Acta biomaterialia最新文献

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.

Emergency corneal injuries necessitate immediate intervention to minimize the risk of infection and maintain optical clarity. However, corneal transplantation is unsuitable due to donor shortage and surgical complexity. Inspired by the synergistic role of collagen and glycosaminoglycans in the natural cornea extracellular matrix, a visible light-initiated, in situ dual-crosslinked hydrogel bioadhesive (GelMA-CSMA-NHS) is prepared by combining gelatin methacryloyl (GelMA) and N-hydroxysuccinimide-modified chondroitin sulfate methacrylate (CSMA-NHS). Upon exposure to 405 nm light, the bioadhesive precursor rapidly forms a hydrogel within 3 min directly on the injured cornea. It establishes strong interfacial integration with the tissue through topological entanglement and NHS-amine covalent crosslinking, thereby serving as a suture-free alternative for corneal repair. The dual-crosslinking mechanism significantly enhances the mechanical cohesion of the hydrogel, which synergistically improves its adhesive performance. The resulting hydrogel demonstrates high transparency, stable swelling behavior, good biocompatibility and biodegradability, and high burst pressure resistance. Using established models of partial stromal defects and full-thickness corneal lacerations, the bioadhesive integration and pro-healing effects of the hydrogel were evaluated. The results showed that the hydrogel bioadhesive rapidly seals corneal wounds, promotes re-epithelialization, reduces scarring formation, and supports full-thickness corneal regeneration. STATEMENT OF SIGNIFICANCE: To address the limitations of traditional surgical sutures in treating acute corneal injuries, we developed a hydrogel bioadhesive (GelMA-CSMA-NHS). Inspired by the composition of the natural corneal extracellular matrix, the adhesive is fabricated from two derivatives of natural bioactive macromolecules. It can be rapidly crosslinked in situ on the injured cornea under visible light initiation via a dual-crosslinking mechanism, forming a strong adhesive interface with the tissue through topological entanglement and NHS-amine covalent bonding. In terms of performance, the hydrogel bioadhesive exhibits high transparency, good biocompatibility and biodegradability, and high burst pressure resistance. The hydrogel was evaluated in two models of acute corneal injury-partial stromal defects and full-thickness corneal lacerations. It accelerates re-epithelialization, minimizes scarring formation, and supports full-thickness corneal regeneration. Thus, this hydrogel bioadhesive shows considerable potential for emergency corneal repair and regenerative medicine.

In the past 20 years, minimally invasive delivery strategies have emerged to bridge the therapeutic gap between highly invasive surgery and less efficient nonsurgical approaches. New, less invasive technologies, including vascular, transendocardial, thoracoscopic, and inhalation delivery methods, can enhance cardiac targeting, promote drug retention, and minimize trauma compared to conventional interventions. Understanding current therapeutic agents, including biomolecules, biomaterials, and medical devices, along with their respective mechanisms, is essential for optimizing minimally invasive delivery strategies. Despite current therapeutic promises, dynamic heart motion and low delivery efficiency hinder the clinical translation of minimally invasive heart repair. Future studies should aim to address these hurdles by optimizing cardiac uptake, advancing personalized medicine, and developing safer delivery tools. To map the state of the field and its future potential, this review summarizes several minimally invasive cardiac delivery approaches and how to leverage existing techniques in concert to harness the impact of minimally invasive cardiac delivery. STATEMENT OF SIGNIFICANCE: Minimally invasive cardiac delivery techniques represent an important advancement in treating heart diseases, bridging the gap between invasive surgeries and less effective nonsurgical methods. Unlike traditional approaches, these novel methods, including vascular, transendocardial, thoracoscopic, and inhalation techniques, provide targeted drug delivery directly to the heart while reducing trauma. This review uniquely synthesizes current advancements in delivering therapeutic agents such as biomolecules and medical devices, highlighting their improved cardiac targeting and retention capabilities. It identifies critical challenges, including the heart's motion and low delivery efficiency, and discusses opportunities for innovation. Addressing these challenges can significantly impact patient outcomes, enhance personalized treatments, and advance the broader field of minimally invasive cardiovascular medicine.

Metal-directed self-assembly, driven by metal-ligand coordination, represents a highly versatile and efficient strategy for constructing drug delivery systems with precisely tunable properties, inherent imaging capabilities, and broad biomedical applications. Stimuli-responsive metal-directed drug delivery systems (MDDSs), guided by advanced imaging techniques, enable precise control over their size and spatial architecture while facilitating site-specific drug release. Moreover, certain metal ions play a dual role, not only orchestrating the self-assembly process but also serving as therapeutic agents and regulatory components for the treatment of various diseases, including cancer, microbial infections, and Alzheimer's disease. This review provides a comprehensive overview of the self-assembly mechanisms underlying diverse MDDSs and their applications in image-guided therapy. Furthermore, we critically examine existing challenges in the field and propose strategic directions to propel the advancement of metal-directed self-assembly in drug delivery. Given the profound implications of this research, further exploration of the critical roles of metal coordination in self-assembly is imperative for the development of next-generation drug delivery platforms. STATEMENT OF SIGNIFICANCE: This review systematically summarize the self-assembly mechanisms of metal-directed drug delivery systems, outlines their applications in image-guided therapy and discusses the current challenges that remain. Furthermore, it elucidates the unique regulatory roles of metal ions in precise drug release and multimodal therapy, providing valuable insights and broad appeal for the development and clinical translation of next-generation smart nanomedicine platforms.