Biomedical materials (Bristol, England)最新文献

The use of covered self-expandable metal (CSEM) stents for fistulas sealing is a common clinical approach. However, these stents need to be removed once their therapeutic goals are achieved. Our study designed and fabricated a dumbbell-shaped, high-porosity, biodegradable polydioxanone weaving tracheal (PW) stent, and investigated its sealing efficacy and degradation characteristics. A tracheal defect model was created in 24 beagle dogs. Six dogs were implanted with CSEM stents, while the remaining 18 dogs received PW stents. The dogs in the CSEM and PW groups were observed for up to 8 and 14 weeks, respectively, with clinical symptoms, tracheoscopy, computed tomography scans, and fluoroscopy monitored. Subsequently, the stents were retrieved to observe morphological changes, and measure mechanical properties. The PW stents exhibited excellent airtightness, with significantly fewer complications such as stent displacement and granulation tissue hyperplasia compared to the CSEM stents. The tracheal tissue response to the PW stent was relatively mild. After PW stent implantation, collagen fiber deposition at the defect site gradually increased, and cartilage structure regeneration was observed in later stages. Notably, cilia were largely absent in the tracheal epithelium, with squamous metaplasia observed even in the later stages of the experiment following PW stent implantation. Additionally, the PW stents remained mostly intact in the canine airways until week 12, and were completely degraded and disappeared from the canine airways at week 14, without causing severe complications. The PW stent, featuring excellent biocompatibility and uniform degradation in the large-animal airway, demonstrated clinical effectiveness in sealing tracheal defects.

Traumatic bleeding and tissue damage pose complex clinical challenges requiring rapid hemostasis and concurrent tissue regeneration. Although traditional hemostatic agents primarily focus on controlling bleeding, they generally lack additional functionalities such as preventing adhesion and promoting tissue regeneration, limiting their clinical utility. This study developed a composite regenerative hemostatic agent based on a porcine decellularized extracellular matrix (ECM) to address these limitations. This agent is designed to achieve rapid hemostasis, prevent adhesions, and promote tissue regeneration. Its functionality was evaluated using a mouse liver laceration model to explore its clinical applicability. Hemostatic efficacy was assessed by measuring the bleeding time and blood loss, and comparing the composite agent with conventional commercial hemostatic agents. Additionally, the degree of adhesion between the liver and surrounding tissues was evaluated after re-opening the abdomen to confirm the anti-adhesion effects. Tissue regeneration and inflammatory responses at the injury site were further analyzed using hematoxylin and eosin staining, Masson's trichrome (MT) staining, and Ki-67 immunohistochemistry. The ECM-based hemostatic agent significantly reduced the bleeding time compared to conventional products and markedly reduced adhesion formation. In the experimental group, the agent enhanced cell attachment and proliferation at the damaged tissue site, to facilitate the natural tissue regeneration process, without inducing inflammatory or pathological changes. The developed composite hemostatic agent could overcome the limitations of existing products by integrating three crucial functions: rapid hemostasis, preventing adhesion, and promoting tissue regeneration. These findings suggest the potential for hepatocyte proliferation and tissue remodeling, which require further validation, and indicate promising applicability in complex surgical environments.

Regenerating injured bone tissue remains a critical challenge, necessitating the development of functional scaffolds to support the intricate process of neo-bone growth. Various natural and synthetic materials combined with bioactive factors have been explored, but decellularized extracellular matrices (dECM) continue to stand out as excellent scaffolding materials due to their intrinsic bioactivity. In this study, we fabricated cryogel-type scaffolds with interconnected pores from decellularized bone ECM (DBM) after mineral removal. To enhance their angiogenic and osteogenic properties, we incorporated laponite (LAP), which is a kind of lithium magnesium silicate. For improved mechanical strength, the DBM was modified with methacrylic anhydride to enable chemical crosslinking among collagen macromolecules. The addition of LAP further contributed to mechanical reinforcement. The resulting composite cryogel demonstrated exceptional cyclic compressive stability, maintaining structural integrity and mechanical strength under repetitive loading.In vitroassays revealed its significant promotion of vascularization and osteogenic differentiation.In vivostudies using a rat cranial defect model confirmed substantial new bone formation and enhanced regeneration of vascularized bone tissue. These findings highlight the potential of bone-derived dECM materials for effectivein situbone regeneration.

Mesoporous silica nanoparticles (MSNs) have been demonstrated to promote osteoblast differentiation; however, the unclear impact of their surface roughness on osteogenesis, coupled with inadequate targeting capability and suboptimal therapeutic outcomes, presents major challenges. Herein, we developed a biomimetic nanoplatform, CM@DEX-R-MSN, by coating dexamethasone (DEX) loaded-rough MSN (R-MSN) with mesenchymal stem cell (MSC) membranes (CM) to enhance osteogenic differentiation of MSCs for improved bone regeneration. The CM@DEX-R-MSN showed retained rough surfaces with a hydrodynamic diameter of 164.35 ± 5.81 nm, a Zeta potential of -11.98 ± 1.37 mV with good MSC membrane integrity, negligible cytotoxicity bothin vitroandin vivo. CM@DEX-R-MSN exhibited significantly enhanced MSC internalization compared to uncoated MSN. They markedly upregulated alkaline phosphatase activity, osteogenic markers, and mineralization nodule formationin vitro. In bone defect model established in rabbits, CM@DEX-R-MSN restored bone volume and prolonged retention at the defect site. More importantly, we experimentally observed that both R-MSN and CM-coated nanoparticles exhibited superior osteogenic differentiation effects compared to conventional MSNs and non-coated counterparts, respectively-with CM@DEX-R-MSN demonstrating the most potent efficacy. Our results demonstrated that CM@DEX-R-MSN synergistically integrates MSC membrane-mediated homotypic targeting, nanotopography of R-MSN, and DEX-driven osteogenic differentiation, offering a promising targeted therapeutic strategy for bone regeneration. Their enhanced biocompatibility, osteogenic efficacy, and sustained retention underscore its translational potential for orthopedic applications.

Bone morphogenetic protein-2 (BMP-2) is a highly potent osteoinductive factor that has received approval from the U.S. Food and Drug Administration due to its significant osteogenic properties. Nonetheless, its clinical utility is limited by adverse effects linked to supraphysiological dosing and its brief half-life. Consequently, there is a pressing need for a safe and effective delivery system to enable the sustained release of BMP-2. In this study, we have developed bilayer-structured oxidized sodium alginate-carboxymethyl chitosan (OAC) microspheres through the application of electrospraying and the Schiff reaction. The inner layer, composed of oxidized sodium alginate, electrostatically adsorbs BMP-2, while the porous polyelectrolyte membrane on the surface enhances adsorption, thereby effectively regulating the prolonged and controlled release of BMP-2. We assessed the minimal osteogenic induction concentration of BMP-2 on rat bone marrow mesenchymal stem cells (rBMSCs) to optimize the BMP-2 loading concentration within the microspheres.In vitroexperiments demonstrated that the bilayer membrane structure of the hydrogel microspheres significantly delayed the release of BMP-2, facilitating a long-term, sustained release. Furthermore, the microspheres facilitated the proliferation, migration, and osteogenic differentiation of rBMSCs. The osteogenic-promoting efficacy of the BMP-2-encapsulated OAC microspheres was further corroboratedin vivothrough implantation alongside calcium phosphate cement into the dorsal region of nude mice. Collectively, the BMP-2-encapsulated OAC microspheres we developed constitute a promising clinical approach to augment scaffold degradation and osteogenesis for the repair of bone defects.

Endothelialisation is critical for the success of coronary stents, as it mitigates thrombosis risk and ensures long-term vascular healing. While advancements in stent materials, surface modifications and surface coatings have improved stent performance, the influence of stent cell geometry (particularly cell shape and size) on endothelialisation remains underexplored. This review examines the principles of cell growth influenced by geometry, drawing insights from non-coronary stent applications to identify research gaps in coronary stent applications. While recent studies highlight the role of surface microstructure in endothelialisation, the impact of stent cell geometry remains largely unexplored. Moreover, insights from tissue engineering suggest that optimising scaffold geometry could enhance endothelial cells (ECs) adhesion and proliferation, thereby accelerating re-endothelialisation. Based on these considerations, this review hypothesizes that optimising stent cell geometry could directly regulate ECs behaviour, thereby influencing endothelialisation performance. Finally, this paper critically evaluates the limitations of existing research and proposes future directions for leveraging cell geometry in the development of next-generation stents with improved biocompatibility and endothelialisation performance.

ZnO-doped hydroxyapatite (HAp) coatings were developed on thermally sensitive polyetheretherketone (PEEK) substrates using a hybrid plasma spraying approach that combines powder and solution precursor feedstocks. Three coating architectures with different ZnO contents were designed to assess the influence of zinc incorporation on antibacterial and osteogenic performance. All coatings were deposited at a low plasma power (5.7 kW), enabling successful deposition without thermal degradation of the PEEK substrate, and achieving bond strengths up to 17 MPa. ZnO-doped coatings exhibited antibacterial activity againstE. coliandS. aureus, with significantly higher efficacy againstE. coli. In vitrotests using MC3T3-E1 pre-osteoblasts showed enhanced cytocompatibility and osteogenic differentiation at low ZnO concentrations, as indicated by increased alkaline phosphatase (ALP) activity and calcium deposition exceeding those of undoped HAp coatings by over 50% after 21 d. The combination of antimicrobial and osteoinductive properties suggests that ZnO-doped HAp coatings are promising candidates for PEEK-based orthopedic implants.

Sonodynamic therapy (SDT) is a viable alternative to traditional photodynamic therapy owing to its ability to penetrate tissue. However, the therapeutic efficacy of a single SDT treatment is constrained by the prolonged hypoxia of the tumor, rendering SDT ineffective for treating disease. SDT was used in conjunction with nitric oxide (NO) gas in this study to induce apoptosis and ferroptosis in hepatocellular carcinoma (HCC) cells for treating cancer treatment. We synthesized 5,10,15,20-tetra (4-aminophenyl) porphyrin nanobubbles (TAPP@NBs) for the SDT treatment. S-nitroso glutathione (GSNO) was used as an NO gas donor. Thein vitroanticancer effect of the combined treatment was examined using HepG2 and HUH7 hepatoma cell lines. Reactive oxygen species and NO were examined using 2,7-dichlorodihydrofluorescein diacetate and 3-amino,4-aminomethyl-2',7'-difluorescein diacetate staining, respectively. Cell proliferation and apoptosis were analyzed using CCK-8 and flow cytometry, respectively. Ferroptosis was evidenced using glutathione and malondialdehyde assays. The cellular migratory capacity was assessed using a Transwell assay. TAPP@NBs can serve as a sonosensitizer for the SDT. GSNO serves as an NO donor under ultrasound and contributes to gas treatment, considerably increasing SDT efficacy. HCC cell proliferation and migration were considerably lower after combined SDT and NO gas therapy. Combined SDT and NO gas therapy induced apoptosis and ferroptosis in HCC cells. This paper describes a novel approach for optimizing tumor treatment.

A key challenge in bone tissue engineering (BTE) is designing structurally supportive scaffolds, mimicking the native bone matrix, yet also highly porous to allow nutrient diffusion, cell infiltration, and proliferation. This study investigated the effect of scaffold interconnectivity on human bone marrow stromal cell (BMSC) behaviour. Highly interconnected, porous scaffolds (polyHIPEs) were fabricated using the emulsion templating method from 2-ethylhexyl acrylate/isobornyl acrylate (IBOA) and stabilised with ∼200 nm IBOA particles. Pore interconnectivity was tuned by varying the internal phase fraction from 75%-85% and characterised by the degree of openness, Euler number, frequency, and size of pore interconnects. The attachment, proliferation, infiltration, and osteogenic differentiation of the BMSC cell line (Y201) were evaluated on these scaffolds. Results showed that high pore interconnectivity facilitated diffusion and cell infiltration throughout the scaffolds. Furthermore, the most interconnected scaffolds enhanced osteogenic differentiation of Y201 cells, as evidenced by elevated alkaline phosphatase activity and increased calcium and collagen production compared to less interconnected scaffolds. These findings emphasise the importance of scaffold interconnectivity in BTE for efficient nutrient transport, facilitating cell migration and infiltration, and supporting the development of interconnected cell networks that positively influence osteogenic differentiation.

Cell-based therapies are gaining attention as a promising approach for repairing damaged tissues and organs, offering alternatives to invasive treatments like organ transplants and powerful medications. Recent research has shifted towards extracellular vesicles (EVs), membrane-bound particles that can carry therapeutic compounds like DNA, RNA, and proteins, which may offer advantages over cell-based therapies, such as higher potency and reduced immune reactions. A key challenge in EV therapy is ensuring that the vesicles reach their intended target tissues. While EVs are often delivered via injection, systemic administration can result in off-target effects. To address this, we highlight the microfluidic encapsulation of EVs in hydrogel microcapsules that include a CD9 binding peptide (CD9BP), allowing for controlled EV release in response to a shift in environmental pH. By encapsulating CD9+ EVs in CD9BP hydrogel capsules, we demonstrate the release of their contents in acidified environments typical of damaged tissues. This method allows for targeted, localized EV delivery. The approach promises more effective tissue regeneration while reducing the need for broad, non-specific drug delivery.