Advanced healthcare materials

Việc tăng tốc và điều trị triệt để các vết thương mãn tính vẫn đang là một nhu cầu y tế lớn chưa được đáp ứng do các triệu chứng phức tạp từ rối loạn chuyển hóa của vi môi trường vết thương. Mặc dù có nhiều chiến lược và các hydrogel sinh học được phát triển, một phương pháp điều trị vết thương mãn tính hiệu quả và phổ biến vẫn là một điểm nghẽn. Với mục tiêu đẩy nhanh quá trình chữa lành vết thương mãn tính, nhiều hydrogel băng gạc có chức năng chống oxy hóa đã xuất hiện và được chứng minh là có thể tăng tốc độ chữa lành vết thương, đặc biệt là trong việc sửa chữa vết thương mãn tính. Chiến lược mới trong điều trị vết thương mãn tính do hydrogel chống oxy hóa mang lại có ý nghĩa to lớn đối với sức khỏe con người. Ở đây, ứng dụng của hydrogel chống oxy hóa trong việc sửa chữa vết thương mãn tính được thảo luận một cách hệ thống, nhằm cung cấp một tài liệu tham khảo lý thuyết quan trọng cho những đột phá tiếp theo trong việc chữa lành vết thương mãn tính.

Recent advances in 3D printing have enabled the creation of novel 3D constructs and devices with an unprecedented level of complexity, properties, and functionalities. In contrast to manufacturing techniques developed for mass production, 3D printing encompasses a broad class of fabrication technologies that can enable 1) the creation of highly customized and optimized 3D physical architectures from digital designs; 2) the synergistic integration of properties and functionalities of distinct classes of materials to create novel hybrid devices; and 3) a biocompatible fabrication approach that facilitates the creation and cointegration of biological constructs and systems. This progress report describes how these capabilities can potentially address a myriad of unmet clinical needs. First, the creation of 3D‐printed prosthetics to regain lost functionalities by providing structural support for skeletal and tubular organs is highlighted. Second, novel drug delivery strategies aided by 3D‐printed devices are described. Third, the advancement of medical research heralded by 3D‐printed tissue/organ‐on‐chips systems is discussed. Fourth, the developments of 3D‐printed tissue and organ regeneration are explored. Finally, the potential for seamless integration of engineered organs with active devices by leveraging the versatility of multimaterial 3D printing is envisioned.

Catheter‐associated urinary tract infections (CAUTIs) are one of the most commonly occurring hospital‐acquired infections. Current coating strategies to prevent catheter‐associated biofilm formation are limited by their poor long‐term efficiency and limited applicability to diverse materials. Here, the authors report a highly effective non‐fouling coating with long‐term biofilm prevention activity and is applicable to diverse catheters. The thin coating is lubricous, stable, highly uniform, and shows broad spectrum prevention of biofilm formation of nine different bacterial strains and prevents the migration of bacteria on catheter surface. The coating method is adapted to human‐sized catheters (both intraluminal and extraluminal) and demonstrates long‐term biofilm prevention activity over 30 days in challenging conditions. The coated catheters are tested in a mouse CAUTI model and demonstrate high efficiency in preventing bacterial colonization of both Gram‐positive and Gram‐negative bacteria. Furthermore, the coated human‐sized Foley catheters are evaluated in a porcine CAUTI model and show consistent efficiency in reducing biofilm formation by Escherichia coli (E. coli) over 95%. The simplicity of the coating method, the ability to apply this coating on diverse materials, and the high efficiency in preventing bacterial adhesion increase the potential of this method for the development of next generation infection resistant medical devices.

Non‐small cell lung cancer (NSCLC) is the most common type of lung cancer with substantial morbidity and mortality. Herein, a new signal‐on electrochemiluminescence (ECL) immunosensor based on multiple amplification strategies is constructed for ultrasensitive detection of cytokeratin 19 fragment antigen 21‐1 (CYFRA21‐1) biomarker related to NSCLC. Polyethyleneimine (PEI) functionalized MXene is decorated with NiMn layer double hydroxide (NiMn LDH) to form MXene‐PEI‐NiMn LDH composite. Specially, the La‐MOF@ZIF‐67 bimetallic organic framework (named as LZBM) and MXene‐PEI‐NiMn LDH both served as coreaction accelerators to improve the ECL emission of the luminol‐H₂O₂ system. To be specific, Au nanoparticles (AuNPs) coated MXene‐PEI‐NiMn LDH is applied to immobilize primary CYFRA21‐1 antibody (Ab₁), while AuNPs decorated LZBM was used for the loading of luminol and secondary CYFRA21‐1 antibody (Ab₂) to form tracer label. Therefore, the ECL signal of the sandwich‐type immunosensor is significantly enhanced due to the high loading capability for luminol and the synergistic catalytic ability for the decomposition of H₂O₂ into reactive oxygen species (ROS). Under the optimal experimental conditions, the ECL immunosensor exhibited good analytical performances for CYFRA21‐1 detection with a wide linear range (100 fg mL⁻¹−100 ng mL⁻¹) and a low limit of detection (85.20 fg mL⁻¹), providing a promising method for early diagnosis of NSCLC.

This study is focused on the crucial issue of biodegradability of graphene under in vivo conditions. Characteristic Raman signatures of graphene are used to three dimensionally (3D) image its localization in lung, liver, kidney and spleen of mouse and identified gradual development of structural disorder, happening over a period of 3 months, as indicated by the formation of defect‐related D'band, line broadening of D and G bands, increase in I_D/I_G ratio and overall intensity reduction. Prior to injection, the carboxyl functionalized graphene of lateral size ∼200 nm is well dispersed in aqueous medium, but 24 hours post injection, larger aggregates of size up to 10 μm are detected in various organs. Using Raman cluster imaging method, temporal development of disorder is detected from day 8 onwards, which begins from the edges and grows inwards over a period of 3 months. The biodegradation is found prominent in graphene phagocytosed by tissue‐bound macrophages and the gene expression studies of pro‐inflammatory cytokines indicated the possibility of phagocytic immune response. In addition, in vitro studies conducted on macrophage cell lines also show development of structural disorder in the engulfed graphene, reiterating the role of macrophages in biodegradation. This is the first report providing clear evidence of in vivo biodegradation of graphene and these results may radically change the perspective on potential biomedical applications of graphene.

Despite the enormous therapeutic potential of siRNAs, their delivery is still problematic due to unfavorable biodistribution profiles and poor intracellular bioavailability. Calcium phosphate co‐precipitate has been used for nearly 40 years for in vitro transfection due to its non‐toxic nature and simplicity of preparation. However, rapid particle growth has largely prevented the translation of this method for in vivo purposes. It has recently been shown that bisphosphonate derivatives can physically stabilize calcium phosphate nanoparticles while still allowing for efficient cell transfection with plasmid DNA. Herein, two novel PEGylated chelating agents (PEG‐alendronate and PEG‐inositolpentakisphosphate) with enhanced stabilizing properties are introduced, and it is demonstrated that the bisphosphonate‐stabilized nanoparticles can efficiently deliver siRNA in vitro. The nanoparticles are mainly taken up by clathrin‐dependent endocytosis, and acidification of the endosomal compartment is required to release the entrapped siRNA into the cytosol. Furthermore, particle uptake enhances the inhibition of the mevalonate pathway by the bisphosphonate in macrophages.

Viral nanoparticles have attracted extensive research interests in diverse applications of diagnosis and therapy. In particular, filamentous M13 bacteriophages have shown great potential in biomedical applications. However, its pathways entering into cells still remain unclear, and this greatly hinders its further use as a drug or gene carrier. Here, a ratiometric M13 pH probe is designed by conjugating two fluorescent dyes onto the surface of M13. Since the intensity ratio is not influenced by probe concentration, ion strength, temperature, photobleaching, and optical path length, this ratiometric probe can be used to investigate the intracellular pH map of M13. More importantly, the internalization mechanism of M13 can be elucidated. It is found that this filamentous phage shows great cell‐type dependence in interaction with cells and internalization mechanism. The phage tends to be bounded on the cell membrane of only epithelial cells, not endothelial cells. Furthermore, the M13 phage enters into cells through endocytosis with specific mechanism: clathrin‐mediated endocytosis and macropinocytosis for HeLa; vesicular transport, clathrin‐mediated endocytosis, and macropinocytosis for MCF‐7; caveolae‐mediated endocytosis for human dermal microvascular endothelial cell (HDMEC). This work provides key notes for cancer diagnosis and therapy based on filamentous bacteriophage, especially for design of pH‐sensitive drug delivery systems.

Biomimetic, self‐assembled calcium carbonate (CaCO₃) concentric microgrooves with groove widths of 5.0 and 10 μm were fabricated through simply controlling incubation temperature. Mouse pre‐osteoblastic MC3T3‐E1 cells were cultured on flat and microgrooved substrates of CaCO₃ and their adhesion, spreading, proliferation, alkaline phosphatase activity, and calcium content were remarkably enhanced by the microgrooves, in particular, the narrower ones. Furthermore, focal adhesions and actin filaments of MC3T3‐E1 cells could be aligned on both 5.0‐μm and 10‐μm‐wide CaCO₃ grooves. Compared with the original round nuclei on the flat substrates and expanded round nuclei on the narrower microgrooves, the MC3T3‐E1 cell nuclei on 10‐μm‐wide CaCO₃ grooves demonstrated preferred entrapment in the grooves and significant alignment with a smaller area after two‐day culture.

Macrophage activation determines the fate of biomaterials implantation. Though researches have shown that fibronectin (FN) is highly involved in integrin‐induced macrophage activation on biomaterials, the mechanism of how nanosized structure affects macrophage behavior is still unknown. Here, titanium dioxide nanotube structures with different sizes are fabricated to investigate the effects of nanostructure on macrophage activation. Compared with larger sized nanotubes and smooth surface, 30 nm nanotubes exhibit considerable lesser pro‐inflammatory properties on macrophage differentiation. Confocal protein observation and molecular dynamics simulation show that FN displays conformation changes on different nanotubes in a feature of “size‐confined,” which causes the hiding of Arg‐Gly‐Asp (RGD) domain on other surfaces. The matching size of nanotube with FN allows the maximum exposure of RGD on 30 nm nanotubes, activating integrin‐mediated focal adhesion kinase (FAK)‐phosphatidylinositol‐3 kinase γ (PI3Kγ) pathway to inhibit nuclear factor kappa B (NF‐κB) signaling. In conclusion, this study explains the mechanism of nanostructural‐biological signaling transduction in protein and molecular levels, as well as proposes a promising strategy for surface modification to regulate immune responses on bioimplants.