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Assessing the mechanisms of action of natural molecules/extracts for phase-directed wound healing in hydrogel scaffolds.

ABSTRACT: Hydrogels are proving to be very versatile as wound healing devices. In addition to their capabilities of providing a moist cellular environment and adaptive mechanical properties mimicking the extracellular matrix, they allow the incorporation of small molecules, which have potential impacts on cellular behaviour, in their nanostructures. This strategy can allow for specific targeting of the different stages of wound healing namely hemostasis, inflammation, and proliferative and remodelling phases. The latter include interlinked processes such as angiogenesis, collagen synthesis, growth factor release, collagen maturation and re-epithelialization. In this review, we attempt to match the mechanisms of action of natural molecules/extracts to the different stages of wound healing so that they can be used in a novel approach of multiphase-directed tissue regeneration using loaded hydrogel scaffolds.

SUBMITTER: Chummun I

PROVIDER: S-EPMC8459329 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Assessing the mechanisms of action of natural molecules/extracts for phase-directed wound healing in hydrogel scaffolds.

Chummun Itisha I Bekah Devesh D Goonoo Nowsheen N Bhaw-Luximon Archana A

RSC medicinal chemistry 20210702 9

Hydrogels are proving to be very versatile as wound healing devices. In addition to their capabilities of providing a moist cellular environment and adaptive mechanical properties mimicking the extracellular matrix, they allow the incorporation of small molecules, which have potential impacts on cellular behaviour, in their nanostructures. This strategy can allow for specific targeting of the different stages of wound healing namely hemostasis, inflammation, and proliferative and remodelling pha ...[more]

PMID: 34671732

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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.

Project description:IntroductionWound healing is a complex process to restore homeostasis after injury and insufficient skin wound healing is a considerable problem in medicine. Whereas many attempts of regenerative medicine have been made for wound healing with growth factors and cell therapies, simple pharmacological and immunological studies are lagging behind. We investigated how fibrin hydrogels modulate immune cells and molecules in skin wound healing in mice.MethodsPhysiological fibrin hydrogels (3.5 mg/mL fibrinogen) were generated, biophysically analyzed for stiffness and protein contents and were structurally studied by scanning electron microscopy. Physiological fibrin hydrogels were applied to full thickness skin wounds and, after 3 days, cells and molecules in wound tissues were analyzed. Leukocytes, endothelial cells, fibroblasts and keratinocytes were explored with the use of Flow Cytometry, whereas cytokines and matrix metalloproteinases were analyzed with the use of qPCR, ELISAs and zymography. Skin wound healing was analyzed microscopically at day 3, macroscopically followed daily during repair in mice and compared with commercially available fibrin sealant Tisseel.ResultsExogenous fibrin at physiological concentrations decreased neutrophil and increased non-classical Ly6Clow monocyte and resolutive macrophage (CD206+ and CX3CR1+) populations, at day 3 after injury. Fibrin hydrogel reduced the expression of pro-inflammatory cytokines and increased IL-10 levels. In line with these findings, gelatinase B/MMP-9 was decreased, whereas gelatinase A/MMP-2 levels remained unaltered. Frequencies of dermal endothelial cells, fibroblasts and keratinocytes were increased and keratinocyte migration was enhanced by fibrin hydrogel. Importantly, physiological fibrin accelerated the healing of skin wounds in contrast to the highly concentrated fibrin sealant Tisseel, which delayed wound repair and possessed a higher fiber density.ConclusionCollectively, we show that adding a tailored fibrin hydrogel scaffold to a wound bed positively influences the healing process, modulating leukocyte populations and inflammatory responses towards a faster wound repair.

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Assessing the mechanisms of action of natural molecules/extracts for phase-directed wound healing in hydrogel scaffolds.

Publications

Assessing the mechanisms of action of natural molecules/extracts for phase-directed wound healing in hydrogel scaffolds.

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