scholarly journals Cyclodextrin-Based Supramolecular Complexes of Osteoinductive Agents for Dental Tissue Regeneration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 136
Author(s):  
Masahiko Terauchi ◽  
Atsushi Tamura ◽  
Yoshinori Arisaka ◽  
Hiroki Masuda ◽  
Tetsuya Yoda ◽  
...  
Keyword(s):  
Growth Factors ◽  
Bone Formation ◽  
Small Molecule ◽  
Tissue Regeneration ◽  
Alveolar Bone ◽  
Inclusion Complexation ◽  
Dental Tissue ◽  
Polyelectrolyte Complexes ◽  
Small Molecule Drugs

Oral tissue regeneration has received growing attention for improving the quality of life of patients. Regeneration of oral tissues such as alveolar bone and widely defected bone has been extensively investigated, including regenerative treatment of oral tissues using therapeutic cells and growth factors. Additionally, small-molecule drugs that promote bone formation have been identified and tested as new regenerative treatment. However, treatments need to progress to realize successful regeneration of oral functions. In this review, we describe recent progress in development of regenerative treatment of oral tissues. In particular, we focus on cyclodextrin (CD)-based pharmaceutics and polyelectrolyte complexation of growth factors to enhance their solubility, stability, and bioactivity. CDs can encapsulate hydrophobic small-molecule drugs into their cavities, resulting in inclusion complexes. The inclusion complexation of osteoinductive small-molecule drugs improves solubility of the drugs in aqueous solutions and increases in vitro osteogenic differentiation efficiency. Additionally, various anionic polymers such as heparin and its mimetic polymers have been developed to improve stability and bioactivity of growth factors. These polymers protect growth factors from deactivation and degradation by complex formation through electrostatic interaction, leading to potentiation of bone formation ability. These approaches using an inclusion complex and polyelectrolyte complexes have great potential in the regeneration of oral tissues.

scholarly journals A Graded Multifunctional Hybrid Scaffold with Superparamagnetic Ability for Periodontal Regeneration

2018 ◽  
Vol 19 (11) ◽  
pp. 3604 ◽  
Author(s):  
Simone Sprio ◽  
Elisabetta Campodoni ◽  
Monica Sandri ◽  
Lorenzo Preti ◽  
Tobias Keppler ◽  
...  
Keyword(s):  
Cell Fate ◽  
Alveolar Bone ◽  
Tape Casting ◽  
Periodontal Regeneration ◽  
Dental Tissue ◽  
Hybrid Scaffold ◽  
Dental Tissues ◽  
Biomineralization Process ◽  
Direct Cell

The regeneration of dental tissues is a still an unmet clinical need; in fact, no therapies have been completely successful in regenerating dental tissue complexes such as periodontium, which is also due to the lack of scaffolds that are able to guide and direct cell fate towards the reconstruction of different mineralized and non-mineralized dental tissues. In this respect, the present work develops a novel multifunctional hybrid scaffold recapitulating the different features of alveolar bone, periodontal ligament, and cementum by integrating the biomineralization process, and tape casting and electrospinning techniques. The scaffold is endowed with a superparamagnetic ability, thanks to the use of a biocompatible, bioactive superparamagnetic apatite phase, as a mineral component that is able to promote osteogenesis and to be activated by remote magnetic signals. The periodontal scaffold was obtained by engineering three different layers, recapitulating the relevant compositional and microstructural features of the target tissues, into a monolithic multifunctional graded device. Physico-chemical, morphological, and ultrastructural analyses, in association with preliminary in vitro investigations carried out with mesenchymal stem cells, confirm that the final scaffold exhibits a good mimicry of the periodontal tissue complex, with excellent cytocompatibility and cell viability, making it very promising for regenerative applications in dentistry.

scholarly journals Sol-Gel Derived Mg-Based Ceramic Scaffolds Doped with Zinc or Copper Ions: Preliminary Results on Their Synthesis, Characterization, and Biocompatibility

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Georgios S. Theodorou ◽  
Eleana Kontonasaki ◽  
Anna Theocharidou ◽  
Athina Bakopoulou ◽  
Maria Bousnaki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tissue Regeneration ◽  
Copper Ions ◽  
Sol Gel ◽  
Antimicrobial Properties ◽  
Biological Response ◽  
Oral Bacteria ◽  
Dental Tissue ◽  
Bioactive Scaffolds

Glass-ceramic scaffolds containing Mg have shown recently the potential to enhance the proliferation, differentiation, and biomineralization of stem cells in vitro, property that makes them promising candidates for dental tissue regeneration. An additional property of a scaffold aimed at dental tissue regeneration is to protect the regeneration process against oral bacteria penetration. In this respect, novel bioactive scaffolds containing Mg2+and Cu2+or Zn2+, ions known for their antimicrobial properties, were synthesized by the foam replica technique and tested regarding their bioactive response in SBF, mechanical properties, degradation, and porosity. Finally their ability to support the attachment and long-term proliferation of Dental Pulp Stem Cells (DPSCs) was also evaluated. The results showed that conversely to their bioactive response in SBF solution, Zn-doped scaffolds proved to respond adequately regarding their mechanical strength and to be efficient regarding their biological response, in comparison to Cu-doped scaffolds, which makes them promising candidates for targeted dental stem cell odontogenic differentiation and calcified dental tissue engineering.

Bone Regenerative Properties of Injectable Calcium Phosphate/PLGA Cement in an Alveolar Bone Defect

2012 ◽  
Vol 529-530 ◽  
pp. 300-303 ◽  
Author(s):  
R.P. Félix Lanao ◽  
J.W.M. Hoekstra ◽  
Joop G.C. Wolke ◽  
Sander C.G. Leeuwenburgh ◽  
A.S. Plachokova ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Calcium Phosphate ◽  
Bone Formation ◽  
Bone Substitute ◽  
Alveolar Bone ◽  
Bone Defects ◽  
Plga Microspheres ◽  
Bone Substitute Material ◽  
Substitute Material

Periodontitis is one of the most common inflammatory diseases, which can lead to early tooth loss. The conventional treatment of periodontitis is to arrest the disease progression. Most reconstructive procedures involve application of bone substitutes, barrier membranes or a combination of both into the bony defects. Calcium phosphate cements (CPCs) are the predominant type of bone substitute material used for reasons of injectability and hence perfect filling potential for bone defects. Recently, injectable apatitic CPCs demonstrated to be more rapidly degradable when combined with poly (lactic-co-glycolic) acid (PLGA) microspheres. Further, PLGA microspheres can be used as a delivery vehicle for growth factors. In this study, the performance of injectable CPCs as a bone substitute material for alveolar bone defects created in Beagle dogs was evaluated. Four CPC-formulations were generated by incorporating hollow or dense PLGA microspheres, either or not loaded with the growth factors (platelet derived growth factor (PDGF) and insulin-like growth factor (IGF). Implantation period was 8 weeks. Bone formation was based on histological and histomorphometrical evaluation. The results demonstrated that filling alveolar bone defects with CPC-dense PLGA revealed significant more bone formation compared to CPC-hollow PLGA either or not loaded with IGF and PDGF. In summary, we conclude that injectable CPC-dense PLGA composites proved to be the most suitable material for a potential use as off the shelf material due to its good biocompatibility, enhanced degradability and subsequent bone formation.

scholarly journals Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
James O’Connell ◽  
John Porter ◽  
Boris Kroeplien ◽  
Tim Norman ◽  
Stephen Rapecki ◽  
...  
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Protein Interactions ◽  
General Mechanism ◽  
Protein Protein Interactions ◽  
Biologic Drugs ◽  
Small Molecule Drugs ◽  
Necrosis Factor

AbstractTumour necrosis factor (TNF) is a cytokine belonging to a family of trimeric proteins; it has been shown to be a key mediator in autoimmune diseases such as rheumatoid arthritis and Crohn’s disease. While TNF is the target of several successful biologic drugs, attempts to design small molecule therapies directed to this cytokine have not led to approved products. Here we report the discovery of potent small molecule inhibitors of TNF that stabilise an asymmetrical form of the soluble TNF trimer, compromising signalling and inhibiting the functions of TNF in vitro and in vivo. This discovery paves the way for a class of small molecule drugs capable of modulating TNF function by stabilising a naturally sampled, receptor-incompetent conformation of TNF. Furthermore, this approach may prove to be a more general mechanism for inhibiting protein–protein interactions.

scholarly journals Current Insight of Collagen Biomatrix for Gingival Recession: An Evidence-Based Systematic Review

Polymers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2081
Author(s):  
Ruth Naomi ◽  
Retno Ardhani ◽  
Osa Amila Hafiyyah ◽  
Mh Busra Fauzi
Keyword(s):  
Systematic Review ◽  
Tissue Regeneration ◽  
Literature Search ◽  
Gingival Recession ◽  
Current Treatment ◽  
Gingival Tissue ◽  
Dental Tissue ◽  
Comprehensive Literature Search

Collagen (Col) is a naturally available material and is widely used in the tissue engineering and medical field owing to its high biocompatibility and malleability. Promising results on the use of Col were observed in the periodontal application and many attempts have been carried out to inculcate Col for gingival recession (GR). Col is found to be an excellent provisional bioscaffold for the current treatment in GR. Therefore, the aim of this paper is to scrutinize an overview of the reported Col effect focusing on in vitro, in vivo, and clinical trials in GR application. A comprehensive literature search was performed using EBSCOhost, Science Direct, Springer Link, and Medline & Ovid databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) collagen OR scaffold OR hybrid scaffold OR biomaterial AND (2) gingiva recession OR tissue regeneration OR dental tissue OR healing mechanism OR gingiva. Only articles published from 2015 onwards were selected for further analysis. This review includes the physicochemical properties of Col scaffold and the outcome for GR. The comprehensive literature search retrieved a total of 3077 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 15 articles were chosen for further review. The results from these articles indicated that Col promoted gingival tissue regeneration for GR healing. Therefore, this systematic review recapitulated that Col enhances regeneration of gingival tissue either through a slow or rapid process with no sign of cytotoxicity or adverse effect.

scholarly journals Bioactive Synthetic Peptides for Oral Tissues Regeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Mercedes Bermúdez ◽  
Lía Hoz ◽  
Gonzalo Montoya ◽  
Mikado Nidome ◽  
Adriana Pérez-Soria ◽  
...  
Keyword(s):  
Tissue Regeneration ◽  
Synthetic Peptides ◽  
Alveolar Bone ◽  
Biological Effects ◽  
The Body ◽  
Bioactive Molecules ◽  
Tissue Loss ◽  
Complex Nature ◽  
Major Health Problem

Regenerative therapy in oral tissues has gained relevance since tissue loss due to congenital or acquired diseases as well as trauma is a major health problem worldwide. Regeneration depends on the natural capacity of the body and the use of biomaterials and bioactive molecules that can module the processes to replace lost or damaged tissues and restore function. The combined use of scaffolds, cells, and bioactive molecules such as peptides is considered the best approach to achieve tissue regeneration. These peptides can induce diverse cellular processes as they can influence cell behavior and also can modify scaffold properties, giving as a result the enhancement of cell adhesion, proliferation, migration, differentiation, and biomineralization that are required given the complex nature of oral tissues. Specifically, synthetic peptides (SP) have a positive influence on scaffold biocompatibility since in many cases they can mimic the function of a natural peptide or a full-length protein. Besides, they are bioactive molecules easy to produce, process, and modify, and they can be prepared under well-defined and controlled conditions. This review aims to compile the most relevant information regarding advances in SP for dental and periodontal tissue regeneration, their biological effects, and their clinical implications. Even though most of the SP are still under investigation, some of them have been studied in vitro and in vivo with promising results that may lead to preclinical studies. Besides there are SP that have shown their efficacy in clinical trials such as P11-4 for enamel regeneration or caries prevention and ABM/P-15 for cementum, periodontal ligament (PDL), and alveolar bone on a previously calculus- and biofilm-contaminated zone. Also, some SP are commercially available such as PTH1-34 and PepGen P-15 which are used for bone defects treatment.

scholarly journals Comparative Analysis of Proliferation and Differentiation Potentials of Stem Cells from Inflamed Pulp of Deciduous Teeth and Stem Cells from Exfoliated Deciduous Teeth

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Shi Yu ◽  
Shu Diao ◽  
Jinsong Wang ◽  
Gang Ding ◽  
Dongmei Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tissue Regeneration ◽  
Deciduous Teeth ◽  
Inflammatory Factors ◽  
Dental Tissue ◽  
Significant Difference ◽  
Proliferation And Differentiation ◽  
Cell Sources ◽  
Irreversible Pulpitis

Stem cells isolated from exfoliated deciduous teeth (SHEDs) are highly capable of proliferation and differentiation, and they represent good cell sources for mesenchymal stem cell- (MSC-) mediated dental tissue regeneration, but the supply of SHEDs is limited. A previous study found that stem cells could be isolated from inflamed tissues, but it is unknown whether primary dental pulp diagnosed with irreversible pulpitis might contain stem cells with appropriate tissue regeneration capacity. In this study, we aimed to isolate stem cells from both inflamed pulps of deciduous teeth (SCIDs) and SHEDs from Chinese children and to compare their proliferation and differentiation potentials. Our results showed that SCIDs were positive for cell surface markers, including CD105, CD90, and CD146, and they had high proliferation ability and osteogenic, adipogenic, and chondrogenic differentiation potentials. There was no significant difference in proliferation and differentiation potentials between SCIDs and SHEDs. The mRNA of inflammatory factors, including IL-1β, IL-6, and TNF-α, was expressed at similar levels in SCIDs and SHEDs, but SCIDs secreted more TNF-αprotein. In conclusion, ourin vitroresults showed that SCIDs have proliferation and differentiation potentials similar to those of SHEDs. Thus, SCIDs represent a new potentially applicable source for MSC mediated tissue regeneration.

scholarly journals Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms

2020 ◽  
Author(s):  
Ana C. Puhl ◽  
Ethan James Fritch ◽  
Thomas R. Lane ◽  
Longping V. Tse ◽  
Boyd L. Yount ◽  
...  
Keyword(s):  
Cell Lines ◽  
Small Molecule ◽  
Ebola Virus ◽  
Early Stage ◽  
Drug Repurposing ◽  
Marburg Virus ◽  
Small Molecule Drugs ◽  
Speed Up

AbstractSARS-CoV-2 is a newly identified virus that has resulted in over 1.3 M deaths globally and over 59 M cases globally to date. Small molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shown in vitro activity against Ebola virus and demonstrated activity against SARS-CoV-2 in vivo. Most notably the RNA polymerase targeting remdesivir demonstrated activity in vitro and efficacy in the early stage of the disease in humans. Testing other small molecule drugs that are active against Ebola virus would seem a reasonable strategy to evaluate their potential for SARS-CoV-2. We have previously repurposed pyronaridine, tilorone and quinacrine (from malaria, influenza, and antiprotozoal uses, respectively) as inhibitors of Ebola and Marburg virus in vitro in HeLa cells and of mouse adapted Ebola virus in mouse in vivo. We have now tested these three drugs in various cell lines (VeroE6, Vero76, Caco-2, Calu-3, A549-ACE2, HUH-7 and monocytes) infected with SARS-CoV-2 as well as other viruses (including MHV and HCoV 229E). The compilation of these results indicated considerable variability in antiviral activity observed across cell lines. We found that tilorone and pyronaridine inhibited the virus replication in A549-ACE2 cells with IC50 values of 180 nM and IC50 198 nM, respectively. We have also tested them in a pseudovirus assay and used microscale thermophoresis to test the binding of these molecules to the spike protein. They bind to spike RBD protein with Kd values of 339 nM and 647 nM, respectively. Human Cmax for pyronaridine and quinacrine is greater than the IC50 hence justifying in vivo evaluation. We also provide novel insights into their mechanism which is likely lysosomotropic.

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