3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing.
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ABSTRACT:
SUBMITTER: Wu Y
PROVIDER: S-EPMC8071097 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neovascularization is a critical determinant of wound-healing outcomes for deep burn injuries. We hypothesize that dextran-based hydrogels can serve as instructive scaffolds to promote neovascularization and skin regeneration in third-degree burn wounds. Dextran hydrogels are soft and pliable, offering opportunities to improve the management of burn wound treatment. We first developed a procedure to treat burn wounds on mice with dextran hydrogels. In this procedure, we followed clinical practice of wound excision to remove full-thickness burned skin, and then covered the wound with the dextran hydrogel and a dressing layer. Our procedure allows the hydrogel to remain intact and securely in place during the entire healing period, thus offering opportunities to simplify the management of burn wound treatment. A 3-week comparative study indicated that dextran hydrogel promoted dermal regeneration with complete skin appendages. The hydrogel scaffold facilitated early inflammatory cell infiltration that led to its rapid degradation, promoting the infiltration of angiogenic cells into the healing wounds. Endothelial cells homed into the hydrogel scaffolds to enable neovascularization by day 7, resulting in an increased blood flow significantly greater than treated and untreated controls. By day 21, burn wounds treated with hydrogel developed a mature epithelial structure with hair follicles and sebaceous glands. After 5 weeks of treatment, the hydrogel scaffolds promoted new hair growth and epidermal morphology and thickness similar to normal mouse skin. Collectively, our evidence shows that customized dextran-based hydrogel alone, with no additional growth factors, cytokines, or cells, promoted remarkable neovascularization and skin regeneration and may lead to novel treatments for dermal wounds.
| S-EPMC3248550 | biostudies-literature
Project description: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.
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Project description:Epithelial differentiation of adipose-derived stem cells (ADSCs) is mediated by sophisticated interactions of various molecular functions and biological processes, including transcriptional regulation. Runt-related transcription factor 2 (RUNX2) increases osteoblast and adipocyte differentiation of ADSCs. However, the role of RUNX2 in epithelial differentiation of ADSCs is unknown. We first showed that ADSCs possess the potential to differentiate into epithelial lineage. Then, we employed the effect of RUNX2 on epithelial differentiation of ADSCs. Our data showed that RUNX2 promoted epithelial differentiation of ADSCs. Overexpression or knockdown of RUNX2 resulted in increase or decrease of E-cadherin expression, respectively. Abatement of E-cadherin in ADSCs attenuated RUNX2-activated epithelial conversion of ADSCs and epithelial markers cytokeratin 18 (CK18) and zonula occludens protein-1 (ZO-1). We also evaluated the effect of RUNX2 on burn wound healing in vivo. The wound re-epithelialization were accelerated by RUNX2. The wound closure indexs, demis regeneration and revascularization were all improved. Furthermore, RUNX2 binding directly to the E-cadherin promoter region was characterized in ADSCs by chromatin immunoprecipitation (ChIP) and luciferase promoter reporter assays. Taken together, the study demonstrates the role of RUNX2 in epithelial differentiation of ADSCs and suggests that RUNX2 promotes E-cadherin expression, at least in part, through its direct binding to the promoter.
| S-EPMC5788666 | biostudies-literature
Project description:Development of natural protein-based fibrous scaffolds with tunable physical properties and biocompatibility is highly desirable to construct three-dimensional (3D), fully cellularized scaffolds for wound healing. Herein, we demonstrated a simple and effective technique to construct electrospun 3D fibrous scaffolds for accelerated wound healing using a photocrosslinkable hydrogel based on gelatin methacryloyl (GelMA). We found that the physical properties of the photocrosslinkable hydrogel including water retention, stiffness, strength, elasticity and degradation can be tailored by changing the light exposure time. We further observed that the optimized hydrogel fibrous scaffolds which were soft and elastic could support cell adhesion, proliferation and migration into the whole scaffolds, facilitating regeneration and formation of cutaneous tissues within two weeks. Such tunable characteristics of the fibrous GelMA scaffolds distinguished them from other reported substrates developed for reconstruction of wound defects including glutaraldehyde-crosslinked gelatin or poly (lactic-co-glycolic acid) (PLGA), whose physical and chemical properties were difficult to modify to allow cell infiltration into the 3D scaffolds for tissue regeneration. We anticipate that the ability to become fully cellularized will make the engineered GelMA fibrous scaffolds suitable for widespread applications as skin substitutes or wound dressings.Statement of significanceIn present study, we generate three-dimensional photocrosslinkable gelatin (GelMA)-based fibrous scaffolds with tunable physical and biological properties by using a combined photocrosslinking/electrospinning approach. The developed GelMA fibrous scaffolds can not only support cell viability and cell adhesion, but also facilitate cell migration and proliferation, accelerating regeneration and formation of cutaneous tissues. In addition, the physical properties of the engineered fibrous GelMA hydrogel including water retention capability, mechanical properties and biodegradability can be tuned to accommodate different patients' needs, making it a promising candidate for skin tissue engineering.
| S-EPMC5296408 | biostudies-literature
Project description:Overexpression of reactive oxygen species (ROS) can lead to chronic inflammation, which limits skin wound healing. Therefore, it is of great significance to develop materials that can locally control the adverse reactions caused by excessive ROS. In this research, an ROS-sensitive hydrogel with strong free radical scavenging ability was prepared by introducing the thione (Tk) group into carboxymethyl chitosan (CMCTS) hydrogel. CMCTS hydrogel was cross-linked by NH2-Tk-NH2 agent and loaded curcumin (Cur), which possessed favorable nontoxicity, water absorption, mechanical property, biodegradability, drug release behavior, the M2 phenotype, and inflammatory factor regulating the capacity of macrophages. It is worth noting that Cur@CMCTS-Tk hydrogel can significantly inhibit oxidative damage of human fibroblasts in the H2O2-induced microenvironment and protect their viability by reducing the production of intracellular ROS. In vivo, ROS-removing hydrogel effectively accelerated the process of wound healing and possessed good regenerative properties, including hair follicle formation, promotion of new blood vessel formation, and highly orderly arrangement of collagen fibers in the full-thickness skin burn defect rat model. Hence, we expect that the Cur@CMCTS-Tk hydrogel could be used for wound treatment and tissue regeneration due to the ability to scavenge excess ROS.
| S-EPMC8238405 | biostudies-literature
Project description:Biomaterial-associated microbial contaminations in biologically conducive three-dimensional (3D) tissue-engineered constructs have significantly limited the clinical applications of scaffold systems. To prevent such infections, antimicrobial biomaterials are rapidly evolving. Yet, the use of such materials in bioprinting-based approaches of scaffold fabrication has not been examined. This study introduces a new generation of bacteriostatic gelatin methacryloyl (GelMA)-based bioinks, incorporated with varying doses of antibacterial superparamagnetic iron oxide nanoparticles (SPIONs). The SPION-laden GelMA scaffolds showed significant resistance against the Staphylococcus aureus growth, while providing a contrast in magnetic resonance imaging. We simulated the bacterial contamination of cellular 3D GelMA scaffolds in vitro and demonstrated the significant effect of functionalized scaffolds in inhibiting bacterial growth, while maintaining cell viability and growth. Together, these results present a new promising class of functionalized bioinks to 3D bioprint tissue-engineered scaffold with markedly enhanced properties for the use in a variety of in vitro and clinical applications.
| S-EPMC9440295 | biostudies-literature
Project description:The management of diabetic wounds remains a major therapeutic challenge in clinics. Herein, we report a personalized treatment using 3D scaffolds consisting of radially or vertically aligned nanofibers in combination with bone marrow mesenchymal stem cells (BMSCs). The 3D scaffolds have customizable sizes, depths, and shapes, enabling them to fit a variety of type 2 diabetic wounds. In addition, the 3D scaffolds are shape-recoverable in atmosphere and water following compression. The BMSCs-laden 3D scaffolds are capable of enhancing the formation of granulation tissue, promoting angiogenesis, and facilitating collagen deposition. Further, such scaffolds inhibit the formation of M1-type macrophages and the expression of pro-inflammatory cytokines IL-6 and TNF-α and promote the formation of M2-type macrophages and the expression of anti-inflammatory cytokines IL-4 and IL-10. Taken together, BMSCs-laden, 3D nanofiber scaffolds with controlled structure and alignment hold great promise for the treatment of diabetic wounds. STATEMENT OF SIGNIFICANCE: In this study, we developed 3D radially and vertically aligned nanofiber scaffolds to transplant bone marrow mesenchymal stem cells (BMSCs). We personalized 3D scaffolds that could completely match the size, depth, and shape of diabetic wounds. Moreover, both the radially and vertically aligned nanofiber scaffolds could completely recover their shape and maintain structural integrity after repeated loads with compressive stresses. Furthermore, the BMSCs-laden 3D scaffolds are able to promote granulation tissue formation, angiogenesis, and collagen deposition, and switch the immune responses to the pro-regenerative direction. These 3D scaffolds consisting of radially or vertically aligned nanofibers in combination with BMSCs offer a robust, customizable platform potentially for a significant improvement of managing diabetic wounds.
| S-EPMC7207021 | biostudies-literature
Project description:BackgroundPolysaccharide-based hydrogels have been developed for many years to treat burn wounds. Essential oils extracted from aromatic plants generally exhibit superior biological activity, especially antibacterial properties. Studies have shown that antibacterial hydrogels mixed with essential oils have great potential for burn wound healing. This study aimed to develop an antibacterial polysaccharide-based hydrogel with essential oil for burn skin repair.MethodsEucalyptus essential oil (EEO), ginger essential oil (GEO) and cumin essential oil (CEO) were employed for the preparation of effective antibacterial hydrogels physically crosslinked by carboxymethyl chitosan (CMC) and carbomer 940 (CBM). Composite hydrogels were prepared and characterized using antimicrobial activity studies, Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, gas chromatography-mass spectrometery, rheological analysis, viscosity, swelling, water loss rate and water vapor transmission rate studies. In addition, the biocompatibility of hydrogels was evaluated in vivo by cytotoxicity and cell migration assays and the burn healing ability of hydrogels was tested in vivo using burn-induced wounds in mice.ResultsThe different essential oils exhibited different mixing abilities with the hydrogel matrix (CMC and CBM), which caused varying levels of reduction in essential oil hydrogel viscosity, swelling and water vapor transmission. Among the developed hydrogels, the CBM/CMC/EEO hydrogel exhibited optimal antibacterial activities of 46.26 ± 2.22% and 63.05 ± 0.99% against Staphylococcus aureus and Escherichia coli, respectively, along with cell viability (>92.37%) and migration activity. Furthermore, the CBM/CMC/EEO hydrogel accelerated wound healing in mouse burn models by promoting the recovery of dermis and epidermis as observed using a hematoxylin-eosin and Masson's trichrome staining assay. The findings from an enzyme-linked immunosorbent assay demonstrated that the CBM/CMC/EEO hydrogel could repair wounds through interleukin-6 and tumor necrosis factor-α downregulation and transforming growth factor-β, vascular endothelial growth factor (VEGF) and epidermal growth factor upregulation.ConclusionsThis study successfully prepared a porous CBM/CMC/EEO hydrogel with high antibacterial activity, favorable swelling, optimal rheological properties, superior water retention and water vapor transmission performance and a significant effect on skin repair in vitro and in vivo. The results indicate that the CBM/CMC/EEO hydrogel has the potential for use as a promising burn dressing material for skin burn repair.
| S-EPMC8693078 | biostudies-literature
Project description:Recent studies in tissue engineering have adopted extracellular matrix (ECM) derived scaffolds as natural and cytocompatible microenvironments for tissue regeneration. The dentin matrix, specifically, has been shown to be associated with a host of soluble and insoluble signaling molecules that can promote odontogenesis. Here, we have developed a novel bioink, blending printable alginate (3% w/v) hydrogels with the soluble and insoluble fractions of the dentin matrix. We have optimized the printing parameters and the concentrations of the individual components of the bioink for print accuracy, cell viability and odontogenic potential. We find that, while viscosity, and hence printability of the bioinks, was greater in the formulations containing higher concentrations of alginate, a higher proportion of insoluble dentin matrix proteins significantly improved cell viability; where a 1:1 ratio of alginate and dentin (1:1 Alg-Dent) was most suitable. We further demonstrate high retention of the soluble dentin molecules within the 1:1 Alg-Dent hydrogel blends, evidencing renewed interactions between these molecules and the dentin matrix post crosslinking. Moreover, at concentrations of 100 ?g ml-1, these soluble dentin molecules significantly enhanced odontogenic differentiation of stem cells from the apical papilla encapsulated in bioprinted hydrogels. In summary, the proposed novel bioinks have demonstrable cytocompatibility and natural odontogenic capacity, which can be a used to reproducibly fabricate scaffolds with complex three-dimensional microarchitectures for regenerative dentistry in the future.
| S-EPMC5796756 | biostudies-literature
Project description:Background: The repair of wounds usually caused by trauma or other chronic diseases remained challenging in clinics due to the potential risk of inflammation and inadequate tissue regenerative properties. Among them, the behaviour of immune cells, such as macrophages, is critical in tissue repair. Materials and methods: In this study, a water-soluble phosphocreatine-grafted methacryloyl chitosan (CSMP) was synthesized with a one-step lyophilization method, followed by the fabrication of CSMP hydrogel with a photocrosslinked method. The microstructure, water absorption and mechanical properties for the hydrogels were investigated. Then, the macrophages were co-cultured with hydrogels and the pro-inflammatory factors and polarization markers for these macrophages were detected through real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and flow cytometry methods. Finally, the CSMP hydrogel was implanted in a wound defect area in mice to test its ability to promote wound healing. Results: The lyophilized CSMP hydrogel had a porous structure with pores ranging in size from 200 to 400 μm, which was larger than the CSM hydrogel’s. The lyophilized CSMP hydrogel possessed a higher water absorption rate compared with the CSM hydrogel. The compressive stress and modulus of these hydrogels were increased in the initial 7 days immersion and then gradually decreased during the in vitro immersion in PBS solution up to 21 days; the CSMP hydrogel showed a higher value in these parameters versus the CSM hydrogel. The CSMP hydrogel inhibited the expression of inflammatory factors such as interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in an in vitro study cocultured with pro-inflammatory factors in pre-treated bone marrow-derived macrophages (BMM). The mRNA sequencing results showed that the CSMP hydrogel might inhibit the macrophages’ M1 type polarization through the NF-κB signaling pathway. Furthermore, when compared to the control group, the CSMP hydrogel promoted more skin area repair in the mouse wound defect area, and inflammatory factors such as IL-1β, IL-6, and TNF-α were lower in the repaired tissue for the CSMP group. Conclusion: This phosphate-grafted chitosan hydrogel showed great promise for wound healing through regulating the macrophage’s phenotype via the NF-κB signaling pathway.
| S-EPMC10213409 | biostudies-literature