MedComm – Biomaterials and Applications最新文献

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.

With the growth of the market and the number of wearers, contact lenses have been widely used for vision correction and cosmetic purposes for a few years. The current study opens up a new path for their applications. On the one hand, contact lenses are ideal sensing platforms due to advances in the monitoring of relevant indicators in tears such as glucose and intraocular pressure. Aside from detecting a single analyte at a time, multifunctional contact lens sensors were proposed to monitor two or more indicators at the same time. Contact lenses, on the other hand, are also suitable drug delivery platforms due to their good biocompatibility and long contact duration with the cornea. Different drug delivery approaches are being investigated to increase drug duration and bioavailability. In addition, the integration of these novel drug delivery methods into wearable sensors has become a topic for a complete closed-loop program for disease management. We began this review by summarizing the categories and properties of current contact lenses. Then, innovative applications of contact lenses such as biosensors and drug delivery systems were also summarized. In general, the current progress in the applications of contact lenses provides a new possibility for noninvasive diagnosis and therapy of ocular diseases.

Oral hard tissue defects are common concomitant symptoms of oral diseases, which have poor prognosis and often exert detrimental effects on the physical and mental health of patients. Implant materials can accelerate the regeneration of oral hard tissue defects (such as periodontal defects, alveolar bone defects, maxilla bone defects, mandible bone defects, alveolar ridge expansion, and site preservation), but their regenerative efficacy and biocompatibility need to be preclinically validated in vivo with animal-based oral hard tissue defect models. The choice of oral hard tissue defect model depends on the regenerative effect and intended application of the tested implant material. At the same time, factors that need to be considered include techniques for constructing the particular defect model, the scaffold/graft material used, the availability of animal model evaluation techniques and instrumentation, as well as costs and time constraints. In this article, we summarize the common oral hard tissue defect models in various animal species (such as periodontal model, jaw defect model, and implantation defect model) that can be used to evaluate the regenerative efficacy and biocompatibility of implant materials.

DNA origami, a promising branch of structural DNA technology, refers to the technique of folding a single-stranded DNA scaffold into well-defined nanostructures. In recent years, DNA origami nanostructures have shown considerable promise in a variety of biomedical applications, owing to their biodegradability, unique programmability, and addressability. Despite their popularity, the biomedical application of DNA origami techniques, which exploits their unique programmability and addressability, is rare in previous studies. Most recently, mounting evidence has demonstrated the robustness of DNA origami nanostructures in the spatial organization of functional components at the nanoscale in the biomedical field. These examples provide typical paradigms to fully realize the potential of DNA origami techniques by taking advantage of their unique programmability and addressability. This minireview summarizes the recent advancements of DNA origami techniques in biosensing, biocatalysis, and drug delivery, and the representative examples using DNA origami nanostructures for the spatial organization of functional molecules with nanometric precision are highlighted. We further discuss the possible limitations and challenges for in vivo applications, including stability issues and potential immunogenicity, and finally, propose some strategies to overcome these obstacles to fully realize the potential of DNA origami techniques in biomedical applications.

Cetirizine hydrochloride (CTZ), an antiallergic drug, is a new-generation H1 receptor antagonist and a second-generation H1 antihistamine. We aimed to prepare cetirizine hydrochloride liposomes, based on which cetirizine hydrochloride liposomal (CTZL) in situ gel (ISG) was prepared, to improve the retention time in the eye. CTZL were prepared by the ethanol injection method combined with the ammonium sulfate gradient method. A CTZ liposomal temperature-sensitive gel was prepared using the cold dissolution method. Large-eared white rabbits were used in retention and irritation experiments. The liposomes were small single-chambered liposomes, spherical or sphere-like, with a vesicle size of 187.03 ± 6.20 nm, an encapsulation efficiency of 70.39 ± 1.13%, and a drug loading capacity of 4.63 ± 0.06%. The gelling temperatures before and after dilution by simulated tear fluid were 26.1 ± 0.2°C and 34.2 ± 0.2°C, the vesicle size was 184.94 ± 7.28 nm, and the liposomes were spherical or sphere-like in the gel matrix. The in vitro dissolution and release experiments indicate that the gel was released upon dissolution and exhibited a zero-level release pattern. Preparation into liposomes and liposomal gels prolonged the ocular retention time of the formulation without ocular irritation.

Copper (Cu) is an essential trace element in the human body that is involved in the formation of several natural enzymes, such as superoxide dismutase and cyclooxygenase. Due to the high density of the outer electron cloud of Cu, which allows the transfer of multiple electrons, Cu is often used as the catalytic center in various metabolic enzymes. However, both deficiency and excessive accumulation of Cu can result in irreversible damage to cells. Therefore, strategies to regulate Cu metabolism, such as Cu exhaustion and Cu supplementation, have emerged as attractive approaches in anticancer therapy, due to the potential damages caused by Cu metabolism disorders. Notably, recent advancements in nanotechnology have enabled the development of nanomaterials that can regulate Cu metabolism, making this therapy applicable in vivo. In this review, we provide a systematic discussion of the physical and chemical properties of Cu and summarize the applications of nanotechnology in Cu metabolism-based antitumor therapy. Finally, we outline the future directions and challenges of nano-Cu therapy, emphasizing the scientific problems and technical bottlenecks that need to be addressed for successful clinical translation.