Desirability function approach for development of a thermosensitive and bioadhesive nanotransfersome-hydrogel hybrid system for enhanced skin bioavailability and antibacterial activity of cephalexin.

Cellulitis is a common bacterial infection of the skin and soft tissues immediately beneath the skin. Despite the successful use of antibiotics in the treatment of infectious diseases, bacterial infections continue to impose significant global health challenges because of the rapid emergence of antibiotic resistance. The aim of this work was to develop an in situ hydrogel forming system containing highly permeable cephalexin-loaded nanotransfersomes (NTs), suitable for antibacterial drug delivery. Response surface design was applied for the optimization of NTs. Cephalexin NTs were prepared using thin-film hydration method and then embedded into a 3D hydrogel network. The in vitro antibacterial activity of the optimized NTs was assayed against indicator bacteria of Staphylococcus aureus (S. aureus). The drug permeation was evaluated using an ex vivo rat skin model. The in vivo efficacy of the cephalexin NT hydrogel was also determined against rat skin infection. The resulting data verified the formation of NTs, the size of which was approximately 192 nm. The cephalexin NTs exhibited higher antibacterial activity against S. aureus as compared to the untreated drug. The NT hydrogel improved drug penetration through the skin after 8 h. When applied on the rat skin for 10 days, the cephalexin NT hydrogel exhibited superior antibacterial activity with normal hair growth and skin appearance as compared with the plain drug hydrogel. These findings suggest that the cephalexin NT-hydrogel system can serve as a valuable drug delivery platform against bacterial infections.

The Use of Nanomaterials in Tissue Engineering for Cartilage Regeneration; Current Approaches and Future Perspectives.

The repair and regeneration of articular cartilage represent important challenges for orthopedic investigators and surgeons worldwide due to its avascular, aneural structure, cellular arrangement, and dense extracellular structure. Although abundant efforts have been paid to provide tissue-engineered grafts, the use of therapeutically cell-based options for repairing cartilage remains unsolved in the clinic. Merging a clinical perspective with recent progress in nanotechnology can be helpful for developing efficient cartilage replacements. Nanomaterials, < 100 nm structural elements, can control different properties of materials by collecting them at nanometric sizes. The integration of nanomaterials holds promise in developing scaffolds that better simulate the extracellular matrix (ECM) environment of cartilage to enhance the interaction of scaffold with the cells and improve the functionality of the engineered-tissue construct. This technology not only can be used for the healing of focal defects but can also be used for extensive osteoarthritic degenerative alterations in the joint. In this review paper, we will emphasize the recent investigations of articular cartilage repair/regeneration via biomaterials. Also, the application of novel technologies and materials is discussed.

PLA-PCL-PEG-PCL-PLA based micelles for improving the ocular permeability of dexamethasone: development, characterization, and in vitro evaluation.

The aim of the present research was to investigate the feasibility of developing polylactide-polycaprolactone-polyethylene glycol-polycaprolactone-polylactide (PLA-PCL-PEG-PCL-PLA) based micelles to improve ocular permeability of dexamethasone (DEX). PLA-PCL-PEG-PCL-PLA copolymers were synthesized by a ring-opening polymerization method. DEX was loaded into the developed copolymers. The DEX-loaded micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS) methods. Cytotoxicity of the micelles obtained was investigated on L929 cell line. Cellular uptake was followed by fluorescence microscopy and flow cytometry analyses. The release behavior of DEX from the micelles as well as the drug release kinetics was studied. Corneal permeability was also evaluated using an ex vivo bovine model. The pentablock copolymers were successfully synthesized. The TEM results verified the formation of spherical micelles, the sizes of which was approximately 65 nm. The micelles exhibited suitable compatibility on L929 cells. The release profile showed an initial burst release phase followed by a sustained release phase, the kinetic of which was close to the Weibull's distribution model. The micelles showed higher corneal permeability in comparison to a marketed DEX eye drop. Taken together, the results indicated that the PLA-PCL-PEG-PCL-PLA micelles could be appropriate candidates for the ocular delivery of DEX, and probably other hydrophobic drugs.

Evaluation of anti-inflammatory impact of dexamethasone-loaded PCL-PEG-PCL micelles on endotoxin-induced uveitis in rabbits.

The aim of this study was to investigate the capability of polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles in improving the anti-inflammatory effects of dexamethasone (DEX). A film hydration method was used for the preparation of the DEX-loaded PCL-PEG-PCL micelles. In vitro cytotoxicity of the micelles obtained was investigated on L929 cells. Cellular uptake was studied by using flow cytometry and fluorescence microscopy. Anterior uveitis was induced in a group of rabbits by intravitreal injection of endotoxin from Salmonella typhimurium. The severity of inflammation-induced was clinically graded by using Hogan's classification method. Protein concentration in the aqueous humor was also measured. The micelles exhibited suitable compatibility on L929 cells and were taken up by the cells in a concentration- and time-dependent manner. The DEX-loaded micelles could reduce the clinical symptoms of uveitis after a lag-time. At 24 and 36 h after the LPS injection, the PCL-PEG-PCL micelles showed a better inhibitory effect on uveitis than the marketed eye drop, the differences did not reach significant levels though. This study demonstrated the potential of the PCL-PEG-PCL micelles as carriers for DEX in treating anterior uveitis. However, this concept is still to be further investigated.

Box-Behnken experimental design for preparation and optimization of the intranasal gels of selegiline hydrochloride.

Selegiline hydrochloride (SL) is chosen as an adjunct for the control of clinical signs of Parkinsonian patients. The aim of the present work is to develop and optimize thermosensitive gels using Pluronic (F-127) for enhancing transport of SL into the brain through the nasal route. SL gels were prepared using a cold method and the Box-Behnken experimental design methodology. Drug (SL), gelling agent (F-127), and emulsifier (Propylene glycol, PG) were selected as independent variables, while the gelation temperature, gel strength, pH, gel content, and gel erosion were considered as dependent variables. For further understanding of the interaction between the various variables, contour plots and surface plots were also applied. Selected formulations, like S10 (contain 25 mg SL, 20 g F-127, and 1 g PG) and S14 (contain 50 mg SL, 18 g F-127 and 1 g PG), had a clear appearance in the sol form, with gelling temperature of the nasal gel ranging between 33 and 34, respectively. The gel strength of the formulations varied from 4.67 and 0.68 mm and the drug content was 100%. The pH of the formulations ranged between 6.71 and 7.11. Detachment force was acceptable (63.69-244.16 N/cm2) to provide prolonged adhesion. In vitro, drug release studies showed that the prepared formulations could release SL for up to 8 h. Permeation flux for the S10 gel was 0.0002 mg/min/cm2. Results demonstrated that the potential use of SL gels can enhance the therapeutic effect of SL through the intranasal administration.

Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles.

Nanoparticulate drug/gene carriers have gained much attention in the past decades because of their versatile and tunable properties. However, efficacy of the therapeutic agents can be further enhanced using naturally occurring materials-based nanoparticles. Polysaccharides are an emerging class of biopolymers; therefore, they are generally considered to be safe, non-toxic, biocompatible and biodegradable. Considering that the target of nanoparticle-based therapeutic strategies is localization of biomedical agents in subcellular compartments, a detailed understanding of the cellular mechanism involved in the uptake of polysaccharide-based nanoparticles is essential for safe and efficient therapeutic applications. Uptake of the nanoparticles by the cellular systems occurs with a process known as endocytosis and is influenced by the physicochemical characteristics of nanoparticles such as size, shape and surface chemistry as well as the employed experimental conditions. In this study, we highlight the main endocytosis mechanisms responsible for the cellular uptake of polysaccharide nanoparticles containing drug/gene.

Effect of the surface modification, size, and shape on cellular uptake of nanoparticles.

Nowadays successful application of nanoparticles for therapeutic objects needs the effective uptake of them by cells. Hence, studying of the interaction of nanoparticles with cell membrane for effective cellular uptaking seems to be vital and important. Trafficking of lipids, proteins, glucose, and other biomaterials into the cells is possible from two major exocytic and endocytic pathways. The penetration ability of nanoparticles into the cells must be considered in engineering of these particles. Enormous in vivo and in vitro experiments in the field of nanotechnology have confirmed the effect of physiochemistry properties in state of cell-nanoparticles interactions. Thus, the optimization of parameters directly related to physicochemical characteristics through the preparation process seems to be necessary for improving therapeutic effects of nanocarriers. Besides, biological medium and cell division also affect the amount of nanoparticle uptaking into the cells. This study reviews the influence of size, shape, the surface modification of nano particles, medium, and cell division effects on the cellular absorption of drug/gene nanocarriers.

Magnetic hybrid nanovesicles for the precise diagnosis and treatment of central nervous system disorders.

INTRODUCTION: Central nervous system (CNS)-related disorders are increasingly being recognized as a global health challenge worldwide. There are significant challenges for effective diagnosis and treatment due to the presence of the CNS barriers which impede the management of neurological diseases. Combination of nanovesicles (NVs) and magnetic nanoparticles (MNPs), referred to as magnetic nanovesicles (MNVs), is now well suggested as a potential theranostic option for improving the management of neurological disorders with increased targeting efficiency and minimized side effects. AREAS COVERED: This review provides a summary of major CNS disorders and the physical barriers limiting the access of imaging/therapeutic agents to the CNS environment. A special focus on the unique features of MNPs and NV is discussed which make them attractive candidates for neuro-nanomedicine. Furthermore, a deeper understanding of MNVs as a promising combined strategy for diagnostic and/or therapeutic purposes in neurological disorders is provided. EXPERT OPINION: The multifunctionality of MNVs offers the ability to overcome the CNS barriers and can be used to monitor the effectiveness of treatment. The insights provided will guide future research toward better outcomes and facilitate the development of next-generation, innovative treatments for CNS disorders.

Nanoparticle and Stem Cell Combination Therapy for the Management of Stroke.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, the available treatments for stroke are still extremely limited. Indeed, stem cell (SC) therapy is a new option for the treatment of stroke that could significantly expand the therapeutic time window of stroke. Some proposed mechanisms for stroke-based SC therapy are the incorporation of SCs into the host brain to replace dead or damaged cells/tissues. Moreover, acute cell delivery can inhibit apoptosis and decrease lesion size, providing immunomudolatory and neuroprotection effects. However, several major SC problems related to SCs such as homing, viability, uncontrolled differentiation, and possible immune response, have limited SC therapy. A combination of SC therapy with nanoparticles (NPs) can be a solution to address these challenges. NPs have received considerable attention in regulating and controlling the behavior of SCs because of their unique physicochemical properties. By reviewing the pathophysiology of stroke and the therapeutic benefits of SCs and NPs, we hypothesize that combined therapy will offer a promising future in the field of stroke management. In this work, we discuss recent literature in SC research combined with NP-based strategies that may have a synergistic outcome after stroke incidence.

Nanoparticle-based delivery platforms for the enhanced oral delivery of peptides/proteins.

Biopharmaceutical products are currently well-established in nearly all branches of medicine and are believed to have great potential for the treatment of a broad spectrum of diseases. Peptide/protein drugs exhibit a predominant class of new biopharmaceuticals coming on the market in recent years. Oral delivery of peptides/proteins as a non-invasive therapeutic technique has become an appealing alternative to the parenteral route. However, the efficient oral delivery of peptides/proteins is limited because of their high molecular weight, poor stability and low biodistribution. Nanoparticles (NPs) have shown excellent results in peptide/protein delivery research. In this paper, the use of NPs as delivery systems for peptides/proteins and their ability to be efficiently delivered via the oral route have been described.

Medicines made from peptides and proteins have become important for treating various diseases. One challenge is delivering them effectively through the mouth, as they can be fragile and may not distribute well in the body. Scientists have been studying the use of tiny particles called nanoparticles (NPs) to help solve these problems. In this article, we explore how NPs can enhance the delivery of peptide/protein medicines when taken orally. By using NPs as delivery platforms, these medicines can be protected and absorbed more efficiently, leading to better treatment outcomes.

Nanocurcumin Release from Self-Cured Acrylic Resins; Effects on Antimicrobial Action and Flexural Strength.

The placement of orthodontic appliances into the oral area can lead to infection, inflammatory and gingival collapse. Using an antimicrobial and anti-inflammatory material in the matrix of orthodontic appliance may help to reduce these issues. This study aimed to assess the release pattern, the antimicrobial action and the flexural strength of self-cured acrylic resins after adding different weight percentages of curcumin nanoparticles (nanocurcumin). In this in-vitro study, 60 acrylic resin samples were divided into five groups (n = 12) based on the weight percentage of curcumin nanoparticles added to the acrylic powder (0 for control, 0.5, 1, 2.5, and 5%). Then, the dissolution apparatus was used for the release assessment of nanocurcumin form the resins. For antimicrobial action assessment, the disk diffusion method was used and a three-point bending test was performed with a speed of 5 mm/min to determine the flexural strength. Data were analyzed using one-way analysis of variance (ANOVA) and Post-Hoc Tukey tests (with p < 0.05 as significant level). The microscopic images showed the homogeny distribution of nanocuricumin in self-cured acrylic resins in varied concentrations. The release pattern showed a two-step release pattern for all concentrations of nanocurcumin. The one-way ANOVA outcomes indicated that adding curcumin nanoparticles to self-cured resin increased the diameter of the inhibition zones for the groups against Streptococcus mutans (S. mutans) significantly (p < 0.0001). Additionally, as the weight percentage of curcumin nanoparticles increased, the flexural strength decreased (p < 0.0001). However, all strength values were higher than the standard value (50 MPa). No significant difference was detected between the control group and the group with 0.5 percent (p = 0.57). Considering the proper release pattern and the potent antimicrobial activity of curcumin nanoparticles, then the preparing self-cured resins containing curcumin nanoparticles can be beneficial for antimicrobial aims without damaging the flexural strength to use in orthodontic removable applications.

Nanoparticle Formulations of Antioxidants for the Management of Oxidative Stress in Stroke: A Review.

Stroke is currently one of the primary causes of morbidity and mortality worldwide. Unfortunately, there has been a lack of effective stroke treatment. Therefore, novel treatment strategies are needed to decrease stroke-induced morbidity and promote the patient's quality of life. Reactive oxygen species (ROS) have been recognized as one of the major causes of brain injury after ischemic stroke. Antioxidant therapy seems to be an effective treatment in the management of oxidative stress relevant to inflammatory disorders like stroke. However, the in vivo efficacy of traditional anti-oxidative substances is greatly limited due to their non-specific distribution and poor localization in the disease region. In recent years, antioxidant nanoparticles (NPs) have demonstrated a clinical breakthrough for stroke treatment. Some NPs have intrinsic antioxidant properties and act as antioxidants to scavenge ROS. Moreover, NPs provide protection to the antioxidant agents/enzymes while effectively delivering them into unreachable areas like the brain. Because of their nanoscale dimensions, NPs are able to efficiently pass through the BBB, and easily reach the damaged site. Here, we discuss the challenges, recent advances, and perspectives of antioxidant NPs in stroke treatment.

Nano-Catechin Gel as a Sustained Release Antimicrobial Agent against Clinically Isolated Porphyromonas gingivalis for Promising Treatment of Periodontal Diseases.

During the last two decades, new drug delivery strategies have been invented that have been able to solve microbial resistance against antibiotics. The goal of the current report was to assess the antimicrobial effects of nano-catechin gels against clinically isolated Porphyromonas gingivalis, one of the main causes of periodontal disease. Catechin-loaded chitosan nanoparticles were prepared by adding a catechin solution to a chitosan solution. Then, the mean particle size and the mean surface charge (zeta potential) of the nanoparticles were detected through photon correlation spectroscopy and zeta sizer, respectively. Nano-catechin gels (1000, 500, 250, 125, 62.5, and 31.2 µg/mL) were prepared, and the antimicrobial assay was performed against clinically isolated Porphyromonas gingivalis (P. gingivalis). The clinically obtained P. gingivalis isolates were obtained from periodontitis patients (N = 15). The consequences are specified as descriptive indices. The normality of data was detected by the Shapiro-Wilk test. Then, to compare the data between groups (with a p value < 0.05 as the significance level), SPSS software (version 22) was used via a Mann-Whitney U test. The results showed a nanometer particle size range and a positive zeta potential for the prepared nanoparticles. All the concentrations (1000, 500, 250, 125, 62.5, and 31.2 µg/mL) of nano-catechin gels showed sustained release patterns and were non-toxic against dental pulp stem cells as well. There were no significant differences between the minimal inhibitory concentrations (MICs) for nano-catechin gel (test group) and Chlorhexidine (control group) against 15 isolates (p > 0.05). Then, two groups showed similar antimicrobial effects. The similar antimicrobial activity of catechin nanoparticles and Chlorhexidine, as a potent antimicrobial agents, against clinically isolated P. gingivalis showed that catechin nanoparticles can be used as a potent antimicrobial material for the treatment of periodontal diseases in the near future.

Gelatin-Curcumin Nanocomposites as a Coating for Implant Healing Abutment: In Vitro Stability Investigation.

Regarding the importance of preventing peri-implantitis in dental implants, the current study aimed to coat a healing abutment with gelatin−curcumin nanocomposites, and the stability of this coating on the healing abutment was evaluated. A cell viability measuring test was used to determine the cytotoxicity of nanocomposites against dental pulp stem cells. To show the pattern of curcumin release from nanocomposites, drug dissolution apparatus two was applied. Then, 16 healing abutments were examined in vitro. Titanium healing abutments were coated with the gelatin−curcumin nanocomposite. The dip coating method was applied for coating and the consistency of coated cases was evaluated at intervals of one, 30, and 60 days after coating inside the simulated body fluid (SBF) solution. A scanning electron microscope (SEM) was used for investigating the microstructure and morphology of coatings, and an energy dispersive X-ray (EDX) was applied for determining the combination of the coating. Moreover, the healings were weighed before and after coating via an accurate digital scale with an accuracy of 0.0001. Finally, the data were analyzed using SPSS software. The prepared nanocomposite was non-cytotoxic against tested cells. The nanocomposite showed a relatively rapid release pattern in the first 10 days for curcumin. The release of curcumin from the nanoparticles continued slowly until the 30th day. The weight changes were statistically significant (p-value < 0.001) during this time. Based on the post hoc test, the weight between two times immediately after coating and 30 days after coating, and also one day after coating and 30 days after coating, was statistically insignificant. The results revealed that the coating of the gelatin−curcumin nanocomposite on the healing was successful and this consistency was kept for at least one month. It is necessary to investigate more evaluations in different fields of physicochemical, mechanical, and antimicrobial aspects for coated healing abutments.

Development and characterization of a novel mucoadhesive sol-gel suppository of sumatriptan: design, optimization, in vitro and ex vivo evaluation for rectal drug delivery.

Aim: Sumatriptan (ST) is used for the treatment of migraine and cluster headaches. However, it exhibits low oral bioavailability (15%) due to the high first-pass metabolism. The aim of this work was to formulate an ST rectal hydrogel. Methods: Hydrogels were formulated according to a Box-Behnken design using pluronic F-127 (PF-127) and chitosan as thermogelling and mucoadhesive agents, respectively. The rectal permeability was examined using a sheep rectal mucosa. Results: Among all the formulations, the hydrogel S2 showed satisfactory drug content (4.50%), gelling temperature (32°C), pH (6.41), viscosity (105 cP) and strength (15.90 sec). Mucoadhesive strength was adequate to provide a prolonged residence time. The flux of hydrogel S2 was calculated to be 0.0003 µg/cm2.min. Conclusion: The ST hydrogel can provide a potential opportunity to overcome the first pass metabolism and reduce drug dose.

Safety issues of nanomaterials for dermal pharmaceutical products.

Nanomaterials (NMs) have favorable application in the medicine area, specifically in regard to the carry of pharmaceutical ingredients to provide targeted drug delivery systems. The skin is an excellent route for the delivery of pharmaceutical nano-transporters for skin-related applications. The physicochemical properties of nanomaterials such as size, hydrophobicity, loading capacity, charge and weight are vital for a skin penetrating system. Many nanocarriers such as polymeric nanoparticles, inorganic nanomaterials and, lipid nanostructures have been utilized for dermal delivery of active ingredients and others such as carbon nanotubes and fullerenes require more examination for future application in the skin-related area. Some negative side effects and nano-cytotoxicity of nanomaterials require special attention while investigating different nanomaterials for medicinal applications. Then, in the current review, we had a view on the safety issues of nanomaterials for dermal pharmaceutical products.

Targeting Multidrug Resistance With Antimicrobial Peptide-Decorated Nanoparticles and Polymers.

As a category of small peptides frequently found in nature, antimicrobial peptides (AMPs) constitute a major part of the innate immune system of various organisms. Antimicrobial peptides feature various inhibitory effects against fungi, bacteria, viruses, and parasites. Due to the increasing concerns of antibiotic resistance among microorganisms, development of antimicrobial peptides is an emerging tool as a favorable applicability prospect in food, medicine, aquaculture, animal husbandry, and agriculture. This review presents the latest research progress made in the field of antimicrobial peptides, such as their mechanism of action, classification, application status, design techniques, and a review on decoration of nanoparticles and polymers with AMPs that are used in treating multidrug resistance. Lastly, we will highlight recent progress in antiviral peptides to treat emerging viral diseases (e.g., anti-coronavirus peptides) and discuss the outlook of AMP applications.

Antimicrobial Benefits of Flavonoids and their Nanoformulations.

Nowadays, there is an urgent need to discover and develop long-term and effective antimicrobial and biofilm-inhibiting compounds. Employing combination therapies using novel drug delivery systems and also natural antimicrobial substances is a promising strategy in this field. Nanoparticles (NPs)-based materials have become well appreciated in recent times due to their function as antimicrobial agents or carriers for promoting the bioavailability and effectiveness of antibiotics. Flavonoids belong to the promising groups of bioactive compounds abundantly found in fruits, vegetables, spices, and medicinal plants with strong antimicrobial features. Flavonoids and NPs have the potential to work as alternatives to the conventional antimicrobial agents, when used alone as well as in combination. Different classes of flavonoid NPs may be particularly advantageous in treating microbial infections. The most important antimicrobial mechanisms of flavonoid NPs include oxidative stress induction, non-oxidative mechanisms, and metal ion release. However, the efficacy of flavonoid NPs against pathogens and drug-resistant pathogens changes according to their physicochemical characteristics as well as the particular structure of microbial cell wall and enzymatic composition. In this review, we provide an outlook on the antimicrobial mechanism of flavonoid-based NPs and the crucial factors involved in it.

The Therapeutic Benefits of Intravenously Administrated Nanoparticles in Stroke and Age-related Neurodegenerative Diseases.

The mean global lifetime risk of neurological disorders such as stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) has shown a large effect on economy and society. Researchers are still struggling to find effective drugs to treat neurological disorders and drug delivery through the blood-brain barrier (BBB) is a major challenge to be overcome. The BBB is a specialized multicellular barrier between peripheral blood circulation and neural tissue. Unique and selective features of the BBB allow it to tightly control brain homeostasis as well as the movement of ions and molecules. Failure in maintaining any of these substances causes BBB breakdown and subsequently enhances neuroinflammation and neurodegeneration. BBB disruption is evident in many neurological conditions. Nevertheless, the majority of currently available therapies have tremendous problems with drug delivery into the impaired brain. Nanoparticle (NP)-mediated drug delivery has been considered a profound substitute to solve this problem. NPs are colloidal systems with a size range of 1-1000 nm which can encapsulate therapeutic payloads, improve drug passage across the BBB, and target specific brain areas in neurodegenerative/ischemic diseases. A wide variety of NPs has been displayed for the efficient brain delivery of therapeutics via intravenous administration, especially when their surfaces are coated with targeting moieties. Here, we discuss recent advances in the development of NP-based therapeutics for the treatment of stroke, PD, and AD, as well as the factors affecting their efficacy after systemic administration.

Portland Cement: An Overview as a Root Repair Material.

Portland cement (PC) is used in challenging endodontic situations in which preserving the health and functionality of pulp tissue is of considerable importance. PC forms the main component of mineral trioxide aggregate (MTA) and demonstrates similar desirable properties as an orthograde or retrograde filling material. PC is able to protect pulp against bacterial infiltration, induce reparative dentinogenesis, and form dentin bridge during the pulp healing process. The biocompatibility, bioactivity, and physical properties of PC have been investigated in vitro and in animal models, as well as in some limited clinical trials. This paper reviews Portland cement's structure and its characteristics and reaction in various environments and eventually accentuates the present concerns with this material. This bioactive endodontic cement has shown promising success rates compared to MTA; however, considerable modifications are required in order to improve its characteristics and expand its application scope as a root repair material. Hence, the extensive chemical modifications incorporated into PC composition to facilitate preparation and handling procedures are discussed. It is still important to further address the applicability, reliability, and cost-effectiveness of PC before transferring into day-to-day clinical practice.