Enantioselective synthesis of a chiral coordination polymer with circularly polarized visible laser.

Circular dichroism is known to be the feature of a chiral agent which has inspired scientist to study the interesting phenomena of circularly polarized light (CPL) modulated molecular chirality. Although several organic molecules or assemblies have been found to be CPL-responsive, the influence of CPL on the assembly of chiral coordination compounds remains unknown. Herein, a chiral coordination polymer, which is constructed from achiral agents, was used to study the CPL-induced enantioselective synthesis. By irradiation with either left-handed or right-handed CPL during the reaction and crystallization, enantiomeric excesses of the crystalline product were obtained. Left-handed CPL resulted in crystals with a left-handed helical structure, and right-handed CPL led to crystals with a right-handed helical structure. It is exciting that the absolute asymmetric synthesis of a chiral coordination polymer could be enantioselective when using CPL, and provides a strategy for the control of the chirality of chiral coordination polymers.

Research progress on optimization of in vitro isolation, cultivation and preservation methods of dental pulp stem cells for clinical application.

Due to high proliferative capacity, multipotent differentiation, immunomodulatory abilities, and lack of ethical concerns, dental pulp stem cells (DPSCs) are promising candidates for clinical application. Currently, clinical research on DPSCs is in its early stages. The reason for the failure to obtain clinically effective results may be problems with the production process of DPSCs. Due to the different preparation methods and reagent formulations of DPSCs, cell characteristics may be affected and lead to inconsistent experimental results. Preparation of clinical-grade DPSCs is far from ready. To achieve clinical application, it is essential to transit the manufacturing of stem cells from laboratory grade to clinical grade. This review compares and analyzes experimental data on optimizing the preparation methods of DPSCs from extraction to resuscitation, including research articles, invention patents and clinical trials. The advantages and disadvantages of various methods and potential clinical applications are discussed, and factors that could improve the quality of DPSCs for clinical application are proposed. The aim is to summarize the current manufacture of DPSCs in the establishment of a standardized, reliable, safe, and economic method for future preparation of clinical-grade cell products.

Anti-inflammatory effect of dental pulp stem cells.

Dental pulp stem cells (DPSCs) have received a lot of attention as a regenerative medicine tool with strong immunomodulatory capabilities. The excessive inflammatory response involves a variety of immune cells, cytokines, and has a considerable impact on tissue regeneration. The use of DPSCs for controlling inflammation for the purpose of treating inflammation-related diseases and autoimmune disorders such as supraspinal nerve inflammation, inflammation of the pulmonary airways, systemic lupus erythematosus, and diabetes mellitus is likely to be safer and more regenerative than traditional medicines. The mechanism of the anti-inflammatory and immunomodulatory effects of DPSCs is relatively complex, and it may be that they themselves or some of the substances they secrete regulate a variety of immune cells through inflammatory immune-related signaling pathways. Most of the current studies are still at the laboratory cellular level and animal model level, and it is believed that through the efforts of more researchers, DPSCs/SHED are expected to be transformed into excellent drugs for the clinical treatment of related diseases.

Potential of dental pulp stem cells and their products in promoting peripheral nerve regeneration and their future applications.

Peripheral nerve injury (PNI) seriously affects people's quality of life. Stem cell therapy is considered a promising new option for the clinical treatment of PNI. Dental stem cells, particularly dental pulp stem cells (DPSCs), are adult pluripotent stem cells derived from the neuroectoderm. DPSCs have significant potential in the field of neural tissue engineering due to their numerous advantages, such as easy isolation, multidifferentiation potential, low immunogenicity, and low transplant rejection rate. DPSCs are extensively used in tissue engineering and regenerative medicine, including for the treatment of sciatic nerve injury, facial nerve injury, spinal cord injury, and other neurodegenerative diseases. This article reviews research related to DPSCs and their advantages in treating PNI, aiming to summarize the therapeutic potential of DPSCs for PNI and the underlying mechanisms and providing valuable guidance and a foundation for future research.

Vascular transplantation with dual-biofunctional ePTFE vascular grafts in a porcine model.

Cardiovascular disease (CVD) poses serious health concerns worldwide. The lack of transplantable vascular grafts is an unmet clinical need in the surgical treatment of CVD. Although expanded polytetrafluoroethylene (ePTFE) vascular grafts have been used in clinical practice, a low long-term patency rate in small-diameter transplantation application is still the biggest challenge. Thus, surface modification of ePTFE is sought after. In this study, polydopamine (PDA) was used to improve the hydrophilia and provide immobilization sites in ePTFE. Bivalirudin (BVLD), a direct thrombin inhibitor, was used to enhance the anti-thrombotic activity of ePTFE. The peptides derived from extracellular matrix proteins were used to elevate the bioactivity of ePTFE. The morphology, chemical composition, peptide modified strength, wettability, and hemocompatibility of modified ePTFE vascular grafts were investigated. Then, an endothelial cell proliferation assay was used to evaluate the best co-modification strategy of the ePTFE vascular graft in vitro. Since a large animal could relatively better mimic human physiology, we chose a porcine carotid artery replacement model in the current study. The results showed that the BVLD/REDV co-modified ePTFE vascular grafts had a satisfactory patency rate (66.7%) and a higher endothelial cell coverage ratio (70%) at 12 weeks after implantation. This may offer an opportunity to produce a multi-biofunctional ePTFE vascular graft, thereby yielding a potent product to meet the clinical needs.

Fabrication of flexible composite drug films via foldable linkages using electrohydrodynamic printing.

The simple method to manufacture a flexible multi-drug with hydrophilic and hydrophobic molecules-loaded composite membrane via three dimensional (3D) electrohydrodynamic (EHD) printing has been demonstrated in this study. The composite membrane consists of two different drug-loaded sections: cellulose acetate-ibuprofen (CA-IBU) and cellulose acetate-paracetamol (CA-Para), respectively, with an intermediate polycaprolactone (PCL) folding component. The composite membranes can be folded and housed in commercial capsules to aid swallowing. By changing the number of PCL layers in the intermediate layers, it is possible to control and modify the mechanical and unfolding properties of the composite membrane. IBU and Para are loaded into the CA polymeric matrix in their amorphous states, with the matrices exhibiting Higuchi and first order release kinetics, respectively. The combination of IBU and Para can potentially be used as analgesic for patients. Magnetic nanoparticles as a functional material can be incorporated into the PCL matrix for wide targeting and traceable applications. The composite membrane here possesses good biocompatibility and flexibility; enabling extensive application prospects in drug combination therapy and personalized medicine.

A biodegradable multifunctional nanofibrous membrane for periodontal tissue regeneration.

Biomaterial-based membranes represent a promising therapeutic option for periodontal diseases. Although conventional periodontal membranes function greatly in preventing the ingrowth of both fibroblasts and epithelial cells as well as connective tissues, they are not capable of promoting periodontal tissue regeneration. Here, we report a multifunctional periodontal membrane prepared by electrospinning biodegradable polymers with magnesium oxide nanoparticles (nMgO). nMgO is a light metal-based nanoparticle with high antibacterial capacity and can be fully resorbed in the body. Our results showed that incorporating nMgO into poly(L-lactic acid) (PLA)/gelatin significantly improved the overall properties of membranes, including elevated tensile strength to maintain structural stability and adjusted degradation rate to fit the time window of periodontal regeneration. Acidic degradation products of PLA were neutralized by alkaline ions from nMgO hydrolysis, ameliorating pH microenvironment beneficial for cell proliferation. In vitro studies demonstrated considerable antibacterial and osteogenic properties of nMgO-incorporated membranes that are highly valuable for periodontal regeneration. Further investigations in a rat periodontal defect model revealed that nMgO-incorporated membranes effectively guided periodontal tissue regeneration. Taken together, our data indicate that nMgO-incorporated membranes might be a promising therapeutic option for periodontal regeneration. STATEMENT OF SIGNIFICANCE: Traditional clinical treatments of periodontal diseases largely focus on the management of the pathologic processes, which cannot effectively regenerate the lost periodontal tissue. GTR, a classic method for periodontal regeneration, has shown promise in clinical practice. However, the current membranes might not fully fulfill the criteria of ideal membranes. Here, we report bioabsorbable nMgO-incorporated nanofibrous membranes prepared by electrospinning to provide an alternative for the clinical practice of GTR. The membranes not only function greatly as physical barriers but also exhibit high antibacterial and osteoinductive properties. We therefore believe that this study will inspire more practice work on the development of effective GTR membranes for periodontal regeneration.

Precision Printing of Customized Cylindrical Capsules with Multifunctional Layers for Oral Drug Delivery.

Advances in personalized medicine will require custom drug formulations and delivery mechanisms. Herein, we demonstrate a new type of personalized capsule comprising of printed concentric cylindrical layers with each layer having a distinctive functional drug component. Poly ε-caprolactone (PCL) with paracetamol (APAP) and chlorpheniramine maleate (CM), synergistic drugs commonly used to alleviate influenza symptoms, are printed as an inner layer and outer layer, respectively, via microscaled electrohydrodynamic (EHD) printing. Polyvinylpyrrolidone (PVP) nanofibers are embedded as interlayers between the two printed PCL-drug layers using electrospinning (ES) techniques. The complete concentric cylindrical capsule with a 6 mm inner diameter and 15 mm length can be swallowed for oral drug delivery. After dissolution of the PVP interlayer, the capsule separates in two, with inner and outer capsules for continuous drug dosing and targeting. Imaging was achieved using a 3T MRI system which allowed temporal observations of the targeted release through the incorporation of nanoparticles (Fe3O4). The morphology and structure, chemical composition, mechanical properties, and biocompatibility of the capsules were studied in vitro. In summary, this new type of custom printed and electrospun capsule that enabled component separation, targeted drug release may advance personalized medicine via multidrug oral delivery.

Three-Dimensional Electrohydrodynamic Printing and Spinning of Flexible Composite Structures for Oral Multidrug Forms.

A simple method to rapidly customize and to also mass produce oral dosage forms is arguably a current bottleneck in the development of modern personalized medicine. Specifically, delayed-release mechanisms with well-controlled dosage profiles for combinations of traditional Chinese herbal extracts and Western medications are not well established. Herein, we demonstrate a novel multidrug-loaded membrane sandwich with structures infused with ibuprofen (IBU) and Ganoderma lucidum polysaccharide (GLP) using three-dimensional electrohydrodynamic printing and electrospinning techniques. The resulting flexible membrane consists of microscaled, multilayered cellulose acetate (CA) membranes loaded with IBU in the shape of either concentric squares or circles, as the top and bottom layers of a sandwich structure. In between the CA-IBU layers are randomly electrospun polyvinyl pyrrolidone (PVP) layers loaded with GLP. The complete fibrous membrane sandwich can be folded and embedded into a 0-size capsule to achieve oral compliance. Simulated in vitro testing of gastric and intestinal fluids demonstrated a triphasic release profile. There was an immediate release of GLP after gastric juices dissolved the capsule shell and the PVP, followed by the short-term release of 60% of the IBU within an hour afterward, and the remaining IBU was released in a sustained manner following a Fickian diffusion profile. In summary, this multidrug (both hydrophilic and/or hydrophobic) oral system with precision-designed structures should enable personalized therapeutic dosing.