Background aims: The treatment of chronic refractory skin wounds still remains a serious clinical challenge. Stem cells and hydrogels are widely used in healing of skin wound of various types due to their superior bioactivities and biocompatibility. This study aimed to demonstrate the wound healing effect of a hydrogel compound loaded with enucleated stem cells expressing the platelet-derived growth factor (PDGF).

Methods: An injectable hydrogel was formulated using 22% poloxamer 407, 1% poloxamer 188, and 1% hyaluronic acid. A PDGF-B transgenic cell line of mouse bone marrow mesenchymal stem cells (BMSCs) was generated by lentiviral infection. Cells were enucleated and embedded in hydrogel. The healing effects of the compound was tested in a full-thickness skin wound model of Balb/c mice. The wound models were randomly divided into four groups: the control group applied with PBS buffer; the hydrogel group with hydrogel only; the BMSC group with hydrogel mixed with normal BMSCs; and the BMSC-PDGF group with hydrogel mixed with enucleated BMSCs expressing PDGF.

Results: Overexpression of PDGF-B in transgenic cell line of BMSCs was verified by RT-PCR, immunofluorescence staining and western blot. When enucleated, the viability measured by Calcein-AM staining reduced to 54.29% at 48 h. Conditioned medium was collected with or without hydrogel layered over cells. PDGF concentration measured by ELISA reached 14.66 ng/μL and 257.89 ng/μL respectively after 48-h cultivation, suggesting a possible slow releasing effect in the presence of hydrogel. When applied to the skin wound, the healing rates of the BMSC-PDGF group was significantly higher than that of the control group on day 3. BMSC-PDGF group had significantly more neovascularization and cutaneous appendages from day 7. The proliferation of collagen fibers in BMSC-PDGF group was significantly higher than the control group on day 3 and day 7. Finally, BMSC-PDGF group had significantly lower amount of the inflammatory factors TNF-α, IL-1β, IL-6, MMP-3 and MMP-9 than that of the control group on day 7.

Conclusions: PDGF-stem cell-hydrogel compound significantly improved wound healing and reduced wound inflammatory factor expression in Balb/c mice. This biomaterial-based approach provides a new powerful reference for the treatment of chronically wounded skin.

Keywords: enucleated cells; hydrogel; platelet-derived growth factor; stem cells; wound healing.

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