Biomedical materials (Bristol, England)最新文献

Shear stress serves as a key physical stimulus in three-dimensional (3D) cell culture systems, regulating critical physiological processes such as cell alignment, polarity maintenance, and functional maturation. This review systematically analyses 87 peer-reviewed studies published between 2021 and 2025, focusing on the effects of shear stress across various 3D tissue culture models, including the liver, kidney, intestine, brain, heart, and vasculature. Rather than dividing organoid and organ module studies, we take an integrated view of 3D cellular systems, quantitatively and qualitatively comparing the optimal shear stress ranges and biological responses required for different organs. Our analysis reveals that while organoid-based studies have actively investigated shear stress, organ module systems with their higher structural complexity require more precise and dynamic shear regulation yet lack sufficient quantitative approaches. Furthermore, organ-specific sensitivity to shear stress is rooted in anatomical and physiological differences, which must be accounted for in the design of advanced 3D culture platforms. This review consolidates key findings on structural design parameters, organ-specific shear thresholds, and engineering strategies, while also exploring the potential integration of automation and artificial intelligence-based control frameworks. Based on these insights, we propose future directions for constructing physiologically relevant and reproducible smart bioreactor systems for regenerative medicine and artificial organ applications.

On-demand drug delivery systems (DDS) offer precise control over therapeutic agents' timing, location, and dosage, enabling treatment tailored to individual patient needs. In particular, wireless on-demand DDS overcomes the limitations of wired connections by using external stimuli-such as electric fields, magnetic fields, ultrasound, microwaves, and near-infrared (NIR) light-to trigger drug release remotely. This approach allows real-time dose adjustment, improves patient compliance, and reduces hospital visits, particularly for chronic diseases. Advances in nanomaterials, implantable microdevices, and wireless communication technologies have facilitated the integration of sensors, responsive polymers, and microelectronics into modular platforms for targeted therapy. This review highlights clinical applications, including NIR-triggered nanoparticles for cancer therapy, glucose-sensitive systems for insulin delivery, and seizure-responsive neurotherapeutics. While these strategies promise to enhance therapeutic efficacy and minimize side effects, challenges persist in large-scale manufacturing, regulatory approval, and cyber-physical security. The integration of smart materials, wireless power transfer, and closed-loop control systems with nano-bio-interface holds significant potential to transform personalized medicine, enabling patient-specific drug delivery in the near future.

In cartilage tissue, the exchange of nutrients and metabolic waste products occur solely through diffusion within the extracellular matrix. Due to the avascular nature of cartilage, once it is damaged, its inherent regenerative capacity is limited. Laryngeal cartilage defects often result from surgical interventions, such as those performed for laryngeal tumors, traumatic injuries to the larynx, and congenital laryngeal deformities. Clinically, autologous cartilage or synthetic substitutes are commonly used for repairing and reconstructing laryngeal cartilage. However, these conventional approaches fail to fundamentally restore the original structure and function of the cartilage tissue. In this study, we employed three-dimensional printing technology to develop and optimize gelatin (Gel)/alginate (Alg)/hyaluronic acid (HA) hydrogel scaffolds, which possess desirable mechanical properties and uniform porosity. These scaffolds were fabricated using a temperature and Ca2+ mediated dual-crosslinking method. To enhance the regenerative potential, exosomes and bone marrow-derived mesenchymal stem cells (BMSCs) were incorporated into the Alg/Gel/HA composite hydrogel, forming a bioactive scaffold designed for the effective repair of laryngeal cartilage defects. The efficacy of the scaffold was evaluatedin vivoby implanting the constructs into animal models, with specimens retrieved at 6 and 12 weeks post-implantation. Histological analysis of the repair site was performed using hematoxylin and eosin staining, toluidine blue staining, Masson's trichrome staining, and type II collagen immunohistochemistry. The results demonstrated that the inclusion of exosomal growth factors significantly promoted the chondrogenic differentiation of BMSCs, resulting in superior cartilage repair compared to controls. By synergizing the therapeutic effects of bioactive molecules with biomaterial scaffolds, the bioactive scaffold developed in this study provides a novel tissue engineering approach for the repair of laryngeal cartilage defects. This strategy holds great potential for advancing the field of laryngeal cartilage reconstruction, offering a promising solution for restoring the structure and function of damaged laryngeal cartilage.

Traditional polymethyl methacrylate (PMMA) bone cement faces challenges, including stress shielding due to its high elastic modulus and thermal damage from polymerization exotherm. This study develops a novel BiInSn-PMMA composite bone cement that simultaneously addresses these limitations. The results demonstrate that the mechanical properties of the composite bone cement can be effectively controlled by adjusting the ratio of BiInSn powder, thus meeting the requirements of different bone tissues. The phase change characteristics of BiInSn significantly reduce thermal risk, lowering the peak temperature in surrounding tissues from 57.6°C to 48.3°C and shortening the duration above 47°C from 210 seconds to 39 seconds. In addition, the introduction of BiInSn provides the composite bone cement with good radiographic visibility while exhibiting excellent cytocompatibility in vitro. Overall, this BiInSn-PMMA composite bone cement possesses adjustable mechanical properties, low risk of thermal damage, good radiographic visibility, and low cytotoxicity, demonstrating its potential value in bone defect repair.

Biomedical implants play a critical role in restoring tissue function; however, their long-term performance is often hindered by challenges such as infection, inflammation, and poor integration with the host tissue. Recent advances in polymer-based coatings, particularly those incorporating drug-loaded microparticles and nanostructured fillers, have demonstrated outstanding potential in overcoming these limitations. These multifunctional coatings not only enhance biocompatibility and mechanical stability but also enable controlled, localized drug delivery, thereby reducing systemic side effects and improving therapeutic outcomes. This review differentiate three different categories of polymer coatings which can be mostly found in research works including: Natural polymers with their remarkable promise due to their biodegradability, inherent bioactivity, and ability to support cell adhesion and tissue regeneration; Synthetic polymers, which can further contribute tunable degradation rates and mechanical versatility, making them suitable for a wide range of clinical applications; Hybrid/composite coatings, whose design rely on integrating both natural and synthetic polymers to enable to tackle more bottlenecks and expand the therapeutic scope of implants by providing infection resistance, anti-inflammatory effects, and osteogenic stimulation. Furthermore, this review brings together recent advances in micro- and nanoengineered drug-eluting coatings for medical implants, highlighting their design strategies, functional performance, and clinical relevance. Emerging trends and future directions are discussed to underscore the transformative potential of these systems in advancing next-generation implantable medical devices.

Wound healing is a complex, self-regulated biological process primarily driven by the immune response. However, this normal process can be disrupted by several factors such as infection or prolonged inflammation leading to chronic wounds. Zinc oxide nanoparticles (ZnONPs) have emerged as promising nanomaterials for wound therapy due to their broad antimicrobial, anti-inflammatory, and antioxidant properties. Despite their therapeutic potential, the clinical use of ZnONPs has been hindered by concerns like cytotoxicity, instability, and uncontrolled zinc ion release. To overcome these limitations, natural, synthetic, and hybrid polymer-based nanocomposites have been developed as advanced delivery platforms. In addition to acting as a carrier for ZnONPs, improving their biocompatibility, many polymers have wound healing activities, providing scaffolds that promote cellular proliferation and angiogenesis. This review highlights recent progress in ZnONPs-loaded polymer nanocomposites, such as hydrogels, nanofibers, and porous films, focusing on their fabrication methods, characterization tools, and application in wound healing, while emphasizing the need for optimizing these platforms to move toward clinical translation.

Oral diseases like periodontitis and tooth loss affect billions worldwide, causing alveolar bone resorption and complicating implant placement and bone regeneration. Guided bone regeneration addresses these defects using barrier membranes that block soft tissue infiltration and promote bone growth. CollaTape®, a type I bovine collagen membrane, is widely used for its biocompatibility and resorbability, though its bioactivity and antibacterial properties could be improved. This study compares two functionalization methods for enhancing CollaTape® membranes: adsorption of GBMP1α peptide (a BMP-2 biomimetic) and covalent anchoring of its analogue Aoa-GBMP1α. Both functionalizations were performed at concentrations of 0.25, 0.5, 1, and 1.5 mg ml^-1. Optimal conditions were selected basing on osteoblast mineralization assays and resulted to be 0.25 mg ml^-1for adsorption and 1.5 mg ml^-1for covalent binding. Peptide surface density analysis revealed values of 0.040 μmol cm^-2for adsorption and 0.278 μmol cm^-2for covalent anchoring. Biological assays assessed mineralization, proliferation, and gene expression (SPP1, RUNX2) in human osteoblasts, and antibacterial activity againstStaphylococcus aureusandEscherichia coli. All functionalized membranes improved osteoblast activity, with adsorption showing superior results. Antibacterial tests showed slight but significant reductions in bacterial colonies, especially for adsorption. Additional mechanical tests via unconfined compression were performed to evaluate the effect of functionalization on the membranes' mechanical properties. These tests confirmed that neither functionalization method compromised the stiffness of the membrane, a critical parameter in clinical applications. Overall, peptide adsorption is a simple and clinically adaptable strategy to enhance CollaTape®'s bioactivity and antibacterial properties while maintaining their original mechanical properties.

Astaxanthin (ATX) is a potent antioxidant with broad biological activities, yet its poor water dispersibility, low stability, and high cost have markedly limited its practical utilization. Recently, lipid-based nanocarriers have emerged as promising delivery systems to enhance the efficiency of bioactive compounds in skin protection. In this study, enriched ATX extract from Haematococcus pluvialis (ATXex) was encapsulated into nanoemulsions (NE-ATXex) and nanoliposomes (NL-ATXex) to evaluate radioprotective and wound healing effects through in vitro and in vivo studies. NE-ATXex and NL-ATXex were prepared using high-shear homogenization and thin-film hydration, respectively, each followed by ultrasonication. Their biological activities were assessed in vitro by measuring reactive oxygen species, DNA double-strand breaks, and dead cells after X-ray exposure, as well as by scratch wound healing assays. In vivo activities were further evaluated using mouse models of X-ray-induced skin damage and full-thickness excisional wounds. The results showed that nanocarrier formulations have high physical stability during storage and in culture medium. Treatment with NE-ATXex and NL-ATXex at ATX concentrations of 0.25-0.5 µg/mL reduced intracellular ROS levels by approximately 80%, as well as DNA damage and cell death by around 50%, compared with cells exposed to 2 Gy X-irradiation. In addition, both formulations promoted scratch wound closure, reaching approximately 60% at 24 h and over 90% at 48 h. NE-ATXex at an ATX concentration of 0.5 µg/mL showed notable cytoprotective effects, whereas NL-ATXex at the same concentration was more favorable for skin applications, specifically in tissue regeneration. NL-ATXex accelerated wound healing and promoted scar remodeling by regenerating hair follicles and adipocytes. Both nanocarriers enhanced skin radioprotection by reducing damage to epidermis, adipocytes, hair follicles, and sebaceous glands following cumulative X-irradiation at 30 Gy. These results highlight the skin protective potential of ATXex in lipid-based nanocarriers, supporting its promise for biomedical applications.

Cardiovascular disease remains a significant global health challenge. Artificial blood vessel transplantation is considered one of the most effective strategies for treating severe cardiovascular diseases. While autologous blood vessels are the preferred source for transplantation, their limited availability in patients presents considerable obstacles to clinical procedures. Most commercial artificial blood vessels are fabricated from polymers and are susceptible to complications such as thrombosis and restenosis. Consequently, there is an urgent clinical need for tissue-engineered vascular grafts that are non-thrombogenic and possess mechanical properties comparable to those of native blood vessels. In recent years, 3D bioprinting, an advanced research area at the forefront of biomedical engineering, has garnered considerable attention as a potential key driver of the so-called 'third industrial revolution.' Compared to conventional manufacturing methods, 3D bioprinting utilizing biomaterials enables the fabrication of artificial blood vessels with enhanced anatomical adaptability. This review summarizes recent advancements in the field of 3D bioprinting of artificial blood vessels, with an emphasis on commonly used 3D bioprinting technologies, underlying principles, and printing materials, and provides a comprehensive overview of the current applications of 3D bioprinted artificial blood vessels across various domains. Additionally, this article discusses prospective opportunities, remaining challenges, and future research directions in 3D bioprinting technology for artificial blood vessels.

Cartilage defects pose significant clinical challenges due to limited regenerative capacity. Dynamic matrix stiffness, mimicking the physiological mechanical microenvironment, shows promise in directing stem cell chondrogenesis, but its molecular mechanisms remain unclear. Bone marrow mesenchymal stem cells (BMSCs) were cultured on engineered hydrogels with static soft (0.033 kPa), dynamic (0.031-0.126 kPa, time-dependent stiffening), and static stiff (0.126 kPa) conditions. We performed small interfering RNA-mediatedIhhknockdown andRcan1overexpression, with chondrogenic differentiation assessed via COL2/SOX9 immunofluorescence. For molecular analyses, we conducted qPCR, CUT&Tag-PCR, Western blot, RNA-seq, H3K18la-targeted CUT&Tag sequencing, and transmission electron microscopy (TEM) for mitochondrial morphology assessment. Dynamic stiffness significantly enhanced chondrogenic differentiation, as evidenced by immunofluorescence detection of elevated COL2 and SOX9 expression.IhhmRNA expression levels were upregulated by dynamic stiffness. Transcriptome profiling analysis revealed thatIhhknockdown disrupted the expression of genes involved in the glycolytic pathway, while Western blot results showed thatIhhknockdown inhibited histone H3 lysine 18 lactylation (H3K18la). CUT&Tag sequencing revealedIhh-dependent H3K18la enrichment at regulatory regions of mitochondria-associated genes, notablyRcan1. Ihhdeficiency promoted mitochondrial fission, as evidenced by increasedDrp1andFis1mRNA expression levels and direct observation of enhanced mitochondrial fission via TEM. Crucially,Rcan1overexpression rescued mitochondrial fusion, downregulated fission markers, and reinstated chondrogenic marker expression. Consistently, the LDHA inhibitor FX11 reduced lactate levels, diminished H3K18la, and downregulatedRcan1, confirming the metabolic dependence of this axis. RNA-seq analysis further established thatRcan1overexpression reprogrammed signaling pathways critical for cell differentiation, including ECM-receptor interaction. Dynamic stiffness promotes BMSC chondrogenesis via theIhh-H3K18la-Rcan1axis, linking mechanical cues to epigenetic regulation of mitochondrial remodeling and providing a novel target for cartilage repair.