Biomedical materials (Bristol, England)最新文献

Stainless steel has been widely used as an implant material for its good biocompatibility, suitable mechanical strength, and high corrosion resistancein vivo. However, its biomedical applications suffer from delayed healing due to its high density and stiffness. Here we proposed body-centered cubic lattice structures with various unit sizes to adjust the density and stiffness of 17-4 PH stainless steel implants to simulate the bone structure and mechanical performance. The mechanical properties satisfy the requirement to be used with the human body with a yielding strength over 60 MPa and Young's modulus over 1.7 GPa. Corrosion resistance characterization indicates that the implants have negligible changes in microstructures and mechanical properties in simulated body fluid for 6 months. The implants were modified by inserting calcium sulphate-based bone cement into the voids of the lattice to improve their biocompatibility. Cytotoxicity results showed that both the implants and modification have no toxicity to human bone marrow mesenchymal stem cells.In vivosafety and osseointegration testing of the implants were conducted by implantation in rabbit distal femur, showing an improved recovery and bone integration of the implants. The presence of calcium sulphate and tailored lattice structure synergistically promotes osteogenesis through controlled calcium ions release and matching the mechanical properties of the bone.

Hydrogel-based functional dressings for wound healing have garnered increasing attention due to their excellent hydrophilicity, adjustable mechanical properties, and superior biocompatibility. In this study, a composite hydrogel was facilely fabricated through the Schiff base reaction betweenϵ-poly-L-lysine modified chitosan (CS-PL) and oxidized dextran (Odex). The formed hydrogel displayed the interconnected microstructure (100-200 μm), injectability, and adjustable mechanical properties. Macroscopic observation and alternating strain rheological analysis confirmed the good self-healing ability of the hydrogel. Furthermore, with the incorporation of epigallocatechin-3-gallate, the composite hydrogel exhibited an improved reactive oxygen species (ROS) scavenging capability and good antibacterial activity againstE. coliandS. aureus. The designed composite hydrogel dressings exhibited hemolysis rates of 0.75 ± 0.60% to 0.81 ± 0.31%, indicating their excellent hemocompatibility. Moreover, CCK-8 analysis and fluorescent images confirmed the excellent cytocompatibility of the hydrogels after co-culturing with NIH 3T3 cells for various periods. The above results offer a promising strategy for preparing functional hydrogel dressings viaϵ-PL modification on CS for wound healing applications.

Polylactic acid (PLA) has been widely studied as a scaffold material for bone tissue engineering, but still faces challenges, including as insufficient mechanical strength, slow degradation rate, and poor biomineralization and cellular response. In this study, PLA-based composite bone scaffolds incorporating basic magnesium sulfate whiskers (BMSW) at concentrations of 0, 2.5, 5.0, 7.5, and 10 wt% were fabricated via fused deposition modeling (FDM) 3D printing technology. The compression properties of the scaffolds increased with increasing BMSW content and peaked at 5 wt% BMSW, with the strength and modulus reaching 21.51 MPa and 297.38 MPa, respectively, 73% and 50% higher than those of PLA due to the reinforcing effect and uniform distribution of BMSW whiskers. The addition of BMSW accelerated the degradation of the PLA scaffold, with faster degradation observed at higher BMSW contents. Specifically, the alkaline ions (e.g. OH^-) released by BMSW neutralized the acidic products generated during the degradation of PLA, thereby accelerating the degradation of the scaffold through the synergistic effect of acid and base. Magnesium ions steadily released from BMSW degradation due to the encapsulation effect of the PLA matrix, and their release rate could be controlled by varying the BMSW content. The incorporation of BMSW also enhanced the biomineralization capacity of the composite scaffolds in simulated body fluid and promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells, as confirmed by fluorescence and alkaline phosphatase staining. This study demonstrates that incorporating inorganic whiskers containing bioactive and alkaline ions into polymer can enhance its overall performance, making it more suitable for bone scaffold development.

Tumor acidosis is a consequence of altered metabolism that primarily takes place due to lactate secretion from anaerobic glycolysis. As a result, many regions within the tumors are chronically hypoxic and acidic. To measure the intratumor pH dynamically, we have fabricated a biocompatible pH nanoparticle sensor using surface-enhanced Raman spectroscopy (SERS-pNPS) and monitored continuous pH levels in three-dimensional multicellular spheroids. The 3D multicellular spheroids were cultured using a micro-well array chip made of polydimethylsiloxane (PDMS). The SERS-pNPS were synthesized by linking 4-Mercaptobenzoic acid (4-MBA) to silver nanoparticles (AgNPs) of size 50 nm. The calibration curve demonstrates a linear correlation between the ratio of Raman peak intensities (1378 cm^-1/1620 cm^-1) with the pH level. The sensor exhibits a detection limit of pH 4.4 and demonstrates linearity within the physiological pH range (pH 4.4-pH 8.23). The SERS-pNPS was applied for pH measurement in different 3D co-cultured spheroid models such as lung cancer (A549-NIH3T3), breast cancer (MCF-NIH3T3), colon cancer (HCT8-NIH3T3) and mono-cultured spheroids using fibroblast (NIH3T3) cells. The detailed analysis indicated that the 3D co-cultured cancerous tumor models have 16% more acidic microenvironment as compared to 3D mono-cultured spheroid model. Also, a presence of a decreasing pH gradient from peripheral to the core region is observed in both the cases indicating acidosis in the core region. The SERS-pNPS platform facilitates a non-invasive and dynamic pH tracking, and thus offers an improved insight into the acidic microenvironment in various tumor models.

With the growing global burden of cartilage degeneration in aging populations and the limitations of conventional surgical interventions, tissue-engineered hydrogels have emerged as a transformative strategy for functional cartilage regeneration. Here, we report an innovative bioinspired composite hydrogel fabricated through carbodiimide-mediated crosslinking of silk fibroin (SF) and hyaluronic acid (HA) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC)/N-hydroxysuccinimide (NHS) in MES buffer. The engineered hydrogel exhibited an optimally interconnected porous architecture (pore size: 50-100 μm), tunable compressive modulus ( 86.51 KPa mimicking native cartilage), and swelling performance (570 ± 15%), addressing critical requirements for minimally invasive delivery and mechanical stability. Comprehensive in vitro characterization demonstrated exceptional cytocompatibility, with close to 100% hBMSC viability over 7 days. Most notably, the SF/HA hydrogel significantly promoted chondrogenic differentiation, as evidenced by: (1) 1.8 fold increased in progressive glycosaminoglycan (GAG) deposition (Alcian blue staining), (2) upregulation of SOX9, COL2, and AGG gene expression (RT-qPCR, 1.4, 0.4 and 1.3 fold vs. control), and (3) enhanced type II collagen synthesis (Western blot). These results demonstrate the potential of SF/HA hydrogel for cell-based cartilage repair and osteoarthritis therapy.

Large-scale cellular production systems offer a significant and diverse benefit impacting the therapeutic (stem cell and vaccine production) and cellular agriculture (lab-grown meat) sectors. Producing desired cells at mass can improve production yield whilst reducing the environmental and ethical burden associated with industrialised agriculture and production of therapeutic goods. Many existing large-scale cultivation strategies of adherent cells leverage the use of microcarriers (MCs) within bioreactors. However, currently commercial MCs are not dissolvable and lack specificity for different cell types and bioprocessing contexts. In this work, we validate the effectiveness of customisable, polymeric MCs engineered to enhance cell growth and productivity. These MCs, which can be adjusted in terms of stiffness, surface charge, and size, maintain their structural integrity while offering precise property modifications. Under specific bioprocessing conditions, the custom MCs demonstrated significant improvements in cell productivity and sustainability compared to other commercial options. Our study (1) highlights how tailored substrate properties, particularly stiffness, can significantly impact cell yield and outcomes, and (2) suggests additional optimisations in surface charge and size that could further enhance MC technology. These advancements have the potential to improve large-scale cell and virus production efficiency, ultimately reducing the cost of production.

Guided bone regeneration (GBR) is a promising technology for enhancing osteogenesis while preventing the invasion of fibrous tissue in implantation. Although collagen membranes have been widely utilized in GBR applications, their ability to support sufficient bone formation remains limited. Herein, we developed collagen-sodium alginate membranes (CSaM) with ultrasmall calcium phosphate oligomers (CPOs) incorporation by either physical adsorption (CSaM-em) or coprecipitation (CSaM-im). These two forms of organic-inorganic interaction facilitated biomimetic mineralizationin situ, exhibiting high hydrophilicity, proper degradable rate, good mechanical properties, and favorable biocompatibility. Furthermore,in vivotest illustrated that CSaM-im membrane exhibited superior bone formation ability. These results suggested that CSaM with CPOs coprecipitation enhanced physicochemical properties and improved osteogenesis, highlighting their significant potential for applications in GBR.

Tumor microenvironment (TME)-responsive nanomedicines have emerged as a promising precision therapeutic strategy in cancer treatment. By incorporating stimuli-responsive properties, these nanomedicines can achieve targeted delivery and controlled release at tumor sites, thereby enhancing therapeutic efficacy while minimizing side effects. This review provides a comprehensive overview of the latest advancements in TME-responsive nanomedicines for cancer immunotherapy, covering various stimulus-responsive mechanisms (such as pH, reactive oxygen species, hypoxia, enzymes, and ATP) and their applications in improving immune efficacy and reducing immune-related adverse effects. In addition to discusses the key challenges associated with the clinical translation of these nanomedicines and proposes future research directions. This work aims to offer a theoretical foundation and design reference for the further development and application of tumor-responsive nanomedicines.

Hyaluronic acid (HA) is a large molecular acidic glycosaminoglycan that is widely present in the extracellular matrix (ECM) of cells. Aside from being an important component of the ECM, HA is an excellent biomaterial that is known for its good biocompatibility and mechanical properties. This study aimed to investigate the employment and effectiveness of HA in cell culture. We performed a review on the physicochemical properties of HA and its application in cell culture. HA is widely used in a number ofin vitrocell cultures, especially in stem cell cultivation and differentiation and in tissue-engineering applications, which has greatly expanded the scope and field of its applications. This article provides a brief overview of the applications of HA in various cell culture fields, thereby providing a reference for related research on HA.

This study investigates a novel strategy combining biphasic calcium phosphate (BCP) bioceramics with autocrine induced membranes (IMs) to enhance osteogenesis and vascularization for bone regeneration. Highly bioactive, porous BCP scaffolds (porosity: 68.1 ± 1.7%; pore size: 526-1000 µm) were combined with autocrine membranes in a rat femoral defect model. The optimal membrane formation time was determined by ELISA analysis of osteogenic and angiogenic factors (BMP-2, VEGF, ANG-II, PEG-2, FGF-2). Material characterization included SEM, XRD, and mercury intrusion porosimetry.In vivobone regeneration was evaluated via micro-CT, histological analysis, and osteogenic marker expression (Alp, Bmp2, Col-1, Ocn, Opn, Runx2). The 4-week autocrine membrane exhibited superior osteogenic and angiogenic activity. Combined with BCP scaffolds, it accelerated bone regeneration, with micro-CT and histology showing significant new bone formation by 3 weeks and near-complete defect repair by 6 weeks. Osteogenic gene/protein expression (Alp, Bmp2, Col-1, Ocn, Opn, Runx2) was consistently higher in the BCP + IM group (BCP bioceramics with autocrine IMs) when compared to that of the BCP group and the control group, corroborating histological outcomes. Autocrine IMs significantly enhance the osteogenic efficacy of BCP bioceramics, demonstrating promise for weight-bearing bone defect repair.