ACS Biomaterials Science & Engineering最新文献

Mussels, an ecologically diverse group of bivalve molluscs, have attracted attention due to phenomenal adaptability across marine and estuarine environments and an exceptional ability to adhere strongly to wet and dynamic substrata by secreting specialized adhesive structures called byssal threads. These proteinaceous structures, which are secured by sticky plaques, enable mussels to sustain harsh environments and powerful currents. The cuticular covering of byssal thread is mechanically strong but flexible, with reversible metal-ligand coordination, particularly Fe³⁺-DOPA bonds that provide load-dissipating and self-healing properties. The unique combination of different properties, including mechanical, metal-binding, and self-healing, has been attributed to unique proteins synthesized by mussels called mussel foot proteins (mfps) found within the byssus, which is rich in catechol-containing residues such as DOPA. Numerous environmental factors affect the development and functional efficacy of byssus. Motivated by the remarkable properties of mussels, scientists have developed a wide range of bioinspired materials. This review presents an overview of different mussel species as well as structural and functional characteristics of the byssal threads. Besides focusing on their mechanical strength and biocompatibility, this study examines recent advancements in mussel-inspired hydrogels and scaffolds for bone regeneration, motion detection, and wound healing. Further emphasizing unique adhesion chemistry, this review highlights the development of next-generation biomaterials and healthcare technologies, especially smart biosensors and multifunctional theranostic platforms for integrated disease diagnostics and targeted therapy.

Chronic wounds associated with diabetes mellitus exhibit delayed healing primarily due to hypoxia-induced impairment of angiogenesis and persistent inflammation. Recently, microalgae-based hydrogel dressings have emerged as promising candidates for managing diabetic chronic wounds. However, the survival and functional stability of microalgae within hydrogels remain poorly understood, as limited research has focused on developing matrices conducive to algal viability. In this study, we developed a novel hydrogel (HA-gel@CV) tailored to the survival environment of Chlorella vulgaris (CV) to enhance algal viability and accelerate diabetic wound healing. The hydrogel was synthesized through self-assembly using hyaluronic acid (HA) as the scaffold to load CV, sequentially incorporating ceramide, urea, Portulaca oleracea (PO) extract, and nicotinamide solution, with gelation shaped by peach gum polysaccharide (PGP). CV viability in HA-gel@CV was assessed over 5 days by quantifying cell density, total chlorophyll content, and oxygen production. Light and fluorescence microscopy, as well as macroscopic color analysis, confirmed that CV remained stable for more than 7 days and exhibited proliferation within the gel. In vitro studies demonstrated that HA-gel@CV enhanced cell proliferation, migration, and angiogenesis, while in vivo experiments showed reduced inflammation and improved vascular and tissue regeneration in diabetic wounds. In summary, HA-gel@CV represents a multifunctional hydrogel integrating oxygenation, anti-inflammatory, moisturizing, and reparative properties, demonstrating strong potential for treating diabetic chronic wounds.

Polymeric microneedle patches represent a promising noninvasive platform for the transdermal delivery of peptide and protein therapeutics, and FDA-approved polymers are widely used for this purpose. However, maintaining peptide and protein stability during microneedle fabrication remains a significant challenge. Conventional strategies involve encapsulating within polymer nanoparticles/microparticles, or codissolving them with polymers in organic solvents before microneedle fabrication. These approaches are time-consuming and often lead to low loading efficiency and drug loss. In this study, we developed a novel direct emulsion-based encapsulation strategy that integrates peptides within the PLGA matrix during microneedle formation. This approach generates a uniform water-in-oil (W/O) emulsion that ensures homogeneous peptide dispersion while minimizing interfacial stress, eliminating the need for multistep spraying or postloading processes. The optimized PLGA-based microneedles exhibited uniform geometry, high drug-loading capacity, and strong mechanical integrity suitable for skin penetration. The encapsulated peptide maintains its biological activity after fabrication and during storage, confirming excellent peptide stability. In vivo studies demonstrated successful skin insertion and sustained peptide release for up to 72 h, supporting the potential of this platform for prolonged transdermal peptide delivery. Overall, this work presents a scalable, biocompatible, and solvent-safe microneedle fabrication strategy that preserves peptide functionality while enabling controlled drug release, making it a promising strategy for transdermal peptide therapeutics.

Hepatocellular carcinoma (HCC) remains a clinically challenging malignancy, and it is imperative to develop novel therapeutic strategies for HCC treatment. In this study, we developed a novel mRNA-based nanovaccine (SK-mRNA) targeting the tumor-associated antigen glypican-3 (GPC3). The SK-mRNA vaccine consists of in vitro-transcribed mRNA encoding 3 × GPC3_127-136 CTL epitopes fused with HSP70, which self-assembles with the cationic peptide SP94-GGG-K18 to form a uniform spherical nanostructure. This nanovaccine facilitates the targeted delivery of mRNA to tumors via SP94 binding with its cognate receptor on tumor cells, enabling the expression and secretion of the 3 × GPC3_127-136-HSP70 fusion protein. Subsequently, dendritic cells internalize this protein through its receptors on dendritic cells, leading to the presentation of CTL epitope GPC3_127-136 to T cells. Experimental vaccination elicited robust antigen-specific T-cell responses, as evidenced by the significant increase in CD8⁺ T cells observed in both spleens and tumors, along with enhanced IFN-γ secretion in response to the GPC3_127-136 peptide. The combination of SK-mRNA nanovaccine with anti-PD-L1 immunotherapy exhibited potent synergistic antitumor effects. These findings collectively suggest that SK-mRNA nanovaccines can effectively stimulate immune responses and synergize with immune checkpoint blockade therapies to mediate powerful antitumor effects, offering a promising strategy for the effective treatment of HCC.

Bacterial infection remains a major challenge in biomedical applications, particularly with the rise of antibiotic-resistant pathogens. Developing antibacterial biomaterials that both prevent infection and support tissue regeneration has become an essential goal in biomedical research. Silk fibroin (SF) is a natural protein derived from Bombyx mori which has been identified as a broad-spectrum, biocompatible, and programmable material in biomedical applications. This review emphasizes SF for antibacterial infection, summarizing its structural features and modulations to immune responses and synergistic combination with multiple antibacterial agents. The unique β-sheet structure of silk fibroin provides resilience and tunable functionality, allowing it to serve as a stable matrix for diverse antibacterial agents. Antibacterial agents enhance antibacterial performance by generating reactive oxygen species, disrupting bacterial membranes, and suppressing biofilm formation. Silk fibroin supports immune modulation by promoting macrophage polarization and reducing inflammation, thereby facilitating tissue repair and wound healing. Overall, SF represents a next-generation antibacterial biomaterial that integrates antimicrobial efficacy with immune modulation, structural tunability, and biocompatibility, having strong potential for infection control and tissue regeneration in clinical applications. Despite advancements in biofunctionality, optimization of controlled release and long-term compatibility challenges still exist for SF's clinical applications, particularly against antibiotic-resistant pathogens.

The first-line treatment for unresectable HPV-negative squamous cell carcinoma of head and neck (SCCHN) patients involves weekly or triweekly systemic cisplatin chemotherapy concurrently with radiotherapy. Cisplatin induces severe systemic toxicity that prevents a portion of patients from receiving the standard of care while redirecting them to less effective alternatives. This means worsening prognosis and overall survival (OS). A single-dose long-acting cisplatin limits toxicity. This is an injectable, biodegradable polyanhydride derived from sebacic acid (SA) and ricinoleic acid (RA) investigated as a targeted small-volume, high-payload carrier to improve safety and enhance efficacy.

Cancer is the leading cause of death in most developed nations. Although significant efforts have been made to develop targeted cancer chemotherapy drugs for decades, dosing of chemotherapy drugs is still limited by systematic toxic side effects. To reduce the toxicities of chemotherapy, we have designed a 3D printed biosponge adsorber that can capture the excess untrapped chemotherapy drugs in situ before they circulate throughout the body. Specifically, we focused on liver cancer because of the liver's proximity to the heart with a model drug, doxorubicin (Dox), a highly effective chemotherapy drug with severe cardiac failure risk. Our adsorbers were prepared by forming porous lattice scaffolds via 3D printing and then adding a thin drug (Dox)-adsorbing layer of sulfonated nanostructured block copolymer on the scaffolds. The porous lattices were designed to provide a large surface area for effective drug capture but not to impair the blood flow. The drug-adsorbing block of the polymer layer is polystyrenesulfonate (PSS), which strongly binds to Dox. Using these design parameters, we have successfully placed the adsorbers in the veins downstream of the liver, i.e., the hepatic veins and inferior vena cava (IVC) draining the liver, while the drug (Dox) was injected directly to the liver, mimicking the state-of-the-art, intra-arterial chemotherapy (IAC) procedure for liver cancer patients. Our adsorbers can capture a significant amount of the excess untrapped Dox in situ. The adsorbers can significantly reduce Dox accumulation in the heart (50%) and kidneys (36%) as well as in the surrounding bloodstream (25-45%). Cell viability studies using H9c2 cells confirmed that our adsorbers reduce Dox-induced cardiotoxicity. Additionally, the placement of the adsorbers neither severely impairs the blood flow nor significantly raises blood pressure in the adjacent veins. This confirms the feasibility of the in vivo adsorption approach. Our development poses a potential new route to minimize off-target chemotherapy toxicities and thus help people fight cancer by enabling high-dose locoregional chemotherapy.

Ascites, or a pathologic accumulation of intra-abdominal fluid, is a key feature of intraperitoneally disseminating cancers, such as ovarian cancer. This pathological fluid buildup can influence the adhesive abilities of ovarian cancer cells, as they spread throughout the abdominal cavity to form metastatic implants on organs lined with a specialized monolayer of mesothelial cells. Robust methods for assessing the impact of fluid shear stress on this cell-cell interaction are lacking. Here, we develop and characterize a novel microfluidic device that allows for the determination of the attachment of ovarian tumor cells to mesothelial cells under the influence of fluid flow. We show that the attachment of ovarian tumor cells to mesothelium is impacted by fluid shear stresses in a dynamic manner. We find that ovarian tumor cells secrete factor(s) that enhance the ability of ovarian tumor cells to more efficiently attach, and remain attached, to the mesothelium in the presence of fluid shear stress. This work advances the study of ovarian tumor cell metastasis, describing a robust method to screen and identify therapeutically targetable pathways of ovarian tumor cell-mesothelial cell intercommunication to potentially mitigate ovarian cancer progression.

Interrogating molecular biomarkers in bodily fluids has emerged as a clinically useful strategy for the early diagnosis of many cancer types. Interstitial skin fluid is currently being explored as a possible alternative to blood, containing the same types of biomarkers but lacking cells and debris that hold little or no clinical value. The discovery and validation of molecular biomarkers with diagnostic or prognostic value and the development of clinical tests based on their detection require minimally invasive technologies capable of sampling this fluid in a pain-free manner. Biomarkers must also be easily recoverable for follow-on analysis. Herein, we combine standard genomic approaches with innovative bioengineering technologies to demonstrate that short noncoding miRNAs are significantly deregulated in extracellular skin fluid surrounding malignant skin lesions, providing a yet largely unexplored window of opportunity for early diagnosis of skin cancers. Hydrogel-based microneedle patches offering clinically useful sampling capacity were developed that enable the rapid capture and recovery of endogenous miRNAs from human skin through deformation of the epidermal-dermal junction. Using mouse models of cutaneous squamous cell carcinoma, a significantly greater level of deregulation of selected miRNAs was observed in perilesional skin fluid compared to that in blood levels.

host-guest (βCD/adamantane) cross-linked hydrogels have received increasing attention in recent years for cell culture applications. A major challenge of these systems remains the lack of stability and mechanical integrity, which has led to the development of dual cross-linked gels mainly by combining the host-guest (βCD/adamantane) interaction with other physical cross-links based on ionic interactions or H-bonding. In this research, 11 dual-cross-linked hydrogels were produced on the basis of defined βCD/adamantane interactions in addition to covalent cross-linking with PEGDA₃₅₀₀ of thiol-functionalized copolymers. The dual-cross-linked hydrogels exhibit high mechanical strength and improved stability compared with βCD/Ada control hydrogels. The ability to self-heal depends on the initial strength of the gels. Encapsulation of B16F1 cells in these gels showed their uniform distribution and good cytocompatibility. It is particularly noteworthy that a higher number of living B16F1 cells were found in RGD-modified gels compared with Matrigel as a control.