MedComm – Biomaterials and Applications最新文献

The development of hydrogen sulfide (H₂S) sensors is essential to address H₂S-related pharmacology since slow-releasing H₂S medications have been identified to be prospective options for cancer treatments. Here, we described an electrochemical sensor for highly selective and sensitive detection of aqueous H₂S, using a thin film of fumarate-based face-centered cubic (fcu)-based metal–organic frameworks (fum-fcu-MOF) modified on laser-scribed graphene (LSGE). The fum-fcu-MOF has shown a strong affinity and chemical stability to H₂S analysis. The electrochemical and H₂S catalytic properties were studied for fum-fcu-MOF/LSGE. An amperometry and differential pulse voltammetry techniques were demonstrated to validate the sensor. The resulting sensor delivered acceptable analytical parameters in terms of; detection limit (3.0 µM), dynamic range (10–500 µM), reproducibility, and stability (94.7%). The sensor's practical validity was demonstrated in bacterial cells and H₂S-releasing drug, where the sensor was able to monitor the continuous release of in-situ H₂S. The pharmacokinetics of a slow releasing H₂S donor is accessed at different time intervals and different concentration levels. Our research indicate that this fum-fcu-MOF based H₂S sensor holds potential in understanding pharmacokinetics of H₂S releasing drugs.

The scientific community has widely recognized thermosensitive hydrogels as highly biocompatible material with immense potential in drug delivery systems. When the temperature of these hydrogels approaches that of human body, a phase change occurs, enhancing their usefulness in a range of medical scenarios. This review article highlighted the background of thermosensitive hydrogels, their properties, and their applications in transdermal, oral, ophthalmic, intravaginal, nasal, rectal, cancer therapy, and cell-loaded drug delivery systems. The literature suggests numerous advantages of these hydrogels over conventional drug delivery systems and find applications in various fields, such as therapeutic systems, filling processes, and sustained drug delivery systems. One of their key benefits is the ability to eliminate invasive procedures like surgery, providing a noninvasive alternative for drug administration. Moreover, they streamline the formulation process for both hydrophilic and hydrophobic drug delivery systems, simplifying the development of effective treatments. The thermosensitive hydrogels have been found to be green materials with negligible side effects and desirable drug delivery properties. The thermosensitive hydrogel's sustained-release characteristics, immunogenicity, and biodegradability have also gained increased interest. Some of the disadvantages of thermosensitive hydrogels include delayed temperature response, weak mechanical characteristics, and poor biocompatibility, which limits their potential use in drug delivery applications.

Prince et al.¹ have been exploring cancer pathophysiology approaches by successfully culturing in vitro patient-derived tumor organoids (PDOs). Indeed, cancer remains one of the world's most devastating diseases, with a substantial and growing global burden. In 2019, there were an estimated 23.6 million new cancer cases and 10.0 million cancer deaths globally. Since 2010, these have represented a 26.3% increase in new cases and a 20.9% increase in deaths.² From those, breast cancer is still the most common cancer worldwide and has a mortality-to-incidence ratio of 15%. It holds highly intrinsic tumor genetic/phenotypic variations and intratumor heterogeneity, making each patient with breast cancer unique.

The current breast cancer in vitro models to study drug development and native pathophysiological mechanisms have shown an absence of patient specificity, limited structural integrity, stability over the cell culture period, and limited recreation of the complex three-dimensional tumor microenvironment, which almost exclusively depends on the culture of PDOs in basement membrane extract (BME) systems.³ Hydrogels have emerged as a viable method for promoting the development and maintenance of organoids in vitro in recent years. In fact, biomimetic hydrogels, by emulating the extracellular matrix (ECM), can create a more physiologically realistic microenvironment for cells while providing physical support, hence enhancing their growth, development, and function. Recently, Prince et al.¹ proposed a biomimetic hydrogel that supports the initiation and growth of PDOs, EKGel, as an alternative culture system for BME, such as Cultrex, which are commercially available matrices derived from mouse tumor that contains high levels of ECM proteins (e.g., laminin, collagen IV).

EKGel is a nanofibrillar hydrogel that consists of Schiff base crosslinks between aldehyde groups on the surface of cellulose nanocrystals (a-CNCs) and amine groups of lysine residues in gelatin (Figure 1A). On one hand, the arginine–glycine–aspartate integrin receptor-binding motif, present in gelatin, is also present in native ECM proteins, which facilitate cell–matrix interactions. On the other hand, the network of fibers formed by the rod-like a-CNCs have similar dimensions (43 ± 17 nm) to in vivo tumor collagen fibrils. EKGel showed a Darcy permeability, which measures the convection-driven transport, more than two orders of magnitude larger than the reported values for BME (1.9 × 10⁻¹¹ cm²), due to its significantly larger pores. By changing a-CNC concentration (0.5–3.75 wt%), EKGel obtained Young's modulus (24–3738 Pa) within the stiffness range of ECM in breast tumor biopsies (1.2–3.7 kPa). Furthermore, EKGel was more stable under shear-induced stress (14% relative volume reduction) than BME (60% relative volume reduction), Figure 1B. The imine co

Fabricating engineered vasculature within biological scaffolds is one of the most common strategies to maintain high cell viability before implantation. Many studies have been conducted from the aspects of the manufacturing process, materials science, and cell biology to fabricate engineered vasculature with the aim of enhancing the integration between scaffold and host. Among them, the method of combining three-dimensional (3D) printing and sacrifice-based technique has attracted extensive attention. Taking advantage of 3D printing, the method of separating the printed sacrificial template from the biological scaffold to form a 3D channel has become a widely used approach to advance the engineered vasculature. With the development of 3D printing techniques and material science, numerous sacrificial materials have shown their potential in fabricating engineered vasculature. However, several issues remain in this multimethod design, including, but not limited to, the printing process, removal method of sacrificial material, and cell seeding method. This review aims to summarize recent strategies for 3D printing sacrificial templates for fabricating engineered vasculature. The pros and cons of sacrificial materials used in these studies are analyzed. Future perspectives are proposed to fabricate biomimetic-engineered vasculature. Flexible fabrication processes and materials should be advanced to support the 3D printing of sacrificial templates.

Although cartilage regeneration is a continuously changing, complex process, most studies on cartilage tissue regeneration have focused on specific stages, thereby promoting regeneration in only a limited period rather than over the entire repair process. The ideal adaptive scaffolds for cartilage tissue engineering should exhibit dynamic and spatiotemporally controlled evolution according to the physiological microenvironments during each phase of cartilage repair. Moreover, scaffolds should have a specific feedback regulation capability, including long-term feedback for the controlled delivery of multiple factors, which would better meet the requirements of cartilage regeneration. Adaptive scaffolds matching the whole evolving stages of cartilage repair are still under exploration. This review highlights the development of dynamically adaptive scaffolds to provide the appropriate microenvironments for cartilage regeneration, including scaffolds that manipulate the immune microenvironments from the inflammation stage to the regeneration stage, scaffolds that release cytokines on demand across several stages, and scaffolds that adapt according to the mechanical properties of extracellular matrices over time, and also discusses the future challenges and development directions of adaptive scaffolds in cartilage tissue regeneration. This understanding is expected to inspire the application of adaptive scaffolds for cartilage repair.

The lack of advanced biomaterials is a major challenge in bio-printing. Gelatin-methacryloyl (GelMA) hydrogel, as one of the most commonly used biomaterials in 3D printing, has limited the applications of medicine because of its low mechanical properties. In this study, to enhance the mechanical strength of GelMA hydrogels, we prepared a composite hydrogel based on F127 diacrylate (F127DA) and GelMA, followed by lyophilization and tannic acid (TA) treatment. In this composite hydrogel, the F127DA could self-assemble into nanomicelles as crosslinking centers for monomer polymerization, which provides additional energy dissipation in hydrogels due to the synergistic deformation of micelles and internal rearrangement of physical binding. After lyophilization of the composite hydrogel, the porous hydrogel was formed. The subsequent treatment of TA could diffuse into the inner of the hydrogel and react with the hydrogel via hydrogen bonds, resulting in the significant enhancement of mechanical properties. The maximum tensile deformation of the obtained hydrogel was about 11 times higher than that of GelMA. This work demonstrates a method to enhance the mechanical properties of 3D-printed GelMA hydrogel with promising application in bioprinting.

The demand-to-supply gap, rejection rates, and the chances of infection associated with organ/tissue transplantation prompted researchers to find alternative solutions such as tissue engineering. Here, healthy cells are cultured over a biomaterial framework supplemented with growth factors to create bioartificial tissues. As a scaffolding biomaterial, silk fibroin (SF), a biopolymer obtained from Bombyx mori silk cocoons, offers unique properties. However, natural polymers, including SF, were criticized for preconceived source-dependent batch-to-batch variations. Therefore, this study aims to prepare B. mori SF-based films and investigate source-dependent variations, if any. For this purpose, we have sourced silk cocoons from three geographical locations in India and processed them into films with a solvent-casting approach. As a whole, our results indicate that there were slight variations in the morphological features in the raw cocoon stage; however, once processed, there were no significant differences in their topological, physical, chemical, optical, mechanical, or degradable properties with respect to the source. Further, all the films were found to be noncytotoxic and cytocompatible with corneal cells in vitro. Therefore, the study indicates no source-dependent variations in biopolymers and suggested that SF from any source can be processed into biomaterials for potential biomedical applications.

With the aging of global population, the early diagnosis and treatment of neurodegenerative diseases such as Parkinson's disease (PD) have attracted considerable attention. Despite great advances achieved during the past decades, PD as the second largest neurodegenerative disease is still incurable. In the clinical practice, PD patients are mainly treated by drugs, and supplemented with deep brain stimulation or nerve nucleus destruction. The existing drugs can only relieve the symptoms of motor disorder, and cannot stop the progression of PD. Compared with small molecular drugs, nanoparticles exhibit multiple functions in the neuroprotection and neurorepair due to their tunable physical and chemical properties, easy modification and functionalization. Herein, we first briefly review the characteristics of nanoparticles crossing the blood–brain barrier, which is a primary challenge for the treatment of PD. Then, we summarize the pathologic mechanisms of PD and comprehensively discuss the novel PD therapy based on diverse nanoparticles, including alleviating oxidative stress, scavenging α-synuclein aggregates, chelating metal ions, delivering neurotrophic factors and genes, and transplanting stem cells. This review aims to highlight the great potential of advanced nanoparticles in the therapy of PD.

A publication in Nature Nanotechnology by James E. Dahlman et al. reported a novel screening technique for lipid nanoparticles (LNPs) delivery vectors called single-cell nanoparticle targeting-sequencing (SENT-seq).¹ This technology may be a significant leap forward in the realization of high-throughput screening of LNPs formulations, LNPs delivery mechanism research, and optimization of mRNA therapy.

mRNA is a transient carrier of genetic information. A wide range of diseases can be treated in clinical applications by delivering mRNA that can express infectious diseases or cancer antigens, gene-editing components, and disease-associated therapeutic proteins in the cells.² Effective mRNA therapy requires adequate cytoplasmic mRNA translation. Therefore, a series of delivery formulations have been developed to help mRNA cross multiple biological barriers and successfully enter the cytoplasm to fulfill its biological function. Among them, LNPs are the most extensively studied and clinically advanced mRNA vectors.³ The formulation of LNPs include ionizable lipids (or cationic lipids), neutral auxiliary lipids, cholesterol, pegylated lipids, and nucleic acid molecules. How can the optimal delivery efficiency of nucleic acid molecules be achieved with LNPs? For example, research has screened LNP compositions with the best delivery efficiency in vitro by changing the formulation of LNP.⁴ However, the results in vitro cannot summarize the results in vivo. In addition, the influence of different cell subsets on LNPs uptake during in vivo delivery has yet to be fully studied. Therefore, Dahlman et al. proposed a solution suitable for screening and examining the biological distribution of LNPs delivery in vivo, defining cells according to transcriptional states rather than cell surface markers, and analyzing the effects of cell subsets with different transcription states (heterogeneity) on LNPs uptake.¹

Dahlman et al. designed a multiomics NP delivery system, SENT-seq, to examine the effect of cell heterogeneity on LNPs delivery.¹ Using this technique, they were able to quantify the biodistribution (the number of LNPs entering cells), functional delivery (mRNA translated into functional proteins), and transcriptome level of cells. They used DNA barcoding technology to quantify LNPs entering the cell. They inserted different DNA sequences into different LNPs such that each LNP had a DNA barcode. The number of LNPs that entered a single cell was characterized by barcode readouts. However, one of the significant barriers in the intracellular delivery of nucleic acid molecules is that the nucleic acid molecules degrade in the endosomes, hence, the mRNA delivered into the cell does not necessarily express a functional protein.² Here, the expression of the mRNA functional aVH

Hydroxyapatite (HA) bioceramics have been extensively employed as bone tissue scaffolds owing to their biodegradability and osteoinductivity. In our work, HA, a significant component of natural bone tissue used as the raw material to produce porous scaffolds employing three-dimensional (3D)-printing technology. Physical and chemical properties, porosity, and compression resistance of the scaffolds were investigated in vitro. The scaffold was confirmed to have a large number of interconnected pore structures on the surface and inside HA scaffolds showed good cell compatibility and cell adhesion in cell text. To analyze the effect of the scaffold on bone repair and regeneration in vivo, the large-size defect of beagle skull was repaired with a 3D printing group and an autologous bone group (ABG) for 8 months. Images and histological analysis of the 3D printing group indicated better integration with adjacent tissues. However, there were obvious gaps in the ABG, which indicates weak bone regeneration ability of this group due to unmatched implant dimension. Immunohistochemistry and immunofluorescence results showed that 3D-printed scaffolds had a highly vascularized structure. This study indicates that 3D-printed bioceramics scaffolds that are osteoinductivity and biodegradable have great potential in maxillofacial bone regeneration.