Biomaterials Research最新文献

Background: Drug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation of reactive oxygen species (ROS). An effective solution would be to not only combat bacterial infections but also scavenge ROS to relieve inflammation at the wound site. Scaffolds with antioxidant properties are attractive for their ability to scavenge ROS, and there is medical demand in developing antioxidant enzyme-mimicking nanomaterials for wound healing.

Methods: In this study, we fabricated copper-coordination polymer nanoparticles (Cu-CPNs) through a self-assembly process. Furthermore, ε-polylysine (EPL), an antibacterial and cationic polymer, was integrated into the Cu-CPNs structure through a simple one-pot self-assembly process without sacrificing the glutathione peroxidase (GPx) and superoxide dismutase (SOD)-mimicking activity of Cu-CPNs.

Results: The resulting Cu-CPNs exhibit excellent antioxidant propertiesin mimicking the activity of glutathione peroxidase and superoxide dismutase and allowing them to effectively scavenge harmful ROS produced in wound sites. The in vitro experiments showed that the resulting Cu-CPNs@EPL complex have superior antioxidant properties and antibacterial effects. Bacterial metabolic analysis revealed that the complex mainly affects the cell membrane integrity and nucleic acid synthesis that leads to bacterial death.

Conclusions: The Cu-CPNs@EPL complex has impressive antioxidant properties and antibacterial effects, making it a promising solution for treating drug-resistant bacterial infections in chronic wounds. The complex's ability to neutralize multiple ROS and reduce ROS-induced inflammation can help relieve inflammation at the wound site. Schematic illustration of the ROS scavenging and bacteriostatic function induced by Cu-CPNs@EPL nanozyme in the treatment of MRSA-infected wounds.

The global increase of cutaneous wounds imposes huge health and financial burdens on patients and society. Despite improved wound healing outcomes, conventional wound dressings are far from ideal, owing to the complex healing process. Smart wound dressings, which are sensitive to or interact with changes in wound condition or environment, have been proposed as appealing therapeutic platforms to effectively facilitate wound healing. In this review, the wound healing processes and features of existing biomaterials are firstly introduced, followed by summarizing the mechanisms of smart responsive materials. Afterwards, recent advances and designs in smart and versatile materials of extensive applications for cutaneous wound healing were submarined. Finally, clinical progresses, challenges and future perspectives of the smart wound dressing are discussed. Overall, by mapping the composition and intrinsic structure of smart responsive materials to their individual needs of cutaneous wounds, with particular attention to the responsive mechanisms, this review is promising to advance further progress in designing smart responsive materials for wounds and drive clinical translation.

Currently, the clinical treatment of critical bone defects attributed to various causes remains a great challenge, and repairing these defects with synthetic bone substitutes is the most common strategy. In general, tissue engineering materials that mimic the structural, mechanical and biological properties of natural bone have been extensively applied to fill bone defects and promote in situ bone regeneration. Hydrogels with extracellular matrix (ECM)-like properties are common tissue engineering materials, among which methacrylate-based gelatin (GelMA) hydrogels are widely used because of their tunable mechanical properties, excellent photocrosslinking capability and good biocompatibility. Owing to their lack of osteogenic activity, however, GelMA hydrogels are combined with other types of materials with osteogenic activities to improve the osteogenic capability of the current composites. There are three main aspects to consider when enhancing the bone regenerative performance of composite materials: osteoconductivity, vascularization and osteoinduction. Bioceramics, bioglass, biomimetic scaffolds, inorganic ions, bionic periosteum, growth factors and two-dimensional (2D) nanomaterials have been applied in various combinations to achieve enhanced osteogenic and bone regeneration activities. Three-dimensional (3D)-bioprinted scaffolds are a popular research topic in bone tissue engineering (BTE), and printed and customized scaffolds are suitable for restoring large irregular bone defects due to their shape and structural tunability, enhanced mechanical properties, and good biocompatibility. Herein, the recent progress in research on GelMA-based composite hydrogel scaffolds as multifunctional platforms for restoring critical bone defects in plastic or orthopedic clinics is systematically reviewed and summarized. These strategies pave the way for the design of biomimetic bone substitutes for effective bone reconstruction with good biosafety. This review provides novel insights into the development and current trends of research on GelMA-based hydrogels as effective bone tissue engineering (BTE) scaffolds for correcting bone defects, and these contents are summarized and emphasized from various perspectives (osteoconductivity, vascularization, osteoinduction and 3D-bioprinting). In addition, advantages and deficiencies of GelMA-based bone substitutes used for bone regeneration are put forward, and corresponding improvement measures are presented prior to their clinical application in near future (created with BioRender.com).

Background: The reconstruction of tendons with large defects requires grafts with high mechanical strength and is often hindered by complications such as infection and adhesion. Hence, grafts combining the advantages of mechanical resilience and antibacterial/antiadhesion activity are highly sought after.

Methods: The silver nanoparticles (GA-Ag NPs) synthesized from gallic acid and silver nitrate were attached to a decellularized extracellular matrix (Decellularized Tendon crosslinking GA-AgNPs, DT-Ag). We examined the histological structure, mechanical property, morphology, Zeta potential, cytotoxicity, antibacterial properties, antioxidant and anti-inflammatory properties, and ability of the DT-Ag to treat tendon defects in animals.

Results: Approximately 108.57 ± 0.94 μg GA-Ag NPs loaded per 50 mg DT, the cross-linked part of GA-Ag NPs was 65.47 ± 0.57%, which provided DT-Ag with long-lasting antibacterial activity. Meanwhile, GA endowed DT-Ag with good antioxidant and anti-inflammatory activities. Additionally, The DT-Ag facilitated M2 macrophage polarization, and suppressed fibrin deposition by hindering fibroblast adhesion. Mormore, the main advantages of DT-Ag, namely its long-lasting antibacterial activity (tested using Escherichia coli and Staphylococcus aureus as models) and the ability to prevent tissue adhesion were confirmed in vivo.

Conclusion: The fabricated multifunctional tendon graft was highly hydrophilic, biocompatible, and mechanically resilient, and concluded to be well suited for dealing with the main complications of surgical tendon reconstruction and has bright application prospects.

Background: Bioresorbable stents are designed to provide temporary mechanical support to the coronary arteries and then slowly degrade in vivo to avoid chronic inflammation. Zinc (Zn) is a promising material for bioresorbable stents; However, it can cause inflammation and neointimal formation after being implanted into blood vessels.

Methods: To improve biocompatibility of Zn, we first coated it with polydopamine (PDA), followed by immobilization of endothelial vascular growth factor (VEGF) onto the PDA coatings. Adhesion, proliferation, and phenotype maintenance of endothelial cells (ECs) on the coated Zn were evaluated in vitro. Then, a wire aortic implantation model in rats mimicking endovascular stent implantation in humans was used to assess vascular responses to the coated Zn wires in vivo. Thrombosis in aortas post Zn wire implantation, degradation of Zn wires in vivo, neointimal formation surrounding Zn wires, and macrophage infiltration and extracellular matrix (ECM) remodeling in the neointimas were examined.

Results: In vitro data showed that the PDA-coated Zn encouraged EC adhesion, spreading, proliferation, and phenotype maintenance on its surfaces. VEGF functionalization on PDA coatings further enhanced the biocompatibility of Zn to ECs. Implantation of PDA-coated Zn wires into rat aortas didn't cause thrombosis and showed a faster blood flow than pure Zn or the Zn wires coated with VEGF alone. In addition, the PDA coating didn't affect the degradation of Zn wires in vivo. Besides, the PDA-coated Zn wires reduced neointimal formation, increased EC coverage, decreased macrophage infiltration, and declined aggrecan accumulation in ECM. VEGF immobilization onto PDA coatings didn't cause thrombosis and affect Zn degradation in vivo as well, and further increased the endothelization percentage as compared to PDA coating alone, thus resulting in thinner neointimas.

Conclusion: These results indicate that PDA coatings with VEGF immobilization would be a promising approach to functionalize Zn surfaces to increase biocompatibility, reduce inflammation, and inhibit neointimal formation after Zn implantation in vivo.

Background: Despite the effectiveness of glucagon-like peptide-1 agonist (GLP-1A) in the treatment of diabetes, its large molecular weight and high hydrophilicity result in poor cellular permeability, thus limiting its oral bioavailability. To address this, we developed a chimeric GLP-1A that targets transporter-mediated endocytosis to enhance cellular permeability to GLP-1A by utilizing the transporters available in the intestine, particularly the apical sodium-dependent bile acid transporter (ASBT).

Methods: In silico molecular docking and molecular dynamics simulations were used to investigate the binding interactions of mono-, bis-, and tetra-deoxycholic acid (DOCA) (monoDOCA, bisDOCA, and tetraDOCA) with ASBT. After synthesizing the chimeric GLP-1A-conjugated oligomeric DOCAs (mD-G1A, bD-G1A, and tD-G1A) using a maleimide reaction, in vitro cellular permeability and insulinotropic effects were assessed. Furthermore, in vivo oral absorption in rats and hypoglycemic effect on diabetic db/db mice model were evaluated.

Results: In silico results showed that tetraDOCA had the lowest interaction energy, indicating high binding affinity to ASBT. Insulinotropic effects of GLP-1A-conjugated oligomeric DOCAs were not different from those of GLP-1A-Cys or exenatide. Moreover, bD-G1A and tD-G1A exhibited improved in vitro Caco-2 cellular permeability and showed higher in vivo bioavailability (7.58% and 8.63%) after oral administration. Regarding hypoglycemic effects on db/db mice, tD-G1A (50 μg/kg) lowered the glucose level more than bD-G1A (50 μg/kg) compared with the control (35.5% vs. 26.4%).

Conclusion: GLP-1A was conjugated with oligomeric DOCAs, and the resulting chimeric compound showed the potential not only for glucagon-like peptide-1 receptor agonist activity but also for oral delivery. These findings suggest that oligomeric DOCAs can be used as effective carriers for oral delivery of GLP-1A, offering a promising solution for enhancing its oral bioavailability and improving diabetes treatment.

Background: Human omentum-derived mesenchymal stem cells (hO-MSCs) possess great potential to differentiate into multiple lineages and have self-renewal capacity, allowing them to be utilized as patient-specific cell-based therapeutics. Although the use of various stem cell-derived β-cells has been proposed as a novel approach for treating diabetes mellitus, developing an efficient method to establish highly functional β-cells remains challenging.

Methods: We aimed to develop a novel cell culture platform that utilizes a fibroblast growth factor 2 (FGF2)-immobilized matrix to regulate the adhesion and differentiation of hO-MSCs into insulin-producing β-cells via cell-matrix/cell-cell interactions. In our study, we evaluated the in vitro differentiation potential of hO-MSCs cultured on an FGF2-immobilized matrix and a round-bottom plate (RBP). Further, the in vivo therapeutic efficacy of the β-cells transplanted into kidney capsules was evaluated using animal models with streptozotocin (STZ)-induced diabetes.

Results: Our findings demonstrated that cells cultured on an FGF2-immobilized matrix could self-organize into insulin-producing β-cell progenitors, as evident from the upregulation of pancreatic β-cell-specific markers (PDX-1, Insulin, and Glut-2). Moreover, we observed significant upregulation of heparan sulfate proteoglycan, gap junction proteins (Cx36 and Cx43), and cell adhesion molecules (E-cadherin and Ncam1) in cells cultured on the FGF2-immobilized matrix. In addition, in vivo transplantation of differentiated β-cells into animal models of STZ-induced diabetes revealed their survival and engraftment as well as glucose-sensitive production of insulin within the host microenvironment, at over 4 weeks after transplantation.

Conclusions: Our findings suggest that the FGF2-immobilized matrix can support initial cell adhesion, maturation, and glucose-stimulated insulin secretion within the host microenvironment. Such a cell culture platform can offer novel strategies to obtain functional pancreatic β-cells from patient-specific cell sources, ultimately enabling better treatment for diabetes mellitus.

Background: Exosomes are extracellular vesicles secreted by eukaryotic cells and have been extensively studied for their surface markers and internal cargo with unique functions. A deeper understanding of exosomes has allowed their application in various research areas, particularly in diagnostics and therapy.

Main body: Exosomes have great potential as biomarkers and delivery vehicles for encapsulating therapeutic cargo. However, the limitations of bare exosomes, such as rapid phagocytic clearance and non-specific biodistribution after injection, pose significant challenges to their application as drug delivery systems. This review focuses on exosome-based drug delivery for treating rheumatoid arthritis, emphasizing pre/post-engineering approaches to overcome these challenges.

Conclusion: This review will serve as an essential resource for future studies to develop novel exosome-based therapeutic approaches for rheumatoid arthritis. Overall, the review highlights the potential of exosomes as a promising therapeutic approach for rheumatoid arthritis treatment.

Human skin is an organ located in the outermost part of the body; thus, it frequently exhibits visible signs of physiological health. Ethical concerns and genetic differences in conventional animal studies have increased the need for alternative in vitro platforms that mimic the structural and functional hallmarks of natural skin. Despite significant advances in in vitro skin modeling over the past few decades, different reproducible biofabrication strategies are required to reproduce the pathological features of diseased human skin compared to those used for healthy-skin models. To explain human skin modeling with pathological hallmarks, we first summarize the structural and functional characteristics of healthy human skin. We then provide an extensive overview of how to recreate diseased human skin models in vitro, including models for wounded, diabetic, skin-cancer, atopic, and other pathological skin types. We conclude with an outlook on diseased-skin modeling and its technical perspective for the further development of skin engineering.

Background: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) gain attention as a potent cell source in regenerative medicine and drug discovery. With the necessity of the demands for experimental models to create a more physiologically relevant model of the heart in vitro we herein investigate a 3D culturing platform and a method for assessing rhythm in hiPSC-CMs.

Methods: The 3D cell culture PAMCELL™ plate is designed to enable cells to attach exclusively to adhesive patterned areas. These cell adhesive zones, named as micro-patterned pads, feature micron silica beads that are surface-modified with the well-known arginyl-glycyl-aspartic acid (RGD) peptide. RGD binding to the surface of hiPSC-CMs facilitates cell-cell attachment and the formation of uniform-size spheroids, which is controlled by the diameter of the micro-patterned pads. The assessment and evaluation of 3D hiPSC-CMs beating pattern are carried out using reflective properties of retroreflective Janus micro-particle (RJP). These RJPs are modified with an antibody targeting the gap junction protein found on the surface of hiPSC-CM spheroids. The signal assessment system comprises a camera attached to an optical microscope and a white light source.

Results: The 3D PAMCELL™ R100 culture plate efficiently generate approximately 350 uniform-sized hiPSC-CM spheroids in each well of a 96-well plate and supported a 20-day culture. Analysis of genes and protein expression levels reveal that iPSC-CM spheroids grown on PAMCELL™ R100 retain cardiac stem cell characteristics and functions, outperforming traditional 2D culture platform. Additionally, the RJPs enable monitoring and evaluation of in vitro beating properties of cardiomyocytes without using complex monitoring setup. The system demonstrates its capability to identify alteration in the rhythmic activity of cardiac cells when exposed to ion channel blockers, nifedipine and E4031.

Conclusions: The integration of the 3D culture method and RJPs in this study establishes a platform for evaluating the rhythmic properties of 3D hiPSC-CMs. This approach holds significant potential for identifying arrhythmias or other cardiac abnormalities, ultimately contributing to the development of more effective therapies for heart diseases.