Biomaterials Science最新文献

The dissemination of metastatic cells from the primary tumor into the surrounding tissue is a key event in the progression of cancer. This process involves the migration of cells across defined tissue interfaces that separate the dense tumor tissue from the adjacent healthy tissue. Prior research showed that cell transmigration across collagen I matrix interfaces induces a switch towards a more aggressive phenotype including a change in directionality of migration and chemosensitivity correlated to increased DNA damage during transmigration. Hence, mechanical forces acting at the nucleus during transmigration are hypothesized to trigger phenotype switching. Here, we present results from a particle image velocimetry (PIV) based live cell analysis of breast cancer cell transmigration across sharp matrix interfaces constituted of two collagen type I networks with different pore sizes. We found strong and highly localized collagen network deformation caused by cellular forces at the moment of crossing interfaces from dense into open matrices. Additionally, an increased contractility of transmigrated cells was determined for cells with the switch phenotype. Moreover, studies on mechanotransductive signaling at the nucleus, emerin translocation and YAP activation, indicated a misregulation of these signals for transmigrated cells with altered phenotype. These findings show that matrix interfaces between networks of different pore sizes mechanically challenge invasive breast cancer cells during transmigration by a strong asymmetry of contracting forces, impeding nuclear mechanotransduction pathways, with a subsequent trigger of more aggressive phenotypes.

Yielding of dynamically crosslinked hydrogels, or the transition between a solid-like and liquid-like state, allows facile injection and utility in translational biomedical applications including delivery of therapeutic cells. Unfortunately, the time-varying nature of the transition is not well understood, nor are there design rules for understanding the effects of yielding on encapsulated cells. Here, we unveil underlying molecular mechanisms governing the yielding transition of dynamically crosslinked gels currently being researched for use in cell therapy. We demonstrate through nonlinear rheological characterization that the network dynamics of the dynamic hydrogels dictate the speed and character of their yielding transition. Rheological testing of these materials reveals unexpected elastic strain stiffening during yielding, as well as characterization of the rapidity of the yielding transition. A slower yielding speed explains enhanced protection of directly injected cells from shear forces, highlighting the importance of mechanical characterization of all phases of yield-stress biomaterials.

Background: Calcium oxalate (CaOx) crystal deposition and its resultant cellular oxidative damage and inflammation are important causes of renal stone formation. It is clinically important to conduct research on multifunctional anti-stone drugs targeting these predisposing factors. Methods: We modified natural Undaria pinnatifida polysaccharide (UPP0) by sulfation via the sulfur trioxide-pyridine method, resulting in four sulfated polysaccharides with varying sulfate group (–OSO₃⁻) contents: 1.59% (UPP0), 6.03% (UPP1), 20.83% (UPP2), and 36.39% (UPP3), and compared their differences in the inhibition of crystalline formation, renal injury, and inflammation in the process of renal stone formation at chemical and cellular levels. Results: The UPPS were able to inhibit the nucleation, growth and aggregation of CaOx crystals in vitro. Among them, UPP3 with the maximum sulfate group content showed the greatest crystallization inhibition ability. The nucleation inhibition and aggregation inhibition of UPP3 at a concentration of 0.5 mg mL⁻¹ were as high as 80.21% and 72.34%, respectively. The CaOx crystal size regulated by UPP3 was significantly reduced from 25.9 ± 2.8 μm to 5.9 ± 1.2 μm. Furthermore, UPPS were observed to up-regulate the expression of the antioxidant enzyme superoxide dismutase (SOD) in cells, reduce the levels of ROS and malonaldehyde (MDA), enhance lysosomal integrity, decrease intracellular Ca²⁺ levels, inhibit the decline in mitochondrial membrane potential, reduce the production of cellular inflammatory factors (TNF-α, MCP-1, IL-18, and IL-1β), and ultimately inhibit cell apoptosis. Conclusion: UPPS combine multiple biological functions of crystallization regulation, antioxidant and anti-inflammatory, and have important potential in the prevention of kidney stones. Sulfation modification can improve the biological activity of UPP0 and provide a reference for screening and optimization methods of stone drugs.

Correction for ‘3D printing of wearable sensors with strong stretchability for myoelectric rehabilitation’ by Jianan Zhan et al., Biomater. Sci., 2025, https://doi.org/10.1039/d4bm01434k.

Overcoming poor in vivo pharmacokinetics is a critical challenge in developing therapeutic aptamers, and conjugation to poly(ethylene glycol) (PEG) is a well-established technique for aptamers to prolong blood circulation. However, the existence of antibodies that specifically recognize PEG and their adverse effects on in vivo behaviors have been increasingly reported, highlighting the necessity of alternative modification strategies for aptamers. To address this issue, we focused on a zwitterionic polymer, particularly poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), as a PEG alternative to modify DNA aptamers. We conjugated PMPC to a DNA aptamer targeting IFN-gamma and investigated the properties of the PMPC-conjugated DNA aptamer as a therapeutic agent. PMPC modification did not affect the neutralizing activity of the aptamer. PMPC demonstrated lower reactivity against anti-PEG antibodies than PEG-like aptamer modifiers previously reported to exhibit low reactivity against PEG antibodies. In addition, PMPC extended the blood circulation time of the aptamer as long as or longer than PEG with a similar molecular size. In the LPS-induced inflammation animal model, the survival rate after treatment with the PMPC-aptamer conjugate was significantly superior to that with unmodified aptamer. These results indicate that PMPC has potential as an aptamer or other nucleic acid drug modifier to replace or be compatible with PEG.

Polymer–nanoparticle (PNP) hydrogels are a promising injectable biomaterial platform that has been used for a wide range of biomedical applications including adhesion prevention, adoptive cell delivery, and controlled drug release. By tuning the chemical, mechanical, and erosion properties of injected hydrogel depots, additional control over cell compatibility and pharmaceutical release kinetics may be realized. Here, we employ thiol–ene click chemistry to prepare a library of modified hydroxypropylmethylcellulose (HPMC) derivatives for subsequent use in PNP hydrogel applications. When combined with poly(ethylene glycol)-b-poly(lactic acid) nanoparticles, we demonstrate that systematically altering the hydrophobic, steric, or pi stacking character of HPMC modifications can readily tailor the mechanical properties of PNP hydrogels. Additionally, we highlight the compatibility of the synthetic platform for the incorporation of cysteine-bearing peptides to access PNP hydrogels with improved bioactivity. Finally, through leveraging the tunable physical properties afforded by this method, we show hydrogel retention time in vivo can be dramatically altered without sacrificing mesh size or cargo diffusion rates. This work offers a route to optimize PNP hydrogels for a variety of translational applications and holds promise in the highly tunable delivery of pharmaceuticals and adoptive cells.

The inherent carbohydrate-binding specificities of human galectins can serve as recognition elements in both biotechnological and biomedical applications. The combination of the carbohydrate-recognition domain (CRD) of galectins fused to peptides or proteins for purification, immobilization, and imaging enables multifunctional utilization within a single protein. We present here a library of color-coded galectin fusion proteins that incorporate a His₆-tag, a fluorescent protein, and a SpyCatcher or SpyTag unit to enable immobilization procedures. These galectin fusion proteins exhibit similar binding properties to the non-fused galectins with micromolar apparent binding affinities. N- and C-terminal fusion partners do not interfere with the SpyCatcher/SpyTag immobilization. By applying SpyCatcher/SpyTag-mediated SC–ST-Gal-3 conjugates, we show the stepwise formation of a three-layer ECM-like structure in vitro. Additionally, we demonstrate the SpyCatcher/SpyTag-mediated immobilization of galectins in microgels, which can serve as a transport platform for localized targeting applications. The proof of concept is provided by the galectin-mediated binding of microgels to colorectal cancer cells.

Nanotechnology and 3D bioprinted scaffolds are revolutionizing the field of wound healing and skin regeneration. By facilitating proper cellular movement and providing a customizable structure that replicates the extracellular matrix, such technologies not only expedite the healing process but also ensure the seamless integration of new skin layers, enhancing tissue repair and promoting overall cell growth. This study centres on the creation and assessment of a nanostructured lipid carrier containing curcumin (CNLC), which is integrated into a 3D bioprinted PLA scaffold system. The goal is to investigate its potential as a vehicle for delivering poorly soluble curcumin for enhanced wound healing. The developed CNLC exhibited an oval morphology and average particle size of 292 nm. The entrapment efficiency (EE) was 81.37 ± 0.85%, and the drug loading capacity was 6.59 ± 1.61%. CNLC was then integrated into PLA-based 3D bioprinted scaffolds, and physicochemical analyses were conducted to evaluate their properties. Cell viability studies carried out using fibroblast cells demonstrated that the PLA/CNLC scaffolds are non-cytotoxic. In vivo experiments showed that the PLA/CNLC scaffolds exhibited complete wound contraction and closure of full-thickness wounds within a period of 21 days. The findings confirmed the scaffold's capacity as a tool for accelerating wound healing. The research emphasises the need for using biomimetic 3D printed scaffold materials and the promise of nanobiotechnology in enhancing treatment efficacy.

Extracellular vesicles (EVs) are secreted by almost all cell types and contain DNA, RNA, proteins, lipids and other metabolites. EVs were initially believed to be cellular waste but now recognized for their role in cell-to-cell communication. Later, EVs from immune cells were discovered to function similarly to their parent cells, paving the way for their use as gene and drug carriers. EVs from different cell types or biological fluids carry distinct cargo depending on their origin, and they perform diverse functions. For instance, EVs derived from stem cells possess pluripotent properties, reflecting the cargo from their parent cells. Over the past two decades, substantial preclinical and clinical research has explored EVs-mediated drug and gene delivery to various organs, including the brain. Natural or intrinsic EVs may be effective for certain applications, but as drug or gene carriers, they demonstrate broader and more efficient potential across various diseases. Here, we review research on using EVs to treat central nervous system (CNS) diseases, such as Alzheimer's Disease, Parkinson diseases, depression, anxiety, dementia, and acute ischemic strokes. We first reviewed the naïve EVs, especially mesenchymal stem cell (MSC) derived EVs in CNS diseases and summarized the clinical trials of EVs in treating CNS diseases and highlighted the reports of two complete trials. Then, we overviewed the preclinical research of EVs as drug and gene delivery vehicles in CNS disease models, including the most recent two years’ progress and discussed the mechanisms and new methods of engineered EVs for targeting CNS. Finally, we discussed challenges and future directions and of EVs as personalized medicine for CNS diseases.

Living materials, which include various types of cells, organelles, and biological components from animals, plants, and microorganisms, have become central to recent investigations in micro and nanorobotics. Living material-derived intelligent micro/nanorobots (LMNRs) are self-propelled devices that combine living materials with synthetic materials. By harnessing energy from external physical fields or biological sources, LMNRs can move autonomously and perform various biomedical functions, such as drug delivery, crossing biological barriers, medical imaging, and disease treatment. This review, from a biomimetic strategy perspective, summarized the latest advances in the design and biomedical applications of LMNRs. It provided a comprehensive overview of the living materials used to construct LMNRs, including mammalian cells, plants, and microorganisms while highlighting their biological properties and functions. Lastly, the review discussed the major challenges in this field and offered suggestions for future research that may help facilitate the clinical application of LMNRs in the near future.