Excessive
scar formation has adverse physiological and psychological
effects on patients; therefore, a therapeutic strategy for rapid wound
healing and reduced scar formation is urgently needed. Herein, bilayered
thiolated alginate/PEG diacrylate (BSSPD) hydrogels were fabricated
for sequential release of small extracellular vesicles (sEVs), which
acted in different wound healing phases, to achieve rapid and scarless
wound healing. The sEVs secreted by bone marrow derived mesenchymal
stem cells (B-sEVs) were released from the lower layer of the hydrogels
to promote angiogenesis and collagen deposition by accelerating fibroblast
and endothelial cell proliferation and migration during the early
inflammation and proliferation phases, while sEVs secreted by miR-29b-3p-enriched
bone marrow derived mesenchymal stem cells were released from the
upper layer of the hydrogels and suppressed excessive capillary proliferation
and collagen deposition during the late proliferation and maturation
phases. In a full-thickness skin defect model of rats and rabbit ears,
the wound repair rate, angiogenesis, and collagen deposition were
evaluated at different time points after treatment with BSSPD loaded
with B-sEVs. Interestingly, during the end of the maturation phase
in the in vivo model, tissues in the groups treated
with BSSPD loaded with sEVs for sequential release (SR-sEVs@BSSPD)
exhibited a more uniform vascular structure distribution, more regular
collagen arrangement, and lower volume of hyperplastic scar tissue
than tissues in the other groups. Hence, SR-sEVs@BSSPD based on skin
repair phases was successfully designed and has considerable potential
as a cell-free therapy for scarless wound healing.
Antibacterial hydrogel has emerged as an excellent candidate for wound dressing with the ability to eliminate infection and promote wound healing. Herein, a dynamic hydrogel was developed by Schiff base reaction of mixed charged polypeptides and oxidized dextran (ODex). Specifically, biodegradable polypeptides of 1‐(propylthio)acetic acid‐3‐butylimidazole‐modified poly(L‐lysine) (PLL‐PBIM) and adipate dihydrazide‐modified poly(L‐glutamic acid) (PLG‐ADH) were achieved with tunable substitution and charge. By mixing with ODex, charged polypeptides of PLL‐PBIM and PLG‐ADH led to an injectable and self‐healing hydrogel in seconds. The injectable and self‐healing performances of the hydrogels were ascribed to the reversible imine and hydrazone bonds formed between polypeptides and ODex. The positive charged hydrogels exhibited over 95% antibacterial activity against E. coli and S. aureus. An optimized balancing of PLG‐ADH and PLL‐PBIM significantly reduced the hemolysis rate and cytotoxicity of hydrogels. Therefore, the dynamic hydrogel with excellent biocompatibility and inherently antibacterial ability could have potential application for wound dressing.This article is protected by copyright. All rights reserved
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