Acta biomaterialia最新文献

Chronic liver diseases (CLDs), encompassing a spectrum from steatosis and inflammation to fibrosis, cirrhosis, represent a major global health burden, causing approximately 2 million deaths annually [1]. The management of CLDs is significantly hampered by the limitations of conventional approaches, including non-targeted drug delivery, systemic toxicity, and inadequate diagnostic sensitivity for early-stage lesions. Nanotechnology-driven biomaterial platforms have emerged as pioneering solutions to these challenges, enabling precise theranostic strategies tailored to the distinct pathophysiology of each disease stage. This review systematically elaborates on these advancements by aligning with the natural progression of CLDs [non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatitis B, liver fibrosis, and cirrhosis]. We detail how engineered platforms enhance therapeutic efficacy by achieving superior hepatic accumulation, controlled drug release, and improved metabolic, antiviral, and antifibrotic effects. Concurrently, we explore their role in diagnostics, where nanotechnology-enhanced imaging agents and nanosensors provide unprecedented sensitivity for early detection and accurate staging. By structuring the discussion around the evolving clinical needs from NAFLD and hepatitis to advanced fibrosis and cirrhosis, this review offers a stage-specific roadmap of biomaterial design principles. It aims to provide a foundational theory and forward-looking perspectives for developing next-generation, precision medicine solutions for CLDs, ultimately bridging the gap between benchtop innovation and clinical translation. STATEMENT OF SIGNIFICANCE: This review establishes a stage-specific design paradigm that bridges the gap between biomaterial innovation and the clinical continuum of chronic liver diseases (CLDs). Its significance lies in aligning cutting-edge biomaterial strategies from targeted, stimuli-responsive nanotherapeutics to engineered exosomes and gene delivery systems with the distinct pathophysiological features of each disease stage. This approach moves beyond cataloging materials to critically evaluating their translational feasibility. We analyze how rational material design addresses specific clinical bottlenecks, such as improving drug bioavailability to diseased tissue or enabling sensitive, non-invasive diagnostics for early detection. By providing this clinically focused roadmap, this review aims to accelerate the development of personalized therapies and reshape the theranostic landscape, striving to improve therapeutic outcomes of CLDs.

Zinc and its alloys emerge as promising candidates for next-generation biodegradable implants due to their acceptable biodegradability and biocompatibility, while issues such as localized corrosion and potential cytotoxicity remain to be addressed. Both issues get complicated in intestinal microenvironment with diverse microbiota, especially the effects of Zn degradation on intestinal probiotics viability. Here, Zn-0.1Li and Zn-0.2Mg alloy microwires were manufactured and investigated for their mechanical integrity, degradation behavior, and biological performance toward colorectal surgical applications as staples or self-expanding stents. Alloying with Li and Mg enhanced tensile and yield strengths via second-phase strengthening, together with markedly a more uniform and stable degradation in simulated intestinal fluid (SIF) than in Hanks' solution. The resulting steady Zn²⁺ release in SIF reduced excessive local ion accumulation. Biological assessments confirmed >80% viability of Human Umbilical Vein Endothelial cells (HUVECs) and Caco-2 cells. In particular, we found a growth-promoting effect of Zn²⁺ on Lactobacillus rhamnosus GG (LGG) (probiotics) and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (pathogen). Furthermore, Zn²⁺ selectively precipitated cytotoxic secondary bile acids than Mg²⁺. The integrated time-frequency analysis of electrochemical noise signals and spatio-temporal evolution of interfacial pH and O₂ levels attributed the uniform degradation of Zn alloys microwires to the strong local pH buffering effect of SIF. These findings highlight that Zn-Li and Zn-Mg microwires couple uniform degradation with cytocompatibility, antibacterial activity, and metabolites regulation, is bio-adaptive for intestinal implant applications. STATEMENT OF SIGNIFICANCE: This work demonstrates that Zn-0.1Li and Zn-0.2Mg alloy microwires showed an ultimate tensile strength of 264MPa and 199MPa. Multi-scale in operando electrochemical analyses, electrochemical impedance spectroscopy (EIS) and electrochemical noise (ECN) integrated with mapping of interfacial pH and oxygen reveals that the Zn alloy wires underwent uniform corrosion in simulated intestinal fluid (SIF) but localized corrosion in Hanks' solution. Both Zn-0.1Li and Zn-0.2Mg alloy microwires showed favorable biocompatibility with intestinal epithelial and endothelial cells, along with strong antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and further promoted the probiotic Lactobacillus rhamnosus GG (LGG). Moreover, released Zn²⁺ ions engaged in selective coordination with secondary bile acids, thereby attenuating metabolite-induced epithelial stress. These findings highlight Zn-based alloys as promising candidates for next-generation biodegradable intestinal implants.

To facilitate their dispersion, the miniature wing elements of autorotating winged fruits (samaras) must resist considerable multidirectional flight loadings as they fall from the tree and are carried away by occasional winds. However, the structural-mechanical properties of the samara wing, which stem from its internal composite design and provide it with resistance to deformations, are as yet unexplored. Here, we used structural analyses, composite-material modeling, and finite-element simulations to investigate the structure-mechanics-function relationship in the internal composite design of the samara of the Tipuana tipu tree. We show that the planar orientation of locally parallel fiber arrays varies globally throughout the wing, yielding a thin-layer composite element in which distinct functional regions resist multi-type mechanical deformations. This wing design provides extreme resistance to deformations at non-conventional orientations that are not aligned with the geometrical axes of the wing. The composite design principles of the samara wing can be incorporated into synthetic analogs to develop advanced, bioinspired minuscule wing elements that can effectively resist multidirectional loadings. STATEMENT OF SIGNIFICANCE: The internal composite structure of autorotating plant wings (samaras) exhibits a natural design solution for paper-thin flight elements unfamiliar in conventional engineering frameworks. The orientation of the basic composite unit of the wing varies throughout the wing, thereby forming distinct functional regions with designated deformation-resistance capabilities. Adapting these design principles into simplified models promotes the engineering of ultra-small flight elements for minute aerial units.

Developing bio-piezoelectric materials that simultaneously provide high piezoelectric output and superior mechanical flexibility remains challenging, largely due to difficulties in achieving self-alignment and barriers to scalable synthesis. This study introduces a bio-piezoelectric composite film simply composed of β-glycine and gelatin, fabricated via thermally assisted solvent evaporation. This mechanically flexible film exhibits uniformly oriented β-glycine crystals, with gelatin serving as a biomolecular template to guide crystallization. Hydrogen bonding and electrostatic interactions between gelatin and glycine stabilize the non-centrosymmetric β-phase structure while suppressing α-glycine formation and facilitating directional self-alignment. Molecular dynamics (MD) simulations elucidate synergistic self-assembly mechanisms governed by hydrogen bonding, van der Waals forces, and electrostatic interactions. Mechanical characterization highlights the pivotal role of gelatin in reducing the brittleness of β-glycine, with Young's modulus exhibiting a proportional increase with glycine content. Piezoresponse force microscopy (PFM) and quasi-static piezoelectric coefficient (d₃₃) measurements confirm polarization uniformity in β-glycine crystals, yielding a piezoelectric coefficient of 8.6 pC N^-1, low dielectric constant of 2.8, and voltage output up to 21.9 V, which surpasses current bio-piezoelectric materials. Our β-glycine/gelatin (β-Gly/Gel) composite films exhibit sensitive electromechanical coupling for the detection of dynamic stimuli and possess favorable characteristics, including bio-nontoxicity and biodegradability. This work establishes a bi-phase biomaterial synthesis strategy that integrates high piezoelectric performance, mechanical flexibility, and biocompatibility, thereby advancing next-generation biomedical devices for physiological sensing and energy harvesting. STATEMENT OF SIGNIFICANCE: This work reports a biodegradable, biocompatible, and non-toxic bio-piezoelectric film composed solely of β-glycine and gelatin, fabricated via a simple solvent evaporation method. Gelatin guides the self-aligned crystallization of piezoelectric β-glycine, enhancing mechanical flexibility and stability. The film exhibits high piezoelectric output (piezoelectric coefficient d₃₃=8.6 pC N⁻¹, voltage output of 21.9 V), low dielectric constant, and strong electromechanical sensitivity. Owing to its natural origin, environmental safety, and tissue compatibility, the film holds promise not only for wearable sensors and energy harvesters but also as a potential implantable biomaterial for physiological sensing and bioelectronic repair.

Immunostaining is essential for cancer biomarker detection, such as HER2 and EGFR, but conventional methods often require prolonged incubation and multiple washing steps. Here, we developed self-crosslinkable protein hydrogel (SPH) stamps for simple, rapid, and reusable immunostaining of cells and tissues. Mixing SpyTag-fused lumazine synthase protein nanoparticles (AaLS-ST) with SpyCatcher tandem dimers (SC-SC) at a 2:1 molar ratio formed stable, self-crosslinked hydrogels with hydrophilic pores and high mechanical strength. Flat-disc SPH stamps, mounted on plastic bars, efficiently absorbed antibody solutions and transferred them to target biomarkers via stamping. HER2-overexpressing SKBR-3 and EGFR-overexpressing MDA-MB-468 cells were specifically stained with PE-conjugated anti-HER2 antibody (aHER2-Ab-PE) and APC-conjugated anti-EGFR antibody (aEGFR-Ab-APC), respectively, within 10 min without washing through simple stamping. A single SPH stamp loaded with multiple antibodies selectively stained the corresponding cells without washing steps, while sequential stamping of primary and secondary antibodies enabled simplified two-step immunostaining. Reusability was validated through repeated staining of multiple fixed cell slides and tumor tissue slices with a single antibody loading. SPH stamps provide a rapid, versatile, and reusable platform for immunostaining of cells and tissues, providing a promising alternative to conventional methods. STATEMENT OF SIGNIFICANCE: Immunostaining is central to cancer diagnostics but limited by lengthy incubation and multiple washing steps. Self-crosslinkable protein hydrogel (SPH) stamps are developed, which rapidly absorb and release antibodies, enabling target-specific staining of cells and tissues within minutes without washing. SPH stamps can be reused across multiple samples with a single antibody loading, including tissue sections. They also enable selective staining of corresponding cells with a single loading of multiple antibodies without washing steps, as well as simplified two-step immunostaining using sequential primary and secondary antibody stamping. This platform integrates speed, simplicity, and reusability, offering a promising protein-based alternative for cell and tissue immunostaining with potential impact in diagnostic pathology and high-throughput analysis.

Reconstruction of large-volume soft tissue defects remains a significant challenge in plastic and reconstructive surgery. Autologous fat grafting, though widely used, often suffers from poor volume retention and slow vascularization. This study presents an innovative collagen-guided self-assembling adipose construct from clinical lipoaspirate to create structurally stable engineered fat flaps-Self-Assembly Fat (SAF), driven by the intrinsic crosslinking of type I collagen within the lipoaspirated fat. Supplementation with exogenous type I collagen (SAF⁺) further enhanced the mechanical properties and biological activity of these constructs, increasing their stiffness, elasticity, and resilience. The self-assembly process facilitated collagen network formation, which not only improved tissue stability but also provided a favorable microenvironment for cell adhesion, proliferation, and differentiation. In vitro, SAF⁺ exhibited enhanced adipogenic differentiation and superior stem cell recruitment. In vivo, SAF⁺ significantly accelerated tissue repair by promoting M2 macrophage polarization, angiogenesis, and stem cell homing. Mechanistically, these effects were mediated through activation of the integrin α2β1-FAK/Src signaling pathway. This study provides a mechanistic understanding of adipose tissue self-assembly and presents an autologous, collagen-guided approach for engineering implantable, scaffold-free adipose constructs with enhanced regenerative capacity for soft-tissue repair. STATEMENT OF SIGNIFICANCE: Soft‑tissue reconstruction is hindered by unpredictable resorption and poor vascularization of autologous fat grafts. Biomaterial approaches using synthetic scaffolds or exogenous matrices often suffer biocompatibility issues, foreign‑body responses, and limited integration. We identify an intrinsic, type I collagen-driven self‑assembly capacity in human lipoaspirate and establish a collagen-guided, scaffold-free adipose strategy. By elucidating collagen signaling via integrin α2β1-FAK/Src axis, we link structural consolidation, mechanical tuning, and a pro‑regenerative microenvironment. Modulating collagen availability and crosslinking strengthens cohesion while preserving implantability and handling. The resulting constructs maintain adipose lineage, support vascularization, and integrate with host tissue. Bypassing synthetic scaffolds, this platform advances ECM‑guided assembly and offers a practical, autologous approach to soft‑tissue repair with improved handling, stability, and translational potential.