Cell via Cell Viability Assay Changes Cellular Metabolic Characteristics by Intervening with Glycolysis and Pentose Phosphate Pathway.

The Cell Counting Kit-8 (CCK-8) cell viability assay, also known as WST-8, is widely recognized for its nontoxic nature, making it suitable for further studies on treated cells. This practice is commonly observed in the field of tissue engineering. While live/dead imaging may not readily reveal macroscopic differences, our investigation has uncovered significant intracellular metabolic changes. Notably, we observed substantial down-regulation of metabolites within the glycolysis and pentose phosphate pathways. These metabolic alterations predominantly affect energy metabolism and may potentially impact the cellular redox environment. In light of these findings, we strongly recommend that researchers exercise caution when using cells treated with CCK-8 in subsequent experiments.

Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer.

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.

A Review of Recent Advances in Natural Polymer-Based Scaffolds for Musculoskeletal Tissue Engineering.

The musculoskeletal (MS) system consists of bone, cartilage, tendon, ligament, and skeletal muscle, which forms the basic framework of the human body. This system plays a vital role in appropriate body functions, including movement, the protection of internal organs, support, hematopoiesis, and postural stability. Therefore, it is understandable that the damage or loss of MS tissues significantly reduces the quality of life and limits mobility. Tissue engineering and its applications in the healthcare industry have been rapidly growing over the past few decades. Tissue engineering has made significant contributions toward developing new therapeutic strategies for the treatment of MS defects and relevant disease. Among various biomaterials used for tissue engineering, natural polymers offer superior properties that promote optimal cell interaction and desired biological function. Natural polymers have similarity with the native ECM, including enzymatic degradation, bio-resorb and non-toxic degradation products, ability to conjugate with various agents, and high chemical versatility, biocompatibility, and bioactivity that promote optimal cell interaction and desired biological functions. This review summarizes recent advances in applying natural-based scaffolds for musculoskeletal tissue engineering.

Metabolomics in Bone Research.

Identifying the changes in endogenous metabolites in response to intrinsic and extrinsic factors has excellent potential to obtain an understanding of cells, biofluids, tissues, or organisms' functions and interactions with the environment. The advantages provided by the metabolomics strategy have promoted studies in bone research fields, including an understanding of bone cell behaviors, diagnosis and prognosis of diseases, and the development of treatment methods such as implanted biomaterials. This review article summarizes the metabolism changes during osteogenesis, osteoclastogenesis, and immunoregulation in hard tissue. The second section of this review is dedicated to describing and discussing metabolite changes in the most relevant bone diseases: osteoporosis, bone injuries, rheumatoid arthritis, and osteosarcoma. We consolidated the most recent finding of the metabolites and metabolite pathways affected by various bone disorders. This collection can serve as a basis for future metabolomics-driven bone research studies to select the most relevant metabolites and metabolic pathways. Additionally, we summarize recent metabolic studies on metabolomics for the development of bone disease treatment including biomaterials for bone engineering. With this article, we aim to provide a comprehensive summary of metabolomics in bone research, which can be helpful for interdisciplinary researchers, including material engineers, biologists, and clinicians.

Injectable chitosan hydrogel embedding modified halloysite nanotubes for bone tissue engineering.

Low mechanical strength and untargeted osteoinduction of chitosan hydrogel limit its application for bone regeneration. This study aimed to develop an injectable chitosan hydrogel with enhanced mechanical strength and improved osteoinductivity for bone tissue engineering. For this purpose, chitosan-modified halloysite nanotubes (mHNTs) were synthesized first. Then, icariin as a bone inducer was loaded into mHNTs (IC@mHNTs), resulting in a sustained drug release system. Further, nanocomposite chitosan/mHNTs hydrogels were prepared by the sol-gel transition, leading to decreased gelation time and temperature and enhanced mechanical strength of the resulting scaffolds. The mesenchymal stem cells were encapsulated into the hydrogels, and in vitro viability assays showed scaffold biocompatibility. Moreover, embedded mHNTs or IC@mHNTs in the scaffold resulted in enhanced proliferation and bone differentiation of encapsulated cells. It was collectively demonstrated that the injectable in situ forming nanocomposite chitosan hydrogel loaded with IC@mHNTs is a promising candidate for bone regeneration.

Drug Delivery (Nano)Platforms for Oral and Dental Applications: Tissue Regeneration, Infection Control, and Cancer Management.

The oral cavity and oropharynx are complex environments that are susceptible to physical, chemical, and microbiological insults. They are also common sites for pathological and cancerous changes. The effectiveness of conventional locally-administered medications against diseases affecting these oral milieus may be compromised by constant salivary flow. For systemically-administered medications, drug resistance and adverse side-effects are issues that need to be resolved. New strategies for drug delivery have been investigated over the last decade to overcome these obstacles. Synthesis of nanoparticle-containing agents that promote healing represents a quantum leap in ensuring safe, efficient drug delivery to the affected tissues. Micro/nanoencapsulants with unique structures and properties function as more favorable drug-release platforms than conventional treatment approaches. The present review provides an overview of newly-developed nanocarriers and discusses their potential applications and limitations in various fields of dentistry and oral medicine.

Role of biomaterials in the diagnosis, prevention, treatment, and study of corona virus disease 2019 (COVID-19).

Recently emerged novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting corona virus disease 2019 (COVID-19) led to urgent search for methods to prevent and treat COVID-19. Among important disciplines that were mobilized is the biomaterials science and engineering. Biomaterials offer a range of possibilities to develop disease models, protective, diagnostic, therapeutic, monitoring measures, and vaccines. Among the most important contributions made so far from this field are tissue engineering, organoids, and organ-on-a-chip systems, which have been the important frontiers in developing tissue models for viral infection studies. Also, due to low bioavailability and limited circulation time of conventional antiviral drugs, controlled and targeted drug delivery could be applied alternatively. Fortunately, at the time of writing this paper, we have two successful vaccines and new at-home detection platforms. In this paper, we aim to review recent advances of biomaterial-based platforms for protection, diagnosis, vaccination, therapeutics, and monitoring of SARS-CoV-2 and discuss challenges and possible future research directions in this field.

Quantum dots-ßcyclodextrin-histidine labeled human adipose stem cells-laden chitosan hydrogel for bone tissue engineering.

Mesenchymal stem cells with differentiation ability to diverse cells play a crucial role in tissue engineering. Tracking the fate of these cells during the regeneration of tissue helps to obtain more information about their function. In this study, histidine conjugated ß-cyclodextrin as a cell-penetrating carrier with drug loading ability was attached to QDs nanoparticle (QD-ßCD-His) for stem cell labeling. Traceability of QD-ßCD-His labeled human adipose stem cells (hASCs) was monitored in 2D cell culture and 3D temperature-sensitive chitosan hydrogel scaffold. Dexamethasone (Dex) as an osteoinductive drug was loaded into QD-ßCD-His nano-carrier (QD-ßCD-His@Dex) to induce bone differentiation of labeled cells. Overall results indicated that QD-ßCD-His@Dex is a promising dual-purpose nano-carrier for stem cell labeling with osteoinductive potential in cell therapy as well as tissue engineering scaffolds.

Enhanced Cellular Uptake Of Phenamil Through Inclusion Complex With Histidine Functionalized ß-Cyclodextrin As Penetrative Osteoinductive Agent.

BACKGROUND: Phenamil (PH) is a small molecule that induces bone formation through upregulation of the TRB3 gene in the bone-regeneration process. ß-Cyclodextrins (ßCDs) with hydrophilic surfaces and a relatively hydrophobic cavity can form inclusion complexes with primarily hydrophobic small molecules such as PH, and increase their apparent solubility and dissolution rate. The hydrophilic surface of ßCDs prevents their interaction with the hydrophobic lipids of the cell membrane for penetration. Therefore, binding of penetrative groups, such as lysine, arginine, and histidine (His), to ßCDs for cell penetration is required. AIM: The aim of this study was to investigate the effect of His-conjugated ßCD on cellular uptake of PH for bone differentiation. METHODS: In this study, His-ßCDs were synthesized and used to prepare an inclusion complex of His-ßCD-PH. A hydroxypropyl-ßCD-PH (HP-ßCD-PH) inclusion complex for increasing PH solubility without a penetrative group was prepared for comparison. 3-D geometry of ßCD derivatives and PH-inclusion complexes was investigated by Fourier-transform infrared spectroscopy and molecular docking. Alizarin red staining and real-time PCR were performed to compare bone differentiation of His-ßCD-PH and HP-ßCD-PH. RESULTS: The results suggested that the benzene ring of PH was inserted into the wide side of both His-ßCD and HP-ßCD. Alizarin red staining at 14 days postculture in the presence of His-ßCD-PH at total concentration of 50 µM for PH showed that bone-matrix mineralization increased significantly compared with free PH and HP-ßCD-PH. Real-time PCR confirmed this result, and showed gene expression increased significantly (OPN 1.84-fold, OCN 1.69-fold) when stem cells were cultured with His-ßCD-PH. CONCLUSION: The overall results indicated that His-ßCD-PH is a promising carrier for osteoinductive PH with possible penetration ability and sustained release that reduces BMP2 consumption for differentiation of mesenchymal stem cells to bone tissue.

NMR (¹H, ROESY) spectroscopic and molecular modelling investigations of supramolecular complex of ß-cyclodextrin and curcumin.

In this paper we have investigated the solubility enhancement of curcumin through inclusion complexation by ß-cyclodextrin as well as the topology and geometry of interaction between curcumin and carrier. For this purpose, the phase solubility of curcumin was assessed using Higuchi and Connors method, and the inclusion complex was characterised by 1D (1)H and 2D ROESY NMR analysis, and finally confirmed by molecular modelling. The phase solubility diagram demonstrated the AL-type which confirms an increase in curcumin solubility by increasing the concentration of ß-cyclodextrin. (1)H NMR and ROESY spectra results showed a cross-peak between H-3 proton of ß-cyclodextrin and the aromatic rings group of curcumin. This revealed the hydrophobic interactions between aromatic rings of curcumin and the cavity of ß-cyclodextrin. Finally, the enthalpy of formation was obtained from molecular modelling results which in turn indicated that the process is exothermic and low-energy interactions are involved in the inclusion complex formation.