Biomaterials research最新文献

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.

Large bone defects are still a persistent challenge in orthopedics. The availability limitations and associated complications of autologous and allogeneic bone have prompted an increasing reliance on tissue engineering and regenerative medicine. In this study, we developed an injectable scaffold combining an acellular extracellular periosteal matrix hydrogel with poly(d,l-lactate-co-glycol-acetate) microspheres loaded with the E7 peptide and miR217 (miR217/E7@MP-GEL). Characterization of the composites included morphological analysis by scanning electron microscopy, degradation and swelling tests, in vitro and in vivo biological evaluation, and the biological activity evaluation of mesenchymal stem cells (MSCs) through their effects on cell recruitment, proliferation, and osteogenic differentiation. The designed hydrogels demonstrated good physical and chemical properties that are cytocompatible and suitable for cell recruitment. In vitro studies confirmed the high biological activity of the release agent, which markedly enhanced the proliferation and osteogenic differentiation of MSCs. In vivo application to a rat model of a femur defect exhibited a significant increase in bone volume and density over 7 weeks, resulting in enhanced bone regeneration. Acellular periosteum-based hydrogels combined with the E7 peptide and miR217-loaded poly(d,l-lactate-co-glycol-acetate) microspheres can promote effective bone regeneration through the recruitment, proliferation, and osteogenic differentiation of MSCs, which provides a promising approach for the treatment of large bone defects.

Angiogenesis is mediated by vascular endothelial growth factor (VEGF), a protein that plays a key role in wound healing, inflammatory diseases, cardiovascular processes, ocular diseases, and tumor growth. Indeed, modulation of angiogenesis represents a potential approach to treating cancer and, as such, therapeutic approaches targeting VEGF and its receptors have been widely investigated as part of the broader search for curative interventions. Equally, RNA interference is a powerful tool for treating diseases, but its application as a disease treatment has been limited in part because of a lack of efficient small interfering RNA (siRNA) delivery systems. The purpose of this study was to characterize an amphipathic cell-penetrating peptide, Ara27, and its potential as an effective delivery vehicle as a conjugate with VEGF siRNA (siVEGF). In our study, we demonstrate that exposure of human umbilical vein endothelial cells (HUVECs) with Ara27-siVEGF complexes did not lead to cytotoxicity and can lead to down-regulation of cellular levels of both VEGF mRNA and protein. Moreover, treatment with the Ara27-siVEGF complex attenuates the phosphorylation of VEGFR2, Akt, and ERK in HUVECs and inhibits their capacity for wound healing and tube formation, both of which characteristics reflective of angiogenesis. In addition, we performed an ex vivo study to find that treatment with the Ara27-siVEGF complex inhibits aorta ring sprouting. Furthermore, the complex did not induce immunotoxicity in THP-1 and RAW264.7 cells. Taken together, our studies demonstrate that an Ara27-siVEGF conjugate is efficient for knockdown of VEGF in HUVECs to inhibit angiogenesis, without marked cytotoxic and immunotoxic effects.

Glioblastoma multiforme (GBM) is among the most challenging malignant brain tumors, making the development of new treatment strategies highly necessary. Glioma stem cells (GSCs) markedly contribute to drug resistance, radiation resistance, and tumor recurrence in GBM. The therapeutic potential of nanomaterials targeting GSCs in GBM urgently needs to be explored. A magnetic-responsive biomimetic nanosystem (FDPM), coated with glioma stem cell membranes (CMs), was designed for the targeted eradication of GSCs as well as their associated tumor cells. Identified nanobodies were extensively characterized with various assays. The application tests on nanomaterials were conducted in vitro and in vivo. The tumor-suppressive effects of the nanosystem were evaluated in vitro and in vivo. FDPM can be artificially directed under magnetic guidance while inheriting various biological functions from CM. Upon intravenous injection, FDPM was drawn to the tumor site by magnetic attraction, where it could cross the blood-brain barrier aided by CM. Its homologous targeting ability originates from active proteins on CM, enabling it to specifically target GSCs and related tumor cells. The encapsulated doxorubicin (DOX) within the nanoparticle then destroyed these tumor cells. FDPM demonstrated excellent biocompatibility and tumor-targeting efficiency, effectively targeting malignant gliomas initiated by GSCs. FDPM significantly reduced tumor cells, inhibited tumor growth, and notably extended the survival of glioma-bearing nude mice. The findings position FDPM as a promising nanoplatform to target GSCs and related tumor cells for improving the therapeutic effect of glioma.

Hair follicle cells reside within a complex extracellular matrix (ECM) environment in vivo, where physical and chemical cues regulate their behavior. The ECM is crucial for hair follicle development and regeneration, particularly through epithelial-mesenchymal interactions. Current in vitro models often fail to replicate this complexity, leading to inconsistencies in evaluating hair loss treatments. Advanced 3-dimensional (3D) culture systems that better mimic in vivo ECM dynamics are needed for more effective therapeutic assessments. Here, we introduce a 3D co-culture system designed to replicate in vivo ECM dynamics. The system incorporates primary dermal papilla cells from human patients, co-cultured with neonatal keratinocytes. This platform facilitates uniform spheroid formation through cell sliding and aggregation, enabling the evaluation of approximately 60 spheroids per well. The model is optimized for high-throughput screening, allowing precise assessments of hair-loss-inducing compounds under consistent conditions. We successfully generated dermal papilla cell and keratinocyte spheroids that closely resemble the native ECM structure, providing an optimal microenvironment for studying hair follicle biology. The 3D co-culture model supported efficient spheroid formation with consistent cellular organization and polarization, along with enhanced ECM-related gene expression crucial for hair follicle regeneration. Uniform spheroid formation and reproducibility were demonstrated across experiments. Overall, the novel 3D co-culture system provides a robust platform for replicating in vivo-like ECM conditions, enabling effective assessment of potential hair loss treatments through epithelial-mesenchymal interactions. Its high-throughput capacity, combined with reproducibility and ease of use, makes it a valuable tool for screening therapeutic candidates and advancing hair loss treatment development.

[This corrects the article DOI: 10.34133/bmr.0012.].

Magnesium (Mg)-based implants have evolved as a promising innovation in orthopedic trauma surgery, with the potential to revolutionize the treatment of bone diseases, including osteoporotic fractures and bone defects. Available clinical studies mostly show excellent patient outcomes of resorbable Mg-based implants, without the need for subsequent implant removal. However, the occurrence of radiolucent zones around Mg-based implants seems to be a noticeable drawback for a more widespread clinical use. Mechanistically, both in vivo and in vitro studies demonstrated beneficial effects on the formation of new bone, a unique characteristic of Mg-based implants. In this regard, Mg has been shown to exert pleiotropic functions on osteogenic differentiation and migration of osteoblasts and their precursors. Additionally, collective evidence suggests that Mg-based implants promote angiogenesis in newly formed bone and exert immunomodulatory effects in the bone microenvironment. Likewise, Mg-based implants and their degradation products were shown to inhibit bone resorption by impairing osteoclastogenesis. The purpose of this review is to provide a state-of-the-art summary of the clinical and basic science evidence regarding the performance of currently used Mg-based implants. In addition to the status of in vivo and in vitro research and clinical applications, future challenges and perspectives of Mg-based orthopedic implants are discussed.

Intervertebral disc degeneration (IDD)-induced lower back pain (LBP) brings heavy burden worldwide. In the degenerated intervertebral disc, there is an increase in the accumulation of reactive oxygen species (ROS) and the infiltration of M1 macrophages, which leads to abnormal local inflammatory microenvironment and exacerbates IDD. In this study, we developed a novel injectable polyethylene glycol (PEG)-capped cerium ion-manganese ion (Ce-Mn) bimetallic nanozyme (CeMn-PEG) with strong ROS scavenging and M2-type macrophage polarizing abilities to efficiently alleviate IDD. In vitro experiments demonstrated that CeMn-PEG effectively scavenged excess ROS in both nucleus pulposus (NP) and RAW264.7 cells. In addition, we found that CeMn-PEG markedly protected NP cells from H₂O₂-induced overproduction of inflammatory cytokines, excessive cell apoptosis and autophagy, and imbalance between extracellular matrix (ECM) degradation. Moreover, CeMn-PEG induced macrophages to transition from the M1 phenotype to the M2 phenotype and the increased M2-type macrophages could alleviate H₂O₂-induced ECM degradation and cell apoptosis in NP cells. In a puncture-induced mouse IDD model, CeMn-PEG treatment could effectively ameliorate the progression of disc degeneration and mitigate puncture-induced mechanical hyperalgesia. Thus, our study demonstrated the effectiveness of CeMn-PEG as a novel treatment strategy for the treatment of IDD and a range of other inflammatory diseases.

Despite that the clinical application of titanium-based implants has achieved great success, patients' own diseases and/or unhealthy lifestyle habits often lead to implant failure. Many studies have been carried out to modify titanium implants to promote osseointegration and implant success. Recent studies showed that exosomes, proactively secreted extracellular vesicles by mammalian cells, could selectively target and modulate the functions of recipient cells such as macrophages, nerve cells, endothelial cells, and bone marrow mesenchymal stem cells that are closely involved in implant osseointegration. Accordingly, using exosomes to functionalize titanium implants has been deemed as a novel and effective way to improve their osseointegration ability. Herein, recent advances pertaining to surface functionalization of titanium implants with exosomes are analyzed and discussed, with focus on the role of exosomes in regulating the functions of osseointegration-related cells, and their immobilization strategies as well as resultant impact on osseointegration ability.