ACS Biomaterials Science & Engineering最新文献

Using the coordination bonds between transition metal atoms and electron-rich functional groups, we synthesized two kinds of micelle-like nanoparticles. Using magnetic Fe₃O₄ as the core, poly(methyl methacrylate) (PMMA) and poly(acrylic acid) (PAA) brushes were grafted via activators regenerated by electron transfer for atom transfer radical polymerization (ARGET-ATRP), which formed micelle-like magnetic nanoparticles Fe₃O₄/PAA-PMMA with a hydrophobic outer layer and Fe₃O₄/PMMA-PAA with a hydrophilic outer layer. Both the micelle-like nanoparticles had amphiphilic properties and can be used to load hydrophilic or hydrophobic drugs. Even loaded with hydrophobic drugs, the micelle-like nanoparticles can still be dispersed in aqueous solution, and Fe₃O₄/PAA-PMMA had a higher loading content. As the drug carrier, these two micelle-like nanoparticles can be used for magnetically targeted drug delivery and magnetic resonance imaging due to superparamagnetic Fe₃O₄. In addition, due to the magnetic retention effect, the drug-loaded micelle-like nanoparticles remained at the tumor site, increasing the local drug concentration. At the same time, the drug-loaded micelle-like nanoparticles generated a magnetocaloric effect under the alternating magnetic field, which not only killed tumor cells by magnetic hyperthermia but also promoted the rapid release of drugs at the tumor site. In general, magnetically enhanced chemotherapy showed the best therapeutic effect on tumors.

Hydrogels have become common in wound treatment because they form very stable and biocompatible environments that promote healing. However, due to the highly porous hydrogel structure, any therapeutic added to these gels tends to diffuse quickly and impact delivery to the target site. Aptamers are short, single-stranded DNA or RNA sequences that bind specifically to a target, so aptamers that bind to hydrogels could serve as tags for therapeutics to prevent rapid diffusion and allow for extended delivery. An in vitro selection approach was developed to identify DNA aptamers for alginate hydrogels. Two DNA aptamers were shown to bind hydrogels ranging from 0.5 to 2% alginate and could be either encapsulated during gelation or introduced to preformed gels. Both aptamers also showed specificity for binding to alginate compared to agarose. To demonstrate the functional aspect of the aptamers as tethers for other biomolecules, both aptamers were conjugated to BSA. Aptamer-conjugated BSA was retained longer in the hydrogel during week-long diffusion studies both when encapsulated or introduced to preformed gels, which adds flexibility to how these aptamers can be deployed in a clinical setting.

Alveolar bone defects caused by oral trauma, alveolar fenestration, periodontal disease, and congenital malformations can severely affect oral function and facial aesthetics. Despite the successful clinical applications of bone grafts or bone substitutes, optimal alveolar bone regeneration continues to be challenging due to the complex oral environment and its unique physiological functions. Hydrogels that serve as promising candidates for tissue regeneration are under development to meet the specific needs for increased bone regeneration capacity and improved operational efficiency in alveolar bone repair. In this review, we emphasize the considerations in hydrogel design for alveolar bone regeneration and summarize the latest applications of hydrogels in prevalent clinical diseases related to alveolar bone defects. The future perspectives and challenges for the application of hydrogels in the field of alveolar bone regeneration are also discussed. Deepening our understanding of these biomaterials will facilitate the advent of novel inventions to improve the outcome of alveolar bone tissue regeneration.

Mechanical stiffness of liver organoid is a key indicator for the progress of hepatic steatosis. Probe indentation is a noninvasive methodology to measure Young's modulus (YM); however, the inhomogeneous nature of the liver organoid induces measurement uncertainty requiring a large number of indentations covering a wide scanning area. Here, we demonstrate that lipid-stained fluorescence imaging-assisted probe indentation significantly reduces the number of measurements by specifying the highly lipid-induced area. Lipid-stained hepatic steatosis model liver organoid shows broad fluorescence distributions that are spatially correlated with a decreased YM on a lipid-filled region with bright fluorescence compared with that measured on a blank region with dark fluorescence. The organoid viability remained robust even after exposure to an ambient condition up to 6 h, showing that probe indentations can be noninvasive methods for liver organoid stiffness measurements.

Cancer cell membrane-derived biomimetic nanovaccines have shown tremendous potential in cancer immunotherapy. However, their efficacy is restricted by the insufficient cross-presentation of cell membrane-associated antigens. Saposins (SAs), which are vital for membrane vesicle disintegration and cell membrane-associated antigen presentation, are severely deficient in the antigen-presenting cells (APCs) within tumors. Herein, we propose a complementary strategy for increasing the efficacy of biomimetic nanovaccines via the use of SAs. Biomimetic nanovaccines were designed using cancer cell membrane shells to provide a comprehensive array of tumor-associated antigens and reactive oxygen species (ROS)-responsive nanoparticle cores that allowed the codelivery of cytosine-guanine dinucleotides (CpGs) and SAs. The biomimetic nanovaccines were ROS-responsive and highly internalized by APCs, which enabled the release of CpGs and SAs in the endo/lysosomes of APCs. Furthermore, biomimetic nanovaccines increased the activation of immunosuppressive APCs and enhanced T-cell priming by delivering SAs to the APCs. Consequently, biomimetic nanovaccines loaded with SAs not only suppressed tumor growth but also exhibited excellent therapeutic effects in combination with immune checkpoint blockade strategies. Overall, our study provides insights into the development of enhanced biomimetic nanovaccines via integrating SAs and offers a promising strategy for highly effective cancer immunotherapy.

Endoscopic submucosal dissection (ESD) is a widely used procedure for the treatment of early and precancerous gastrointestinal lesions and has become the standard treatment. In this procedure, the commonly used materials have a short retention time and a limited lifting capacity, which will prolong the duration of the ESD procedure. Furthermore, these liquids tend to diffuse after ESD surgery, failing to adequately protect the wound. Therefore, we designed and developed injectable hydrogels based on hyaluronic acid. A series of oxidized hyaluronic acid (OHA) and hydrazide hyaluronic acid (AHA) were synthesized, and 16 kinds of injectable hydrogels were fabricated to investigate the effects of molecular structures on the properties of the hydrogels. Among these, the O1A3 hydrogel exhibited a suitable injection performance, gelation time, and mechanical properties, along with good blood and cell compatibility in vitro. Subsequently, in a porcine model of the ESD procedure, the results demonstrated that the O1A3 hydrogel exhibited a good retention time and lifting performance while also significantly reducing the operation time from 1-2 h to ∼10 min. Furthermore, the adhesive property of the O1A3 hydrogel on small bleeding spots and wounds could be observed, which was beneficial in protecting the wound from the complex environment of the gastrointestinal tract. The present work of injectable hyaluronic acid-based hydrogels could be promising to improve the efficiency of ESD surgery.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a very low 5-year survival rate, which is partially attributed to chemoresistance. Although the regulation of chemoresistance through biochemical signaling is well-documented, the influence of three-dimensional (3D) matrix stiffness is poorly understood. In this study, gelatin methacrylate (GelMA) hydrogels were reconstructed with stiffnesses spanning the range from normal to cancerous PDAC tissues, which are termed as the soft group and stiff group. The PDAC cell lines (Mia-PaCa2 and CFPAC-1) encapsulated in the stiff group displayed a chemoresistance phenotype and were prominent against gemcitabine. RNA-sequencing and bioinformatics analysis indicated that glycolysis was apparently enriched in the stiff group versus the soft group, which was also validated through assays of glucose uptake, lactate production, and the expression of GLUT2, HK2, and LDHA. A rescue assay with 2-deoxy-d-glucose and N-acetylcysteine demonstrated that glycolysis is involved in chemoresistance. Furthermore, the expression of Piezo1 and the content of Ca²⁺ were elevated in the stiff group. The addition of Yoda1 (Piezo1 agonist) in the soft group promoted glycolysis, whereas in the stiff group, treatment with GsMTx4 (Piezo1 inhibitor) inhibited glycolysis, which showcased that Piezo1 participated in 3D matrix stiffness-induced glycolysis. Taken together, Piezo1-mediated glycolysis was involved in PDAC chemoresistance triggered by the 3D matrix stiffness. Our study sheds light on the mechanism underlying chemoresistance in PDAC from the perspective of 3D mechanical cues.

Maintaining undifferentiated states of human pluripotent stem cells (hPSCs) is key to accomplishing successful hPSC research. Specific culture conditions, including hPSC-compatible substrates, are required for the hPSC culture. Over the past two decades, substrates supporting hPSC self-renewal have evolved from undefined and xenogeneic protein components to chemically defined and xenogeneic-free materials. However, these synthetic substrates are often costly and complex to use, leading many laboratories to continue using simpler undefined extracellular matrix (ECM) protein mixtures. In this study, we present a method using poly(norepinephrine) (pNE) for surface modification to enhance the immobilization of ECM proteins on various substrates, including polydimethylsiloxane (PDMS) and ultralow attachment (ULA) hydrogels, thereby supporting hPSC culture and maintenance of pluripotency. The pNE-mediated surface modification enables spatial patterning of ECM proteins on nonadhesive ULA surfaces, facilitating tunable macroscopic cell patterning. This approach improves hPSC attachment and growth and allows for cell patterning to study the effects of anisotropic environments on the hPSC fate. Our findings demonstrate the versatility and simplicity of pNE-mediated surface modification for improving hPSC culture and spatially controlled differentiation into endothelial cells and cardiomyocytes on previously nonamenable substrates, providing a valuable tool for tissue engineering and regenerative medicine applications.

Dynamic protein hydrogels have attracted increasing attention owing to their tunable physiochemical and mechanical properties, customized functionality, and biocompatibility. Among the different types of dynamic hydrogels, photoresponsive hydrogels are of particular interest. Here, we report the engineering of a photoresponsive protein hydrogel by using the photocleavable protein PhoCl. We employed the well-developed SpyTag and SpyCatcher chemistry to engineer PhoCl-containing covalently cross-linked hydrogels. In the hydrogel network, PhoCl, which can be cleaved into two fragments upon violet irradiation, is employed as a dynamic structural motif to regulate the cross-linking density of the hydrogel network. The resultant PhoCl-containing hydrogels showed photoresponsive viscoelastic properties. Upon violet irradiation, the PhoCl hydrogels soften, leading to an irreversible reduction in the storage moduli. However, no gel-sol transition was observed. Leveraging this light-induced stiffness change, we employed this hydrogel as a cell culture substrate to investigate the mechanobiological response of NIH-3T3 fibroblast cells. Our results showed that 3T3 cells can change their morphologies in response to the stiffness change of the PhoCl hydrogel substrate dynamically, rendering PhoCl-based hydrogels a useful substrate for other mechanobiological studies.

Endometritis, a prevalent obstetric condition primarily caused by Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), significantly threatens the reproductive performance of female animals. In this study, thermosensitive injectable chitosan (CS)/β-glycerophosphate (β-GP) hydrogels loaded with berberine (BBR) and carvacrol (CAR) were prepared for endometritis treatment. In vitro, BBR/CAR-CS/β-GP hydrogels exhibited rapid gelation within 5 min at 37 °C, excellent injectability, and more than 90% degradation within 30 days under enzymatic action. The dual drug-loaded system also exhibited controlled release of BBR and CAR and demonstrated the antimicrobial activity against E. coli and S. aureus. In vivo, uterine injection of BBR/CAR-CS/β-GP hydrogels alleviated infection-induced injuries and reduced the bacterial load in infected uterine tissues. In summary, these findings highlight the potential of BBR/CAR-CS/β-GP hydrogels as innovative carriers for drug delivery targeting endometritis.