The ability of mesenchymal stem cells
(MSCs) to enhance cutaneous
wound healing has been well established. Extensive expansion of cells
to reach sufficient cell numbers for regenerating tissues has always
limited cell-based therapies. An ingenious solution to address this
challenge is to develop a strategy to increase the immunomodulatory
effects of MSCs without expanding them. In this study, we employed
a simple characteristic of cells. It was observed that an optimized
three-dimensional (3D) MSC culture in spheroid forms significantly
improved their paracrine effects. An electrospray (ES) encapsulation
apparatus was used to encapsulate individual or 3D spheroid MSCs into
microscale alginate beads (microbeads). Furthermore, alginate microbeads
were embedded in an injectable thermosensitive hydrogel matrix, which
gels at skin temperature. The hydrogel fills and seals the wounds
cavities, maintains high humidity at the wound area, absorbs exudate,
and fixes microbeads, protecting them from direct contact with the
harsh wound environment. In vitro investigations revealed that secretion
of interleukin 10 (IL-0) and transforming growth factor β1 (TGF-β1)
gene was gradually enhanced, providing a delivery platform for prolonged
release of bioactive molecules. In vivo study on full-thickness wounds
showed granulation and re-epithelialization, only after 7 days. Moreover,
increased expression of α-smooth muscle actin (α-SMA)
in the first 14 days after treatment ensured wound contraction. Besides,
a gradual decrease in α-SMA secretion resulted in reduced scar
formation. Well-organized collagen fibrils and high expression of
the angiogenesis biomarker CD31 confirmed the promoting effect of
the hydrogel on the wound-healing process. The proposed wound-dressing
system would potentially be used in scalable and effective cell-based
wound therapies.
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