition by determining the total bioactive (total phenolic and total flavonoid) contents and UHPLC-MS secondary metabolites analysis. For phytopharmacological evaluation, in vitro antioxidant (including DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation antioxidant assays) activities, enzyme inhibition potential (against AChE, BChE, α-amylase, and tyrosinase enzymes), and in vivo wound healing potential were determined. The tested extract has been shown to contain considerable flavonoid (46.75 mg RE/g extract) and phenolic (33.71 mg GAE/g extract) contents. The plant extract presented considerable antioxidant potential, being the most active for CUPRAC assays. Secondary metabolite UHPLC-MS characterization, in both the positive and negative ionization modes, indicated the tentative presence of 17 different phytocompounds, mostly derivatives of sesquiterpene, alkaloids, and flavonoids. Similarly, the tested extract exhibited considerable inhibitory effects on tyrosinase (81.72 mg KAE/g extract), whereas it showed weak inhibition ability against other tested enzymes. Moreover, in the case of in vivo wound healing assays, significant improvement in wound healing was observed in both the tested models at the doses of 0.5 percent w/w (p < 0.001) and 2.0 percent w/w (p < 0.01) on the 16th day. The outcomes of the present research work suggested that C. gigantea (L.) Dryand plant extract could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.


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