Biomaterials research最新文献

The field of infected wound management continues to face challenges, and traditional methods used to cope with wounds include debridement, gauze coverage, medication, and others. Currently, synthetic and natural biomaterials are readily available today, enabling the creation of new wound dressings that substantially enhance wound healing. Considerable attention is being paid to hydrogels based on natural materials, which have good biocompatibility and degradability properties, while exhibiting higher similarity to natural extracellular matrix as compared to synthetic materials. In this study, we extracted the active ingredients of oxidized konjac glucomannan (OKGM) and fresh egg white (EW) from 2 foods, konjac, and egg, respectively, and formed a self-repairing hydrogel based on the cross-linking of a Schiff base. Subsequently, a natural active peptide, glycyl-l-histidyl-l-lysine-Cu (GHK-Cu), was loaded, and an all-natural composite hydrogel dressing, EW/OKGM@GHK-Cu (GEK), was developed. The GEK hydrogel, exhibiting both antibacterial and anti-inflammatory properties, plays a hemostatic role by adhering to tissues and promoting neovascularization and serves as an optimal dressing for skin regeneration. Taken together, GEK hydrogel dressings derived from natural food sources therefore constitute an efficient and cost-effective strategy for managing infected wound healing and have significant potential for clinical application and transformation.

This study introduces a novel gene delivery system, polyethyleneimine modified with isoprenaline (PEI-isoprenaline), to enhance targeted gene delivery in the context of asthma therapy and airway remodeling. In vitro investigations used Beas2B cells to assess the biocompatibility of isoprenaline, PEI-isoprenaline, and small interfering RNA (siRNA)/PEI-isoprenaline complexes, with cytotoxicity evaluations confirming their safety. The transfection efficiency of the siRNA/PEI-isoprenaline complex was scrutinized in THP-1 cells and displayed superior performance in delivering siRNA to cells expressing the β2 adrenergic receptor (ADRB2). In vivo studies used a murine chronic asthma model to evaluate gene delivery to ADRB2-expressing cells in bronchoalveolar fluid and lung tissues. Therapeutic effects were comprehensively assessed through cell analyses, revealing substantial reductions in airway inflammatory cells and fibrosis, particularly in the Arg1 siRNA/PEI-isoprenaline group. The siRNA/PEI-isoprenaline complex exhibited an impressive 80% delivery rate, greatly surpassing the performance of polyethyleneimine 2K (20%). Notably, the complex achieved a substantial 63% reduction in arginase-1 gene expression, validating its therapeutic potential. Noteworthy inhibitory effects on airway hyperresponsiveness were observed, underscoring the complex's potential as a targeted gene delivery system for asthma treatment. Our findings underscore the promise and effectiveness of the PEI-isoprenaline complex as a gene delivery system, with its demonstrated biocompatibility, transfection efficiency, and therapeutic outcomes, including arginase-1 gene knockdown and mitigation of airway inflammation and fibrosis, indicating it as a promising candidate for advancing asthma therapy and contributing to the understanding and control of airway remodeling in respiratory diseases.

Insufficient radio-frequency ablation (IRFA) of hepatocellular carcinoma accelerates the recurrence of residual tumor, leading to a poor prognosis. Neutrophils (NEs), as the initial leukocytes to infiltrate the IRFA-associated inflammatory area, were utilized as drug carriers due to their inherent chemotactic properties for targeted delivery of chemotherapy drugs to the inflammatory site where residual tumor persists post-IRFA. Previous research has highlighted that the immunosuppressive cytokines in the tumor microenvironment could promote the transition of NEs into a protumorigenic phenotype. However, it is unclear whether NEs used as drug delivery carriers undergo similar changes and how this transition affects treatment effectiveness. Here, we present novel findings demonstrating the phenotypic transition of NEs in the residual tumor microenvironment from an antitumorigenic to a protumorigenic state following IRFA treatment. More critically, we found for the first time that NE carriers undergo a comparable phenotypic transition in the residual tumor, thereby attenuating the therapeutic outcome. Ingeniously, coloading NE carriers with perfluorohexane not only enabled ultrasound imaging but also facilitated spatiotemporally controllable drug release through ultrasound irradiation, thus preventing the protumorigenic transition of NE carriers and maintaining an inflammatory microenvironment at the residual tumor zone. This significantly improved the sequential targeting effect of NE carriers and ultimately enhanced the treatment of residual tumor post-IRFA. Our study provided novel insights into the modulatory role of the immune microenvironment on the phenotypic transition of live NE carriers in the drug delivery system and presented a strategy to prevent adverse effects and enhance residual tumor treatment.

Low fracture toughness, low-temperature degradation (LTD) susceptibility, and inadequate soft tissue integration greatly limit the application of zirconia ceramic abutment. Integrating the "surface" of hard all-ceramic materials into the gingival soft tissue and simultaneously promoting the "inner" LTD resistance and fracture toughness is challenging. Composite ceramics are effective in improving the comprehensive properties of materials. In this study, we aim to develop a zirconia composite abutment with high "inner" structure stability and "surface" bioactivities simultaneously and to explore the mechanism of performance improvement. Therefore, elongated SrAl₁₂O₁₉ and equiaxed Al₂O₃ were introduced into the zirconia matrix by using the Pechini method. Reinforcements of different shapes can promote the density, reduce the grain size, and increase the phase stability of composite ceramics, which improves the fracture toughness and LTD susceptibility. In addition, the released strontium ions (Sr²⁺), without sacrificing the mechanical properties of the material, could activate the biological capacity of the zirconia surface by activating the M2 polarization of macrophages through the Sr²⁺/calcium-sensing receptor/SH3 domain-binding protein 5 axis, thereby promoting the collagen matrix synthesis of fibroblasts and the angiogenesis of vascular endothelial cells. This successful case proposes a novel strategy for the development of advanced high-strength and bioactive all-ceramic materials by introducing reinforcements containing biofunctional elements into the ceramic matrix. The approach paves the way for the widespread application of such all-ceramic materials in soft-tissue-related areas.

As a complex and dynamically regulated process, wound healing is collaboratively carried out by multiple types of cells. However, the precise mechanisms by which these cells contribute to immune regulation are not yet fully understood. Although research on bone regeneration has been quite extensive, the application of bioactive glass (BG) in skin tissue repair remains still relatively underexplored. The review focuses on the principles and the latest progress of using BGs for skin tissue repair, highlighting BGs' special performance requirements, including biological activity, biocompatibility, biodegradability, and antibacterial properties, emphasizing their potential for skin tissue repair. In addition, BGs play a substantial role in regulating various inflammatory cells (neutrophils, macrophages, mast cells, etc.) and tissue repair cells [fibroblasts, vascular endothelial cells, mesenchymal stem cells (MSCs), etc.] involved in wound healing. The review also covers recent developments in composite materials incorporating BGs, demonstrating their ability to promote angiogenesis, inhibit wound biofilms, and improve inflammatory responses in chronic wounds. Furthermore, BGs have shown effectiveness in promoting epithelial regeneration and collagen deposition in burn wounds as well as their applications in scar management and post-tumor resection wound care. Finally, we summarize our views on challenges and directions in the emerging field of BGs for skin tissue regeneration research in the future.

The use of hypoxia-activated prodrugs is a promising strategy to address the limitations of photodynamic therapy (PDT) caused by a hypoxic tumor microenvironment. However, the controlled release of these hypoxia-activated prodrugs during PDT remains a challenge. In this study, we present a metal-organic framework (MOF) with a core-shell structure that can achieve a high PDT efficacy and on-demand release of hypoxia-activated prodrugs (AQ4N) for hypoxic tumor therapy. The nanocomposites were created by assembling zeolitic imidazolate frameworks (ZIF-8) onto the surface of AQ4N-encapsulated porphyrinic MOF, followed by surface functionalization with folic acid-conjugated polyethylene glycol. AQ4N is entrapped in the mesopores of MOFs, and it shows acidic environment-triggered release due to the degradation of the ZIF-8. When exposed to laser, porphyrinic MOFs can produce reactive oxygen species for PDT. At the same time, PDT exacerbates hypoxia at the tumor site, leading to the bioreduction of AQ4N to AQ4 for enhanced anticancer activity. This work presents a practical approach to improve the tumor-targeting and therapeutic efficiency of hypoxic tumors.

Tendon/ligament-bone junctions (T/LBJs) are susceptible to damage during exercise, resulting in anterior cruciate ligament rupture or rotator cuff tear; however, their intricate hierarchical structure hinders self-regeneration. Multiphasic strategies have been explored to fuel heterogeneous tissue regeneration and integration. This review summarizes current multiphasic approaches for rejuvenating functional gradients in T/LBJ healing. Synthetic, natural, and organism-derived materials are available for in vivo validation. Both discrete and gradient layouts serve as sources of inspiration for organizing specific cues, based on the theories of biomaterial topology, biochemistry, mechanobiology, and in situ delivery therapy, which form interconnected network within the design. Novel engineering can be constructed by electrospinning, 3-dimensional printing, bioprinting, textiling, and other techniques. Despite these efforts being limited at present stage, multiphasic scaffolds show great potential for precise reproduction of native T/LBJs and offer promising solutions for clinical dilemmas.

Due to their exceptional cell compatibility, biodegradability, and capacity to trigger tissue regeneration, extracellular matrix (ECM) materials have drawn considerable attention in tissue healing and regenerative medicine. Interestingly, these materials undergo continuous degradation and release antimicrobial peptides (AMPs) while simultaneously promoting tissue regeneration, thereby exerting a potent antibacterial effect. On this basis, a variety of basic properties of ECM materials, such as porous adsorption, hydrophilic adsorption, group crosslinking, and electrostatic crosslinking, can be used to facilitate the integration of ECM materials and antibacterial agents through physical and chemical approaches in order to enhance the antibacterial efficacy. This article reviews the recent advancements in the study of ECM antibacterial materials, including the antibacterial function and antibacterial mechanism of free-standing ECM materials and ECM-based composite materials. In addition, the urgent challenges and future research prospects of ECM materials in the anti-infection industry are discussed.

Cutaneous photoaging, induced by chronic exposure to ultraviolet (UV) radiation, typically manifests as alterations in both the physical appearance and functional properties of the skin and may predispose individuals to cancer development. Recent studies have demonstrated the reparative potential of exosomes derived from mesenchymal stem cells in addressing skin damage, while specific reports highlight their efficacy in ameliorating skin photoaging. However, the precise role of exosomes derived from human hair follicle mesenchymal stem cells (HFMSC-Exos) in the context of cutaneous photoaging remains largely unexplored. We successfully isolated HFMSC-Exos using the ultracentrifugation technique. In cellular experiments, we assessed the migration of human dermal fibroblasts (HDFs) through scratch and transwell assays, evaluated the angiogenesis of human umbilical vein endothelial cells through angiogenesis assays, and examined the expression levels of collagen and matrix metalloproteinase 1 (MMP-1) using Western blotting and quantitative reverse transcription polymerase chain reaction. Furthermore, we established a nude mouse model of photoaging to observe wrinkle formation on the dorsal surface of the animals, as well as to assess dermal thickness and collagen fiber generation through histological staining. Ultimately, we performed RNA sequencing on skin tissues from mice before and after treatment to elucidate the relevant underlying mechanisms. Our findings revealed that HFMSC-Exos effectively enhanced the migration and proliferation of HDFs and upregulated the expressions of transforming growth factor-β1 (TGF-β1), p-Smad2/p-Smad3, collagen type 1, and collagen type 3 while concurrently down-regulating MMP-1 levels in HDFs. Additionally, mice in the HFMSC-Exo group showed quicker wrinkle healing and increased collagen production. HFMSC-Exos miR-125b-5p was demonstrated to reduce skin photoaging by increasing profibrotic levels via TGF-β1 expression. UV-irradiated HDFs and photoaged nude mouse skin showed low TGF-β1 expressions, whereas overexpression of TGF-β1 in HDFs increased collagen type 1, collagen type 3, and p-Smad2/p-Smad3 expressions while decreasing MMP-1 expression. HDFs overexpressing TGF-β1 produced more collagen and altered the Smad pathway. This study demonstrated, both in vitro and in vivo, that HFMSC-Exos increased collagen formation, promoted HDF cell proliferation and migration, and reversed the senescence of UV-irradiated HDFs. TGF-β1 was identified as a target of HFMSC-Exos miR-125b-5p, which controls photoaging via regulating the Smad pathway. The antiphotoaging capabilities of HFMSC-Exos may occur via the miR-125b-5p/TGF-β1/Smad axis, suggesting a promising therapeutic approach for treating skin photoaging.