ACS Applied Bio Materials最新文献

Cancer has become a highly prevalent disease and poses serious threats to human health. Conventional cancer treatments still face high risks of recurrence. Training the immune system to recognize and eliminate tumors via external stimulation, such as vaccines, emerges as a promising approach for cancer prevention and treatment. However, injectable vaccines may have limited immune activation, causing difficulties in maintaining long-term immune surveillance of tumorigenesis by tumor-specific cytotoxic T cells. Here, degradable zwitterionic cryogels were prepared using the cryogelation technique. The cryogenic preparation maintained the biological activities of tumor antigens and immune adjuvants loaded in the cryogels. The macroporous structure endowed the injectability of cryogels into the body via conventional syringes. In the presence of proteases, the cryogels degraded, allowing sustained release of antigens and adjuvants, ensuring continued dendritic cell (DC) recruitment and antigen presentation to maturing tumor-specific cytotoxic T cells. In vivo experiments demonstrated that the cryogel cancer vaccines elicited robust immune activation and effectively modulated tumor microenvironments. The combination with photothermal therapy significantly inhibited tumor growth, showing great potential for preventing postoperative recurrence. Additionally, the zwitterionic cryogels were biocompatible without obvious toxicities during degradation. The cryogels could serve as effective vaccine platforms to prevent cancer recurrence after surgery.

The aim of this study is to design a therapeutic enhanced three-dimensional (3D) silk fibroin (SF)-based scaffold containing propolis (Ps)-loaded chitosan (CH) nanocarriers. To this aim, we initially synthesized a hybrid gel-based ink by a synergistic sol-gel and self-assembly approach and then processed the resulting gels by microextrusion-based 3D printing followed by supercritical drying to obtain 3D hybrid aerogel scaffolds. Ps was utilized to enhance the final scaffold's bactericidal efficacy and cell responsiveness. For the synthesis of the scaffold, two Ps loading methods (in preprint and postprinting steps) were investigated in order to optimize the Ps drug quantities in the scaffold and maximize the antibacterial properties of scaffold. In the postprinting Ps loading step, the hybrid silica-oxidized SF (SFO)-CH hydrogel ink was 3D printed into a construct with an interconnected porous structure, and then, Ps was loaded into the printed construct. In the preprint loading method, PS was incorporated into the SF and a hydrolyzed silane solution prior to gelation. The morphological studies demonstrate that the addition of Ps encapsulated CH nanoparticles (NPs) into the hydrogel solution improved the porosity of the developed scaffolds. The rheological analysis of the designed gel ink with and without Ps loading and the release kinetics were studied. The antimicrobial results show that the Ps-loaded scaffolds in the postprinting step exhibited superior antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) strains compared to a preprinted Ps-loaded scaffold. Direct and indirect in vitro cytotoxicity tests also confirmed the designed Ps-loaded scaffold biocompatibility toward a mouse fibroblast (L929) cell line. We demonstrated that the scaffold formulated by propolis-loaded chitosan NPs can enhance the migration and proliferation of L929 fibroblast cells. The obtained results prove the promise of the designed 3D printed silica-SFO-CH-Ps scaffolds as a potent 3D scaffold to mediate tissue regeneration but also as an antibacterial highly porous matrix to support wound healing.

Superoxide anion (O₂^•-) is a highly reactive oxygen species (ROS) within tumor cells, and its abnormal concentrations can lead to various diseases such as cancer, inflammation, and premature aging disorders. Here, we obtained a series of bioluminescence resonance energy transfer (BRET) systems that can be used for sensitive and specific detection of O₂^•- by varying the type and reaction time of quantum dots (QDs) and combining them with different concentrations of recombinant aequorin. Among them, the recombinant aequorin-conjugated CdTe/CdSe QDs had the highest conjugation efficiency as the Aeq-QD BRET sensor, which has a remarkable energy transfer efficiency of 35.6% and an extremely low limit of 4 nM for detecting O₂^•-, which exceeds traditional chemiluminescence detection relying on coelenterazine. The applicability of this sensor for assessing tumor oxidative stress levels was also validated in diverse cell types and cancer mice. This study effectively contributes to the field of cancer research and tumor oxidative stress biology based on O₂^•- sensing.

The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC₅₀ value of 146.37 μg/ml and 105.90 μg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer.

Several clinical issues are associated with reduced oxygen delivery to tissues due to impaired vascular perfusion; moreover, organs procured for transplantation are subjected to severe hypoxia during preservation. Consequently, alternative tissue oxygenation is an active field in biomedical research where several innovative approaches have been recently proposed. Among these, intravascular photosynthesis represents a promising approach as it relies on the intrinsic capacity of certain microorganisms to produce oxygen upon illumination. In this context, this work aims at the development of photosynthetic perfusable solutions that could be applied to preserve organs for transplantation purposes. Our findings demonstrate that a biocompatible physiological solution containing the photosynthetic microalgae Chlamydomonas reinhardtii can fulfill the metabolic oxygen demand of rat kidney slices in vitro. Furthermore, intravascular administration of this solution does not induce tissue damage in the rat kidneys. Moreover, kidney slices obtained from these algae-perfused organs exhibited significantly improved preservation after 24 h of incubation in hypoxia while exposed to light, resulting in reduced tissue damage and enhanced metabolic status. Overall, the results presented here contribute to the development of alternative strategies for tissue oxygenation, supporting the use of perfusable photosynthetic solutions for organ preservation in transplantation.

Multidrug resistance (MDR) is a major obstacle to traditional cancer treatment using chemotherapeutic agents like doxorubicin (DOX). MDR affects drug dosage regimens and enables the recurrence and metastasis of cancer. Because DOX causes severe side effects at high dosages, it is important to use an MDR modulator to make cancer cells sensitive to DOX. This work focused on a liposome-based codelivery system containing curcumin (CUR) and DOX, focusing on CUR as an MDR modulator. The synergistic effect was maximized when the ratio of DOX and CUR was 1:1, and the synthesis of liposomal drugs was successfully verified. In addition, a successful MDR reversal effect was demonstrated through rhodamine 123 assay, Western blotting, and immunofluorescence. Compared to the conventional DOX treatment, the dual-drug treatment exhibits a significantly improved anticancer effect. In the murine metastasis 4T1 IP tumor model, the dual-drug-encapsulating liposomes successfully suppressed tumor growth and reversed the tumoral effect (omental tumor metastasis, fat, and muscle weight loss) into a normal state.

Developing implantable medical materials with excellent comprehensive performance has important practical applications. Cardiovascular and bile ducts are characterized by various forms of diseases and high morbidity and mortality. One of the effective treatment modalities for such diseases is replacement surgery. Since commercially available materials for tubular organ sites are in short supply and the number of autologous and natural grafts is limited, the study of implantable materials that can be prepared in tubes is of great significance. This study reports on an implantable medical polyurethane material (IBP-PU) with a binary soft segment structure prepared by microwave synthesis. The material exhibits excellent mechanical properties (with a mechanical strength of 33.00 ± 4.02 MPa and a strain at break of 519.93 ± 53.44%), and stable thermomechanical properties (T_d5% > 250 °C). The excellent biocompatibility of IBP-PU (hemolysis rate = 2.55% and cell survival on the fifth day over 100%, etc.) makes it suitable for implantable medical applications. Its appropriate degradation rate allows for slow in vivo degradation with the generation of tissues, and the degradation products are nontoxic and do not require removal by secondary surgery. Additionally, the material has been successfully prepared using electrostatic spinning technology, resulting in a 5 mm caliber. It is significant for small-caliber cardiovascular, bile duct, and other in vivo tubular grafts.

A promising approach for wound treatment is using multilayer wound dressings that offer multifunctional properties. In this study, a bilayered electrospun/hydrogel gelatin-based scaffold integrated with honey and curcumin was developed to treat wounds under an in vivo study. The first layer consisted of an enzymatic cross-linked gelatin hydrogel containing honey and curcumin, which gelatin/PCL nanofibers reinforced. The physicochemical, mechanical, and biological properties of both layers were evaluated. Then, the bilayered wound dressing was compared to a commercial wound dressing in an in vivo study. The results showed that this strategy provided the wound dressing with a strength of 40 MPa, 70% elongation, 800% swelling rate, and 8 g/h/m² water vapor permeability. Furthermore, MTT and histopathological staining demonstrated that the bilayered wound dressing promoted wound closure accelerated collagen production and tissue granulation, and promoted immune system response and re-epithelialization compared to other groups. The presence of a nanofibrous layer on the surface of the wound dressing facilitated its use, and the inclusion of honey and gelatin in the hydrogel layer prevented adhesion to the wound tissue and allowed for easy replacement without damaging the wound bed. Overall, the bilayered dressing with multifunctional properties holds great potential for developing wound dressings.

Wound pH has emerged as a promising therapeutic target in diabetic foot ulcers (DFU). Here, we aimed to develop a microparticle-loaded hydrogel for pH modulation in wound fluid. In a screen of polymeric and inorganic microparticles, zeolites were identified as pH-modulating microparticles. Zeolites were encapsulated in a calcium cross-linked alginate hydrogel, a biocompatible matrix clinically used as a wound dressing. This hydrogel potently neutralized hydroxide ions in serum-containing simulated wound fluid. These findings encourage a further development of this pH-modulating device as a molecular therapeutic system for DFUs.