Regenerative Biomaterials最新文献

Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.

Platelet-rich plasma (PRP) is one of the most popular biomaterials in regenerative medicine. However, the difficulties encountered in its preservation, and the requirement for on-demand preparation severely limit its application. In addition, its rapid degradation in the wound microenvironment makes the sustained release of growth factors impossible and finally reduces the therapeutic effect on chronic wounds. Here, a multifunctional dressing based on triple-layered core-shell fibers for loading and enduring preservation of PRP was developed using a one-step coaxial bioprinting technique combined with freeze-drying. The platelets were effectively dispersed and immobilized in the core layer of the fiber, leading to a sustained release of growth factors from the PRP. The rate of release can be controlled by adjusting the triple-layered core-shell structure. Simultaneously, the triple-layered core-shell structure can reduce the deactivation of PRP during freezing and storage. The experimental findings suggest that PRP exhibits sustained activity, facilitating the process of wound healing even after a storage period of 180 days. Furthermore, the protective mechanism of PRP by the triple-layered core-shell fiber was investigated, and the conditions for freeze-drying and storage were optimized, further enhancing the long-term storability of PRP. As a result, the multifunctional core-shell fiber dressings developed in this study offer a novel approach for sustained growth factor release and the enduring preservation of active PRP.

Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and in vivo adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the in vivo adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the in vivo adaptation process of decellularized vascular grafts in small animal model.

Peri-implant lesion is a grave condition afflicting numerous indi-viduals with dental implants. It results from persistent periodontal bacteria accumulation causing inflammation around the implant site, which can primarily lead to implant loosening and ultimately the implant loss. Early-stage peri-implant lesions exhibit symptoms akin to gum disease, including swelling, redness and bleeding of the gums surrounding the implant. These signs indicate infection and inflammation of the peri-implant tissues, which may result in bone loss and implant failure. To address this problem, a thermionic strategy was applied by designing a cuprorivaite-hardystonite bioceramic/alginate composite hydrogel with photothermal and Cu/Zn/Si multiple ions releasing property. This innovative approach creates a thermionic effect by the release of bioactive ions (Cu²⁺ and Zn²⁺ and ${\text{SiO}}_3^{2-}$) from the composite hydrogel and the mild heat environment though the photothermal effect of the composite hydrogel induced by near-infrared light irradiation. The most distinctive advantage of this thermionic effect is to substantially eliminate periodontal pathogenic bacteria and inhibit inflammation, while simultaneously enhance peri-implant osseointegration. This unique attribute renders the use of this composite hydrogel highly effective in significantly improving the survival rate of implants after intervention in peri-implant lesions, which is a clinical challenge in periodontics. This study reveals application potential of a new biomaterial-based approach for peri-implant lesion, as it not only eliminates the infection and inflammation, but also enhances the osteointegration of the dental implant, which provides theoretical insights and practical guidance to prevent and manage early-stage peri-implant lesion using bioactive functional materials.

Endothelial cell proliferation plays an important role in angiogenesis and treatment of related diseases. The aim of this study was to evaluate the effect of polyethylenimine (PEI)-modified graphene quantum dots (GQDs) gene vectors on endothelial cell proliferation. The GQDs-cationic polymer gene vectors were synthesized by amidation reaction, and used to deliver pZNF580 gene to Human umbilical vein endothelial cells (HUVECs) for promoting their proliferation. The chemical modification of GQDs can adjust gene vectors' surface properties and charge distribution, thereby enhancing their interaction with gene molecules, which could effectively compress the pZNF580 gene. The CCK-8 assay showed that the cell viability was higher than 80% at higher vector concentration (40 μg/mL), demonstrating that the GQDs-cationic polymer gene vectors and their gene complex nanoparticles (NPs) having low cytotoxicity. The results of the live/dead cell double staining assay were consistent with those of the CCK-8 assay, in which the cell viability of the A-GQDs/pZNF580 (94.38 ± 6.39%), C-GQDs-PEI- polylactic acid-co-polyacetic acid (PLGA)/pZNF580 (98.65 ± 6.60%) and N-GQDs-PEI-PLGA/pZNF580 (90.08 ± 1.60%) groups was significantly higher than that of the Lipofectamine 2000/pZNF580 (71.98 ± 3.53%) positive treatment group. The results of transfection and western blot experiments showed that the vector significantly enhanced the delivery of plasmid to HUVECs and increased the expression of pZNF580 in HUVECs. In addition, the gene NPs better promote endothelial cell migration and proliferation. The cell migration rate and proliferation ability of C-GQDs-PEI-PLGA/pZNF580 and N-GQDs-PEI-PLGA/pZNF580 treatment groups were higher than those of Lipofectamine 2000/pDNA treatment group. Modified GQDs possess the potential to serve as efficient gene carriers. They tightly bind gene molecules through charge and other non-covalent interactions, significantly improving the efficiency of gene delivery and ensuring the smooth release of genes within the cell. This innovative strategy provides a powerful means to promote endothelial cell proliferation.

Cartilage defects may lead to severe degenerative joint diseases. Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair. However, the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully clarified. Herein, we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced chondrogenesis. Results showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-β signaling pathway, and integrin-β1 (ITGB1), a receptor of collagen, was highly expressed in bone marrow mesenchymal stem cells (BMSCs). Further analysis showed genes such as COL2A1 and Tenascin C (TNC) that interacted with ITGB1 were significantly enriched in extracellular matrix (ECM) structural constituents in the chondrogenic induction group. Knockdown of ITGB1 led to the downregulation of cartilage-specific genes (SOX9, ACAN, COL2A1), SMAD2 and TNC, as well as the downregulation of phosphorylation of SMAD2/3. Knockdown of TNC also resulted in the decrease of cartilage markers, ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite trend. Finally, in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage regeneration. In summary, we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen hydrogel. It can activate TGF-SMAD2/3 signaling, followed by impacting TNC expression, which in turn promotes the interaction of ITGB1 and TGF-SMAD2/3 signaling to enhance chondrogenesis. These may provide concernful support for cartilage tissue engineering and biomaterials development.