Future of Decellularized Dental Pulp Matrix in Regenerative Endodontics

With the advancements in tissue engineering, the repair and regeneration of oral/dental tissue are becoming possible and productive. Due to periodontal diseases, the tooth loses bone support resulting in tooth loss, but bone grafting stabilizes with new bone. It is seen that due to the progression of dental caries, pulp damage happens, and the vitality of the tooth is compromised. The current theme of dental pulp regeneration through biological and synthetic scaffolds, is becoming a potential therapy for pulp revitalization.

The Synthetic Scaffolds for Ventral Hernia Repair: Perspectives for Regenerative Surgery—Systematic Review

Ventral hernia (VH) frequently affects patients after abdominal surgery. The use of a mesh is often recommended. Different materials are described, from synthetic non-resorbable meshes to biological meshes. New generation meshes, also named scaffolds, aim to combine the advantages of both materials. The aim of this review is to provide an overview of the cytological, histological, biomechanical, and clinical outcomes of the use of the newest resorbable synthetic scaffolds in VH repair, based on experimental studies in a pre-clinical setting. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and to the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines. Only experimental studies were included. Outcome parameters were building technique, in vitro cytocompatibility, in vivo histocompatibility, biomechanical analysis, and clinical outcomes. The articles included were nine. The total number of cases treated was 257. Materials analyzed included electrospun silk fibroin (SF)/poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hybrid scaffolds, biodegradable polyester poly-ε-caprolactone (PCL) in the form of nanofibers, biodegradable mesh in poly-4-hydroxybutyrate (P4HB), nanofibrous polylactic acid (PLA) scaffold with a polypropylene (PP) material to generate a sandwich-like mesh, the collagen sponge (CS) group, the hybrid scaffold (HS) containing CS and poly-L-lactide (PLLA), and the hybrid scaffold (HS) + bone marrow (HSBM). Resorbable synthetic scaffolds are new, safe, surgical materials for the treatment or prevention of ventral hernia in animal models. Scaffolds should be tested in a contaminated surgical field for emergency use. Rigorous schematic indications for data collection are needed to improve the quality of the data in order to definitively clarify the pathway involved in inflammatory induced response.

Theoretical Prediction and Explanation of Reaction Site Selectivity in the Addition of a Phenoxy Group to Perfluoropyrimidine, Perfluoropyridazine, and Perfluoropyrazine

Perfluoroaromatics, such as perfluoropyridine and perfluorobenzene, are privileged synthetic scaffolds in organofluorine methodology, undergoing a series of regioselective substitution reactions with a variety of nucleophiles. This unique chemical behavior allows for the synthesis of many perfluoroaromatic derived molecules with unique and diverse architectures. Recently, it has been demonstrated that perfluoropyridine and perfluorobenzene can be utilized as precursors for a variety of materials, ranging from high performance polyaryl ethers to promising drug scaffolds. In this work, using density functional theory, we investigate the possibility of perfluoropyrimidine, perfluoropyridazine, and perfluoropyrazine participating in similar substitution reactions. We have found that the first nucleophilic addition of a phenoxide group substitution on perfluoropyrimidine and on perfluoropyridazine would happen at a site para to one of the nitrogen atoms. While previous literature points to mesomeric effects as the primary cause of this phenomenon, our work demonstrates that this effect is enhanced by the fact that the transition states for these reactions result in bond angles that allow the phenoxide to π-complex with the electron-deficient diazine ring. The second substitution on perfluoropyrimidine and on perfluoropyridazine is most likely to happen at the site para to the other nitrogen. The second substitution on perfluoropyrazine is most likely to happen at the site para to the first substitution. The activation energies for these reactions are in line with those reported for perfluoropyridine and suggest that these platforms may also be worth investigation in the lab as possible monomers for high performance polymers.

Pulmonary valve tissue engineering strategies in large animal models

In the last 25 years, numerous tissue engineered heart valve (TEHV) strategies have been studied in large animal models. To evaluate, qualify and summarize all available publications, we conducted a systematic review and meta-analysis. We identified 80 reports that studied TEHVs of synthetic or natural scaffolds in pulmonary position (n = 693 animals). We identified substantial heterogeneity in study designs, methods and outcomes. Most importantly, the quality assessment showed poor reporting in randomization and blinding strategies. Meta-analysis showed no differences in mortality and rate of valve regurgitation between different scaffolds or strategies. However, it revealed a higher transvalvular pressure gradient in synthetic scaffolds (11.6 mmHg; 95% CI, [7.31–15.89]) compared to natural scaffolds (4,67 mmHg; 95% CI, [3,94–5.39]; p = 0.003). These results should be interpreted with caution due to lack of a standardized control group, substantial study heterogeneity, and relatively low number of comparable studies in subgroup analyses. Based on this review, the most adequate scaffold model is still undefined. This review endorses that, to move the TEHV field forward and enable reliable comparisons, it is essential to define standardized methods and ways of reporting. This would greatly enhance the value of individual large animal studies.

Synthesis and Characterization of Electrospun Polyvinylidene Fluoride-based (PVDF) Scaffolds for Renal Bioengineering

With the continuous search for alternative treatment for End Stage Renal Disease (ESRD), the use of synthetic scaffolds as a prospect is becoming a forefront in regenerative medicine. This study aimed to fabricate and evaluate the effects of varying electrospinning parameters (the applied voltage, spinning distance and flowrate) to the fiber diameter and pore size of the scaffolds produced using polyvinylidene fluoride (PVDF). Electrospun scaffolds were subjected to scanning electron microscopy (SEM) and strain apparatus to assess structural and tensile properties. Results showed that applied voltage, spinning distance, and flowrate directly affect the overall pore size and fiber diameter of the electrospun scaffolds, as well as resulting in a direct effect to the tensile strength of the electrospun scaffold. The optimal values for the parameters in fabricating a PVDF electrospun scaffold would be a voltage of 20kV, a spinning distance of 100mm and a flowrate of 0.5ml/h. Results also show that spinning distance and flowrate have statistically more impact on the outcome of the fiber diameters, while applied voltage and spinning have statistically more impact on the outcome of the pore sizes. Moreover, the electrospun scaffolds acquired thinner fiber diameters and smaller pores sizes when compared to that of the native kidney tissue. Nonetheless, the promising mechanical integrity of the electrospun PVDF-based scaffolds offer a potential approach to addressing ESRD.

Targeting Monoacylglycerol Lipase in Pursuit of Therapies for Neurological and Neurodegenerative Diseases

Neurological and neurodegenerative diseases are debilitating conditions, and frequently lack an effective treatment. Monoacylglycerol lipase (MAGL) is a key enzyme involved in the metabolism of 2-AG (2-arachidonoylglycerol), a neuroprotective endocannabinoid intimately linked to the generation of pro- and anti-inflammatory molecules. Consequently, synthesizing selective MAGL inhibitors has become a focus point in drug design and development. The purpose of this review was to summarize the diverse synthetic scaffolds of MAGL inhibitors concerning their potency, mechanisms of action and potential therapeutic applications, focusing on the results of studies published in the past five years. The main irreversible inhibitors identified were derivatives of hexafluoroisopropyl alcohol carbamates, glycol carbamates, azetidone triazole ureas and benzisothiazolinone, whereas the most promising reversible inhibitors were derivatives of salicylketoxime, piperidine, pyrrolidone and azetidinyl amides. We reviewed the results of in-depth chemical, mechanistic and computational studies on MAGL inhibitors, in addition to the results of in vitro findings concerning selectivity and potency of inhibitors, using the half maximal inhibitory concentration (IC50) as an indicator of their effect on MAGL. Further, for highlighting the potential usefulness of highly selective and effective inhibitors, we examined the preclinical in vivo reports regarding the promising therapeutic applications of MAGL pharmacological inhibition.

Modulation of Synthetic Tracheal Grafts with Extracellular Matrix Coatings

Synthetic scaffolds for the repair of long-segment tracheal defects are hindered by insufficient biocompatibility and poor graft epithelialization. In this study, we determined if extracellular matrix (ECM) coatings improved the biocompatibility and epithelialization of synthetic tracheal grafts (syn-TG). Porcine and human ECM substrates (pECM and hECM) were created through the decellularization and lyophilization of lung tissue. Four concentrations of pECM and hECM coatings on syn-TG were characterized for their effects on scaffold morphologies and on in vitro cell viability and growth. Uncoated and ECM-coated syn-TG were subsequently evaluated in vivo through the orthotopic implantation of segmental grafts or patches. These studies demonstrated that ECM coatings were not cytotoxic and, enhanced the in vitro cell viability and growth on syn-TG in a dose-dependent manner. Mass spectrometry demonstrated that fibrillin, collagen, laminin, and nephronectin were the predominant ECM components transferred onto scaffolds. The in vivo results exhibited similar robust epithelialization of uncoated and coated syn-TG patches; however, the epithelialization remained poor with either uncoated or coated scaffolds in the segmental replacement models. Overall, these findings demonstrated that ECM coatings improve the seeded cell biocompatibility of synthetic scaffolds in vitro; however, they do not improve graft epithelialization in vivo.

Facial Cartilaginous Reconstruction—A Historical Perspective, State-of-the-Art, and Future Directions

Importance: Reconstruction of facial deformity poses a significant surgical challenge due to the psychological, functional, and aesthetic importance of this anatomical area. There is a need to provide not only an excellent colour and contour match for skin defects, but also a durable cartilaginous structural replacement for nasal or auricular defects. The purpose of this review is to describe the history of, and state-of-the-art techniques within, facial cartilaginous surgery, whilst highlighting recent advances and future directions for this continually advancing specialty.Observations: Limitations of synthetic implants for nasal and auricular reconstruction, such as silicone and porous polyethylene, have meant that autologous cartilage tissue for such cases remains the current gold standard. Similarly, tissue engineering approaches using unrelated cells and synthetic scaffolds have shown limited in vivo success. There is increasing recognition that both the intrinsic and extrinsic microenvironment are important for tissue engineering and synthetic scaffolds fail to provide the necessary cues for cartilage matrix secretion.Conclusions and Relevance: We discuss the first-in-man studies in the context of biomimetic and developmental approaches to engineering durable cartilage for clinical translation. Implementation of engineered autologous tissue into clinical practise could eliminate donor site morbidity and represent the next phase of the facial reconstruction evolution.