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Microskin-Inspired Injectable MSC-Laden Hydrogels for Scarless Wound Healing with Hair Follicles.

ABSTRACT: Scarless skin regeneration with functional tissue remains a challenge for full-thickness wounds. Here, mesenchymal stem cell (MSC)-laden hydrogels are developed for scarless wound healing with hair follicles. Microgels composed of aligned silk nanofibers are used to load MSCs to modulate the paracrine. MSC-laden microgels are dispersed into injectable silk nanofiber hydrogels, forming composites biomaterials containing the cells. The injectable hydrogels protect and stabilize the MSCs in the wounds. The synergistic action of silk-based composite hydrogels and MSCs stimulated angiogenesis and M1-M2 phenotype switching of macrophages, provides a suitable niche for functional recovery of wounds. Compared to skin defects treated with MSC-free hydrogels, the defects treated with the MSC-laden composite hydrogels heal faster and form scarless tissues with hair follicles. Wound healing can be further improved by adjusting the ratio of silk nanofibers and particles and the loaded MSCs, suggesting tunability of the system. To the best of current knowledge, this is the first time scarless skin regeneration with hair follicles based on silk material systems is reported. The improved wound healing capacity of the systems suggests future in vivo studies to compare to other biomaterial systems related to clinical goals in skin regeneration in the absence of scarring.

SUBMITTER: Zheng X

PROVIDER: S-EPMC7473495 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The revolutionary role of tissue adhesives in wound closure, tissue sealing, and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing. In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators (exemplified by sodium periodate and silver nitrate), herein, the natural polyphenolic compound tannic acid (TA) was used to achieve near instantaneous (<25s), hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant, anti-inflammatory, and antimicrobial activities (3A-TCMBAs). The resulting materials were self-healing and possessed low swelling ratios (<60%) as well as considerable mechanical strength (up to ∼1.0 MPa), elasticity (elongation ∼2700%), and adhesion (up to 40 kPa). The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability, favorable cytocompatibility and cell migration, as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli (>90% bacterial death upon near-infrared (NIR) irradiation). In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs + NIR treatment could promote wound closure and collagen deposition and improve the collagen I/III ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines. Further, phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation & remodeling of the extracellular matrix (ECM) in the late stage (supported by phased CD31 (platelet endothelial cell adhesion molecule-1) PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor) expression as well as elevated matrix metalloprotein-9 (MMP-9) expression on day 21), resulting in scarless wound healing. The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant, new class of bioadhesive.

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Microskin-Inspired Injectable MSC-Laden Hydrogels for Scarless Wound Healing with Hair Follicles.

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