Assessing the mechanisms of action of natural molecules/extracts for phase-directed wound healing in hydrogel scaffolds.
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ABSTRACT:
SUBMITTER: Chummun I
PROVIDER: S-EPMC8459329 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Natural molecules/extracts have numerous beneficial effects on wound healing processes which are challenged by appropriate use and non-toxic dosage. Polysucrose-based (PSucMA) hydrogels have been synthesized with in situ loading of one or more natural molecules/extracts namely Manuka honey (MH), Eucalyptus honey (EH1, EH2), Ginkgo biloba (GK), thymol (THY) and metformin (MET). EH1 presented low amounts of hydroxymethylfurfural and methylglyoxal compared to MH indicating that EH1 was not temperature-abused. It also showed high diastase activity and conductivity. GK was added to PSucMA solution along with other additives including MH, EH1 and MET and crosslinked to form dual loaded hydrogels. The in vitro release profiles of EH1, MH, GK and THY from the hydrogels followed the exponential Korsmeyer-Peppas equation, with a release exponent value of less than 0.5 indicating a quasi-Fickian diffusion mechanism. The IC50 values of these natural products using L929 fibroblasts and RAW 264.7 macrophages indicated that EH1, MH and GK were cytocompatible at relatively high concentrations compared to MET, THY and curcumin used as a control. MH and EH1 induced high IL6 concentration compared to GK. In vitro studies were modelled to mimic the overlapping wound healing phases using human dermal fibroblasts (HDFs), macrophages and human umbilical endothelial cells (HUVECs) in dual culture. HDFs showed a highly interconnected cellular network on GK loaded scaffolds. EH1 loaded scaffolds were seen to induce formation of spheroids which increased in number and size in co-culture studies. The SEM images of HDF/HUVEC seeded GK, GKMH and GKEH1 loaded hydrogels indicated formation of vacuoles and lumen structures. These results indicated that a combination of GK and EH1 in the hydrogel scaffold would accelerate tissue regeneration by acting on the four overlapping phases of wound healing.
| S-EPMC10034044 | 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:Current strategies to improve wound healing are often created from multiple components that may include a scaffold, cells, and bioactive cues. Acellular natural hydrogels are an attractive approach since the material's intrinsic biological activity can be paired with mechanical properties similar to soft tissue to induce a host's response toward healing. In this report, a systematic evaluation was conducted to study the effect of hydrogel scaffold implantation in skin healing using a human-relevant murine wound healing model. Fibrin, micro porous hyaluronic acid, and composite hydrogels were utilized to study the effect of conductive scaffolds on the wound healing process. Composite hydrogels were paired with plasmin-degradable VEGF nanocapsules to investigate its impact as an inductive composite hydrogel on tissue repair. By 7 days, wound healing and vessel maturation within the newly formed tissue was significantly improved by the inclusion of porous scaffold architecture and VEGF nanocapsules.
| S-EPMC4618322 | biostudies-literature
Project description:Severe burns are challenging to heal and result in significant death throughout the world. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising treatment for full-thickness burn healing but are impeded by their low viability and efficiency after grafting in vivo. Nitric oxide (NO) is beneficial in promoting stem cell bioactivity, but whether it can function effectively in vivo is still largely unknown. In this study, we bioprinted an efficient biological scaffold loaded with ADSCs and NO (3D-ADSCs/NO) to evaluate its biological efficacy in promoting severe burn wound healing. The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting. Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells (HUVECs). Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition. Notably, immunohistochemistry of CD31 suggested an increase in neovascularization, supported by the upregulation of vascular endothelial growth factor (VEGF) mRNA in ADSCs in the 3D biosystem. These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway. This scaffold may be considered a promising strategy for healing severe burns.
| S-EPMC8071097 | biostudies-literature
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:Chronic wounds cost several billion dollars of public healthcare spending annually and continue to be a persistent threat globally. Several treatment methods have been explored, and all of them involve covering up the wound with therapeutic dressings that reduce inflammation and accelerate the healing process. In this present study, morin (MOR) was loaded onto hydrogel scaffolds prepared from psyllium seed husk polysaccharide (PSH), and human hair keratins (KER) crosslinked with sodium trimetaphosphate. ATR-FTIR confirmed the presence of the constituent chemical ingredients. SEM images of the scaffold surface reveal a highly porous architecture, with about 80% porosity measured by liquid displacement measurement, irrespective of the morin concentration. Swelling assays carried out on the scaffolds portray an ability to absorb up to seven times their dry weight of fluids. This makes them attractive for guiding moist wound healing on medium exuding wounds. An Alamar blue assay of NIH/3T3 fibroblast cells shows that cell viability decreases in the first 24 h but recovers to 85% in comparison to a control after 48 h. SEM images of fibroblast cells grown on the scaffolds confirm cellular attachment. An in vivo diabetic wound healing study showed that PSH + KER + MOR scaffold treatment significantly reduced the re-epithelialization time (p < 0.01) and enhanced the rate of wound contraction (p < 0.001), by accelerating collagen synthesis in diabetic rats compared to controls.
| S-EPMC9077386 | biostudies-literature
Project description:Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Herein, a nanofiber/hydrogel core-shell scaffold with three-dimensional (3D) multilayer patterned structure (3D-PT-P/GM) was introduced for promoting diabetic wound healing with improved angiogenesis. The results showed that the 3D-PT-P/GM scaffolds possessed multilayered structure with interlayer spacing of about 15-80 μm, and the hexagonal micropatterned structures were uniformly distributed on the surface of each layer. The nanofibers in the scaffold exhibited distinct core-shell structures with Gelatin methacryloyl (GelMA) hydrogel as the shell and Poly (D, L-lactic acid) (PDLLA) as the core. The results showed that the porosity, water retention time and water vapor permeability of the 3D-PT-P/GM scaffolds increased to 1.6 times, 21 times, and 1.9 times than that of the two-dimensional (2D) PDLLA nanofibrous scaffolds, respectively. The in vitro studies showed that the 3D-PT-P/GM scaffolds could significantly promote cell adhesion, proliferation, infiltration and migration throughout the scaffolds, and the expression of cellular communication protein-related genes, as well as angiogenesis-related genes in the same group, was remarkably upregulated. The in vivo results further demonstrated that the 3D-PT-P/GM scaffolds could not only effectively absorb exudate and provide a moist environment for the wound sites, but also significantly promote the formation of a 3D network of capillaries. As a result, the healing of diabetic wounds was accelerated with enhanced angiogenesis, granulation tissue formation, and collagen deposition. These results indicate that nanofiber/hydrogel core-shell scaffolds with 3D multilayer patterned structures could provide a new strategy for facilitating chronic wound healing.
| S-EPMC8742387 | biostudies-literature
Project description:BackgroundDuring wound healing, the overproduction of reactive oxygen species (ROS) can break the cellular oxidant/antioxidant balance, which prolongs healing. The wound dressings targeting the mitigation of ROS will be of great advantages for the wound healing. puerarin (PUE) and ferulic acid (FA) are natural compounds derived from herbs that exhibit multiple pharmacological activities, such as antioxidant and anti-inflammatory effects. Polydopamine (PDA) is made from natural dopamine and shows excellent antioxidant function. Therefore, the combination of natural antioxidants into hydrogel dressing is a promising therapy for wound healing.ResultsHydrogel wound dressings have been developed by incorporating PUE or FA via PDA nanoparticles (NPs) into polyethylene glycol diacrylate (PEG-DA) hydrogel. This hydrogel can load natural antioxidant drugs and retain the drug in the gel network for a long period due to the presence of PDA NPs. Under oxidative stress, this hydrogel can improve the activity of superoxide dismutase and glutathione peroxidase and reduce the levels of ROS and malondialdehyde, thus preventing oxidative damage to cells, and then promoting wound healing, tissue regeneration, and collagen accumulation.ConclusionOverall, this triple antioxidant hydrogel accelerates wound healing by alleviating oxidative injury. Our study thus provides a new way about co-delivery of multiple antioxidant natural molecules from herbs via antioxidant nanoparticles for wound healing and skin regeneration.
| S-EPMC8359571 | biostudies-literature
Project description:Diabetic wound repair and skin regeneration remains a worldwide challenge due to the impaired functionality of re-vascularization. Methods: This study reports a bioactive self-healing antibacterial injectable dual-network silica-based nanocomposite hydrogel scaffolds that can significantly enhance the diabetic wound healing/skin tissue formation through promoting early angiogenesis without adding any bioactive factors. The nanocomposite scaffold comprises a main network of polyethylene glycol diacrylate (PEGDA) forming scaffolds, with an auxiliary dynamic network formed between bioactive glass nanoparticles containing copper (BGNC) and sodium alginate (ALG) (PABC scaffolds). Results: PABC scaffolds exhibit the biomimetic elastomeric mechanical properties, excellent injectabilities, self-healing behavior, as well as the robust broad-spectrum antibacterial activity. Importantly, PABC hydrogel significantly promoted the viability, proliferation and angiogenic ability of endothelial progenitor cells (EPCs) in vitro. In vivo, PABC hydrogel could efficiently restore blood vessels networks through enhancing HIF-1α/VEGF expression and collagen matrix deposition in the full-thickness diabetic wound, and significantly accelerate wound healing and skin tissue regeneration. Conclusion: The prominent multifunctional properties and angiogenic capacity of PABC hydrogel scaffolds enable their promising applications in angiogenesis-related regenerative medicine.
| S-EPMC7163448 | biostudies-literature
Project description:This review will explore the latest advancements spanning several facets of wound healing, including biologics, skin substitutes, biomembranes and scaffolds.
| S-EPMC4934597 | biostudies-literature