Biomaterials research最新文献

The high prevalence of traumatic brain injury (TBI) poses an important global public health challenge. Current treatment modalities for TBI primarily involve pharmaceutical interventions and surgical procedures; however, the efficacy of these approaches remains limited. In the field of regenerative medicine, hydrogels have garnered significant attention and research efforts. This review provides an overview of the existing landscape and pathological manifestations of TBI, with a specific emphasis on delineating the therapeutic potential of hydrogels incorporated with various bioactive agents for TBI management. Particularly, the review delves into the utilization and efficacy of hydrogels based on extracellular matrix (ECM), stem cell-loaded, drug-loaded, self-assembled peptide structures or conductive in the context of TBI treatment. These applications are shown to yield favorable outcomes such as tissue damage mitigation, anti-inflammatory effects, attenuation of oxidative stress, anti-apoptotic properties, promotion of neurogenesis, and facilitation of angiogenesis. Lastly, a comprehensive analysis of the merits and constraints associated with hydrogel utilization in TBI treatment is presented, aiming to steer and advance future research endeavors in this domain.

Nanotechnology has been increasingly utilized in anticancer treatment owing to its ability of engineering functional nanocarriers that enhance therapeutic effectiveness while minimizing adverse effects. Inorganic nanoparticles (INPs) are prevalent nanocarriers to be customized for a wide range of anticancer applications, including theranostics, imaging, targeted drug delivery, and therapeutics, because they are advantageous for their superior biocompatibility, unique optical properties, and capacity of being modified via versatile surface functionalization strategies. In the past decades, the high adaptation of INPs in this emerging immunotherapeutic field makes them good carrier options for tumor immunotherapy and combination immunotherapy. Tumor immunotherapy requires targeted delivery of immunomodulating therapeutics to tumor locations or immunological organs to provoke immune cells and induce tumor-specific immune response while regulating immune homeostasis, particularly switching the tumor immunosuppressive microenvironment. This review explores various INP designs and formulations, and their employment in tumor immunotherapy and combination immunotherapy. We also introduce detailed demonstrations of utilizing surface engineering tactics to create multifunctional INPs. The generated INPs demonstrate the abilities of stimulating and enhancing the immune response, specific targeting, and regulating cancer cells, immune cells, and their resident microenvironment, sometimes along with imaging and tracking capabilities, implying their potential in multitasking immunotherapy. Furthermore, we discuss the promises of INP-based combination immunotherapy in tumor treatments.

Although curcumin has been well known as a phytochemical drug that inhibits tumor promotion by modulating multiple molecular targets, its potential was not reported as a targeting ligand in the field of drug delivery system. Here, we aimed to assess the tumor-targeting efficiency of curcumin and its derivatives such as phenylalanine, cinnamic acid, coumaric acid, and ferulic acid. Curcumin exhibited a high affinity for estrogen receptors through a pull-down assay using the membrane proteins of MCF-7, a breast cancer cell line, followed by designation of a polymer-based gene therapy system. As a basic backbone for gene binding, dextran grafted with branched polyethylenimine was synthesized, and curcumin and its derivatives were linked to lysine dendrimers. In vitro and in vivo antitumor effects were evaluated using plasmid DNA expressing anti-bcl-2 short hairpin RNA. All synthesized gene carriers showed excellent DNA binding, protective effects against nuclease, and gene transfection efficiency in MCF-7 and SKBr3 breast cancer cells. Preincubation with curcumin or 17α-estradiol resulted in a marked dose-dependent decrease in gene transfer efficiency and suggested targeting specificity of curcumin. Our study indicates the potential of curcumin and its derivatives as novel targeting ligands for tumor cells and tissues.

Despite marked advancements in cancer immunotherapy over the past few decades, there remains an urgent need to develop more effective treatments in humans. This review explores strategies to overcome hurdles in cancer immunotherapy, leveraging innovative technologies including multi-specific antibodies, chimeric antigen receptor (CAR) T cells, myeloid cells, cancer-associated fibroblasts, artificial intelligence (AI)-predicted neoantigens, autologous vaccines, and mRNA vaccines. These approaches aim to address the diverse facets and interactions of tumors' immune evasion mechanisms. Specifically, multi-specific antibodies and CAR T cells enhance interactions with tumor cells, bolstering immune responses to facilitate tumor infiltration and destruction. Modulation of myeloid cells and cancer-associated fibroblasts targets the tumor's immunosuppressive microenvironment, enhancing immunotherapy efficacy. AI-predicted neoantigens swiftly and accurately identify antigen targets, which can facilitate the development of personalized anticancer vaccines. Additionally, autologous and mRNA vaccines activate individuals' immune systems, fostering sustained immune responses against cancer neoantigens as therapeutic vaccines. Collectively, these strategies are expected to enhance efficacy of cancer immunotherapy, opening new horizons in anticancer treatment.

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen species and inflammatory response contribute to secondary damage following ischemic insult. Nanozymes with robust anti-oxidative stress properties possess therapeutic possibility for ischemic insult. However, insufficiency of nanozyme accumulation in the neuronal mitochondria hindered their application. Herein, we constructed polydopamine-coated Prussian blue nanoparticles (PB@PDA NPs) to realize the targeting neuronal mitochondria for ischemic stroke, with the properties of antioxidant and anti-inflammation. After administration, much higher accumulation of PB@PDA NPs in the brain was observed compared to that in the PB NP group. Moreover, PB@PDA NPs effectively attenuated brain infarct than that of PB NPs in neonatal mice following hypoxia-ischemia (HI) insult. PB@PDA NPs mainly colocated with neuronal mitochondria in vivo and in vitro. Apart from attenuating oxidative stress, PB@PDA NPs also suppressed neuronal apoptosis and counteracted inflammation, which effectively promote a short- and long-term functional recovery in HI mice. Further, the therapeutic efficacy of PB@PDA NPs was also found in adult ischemic mice via tail vein injection. Collectively, these findings illustrate that PB@PDA NPs via system injection accumulate in neuronal mitochondria and are beneficial for ischemic stroke.

Gelatin methacryloyl (GelMA) stands out for its biocompatibility, tunability, and functionality, being often selected as a scaffolding material. However, the biological modulations induced by its photocrosslinking process on mesenchymal stem cells as well as stress mitigation measures remain insufficiently explored. By using GelMA of Good Manufacturing Practice (GMP) grade, this study aimed (a) to achieve a comprehensive understanding of the biological effects of photocrosslinking process with a specific focus on oxidative stress and (b) to develop a strategy to mitigate the adverse effects by employing conditioned medium (CM) by dental pulp stem cells (DPSCs). Following photocrosslinking, pathways related to oxidative phosphorylation and DNA repair were enriched in the presence of DPSC-CM carrying various antioxidants such as peroxiredoxin (PRDX) 1-6 and superoxide dismutase type 1 (SOD1), while the control samples exhibited enrichment in inflammatory signaling pathways. Incorporating DPSC-CM into the hydrogel notably reduced the degree of cellular oxidation caused by photocrosslinking and stress responses, resulting in improved cell viability, growth, motility, and osteogenic differentiation, as well as fewer apoptotic and senescent cells compared to those without DPSC-CM. The deteriorated biocompatibility of freshly crosslinked GelMA hydrogel was confirmed by the disrupted vasculature of chorioallantoic membranes in chicken embryos after implantation, which was prevented by DPSC-CM. In conclusion, this study demonstrates the robust antioxidative effects of DPSC-CM, mitigating the negative effect of GelMA photocrosslinking processes.

Skin damage caused by chemical corrosion is currently one of the common skin diseases and poisoning symptoms, with nitrogen mustard compounds causing the most persistent and severe damage. These chemicals penetrate the top layer of the skin, enter the dermis, and cause DNA damage, oxidative stress, and inflammation. However, to date, no effective drug treatment has been found. Even the potential antidotes could not effectively penetrate the top layer of the skin to exert their effects due to the skin barrier. To address this problem, an innovative transdermal drug delivery strategy based on aspirin microneedles was proposed. The classic medicine aspirin was first discovered not only to reduce inflammation and oxidative stress but also to promote DNA repair and reduce DNA damage. The aspirin microneedles directly delivered the drug to the damaged area, released aspirin through the skin barrier, and exhibited good biocompatibility. These findings indicate that aspirin microneedles have great potential for promoting wound healing and broad application prospects.

Background: Antioxidant therapy aimed at reducing excessive local oxidative stress is one of the most important strategies for promoting diabetic wound repair. The reversible transformation of Ce³⁺/Ce⁴⁺ in ceria (CeO₂) can reduce excessive local oxidative stress. However, inducing angiogenesis, local anti-inflammatory effects, and other positive effects are challenging. Therefore, ideal dressings for chronic diabetic wound management must concurrently reduce excessive oxidative stress, promote angiogenesis, and have anti-inflammatory effects. Methods: In this study, Ce-doped borosilicate bioactive glasses (BGs) were prepared using the sol-gel method, and CeO₂ nanocrystals (CeO₂-NCs) were precipitated on the glass surface by heat treatment to obtain BG-xCe composite glass nanospheres. Subsequently, nanospheres were modified by amino group and combined with dopamine and acrylamide to obtain BG-xCe/polydopamine/polyacrylamide (PDA/PAM) composite hydrogel. Then, the morphology and properties of composite hydrogels were detected, and the properties to treat the diabetic wounds were also evaluated. Results: The results demonstrated that the BG-10Ce/PDA/PAM composite hydrogel possessed excellent tensile and adhesive properties. In vitro, the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) and fibroblasts (L929) were enhanced by reducing reactive oxygen species (ROS) levels in the conditioned medium. Animal experiments have shown that CeO₂-NCs in hydrogels effectively scavenge ROS in diabetic wounds, and Sr dissolved from the glassy phase can modulate macrophage polarization to the M2 phenotype. Conclusions: The synergistic effect of both amorphous materials and nanocrystals provides the BG-10Ce/PDA/PAM composite hydrogel with great potential for diabetic wound healing.

Severe open wounds should be closed immediately and regularly undergo re-examination and debridement. Therefore, dressings should effectively cover the wound, creating a moist environment for healing while meeting mechanical requirements for daily movement and adaptability. Herein, a low-cost and easy-to-prepare plant polysaccharide hydrogel was reported. The Mesona chinensis Benth polysaccharide strengthened the hydrogel network by hydrogen bonding and changed the phase transition temperature, but retained the thermal response characteristics of the hydrogel. By adjusting the polysaccharide concentration, MepGel(1) can be prepared to remain stable as a semisolid at body temperature and transform into a shear-thinning semifluid state when appropriately heated. The composite hydrogel could be easily shaped, effectively closing wounds of different shapes, while maintaining excellent mechanical properties. Importantly, this composite hydrogel had a near-infrared photothermal effect resulting in excellent antibacterial effect and collided with its own thermal response producing functions conducive to wound care, like accelerating the self-healing of the dressing, achieving re-adhesion, and further covering the wound. Furthermore, the hydrogel had excellent biocompatibility, enhancing immunity and promoting healing of bacterial-infected wounds. The low cost and rich functionality demonstrated by MepGel had the potential to face the enormous challenges and economic burden of clinical wound healing.

Periprosthetic infections resulting from bacterial biofilm formation following surgical bone fracture fixation present important clinical challenges. Conventional orthopedic implant materials, such as titanium, are prone to biofilm formation. This study introduces a novel surface for orthopedic titanium plates, optimized for clinical application in human bone fractures. Leveraging nanostructure-based surface coating technology, the plate achieves an antibacterial/immunonegative surface using biocompatible materials, including poloxamer 407, epigallocatechin gallate, and octanoic acid. These materials demonstrate high biocompatibility and thermal stability after autoclaving. The developed plate, named antibacterial immunonegative surface, releases antibacterial agents and prevents adhesion between human tissue and metal surfaces. Antibacterial immunonegative surface plates exhibit low cell toxicity, robust antibacterial effects against pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, high resistance to biofilm formation on the implant surface and surrounding tissues, and minimal immune reaction in a rabbit femoral fracture model. This innovation holds promise for addressing periprosthetic infections and improving the performance of orthopedic implants.