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.
An in situ formed hydrogel was synthesized by sodium alginate and cysteine methyl ester, which turned the sodium alginate into thiolated alginate (SA-SH). SA-SH can in situ formed into hydrogel (SA-SS-SA) with a large amount of water through covalent bond in less than 20 s. The structure characterization showed that the mechanism of SA-SH gelation was thiol-disulfide transformation. The rheology and cytotoxicity experiments of SA-SS-SA hydrogel were also investigated, which indicated that SA-SS-SA hydrogel had an appropriate mechanical strength as well as an excellent biocompatibility. The SA-SS-SA hydrogel would degrade under certain conditions after a few days and its mechanism was disulfide alkaline reduction. Finally, the hemostatic property of SA-SH was tested by rat tail amputation experiment. The time to hemostasis of rat reduced from 8.26 min to 3.24 min, which proved that SA-SH had an excellent hemostatic property.
Supramolecular dendritic polymers (SDPs) provide a new opportunity for the precision diagnosis and treatment of diseases. SDPs are a novel class of non-covalently bonded macromolecules with highly branched structure and three-dimensional globular topology, which exhibit dynamic/ reversible features and unique physical/chemical properties (e.g., high solubility, low viscosity, and numerous functional terminal groups). The reversibility of non-covalent interactions endows SDPs with the ability of facile preparation, smart responsiveness, and simple metabolism. These special characteristics determine the properties of SDPs, which are the key points for theranostic applications, including diagnosis, therapy, and theranostics. In this review, we briefly summarize the design and synthesis of SDPs with aimed structures, properties, functions as well as their present diagnostic and theranostic applications. These developments on the preparation and applications of SDPs for diagnostic and theranostic purpose promote interdisciplinary research fields of chemistry, material and biomedical science.
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