Regenerative Biomaterials最新文献

This study investigates a novel pH-responsive hydrogel composed of polyvinyl alcohol (PVA) and boric acid (BA) designed for the controlled release of salvianolic acid B (SAB), addressing the critical challenge of scar formation and skin regeneration. The dual-crosslinked network architecture of the hydrogel exhibits remarkable pH sensitivity, enabling it to achieve a peak SAB release within 48 hours in the acidic microenvironment characteristic of early-stage wound healing. In vitro assessments demonstrated that the PVA-BA-SAB hydrogel significantly inhibits fibroblast activation and mitigates abnormal collagen deposition, effectively preventing excessive scar formation. Transcriptome sequencing reveals the potential role of PVA-BA-SAB hydrogel in balancing TGF-β and Wnt signaling pathways. Furthermore, in vivo studies revealed enhanced tissue regeneration, characterized by improved collagen organization and increased vascularization, as well as the promotion of mature hair follicle development. The hydrogel's biocompatibility, mechanical robustness and adhesive properties were also thoroughly evaluated, confirming its suitability for clinical applications. These findings suggest that the PVA-BA-SAB hydrogel fully exerts the excellent characteristics of biomaterials and maximizes the pharmacological effect of SAB. Our innovative drug delivery system not only facilitates enhanced wound healing but also offers a strategic approach to minimize scarring. This research provides valuable insights into innovative therapeutic strategies for effective wound management and tissue repair.

During the implantation process of cardiovascular implants, vascular damage caused by inflammation occurs, and the inflammatory process is accompanied by oxidative stress. Currently, carbon monoxide (CO) has been demonstrated to exhibit various biological effects including vasodilatation, antithrombotic, anti-inflammatory, apoptosis-inducing and antiproliferative properties. In this study, hemoglobin/epigallocatechin-3-gallate (EGCG) core-shell nanoparticle-containing coating on stainless steel was prepared for CO loading and inflammation modulation. Inspired by strong coordination ability with CO, hemoglobin nanoparticle was first prepared and encapsulated into EGCG metal-phenolic networks. A polydopamine (PDA) linking layer was then coated on 316 stainless steel, and the hemoglobin/EGCG nanoparticles were loaded with the subsequent PDA deposition. It showed that the maximum release amount of CO by the coating was 17.0 nmol/cm² in 48 h. In vitro evaluations conducted in a simulated inflammatory environment revealed that the coating, which released CO from hemoglobin/EGCG nanoparticles, effectively mitigated the lipopolysaccharide-induced inflammatory response in macrophages. Specifically, it decreased the expression of tumor necrosis factor-α, increased the expression of interleukin-10, suppressed the polarization of macrophages toward the M1 phenotype and reduced intracellular reactive oxygen species (ROS). Furthermore, under simulated oxidative stress conditions, the coating decreased the apoptosis of endothelial cells induced by oxidative stress and down-regulated intracellular ROS levels. In vivo implantation results further confirmed that the coating, with its hemoglobin/EGCG nanoparticles and CO release capabilities, reduced macrophage-mediated inflammatory responses and modulated the polarization phenotype of macrophages.

The detection of residual nuclei in decellularized extracellular matrix (dECM) biomaterials is critical for ensuring their quality and biocompatibility. However, current evaluation methods have limitations in addressing impurity interference and providing intelligent analysis. In this study, we utilized four staining techniques-hematoxylin-eosin staining, acetocarmine staining, the Feulgen reaction and 4',6-diamidino-2-phenylindole staining-to detect residual nuclei in dECM biomaterials. Each staining method was quantitatively evaluated across multiple parameters, including area, perimeter and grayscale values, to establish a semi-quantitative scoring system for residual nuclei. These quantitative data were further employed as learning indicators in machine learning models designed to automatically identify residual nuclei. The experimental results demonstrated that no single staining method alone could accurately differentiate between nuclei and impurities. In this study, a semi-quantitative scoring table was developed. With this table, the accuracy of determining whether a single suspicious point is a cell nucleus has reached over 98%. By combining four staining methods, false positives caused by impurity contamination were eliminated. The automatic recognition model trained based on nuclear parameter features reached the optimal index of the model after several iterations of training in 172 epochs. The trained artificial intelligence model achieved a recognition accuracy of over 90% for detecting residual nuclei. The use of multidimensional parameters, integrated with machine learning, significantly improved the accuracy of identifying nuclear residues in dECM slices. This approach provides a more reliable and objective method for evaluating dECM biomaterials, while also increasing detection efficiency.

Osteoarthritis (OA) is a frequent chronic illness in orthopedics that poses a major hazard to patient health. In situ cell therapy is emerging as a therapeutic option, but its efficacy is influenced by both the inflammatory milieu and the amount of stem cells, limiting its use. In this study, we designed a novel injectable porous microsphere (PM) based on microfluidic technology that can support in situ mesenchymal stem cells (MSCs) therapy by combining polylactic-glycolic acid copolymer, kartogenin, polydopamine, stromal cell-derived factor-1, and copper-doped bioactive glass (CuBG). The ex vivo tests demonstrated that PMs@CuBG microspheres were biocompatible and facilitated the transformation of synovial macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes by releasing CuBG to reduce joint inflammation. At the same time, the microspheres are able to recruit MSCs into the joint cavity and encourage their differentiation into chondrocytes, thereby treating articular cartilage injury. The in vivo rat experimental results show that intra-articular injection of PMs@CuBG in rats with OA improves OARSI scores, aggrecan content and the ratio of col-2α-positive cells, indicating a reparative effect on damaged cartilage within the joint. As a result, PMs@CuBG microspheres are predicted to provide a novel and successful approach to in situ cell therapy for OA.

Periodontitis, a widespread inflammatory disease, is the major cause of tooth loss in adults. While mechanical periodontal therapy benefits the periodontal disease treatment, adjunctive periodontal therapy is also necessary. Topically applied anti-inflammatory agents have gained considerable attention in periodontitis therapy. Although azithromycin (AZM) possesses excellent anti-inflammatory properties, its bioavailability is limited owing to poor water solubility and the absence of sustained release mechanisms. Herein, we synthesized biodegradable microspheres (AZM@PLGA-SF) for sustained AZM release to locally ameliorate periodontal inflammation and facilitate periodontal tissue regeneration. AZM was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres (AZM@PLGA) using single emulsion-solvent evaporation, followed by surface coating with silk fibroin (SF) via electrostatic adsorption, reducing the initial burst release of AZM. In vivo, local treatment with AZM@PLGA-SF microspheres significantly reduced periodontal inflammation and restored periodontal tissue to healthy levels. Mechanically, the formulated microspheres regulated the periodontal inflammatory microenvironment by reducing the levels of pro-inflammatory cytokines (tumor necrosis factor -α, interleukin [IL]-6, interferon-γ, IL-2, and IL-17A) in gingival crevicular fluid and promoted the expression of anti-inflammatory cytokines (IL-4 and IL-10). AZM@PLGA-SF microspheres demonstrated excellent biological safety. Therefore, we introduce an anti-inflammatory therapy for periodontitis with substantial potential for mitigating periodontal inflammation and encouraging the repair and regeneration of periodontal tissues.

Myocardial infarction (MI) poses a substantial threat to human health, prompting extensive research into effective treatment modalities. Preclinical studies have demonstrated the therapeutic potential of mesenchymal stem cell-derived exosomes for cardiac repair. Despite their promise, the inherent limitations of natural exosomes, mainly their restricted targeting capabilities, present formidable barriers to clinical transformation. To address this, it is proposed to enhance their targeting specificity and retention in infarcted myocardium by fusing exosomes with neutrophil-derived apoptotic body membranes (NAM). These NAM inherit the surface signals from neutrophils, which allow them to home in on the damaged tissues and participate in regulating inflammatory responses. In this current work, we utilized a membrane fusion technique to create NAM-fused exosomes (NAM-Exo) for MI treatment. Compared to their native counterparts, NAM-Exo demonstrated enhanced adhesion to inflammatory endothelial cells, replicating the neutrophil recruitment mechanism at sites of myocardial injury in MI. Furthermore, our findings revealed that NAM-Exo not only significantly modulated inflammation responses but also promoted angiogenesis in a mouse model of MI, ultimately leading to improved cardiac function and ventricular remodeling post-treatment. These results underscore the potential of membrane fusion as an effective strategy to enhance the therapeutic efficacy of exosome-based cardiac repair and regeneration therapies, thereby paving the way for their translation into clinical practice.

Injury caused by excess reactive oxygen species (ROS) may lead to susceptibility to bacterial infection and sustained inflammatory response, which are the major factors impeding diabetic wound healing. By utilizing optimal anti-inflammatory, antioxidant and antibacterial biomaterials for multifunctional wound dressings is critical in clinical applications. In this study, a novel electrospun PLGA/MoS₂@Pd nanofiber membrane was synthesized by encapsulating antioxidant and near-infrared (NIR) responsive MOS₂@Pd nanozymes in PLGA nanofibers to form a multifunctional dressing for diabetic wound repair. With excellent biocompatibility and hemostatic ability, this novel PLGA/MoS₂@Pd nanofiber membrane can effectively reduce oxidative stress damage and intracellular inflammatory factors expression in fibroblasts by scavenging ROS. Additionally, the PLGA/MoS₂@Pd nanofiber membrane exhibited favorable NIR-mediated photothermal antibacterial activity in vitro, with inhibition rates of 97.14% and 97.07% against Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli), respectively. In a diabetic rat wound infection model, NIR-assisted PLGA/MoS₂@Pd nanofiber membrane effectively inhibited bacterial growth in the wound, reduced infection-induced inflammatory response, and promoted tissue epithelialization and collagen deposition, resulting in a wound healing rate of up to 98.5% on Day 14. This study highlighted the construction of a multifunctional nanofiber membrane platform and demonstrated its promising potential as a clinical dressing for diabetic wounds.

Modification of polylactic acid (PLA) is a promising strategy for the next generation of bioresorbable vascular stent biomaterials. With this focus, FeMOFs nanoparticles was incorporated in PLA, and then post loading of carbon monoxide (CO) was performed by pressurization. It showed FeMOFs incorporation increased hydrophilicity of the surface and CO loading, and CO release was sustained at least for 3 days. It is well acknowledged NETosis and macrophage mediated inflammation are the principal effectors of atherosclerosis and cardiovascular disease, and it further increases the risk of late stent thrombosis and restenosis. In this study, the effects of CO release of PLA/FeMOFs/CO on NETosis and macrophage behavior were thoroughly explored. In vitro evaluation results showed that PLA/FeMOFs/CO significantly inhibited neutrophil extracellular traps (NETs) release and neutrophil elastase expression by reducing intracellular reactive oxygen species in a simulated inflammatory environment. It reduced Lipopolysaccharide-induced macrophage inflammation with decreased tumor necrosis factor-α expression and increased IL-10 expression. Meanwhile it enhanced endothelial cell activity and growth in inflammatory environment, and inhibited platelet adhesion and activation. In vivo implantation results confirmed that PLA/FeMOFs/CO reduced the macrophages and neutrophils mediated inflammatory response, thus reduced the neointimal hyperplasia. Overall, PLA/FeMOFs/CO effectively prevented the inflammation and restenosis associated with PLA implantation. Our study provides a new strategy to improve the immunocompatibility of PLA implant materials.

Electrospinning is a remarkably straightforward and adaptable technique that can be employed to process an array of synthetic and natural materials, resulting in the production of nanoscale fibers. It has emerged as a novel technique for biomedical applications and has gained increasing popularity in the research community in recent times. In the context of tissue repair and tissue engineering, there is a growing tendency toward the integration of biomimetic scaffolds and bioactive macromolecules, particularly proteins and growth factors. The design of 'smart' systems provides not merely physical support, but also microenvironmental cues that can guide regenerative tissue repair. Electrospun nanofibrous matrices are regarded as a highly promising tool in this area, as they can serve as both an extracellular matrix (ECM)-mimicking scaffold and a vehicle for the delivery of bioactive proteins. Their highly porous architecture and high surface-to-volume ratio facilitate the loading of drugs and mass transfer. By employing a judicious selection of materials and processing techniques, there is considerable flexibility in efficiently customizing nanofiber architecture and incorporating bioactive proteins. This article presents a review of the strategies employed for the structural modification and protein delivery of electrospun nanofibrous materials, with a focus on the objective of achieving a tailored tissue response. The article goes on to discuss the challenges currently facing the field and to suggest future research directions.

Decellularization is the process of obtaining acellular tissues with low immunogenic cellular components from animals or plants while maximizing the retention of the native extracellular matrix structure, mechanical integrity and bioactivity. The decellularized tissue obtained through the tissue decellularization technique retains the structure and bioactive components of its native tissue; it not only exhibits comparatively strong mechanical properties, low immunogenicity and good biocompatibility but also stimulates in situ neovascularization at the implantation site and regulates the polarization process of recruited macrophages, thereby promoting the regeneration of damaged tissue. Consequently, many commercial products have been developed as promising therapeutic strategies for the treatment of different tissue defects and lesions, such as wounds, dura, bone and cartilage defects, nerve injuries, myocardial infarction, urethral strictures, corneal blindness and other orthopedic applications. Recently, there has been a growing interest in the decellularization of fish tissues because of the abundance of sources, less religious constraints and risks of zoonosis transmission between mammals. In this review, we provide a complete overview of the state-of-the-art decellularization of fish tissues, including the organs and methods used to prepare acellular tissues. We enumerated common decellularized fish tissues from various fish organs, such as skin, scale, bladder, cartilage, heart and brain, and elaborated their different processing methods and tissue engineering applications. Furthermore, we presented the perspectives of (i) the future development direction of fish tissue decellularization technology, (ii) expanding the sources of decellularized tissue and (iii) innovating decellularized tissue bio-inks for 3D bioprinting to unleash the great potential of decellularized tissue in tissue engineering and regenerative medicine applications.