Biomaterials Translational最新文献

N⁶-methyladenosine RNA methylation (m⁶)A is one of the most common and widespread RNA modifications in eukaryotic cells. m⁶A plays a crucial role in the regulation of pathophysiological processes of eukaryotes. Three types of m⁶A regulators, including methyltransferases, demethylases and m⁶A-binding proteins, are involved in the reversible epigenetic modification of m⁶A. Bone is a vital organ with irreplaceable functions of movement, haematopoiesis, and protection of other organs. Its physiological homeostasis is mainly determined by the synergy of corresponding cells such as bone marrow derived stem cells, osteoblasts, and osteoclasts. Once the physiological equilibrium is broken, the bones will transform into a pathological state, resulting with diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma. Here, we review the composition of m⁶A and its regulation mechanism in bone physiology and pathology.

Bacterial extracellular vesicles (BEVs) are emerging as promising therapeutic agents and drug delivery vehicles due to their unique properties. These nanoscale vesicles possess stable membrane structure and naturally encapsulate a variety of bioactive molecules, making them versatile tools in biomedical applications. However, clinical translation of BEVs faces challenges such as insufficient display of disease-specific antigens, excessive toxicity, and rapid clearance. Addressing these issues is crucial for the clinical translation of BEVs. In this review, we discuss recent advances in BEV engineering strategies aimed at addressing these limitations and expanding their therapeutic applications. We highlight approaches for loading exogenous cargo into BEVs, detoxification strategies, and the latest progress in the application of engineered BEVs for treating infectious diseases, cancer, and other disorders. Despite promising preclinical results, clinical translation is hindered by safety concerns, standardisation difficulties, and scalability issues. Future research should focus on optimising detoxification processes, establishing global standardisation, and improving production methods to facilitate successful clinical translation of engineered BEVs. This review provides insights into the current status and future perspectives of BEV engineering for therapeutic applications.

The transdermal drug delivery system is a highly safe and well-tolerated therapeutic approach with significant potential for treating musculoskeletal disorders. However, its clinical application is limited by the low skin permeability of many active drugs in its formulations. To overcome this challenge, advancements in skin permeation enhancement techniques are essential. Over the past decade, natural polymers have been increasingly incorporated into various nanocarriers due to their availability, biodegradability, and biocompatibility, offering new options for the effective dispersion of suspended solids. Furthermore, surface functionalisation of the numerous functional groups found in natural polymers allows them to be transformed into targeted and stimulus-responsive materials, enabling precise drug delivery to musculoskeletal tissues. This review examines the mechanisms of action of natural polymer-based transdermal drug delivery system, covering penetration enhancers, nanoparticles, microneedles, hydrogels, and nanofibres derived from chitosan, hyaluronic acid, sodium alginate, cellulose, and proteins, and their applications in treating musculoskeletal disorders. Moreover, it outlines the current challenges and prospects of polymer-based transdermal drug delivery system for localised treatment, offering insights into current therapeutic approaches and proposing new directions for advancements in this field.

Fullerenes are one of the most popular nanomaterials, and C₇₀ fullerene is the second most common fullerene after C₆₀ buckminsterfullerene. Minor modification of fullerenes derivatives can change their biological effects and antioxidant properties. A plethora of water-soluble derivatives can be synthesised based on buckminsterfullerenes. In the present study, we synthesised three water-soluble C₇₀ fullerene derivatives with thiophene-based solubilising addends and tested their cytotoxicity and the transcriptional activity of genes, which regulate an oxidative metabolism. Aliphatic chain length in the structure of the solubilising addend of the water-soluble fullerene derivative has been varied, and we revealed that a longer chain resulted in more pronounced antioxidant activity. Thus, the surface modification enhances the antioxidant properties of the compound and changes the nanoparticles impact on the genetic apparatus of the cell. Interestingly, even slight modifications of the functional addend's structure can significantly affect the final cell response. The data obtained can be harnessed to develop novel and efficient medications for the management of ischaemia, stress-related conditions, the prevention of ageing, and the resolution of other practical healthcare challenges.

Spinal cord injury (SCI) often leads to partial or complete loss of motor, sensory, and autonomic functions. We have previously shown that the transplantation of hierarchically aligned fibrin nanofibre hydrogel scaffolds (AFGs) facilitates robust neuroregeneration and functional recovery in rat and dog SCI models. Given these positive results, we aimed to evaluate the biosafety and efficacy of AFGs in a non-human primate SCI model before exploring its potential in the clinic. In the present study, no significant adverse reactions were observed over 24 weeks following AFG implantation into 1-cm gaps in the hemisected thoracic spinal cords of monkeys (Macaca fascicularis). Scaffold implantation also reduced cystic cavity formation and encouraged axonal sprouting across the lesion site. Notably, detailed histological analysis demonstrated that AFG promoted high-density, sequential, and aligned nerve fibre regeneration, resulting in remyelination and vascularisation, ultimately leading to remarkable motor function recovery. These results indicate that AFG transplantation exhibits reliable biocompatibility and effectiveness in promoting spinal cord repair in a non-human primate SCI model. Owing to the similarities in genetics and physiology between non-human primates and humans, AFG transplantation therapy is likely suitable for use in human spinal cord repair.

Osteoporosis has long been a key area of medical research, as the Wnt signalling pathway is essential for bone formation and maintaining bone balance. The purpose of this study was to perform a bibliometric analysis of the literature on osteoporosis and Wnt signalling to identify research trends, hot topics, and emerging areas of interest in this field. A visual analysis of the literature on osteoporosis and Wnt signalling offers a clearer perspective on the current research landscape, highlighting key topics and emerging trends in this area. The present study analysed publications related to osteoporosis and Wnt signalling from January 1, 2002 to December 31, 2021, using data from the Web of Science Core Collection. A total of 1553 publications were examined via tools, such as Microsoft Excel, CiteSpace, Vosviewer, and the Bibliometrics online analysis platform. The findings indicated that China has the highest number of publications in this area, with 489 articles. Warman Mathew's work has the most citations, totalling 1031 articles, and the journal Bone has published the most articles, with 89 publications. Current research in this field has focused primarily on osteogenesis, metabolism, fractures, and osteoblasts. The present study highlights the significant role of Wnt signalling in bone homeostasis and disease, suggesting that future research will explore novel metabolic therapies for osteoporosis by targeting the Wnt signalling pathway with drugs.

Organ-on-a-chip (OoC) has emerged as a revolutionary technique in recent decades, capable of replicating essential aspects of physiological and pathophysiological processes of human organs in vitro. Serving as an effective tissue culture method for creating digital twins, OoCs show significant promise and have found applications in disease modelling, drug screening, and tissue engineering. However, there has been a lack of emphasis on the fundamental design principles of OoCs in existing literature, a crucial aspect that cannot be overlooked, especially for beginners venturing into the realm of OoCs. Therefore, this paper endeavors to provide a comprehensive overview by delving into the historical development of OoCs, outlining the characteristics of their scaffolds, presenting design strategies for both conceptualisation and fabrication processes, and offering a detailed description of design mechanisms and guidelines based on recent research publications. Furthermore, it explores future prospects and challenges within the OoC domain. Serving as a foundational guide for those new to OoC exploration, this paper aims to furnish a thorough introduction to the fabrication and design strategies employed in OoCs.

Electrostrategies encompassing electrical stimulation and biomaterials with conductive or piezoelectric properties have garnered escalating interest within the orthopaedic research domain. We conducted a comprehensive bibliometric analysis of 2810 publications on electrostrategies in orthopaedic research a field for which no extensive overview has been provided to date. This study highlighted two main phases of progress since 1980 indicating an increasing emphasis on electrostrategies. We identified key contributors including institutions and authors with concentrated activity in North America, Europe and Asia. The study also outlined the most influential and co-cited journals in this domain. Our keyword analysis underscored "electrical-stimulation" "bone" and "in vitro" as prevalent themes with a significant focus on the effects of electrical stimulation on bone growth proliferation differentiation and its applications in bone surgeries. The keyword co-occurrence analysis revealed four major thematic clusters: "electrical-stimulation" "bone" "surgery" and "bone-mineral density." Our findings underscored essential research directions such as the manufacturing and application of conductive and piezoelectric biomaterials and electrically-guided stem cell differentiation. The study also pointed out the potential to enhance orthopaedic treatment methods and patients' quality of life. Future research should focus on refining electrical stimulation conditions developing new piezoelectric materials and advancing personalised tissue engineering strategies. In conclusion this study illuminates the global trends and emerging hotspots of electrostrategies in orthopaedic research providing a valuable reference for its further application and understanding in the field.

Addressing bone defects caused by degenerative diseases, trauma, and cancer through bone tissue engineering remains a significant global health challenge. The osteoinductive properties of bone morphogenetic protein-2 (BMP2) have become a key therapeutic strategy in bone regeneration. However, the development of biodegradable composites that ensure biocompatibility, stability, efficient BMP2 loading, and controlled release remains unresolved. In this study, we designed PBVHx/soy lecithin (SL)/BMP2 controlled-release microspheres (sB2PM) based on the biodegradable material poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx), incorporating SL to enable sustained BMP2 delivery and enhance capture. sB2PM microspheres exhibited uniform size (approximately 5 μm) and high BMP2 encapsulation efficiency (80.29%) compared to pure PBVHx-based microspheres (pPM). Due to PBVHx's biodegradability, BMP2 release was primarily degradation-driven, resulting in a controlled biphasic release profile. sB2PM achieved 62.79% cumulative BMP2 release over four weeks and continued to release BMP2 sustainably thereafter. Co-culturing sB2PM microspheres with human bone marrow-derived mesenchymal stem cells (hBMSCs) in a Transwell system showed enhanced cell proliferation, biocompatibility, and collagen secretion. Compared with pPM and B2PM, sB2PM significantly promoted osteogenic differentiation, increased alkaline phosphatase (ALP) activity, and upregulated osteogenic gene expression in hBMSCs, outperforming commercial hydroxyapatite microspheres. In a mouse hindlimb unloading osteoporosis model, micro computed tomography and histological evaluations confirmed that injectable sB2PM microspheres significantly enhanced bone regeneration, collagen secretion, and ALP and runt-related transcription factor 2 protein expression. This study highlights the potential of sB2PM microspheres with controlled BMP2 release for future bone regeneration therapies.

Bones can fulfill functions in movement, attachment, and protection of internal organs. Bone diseases caused by ageing, trauma, infection, and other reasons may seriously affect the daily life of patients. Magnesium ions are closely associated with the maintenance of bone health. Integrating magnesium ions into delivery systems and hydrogels can improve their application, thus directly acting on the osteoblast cell lineage and influencing the proliferation and differentiation of relevant cells. The slow release of magnesium ions allows for their effects on the target site for a long time, reducing the clearance of magnesium ions in the body, which significantly contributes to bone repair. Magnesium-based bioalloy scaffolds have received widespread attention for their favourable biocompatibility, degradability, and bone-forming properties and play an important role in bone regeneration and repair. This article presents a review on the role and mechanism of magnesium-containing materials in bone repair and regeneration. By discussing the current challenges and future directions for magnesium-containing biomaterials, new insights are provided into the development of these materials in the field of orthopaedics. In conclusion, magnesium-containing biomaterials have great application value in orthopaedics.